Mitokondriesykdommer (mitokondrielle sykdommer) (legehandboka.no) (f rambu.no) (frambu.no) (frambu.no) (unn.no)

Mitochondria, Cell Energy, ATP Synthase | Learn Science at ... (nature.com)

Mitochondria (illustration) (U.S. National Library of Medicine) (qiagen.com)

Mitokondrie ...dei er sete for tilverting av energi (oksidasjon av pyruvat og feittsyrer til karbondioksid og NADH som gir elektronar til ATP-syntesen) (Norsk medisinsk ordbok) (youtube.com) (socialstyrelsen.se)

Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9)

Hyperlactatemia, metabolic acidosis, and peripheral neuropathy are adverse effects of linezolid,2,3 which could be related to the drug's capacity for interference with mitochondrial function.4 (NEJM 2005;353:2305-2306)

Steroids cause "catastrophic" brain damage (netdoctor.co.uk 3.10.2006)

Parasitt-RNA i genterapi mot mitokondriesykdom? (Tidsskr Nor Lægeforen 2007; 127: 11 (4.1.2007))

Antidepressiva linket til forverring av hvit substans hos eldre (Reuters Health 17.3.2008)

Kan fysiske symptomer ved depresjon skyldes lav energiproduksjon (medicalnewstoday.com 28.3.2008)

- Energimotoren i cellene våre stammer fra bakterier. (- Fascinerende evolusjon. De første cellene på Jorda var bakterier og arkebakterier. Arkebakterier skiller seg fra bakterier blant annet ved at de klarer seg i ekstreme omgivelser. De var alle prokaryote. De prokaryote cellene er de enkleste cellene på Jorda og ble dannet allerede for 3,5 milliarder år siden. Til sammenligning er Jorda 4,6 milliarder år gammel. – Hele livet stammer fra én eneste celle, forteller Klaus Høiland på Institutt for biovitenskap.)

(Anm: Energimotoren i cellene våre stammer fra bakterier. For halvannen milliard år siden slo to bakterier seg sammen og dannet energimotoren i cellene våre. Uten denne sjenerøse handlingen hadde ikke det moderne livet på Jorda vært til. 50 ÅR: Professorene Kamran Shalchian-Tabrizi og Klaus Høiland feirer i november 50-årsdagen for lanseringen av endosymbioseteorien – som forklarer hvorfor celler fikk energimotor og klorofyll. I 1967 – for femti år siden – lanserte en av verdens mest kjente biologer, den amerikanske professoren Lynn Margulis (1938–2011), en oppsiktsvekkende og kontroversiell teori om hvordan helt vesentlige egenskaper i cellene til både planter, dyr og oss mennesker ble dannet. Etter et par tiår med diskusjoner og dyp skepsis, ble teorien omsider anerkjent. I november blir femtiårsdagen for teorien markert med et stort symposium ved Universitetet i Oslo. (…) Fascinerende evolusjon De første cellene på Jorda var bakterier og arkebakterier. Arkebakterier skiller seg fra bakterier blant annet ved at de klarer seg i ekstreme omgivelser. De var alle prokaryote. De prokaryote cellene er de enkleste cellene på Jorda og ble dannet allerede for 3,5 milliarder år siden. Til sammenligning er Jorda 4,6 milliarder år gammel. – Hele livet stammer fra én eneste celle, forteller Klaus Høiland på Institutt for biovitenskap. Han har de siste 25 årene fått en rekke priser for sin evne til å formidle biologi på en folkelig måte. (…) Energimotoren En av organellene med dobbeltmembran er mitokondrie. Den er energimotoren i cellene våre. Uten mitokondriene hadde ikke cellene våre klart å leve mer enn noen timer. En del av endosymbioseteorien handler nettopp om hvordan mitokondriene ble en del av cellene våre. Mitokondriene ble til etter at atmosfæren fikk oksygen. Jobben til mitokondriene er å danne energi ved å forbrenne glukose med oksygen. Da dannes energien ATP, som er brenselet i cellene våre. – Når du sykler, trenger muskelcellene dine energi. Da trenger cellene ATP. Uten ATP ville du ikke ha kommet så langt, forklarer Klaus Høiland. En annen organelle, som også stammer fra endosymbiose, er kloroplast. Kloroplast finnes bare i planter og i alger. Jobben dens er å danne glukose fra fotosyntesen. Med moderne DNA-metoder vet biologene i dag at mitokondriene ble skapt før kloroplastene. Mitokondriene la grunnlaget for dyr og sopp. I neste omgang kom kloroplasten – som la grunnlaget for planter og alger. – Endosymbiosen av mitokondriene og kloroplastene er to av de viktigste hendelsene i livets historie – både for oss mennesker og for den enorme biodiversiteten på Jorda. Lanseringen av endosymbioseteorien er derfor så viktig at den burde ha fått en merkedag i kalenderen. Mitokondriene og kloroplastene er eksempler på biologisk innovasjon med kolossale konsekvenser, poengterer Kamran Shalchian-Tabrizi.  (apollon.no 31.10.2017).)

- Teknologi fra hydrogenbiler kan forklare hvorfor livet oppstod.

(Anm: Teknologi fra hydrogenbiler kan forklare hvorfor livet oppstod. (…) I cellene til mennesker og dyr blir energien produsert i det som kalles cellenes kraftverk, mitokondriene. De har et membran, som på mange måter tilsvarer membranet i brenselcellen. (nrk.no 21.3.2014).)

(Anm: What is a cell? (medicalnewstoday.com 8.2.2018).)

(Anm: What are mitochondria? (medicalnewstoday.com 8.2.2018).)

(Anm: Mitochondria: back to the future. Nature Reviews Molecular Cell Biology 19, 76 (2018).)

- Livet ville ikke vært mulig uten ATP. Forbindelsen er blitt kalt «livets molekyl».

(Anm: Adenosintrifosfat (ATP) er en energirik kjemisk forbindelse som er involvert i alle energikrevende prosesser i menneskekroppen, som muskelsammentrekning, overføring av signaler i nerver, oppbygging av proteiner, kopiering av arvestoffer med mer. (…) ATP kan oppfattes som en universell energileverandør i alle celler og vev. Livet ville ikke vært mulig uten ATP. Forbindelsen er blitt kalt «livets molekyl». Kilde: Store norske leksikon.)

(Anm: NeuroAge (uib.no).)

- ATP- syntese, et mål for demens og aldring?

(Anm: ATP Synthase, a Target for Dementia and Aging? Abstract Advancing age is the biggest risk factor for development for the major life-threatening diseases in industrialized nations accounting for >90% of deaths. Alzheimer's dementia (AD) is among the most devastating. Currently approved therapies fail to slow progression of the disease, providing only modest improvements in memory. Recently reported work describes mechanistic studies of J147, a promising therapeutic molecule previously shown to rescue the severe cognitive deficits exhibited by aged, transgenic AD mice. Apparently, J147 targets the mitochondrial alpha-F1-ATP synthase (ATP5A). Modest inhibition of the ATP synthase modulates intracellular calcium to activate AMP-activated protein kinase to inhibit mammalian target of rapamycin, a known mechanism of lifespan extension from worms to mammals. Rejuvenation Res. 2018 Feb;21(1):61-66.)

- Den økende status for mitokondrier innen medisinen. (- En gang utelukkende betraktet som cellers kraftverk, er mitokondrier nå anerkjent for å utføre flere essensielle funksjoner utover energiproduksjon, som påvirker de fleste områder av cellebiologi og medisin. (- Mitokondrier gjennomgår funksjonsdefinerte dynamiske formendringer, kommuniserer med hverandre, regulerer genuttrykk i cellekjerner, modulerer synaptisk transmisjon i hjernen, frigjør molekyler som bidrar til onkogen transformasjon og utløser inflammatoriske responser systemisk og påvirker reguleringen av komplekse fysiologiske systemer.)

(Anm: The rise of mitochondria in medicine. Abstract Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel mitopathogenic mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article, we overview specific aspects of mitochondrial biology that have contributed to – and likely will continue to enhance the progress of modern medicine. Mitochondrion 2017;30:105-116 (September 2016).)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Legemiddelindusert kreft og andre typer celleskader (mintankesmie.no).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

(Anm: Mitochondria are required for proageing features of the senescent phenotype. The EMBO Journal 2016 (Published online 04.02.2016 ).)

- Mitokondrier: En organelle av bakteriell opprinnelse som kontrollerer betennelse.

(Anm: Mitochondria: An Organelle of Bacterial Origin Controlling Inflammation. Mitochondria: An Organelle of Bacterial Origin Controlling Inflammation Inflammation is a cellular and molecular response to infection and/or tissues injury. While a suited inflammatory response in intensity and time allows for killing pathogens, clearing necrotic tissue, and healing injury; an excessive inflammatory response drives various diseases in which inflammation and tissues damages/stress self-sustain each other. Microbes have been poorly implied in non-resolving inflammation, emphasizing the importance of endogenous regulation of inflammation. Mitochondria have been historically identified as the main source of cellular energy, by coupling the oxidation of fatty acids and pyruvate with the production of high amount of adenosine triphosphate by the electron transport chain. Mitochondria are also the main source of reactive oxygen species. Interestingly, research in the last decade has highlighted that since its integration in eukaryote cells, this organelle of bacterial origin has not only been tolerated by immunity, but has also been placed as a central regulator of cell defense. In intact cells, mitochondria regulate cell responses to critical innate immune receptors engagement. Downstream intracellular signaling pathways interact with mitochondrial proteins and are tuned by mitochondrial functioning. Moreover, upon cell stress or damages, mitochondrial components are released into the cytoplasm or the extra cellular milieu, where they act as danger signals when recognized by innate immune receptors. Finally, by regulating the energetic state of immunological synapse between dendritic cells and lymphocytes, mitochondria regulate the inflammation fate toward immunotolerance or immunogenicity. As dysregulations of these processes have been recently involved in various diseases, the identification of the underlying mechanisms might open new avenues to modulate inflammation. Front. Immunol., 19 April 2018.)

- Sunshine Policies (retningslinjer for åpenhet om interessekonflikter) og mørke skygger over Europa: Offentliggjøring av legemiddelindustriens utbetalinger til helsepersonell i ni europeiske land. (- Er åpenheten om individuelle data obligatorisk og komplett? Flertallet av de frivillige retningslinjer inkluderer en "opt-out" (frameldelse)-klausul i form av et krav om individuelt samtykke, hvilket undergraver betydningen av en åpenhetspolitikk.)

(Anm: Sunshine Policies (retningslinjer for åpenhet om interessekonflikter) og mørke skygger over Europa: Offentliggjøring av legemiddelindustriens utbetalinger til helsepersonell i ni europeiske land. (Sunshine Policies and Murky Shadows in Europe: Disclosure of Pharmaceutical Industry Payments to Health Professionals in Nine European Countries. (...) Er åpenheten om individuelle data obligatorisk og komplette? Flertallet av de frivillige retningslinjer inkluderer en "opt-out" (frameldelse)-klausul, gjennom et krav om individuelt samtykke, hvilket undergraver betydningen av en åpenhetspolitikk. (The majority of the voluntary codes include an “opt-out” clause, through a requirement for individual consent, that undermines the meaning of a transparency policy.) (...) Disclosure rules must follow EFPIA guidelines, but exceptions are allowed when these provisions are in conflict with national laws or regulations. Int J Health Policy Manag 2018 (ePublished: 14 March 2018).)

(Anm: Habilitet (integritet) (mintankesmie.no).)

(Anm: Media (mediekritikk) (mintankesmie.no).)

(Anm: Interessekonflikter, bestikkelser og korrupsjon (mintankesmie.no).)

(Anm: Sakkyndige legers integritet, partiskhet og habilitet versus løgn i rettssalen (sakkyndighet) (mintankesmie.no).)

- Fatale bivirkninger av legemidler. (- Med ca. 830 000 døgnopphold ved norske sykehus i 2003 tilsier dette flere tusen legemiddelrelaterte dødsfall årlig.)

(Anm: Fatale bivirkninger av legemidler. (...) Legene ved medisinsk avdeling mistenkte bivirkninger i 73,3 % av tilfellene, kirurgene i 27,3 %. Ingen ble meldt Bivirkningsnemnda» (1).) (...) «FDA mottar ved direkte innrapporteringer færre enn 1 % av alvorlige mistenkte legemiddelreaksjoner» (2). (...) Med ca. 830 000 døgnopphold ved norske sykehus i 2003 tilsier dette flere tusen legemiddelrelaterte dødsfall årlig. Flere andre studier bekrefter at forekomsten av alvorlige og dødelige legemiddelreaksjoner er svært høyt (4, 5). Tidsskr Nor Lægeforen 2005; 125: 786.)

(Anm: Myndighetenes innsats for å eliminere risiko for legemiddelskader. (Norra Magasinet - TV2 24.02.1997).)

- NSAID kan forårsake endringer i cellemembraner; funn kan ha store konsekvenser for legemiddelutviklere.

(Anm: NSAIDs can cause changes to cell membranes; findings could have wide repercussions for drug developers Researchers have discovered that three commonly used nonsteroidal anti-inflammatory drugs, or NSAIDs, alter the activity of enzymes within cell membranes. Their finding suggests that, if taken at higher-than-approved doses and/or for long periods of time, these prescription-level NSAIDs and other drugs that affect the membrane may produce wide-ranging and unwanted side effects. (medicalnewstoday.com 25.8.2014).)

(Anm: L17.1.1 Ikke-steroide antiinflammatoriske midler (NSAID) Ikke-selektive NSAID: Acetylsalisylsyre, deksibuprofen, deksketoprofen, diklofenak, diklofenak-misoprostol, ibuprofen, indometacin, ketoprofen, ketorolak, meloksikam, nabumeton, naproksen, naproksen-esomeprazol, piroksikam, tolfenam  (legemiddelhandboka.no 20.1.2017).)

- Villigheten til å påføre andre skade.

(Anm: - Villigheten til å påføre andre skade. Pr. John Braithwaite. CORPORATE CRIME in the Pharmaceutical industry, Routledge & Kegan Paul, 1984 ISBN: 0710200498 (NÆRINGSLIVKRIMINALITET innen legemiddelindustrien, Routledge & Kegan Paul, 1984 ISBN: 0710200498).)

– Bekymret over stort medisinforbruk.

(Anm: – Bekymret over stort medisinforbruk. Helse. (…) Folkehelseinstituttets direktør Camilla Stoltenberg er bekymret over det høye medisinforbruket.) (– Kunnskapen vi har i dag, er for dårlig. Vi har muligheter til å få mye bedre kunnskap om dette, og det haster nå som vi har en eldrebølge foran oss, sier Stoltenberg. (kommunal-rapport.no 12.6.2018).)

- Bekymringer knyttet til studier etter markedsføring som kreves av legemiddelkontrollen FDA. (- En ny analyse fant en foruroligende mangel på rettidig gjennomføring så vel som fundamental informasjon. Spesielt at én av fire studier aldri ble offentlig formidlet.)

(Anm: Bekymringer knyttet til studier etter markedsføring som kreves av legemiddelkontrollen FDA. (The trouble with those post-marketing studies required by the FDA.) For å sikre at et nytt legemiddel virker på rett måte etter at markedsføringstillatelsen er gitt krever Food and Drug Administration (FDA) at et legemiddelfirma regelmessig skal utføre en såkalt studie etter markedsføring. Men en ny analyse fant en foruroligende mangel på rettidig gjennomføring så vel som fundamental informasjon. Spesielt at én av fire studier aldri ble offentlig formidlet. (…) Det var også mangel på oppdatert informasjon om fremdriften på om lag én tredjedel av disse studiekravene. (statnews.com 12.6.2018).)

– Trenger vi en havarikommisjon for legemidler?

(Anm: – Trenger vi en havarikommisjon for legemidler? Nylig ble MS-legemidlet daklizumab (Zinbryta) trukket tilbake etter ett år på markedet. (– Ved et så spektakulært legemiddelkrasj som daklizumab burde alle detaljer i godkjenningsprosessen fra A til Å granskes med lupe av uhildede personer. Pasienter døde eller fikk varig men. Det må vi lære av – det skylder vi dem som ble rammet. (dagensmedisin.no 29.5.2018).)

- Driver forsøksmedisinering på eldre.

(Anm: Driver forsøksmedisinering på eldre. MANGE MEDIKAMENTER: 570.000 eldre fikk fem eller flere ulike legemidler på resept i 2017. 76.000 hjemmeboende eldre fikk minst 15 ulike legemidler i 2017. – Eldre overmedisineres, vi har altfor stor tro på medisiner som løsning på folks problemer, sier sykehjemsoverlege Pernille Bruusgaard. (…) – Det er overmedisineringen som er det største problemet i dag, sier Bruusgaard. (dagensmedisin.no 15.6.2018).)

- Tester medisiner basert på dårlige dyrestudier. (- Færre enn 15 prosent av kliniske studier er vellykkede.) (- Penger og ressurser kastes bort, og i verste fall utgjør forskningen en fare for oss.)

(Anm: Tester medisiner basert på dårlige dyrestudier. De fleste av oss stoler på at vi trygt kan delta i utprøving av nye legemidler. Nå viser en ny studie at godkjenningsinstanser ikke får avgjørende informasjon om forskningen som er gjort på dyr i forkant. De fleste av oss stoler på at vi trygt kan delta i utprøving av nye legemidler. (…) Færre enn 15 prosent av kliniske studier er vellykkede. Det betyr at de aller fleste deltar i slik medisinsk forskning til liten nytte. Penger og ressurser kastes bort, og i verste fall utgjør forskningen en fare for oss. (etikkom.no 15.6.2018).)

- RIPK3 fremmer sepsis-indusert akutt nyreskade via mitokondriell dysfunksjon. (- I nyre-tubulære epitelceller viser vi at RIPK3 fremmer oksidativ stress og mitokondriell dysfunksjon som involverer oppregulering av NADPH-oksidase-4 (NOX4) og inhibering av mitokondriellkompleks I og -III, og at RIPK3 og NOX4 er kritiske for nyre-tubulær skade i vivo).

(Anm: RIPK3 promotes sepsis-induced acute kidney injury via mitochondrial dysfunction. Abstract Sepsis causes acute kidney injury (AKI) in critically ill patients, although the pathophysiology remains unclear. The receptor-interacting protein kinase-3 (RIPK3), a cardinal regulator of necroptosis, has recently been implicated in the pathogenesis of human disease. In mice subjected to polymicrobial sepsis, we demonstrate that RIPK3 promotes sepsis-induced AKI. Utilizing genetic deletion and biochemical approaches in vitro and in vivo, we identify a potentially novel pathway by which RIPK3 aggravates kidney tubular injury independently of the classical mixed lineage kinase domain-like protein-dependent (MLKL-dependent) necroptosis pathway. In kidney tubular epithelial cells, we show that RIPK3 promotes oxidative stress and mitochondrial dysfunction involving upregulation of NADPH oxidase-4 (NOX4) and inhibition of mitochondrial complex I and -III, and that RIPK3 and NOX4 are critical for kidney tubular injury in vivo. Furthermore, we demonstrate that RIPK3 is required for increased mitochondrial translocation of NOX4 in response to proinflammatory stimuli, by a mechanism involving protein-protein interactions. Finally, we observed elevated urinary and plasma RIPK3 levels in human patients with sepsis-induced AKI, representing potential markers of this condition. In conclusion, we identify a pathway by which RIPK3 promotes kidney tubular injury via mitochondrial dysfunction, independently of MLKL, which may represent a promising therapeutic target in sepsis-induced AKI. JCI Insight. 2018 Jun 7;3(11). pii: 98411.)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

- Nyreskade forårsaket av legemidler Man bør alltid vurdere legemidler som årsak ved både akutt og kronisk nyreskade. Medikamenter kan forårsake alle former for nyreskade med forskjellige kliniske manifestasjoner og ulik patogenese.

(Anm: Nyreskade forårsaket av legemidler Man bør alltid vurdere legemidler som årsak ved både akutt og kronisk nyreskade. Medikamenter kan forårsake alle former for nyreskade med forskjellige kliniske manifestasjoner og ulik patogenese. Pasientens alder, hydreringsstatus, opprinnelig nyrefunksjon og eventuell aterosklerose påvirker risikoen for legemiddelrelatert nyreskade. Tidsskr Nor Legeforen 2012; 132:1462-4.)

(Anm: Signaler fra tarmens mikrobiotika til fjerntliggende organer mht. fysiologi og sykdom. (Signals from the gut microbiota to distant organs in physiology and disease.) (Nat Med. 2016 Oct 6;22(10):1079-1089.)

(Anm: - Hadde medisinerne på et tidligere tidspunkt hatt et evolusjonært perspektiv på sin medisinering, ville vi ikke vært i den kritiske situasjon vi er kommet i med hensyn til resistens. (aftenposten.no 22.8.2016)

(Anm: Tannleger og tannhelse (munnhulen er kroppens speil). (mintankesmie.no/).)

- Eget PR-byrå for legemiddelindustrien etablerer seg i Norge. (- Vi gir deg de viktigste legemiddel- og apoteknyhetene. DM Pharma kommer tre ganger i uken til abonnenter.) (- DM Pharma er på lik linje med Dagens Medisin en uavhengig nyhetskanal og følger redaktørplakaten. Alt innhold er opphavsrettslig beskyttet.) (- BRANSJEVETERAN: Lars Henrik Østevold har bakgrunn fra både Novartis og Pfizer, og skal lede det norske kontoret til EFFECTOR.)

(Anm: Eget PR-byrå for legemiddelindustrien etablerer seg i Norge. BRANSJEVETERAN: Lars Henrik Østevold har bakgrunn fra både Novartis og Pfizer, og skal lede det norske kontoret til Effector. Dagens Medisin Pharma er for ledere og ansatte i legemiddelindustrien, apotekene, klinikken, myndighetene og politikere. Vi gir deg de viktigste legemiddel- og apoteknyhetene. DM Pharma kommer tre ganger i uken til abonnenter. Abonnementet gir også tilgang på nyhetsarkivet og frokostmøter. (dagensmedisin.no 16.5.2018).)

- Har antidepressiva en langsiktig nytteverdi? (- Når det gjelder dødelighet av antidepressiva heter det i en studie på 378 400 deltakere at «risikoen for tidlig død ble økt med 33 prosent blant brukere av antidepressiva sammenlignet med ikke-brukere» (4).

(Anm: Har antidepressiva en langsiktig nytteverdi? (...) Når det gjelder dødelighet av antidepressiva heter det i en studie på 378 400 deltakere at «risikoen for tidlig død ble økt med 33 prosent blant brukere av antidepressiva sammenlignet med ikke-brukere» (4). Det er således ikke overraskende at sykefraværet fra det tidspunktet SSRI-preparater ble introdusert på markedet (1993) har økt fra et svært lavt nivå til å bli verdens høyeste (5). Tidsskr Nor Legeforen 2018 (03.05.2018).)

- Varsler hevder Forest bestakk studieleder for å favorisere Cipramil (Celexa).

(Anm: Varsler hevder Forest bestakk studieleder for å favorisere Cipramil (Celexa). Whistleblower Claims Forest Bribed Study's Investigator to Favor Celexa. A whistleblower's complaint from 2011 that was unsealed Jan. 20 in a federal district court alleged that Forest Pharmaceuticals paid the principal investigator of a federally funded antidepressant drug study to fix the results in favor of the company's drug Celexa (United States ex rel. Pigott v. Forest Pharmaceuticals Inc., D. Md., No. 1:11-cv-00717, unsealed 1/20/12) (…) Only Explanation for Study's Bias: Kickbacks According to the complaint, the NIMH initially entered into a contract for the STAR*D study with the University of Texas in September 1999 with Rush as the P.I. Celexa is a selective serotonin reuptake inhibitor or SSRI. SSRIs prevent the body's reuptake or removal of a naturally-occurring neurotransmitter that it is believed to have a positive impact on mood. For More Information The complaint from 2011 can be found at http://op.bna.com/hl.nsf/r?Open=jaqo-8qvqcd. (bna.com 1.2.2012 (BNA - BLOOMBERG).)

(Anm: Habilitet (integritet) (mintankesmie.no).)

- Hvorfor ledere av legemiddelfirmaer i virkeligheten ikke er blitt rettsforfulgt for opioidkrisen. (- Leger, ofte uvitende om hvordan Purdue Pharma hadde forrådt dem, fortsatte å øke sin bruk av opioider med titalls millioner av årlige forskrevne resepter. Og i de fem årene etter sakens forlik, døde omtrent 100 000 amerikanere av overdoser.)

(Anm: Hvorfor ledere av legemiddelfirmaer faktisk ikke er blitt rettsforfulgt for opioidkrisen. (- Eierne og noen tidligere og nåværende ledere for OxyContin-produsenten Purdue Pharma ble saksøkt den 12. juni av Massachusetts påtalemyndighet, som hevder at firmaet bevisst villede leger og forbrukere om farene ved sitt produkt - noe Purdue nektet i en uttalelse. Dette tatt i betraktning en tidligere, separat - og avslørende sak mot firmaet for over ti år siden. "Det er total avsporing," sa Specter. "Jeg ser ikke hvordan du kan komme til en konklusjon om at enkeltpersoner ikke var lovbrytere som fortjener fengsel." Men aktor, John Brownlee, sa at han trodde at den svake siktelsen mot lederne var "hensiktsmessig" gitt saken bevis.) (- Leger, ofte uvitende om hvordan Purdue Pharma hadde forrådt dem, fortsatte å øke sin bruk av opioider med titalls millioner av årlige forskrevne resepter. Og i de fem årene etter sakens forlik, døde omtrent 100 000 amerikanere av overdoser. (time.com 17.6.2018).)

(Anm: VW-topp sier seg skyldig – risikerer 169 år i fengsel. Den tidligere VW-toppen i USA, Oliver Schmidt, innrømmer å ha forsøkt å dekke over utslippsjukset. Nå risikerer han mange år bak murene. (tv2.no 28.7.2017).)

(Anm: Audi-sjefen pågrepet i Tyskland. Audis administrerende direktør Rupert Stadler er pågrepet i Tyskland i forbindelse med etterforskningen av utslippsskandalen. (aftenposten.no 16.6.2018).)

- En gruppe forskere vil at American Journal of Psychiatry skal trekke tilbake en studie publisert i 2004 etter at nylig tilgjengelige dokumenter tyder på at Forest Laboratories, firmaet som solgte legemidlet som var gjenstand for studien, villedet legemiddelkontrollen om nøkkeldetaljer.

(Anm: Psykiatritidsskrift oppfordres til å trekke tilbake kontroversiell Celexa (Cipramil)-studie etter nylige avslørte detaljer. (Psychiatry journal is urged to retract controversial Celexa study over newly disclosed details.) En gruppe forskere vil at American Journal of Psychiatry skal trekke tilbake en studie publisert i 2004 etter at nylig tilgjengelige dokumenter tyder på at Forest  Laboratories, firmaet som solgte legemidlet som var gjenstand for studien, villedet legemiddelkontrollen om nøkkeldetaljer. (…) Statsadvokat oppfordrer til å gjenåpne en undersøkelse av en Allergan-enhet for påstått bedrageri. For nesten åtte år siden betalte en Allergan-enhet (AGN) 150 millioner dollar for å forlike kriminelle anklager om ulovlig markedsføring av tre legemidler. (…) Spesielt indikerer dokumentene at Forest Laboratories skjulte kritisk informasjon som viser at antidepressivet Celexa (Cipramil) ikke var effektivt hos barn. (statnews.com 8.2.2018 / 21.2.2018).)

(Anm: Habilitet (integritet) (mintankesmie.no).)

- Innsats mot alvorlig korrupsjon må på dagsordenen.

(Anm: Innsats mot alvorlig korrupsjon må på dagsordenen. Korrupsjon er et mangetydig begrep. Korrupsjon er tyveri av politiske, sosiale og økonomiske goder fra befolkningen. I fattige land, men ikke bare der, skaper korrupsjon fattigdom, sosial marginalisering, politisk nepotisme og terrorisme. Korrupsjon ødelegger den sunne konkurransen i næringslivet og tilliten til den offentlige forvaltningen. Bestikkelser av offentlige tjenestemenn er regnet som en alvorlig form for korrupsjon. (aftenposten.no 8.6.2018).)

- Korrupsjon gnager samfunn i stykker. Indirekte bidrag til korrupsjon er også ødeleggende.

(Anm: LEDERARTIKLENE SKRIVES AV AFTENPOSTENS KOMMENTATORER. GRUPPEN LEDES AV POLITISK REDAKTØR TRINE EILERTSEN. Aftenposten mener: Korrupsjon gnager samfunn i stykker. Indirekte bidrag til korrupsjon er også ødeleggende. (…) Stater og selskaper som benytter seg av hemmelige konti i såkalte skatteparadis bidrar indirekte til korrupsjon fordi de bidrar til strukturer som gjør korrupsjon mulig. (aftenposten.no 25.1.2017).)

- Salg av legemidler -- med litt hjelp fra en journalist. (Selling drugs - with a little help from a journalist.)

(Anm: - Salg av legemidler -- med litt hjelp fra en journalist. (Selling drugs - with a little help from a journalist.) Hvordan blir egentlig journalister rekruttert når de arbeider på vegne næringslivsklienter? En annonse rykket inn tidligere i år av PR-firmaet Chandler Chicco Agency gir et innblikk. (How exactly are journalists recruited to work on behalf of corporate clients? An advertisement placed earlier this year by public relations firm Chandler Chicco Agency offers an insight. BMJ 2001;323:1258.)

(Anm: Sponsing av journalistikk (mintankesmie.no).)

(Anm: Journalists: anything to declare? (Journalister: noe å deklarere?) BMJ 2007;335:480 (8 September).)

- Amerikanske selskaper hyret inn pr-firmaer for å drive opp interessen for en aksje – og fikk deretter skribenter til å skrive om aksjen på populære businessblogger. Nå setter det amerikanske finans- og kredittilsynet SEC ned foten. (- Betalte for positive aksjeartikler for å lure investorer – får smekk av myndighetene.)

(Anm: Betalte for positive aksjeartikler for å lure investorer – får smekk av myndighetene. Amerikanske selskaper hyret inn pr-firmaer for å drive opp interessen for en aksje – og fikk deretter skribenter til å skrive om aksjen på populære businessblogger. Nå setter det amerikanske finans- og kredittilsynet SEC ned foten. Hvis et selskap betaler noen for å publisere eller gjøre tilgjengelig artikler om dets aksje, må det gi beskjed til offentligheten og investorer. Disse selskapene, promotørene og skribentene har angivelig villedet investorer ved å skjule betalte kampanjer som objektive og uavhengige analyser, sier direktør Stephanie Avakian i det amerikanske finanstilsynet SEC i en pressemelding. Ifølge finanstilsynet har det siktet 27 individer og mindre selskaper for å ha betalt for skjult reklame, som deretter er blitt publisert på businessmedier- og blogger som Forbes, Seeking Alpha, Yahoo Finance, Benzinga, TheStreet og The MotleyFool, ifølge CNN. Artiklene skal ha vært svært positive til aksjene som er involvert. (dn.no 11.4.2017).)

- Säkerheten i vården bör fokusera på prevention. Lär av flyget, kärnkraftverken och offshoreindustrin! I jämförelse med hur flyg-, kärnkrafts- och offshore-industrin hanterar och analyserar sina risker ligger den svenska sjukvården långt efter.

(Anm: Säkerheten i vården bör fokusera på prevention. Lär av flyget, kärnkraftverken och offshoreindustrin! I jämförelse med hur flyg-, kärnkrafts- och offshore-industrin hanterar och analyserar sina risker ligger den svenska sjukvården långt efter. (…) Studier som belyser omfattningen av medicinska misstag i Sverige saknas; däremot visar ett flertal internationella studier att problemet är omfattande [24]. (Läkartidningen 1999;96:3068-73).)

(Anm: Hjernen (mintankesmie.no).)

(Anm: Helsekostnader, forsikringer, forskning og budsjetter (mintankesmie.no).)

(Anm: Mitochondria (mitokondrie) (mitokondriesykdommer) (mitokondrielle sykdommer). (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Signaler fra tarmens mikrobiotika til fjerntliggende organer mht. fysiologi og sykdom. Signals from the gut microbiota to distant organs in physiology and disease. (Nat Med. 2016 Oct 6;22(10):1079-1089.)

- "Jeg ble instruert å selge OxyContin": En legemiddelkonsulent hos Purdue Pharma forteller om hvordan han ble betalt for å pushe opioider. (- Da Sean Thatcher var salgsrepresentant hos Purdue Pharma, som produserer OxyContin, klaget ofte leger han besøkte over at pasientene deres utviklet toleranse mot smertestillende opioider. Thatcher, som arbeidet for firmaet mellom 2009 og 2015 i Montana ble bedt om å fortelle de forskrivende leger at dosene skulle økes, og å presisere at avhengighet ikke er det samme som toleranse eller "pseudoavhengighet".) (- Han fikk en bonus basert på antall opioidresepter som legene han besøkte forskrev, hvor høyere salg av OxyContin utløste spesielt store bonuser.)

(Anm: “I Was Directed to Market OxyContin”: A Purdue Pharma Rep Tells How He Was Paid to Push Opioids. When Sean Thatcher was a sales rep at Purdue Pharma, which makes OxyContin, doctors he visited often complained that their patients were developing tolerance to the opioid painkiller. Thatcher, who worked for the company between 2009 and 2015 in Montana, was instructed to tell the prescribers to increase the dose, and to clarify that addiction isn’t the same as tolerance, or “pseudoaddiction.” He received a bonus based on the number of opioid prescriptions written by the physicians he visited, with higher sales of OxyContin in particular garnering bigger bonuses. (motherjones.com 6.5.2018).)

(Anm: Legemiddelkonsulenter (sales representatives) (mintankesmie.no).)

(Anm: Legemiddelkonsulenter forteller leger lite om sideeffekter, ifølge studie. (Drug Reps Tell Docs Little of Side Effects: Survey) (Journal of General Internal Medicine 2013 (April).)

– Telomer dysfunksjon forstyrrer makrofagmitokondriell metabolisme og NLRP3 inflammasjon gjennom PGC-1a / TNFAIP3-aksen.) (- Samlet viser studien et regulatorisk paradigme som forbinder telomerer med mitokondriell metabolisme, medfødt immunitet og betennelse, og belyser aldersrelaterte patologier (sykdommer).)

(Anm: Telomere Dysfunction Disturbs Macrophage Mitochondrial Metabolism and the NLRP3 Inflammasome through the PGC-1α/TNFAIP3 Axis. Abstract Immune and inflammation dysregulation have been associated with the aging process and contribute to age-related disorders, but the underlying mechanism remains elusive. Here, we employed late-generation Terc knockout (Terc-/-) mice to investigate the impact of telomere dysfunction on the host defense and function of innate immune cells. Terc-/- mice displayed exaggerated lung inflammation and increased mortality upon respiratory staphylococcal infection, although their pathogen-clearing capacity was uncompromised. Mechanistically, we found that telomere dysfunction caused macrophage mitochondrial abnormality, oxidative stress, and hyperactivation of the NLRP3 inflammasome. The ubiquitin-editing enzyme TNFAIP3, together with PGC-1α, was critically involved in the regulation of mitochondrial and inflammatory gene expression and essential for the homeostatic role of telomeres. Together, the study reveals a regulatory paradigm that connects telomeres to mitochondrial metabolism, innate immunity, and inflammation, shedding light on age-related pathologies. Together, the study reveals a regulatory paradigm that connects telomeres to mitochondrial metabolism, innate immunity, and inflammation, shedding light on age-related pathologies. Cell Rep. 2018 Mar 27;22(13):3493-3506.)

(Anm: Telomere length predicts cardiovascular disease. BMJ 2014;349:g4373 (08 July 2014).)

(Anm: Telomer, struktur i hver ende av kromosomet i eukaryote celler. Telomeren inneholder en repetert DNA-sekvens og er nødvendig for å stabilisere kromosomet og beskytte mot uregelmessig rekombinasjon. Hos mennesket og andre vertebrater består den repeterte enheten av basene TTAGGG (T = thymin, A = adenin, G = guanin). Den er repetert ca. 2500 ganger, som tilsvarer en lengde på ca. 15 000 basepar. Kilde: Store norske leksikon.)

(Anm: Linking telomere loss and mitochondrial dysfunction in chronic disease. (…) Drawing a mechanistic connection between telomere function and mitochondria biology will provide a broader perspective for understanding the pathophysiology of diseases and their relation to the aging process, and may provide opportunities for new possible treatments. Front Biosci (Landmark Ed). 2017 Jan 1;22:117-127.)

- Dette er første gang at en undersøkelse viser at mitokondrier er nødvendige for cellulær aldring. (- Mitokondrier får nerver til å gro.)

Eradicating mitochondria from cells may reverse aging
medicalnewstoday.com 5.2.2016
For første gang har forskere vist at mitokondriene - cellenes "kraftstasjoner" - er avgjørende for aldring, dette etter å ha påvist at fjerning av mitokondrier fra menneskelige celler reduserte nivåer av markører for cellulær aldring, hvilket trigger en prosess med foryngelse. (For the first time, scientists have shown that mitochondria - the "powerhouses" of cells - are crucial for aging, after finding that removing mitochondria from human cells reduced levels of markers for cellular aging, triggering a process of rejuvenation.)

Studieleder Dr. João Passos ved Institutt for Aging ved Newcastle University i Storbritannia og hans team uttalte at resultatene baner vei for nye strategier for å reversere aldringsprosessen. (Study leader Dr. João Passos, of the Institute for Aging at Newcastle University in the UK, and his team say their findings pave the way for new strategies to reverse the aging process.)

Resultatene er publisert i The Embo Journal. (They publish their findings in The Embo Journal.)

(Anm: What is a cell? (medicalnewstoday.com 8.2.2018).)

(Anm: What are mitochondria? (medicalnewstoday.com 8.2.2018).)

(Anm: Mitochondria: back to the future. Nature Reviews Molecular Cell Biology 19, 76 (2018).)

- SIRT3-deregulering er linket til mitokondriell dysfunksjon ved Alzheimers sykdom.

(Anm: SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer's disease. Summary Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. (…) Our results indicate that SIRT3 dysfunction leads to p53‐mediated mitochondrial and neuronal damage in AD. Therapeutic modulation of SIRT3 activity may ameliorate mitochondrial pathology and neurodegeneration in AD. Aging Cell. 2018 Feb; 17(1): e12679.)

(Anm: Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise, and Metabolic and Excitatory Challenges. Cell Metab. 2016 Jan 12; 23(1): 128–142.)

(Anm: Sirt3 protects mitochondrial DNA damage and blocks the development of doxorubicin-induced cardiomyopathy in mice. Abstract Doxorubicin (Doxo) is a chemotherapeutic drug widely used to treat variety of cancers. (…) In summary, our results described here demonstrate that Doxo toxicity to the heart is associated with reduced SIRT3 levels and mtDNA damage. Because SIRT3 levels are also reduced with aging of humans, it is tempting to believe that the delayed toxicity of this drug therapy could be partly linked with reduced cardiac SIRT3 levels with age. Therefore, strategies targeted to maintain mitochondrial SIRT3 levels should be able to protect to the heart from Doxo-meditated toxicity. Am J Physiol Heart Circ Physiol. 2016 Apr 15; 310(8): H962–H972.)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

- Supplement av koenzym Q-10 ved aldring og sykdom.

(Anm: Coenzyme Q10 Supplementation in Aging and Disease. There is a need for further studies and clinical trials involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in metabolic syndrome and diabetes, neurodegenerative disorders, kidney diseases, and human fertility. Front Physiol. 2018 Feb 5;9:44.)

(Anm: Zinc improves mitochondrial respiratory function and prevents mitochondrial ROS generation at reperfusion by phosphorylating STAT3 at Ser727. (…) The preservation of ND6 mtDNA and the inhibition of SDH activity may account for the role of STAT3 in the beneficial action of zinc on the mitochondrial oxidative phosphorylation and ROS generation at reperfusion. J Mol Cell Cardiol. 2018 Mar 29. pii: S0022-2828(18)30091-9.)

(Anm: Diabetes (mintankesmie.no).)

(Anm: Diabetes øker risikoen for å dø av noen kreftformer (dagensmedisin.no 3.10.2013).)

- Mitokondriell dysfunksjon ved diabetisk nevropati kan være involvert i utviklingen av nevropatisk smerte via en reduksjon i nevrosteroidsyntese.

(Anm: Mitochondrial dysfunction in diabetic neuropathy may be involved in the development of neuropathic pain via a reduction in neurosteroid synthesis. Abstract Background: Recent work in a model of diabetic neuropathy revealed that layer 2/3 cortical pyramidal neurones of the pain pathway exhibited reduced endogenous neurosteroid modulation of the GABA AR and exogenously applied neurosteroids had an exaggerated impact. It is postulated that this is related to reduced precursor synthesis, due to mitochondrial dysfunction in diabetic neuropathy. Benzodiazepines are also known to activate neurosteroidogenesis by binding to mitochondrial translocator protein (TSPO). This study explored the differential effect of diazepam on GABA AR modulation via neurosteroidogenesis in diabetic and wild type (WT) mice. Conclusions: The exaggerated effect of diazepam on GABAergic inhibitory tone in the ob/ob, despite the presence of the GABA AR benzodiazepine antagonist flumazenil is likely observed due to physiological upregulation of key neurosteroidogenic enzymes in response to the reduced pregnenolone synthesis by the mitochondria. By increasing pregnenolone via TSPO activation, it is possible to promote enhanced neurosteroidogenesis and increase GABAergic inhibitory tone via an alternate route. In diabetic neuropathic pain, mitochondrial dysfunction may play an important role. Enhancing the GABAergic neurosteroid tone could be of potential therapeutic benefit. F1000Res. 2017 Apr 18;6:506.)

(Anm: Antidepressiva og antipsykotika gir økt risiko for diabetes hos barn og voksne (50 til 700 %) (mintankesmie.no).)

(Anm: Risk of fetal death is increased in pregnant women with pre-existing diabetes - Pre-existing maternal diabetes more than quadrupled the risk of fetal death OBG Manag. 2014 February;26(2).)

- Sudden adult death syndrome (SADS) ved m.3243A> G-relatert mitokondriell sykdom: en ukjent klinisk realitet hos unge, asymptomatiske voksne.

(Anm: Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults. Abstract AIMS: To provide insight into the mechanism of sudden adult death syndrome (SADS) and to give new clinical guidelines for the cardiac management of patients with the most common mitochondrial DNA mutation, m.3243A>G. These studies were initiated after two young, asymptomatic adults harbouring the m.3243A>G mutation died suddenly and unexpectedly. The m.3243A>G mutation is present in ∼1 in 400 of the population, although the recognized incidence of mitochondrial DNA (mtDNA) disease is ∼1 in 5000. CONCLUSION: Our findings suggest that SADS is an important cause of death in patients with m.3243A>G and likely to be due to widespread respiratory chain deficiency in cardiac muscle. The involvement of asymptomatic relatives highlights the importance of family tracing in patients with m.3243A>G and the need for specific cardiac arrhythmia surveillance in the management of this common genetic disease. In addition, these findings have prompted the derivation of cardiac guidelines specific to patients with m.3243A>G-related mitochondrial disease. Finally, due to the prevalence of this mtDNA point mutation, we recommend inclusion of testing for m.3243A>G mutations in the genetic autopsy of all unexplained cases of SADS. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology. Eur Heart J. 2016 Aug 21;37(32):2552-9.)

(Anm: Information for the family and relatives of a young person who has died of Sudden Arrhythmic Death Syndrome – SADS sometimes called sudden adult death syndrome. (sads.org.uk).)

- Mitokondrielt DNA-innhold: En ny biomarkør for plutselig intrauterint uforklarlig dødssyndrom (SIUDS).

(Anm: Mitochondrial DNA content: A new biomarker for sudden intrauterine unexplained death syndrome (SIUDS). Abstract In literature there are no data related to mitochondrial DNA (mtDNA) content in sudden intrauterine unexplained death syndrome (SIUDS). To test the hypothesis that a quantitative excess of mtDNA could play a role in the pathogenesis of SIUDS, mtDNA content was measured in cerebral cortex of 9 SIUDS and in 7 controls. The median (interquartile range) mtDNA in SIUDS and controls was 14,000 (8600-33,500), 3400 (0-8500) copies per nuclear DNA, respectively (p=0.007). If mitochondria are involved in SIUDS, then higher mitochondrial DNA content may be a biomarker of this syndrome. Mitochondrion. 2018 May;40:13-15.)

- Hvorfor plantevernmidler (pesticider) kan forårsake Parkinsons sykdom hos noen mennesker. Ny forskning avslører hvordan pesticidene paraquat og maneb endrer genuttrykk og kan føre til Parkinsons sykdom hos mennesker som er genetisk utsatt for sykdommen.

(Anm: Hvorfor plantevernmidler kan forårsake Parkinsons sykdom hos noen mennesker. Ny forskning avslører hvordan pesticider (plantevernmidler) paraquat og maneb endrer genuttrykk og kan føre til Parkinsons sykdom hos mennesker som er genetisk utsatt for sykdommen. (Why pesticides may cause Parkinson's in some people. New research reveals how the pesticides paraquat and maneb alter gene expression and may lead to Parkinson's disease in people who are genetically predisposed to the illness. (…) The National Institutes of Health (NIH) note that environmental exposure to pesticides, for example, might increase the risk of developing Parkinson's. Senior study author Scott Ryan, a professor of molecular and cellular biology at U of G, explains the motivation behind the research. He notes, "People exposed to these chemicals are at about a 250 percent higher risk of developing Parkinson's disease than the rest of the population." "We wanted to investigate what is happening in this susceptible population that results in some people developing the disease," Prof. Ryan adds. The findings were published in the journal Federation of American Societies for Experimental Biology. (medicalnewstoday.com 24.5.2018).)

- Parkinsons: Kan denne "missing link" være en årsak? Misdannelser i mitokondrier finnes ofte i Parkinsons sykdom.)

(Anm: Parkinson's: Could this 'missing link' be a cause? (…) A paper that is now published in the journal Cell Metabolism describes how the team — at Baylor College of Medicine in Houston, TX — made the unexpected discovery in a fruit fly model of a faulty gene condition with Parkinson's-like symptoms. (…) They also found several other abnormalities, including malformed mitochondria and abnormally large lysosomes. Mitochondria are compartments inside cells that make energy for the cell. Abnormalities in mitochondria are often found in Parkinson's disease. (medicalnewstoday.com 15.6.2018).)

- Nitrering av mikrotubuli blokkerer aksonal mitokondriell transport i en menneskelig pluripotent stamcellemodell ved Parkinsons sykdom. (- Abstrakt. Nevuronalt tap ved Parkinsons sykdom (PD) er assosiert med avvikende mitokondriell funksjon hos dopaminergiske (DA) nevroner av substantia nigra pars compacta.)

http://www.mintankesmie.no/miljo_og_helse.php#blokkerer_aksonal_mitokondriell_transport

(Anm: Nitrering av mikrotubuli blokkerer aksonal mitokondriell transport i menneskers pluripotent stamcellemodell ved Parkinsons sykdom. Abstrakt. Nevuronalt tap ved Parkinsons sykdom (PD) er assosiert med avvikende mitokondriell funksjon i dopaminergiske (DA) nevroner av substantia nigra pars compacta. FASEB J. 2018 Apr 24:fj201700759RR.)

(Anm: Mikrotubulus, flertall mikrotubuli, lang, rørformet struktur i cellen, bygd opp av globulære proteiner (tubuliner) som ligger etter hverandre i lange tråder kalt protofilamenter. Tretten protofilamenter danner til sammen en mikrotubulus. Mikrotubulus utgjør en viktig del av celleskjelettet (se cellen). Ulike proteiner assosiert med mikrotubulus bidrar til å regulere oppbyggingen og nedbrytingen av mikrotubulus.  Kilde: Store norske leksikon.)

(Anm: Mitochondria (mitokondrie) (mitokondriesykdommer) (mitokondrielle sykdommer). (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

- Nevrokjemiske endringer i plutselige uforklarlige perinatal dødsfall - en gjennomgang.

(Anm: Neurochemical Alterations in Sudden Unexplained Perinatal Deaths-A Review. Abstract Sudden unexpected perinatal collapse is a major trauma for the parents of victims. Sudden infant death syndrome (SIDS) is unexpected and mysterious death of an apparently healthy neonate from birth till 1 year of age without any known causes, even after thorough postmortem investigations. However, the incidence of sudden intrauterine unexplained death syndrome (SIUDS) is seven times higher as compared with SIDS. This observation is approximated 40-80%. Stillbirth is defined as death of a fetus after 20th week of gestation or just before delivery at full term without a known reason. Pakistan has the highest burden of stillbirth in the world. This basis of SIDS, SIUDS, and stillbirths eludes specialists. The purpose of this study is to investigate factors behind failure in control of these unexplained deaths and how research may go ahead with improved prospects. Animal models and physiological data demonstrate that sleep, arousal, and cardiorespiratory malfunctioning are abnormal mechanisms in SIUDS risk factors or in newborn children who subsequently die from SIDS. This review focuses on insights in neuropathology and mechanisms of SIDS and SIUDS in terms of different receptors involved in this major perinatal demise. Several studies conducted in the past decade have confirmed neuropathological and neurochemical anomalies related to serotonin transporter, substance P, acetylcholine α7 nicotine receptors, etc., in sudden unexplained fetal and infant deaths. There is need to focus more on research in this area to unveil the major curtain to neuroprotection by underlying mechanisms leading to such deaths. Front Pediatr. 2018 Jan 25;6:6.)

- Høyt nivå av serotonin i blodvæske (serum) ved krybbedød (Sudden Infant Death Syndrome – SIDS).

(Anm: Høyt nivå av serotonin i blodvæske (serum) ved krybbedød (Sudden Infant Death Syndrome – SIDS). High serum serotonin in sudden infant death syndrome. Proc Natl Acad Sci U S A. 2017 Jul 3. pii: 201617374. [Epub ahead of print].)

(Anm: Serotonin i hjerne og blod (mintankesmie.no).)

(Anm: Serotonin syndrom (SS), kramper, parkinsonisme osv. (forhøyet kroppstemperatur) (mintankesmie.no).)

- Mitokondrielle bidrag til nevronal utvikling og funksjon. (- I denne artikkelen diskuterer vi de nyeste funnene som er relevante for involvering av mitokondrier i nevronal utvikling, med vekt på mitokondriell metabolisme og dynamikk.)

(Anm: Mitochondrial contributions to neuronal development and function. Abstract Mitochondria are critical to tissues and organs characterized by high-energy demands, such as the nervous system. They provide essential energy and metabolites, and maintain Ca2+ balance, which is imperative for proper neuronal function and development. Emerging findings further underline the role of mitochondria in neurons. Technical advances in the last decades made it possible to investigate key mechanisms in neuronal development and the contribution of mitochondria therein. In this article, we discuss the latest findings relevant to the involvement of mitochondria in neuronal development, placing emphasis on mitochondrial metabolism and dynamics. In addition, we survey the role of mitochondrial energy metabolism and Ca2+ homeostasis in proper neuronal function, and the involvement of mitochondria in axon myelination. Biol Chem. 2017 Dec 20.)

- Er glaukom en mitokondriell neurodegenerativ sykdom.

(Anm: Er glaukom en mitokondriell neurodegenerativ sykdom. [Is glaucoma a mitochondrial neurodegenerative disease]. Abstract. The retinal ganglion cell, due to peculiar structural and energetic constraints, appears acutely susceptible to mitochondrial dysfunction. Emerging evidence suggests that changes in the mitochondrial DNA(mtDNA)and in nuclear DNA genes that encode mitochondrial proteins may influence mitochondrial structure and function and, therefore, contribute to the pathogenesis of primary open angle glaucoma. As the main glaucoma risk factors are elevated intraocular pressure and older age, we discuss their relationship with mitochondrial dysfunction. If the contribution of mitochondrial dysfunction to glaucoma pathogenesis is further established, emerging therapies aiming to optimize mitochondrial function represent potential clinical treatments. (Chin J Ophthalmol, 2016, 52: 714-717).  Zhonghua Yan Ke Za Zhi. 2016 Sep 11;52(9):714-7.)

(Anm: Antidepressiva (øyesykdommer). (mintankesmie.no).)

(Anm: Øyesykdommer (øyner er sjelens vindu). (mintankesmie.no).)

- Mitochondrial Evolution: Going, Going, Gone.

(Anm: Mitochondrial Evolution: Going, Going, Gone. Abstract Monocercomonoides is the first example of a eukaryote lacking even the most reduced form of a mitochondrion-related organelle. This has important implications for cellular processes and our understanding of reductive mitochondrial evolution across the eukaryotic tree of life. Curr Biol. 2016 May 23;26(10):R410-2.)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: RE: Studier som stikkes under stol Minileder (...) Studiens «darwinistiske» toksisitetstest viser at legemidlet paroxetine (Seroxat, Paxil etc.) i dyreforsøk forårsaker bl.a. endokrine forstyrrelser, vedvarende svekket helse, økt dødelighet etc. Tidsskr Nor Legeforen 2015; 135:617 (25.5.2015).)

- Studie: Forsøg med ny medicin godkendes ofte på mangelfuldt grundlag. Prækliniske forsøg har ofte ikke undersøgt nye lægemidlers effekt tilstrækkeligt, og de betyder, at regulatoriske myndigheder tillader forsøg med mennesker på et uoplyst grundlag, konkluderer ny forskning.

(Anm: - Studie: Forsøg med ny medicin godkendes ofte på mangelfuldt grundlag. Prækliniske forsøg har ofte ikke undersøgt nye lægemidlers effekt tilstrækkeligt, og de betyder, at regulatoriske myndigheder tillader forsøg med mennesker på et uoplyst grundlag, konkluderer ny forskning. (- I stedet skeler regulatoriske myndigheder oftere til data for sikkerhed og toksitisitet end effekt, siger han. "Det stoler mere eller mindre på, at pengemændene bag det kliniske forsøg, industrien og investigatorerne, aldrig ville udføre kliniske forsøg, med mindre de var overbeviste om midlernes effektivitet," siger han. (medwatch.dk 9.4.2018).)

- Den nye studien kan bidra til å forklare hvorfor så mange oppmuntrende resultater i dyreforsøk ikke holder mål i studier på mennesker. (- "Dette er utrolig alarmerende," sier Shai Silberberg, direktør for forskningskvalitet ved National Institute of Neurological Disorders and Stroke i Bethesda, Maryland, som ikke var involvert i studien. Studien viser at beslutningstakere for etikk knyttet til kliniske forsøk ikke får den informasjonen de virkelig trenger for å evaluere disse prekliniske forsøkene.")

(Anm: Den nye studien kan bidra til å forklare hvorfor så mange oppmuntrende resultater i dyreforsøk ikke holder mål i studier på mennesker. (The new study may help explain why so many encouraging results in animal studies don't hold up in human trials.) "Dette er utrolig alarmerende," sier Shai Silberberg, direktør for forskningskvalitet ved National Institute of Neurological Disorders and Stroke i Bethesda, Maryland, som ikke var involvert i studien. Studien viser at beslutningstakere for etikk knyttet til kliniske forsøk ikke får den informasjonen de virkelig trenger for å evaluere disse prekliniske forsøkene.") Studien viser at beslutningstakere for etikk knyttet til kliniske forsøk ikke får den informasjonen de virkelig trenger for å evaluere disse prekliniske forsøkene." (Science - Apr. 5, 2018).)

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

(Anm: Effekten av psykostimulerende legemidler på blod-hjerne barrierens funksjon og nevroinflammasjon. (The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation) (Front. Pharmacol. 2012;3:121 (Published online: 29 June 2012).)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Antipsykotika (psykofarmaka etc.) (mintankesmie.no).)

(Anm: Antipsykotika forårsaker ansiktsgrimasering og andre typer mulige varige hjerneskader (mintankesmie.no).)

- Harvard forskere sier at de har "reversert" et tegn på aldring hos mus: Studie.

(Anm: Harvard researchers say they have 'reversed' a sign of aging in mice: Study. - Researchers writing in the journal Cell say they have identified a gene in mice that is associated with the growth of new blood vessels, potentially allowing for the reversal of one sign of aging, reported ABC News. - In the study, researchers identified a chemical compound that could indirectly stimulate the gene. The chemical was given to a group of 18-month-old mice, the approximate equivalent of a 70-year-old human, in their drinking water for a period of two months. (…) The authors noted that the chemical had no effect on younger sedentary mice, suggesting that its effect is unique to the process of aging, rather than boosting health generally. (firstwordpharma.com 28.3.2018).)

- Studie antyder metode for å øke veksten av blodkar og muskler. Aktivering av proteiner knyttet til levetid kan bidra til å øke utholdenheten og bekjempe svakhet hos eldre. Etter hvert som vi blir eldre, reduseres utholdenheten, delvis fordi våre blodårer mister noe av deres evne til å levere oksygen og næringsstoffer til muskelvev.

(Anm: Study suggests method to boost growth of blood vessels and muscle. Activating proteins linked to longevity may help to increase endurance and combat frailty in the elderly. As we get older, our endurance declines, in part because our blood vessels lose some of their capacity to deliver oxygen and nutrients to muscle tissue. An MIT-led research team has now found that it can reverse this age-related endurance loss in mice by treating them with a compound that promotes new blood vessel growth. (…) Benefits of exercise The researchers also found that SIRT1 activity in endothelial cells is critical for the beneficial effects of exercise in young mice. In mice, exercise generally stimulates growth of new blood vessels and boosts muscle mass. However, when the researchers knocked out SIRT1 in endothelial cells of 10-month-old mice, then put them on a four-week treadmill running program, they found that the exercise did not produce the same gains seen in normal 10-month-old mice on the same training plan. If validated in humans, the findings would suggest that boosting sirtuin levels may help older people retain their muscle mass with exercise, Guarente says. Studies in humans have shown that age-related muscle loss can be partially staved off with exercise, especially weight training. "What this paper would suggest is that you may actually be able to rescue muscle mass in an aging population by this kind of intervention with an NAD precursor," Guarente says. In 2014, Guarente started a company called Elysium Health, which sells a dietary supplement containing a different precursor of NAD, known as NR, as well as a compound called pterostilbene, which is an activator of SIRT1. (sciencedaily.com 22.3.2018).)

(Anm: Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging. Abstract A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly. Cell. 2018 Mar 22;173(1):74-89.e20.)

 (Anm: Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice. Cell Metab. 2018 Mar 6;27(3):667-676.e4.)

- Mitokondrier som mål for å motvirke aldersrelatert celledysfunksjon. (- Videre er mitokondriell funksjon sterkt knyttet til mitokondriell Ca2 + homeostase og mitokondriell form, som gjennomgår ulike endringer under aldring. Siden mitokondrier spiller en så viktig rolle i en organismes aldringsprosess gir de også lovende mål for manipulering av senescente cellefunksjoner.)

(Anm: Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction. Abstract Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS) ensures a supply of adenosine triphosphate (ATP), but is also the main source of potentially harmful levels of reactive oxygen species (ROS). Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism's process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR) or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria's role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction. Genes (Basel). 2018 Mar 16;9(3). pii: E165.)

- Fjerning av senescente celler fra ledd kan reversere progresjon av osteoartritt (betennelse i ledd og tilgrensende knokkel).

(Anm: Removing senescent cells from joints could reverse progression of osteoarthritis. In a preclinical study in mice and human cells, researchers report that selectively removing old or 'senescent' cells from joints could stop and even reverse the progression of osteoarthritis. The findings, published April 24 in Nature Medicine, support growing evidence that senescent cells contribute to age-related diseases and demonstrate that using drug therapies to remove them from the joint not only reduces the development of post-traumatic osteoarthritis but creates an environment for new cartilage to grow and repair joints. (news-medical.net 2.5.2017).)

(Anm: Mitochondrial peptides modulate mitochondrial function during cellular senescence. Abstract Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). Mitochondria play crucial roles in energy production and cellular signaling, but the key features of mitochondrial physiology and particularly of mitochondria-derived peptides (MDPs), remain underexplored in senescence responses. (…) Targeting metabolism in senescence cells is an important strategy to reduce SASP production for eliminating the deleterious effects of senescence. These results provide insight into the role of MDPs in mitochondrial energetics and the production of SASP components by senescent cells. Aging (Albany NY). 2018 Jun 10.)

- Mitochondrier regulerer sammentrekninger av hjerte gjennom ATP-avhengige mekanismer.

(Anm: Mitochondria regulate cardiac contraction through ATP-dependent and ATP-independent mechanisms. Abstract The multipurpose organelle mitochondria play an essential role(s) in controlling cardiac muscle contraction. Mitochondria, not only function as the powerhouses and the energy source of myocytes, but also modulate intracellular Ca2+ homeostasis, the production of intermediary metabolites/reactive oxygen species (ROS), and other cellular processes. Those molecular events can substantially influence myocardial contraction. Mitochondrial dysfunction is usually associated with cardiac remodeling, and is the causal factor of heart contraction defects in many cases. The manipulation of mitochondria or mitochondria-relevant pathways appears to be a promising therapeutic approach to treat the diseases. Free Radic Res. 2018 Mar 16:1-221.)

(Anm: Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt. (The role of mitochondrial dysfunction in sepsis-induced multi-organ failure). (Virulence. 2013 Nov 1;5(1).)

(Anm: Senescence (/sɪˈnɛsəns/) or biological aging (also spelled biological ageing) is the gradual deterioration of function characteristic of most complex lifeforms, arguably found in all biological kingdoms, that on the level of the organism increases mortality after maturation. (en.wikipedia.org).)

- Dette er forskernes supermodeller. (- Det som gjelder for bakterien E. coli, gjelder for en elefant.) (- Fisk har også blitt benyttet i medisinsk forskning, særlig sebrafisk (Danio rerio), en tropisk fisk som i Norge bare finnes i akvarier.)

(Anm: Dette er forskernes supermodeller. Erik Boye, professor emeritus og Tor Erik Rusten, førsteamanuensis. Det meste vi vet om biologi og medisin kommer fra eksperimenter med enkle organismer, fra virus og gjær til mus. Av 103 nobelpriser i fysiologi eller medisin har 96 blitt gitt til arbeid med modellorganismer. (…) De grunnleggende mekanismene som holder celler i live, altså hvordan de fungerer og hvordan de kommuniserer, er overraskende like i alle organismer. Dette var grunnen til at en annen nobelprisvinner i fysiologi eller medisin (1965), Jacques Monod, kom med den friske uttalelsen om tarmbakterier og elefanter: «Det som gjelder for bakterien E. coli, gjelder for en elefant». (…) Sjødyr Fisk har også blitt benyttet i medisinsk forskning, særlig sebrafisk (Danio rerio), en tropisk fisk som i Norge bare finnes i akvarier. I likhet med C. elegans er den gjennomsiktig, noe som gjør at fenomener lettere kan observeres fra utsiden, og man kan benytte lysende molekyler og følge deres bevegelser og plassering. (…) Alger og frosk I tillegg til organismene vi har nevnt over, råder forskeren over et arsenal av andre modellorganismer. For eksempel mange forskjellige bakterier, alger og sopper, en rekke planter, samt et spekter av dyr som frosk og gnagere – og celler fra mennesker. (aftenposten.no 1.1.2018).)

(Anm: Hjernen (mintankesmie.no).)

- E. coli-toksin (giftstoff) linket til inflammatorisk tarmsykdom.

(Anm: E. coli-toksin (giftstoff) linket til inflammatorisk tarmsykdom. (E. coli toxin linked with inflammatory bowel disease.) Ny forskning tyder på at et toksin produsert av bakterien E. coli kan være det som utløser betennelse ved inflammatorisk tarmsykdom. (- Forskerne fant at microcin B17 faktisk induserer tarmbetennelse in vivo. Denne betennelsen var avhengig av CD1d-proteiner. CD1d-proteiner er molekyler som "formidler presentasjonen av primært lipid- og glykolipidantigener" til T-celler - en type hvite blodlegemer som spiller en nøkkelrolle ved immunitet. Prof. Maxwell forklarer funnene videre og sier "bakteriene som bor i oss har stor innvirkning på velvære." (medicalnewstoday.com 19.5.2018).)

Hvordan påvirker endringer i mtDNA og mitokondriell dysfunksjon kreft- og kreftbehandling?

(Anm: Hvordan påvirker endringer i mtDNA og mitokondriell dysfunksjon kreft- og kreftbehandling? (How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy?) Utfordringer, muligheter og modeller. Abstrakt Flere mutasjoner i nukleære gener som koder for mitokondriske komponenter har blitt assosiert med en økt kreftrisiko eller er selv forårsakende, f.eks. succinat dehydrogenase (SDHB, SDHC og SDHD gener) og iso-citrat dehydrogenase (IDH1 og IDH2 gener). Nylig har studier antydet en fremtredende rolle for mitokondrielle DNA (mtDNA) mutasjoner i utviklingen av et bredt utvalg av kreftformer. Forskjellige studier assosiert med mtDNA abnormiteter, inkludert mutasjoner, slettinger, inversjoner og kopinummerendringer, med mitokondriell dysfunksjon. Mutat Res Rev Mutat Res. 2015 Apr-Jun;764:16-30.)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: The Role of Mitochondrial H+-ATP Synthase in Cancer. (…) Concluding Remarks Reprogramming cellular metabolism is a hallmark of cancer that is necessary to fulfill the metabolic demands imposed by the oncogenic process. In this context, the mitochondrial H+-ATP synthase is a main hub in rewiring energy metabolism and in retrograde signaling to the nucleus programs required for cancer progression. Front. Oncol., 07 March 2018.)

- Det er betydelig bevis som støtter hypotesen om at mitokondriell dysfunksjon er knyttet til nevropsykiatriske lidelser.

(Anm: Det er betydelig bevis som støtter hypotesen om at mitokondriell dysfunksjon er knyttet til nevropsykiatriske lidelser. (There is considerable evidence supporting the hypothesis that mitochondrial dysfunction is associated with neuropsychiatric disorders.) Hjernen utgjør bare 2 % til 3 % av kroppsvekten, men bruker 20 % av vår mitokondrielle energi målt i oksygenforbruk. Derfor, ettersom systemisk mitokondriell energimetabolisme avtar, er hjernen det første organet som får begrenset tilgang til energi, og dropper under dens bioenergetiske terskel hvilket resulterer i nevrologiske symptomer. (The brain is only 2% to 3% of our body’s weight but expends 20% of our mitochondrial energy, as measured by oxygen consumption. Therefore, as systemic mitochondrial energy metabolism declines, the brain is the first organ to become limited for energy, dropping below its bioenergetic threshold and resulting in neurological symptoms.) JAMA Psychiatry  2017 (Published online June 14, 2017).)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

– Mitokondriell dysfunksjon: maternal proteinrestriksjon som utløser av forskjellig reaktive overproduksjoner og energisvikt i hjernestamme i mannlig avkoms hjernestamme.  

(Anm: Mitochondrial dysfunction: maternal protein restriction as a trigger of reactive species overproduction and brainstem energy failure in male offspring brainstem. Abstract Mitochondria are important organelles in eukaryotic organisms, wherein their capacity to produce energy vary among the tissues depending upon the amounts of oxygen consumed. Part of the oxygen consumed during ATP generation produces reactive oxygen species, which if not efficiently removed can trigger a systemic damage to molecular compounds characterized as oxidative stress. Several studies have demonstrated that mitochondrial dysfunction and oxidative stress in the central nervous system (CNS) are related to a plethora of neural disorders. Herein, we hypothesize that a late autonomic imbalance-induced hypertension might be related to long-lasting effects of protein restriction during the critical period of the CNS development on the mitochondrial function and oxidative stress in the brainstem of adult (i.e. 150 days of age) male Wistar rats. (…) Interestingly, the elevated activity of glutathione-S-transferase and the augmented expression of uncoupling protein 2 are likely protective mechanisms induced by lipid peroxidation products, being feasible molecular changes attempting to deal with oxidative stress-induced ageing. Nutr Neurosci. 2018 Mar 1:1-11.)

- Mitokondrielt DNA, mitokondriell dysfunksjon og hjertemanifestasjoner.

(Anm: Mitokondrielt DNA, mitokondriell dysfunksjon og hjertemanifestasjoner. Mitochondrial DNA, mitochondrial dysfunction, and cardiac manifestations. Abstract Mitochondria, the powerhouses of cells, have their own DNA (mtDNA). They regulate the transport of metabolites and ions, which determine cell physiology, survival, and death. Mitochondrial dysfunction, including impaired oxidative phosphorylation, preferentially affects heart function via imbalance of energy supply and demand. Recently, mitochondrial mutations and associated mitochondrial dysfunction were suggested as a causal factor of cardiac manifestations. Oxidative stress largely influences mtDNA stability due to oxidative modifications of mtDNA. (…) Here, we address the possible causes of mitochondrial DNA mutations and their involvement in cardiac manifestations. Current strategies for treatment related to mitochondrial mutations and/or dysfunction in cardiac manifestations are briefly discussed. Front Biosci (Landmark Ed). 2016 Jun 1;21:1410-26.)

(Anm: Mitochondrial dynamics regulate myocardial contractility and vice versa. Int J Cardiol. 2017 Nov 15;247:35.)

- Observasjonsstudie av nesten 9000 pasienter fant at de som ble foreskrevet antidepressiva ved utskrivning fra sykehus etter et hjerteinfarkt hadde 66 % større dødelighetsrisiko ett år senere enn pasienter som ikke ble foreskrevet legemidlene.

(Anm: Observasjonsstudie av nesten 9000 pasienter fant at de som ble foreskrevet antidepressiva ved utskrivning fra sykehus etter et hjerteinfarkt hadde 66 % større dødelighetsrisiko ett år senere enn pasienter som ikke ble foreskrevet legemidlene, selv om de bemerket at årsaken ikke nødvendigvis er relatert direkte til antidepressiva. (Heart attack patients prescribed antidepressants have lower survival rates.) (news-medical.net 5.3.2018).)

- Antidepressive medikamenter påvirker kroppens fettproduksjon. (- SREBP er meget viktig for å regulere produksjon både av kolesterol og av ulike fett-stoffer i kroppens celler. Kolesterol og andre fett-stoffer er viktig for at nevroner skal utvikle seg og fungere normalt, men har også en rolle i utviklingen av hjerte- og karsykdom.)

(Anm: Antidepressive medikamenter påvirker kroppens fettproduksjon. (...) På det molekylære planet tok Ræder i bruk cellestudier og moderne genteknologiske metoder for å vise at de store gruppene av psykiatriske medisiner (antipsykotika og antidepressiva, inkludert SSRI-medikamenter) virker på fettomsetningen i kroppen gjennom en transkripsjonsfaktor kalt SREBP (steroid reseptor-element bindende protein). SREBP er meget viktig for å regulere produksjon både av kolesterol og av ulike fett-stoffer i kroppens celler. Kolesterol og andre fett-stoffer er viktig for at nevroner skal utvikle seg og fungere normalt, men har også en rolle i utviklingen av hjerte- og karsykdom. (...) NY DOKTORGRAD (uib.no (23.9.2006).)

(Anm: Antidepressiva og antipsykotika gir økt risiko for diabetes hos barn og voksne (50 til 700 %) (mintankesmie.no).)

- Antidepressive medikamenter påvirker kroppens fettproduksjon. (- SREBP er meget viktig for å regulere produksjon både av kolesterol og av ulike fett-stoffer i kroppens celler. Kolesterol og andre fett-stoffer er viktig for at nevroner skal utvikle seg og fungere normalt, men har også en rolle i utviklingen av hjerte- og karsykdom.)

(Anm: Antidepressive medikamenter påvirker kroppens fettproduksjon. (...) På det molekylære planet tok Ræder i bruk cellestudier og moderne genteknologiske metoder for å vise at de store gruppene av psykiatriske medisiner (antipsykotika og antidepressiva, inkludert SSRI-medikamenter) virker på fettomsetningen i kroppen gjennom en transkripsjonsfaktor kalt SREBP (steroid reseptor-element bindende protein). SREBP er meget viktig for å regulere produksjon både av kolesterol og av ulike fett-stoffer i kroppens celler. Kolesterol og andre fett-stoffer er viktig for at nevroner skal utvikle seg og fungere normalt, men har også en rolle i utviklingen av hjerte- og karsykdom. (...) NY DOKTORGRAD (uib.no (23.9.2006).)

(Anm: Antidepressiva og antipsykotika gir økt risiko for diabetes hos barn og voksne (50 til 700 %) (mintankesmie.no).)

- Konklusjon Utbredt bruk av antidepressiva kan bidra til langvarig økt risiko for vektøkning på befolkningsnivå. Potensialet for vektøkning bør vurderes når behandling med antidepressiva er indikert.

(Anm: Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study. Abstract Objective To evaluate the long term association between antidepressant prescribing and body weight. (…) Conclusion Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated. BMJ 2018;361:k1951 (Published 23 May 2018).)

(Anm: Antidepressiva og antipsykotika gir økt risiko for diabetes hos barn og voksne (50 til 700 %) (mintankesmie.no).)

- Uheldig virkning av Seroxat/Paxil (paroxetine) på sædceller.

(Anm: Adverse effect of paroxetine on sperm. (…) Abstract OBJECTIVE: To assess the effects of a selective serotonin reuptake inhibitor on semen parameters. (…) CONCLUSION(S): In men with normal semen parameters, paroxetine induced abnormal sperm DNA fragmentation in a significant proportion of subjects, without a measurable effect on semen parameters. The fertility potential of a substantial number of men on paroxetine may be adversely affected by these changes in sperm DNA integrity. Fertil. Steril. 2010;94:1021–1026.)

(Anm: Seroxat (Paxil) (paroxetine; paroksetin) (SSRI) (mintankesmie.no).)

(Anm: Paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

(Anm: Antidepressant use during pregnancy and risk of autism spectrum disorder and attention deficit hyperactivity disorder: systematic review of observational studies and methodological considerations. (…) Conclusions Existing observational studies measuring the risk of ASD and ADHD with antidepressant exposure are heterogeneous in their design. Classical comparisons between exposed and unexposed women during pregnancy are at high risk of residual confounding. Alternative comparisons and sibling designs may aid the interpretation of causality and their utility requires further evaluation, including understanding potential limitations of undertaking meta-analyses with such data. BMC Medicine201816:6.)

- Behandling med antidepressiva og risiko for demens. (- KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva.)

(Anm: Behandling med antidepressiva og risiko for demens: En populasjonsbasert, retrospektiv case-control studie. (…) KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva. (CONCLUSIONS: The incidence of dementia in patients is associated with antidepressant medication use.) J Clin Psychiatry. 2016 Jan;77(1):117-22.)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

- Det er økt risiko for at barnet får engstelig eller deprimert adferd i femårsalderen når mor bruker antidepressiva sent i svangerskapet. ... SAMMENHENG: Forskerne de finner en assosiasjon mellom bruk av SSRI sent i svangerskapet og økt risiko for engstelig eller deprimert atferd når barnet er fem år.

(Anm: Økt risiko for deprimert adferd hos barnet - Psykisk helse - Dagens ... https://www.dagensmedisin.no/.../okt-risiko-for-deprimert-adferd-ved-ssri-sent-i-svan... Bufret For 20 timer siden - Det er økt risiko for at barnet får engstelig eller deprimert adferd i femårsalderen når mor bruker antidepressiva sent i svangerskapet. ... SAMMENHENG: Forskerne de finner en assosiasjon mellom bruk av SSRI sent i svangerskapet og økt risiko for engstelig eller deprimert atferd når barnet er fem år. (google.no 25.1.2018).)

- Mitokondriell dysfunksjon og oksidativt stress ved aldring og kreft. (- Denne vurderingen fokuserer på likhetene mellom aldringsrelatert og kreftassosiert oksidativt stress og mitokondriell dysfunksjon som deres felles fenotype (fremtoningspreg).)

(Anm: Mitochondrial dysfunction and oxidative stress in aging and cancer. Abstract  Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype. Oncotarget. 2016 Jul 19;7(29):44879-44905.)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Legemiddelindusert kreft og andre typer celleskader (mintankesmie.no).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

(Anm: Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking. (Conclusions SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smoking. BMJ Open 2017;7:e016224.)

(Anm: Historical Perspective of Mitochondria in the Toxicological Sciences. Toxicol Sci. 2018 Mar 1;162(1):12-14.)

- Hvordan påvirker endringer i mtDNA og mitokondriell dysfunksjon kreft- og kreftbehandling? Flere mutasjoner i nukleære gener som koder for mitokondriske komponenter har blitt assosiert med en økt kreftrisiko eller er selv forårsakende, f.eks. succinat dehydrogenase (SDHB, SDHC og SDHD gener) og iso-citrat dehydrogenase (IDH1 og IDH2 gener). Nylig har studier antydet en fremtredende rolle for mitokondrielle DNA (mtDNA) mutasjoner i utviklingen av et bredt utvalg av kreftformer. Forskjellige studier assosiert med mtDNA abnormiteter, inkludert mutasjoner, slettinger, inversjoner og kopinummerendringer, med mitokondriell dysfunksjon.

(Anm: Hvordan påvirker endringer i mtDNA og mitokondriell dysfunksjon kreft- og kreftbehandling? Utfordringer, muligheter og modeller. Abstrakt Flere mutasjoner i nukleære gener som koder for mitokondriske komponenter har blitt assosiert med en økt kreftrisiko eller er selv forårsakende, f.eks. succinat dehydrogenase (SDHB, SDHC og SDHD gener) og iso-citrat dehydrogenase (IDH1 og IDH2 gener). Nylig har studier antydet en fremtredende rolle for mitokondrielle DNA (mtDNA) mutasjoner i utviklingen av et bredt utvalg av kreftformer. Forskjellige studier assosiert med mtDNA abnormiteter, inkludert mutasjoner, slettinger, inversjoner og kopinummerendringer, med mitokondriell dysfunksjon. (How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models. Abstract Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction.) Mutat Res Rev Mutat Res. 2015 Apr-Jun;764:16-30

(Anm: Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory Complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates in both the citric acid cycle and the electron transport chain.[1] Histochemical analysis showing high succinate dehydrogenase in muscle demonstrates high mitochondrial content and high oxidative potential.[2] (en.wikipedia.org).)

- Bruk av mitokondrielt DNA som biosensor for tidlig utvikling av kreft.

Using mitochondrial DNA as a biosensor of early cancer development
Editorial British Journal of Cancer 2005; 93:271-272.
Hvordan påvirker endringer i mtDNA og mitokondriell dysfunksjon kreft- og kreftbehandling? Utfordringer, muligheter og modeller. Abstrakt Flere mutasjoner i nukleære gener som koder for mitokondriske komponenter har blitt assosiert med en økt kreftrisiko eller er selv årsakssammenhengende, f.eks. succinat dehydrogenase (SDHB, SDHC og SDHD gener) og iso-citrat dehydrogenase (IDH1 og IDH2 gener). Nylig har studier foreslått en fremtredende rolle for mitokondriale DNA (mtDNA) mutasjoner i utviklingen av et bredt utvalg av kreftformer. Forskjellige studier assosiert med mtDNA abnormiteter, inkludert mutasjoner, deletjoner, inversjoner og kopi tallendringer, med mitokondriell dysfunksjon.Mitochondria can perform multiple cellular functions including energy production, cell proliferation and apoptosis. Each human cell contains hundreds to several thousand copies of the 16.5 kb human mitochondrial genome, which incidentally exhibits a maternal pattern of inheritance. This closed circular genome encodes 13 polypeptides of the respiratory chain complexes, as well as 22 transfer RNAs and two ribosomal RNAs used in mitochondrial protein synthesis. Compared to nuclear DNA, mitochondrial DNA (mtDNA) is highly susceptible to damage because it is not associated with protective histones, it is continually exposed to high levels of reactive oxygen species (ROS) generated by oxidative phosphorylation, and there is a limited capacity for mtDNA repair. The complete mtDNA sequence was determined in 1981 and resequenced in 1999. A growing collection of reported mtDNA mutations and rearrangements has been associated with muscle and neurodegenerative diseases (Birch-Machin, 2000).

(Anm: Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis. Abstract We recently reported that oxidative stress elicited by chronic inflammation increases the mutation of mitochondrial DNA (mtDNA) and possibly correlates with precancerous status. Since severe oxidative stress is elicited in the colorectal mucosa of individuals with ulcerative colitis (UC), the possible occurrence of an mtDNA mutation in the inflammatory colorectal mucosa and colitic cancer was investigated. Br J Cancer. 2005 Aug 8;93(3):331-7.)

(Anm: Researchers discover how the body skillfully extinguishes inflammation. Inflammation needs energy. An important source for this energy is oxygen, which is indispensable for the cells of the immune system to work properly. On the one hand, oxygen is an essential element required for cells to survive; on the other hand, it also adds fuel to the fire of inflammation. Researchers from Department of Medicine 3 - Rheumatology and Immunology at Universitätsklinikum Erlangen at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have discovered that the body skilfully uses this process to extinguish inflammation. Immune cells are tricked into believing that they are lacking oxygen, leading them to retreat from the site of the inflammation in order to save energy. These new findings have been published in the journal Nature Communications (DOI: 10.1038/s41467-017-02683-x). (news-medical.net 23.2.2018).)

- Mitokondriell funksjon ved allergisk sykdom. (- NYLIGE FUNN: Nylig forskning har vist at allergi, astma og metabolsk syndrom er linket til mitokondriell dysfunksjon.

(Anm: Mitokondriell funksjon ved allergisk sykdom. (Mitochondrial Function in Allergic Disease.) NYLIGE FUNN: Nylig forskning har vist at allergi, astma og metabolsk syndrom er linket til mitokondriell dysfunksjon (RECENT FINDINGS: Recent research has shown allergy, asthma and metabolic syndrome to be linked to mitochondrial dysfunction.) Curr Allergy Asthma Rep. 2017 May;17(5):29.)

(Anm: Allergi (allergier). (mintankesmie.no).)

(Anm: Astmalegemidler (astma) (mintankesmie.no).)

(Anm: Tannleger og tannhelse (munnhulen er kroppens speil). (mintankesmie.no/).)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

(Anm: Mitokondriell dysfunksjon ligger bak kognitive defekter som et resultat av nevral stamcelleutarmning og nedsatt neurogenese. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet. 2017 Jun 8.)

(Anm: Astmaspray kan gi munnsopp. (…) Noen er mer plaget av dette enn andre, men du merker det ved at det svir, blir ømt, du blir rød, får sår i munnen og et hvitt belegg på tungen, opplyser Grethe Amdal, seniorrådgiver i Norges Astma- og Allergiforbund (NAAF) til NRK.no. (…) Har du en kraftig immunsvikt som hiv/aids, vil dette spre seg nedover i spiserøret, hvilket er meget ubehagelig, fortsetter han. (…) Munnen avslører sykdom. (…) Han oppfordrer til å oppsøke tannlegen hvis du har sår i munnhulen som ikke går bort. Det kan være ufarlige hudsykdommer, men også noe mer alvorlig, som kreft.) (nrk.no 13.5.2011).)

- Hvorfor forskere tror "hacking av våre celler" kan slå av aldringsprosessen. Kutt i karbohydrater, reduksjon av kalorier, og bruk av nøkkelsupplement kan hjelpe cellene dine til å produsere mer energi og beskytte deg mot mange aldringssykdommer. (- De fant at den fruktoserike dietten førte til betydelig skade på mitokondrielt DNA i leveren (hvor fruktose behandles). Den fruktoserike dietten reduserte også dyrenes evne til å reparere skadene og lage nye mitokondrier.)

(Anm: Why Scientists Think ‘Hacking Our Cells’ Could Turn Off the Aging Process. Cutting carbs, reducing calories, and using key supplements may help your cells produce more energy and protect you against many diseases of aging. If you’ve ever marveled at the boundless energy of little kids, you may have wondered why you don’t have the same vigor. Part of the reason is a decline in your mitochondria. Tucked away in your body’s cells, mitochondria convert the food you eat and the oxygen you breathe into energy. As you age, the amount of mitochondria you have tends to decline. So does their ability to function. This results in less energy, but that’s not all. “The latest research strongly suggests that the vast majority of age-related degenerative diseases have tangled roots in dysfunctional mitochondria,” Dr. Lee Know, author of “Mitochondria and the Future of Medicine,” told Healthline. “This is because everything that happens within the body’s cells requires an input of energy, and it’s the mitochondria that produce over 90% of that energy.” (…) Exercise for healthy mitochondria You already know exercise is good for you. With the study of mitochondria, the reasons why exercise is so good for us are becoming even clearer. “Exercise is the single greatest therapy for mitochondrial health,” Know said. Regular exercise can significantly improve mitochondrial function, including as you get older. (healthline.com 28.2.2018).)

(Anm: Aging Is a Sticky Business. Abstract OBJECTIVE: The objective of this work is to put forward a mechanism by which low-level light [red-to near infrared (NIR) laser or light emitting diodes (LED)] is instrumental in the process of accelerating the healing of wounds. (…) CONCLUSIONS: An understanding of the mechanism of interaction of red-to NIR light with mitochondria, cells, and tissues safeguards progress in the field of low-level light therapy (LLLT) and puts us in the position to design better therapies. Photomed Laser Surg. 2018 Mar 23.)

- Tarm-hjerne-aksen og neurodegenerative lidelser. (- Dette omfatter toveis kommunikasjonskanaler mellom sentralnervesystemet, det enteriske nervesystemet og det endokrine systemet.)

(Anm: Tarm-hjerne-aksen og neurodegenerative lidelser. (Gut-Brain Axis and Neurodegenerative Disorders.) Det er økende anerkjennelse i det medisinske og vitenskapelige samfunnet av forbindelsen mellom tarmen og det sentrale nervesystemets mikrobielle sammensetning, kjent som "tarm-hjerne-aksen". Dette omfatter toveis kommunikasjonskanaler mellom sentralnervesystemet, det enteriske nervesystemet og det endokrine systemet. Videre er tarm-hjerne-aksen ansvarlig for regulering av immunrespons i både tarmene og hjernen, med alle aspekter sterkt påvirket av aktiviteten til intestinale mikroorganismer. (news-medical.net 16.1.2018).)

(Anm: Det enteriske nervesystemet består av flettverk av nerveceller som ligger i veggen i mage-tarmkanalen i hele dens lengde. Det består av et flertall ulike typer av nerveceller med både aktiverende og hemmende synaptiske effekter. Det totale antall nerveceller i det enteriske systemet er meget stort, sammenlignbart med det totale antall nerveceller i hele ryggmargen. Kilde: Store norske leksikon.)

(Anm: Nøkkelen til kronisk utmattelsessyndrom sitter i tarmen, ikke hodet. (Key to chronic fatigue syndrome is in your gut, not head.) (mediarelations.cornell.edu 27.6.2016).)

- Mitokondriell dysfunksjon hos en familie med psykose og kronisk tretthetssyndrom.

(Anm: Mitochondrial dysfunction in a family with psychosis and chronic fatigue syndrome. Abstract Mitochondrial impairment is hypothesized to be involved in chronic fatigue syndrome (CFS) and schizophrenia. We performed a clinical, genetic and functional mitochondrial study in a family consisting of a female presenting schizophrenia in addition to CFS symptoms and her mother and older sister, both presenting with CFS. The three family members showed higher blood lactate levels, higher mitochondrial mass, lower mtDNA content and overall lower mitochondrial enzymatic activities and lower oxygen consumption capacities than healthy women. This family presented mtDNA depletion; however, no mutation was identified neither in the mtDNA nor in the nuclear genes related with mtDNA depletion, even though C16179A and T16519A variants should be further studied. Mitochondrion. 2017 May;34:1-8.)

- Gassdetekteringspille kan diagnostisere dårlig tarmhelse.

(Anm: Gas detecting pill could diagnose poor gut health. Researchers at RMIT in Australia have recently conducted the first human trials of a pill-sized sensor capsule which transmits live data from the intestines of patients. The capsule can measure gas levels and transmit this information to a mobile phone app. The researchers hope that their sensor will provide unprecedented levels of information to better diagnose gastrointestinal disorders and diseases. (bbc.com 23.1.2018).)

- Slutten på giftig kjemoterapi? Blokkering av vitamin B-2 kan stoppe kreft.

(Anm: The end of toxic chemo? Blocking vitamin B-2 may stop cancer. New research published in the journal Aging finds a compound that stops cancer cells from spreading by starving them of vitamin B-2. The findings may revolutionize traditional chemotherapy. A team of British-based researchers set out to find a non-toxic therapeutic agent that targets the mitochondria of cancer cells. Mitochondria are energy-producing organelles found inside each cell. The compound recently found by the scientists can stop cancer stem-like cells from proliferating by interfering with their energy-creating process inside the mitochondria. The team was led by Prof. Michael Lisanti, the chair of translational medicine at the University of Salford in the United Kingdom, and the new study can be accessed here. (medicalnewstoday.com 31.1.2018).)

(Anm: Targeting flavin-containing enzymes eliminates cancer stem cells (CSCs), by inhibiting mitochondrial respiration: Vitamin B2 (Riboflavin) in cancer therapy. Aging (Albany NY). 2017 Dec 16;9(12):2610-2628.)

- Danske forskere skaber banebrydende viden om cellers kalciumpumper. (- Kalciumpumpen er et proteinmolekyle, der pumper kalcium og spalter det cellulære brændstof ATP. Den kaldes også en Ca2+-ATPase. Kalciumpumper genopretter kalcium-balancen i celler fx under muskelarbejde, sanseindtryk og nerveaktivitet.)

(Anm: Danske forskere skaber banebrydende viden om cellers kalciumpumper. grundforskning Når dyr og planter bliver udsat for påvirkninger som bakterieangreb, lugte og kulde, strømmer der kalciumioner ind i cellerne. Ved hjælp af kalcium får cellerne et signal om, hvad der foregår udenfor, men da høje koncentrationer af kalcium er giftigt for cellerne, skal det hurtigt pumpes ud igen. Nu viser forskere fra Aarhus Universitet og Københavns Universitet i grundforskningscentret PUMPkin, at en kalciumpumpe i cellens ydre membran afpasser pumpehastigheden meget præcist efter kalcium-koncentrationen. Forskningsresultaterne er netop offentliggjort i Nature. (…) Kalciumpumpen Kalciumpumpen er et proteinmolekyle, der pumper kalcium og spalter det cellulære brændstof ATP.  Den kaldes også en Ca2+-ATPase. Kalciumpumper genopretter kalcium-balancen i celler fx under muskelarbejde, sanseindtryk og nerveaktivitet. Kalciumpumpen tilhører en større familie af ionpumper kaldet P-type ATPaser, som er helt essentielle for liv. Særlig berømt er natrium-kalium-pumpen, som blev opdaget af professor Jens Chr. Skou fra Aarhus Universitet, der fik Nobelprisen herfor i 1997. (nyheder.ku.dk 21.10.2012).)

- Den mitokondrielle ATP-syntese er et delt legemiddelmål for aldring og demens.

(Anm: The mitochondrial ATP synthase is a shared drug target for aging and dementia. Abstract Aging is a major driving force underlying dementia, such as that caused by Alzheimer's disease (AD). While the idea of targeting aging as a therapeutic strategy is not new, it remains unclear how closely aging and age-associated diseases are coupled at the molecular level.  (…) These findings demonstrate that novel screens for new AD drug candidates identify compounds that act on established aging pathways, suggesting an unexpectedly close molecular relationship between the two. Aging Cell. 2018 Jan 7.)

- Mitokondriell dysfunksjon: En ny potensiell driver for epitelial-mesenkymal transisjon (EMT) for kreft. (Mitochondrial Dysfunction: A Novel Potential Driver of Epithelial-to-Mesenchymal Transition in Cancer.)

(Anm: Mitochondrial Dysfunction: A Novel Potential Driver of Epithelial-to-Mesenchymal Transition in Cancer. Abstract Epithelial-to-mesenchymal transition (EMT) allows epithelial cancer cells to assume mesenchymal features, endowing them with enhanced motility and invasiveness, thus enabling cancer dissemination and metastatic spread. The induction of EMT is orchestrated by EMT-inducing transcription factors that switch on the expression of "mesenchymal" genes and switch off the expression of "epithelial" genes. Mitochondrial dysfunction is a hallmark of cancer and has been associated with progression to a metastatic and drug-resistant phenotype. The mechanistic link between metastasis and mitochondrial dysfunction is gradually emerging. The discovery that mitochondrial dysfunction owing to deregulated mitophagy, depletion of the mitochondrial genome (mitochondrial DNA) or mutations in Krebs' cycle enzymes, such as succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase, activate the EMT gene signature has provided evidence that mitochondrial dysfunction and EMT are interconnected. In this review, we provide an overview of the current knowledge on the role of different types of mitochondrial dysfunction in inducing EMT in cancer cells. We place emphasis on recent advances in the identification of signaling components in the mito-nuclear communication network initiated by dysfunctional mitochondria that promote cellular remodeling and EMT activation in cancer cells. Front Oncol. 2017 Dec 1;7:295. eCollection 2017.)

(Anm: Legemiddelindusert kreft og andre typer celleskader (mintankesmie.no).)

– Mitokondrielt grunnlag for aldring og aldersrelaterte lidelser. (- Aldring er et naturlig fenomen som preges av et (gradvis) tiltagende forfall av vev og organfunksjoner som fører til økt risiko for sykdom og dødelighet. Blant ulike faktorer som bidrar til menneskelig aldring har mitokondriell dysfunksjon dukket opp som et av de viktigste kjennetegn på aldringsprosessen og er linket til utviklingen av mange aldersrelaterte sykdommer, inkludert metabolsk syndrom, neurodegenerative forstyrrelser, kardiovaskulære sykdommer og kreft.

(Anm: The Mitochondrial Basis of Aging and Age-Related Disorders. Abstract Aging is a natural phenomenon characterized by progressive decline in tissue and organ function leading to increased risk of disease and mortality. Among diverse factors that contribute to human aging, the mitochondrial dysfunction has emerged as one of the key hallmarks of aging process and is linked to the development of numerous age-related pathologies including metabolic syndrome, neurodegenerative disorders, cardiovascular diseases and cancer. Mitochondria are central in the regulation of energy and metabolic homeostasis, and harbor a complex quality control system that limits mitochondrial damage to ensure mitochondrial integrity and function. The intricate regulatory network that balances the generation of new and removal of damaged mitochondria forms the basis of aging and longevity. Here, I will review our current understanding on how mitochondrial functional decline contributes to aging, including the role of somatic mitochondrial DNA (mtDNA) mutations, reactive oxygen species (ROS), mitochondrial dynamics and quality control pathways. I will further discuss the emerging evidence on how dysregulated mitochondrial dynamics, mitochondrial biogenesis and turnover mechanisms contribute to the pathogenesis of age-related disorders. Strategies aimed to enhance mitochondrial function by targeting mitochondrial dynamics, quality control, and mitohormesis pathways might promote healthy aging, protect against age-related diseases, and mediate longevity. Genes (Basel). 2017 Dec 19;8(12). pii: E398.)

(Anm: Legemiddelindusert kreft og andre typer celleskader (mintankesmie.no).)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Antipsykotika (psykofarmaka etc.) (mintankesmie.no).)

(Anm: Sovemidler (sovemedisiner) og beroligende midler (mintankesmie.no).)

(Anm: Sovemidler knyttes til dødelighet eller kreft: en matchet kohortstudie. (Hypnotics' association with mortality or cancer: a matched cohort study.)  (...) Målsetting Anslagsvis 6 % -10 % av amerikanske voksne tok et sovemiddel (hypnotika) mot dårlig søvn i 2010. Denne studien underbygger tidligere rapporter som knytter hypnotika (sovemidler) til økt dødelighet. BMJ Open 2012;2:e000850 (27 February).)

(Anm: Flere barn enn antatt får bivirkninger av ADHD-medisiner. (…) Tidligere antok forskere at mellom 1 og 10 prosent av alle barn på ADHD-medisiner opplever nedsatt appetitt, men den nye studien viser at tallet faktisk er over 30 prosent. Dessuten er flere barn enn tidligere antatt triste og irritable, og flere opplever søvnproblemer, når de tar medisiner mot sykdommen. Likevel anbefaler forskerne at barna fortsetter å ta medisinene. (…) Den nye forskingsgjennomgangen er nettopp offentliggjort av Cochrane Library. Cochrane samler vitenskapelig evidens fra mange studier til en stor studie som dermed er mer presis. (forskning.no 18.5.2018).)

(Anm: Protonpumpehemmere (proton pump inhibitors (PPIs) (syrepumpehemmere) (magesyrehemmere) (syrenøytraliserende midler (antacida)). (mintankesmie.no).)

(Anm: Syrepumpehemmere (protonpumpehemmere (PPI) knyttet til alvorlige gastrointestinale infeksjoner. (…) Legemidler som protonpumpehemmere (PPI) knyttet til en økt risiko for tarminfeksjoner med C. difficile og Campylobacter bakterier som kan forårsake betydelig sykdom. (Acid suppression medications linked to serious gastrointestinal infections. (…) Medications such as proton pump inhibitors (PPIs) was linked with an increased risk of intestinal infections with C. difficile and Campylobacter bacteria, which can cause considerable illness.) (medicalnewstoday.com 9.1.2017).)

(Anm: Protonpumpehemmere (proton pump inhibitors (PPIs) (syrepumpehemmere) (magesyrehemmere) (syrenøytraliserende midler (antacida)). (mintankesmie.no).)

(Anm: Diskriminering, feilmedisineringer hos mennesker med utviklingshemming og utfordrende atferd (psykofarmaka; antidepressiva, antipsykotika, sovemedisiner) etc. (mintankesmie.no).)

(Anm: På tide å revurdere? (Time to rethink?) Legemiddelbehandlinger hos mennesker med utviklingshemming og utfordrende atferd (Drug treatments in people with intellectual disability and challenging behaviour disabilities) Editorials (Lederartikkel) BMJ 2014;349:g4323 (Published 04 July 2014).)

(Anm: Sovemidler knyttes til dødelighet eller kreft: en matchet kohortstudie. (Hypnotics' association with mortality or cancer: a matched cohort study.)  (...) Målsetting Anslagsvis 6 % -10 % av amerikanske voksne tok et sovemiddel (hypnotika) mot dårlig søvn i 2010. Denne studien underbygger tidligere rapporter som knytter hypnotika (sovemidler) til økt dødelighet. BMJ Open 2012;2:e000850 (27 February).)

(Anm: Flere barn enn antatt får bivirkninger av ADHD-medisiner. (…) Tidligere antok forskere at mellom 1 og 10 prosent av alle barn på ADHD-medisiner opplever nedsatt appetitt, men den nye studien viser at tallet faktisk er over 30 prosent. Dessuten er flere barn enn tidligere antatt triste og irritable, og flere opplever søvnproblemer, når de tar medisiner mot sykdommen. Likevel anbefaler forskerne at barna fortsetter å ta medisinene. (…) Den nye forskingsgjennomgangen er nettopp offentliggjort av Cochrane Library. Cochrane samler vitenskapelig evidens fra mange studier til en stor studie som dermed er mer presis. (forskning.no 18.5.2018).)

- Ny forskning: Depression hos fisk kan hjælpe med at forstå mennesker. (- Fisk bliver deprimerede på grund af manglende stimulation og små akvarier. (- Deres (mennesker og fisk, red.) neurokemi er så ens, at det er skæmmende.)

(Anm: Ny forskning: Depression hos fisk kan hjælpe med at forstå mennesker. (…) »Deres (mennesker og fisk, red.) neurokemi er så ens, at det er skæmmende,« fortæller Julian Pittman, der er professor i biologi på Troy University i Alabama, til New York Times. (…)  En såkaldte 'guldfiskebowle' er derfor noget af det værste, man som fiskeejer kan købe til sin fisk, da fisken mangler plads, og der samtidig ikke er mulighed for, at man som fisk kan få stillet sin nysgerrighed. (…) Fisk bliver deprimerede på grund af manglende stimulation og små akvarier. (…) Julian Pitmman har gennem de sidste ti år studeret, hvordan blandt andet zebrafisk har mistet interessen i stort set al ting: mad, legetøj, ting - præcis ligesom klinisk deprimerede mennesker. (jyllands-posten.dk 18.10.2017).)

- Medicinrester får fåglar att tappa sexlusten. Starar håller gärna till vid dammar runt reningsverk, där det finns gott om maskar och insekter. Men i vattnet kan också låga halter av läkemedel finnas – exempelvis från antidepressiva medel.

(Anm: Medicinrester får fåglar att tappa sexlusten. Starar håller gärna till vid dammar runt reningsverk, där det finns gott om maskar och insekter. Men i vattnet kan också låga halter av läkemedel finnas – exempelvis från antidepressiva medel. Och dessa ger stararna sämre aptit och minskad sexualdrift visar en brittisk studie av fågelarten, rapporterar Vetenskapsradion. Bland annat slutar hanarna sjunga och visa intresse för honorna, och fåglarna ändrar sina matvanor. Detta kan få allvarliga konsekvenser för en stare. – En fågel utan sexlust får inga ungar och en fågel som inte äter ordentligt överlever inte, säger Kathryn Arnold, miljöforskare vid universitetet i York i England. Antalet starar minskar i många länder, och läkemedelsrester i naturen kan vara en av flera orsaker till det, enligt Arnold. Resultaten presenterades på konferensen SEB Gothenburg 2017, och har ännu inte publicerats. (nyteknik.se 28.8.2017).)

(Anm: Miljø og helse (mintankesmie.no).)

(Anm: Klima, miljø og globalisering (mintankesmie.no).)

- Oppdrettsfisk får hjertelidelse av stress, viser ny doktorgradsstudie. Stress er et kjent problem i bransjen. (– Hjerteproblemer av ulike typer rammer oppdrettsfisk, men vi vet lite om årsakene, sier Ida Beitnes Johansen.)

Blir syke av stress
aftenposten.no 25.3.2011
Får for store hjerter - Smaker dårligere

Oppdrettsfisk får hjertelidelse av stress, viser ny doktorgradsstudie. Stress er et kjent problem i bransjen.

De siste tre og et halvt år har stipendiat Ida Beitnes Johansen ved Institutt for husdyr og akvakulturvitenskap, Universitet for miljø og biovitenskap på Ås, dokumentert de fysiske konsekvensene i hjertet og hjernen av stress hos fisk. Det hun fant, var forvokste fiskehjerter i den gruppen av fisk som viste dårligst evne til å takle stress. – Hjerteproblemer av ulike typer rammer oppdrettsfisk, men vi vet lite om årsakene, sier Ida Beitnes Johansen.– Ved å studere forekomsten av stresshormonet kortisol,som finnes både hos fisk og mennesker, har jeg sett hvordan for høye nivåer kan føre til sykdom og hjertelidelser. (...)

- Det hovedløse samfund: Glemmer du også at tænke selv? Ny teknologi hjælper i hverdagen, men det gør også din hjerne mere overflødig.

(Anm: Det hovedløse samfund: Glemmer du også at tænke selv? Ny teknologi hjælper i hverdagen, men det gør også din hjerne mere overflødig. Hvis du ikke bruger hjernen, så bliver den doven, og det kan få store konsekvenser. Få ekspertens råd til at vække hjernen. (jyllands-posten.dk 4.8.2017).)

(Anm: Miljø og helse (mintankesmie.no).)

- Det er betydelig bevis som støtter hypotesen om at mitokondriell dysfunksjon er knyttet til nevropsykiatriske lidelser. (- There is considerable evidence supporting the hypothesis that mitochondrial dysfunction is associated with neuropsychiatric disorders.)

(Anm: A Mitochondrial Etiology of Neuropsychiatric Disorders. (…) The brain is only 2% to 3% of our body’s weight but expends 20% of our mitochondrial energy, as measured by oxygen consumption. Therefore, as systemic mitochondrial energy metabolism declines, the brain is the first organ to become limited for energy, dropping below its bioenergetic threshold and resulting in neurological symptoms. The milder the bioenergetic defect, the more brain-specific the symptoms, with hyperactivity or depression being likely examples. If a 20% reduction in mitochondrial oxidative phosphorylation (OXPHOS) were sufficient to cause depression, the biochemical defect would not be significantly demonstrable in an individual using current technology. By contrast, analysis of cohorts of patients has revealed statistically significant mean differences in OXPHOS relative to control individuals in the brain as well as in peripheral tissues for a variety of neurological diseases. (…) There is considerable evidence supporting the hypothesis that mitochondrial dysfunction is associated with neuropsychiatric disorders. For example, an ancient mtDNA single-nucleotide polymorphism (SNP) in the mtDNA tRNAGln gene at nucleotide 4336A>G is found in about 3% of patients with Alzheimer disease, about 5% of those with Parkinson disease, and about 7% of those with Alzheimer and Parkinson diseases, but only about 0.4% of the European population.3 Ancient mtDNA lineages harboring function variants (haplogroups) have been associated with predisposition to a broad range of neurological, cardiac, and metabolic diseases.2 Mitochondrial DNA mutations also accumulate with age in tissues, resulting in the age-related decline in mitochondrial function. The progressive mitochondrial defects resulting from these somatic mtDNA mutations can exacerbate inherited nDNA or mtDNA mitochondrial gene defects, ultimately causing a composite energy deficiency that falls below neuronal bioenergetic thresholds resulting in neuropsychiatric symptoms.2 JAMA Psychiatry. Published online June 14, 2017.)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Mitochondrial Toxicity of Tobacco Smoke and Air Pollution. Toxicology. 2017 Aug 21. pii: S0300-483X(17)30229-9.)

- Pasienter behandlet med antipsykotika (nevroleptika) har signifikant senket platelet complex I aktivitet i mitokondrier i likhet med det som er observert ved idiopatisk Parkinsons sykdom.

(Anm: Pasienter behandlet med antipsykotika (nevroleptika) har signifikant senket platelet complex I aktivitet i mitokondrier i likhet med det som er observert ved idiopatisk Parkinsons sykdom. (...) Antipsykotika (nevroleptika) hemmer kompleks I i elektrontransportkjeden. (Neuroleptic medications inhibit complex I of the electron transport chain. (...) Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson’s disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.) Ann Neurol. 1993;33:512-7).)

(Anm: Antipsykotika (psykofarmaka etc.) (mintankesmie.no).)

(Anm: Antipsykotika dobler dødsrisiko allerede etter 180 dagers bruk. Greater Mortality Risk With Antipsychotics in Parkinson's (Større dødsrisiko med antipsykotika ved Parkinsons) (medicalnewstoday.com 21.6.2015).)

- Mitokondriell mangefasettert dysfunksjon ved schizofreni; complex I som et mulig patologisk mål.

(Anm: Mitochondrial multifaceted dysfunction in schizophrenia; complex I as a possible pathological target. Abstract Mitochondria are key players in various essential cellular processes beyond being the main energy supplier of the cell. Accordingly, they are involved in neuronal synaptic transmission, neuronal growth and sprouting and consequently neuronal plasticity and connectivity. (…) In the present article, we overview specific deficits of the mitochondria in schizophrenia, with a focus on the first complex (complex I) of the mitochondrial electron transport chain (ETC). We argue that complex I, being a major factor in the regulation of mitochondrial ETC, is a possible key modulator of various functions of the mitochondria. We review biochemical, molecular, cellular and functional evidence for mitochondrial impairments and their possible convergence to impact in-vitro neuronal differentiation efficiency in schizophrenia. Mitochondrial function in schizophrenia may advance our knowledge of the disease pathophysiology and open the road for new treatment targets for the benefit of the patients. Schizophr Res. 2017 Sep;187:3-10.)

- Dopaminoksidasjon formidler mitokondriell og lysosomal dysfunksjon ved Parkinsons sykdom.

(Anm: Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. Abstract Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation. This toxic cascade was observed in human, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism. Increasing dopamine synthesis or α-synuclein amounts in mouse midbrain neurons recapitulated pathological phenotypes observed in human neurons. Thus, dopamine oxidation represents an important link between mitochondrial and lysosomal dysfunction in PD pathogenesis. Science. 2017 Sep 22;357(6357):1255-1261.)

(Anm: Deprimerede kæmper en hård kamp med deres indre ur. Hjernen hos deprimerede har svært ved at holde sammen på døgnrytmen, som en velfungerende hjerne kan. Ny forskning kan give et praj om hvorfor. (…) Depression rammer op mod hver fjerde kvinde og niende mand i Danmark og er efterhånden blevet en folkesygdom. (...) Alligevel er årsagerne til, at man udvikler depression, meget ringe forståede. Det skriver Videnskab.dk. (jyllands-posten.dk 16.8.2016).)

- ER-mitokondrier signalering ved Parkinsons sykdom. (- Endringer i ER-mitokondriell signalering har pleiotropiske effekter på en rekke intracellulære hendelser som resulterer i mitokondriell skade, Ca2 + dyshomeostase, ER stress og defekter i lipidmetabolisme og autofagi. Oppsiktsvekkende er mange av disse cellulære prosesser forstyrret ved nevrodegenerative sykdommer. Videre viser økende bevis at ER-mitokondriens signalering bidrar til disse sykdommene, inkludert Parkinsons sykdom (PD).)

(Anm: ER-mitochondria signaling in Parkinson's disease. Abstract Mitochondria form close physical contacts with a specialized domain of the endoplasmic reticulum (ER), known as the mitochondria-associated membrane (MAM). This association constitutes a key signaling hub to regulate several fundamental cellular processes. Alterations in ER-mitochondria signaling have pleiotropic effects on a variety of intracellular events resulting in mitochondrial damage, Ca2+ dyshomeostasis, ER stress and defects in lipid metabolism and autophagy. Intriguingly, many of these cellular processes are perturbed in neurodegenerative diseases. Furthermore, increasing evidence highlights that ER-mitochondria signaling contributes to these diseases, including Parkinson's disease (PD). PD is the second most common neurodegenerative disorder, for which effective mechanism-based treatments remain elusive. Several PD-related proteins localize at mitochondria or MAM and have been shown to participate in ER-mitochondria signaling regulation. Likewise, PD-related mutations have been shown to damage this signaling. Could ER-mitochondria associations be the link between pathogenic mechanisms involved in PD, providing a common mechanism? Would this provide a pharmacological target for treating this devastating disease? In this review, we aim to summarize the current knowledge of ER-mitochondria signaling and the recent evidence concerning damage to this signaling in PD. Cell Death Dis. 2018 Mar 1;9(3):337.)

(Anm: Pleiotropi, betegnelse for det fenomen at et arveanlegg/gen innvirker på mer enn én egenskap. For eksempel innvirker genet som koder for hvit øyenfarge hos bananflue også på fargen og formen til visse indre organer samt på fluens fruktbarhet og livslengde. Hos menneske består for eksempel den pleiotrope effekten av det dominante genet for Marfans syndrom i abnormt lange ekstremiteter, fingre og tær, linsefeil i øyet samt hjerte- og kar-defekter. Kilde: Store norske leksikon.)

- Mitokondriell dysfunksjon ved Parkinsons sykdom: Ny mekanisk innsikt og terapeutiske perspektiver.

(Anm: Mitochondrial Dysfunction in Parkinson's Disease: New Mechanistic Insights and Therapeutic Perspectives. Abstract PURPOSE OF REVIEW: Parkinson's disease (PD) is a complex neurodegenerative disorder, the aetiology of which is still largely unknown. Overwhelming evidence indicates that mitochondrial dysfunction is a central factor in PD pathophysiology. Here we review recent developments around mitochondrial dysfunction in familial and sporadic PD, with a brief overview of emerging therapies targeting mitochondrial dysfunction. RECENT FINDINGS: Increasing evidence supports the critical role for mitochondrial dysfunction in the development of sporadic PD, while the involvement of familial PD-related genes in the regulation of mitochondrial biology has been expanded by the discovery of new mitochondria-associated disease loci and the identification of their novel functions. Recent research has expanded knowledge on the mechanistic details underlying mitochondrial dysfunction in PD, with the discovery of new therapeutic targets providing invaluable insights into the essential role of mitochondria in PD pathogenesis and unique opportunities for drug development. Curr Neurol Neurosci Rep. 2018 Apr 3;18(5):21.)

- Sirkadiske rytmer i mitokondriell respirasjon. (- Forstyrrende sirkadiske rytmer på organ eller helkroppsnivå ved sosialt jetlag eller skiftarbeid øker risikoen for å utvikle kroniske metabolske sykdommer som type 2 diabetes mellitus. (- Forstyrret molekylær klokke i dyremodeller fører til opphøyet mitokondriell rytmesitet og endret respirasjon).

(Anm: Circadian rhythms in mitochondrial respiration. Abstract Many physiological processes are regulated with a 24h periodicity to anticipate the environmental changes of day to nighttime and vice versa. These 24h regulations, commonly termed circadian rhythms, amongst others control the sleep-wake cycle, locomotor activity and preparation for food availability during the active phase (daytime for humans, nighttime for nocturnal animals). Disturbing circadian rhythms at the organ or whole-body level by social jetlag or shift work, increases the risk to develop chronic metabolic diseases such as type 2 diabetes mellitus. The molecular basis of this risk is a topic of increasing interest. Mitochondria are essential organelles that produce the majority of energy in Eukaryotes by converting lipids and carbohydrates into ATP through oxidative phosphorylation. To adapt to the ever-changing environment, mitochondria are highly dynamic in form and function and a loss of this flexibility is linked to metabolic diseases. Interestingly, recent studies have indicated that changes in mitochondrial morphology (i.e. fusion and fission) as well as generation of new mitochondria are dependent on a viable circadian clock. In addition, fission and fusion processes display diurnal changes that are aligned to the light/dark cycle. Besides morphological changes, also mitochondrial respiration displays diurnal changes. Disturbing the molecular clock in animal models leads to abrogated mitochondrial rhythmicity and altered respiration. Moreover, mitochondrial-dependent production of reactive oxygen species, which plays a role in cellular signaling, has also been linked to the circadian clock. In this review we will summarize recent advances in the study of circadian rhythms of mitochondria and how this is linked to the molecular circadian clock. J Mol Endocrinol. 2018 Jan 29. pii: JME-17-0196.)

(Anm: Antidepressiva og antipsykotika gir økt risiko for diabetes hos barn og voksne (50 til 700 %) (mintankesmie.no).)

(Anm: Partial loss of complex I due to NDUFS4 deficiency augments myocardial reperfusion damage by increasing mitochondrial superoxide/hydrogen peroxide production. Abstract Recent work has found that complex I is the sole source of reactive oxygen species (ROS) during myocardial ischemia-reperfusion (IR) injury. However, it has also been reported that heart mitochondria can also generate ROS from other sources in the respiratory chain and Krebs cycle. (…) These results correlated with a significant increase in O2●-/H2O2 release rates in mitochondria isolated from NDUFS4 ± hearts subjected to an IR challenge. Taken together, these results demonstrate that the partial absence of complex I sensitizes the myocardium towards IR injury and that the main source of ROS following reperfusion is complex III. Biochem Biophys Res Commun. 2018 Mar 25;498(1):214-220.)

- Forskere identifiserer nevroner som styrer hjernens indre ur. (- Neurotransmitteren dopamin, styrer også hjernens sirkadiske senter (døgnrytmesenteret), eller "indre ur" - området som regulerer spisesykluser, metabolisme og våkne / hvilesykluser - en nøkkelforbindelse som muligens påvirker kroppens evne til å tilpasse seg jetlag og roterende skiftarbeid.)

(Anm: Forskere identifiserer nevroner som styrer hjernens indre ur. (Researchers identify neurons that control brain's body clock.) Neuroner i hjernen som produserer den glede-signaliserende neurotransmitteren dopamin, styrer også hjernens sirkadiske senter (døgnrytmesenteret), eller "indre ur" - området som regulerer spisesykluser, metabolisme og våkne / hvilesykluser - en nøkkelforbindelse som muligens påvirker kroppens evne til å tilpasse seg jetlag og roterende skiftarbeid, har en ny studie ved University of Virginia vist. (medicalxpress.com 3.8.2017).)

(Anm: Direct Midbrain Dopamine Input to the Suprachiasmatic Nucleus Accelerates Circadian Entrainment. Current Biology 2017;27(16):2465–2475.e3 (21 August 2017).)

- Skiftarbeid, søvn og helse blant sykepleiere. Roterende turnus påvirker søvnen mer negativt enn ikke-roterende turnus og nattarbeid.

(Anm: Skiftarbeid, søvn og helse blant sykepleiere. Roterende turnus påvirker søvnen mer negativt enn ikke-roterende turnus og nattarbeid. Hovedbudskap Roterende turnusarbeid er forbundet med et konstant høyere nivå av insomnisymptomer sammenliknet med ikke-roterende turnusarbeid. Det å erfare at jobben virker negativt inn på familielivet, eller motsatt, er assosiert med en økning i insomnisymptomer over tid. Spørreundersøkelsen om skiftarbeid, søvn og helse (SUSSH) har siden 2008/2009 årlig blitt sendt ut til om lag 2900 norske sykepleiere. Årets spørreskjema, som sendes ut i løpet av våren og sommeren 2017, er nummer ni i rekken. For å gjøre resultatene fra spørreundersøkelsen kjent for norske sykepleiere har vi med jevne mellomrom rapportert resultatene i Sykepleien (1–7). (sykepleien.se 30.5.2017).)

- Tap av koenzym Q10 øker risikoen for prediabetes. (- CoQ finnes i mitokondrier, kraftverkene i cellene i kroppen vår, der det er nødvendig for strømmen av elektrisitet til cellens motor som er ansvarlig for energiproduksjon, forklarte han.)

(Anm: Loss of coenzyme Q10 increases pre-diabetes risk. Levels of CoQ and the presence of insulin resistance were analyzed in a range of experimental laboratory settings, mouse models and samples from humans, as part of an ambitious research collaboration conducted with the University of Sydney, Victor Chang Cardiac Research Institute, Duke University School of Medicine, Garvan Institute of Medical Research, Genentech Inc. and the University of New South Wales. Concentrations of CoQ were found to be lower in insulin resistant body fat and muscle tissue. When the researchers replenished CoQ, insulin resistance or pre-diabetes was reversed. Co-author Dr Daniel Fazakerley from the University of Sydney’s School of Life and Environmental Science and Charles Perkins Centre said CoQ provides a vital role in converting nutrients like fat and sugar into usable energy. “CoQ is found in mitochondria, the power plants in the cells of our body, where it is required for the flow of electricity to the cell’s ‘motor’ which is responsible for energy production,” he explained. “Energy production can also generate reactive chemical species – often referred to as ‘reactive oxygen species’ or ‘oxidants’ – as by-products, which can be damaging to cells. (news-medical.net 7.2.2018).)

(Anm: Cellular Respiration in Mitochondria. What is Cellular Respiration? All living things need energy to survive. Without energy our cells cannot function and our bodies shut down. Life cannot exist without this constant supply of energy. But where does it come from? The energy your body uses to pump blood through your veins, inhale air into your lungs, and move your eyes across this page is derived from cellular respiration. Cellular respiration is a multi-step process that converts the chemical energy in food into usable cellular energy in the form of adenosine triphosphate, or ATP. ATP is like the energy currency of cells. It is necessary for cellular function and sustaining your life. This ATP is produced primarily by an organelle called the mitochondria. Mitochondria are cellular organelles (think little organs) that synthesize ATP for our cells. Let's take a look at how cellular respiration works inside the mitochondria. (study.com 4.2.2018).)

(Anm: Molekylære klokker. Arvestoffet (DNA) er stadig gjenstand for mutasjoner, dvs. varige endringer i baserekkefølgen av DNA. Mutasjonene er tilfeldige hendelser, med en gitt sannsynlighet, som for en bestemt del av DNA er tilnærmet konstant gjennom tid. På samme måte som radioaktiv nedbrytning kan omfanget av mutasjoner dermed brukes til å tidfeste hendelser, dvs. de fungerer som molekylære klokker. (…) Den molekylære klokken går ekstra raskt i mitokondrialt DNA, spesielt i det ikke-kodende området kalt D-sløyfen. Dette skyldes at mitokondrialt DNA er mer utsatt for mutasjoner gjennom oksygenradikaler enn nukleært DNA, og at det ser ut til å være mindre omfattende reparasjonssystemer for mitokondrialt DNA. Mitokondrialt DNA brukes derfor i studier av mer nylig evolusjonære hendelser, f.eks. utvikling av menneske og vandringsmønstrene for mennesker etter utvandringen fra Afrika for ca. 100 000 år siden. Kilde: Store norske leksikon.)

(Anm: Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes. (…) Highlights • Pancreatic mitochondrial complex I shows hyperactivity in diabetes. • Complex I hyperactivity is associated with increased NADH/NAD+ redox imbalance. • Complex I hyperactivity is associated with increased oxidative stress and cell death. • Complex I hyperactivity is linked with compromised cellular anti-oxidative stress capacity such as decreased sirt3 and NQO1 expressions. Biochem Biophys Rep. 2017 Sep;11:119-129.)

(Anm: Focus on an unusual rise in pancreatic cancer incidence in France. (…) Conclusion: Pancreatic cancer incidence and mortality exhibited diverging trends. Incidence increased over the last 30 years in France whereas mortality did not vary in men and moderately increased in women. Incidence remained lower than mortality up to 2002. One cannot exclude the possibility that a similar trend may appear in other countries. Etiological studies are required to further explain this increase.Int J Epidemiol. 2017 Dec 1;46(6):1764-1772.)

- Forskere identifiserer nevroner som styrer hjernens indre ur. (- Neurotransmitteren dopamin, styrer også hjernens sirkadiske senter (døgnrytmesenteret), eller "indre ur" - området som regulerer spisesykluser, metabolisme og våkne / hvilesykluser - en nøkkelforbindelse som muligens påvirker kroppens evne til å tilpasse seg jetlag og roterende skiftarbeid.)

(Anm: Forskere identifiserer nevroner som styrer hjernens indre ur. (Researchers identify neurons that control brain's body clock.) Neuroner i hjernen som produserer den glede-signaliserende neurotransmitteren dopamin, styrer også hjernens sirkadiske senter (døgnrytmesenteret), eller "indre ur" - området som regulerer spisesykluser, metabolisme og våkne / hvilesykluser - en nøkkelforbindelse som muligens påvirker kroppens evne til å tilpasse seg jetlag og roterende skiftarbeid, har en ny studie ved University of Virginia vist. (medicalxpress.com 3.8.2017).)

(Anm: Direct Midbrain Dopamine Input to the Suprachiasmatic Nucleus Accelerates Circadian Entrainment. Current Biology 2017;27(16):2465–2475.e3 (21 August 2017).)

- Mitokondrielt oksidativt stress ved kardiell lipidoverbelastning forårsaker intracellulær kalsiumlekkasje og arytmi. (- Disse resultatene tyder på en potensiell rolle for antioksidanter målrettet mitokondrier for å forhindre arytmi og plutselig hjertedød hos overvektige og diabetespasienter.)

(Anm: Mitochondrial oxidative stress during cardiac lipid overload causes intracellular calcium leak and arrhythmia. Abstract BACKGROUND: Diabetes and obesity are associated with an increased risk of arrhythmia and sudden cardiac death. Abnormal lipid accumulation is observed in cardiomyocytes of obese and diabetic patients, which may contribute to arrhythmia, but the mechanisms are poorly understood. A transgenic mouse model of cardiac lipid overload, the peroxisome proliferator-activated receptor-γ (PPARg) cardiac overexpression mouse, has long QT and increased ventricular ectopy. (…) CONCLUSION: During cardiac lipid overload, mitochondrial oxidative stress causes increased SR calcium leak by oxidizing RyR2 channels. This promotes ventricular ectopy, which is significantly reduced in vivo by a mitochondrial-targeted antioxidant. These results suggest a potential role for mitochondrial-targeted antioxidants in preventing arrhythmia and sudden cardiac death in obese and diabetic patients. Heart Rhythm. 2016 Aug;13(8):1699-706).)

– Alkoholforbruk under ungdomsår: En forbindelse mellom mitokondriell skade og alkoholforgiftning (etanolforgiftning). (- I denne vurderingen fokuserer vi på endringene som den unge hjernen gjennomgår etter å ha drukket, og legger særlig vekt på mitokondriell skade og deres konsekvenser på hjernefunksjonen. Til slutt foreslår vi mitokondrier som en viktig mediator for alkoholgiftighet og et potensielt terapeutisk mål for å redusere eller behandle hjernens tilstand assosiert med overdrevent alkoholforbruk.)

(Anm: Alcohol consumption during adolescence: A link between mitochondrial damage and ethanol brain intoxication. Abstract Adolescence is a period of multiple changes where social behaviors influence interpersonal-relations. Adolescents live new experiences, including alcohol consumption which has become an increasing health problem. The age of onset for consumption has declined in the last decades, and additionally, the adolescents now uptake greater amounts of alcohol per occasion. Alcohol consumption is a risk factor for accidents, mental illnesses or other pathologies, as well as for the appearance of addictions, including alcoholism. An interesting topic to study is the damage that alcohol induces on the central nervous system (CNS) in the young population. The brain undergoes substantial modifications during adolescence, making brain cells more vulnerable to the ethanol toxicity. Over the last years, the brain mitochondria have emerged as a cell organelle which is particularly susceptible to alcohol. Mitochondria suffer severe alterations which can be exacerbated if the amount of alcohol or the exposure time is increased. In this review, we focus on the changes that the adolescent brain undergoes after drinking, placing particular emphasis on mitochondrial damage and their consequences against brain function. Finally, we propose the mitochondria as an important mediator in alcohol toxicity and a potential therapeutic target to reduce or treat brain conditions associated with excessive alcohol consumption. Birth Defects Res. 2017 Dec 1;109(20):1623-1639.)

(Anm: Alkohol (mintankesmie.no).)

(Anm: Skader og ulykker i Norge. 2500 dør og 300 000 behandles årlig på sykehus for skader. Mange alvorlige skader er knyttet til alkohol og andre rusmidler, fall og trafikk. (…) Hva er et forgiftningsdødsfall? (fhi.no 14.12.2016).)

(Anm: Link mellom alkohol, hjerneslag, psykiatriske legemidler og demens (- Men også personer som tok medisin mot psykoser og folk som slet med depresjon, fikk forhøyd risiko for å bli rammet av demens tidlig. Høyt blodtrykk kan også øke faren for at man rammes, skriver nyhetsbyrået TT.) (vg.no 14.8.2013).)

(Anm: Etanol eller etylalkohol er den mest kjente alkoholen, og kalles i dagligtalen gjerne for «alkohol». Etanol er den viktigste bestanddelen i brennevin, f.eks. vodka, whisky og rom. Etanol har den kjemiske formelen C2H5OH, og er en fargeløs væske med spesifikk vekt 0,78 kg/l som er blandbar med vann i alle konsentrasjoner. Etanol er forholdsvis flyktig og lett antennelig, og brenner med en klar eller svakt blå flamme. (no.wikipedia.org).)

- Cellulær stress «resetter levetiden betraktelig». Overraskende resultater fra en nylig studie viser at stress på en celle kan reversere tegn på cellulær aldring. Resultatene kan åpne dører for mer vellykkede måter å redusere aldringsprosessen.

(Anm: Cellular stress 'resets lifespan profoundly'. Surprising results from a recent study show that stressing a cell can reverse signs of cellular aging. The findings might open doors to more successful ways to slow the aging process. Although the desire to stave off aging has a whiff of vanity about it, it's not all about reducing wrinkles and covering gray hair; getting older comes with a range of diseases that grow steadily more prevalent as our population ages. Those interested in senescence are keen to understand the molecular pathways involved in aging in the hope that associated disease processes will also be unlocked. Molecular bioscientists from Northwestern University in Evanston, IL, recently gained a new and surprising insight into cellular aging. Their findings are published this week in the journal Cell Reports. This new study focused on the transparent nematode Caenorhabditis elegans. This species is often used as a model for human aging and disease; its cellular properties and biochemical environment are similar to our own.  (…) 'It's like magic'. These surprising findings fly in the face of the previously held notion that stressing mitochondria has negative effects, as Prof. Morimoto explains. He says, "This has not been seen before." "People have always known that prolonged mitochondrial stress can be deleterious," he explains. "But we discovered that when you stress mitochondria just a little, the mitochondrial stress signal is actually interpreted by the cell and animal as a survival strategy. It makes the animals completely stress-resistant and doubles their lifespan. It's like magic." (...) What they found came as a surprise: under these conditions, mitochondria sent out signals to the protein machinery, preventing it from failing. This, in turn, reduced the buildup of badly packed proteins. (medicalnewstoday.com 8.11.2017).)

(Anm: Rask gåing kan hjelpe eldre kvinner til å leve lenger. Brisk walking may help older women live longer. (…) This was the main finding of a large study — by researchers from Brigham and Women's Hospital in Boston, MA — that measured physical activity in older women as they wore sensitive activity trackers and then followed them for up to 4 years. "Physical inactivity is estimated to cause as many deaths globally each year as smoking," note the researchers in a report on the study that was published recently in the journal Circulation. (medicalnewstoday.com 8.11.2017).)

(Anm: Fysisk trening (aktivitet / løping / jogging). (mintankesmie.no).)

- Mitokondriell stress induserer cellulær senescence på en mTORC1-avhengig måte. (- Resultatene avslører en ny sammenheng mellom mitokondriell dysfunksjon, mTORC1-signalering og senesensprogrammet.)

(Anm: Mitochondrial stress induces cellular senescence in an mTORC1-dependent manner. Abstract Although mitochondrial stress is a key determinant of cellular homeostasis, the intracellular mechanisms by which this stress is communicated to the nucleus and its impact on cell fate decisions are not well defined. (…) Consistent with these results, both total and mitochondrial-specific ROS increased in cells undergoing replicative senescence along with ribosomal p70 phosphorylation. The results reveal a novel link between mitochondrial dysfunction, mTORC1 signaling, and the senescence program. Free Radic Biol Med. 2016 Jun;95:133-54.)

(Anm: Drug-induced premature senescence model in human dental follicle stem cells. Oncotarget. 2017 Jan 31;8(5):7276-7293.)

- Gjennombrudd: Forskere reverserer aldring i menneskelige celler.

(Anm: Breakthrough: Scientists reverse aging in human cells. New research published in the journal BMC Cell Biology shows that old human cells can be rejuvenated using chemicals similar to resveratrol, which is a substance found in red wine and dark chocolate. The new study was carried out by researchers at the Universities of Exeter and Brighton, both of which are located in the United Kingdom. (…) The new study builds on previous research from the University of Exeter, which found that so-called splicing factors — which are a type of protein — tend to become inactive as we age. (medicalnewstoday.com 8.11.2017).)

- IMB forskere avslører aldringsprosessens mysterium. Forskere ved Institute of Molecular Biology (IMB) i Mainz har gjort et gjennombrudd i å forstå opprinnelsen til aldringsprosessen.

(Anm: IMB researchers unveil mystery of aging process. esearchers at the Institute of Molecular Biology (IMB) in Mainz have made a breakthrough in understanding the origin of the aging process. They have identified that genes belonging to a process called autophagy, which is one of the cells most critical survival processes, promote health and fitness in young worms but drive the process of aging later in life. This research published in the journal Genes & Development gives some of the first clear evidence for how the aging process arises as a quirk of evolution. These findings may also have broader implications for the treatment of neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's disease where autophagy is implicated. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole body health. Getting old is something that happens to everyone and nearly every species on this planet, but the question is: should it? In a recent publication in the journal Genes & Development titled "Neuronal inhibition of the autophagy nucleation complex extends lifespan in post-reproductive C. elegans," Dr. Holger Richly's lab at IMB has found some of the first genetic evidence that may put this question to rest. (news-medical.net 15.11.2017).)

(Anm: Brain mitochondrial iron accumulates in Huntington's disease, mediates mitochondrial dysfunction, and can be removed pharmacologically. Abstract Mitochondrial bioenergetic dysfunction is involved in neurodegeneration in Huntington's disease (HD). Iron is critical for normal mitochondrial bioenergetics but can also contribute to pathogenic oxidation. The accumulation of iron in the brain occurs in mouse models and in human HD. Yet the role of mitochondria-related iron dysregulation as a contributor to bioenergetic pathophysiology in HD is unclear. (…) Our findings thus demonstrate the significance of iron as a mediator of mitochondrial dysfunction and injury in mouse models of human HD and suggest that targeting the iron-mitochondrial pathway may be protective. Free Radic Biol Med. 2018 Apr 3. pii: S0891-5849(18)30165-5.)

- Neurodegenerasjon: Ny celledødsmekanisme avslørt. Ny forskning viser hvordan en dysfunksjon i hjernens såkalte selvfordøyelsessystem fører til celledød i neurodegenerative lidelser. (- Ved autofagi blir hjernecelledeler som ikke lenger er nyttige brutt ned i enda mindre deler, resirkulert, og brukes deretter til å lage nye celler. Imidlertid er autofag-prosessen feil i neurodegenerative tilstander som demens, Parkinsons, Huntingtons sykdom og mange andre uhelbredelige lidelser.)

(Anm: Neurodegeneration: New cell death mechanism revealed. New research reveals how a dysfunction in the brain's so-called self-digestion system leads to cell death in neurodegenerative disorders. The newly discovered mechanism may lead to new therapies for conditions such as Parkinson's and Alzheimer's disease. In autophagy, brain cell parts that are no longer useful are broken down into even smaller parts, recycled, and are then used to create new cells. However, in neurodegenerative conditions such as dementia, Parkinson's, Huntington's disease, and many other incurable disorders, the autophagy process is faulty. While this is something that researchers already knew, what they didn't know until now were the precise mechanisms by which this happens, and more specifically, how this leads to cell death — particularly in the late stages of the disease. New research uncovers precisely these mechanisms. The groundbreaking study was carried out by scientists at King's College London in the United Kingdom, and the findings were published in the journal Current Biology. While the study used a model of a single, rare neurodegenerative disorder known as dentatorubral-pallidoluysian atrophy (DRPLA), the findings are likely applicable to all neurological conditions that are characterized by faulty autophagy. (medicalnewstoday.com 23.11.2017).)

- Kan vitenskapen om autophagy forbedre helsen din? Lite kjent vitenskapelig prosess blir hyllet som den nye måten å gå ned i vekt på, se yngre ut og forlenge livet.

(Anm: Can the science of autophagy boost your health? A little-known scientific process is being hailed as the new way to lose weight, look younger and prolong life. (…) So what do scientists say? "Certainly the evidence from experiments in mice suggest that would be the case," said Dr David Rubinsztein, professor of molecular neurogenetics at the University of Cambridge and UK Dementia Research Institute. "There are studies where they have switched on the process using genetic tools or drugs or fasting, and in those cases the animals tend to live longer and be in better overall shape." (…) What is autophagy? - The word autophagy comes from the Greek for "self" and "phagein", which means "to eat" - It is the process by which cells degrade and recycle their components - It provides fuel for energy and building blocks for cell renewal - After infection, autophagy can destroy bacteria and viruses - Cells use autophagy to get rid of damaged proteins and organelles, to counteract the negative effects of ageing on the body. (bbc.com 6.5.2018).)

- Alzheimer: Lavt serotoninnivå kan drive utviklingen. En av hypotesene frem til nå har vært at nevrotransmitteren serotonin spiller en nøkkelrolle. (…) Prof. Smith bemerker imidlertid at SSRI-behandling for Alzheimers sykdom ikke har vist seg å være vellykket.

(Anm: Alzheimer: Lavt serotoninnivå kan drive utviklingen. En av hypotesene frem til nå har vært at nevrotransmitteren serotonin spiller en nøkkelrolle. (…) Prof. Smith bemerker imidlertid at SSRI-behandling for Alzheimers sykdom ikke har vist seg å være vellykket. (Alzheimer's: Low serotonin levels may drive development. One of the hypotheses put forth so far has been that the neurotransmitter serotonin plays a key role. In recent years, studies have accumulated evidence that people with Alzheimer's disease have less of this brain chemical, which is known to regulate mood, sleep, appetite, and sexual function, among other things. (…) Prof. Smith notes, however, that SSRI treatment for Alzheimer's disease has not been proven successful. The reason for this, she ventures, might be that SSRIs need to bind to serotonin transporters in order to work, but in patients with Alzheimer's disease, it is precisely these transporters that are missing. She therefore suggests that serotonin receptors - rather than transporters - might be a better therapeutic target. (medicalnewstoday.com 16.8.2017).)

(Anm: Alzheimers sykdom og andre årsaker til demens. (mintankesmie.no).)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Effekten av psykostimulerende legemidler på blod-hjerne barrierens funksjon og nevroinflammasjon. (The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation) (Front. Pharmacol. 2012;3:121 (Published online: 29 June 2012).)

- Legemiddelindusert mitokondriell toksisitet (giftighet). (- Mekanismene for legemiddelindusert mitokondriell svekkelse av funksjonsevne vil bli diskutert sammen med formodede terapeutiske strategier for å motvirke de negative effektene av legemiddelbehandlingen.)

(Anm: Drug-Induced Mitochondrial Toxicity. Abstract The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These 'off-target' pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA. The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical 'weight loss' agent. The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy. Drug Saf. 2016 Jul;39(7):661-74.)

(Anm: RE: Psykisk syke lever kortere. (…)  Som et eksempel kan nevnes at antidepressiva, antipsykotika, sovemidler etc. er nevrotoksiske og mitokondrietoksiske, og derfor medfører risiko for invalidiserende bivirkninger og tidlig død (4-7). Tidsskr Nor Legeforen 2015 (11.08.2015 - 02.09.2015 - 16.10.2015 - 10.11.2015. (PDF).)

(Anm: Mitochondrial Toxicity. Abstract Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ~1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity. We also discuss the potential importance of hormetic effects of mitochondrial stressors. Finally, we comment on future areas of research we consider critical for mitochondrial toxicology, including increased integration of clinical, experimental laboratory, and epidemiological (human and wildlife) studies; improved understanding of biomarkers in the human population; and incorporation of other factors that affect mitochondria, such as diet, exercise, age, and nonchemical stressors. Toxicol Sci. 2018 Jan 11.)

(Anm: Mitochondrial Toxicity. Toxicology. 2017 Nov 1;391:1.)

(Anm: Mitochondrial toxicity (Glu/Gal) assay. Impairment of mitochondrial function is increasingly implicated in the etiology of drug-induced toxicity. For example, mitochondrial dysfunction was found to play a role in the toxicity of troglitazone and cerivastatin which were withdrawn from the US market in 2000 and 2001 respectively.1 Mitochondria produce >90% of the cellular energy requirements in the form of adenosine triphosphate (ATP) via oxidative phosphorylation. (cyprotex.com 1.2.2018).)
(Anm: The significance of mitochondrial toxicity testing in drug development. Drug Discov Today. 2007 Sep;12(17-18):777-85.)

(Anm: Mitochondrial Toxicity. Toxicology. 2017 Nov 1;391:1.)

(Anm: Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Abstract Many highly proliferative cells generate almost all ATP via glycolysis despite abundant O(2) and a normal complement of fully functional mitochondria, a circumstance known as the Crabtree effect. (…) To increase detection of drug-induced mitochondrial effects in a preclinical cell-based assay, HepG2 cells were forced to rely on mitochondrial oxidative phosphorylation rather than glycolysis by substituting galactose for glucose in the growth media. Oxygen consumption doubles in galactose-grown HepG2 cells and their susceptibility to canonical mitochondrial toxicants correspondingly increases. Similarly, toxicity of several drugs with known mitochondrial liabilities is more readily apparent in aerobically poised HepG2 cells compared to glucose-grown cells. Some drugs were equally toxic to both glucose- and galactose-grown cells, suggesting that mitochondrial impairment is likely secondary to other cytotoxic mechanisms. Toxicol Sci. 2007 Jun;97(2):539-47. Epub 2007 Mar 14.)

– Vær opmærksom på mulig risiko for leverskader ved medicinsk behandling af fibromer. Det Europæiske Lægemiddelagentur (EMA) har igangsat en ekstra undersøgelse af lægemidlet Esmya (ulipristal) og risikoen for udvikling af alvorlige leverskader.

(Anm: Vær opmærksom på mulig risiko for leverskader ved medicinsk behandling af fibromer. Det Europæiske Lægemiddelagentur (EMA) har igangsat en ekstra undersøgelse af lægemidlet Esmya (ulipristal) og risikoen for udvikling af alvorlige leverskader. Esmya (ulipristal) bruges til behandling af moderate til svære symptomer på fibromer i livmoderen hos kvinder i den fertile alder. Behandlingen foretages kun hos speciallæger i gynækologi. Det er EMAs bivirkningskomité, PRAC, som står for gennemgangen af, hvorvidt Esmya (ulipristal) giver risiko for udvikling af alvorlige leverskader. PRACs vurdering forventes at være færdig i maj 2018. (lakemedelsvarlden.se d1.2.2018).)

- Linker mitokondriell dynamikk til mitokondriell kvalitetskontroll av protein.

(Anm: Linking mitochondrial dynamics to mitochondrial protein quality control. Abstract Over the last decade, countless discoveries have been made that have expanded our knowledge of mitochondrial biology, and more often than not, these discoveries provided fascinating new insights into the etiology of human disease. For example, advances in mitochondrial genetics exposed the role of mitochondrial mutations in cancer progression, and the discovery of mitophagy highlighted the role of mitochondrial quality control in Parkinson's disease. Additional discoveries underscored the importance of the mTor pathway in aging and disease, and more recently, the mitochondrial unfolded protein response was implicated in the regulation of mammalian lifespan. Some of the most fundamental discoveries though, were made in the context of mitochondrial fusion and fission. The balance between these two opposing forces shapes the mitochondrial population in our cells, and influences mitochondrial function at every level. Here, we highlight the basic biology that underlies mitochondrial fusion and fission, explain how these processes promote human health by solving a problem that is innate to multifarious organelles, and make a novel prediction: that fusion and fission are intimately linked to mitochondrial protein quality control. Curr Opin Genet Dev. 2016 Jun;38:68-74.)

- Cellulær bioenergetikk er svekket hos pasienter med kronisk utmattelsessyndrom (CFS). (Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.) (- Resultatene viste konsekvent lavere målinger av OXPHOS parametere i PBMC som er tatt fra CFS pasienter sammenlignet med sunne kontrollpersoner. Sju nøkkelparametere for OXPHOS ble planlagt: basal respirasjon, ATP-produksjon, protonlekkasje, maksimal respirasjon, reservekapasitet, ikke-mitokondriell respirasjon og koblingseffektivitet.)

(Anm: Cellular bioenergetics is impaired in patients with chronic fatigue syndrome. Abstract Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand. PLoS One. 2017 Oct 24;12(10):e0186802. eCollection 2017.)

(Anm: ME: Jeg ble avfeid med at jeg var lat og oppmerksomhetssyk. Hanne lå på et mørkt rom i to år med ME. Hun veide 28 kilo. (kk.no 2.9.2017).)

(Anm: «Å være på kafé og gå turer har hun krefter til, men ikke å jobbe». (…) Om du gikk fra å kunne jobbe 100 prosent til på enkelte dager ikke ha krefter nok til å komme deg opp av sengen?  (aftenposten.no 19.9.2017).)

(Anm: Kronisk tretthetssyndrom/Myalgisk encefalopati (CFS/ME). (mintankesmie.no).)

(Anm: Chronic Fatigue Syndrome Causes and Treatment (webmd.com 1.6.2016).)

(Anm: Nøkkelen til kronisk utmattelsessyndrom sitter i tarmen, ikke hodet. (Key to chronic fatigue syndrome is in your gut, not head.) (mediarelations.cornell.edu 27.6.2016).)

- Våre (mors) mitokondrier og vårt sinn. (- Det meste av energien vi får å bruke er levert av mitokondrier, svært små levende strukturer som sitter inne i våre celler eller sendes frem og tilbake innvendig hvor de trengs. Mitokondrier produserer energi ved å forbrenne hva som gjenstår av måltider etter at vi har fordøyd det, men på bekostning av stadig å tære på seg selv og oss. (- Vi diskuterer hvorfor motvirkning av mitokondriell tæring mht. antioksidant fra kosttilskudd ofte er uklokt, og hvorfor våre mitokondrier, og derfor vi selv, i stedet har nytte av trening, meditasjon, søvn, solskinn og spesielle matvaner.)

(Anm: Våre (mors) mitokondrier og vårt sinn. Abstrakt Det meste av energien vi får å bruke er levert av mitokondrier, svært små levende strukturer som sitter inne i våre celler eller sendes frem og tilbake innvendig hvor de trengs. Mitokondrier produserer energi ved å forbrenne hva som gjenstår av måltider etter at vi har fordøyd det, men på bekostning av stadig å tære på seg selv og oss. Her vurderer vi hvordan mitokondrier utviklet seg fra invaderende bakterier og har beholdt en liten grad av uavhengighet fra oss; hvordan vi arver dem bare fra vår mor; og hvordan de er tungt involvert i læring, minne, kognisjon og nesten alle mentale eller nevrologiske lidelser. Vi diskuterer hvorfor motvirkning av mitokondriell tæring mht. antioksidant fra kosttilskudd ofte er uklokt, og hvorfor våre mitokondrier, og derfor vi selv, i stedet har nytte av trening, meditasjon, søvn, solskinn og spesielle matvaner. Til slutt beskriver vi hvordan mitokondriell funksjonsfeil tvinger rotter til å bli sosialt underordnet andre, hvordan slike forskjeller kan kompenseres av et vitamin, og hvorfor disse funnene er relevante for oss. (Our (Mother's) Mitochondria and Our Mind. Abstract Most of the energy we get to spend is furnished by mitochondria, minuscule living structures sitting inside our cells or dispatched back and forth within them to where they are needed. Mitochondria produce energy by burning down what remains of our meal after we have digested it, but at the cost of constantly corroding themselves and us. Here we review how our mitochondria evolved from invading bacteria and have retained a small amount of independence from us; how we inherit them only from our mother; and how they are heavily implicated in learning, memory, cognition, and virtually every mental or neurological affliction. We discuss why counteracting mitochondrial corrosion with antioxidant supplements is often unwise, and why our mitochondria, and therefore we ourselves, benefit instead from exercise, meditation, sleep, sunshine, and particular eating habits. Finally, we describe how malfunctioning mitochondria force rats to become socially subordinate to others, how such disparity can be evened off by a vitamin, and why these findings are relevant to us.) Perspect Psychol Sci. 2017 Sep 1:1745691617718356. [Epub ahead of print].)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Fathers can influence the sex of their offspring, scientists show. It has traditionally been thought that in mammals only mothers are able to influence the sex of their offspring. But a new study in wild mice led by Dr Aurelio Malo of Oxford University's Department of Zoology has shown that fathers can, in fact, influence sex ratios. The paper is published in the journal Proceedings of the Royal Society B and involves researchers from the UK, Spain and the USA. (medicalnewstoday.com 13.9.2017).)

(Anm: A father effect explains sex-ratio bias. (…) 'The implications are important, as we now have the proof that fathers matter independently of any maternal effects. Scientists can now improve their predictive models of sex ratios at birth, including not only mothers but also fathers. 'Proc Biol Sci. 2017 Aug 30;284(1861). pii: 20171159. doi: 10.1098/rspb.2017.1159.)

- Antipsykotikas (nevroleptikas) hemming av kompleks I i cortex i normale menneskehjerner er en parallell til den ekstrapyramidale giftigheten til antipsykotika (neuroleptika). (…) Våre data støtter hypotesen om at antipsykotika (nevroleptika)-induserte ekstrapyramidale bivirkninger kan skyldes hemming av mitokondriell respiratorisk kjede.

(Anm: Antipsykotikas (nevroleptikas) hemming av kompleks I i cortex i normale menneskehjerner er en parallell til den ekstrapyramidale giftigheten til antipsykotika (nevroleptika). (…) Våre data støtter hypotesen om at antipsykotika (neuroleptika)-induserte ekstrapyramidale bivirkninger kan skyldes hemming av mitokondriell respiratorisk kjede.(Inhibition of complex I by neuroleptics in normal human brain cortex parallels the extrapyramidal toxicity of neuroleptics. (…) Our data support the hypothesis that neuroleptic-induced extrapyramidal side effects may be due to inhibition of the mitochondrial respiratory chain.) Mol Cell Biochem. 1997 Sep;174(1-2):255-9.)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

(Anm: Kan Lupus øke risikoen for demens? Could lupus raise dementia risk? People living with lupus may be at significantly greater risk of developing dementia than those without the autoimmune disease, a new study suggests. (…) Study co-author Daniela Amital, of the Sackler Faculty of Medicine at Tel Aviv University in Israel, and colleagues recently reported their results in the International Journal of Geriatric Psychiatry. (medicalnewstoday.com 9.11.2017).)

(Anm: Mitochondrial Dysfunction and Altered Renal Metabolism in Dahl Salt-Sensitive Rats. Kidney Blood Press Res. 2017 Sep 19;42(3):587-597.)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

- Mitokondrier i nervesystemet: Fra helse til sykdom, del I.

(Anm: Mitokondrier i nervesystemet: Fra helse til sykdom, del I. (Mitochondria in the nervous system: From Health to Disease, Part I.) (…) Til sist granskes nye måter å redde mitokondriell struktur og funksjon ved akutt og kronisk hjerneskade. (Finally, novel ways to rescue mitochondrial structure and function in acute and chronic brain injury are explored.) Neurochem Int. 2017 Sep 13. pii: S0197-0186(17)30481-3.)

(Anm: Functional Mitochondria in Health and Disease. The ability to rapidly adapt cellular bioenergetic capabilities to meet rapidly changing environmental conditions is mandatory for normal cellular function and for cancer progression. Any loss of this adaptive response has the potential to compromise cellular function and render the cell more susceptible to external stressors such as oxidative stress, radiation, chemotherapeutic drugs, and hypoxia. Mitochondria play a vital role in bioenergetic and biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cell. Increased demand is met by mitochondrial biogenesis and fusion of individual mitochondria into dynamic networks, whereas a decrease in demand results in the removal of superfluous mitochondria through fission and mitophagy. (…) Concluding Remarks The ability to adapt cellular bioenergetics capabilities to meet rapidly changing environmental conditions is mandatory for cellular function and for cancer progression. Any compromise in this adaptive response has the potential to compromise cellular function and render the cell more susceptible to external stressors such as oxidative stress, radiation, chemotherapeutic drugs, hypoxia, etc. Front. Endocrinol. 2017 (03 November 2017).)

(Anm: Fluoksetin (Prozac; SSRI) og mitokondriene: En gjennomgang av de toksikologiske aspekter. (- Fluoksetin induserer også bivirkninger, som for eksempel angst, seksuell dysfunksjon, søvnforstyrrelser, og gastrointestinale svekkelser.) (Fluoxetine and the mitochondria: A review of the toxicological aspects. (Fluoksetin og mitokondriene: En gjennomgang av de toksikologiske aspekter.) Toxicol Lett. 2016 Jul 5. pii: S0378-4274(16)32264-0.)

- Linker mitokondrier og synaptisk overføring: CB1-reseptoren. (- Akutt aktivering av mtCB1 endrer mitokondrisk ATP-generasjon, synaptisk overføring og hukommelse, ytelse.)

(Anm: Linking Mitochondria and Synaptic Transmission: The CB1 Receptor. Abstract CB1 receptors are functionally present within brain mitochondria (mtCB1), although they are usually considered specifically targeted to plasma membrane. Acute activation of mtCB1 alters mitochondrial ATP generation, synaptic transmission, and memory performance. However, the detailed mechanism linking disrupted mitochondrial metabolism and synaptic transmission is still uncharacterized. CB1 receptors are among the most abundant G protein-coupled receptors in the brain and impact on several processes, including fear coping, anxiety, stress, learning, and memory. Mitochondria perform several key physiological processes for neuronal homeostasis, including production of ATP and reactive oxygen species, calcium buffering, metabolism of neurotransmitters, and apoptosis. It is therefore possible that acute activation of mtCB1 impacts on these different mitochondrial functions to modulate synaptic transmission. In reviewing and integrating across the literature in this area, we describe the possible mechanisms involved in the regulation of brain physiology by mtCB1 receptors. Bioessays. 2017 Oct 23. doi: 10.1002/bies.201700126.)

- Alvorlig epilepsi og sirkadisk rytmeprotein linket. Nye funn kan åpne døren til nye behandlinger av epilepsi.

(Anm: Severe epilepsy and circadian rhythm protein linked. New findings may open the door to novel epilepsy treatments. Researchers probing the brain tissue of people with severe forms of epilepsy make a surprising breakthrough: a protein involved in circadian rhythms, called CLOCK, may play a role. Epilepsy is a relatively common brain disorder that causes seizures. It affects around 1.2 percent of people in the United States, and to date, it is not curable. There are drugs available to treat the condition, but side effects can be significant and not all cases of epilepsy respond well. Although certain genetic mutations have been identified that are responsible for inherited forms of epilepsy, these only account for a minority of cases. In most cases, the exact causes are unknown. (medicalnewstoday.com 12.10.2017).)

(Anm: Epilepsi og legemidler (mintankesmie.no).)

- Stor betydning for helsen Forskning tyder på at en dårlig koordinert indre tidtagning øker risikoen for sykdom, for eksempel ved langvarig skiftarbeid.

(Anm: Får nobelpris for oppdagelsen av døgnrytmen. De amerikanske forskerne Jeffrey C. Hall, Michael Rosbash og Michael W. Young tildeles årets nobelpris i medisin eller fysiologi for oppdagelsen av den biologiske klokka. (…) Et selvregulerende urverk i kroppen Årets nobelprisvinnere begynte med å studere et gen som krevdes for bananfluens normale døgnrytme. De viste at genet kodet for et protein som økte om natten men brøt ned til lave nivåer om dagen. De identifiserte flere proteiner og kunne dermed beskrive et selvregulerende urverk i våre celler. Klokken har siden vist seg å fungere med samme prinsipp i andre flercellede organismer, også i menneske. (…) Stor betydning for helsen Forskning tyder på at en dårlig koordinert indre tidtagning øker risikoen for sykdom, for eksempel ved langvarig skiftarbeid. Etter nobelprisvinnernes oppdagelser har cirkadisk biologi utviklet seg til et dynamisk og raskt voksende forskningsfelt, med stor betydning for helsen vår. (nrk.no 2.10.2017).)

(Anm: Interview about the 2017 Nobel Prize in Physiology or Medicine (8 minutes) (nobelprize.org 2017).)

- SSRI-er (lykkepiller) forårsaker en varig serotonerg ubalanse grunnet legemidlenes skadelige endringer mht. serotonin og andre nevrotransmittere, mitokondriell dysfunksjon, avkortet levetid, plutselige dødsfall etc.

(Anm: SSRI-er (lykkepiller) forårsaker en varig serotonerg ubalanse grunnet legemidlenes skadelige endringer mht. serotonin og andre nevrotransmittere, mitokondriell dysfunksjon, avkortet levetid, plutselige dødsfall etc. (- SSRI-er øker nivået av serotonin i deler av hjernen med opptil 700 % (eller mer?), samt reduserer serotonin i blod med opptil 93 %.) (mintankesmie.no).)

(Anm: Effekten av psykostimulerende legemidler på blod-hjerne barrierens funksjon og nevroinflammasjon. (The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation) (Front. Pharmacol. 2012;3:121 (Published online: 29 June 2012).)

(Anm: More than just 'chemo brain': Cancer impacts memory, too. People undergoing cancer treatment often report experiencing "chemo brain," or states of confusion and cognitive impairment due to aggressive chemotherapy treatment. But new research suggests that these cognitive problems might start earlier, with the development of cancer tumors. (…) He adds, "Both factors independently affect brain function in different ways, which can lead to the development of other psychological disturbances, such as anxiety and depression." The team's findings were recently published in the journal Neuroscience. (medicalnewstoday.com 23.11.2017).)

(Anm: Immune cells cross blood-brain barrier in multiple sclerosis. Researchers probing the mechanisms of nerve tissue damage in multiple sclerosis have identified two ways in which white blood cells overcome the blood-brain barrier to wreak havoc in the highly protected environment of the brain and spinal cord. In a paper published in the journal Cell Reports, first study author Sarah Lutz, assistant professor of anatomy and cell biology at the University of Illinois at Chicago, and colleagues describe how they studied mechanisms of immune attack on the central nervous system (CNS) in a mouse model of multiple sclerosis (MS). (medicalnewstoday.com 23.11.2017).)

- [Assosiasjonen for mitokondrie-DNA-oriB-variantene av metabolsk syndrom].

(Anm: [The association of the mitochondrial DNA oriB variants with metabolic syndrome]. Abstract Different genes are involved in the development of pathology and formation the metabolic syndrome (MS) phenotype. In the literature, there is a data connection to the site oriB polymorphisms of mitochondrial DNA (mtDNA), known as 16184-16193 polycytosine tract, with insulin resistance, type 2 diabetes (T2DM) and other metabolic abnormalities in different ethnic populations. It is supposed that for certain polymorphisms at this site decreases mtDNA copy number in the cells. In this study, we have identified different allelic variants of the mtDNA oriB site in MS patients (n=106) and healthy individuals (n=71) using capillary sequencing, and determined the amount of mtDNA copy blood leukocytes by droplet digital polymerase chain reaction (ddPCR). The continuous polycytosine tract was significantly more common in MS patients, and such a link was particularly strong in MS patients with type 2 diabetes (p<0.01). No significant correlation has been found between mtDNA copy number and the oriB site variants, but in general there is a tendency to decreased mtDNA copy number in MS patients. Biomed Khim. 2017 Nov;63(6):533-538.)

(Anm: Diabetes due to Mitochondrial Adipopathy. (…) Overall, this interesting case confirms that mitochondrial diabetes may not only occur due to decreased insulin production but also due to insulin resistance. Although the cause of insulin resistance remains speculative, it is most likely also attributable to the underlying metabolic defect. Intern Med. 2017 Mar 15; 56(6): 747.)

- Tarmbakterier i ung alder kan bidra til MS-utbrudd og progresjon, forklarer studien.

(Anm: Gut bacteria at young age can contribute to MS onset and progression, study suggests. Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to Multiple sclerosis (MS) disease onset and progression. In this study, published in the October 31 issue of the Proceedings of the National Academy of Sciences, Sudhir Yadav PhD, a neuroimmunology post-doctoral fellow in the laboratories of Drs. Kouichi Ito, associate professor of neurology, and Suhayl Dhib-Jalbut, professor and chair of neurology, tested mice that were engineered to have a pre-disposition for MS. Because mice would not normally develop MS, researchers used MS-associated risk genes from real patients to genetically engineer mice for this study. Dr. Ito created this unique model of genetically engineered mice to specifically study the cause of MS. (news-medical.net 17.11.2017).)

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

- Danske forskere har i løbet af få uger ved hjælp af ny metode til identifikation af bakterier identificeret lige så mange bakteriearter, som det har taget alle verdens bakterieforskere 25 år at identificere. (- Forskere verden over har brugt 25 år på at identificere sølle 2 millioner ud af verdens estimerede 1 milliard bakteriearter.)

(Anm: Danske bakterieforskere laver 25 års arbejde på få uger. En danskudviklet metode gør forskere i stand til at identificere millioner af bakterier langt hurtigere, og det kan revolutionere bakterieforskningen. Forskere verden over har brugt 25 år på at identificere sølle 2 millioner ud af verdens estimerede 1 milliard bakteriearter. (…) Derved kan de, i løbet af få uger, identificere det samme antal bakterier, som verdens forskere brugte 25 år på at finde. (…) »Med den her metode kan vi for første gang seriøst overveje at lave et komplet livets træ, hvor alle arter af bakterier og andre mikroorganismer indgår. Rigtig meget videnskab har udgangspunkt i databaser over bakterier, og med den her metode kan databaserne hurtigt udvides mange gange,« fortæller lektor Mads Albertsen fra Institut for Kemi og Biovidenskab ved Aalborg Universitet. Det nye studie er for nylig offentliggjort i det videnskabelige tidsskrift Nature Biotechnology. (…) Læs også: Tarmbakterier kan være nøglen til fremtidens fedmemedicin Vil finde ud af, hvordan bakterier blev til mennesker Personligt ser Mads Albertsen gerne, at metoden bliver brugt til at få kortlagt så mange bakterier, at man kan stykke livets træ sammen og begynde at kortlægge slægtskabet mellem ikke bare bakterier, men også mellem bakterier, planter og dyr. Metoden kan på den måde blive brugt til at skabe en dybere forståelse af, hvordan livet på Jorden har udviklet sig. (videnskab.dk 12.2.2018).)

(Anm: Alzheimer's disease: Could a leaky blood-brain barrier be involved? A study found that the blood-brain barrier was leakier in a group of people with Alzheimer's disease than their healthy counterparts. The researchers suggest this means increased brain-barrier permeability may be a key contributor to the early stages of the disease. The team, including Walter H. Backes, a professor in medical physics at Maastricht University Medical Center in the Netherlands, reports the study in the journal Radiology. Prof. Backes says: "Blood-brain barrier leakage means that the brain has lost its protective means, the stability of brain cells is disrupted and the environment in which nerve cells interact becomes ill-conditioned. These mechanisms could eventually lead to dysfunction in the brain." (medicalnewstoday.com 31.5.2016).)

- Antidepressiva ökar risken för benbrott hos äldre.

(Anm: Antidepressiva ökar risken för benbrott hos äldre. (…) Den förhöjda risken för höftfraktur gällde alla de vanliga antidepressiva läkemedlen, SSRI-preparat, mirtazapin och SNRI-preparat (selektiva serotonin- och noradrenalinåterupptagshämmare. Sambandet gällde även då det kontrollerats för andra faktorer som ålder, annan medicinering som ökar fallrisken, benskörhet, socioekonomisk status, kroniska sjukdomar och psykiatriska diagnoser.) (lakemedelsvarlden.se 12.1.2017).)

- Hvordan trening forynger celler, forlenger levetiden. Ny forskning gir innsyn i hvordan trening, på cellulært nivå, kan øke muskelhelse og til slutt treningskapasitet, som er "den beste indikator på dødelighet i befolkningen."

(Anm: How exercise rejuvenates cells, extending lifespan. New research provides a window into how, on a cellular level, exercise can improve muscle health and, ultimately, exercise capacity, which is "the best predictor of mortality in the general population." A new study published in the journal Nature Communications describes how exercise helps the body to keep the cells in the muscles healthy and strong. "Whether muscle is healthy or not really determines whether the entire body is healthy or not," says lead researcher Prof. Zhen Yan, of the University of Virginia School of Medicine in Charlottesville. "And exercise capacity, mainly determined by muscle size and function," he adds, "is the best predictor of mortality in the general population." According to the new study, exercise improves muscle health by renewing its cellular powerhouse: the mitochondria. Mitochondria are crucial to the good functioning of our bodies, as well as to our overall health and longevity. These tiny parts of the cell turn the food we eat into energy. Mitochondria transform proteins, fats, and sugars into the fuel that the body needs to live. So, how does exercise affect the mitochondria in the muscles? Exercise promotes mitophagy in mice The answer given by the new study is through "mitophagy." Mitophagy describes the process by which damaged or defective mitochondria are selected and removed, usually after a period of stress. In the case of muscles, mitophagy contributes to keeping skeletal muscle healthy and strong. And to show how exercise induces mitophagy, Prof. Yan and team genetically modified mice to carry a gene that helps to report on the effects of physical activity. This gene is called pMitoTimer. It makes mitochondria fluorescent, allowing the researchers to study mitophagy in vivo, after the mice engaged in 90 minutes of treadmill running. Three to 12 hours after the running session, the researchers observed that mitochondria showed signs of stress. After 6 hours, they saw signs of mitophagy. Prof. Yan explains the effect of exercise on mitochondria through an analogy that includes a vehicle inspection, the purpose of which is to remove defective cars from the streets. "Aerobic exercise removes damaged mitochondria in skeletal muscle. If you do it repeatedly, you keep removing the damaged ones. You have a better muscle with better mitochondrial quality. We clean up the clunkers, now the city, the cell, is full of healthy, functional cars." Prof. Zhen Yan Chemical reaction in mitophagy identified The researchers also identified the molecular mechanism behind the process. The treadmill workout seemed to activate a kinase called AMPK. A kinase is an enzyme that modifies other proteins through a process called phosphorylation. In this biochemical process, phosphate groups are added to proteins. The researchers determined that, in a biochemical chain reaction, AMPK triggers another kinase called Ulk1. Prof. Yan continues the vehicle inspection analogy, saying, "When [it's] turned on, Ulk1 activates other components in the cell to execute the removal of dysfunctional mitochondria." "It's analogous to a 911 call where a tow truck removes the clunkers. However," he says, "we still do not know how these activities are coordinated." To confirm their discovery - that Ulk1 plays a critical role in mitophagy - the team created a mouse model lacking the Ulk1 gene. These mice were also subjected to treadmill exercise, but the ensuing mitophagy was considerably inhibited. Mice that were unable to do mitophagy did not have the benefit of exercise," explains study co-author Joshua Drake, a postdoctoral fellow in Prof. Yan's laboratory. "Even though, from an exercise standpoint, they still were able to run just as far as normal mice, they didn't benefit metabolically with training," he adds.
"These findings provide direct evidence of exercise-induced mitophagy and demonstrate the importance of Ampk-Ulk1 signaling in skeletal muscle," the authors conclude. (medicalnewstoday.com 29.9.2017).)

- Ampk fosforylering av Ulk1 er krevet for målretting av mitokondrier til lysosomer i treningsinducert mitofagi. (- Mitokondriell helse er kritisk for skjelettmuskulaturfunksjon og forbedres ved trening gjennom både mitokondriell biogenese og fjerning av skadede / dysfunksjonelle mitokondrier via mitofagi.)

(Anm: Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. Abstract Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3-12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555. Using mice expressing dominant negative and constitutively active Ampk in skeletal muscle, we demonstrate that Ulk1 activation is dependent on Ampk. Furthermore, exercise-induced metabolic adaptation requires Ulk1. These findings provide direct evidence of exercise-induced mitophagy and demonstrate the importance of Ampk-Ulk1 signaling in skeletal muscle.Exercise is associated with biogenesis and removal of dysfunctional mitochondria. Here the authors use a mitochondrial reporter gene to demonstrate the occurrence of mitophagy following exercise in mice, and show this is dependent on AMPK and ULK1 signaling. Nat Commun. 2017 Sep 15;8(1):548.)

(Anm: Unclogging the garbage disposal: how exercise may improve mitochondria in ageing skeletal muscle. J Physiol. 2018 Jun 13.)

- Proteinforskning ved University of Kent kan hjelpe i jakten på en kur mot Alzheimers og Parkinsons.

(Anm: Protein research at University of Kent could help in hunt for Alzheimer's and Parkinson's cures. Research carried out at the University of Kent has the potential to influence the future search for treatment of neurodegenerative diseases that are linked to a family of protein molecules known as 'amyloid'. The findings by a team of scientists led by Dr Wei-Feng Xue in the School of Biosciences could lead to a better understanding of the diseases, and suggest potential diagnostics and therapeutics strategies to combat amyloid-associated disease progression and their possible infectivity. Currently, there is a gap in the knowledge of the factors that govern the infectious potential of amyloid in general. In an article published in the journal eLife, Dr Xue's team report on their investigations into why some forms of amyloid are highly infectious - the so-called prion form associated with BSE (Mad Cow Disease) and the human form, CJD (Creutzfeldt Jakob Disease) - while others are less infectious or even inert. (news-medical.net 11.9.2017).)

- Mitokondrielle nano-tunneler. (- Samlingen av individuelle mitokondrier til dynamiske nettverk av kommunikasjonsorganeller via nanotunneller og andre mekanismer har store implikasjoner for organell og cellulær funksjon.)

(Anm: Mitochondrial Nanotunnels. Abstract Insight into the regulation of complex physiological systems emerges from understanding how biological units communicate with each other. Recent findings show that mitochondria communicate at a distance with each other via nanotunnels, thin double-membrane protrusions that connect the matrices of non-adjacent mitochondria. Emerging evidence suggest that mitochondrial nanotunnels are generated by immobilized mitochondria and transport proteins. This review integrates data from the evolutionarily conserved structure and function of intercellular projections in bacteria with recent developments in mitochondrial imaging that permit nanotunnel visualization in eukaryotes. Cell type-specificity, timescales, and the selective size-based diffusion of biomolecules along nanotunnels are also discussed. The joining of individual mitochondria into dynamic networks of communicating organelles via nanotunnels and other mechanisms has major implications for organelle and cellular behaviors. Trends Cell Biol. 2017 Sep 18. pii: S0962-8924(17)30146-0. [Epub ahead of print].)

(Anm: Jakten på leukemi-cellenes hemmelige nano-tunneler. Maria Omsland disputerer fredag 03.02.2017 for ph.d.-graden ved Universitetet i Bergen med avhandlingen: «Investigation of the intercellular structure tunneling nanotube (TNT) in leukemia». Nanotunnelen er en struktur, som blir brukt til kommunikasjon mellom celler. Den ble beskrevet første gang av Rustom og medarbeidere i 2004. Det er en tynn (50-200 nm) tunnel-lignende struktur, som består av filamentøst-aktin (F-aktin) er dekket av plasmamembran og kan koble sammen celler. Den biologiske funksjonen til nanotunnelen, og det molekylære maskineriet bak dannelsen, er fortsatt ikke kartlagt. Det er derimot kjent at denne strukturen kan tillate transport av ulike komponenter mellom celler. (uib.no 26.1.2017).)

(Anm: Peripheral blood mitochondrial DNA content in relation to circulating metabolites and inflammatory markers: A population study. Abstract Mitochondrial DNA (mtDNA) content might undergo significant changes caused by metabolic derangements, oxidative stress and inflammation that lead to development and progression of cardiovascular diseases. (…) We demonstrated that in a general population relative peripheral blood mtDNA content was associated with circulating metabolites indicative of perturbed lipid metabolism and with inflammatory biomarkers. PLoS One. 2017 Jul 13;12(7):e0181036. doi: 10.1371/journal.pone.0181036. eCollection 2017.)

- Forskere fikk gjennombrudd mht. å forstå kraftverket til menneskelige celler. (- Når det gjelder mitokondrier må proteiner krysse grenser til to membraner for å komme inn i dem. "Vi så etter - og var i stand til å ta bilder med enestående detaljer – av ribosomer festet til mitokondrier.)

(Anm: Scientists make breakthrough in understanding the powerhouse of human cells. Scientists have made a breakthrough in understanding how mitochondria - the "powerhouses" of human cells - are made. Mitochondria, which exist within human cells but have their own DNA, need many different proteins to function - but the process of how they get these has never been imaged in detail. Now a study led by Dr Vicki Gold, of the University of Exeter, has shown that some ribosomes - the tiny factories of cells which produce proteins - are attached to mitochondria. This can explain how proteins are pushed into mitochondria whilst they are being made. The findings open new avenues for studying protein targeting and mitochondrial dysfunction, which has been implicated in diseases including cancer and neurodegenerative disorders such as Parkinson's. "Proteins are responsible for nearly all cellular processes. The cell has to make a huge variety of proteins and target them to the precise location where they are needed to function," said Dr Gold, of Exeter's Living Systems Institute. "In the case of mitochondria, proteins have to cross the boundary of two membranes to get inside them. "We looked for - and were able to image at unprecedented detail - ribosomes attached to mitochondria." The images were taken using cutting-edge technology called cryo-electron microscopy. Dr Gold and her colleague Dr Bertram Daum have both come from Germany to set up a cryo-electron microscopy facility at the University of Exeter. Having made the latest discovery by studying healthy cells, Dr Gold now plans to see how the process works in unhealthy cells. "Mitochondria are the energy factories of the cell, so when they don't function properly it can lead to a huge range of health problems," she said. "In many cases these are age-related disorders like Parkinson's disease. "Our findings may help us understand these conditions better, which is an important step towards better treatments." (medicalnewstoday.com 31.8.2017).)

- Mitokondriesykdommer som modell for neurodegenerasjon. (- "Mitokondrier" delvis autonom (uavhengig) sofistikert cellulær organelle involvert i et bredt spekter av kritiske cellulære funksjoner kjent som cellens kraftverk hvor ATP (adenosintrifosfat) - produksjonen finner sted, som er den cellulære energikilden.)

(Anm: Mitokondriesykdommer som modell for neurodegenerasjon. (Mitochondrial Diseases as Model of Neurodegeneration.) Abstrakt "Mitokondrier" delvis autonom (uavhengig) sofistikert cellulær organelle involvert i et bredt spekter av kritiske cellulære funksjoner kjent som cellens kraftverk hvor ATP (adenosintrifosfat) - produksjonen finner sted, som er den cellulære energikilden. (Mitochondrial Diseases as Model of Neurodegeneration.(Abstract "Mitochondria" partially autonomous sophisticated cellular organelle involved in a wide range of crucial cellular functions, well known as the power house of the cell where ATP (adenosine triphosphate) production takes place, that is the cellular source of energy.) Adv Exp Med Biol. 2017;1007:129-155.)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Fluoksetin (Prozac; SSRI) og mitokondriene: En gjennomgang av de toksikologiske aspekter. (- Fluoksetin induserer også bivirkninger, som for eksempel angst, seksuell dysfunksjon, søvnforstyrrelser, og gastrointestinale svekkelser.) (Fluoxetine and the mitochondria: A review of the toxicological aspects. (Fluoksetin og mitokondriene: En gjennomgang av de toksikologiske aspekter.) Toxicol Lett. 2016 Jul 5. pii: S0378-4274(16)32264-0.)

(Anm: SSRI-er (lykkepiller) forårsaker en varig serotonerg ubalanse grunnet legemidlenes skadelige endringer mht. serotonin og andre nevrotransmittere, mitokondriell dysfunksjon, avkortet levetid, plutselige dødsfall etc. (- SSRI-er øker nivået av serotonin i deler av hjernen med opptil 700 % (eller mer?), samt reduserer serotonin i blod med opptil 93 %.) (mintankesmie.no).)

(Anm: Effekten av psykostimulerende legemidler på blod-hjerne barrierens funksjon og nevroinflammasjon. (The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation) (Front. Pharmacol. 2012;3:121 (Published online: 29 June 2012).)

(Anm: Mitochondrial diseases: Yeast as a model for the study of suppressors. (…) Results support the possibility that a small peptide could correct defects associated with many mt tRNA mutations, suggesting a novel therapy for mitochondrial diseases treatment. The involvement of the mt EF-Tu in cellular heat stress response has also been suggested. Biochim Biophys Acta. 2017 Apr;1864(4):666-673.)

- Dette må du vite for å unngå å bli syk av ris- og pastarestene. - Hovedsynderen er en bakterie som heter Bacillus cereus, sier ekspert. (- Ris og pasta som er lagret over seks timer i romtemperaturer gjøre deg syk.) (- Granum har forsket på Bacillus cereus i mat i over 30 år. Han forklarer at toksinet produseres ved temperaturer mellom 10 og 40 grader, at det dannes raskest ved romtemperatur, og raskere ved lavere enn ved høyere temperaturer: – Toksinet ødelegger mitokondriene i menneskecellene slik at cellen dør. I høye konsentrasjoner vil toksinet kunne gi leversvikt og i verste fall føre til døden.)

(Anm: Dette må du vite for å unngå å bli syk av ris- og pastarestene. - Hovedsynderen er en bakterie som heter Bacillus cereus, sier ekspert. (…) Ifølge Per Einar Granum, som er professor ved Norges miljø- og biovitenskapelige universitet, NMBU, kan ris og pasta som er lagret over seks timer i romtemperaturer gjøre deg syk. Og rester som har ligget i over et døgn i romtemperatur kan i verste fall være dødelige. – Hovedsynderen er en bakterie som heter Bacillus cereus, sier Granum og forklarer at bakterien lever i jorden, og at den på den måten havner i ris, pasta og mel. – Bakterien er lite konkurransedyktig, og så lenge det er andre bakterier tilstede vil den ikke vinne i konkurransen med dem. Problemet oppstår under varmebehandling, når alle andre bakterier dør. Da vil dannede sporer spire, og om maten deretter lagres i temperaturer over 10 grader vil toksinet begynne å dannes. Granum har forsket på Bacillus cereus i mat i over 30 år. Han forklarer at toksinet produseres ved temperaturer mellom 10 og 40 grader, at det dannes raskest ved romtemperatur, og raskere ved lavere enn ved høyere temperaturer: – Toksinet ødelegger mitokondriene i menneskecellene slik at cellen dør. I høye konsentrasjoner vil toksinet kunne gi leversvikt og i verste fall føre til døden. (kk.no 27.9.2017).)

— Behandling med antidepressiva og forverring av hvit substans påvist ved MRI hos eldre. (—  Resultater Bruk av hvilken som helst antidepressiva i løpet av studien ble assosiert med forverring av hvit substans.)

(Anm: Behandling med antidepressiva og forverring av hvit substans påvist ved MRI hos eldre. (…) Resultater — Bruk av hvilken som helst antidepressiva i løpet av studien ble assosiert med forverring av hvit substans.) (Antidepressant Treatment and Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly. (…) Results— Use of any antidepressant during the period of study was associated with worsening white matter.) (Stroke 2008; 39: 857-862).)

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

(Anm: Kan Lupus øke risikoen for demens? Could lupus raise dementia risk? People living with lupus may be at significantly greater risk of developing dementia than those without the autoimmune disease, a new study suggests. (…) Study co-author Daniela Amital, of the Sackler Faculty of Medicine at Tel Aviv University in Israel, and colleagues recently reported their results in the International Journal of Geriatric Psychiatry. (medicalnewstoday.com 9.11.2017).)

- Hvit substans i hjernens kan holde ledetråder til autisme, ADHD.

(Anm: Brain White Matter May Hold Clues to Autism, ADHD. Researchers say there may be a connection between abnormalities in the brain’s white matter and the severity of symptoms in autism and ADHD. There may be a link between white matter in the brain and autism. Researchers at the New York University (NYU) School of Medicine have found a consistent connection between structural abnormalities in the brain’s white matter with the severity of symptoms in people with autism. The study was published earlier this month in JAMA Psychiatry. Researchers say these findings hold true in children with autism spectrum disorder (ASD) as well as, to some degree, in children with attention deficit hyperactivity disorder (ADHD) who have autistic traits. According to the Centers for Disease Control and Prevention (CDC), one in 68 children has some degree of ASD. (medicalnewstoday.com 13.9.2017).)

- Mitokondrier i nervesystemet: Fra helse til sykdom, del I.  (- Til sist granskes nye måter å redde mitokondriell struktur og funksjon ved akutt og kronisk hjerneskade.)

(Anm: Mitochondria in the nervous system: From Health to Disease, Part I. (Mitokondrier i nervesystemet: Fra helse til sykdom,) del I. Abstrakt I denne spesialutgaven om "Mitokondrier i nervesystemet: Fra helse til sykdom" samler redaktører bidrag fra eksperter innen hjernens mitokondrielle forskning for å gi en oppdatert oversikt over mitokondriell funksjon i fysiologi og patologi. Utgaven gir banebrytende vurderinger på klassiske områder av mitokondriell biologi som inkluderer bruk av energisubstrat, kalsiumhåndtering, mitokondrieendoplasmisk retikulumkommunikasjon og celledødsregulering. Ytterligere vurderinger og originale forskningsartikler berører viktige mitokondrielle defekter som er sett på tvers av flere nevrodegenerative tilstander, inkludert fragmentering, tap av respiratorisk kapasitet, kalsiumoverbelastning, forhøyet reaktiv oksygenproduksjon, foruroligende NAD + metabolisme, endret proteinacetylering og kompromittert mitofagi. Linker som anskueliggjøres mellom genetikk mht. nevrodegenerative forstyrrelser og forstyrrelser i mitokondriell funksjon diskuteres, og en ny musemodell av kompleks I-mangel er beskrevet. Endelig utforskes nye måter å redde mitokondriell struktur og funksjon i akutt og kronisk hjerneskade. (Mitochondria in the nervous system: From Health to Disease, Part I.Abstract In Part I of this Special Issue on "Mitochondria in the Nervous System: From Health to Disease", the editors bring together contributions from experts in brain mitochondrial research to provide an up-to-date overview of mitochondrial functioning in physiology and pathology. The issue provides cutting edge reviews on classical areas of mitochondrial biology that include energy substrate utilization, calcium handling, mitochondria-endoplasmic reticulum communication, and cell death regulation. Additional reviews and original research articles touch upon key mitochondrial defects seen across multiple neurodegenerative conditions, including fragmentation, loss of respiratory capacity, calcium overload, elevated reactive oxygen species generation, perturbed NAD+ metabolism, altered protein acetylation, and compromised mitophagy. Emerging links between the genetics of neurodegenerative disorders and disruption in mitochondrial function are discussed, and a new mouse model of Complex I deficiency is described. Finally, novel ways to rescue mitochondrial structure and function in acute and chronic brain injury are explored.) Neurochem Int. 2017 Sep 13. pii: S0197-0186(17)30481-3.)

(Anm: Commentary: Nix restores mitophagy and mitochondrial function to protect against PINK1/Parkin-related Parkinson's disease. Front. Mol. Neurosci., 19 September 2017.)

(Anm: Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010 Jan; 11(1): 45–51. Published online 2009 Dec 11.)

- Mitofagi ved Parkinsons sykdom: Patogene og terapeutiske implikasjoner. Nevroner påvirket av Parkinsons sykdom (PD) opplever mitokondriell dysfunksjon og bioenergetiske underskudd som oppstår tidlig og fremmer den sykdomsrelaterte a-synucleinopati.

(Anm: Mitophagy in Parkinson’s Disease: Pathogenic and Therapeutic Implications. Neurons affected in Parkinson’s disease (PD) experience mitochondrial dysfunction and bioenergetic deficits that occur early and promote the disease-related α-synucleinopathy. Emerging findings suggest that the autophagy-lysosome pathway, which removes damaged mitochondria (mitophagy), is also compromised in PD and results in the accumulation of dysfunctional mitochondria. Studies using genetic-modulated or toxin-induced animal and cellular models as well as postmortem human tissue indicate that impaired mitophagy might be a critical factor in the pathogenesis of synaptic dysfunction and the aggregation of misfolded proteins, which in turn impairs mitochondrial homeostasis. Interventions that stimulate mitophagy to maintain mitochondrial health might, therefore, be used as an approach to delay the neurodegenerative processes in PD. Front. Neurol., 04 October 2017).)

- Stadig flere får Alzheimers sykdom: Når kraftverkene i hjernen svikter. (- Basert på de foreløpige resultatene våre, er det grunn til å tro at viktige bidrag til Alzheimers sykdom i stor grad skyldes at mitokondriene ikke fungerer som de skal.)

(Anm: Stadig flere får Alzheimers sykdom: Når kraftverkene i hjernen svikter. Hjernens behov for energi er enormt. Mitokondriene gjør jobben. Men noen ganger går det galt. (…) Av alt blodet hjertet pumper ut i kroppen, ender hele 20 prosent i hjernen, selv om den bare utgjør rundt to prosent av kroppsvekten. (…) Hjernens forbruk i hvile er hele 60 prosent av kroppens glukose. Det er helt enormt! Kraftverkene Hva er det som omsetter all denne glukosen til energi? Det er mitokondriene, kroppens små og iherdige kraftverk. De finnes inne i cellene. I en hudcelle er det ganske få av dem, i en muskelcelle eller en hjernecelle, flere tusen. (...) En hel verden leter nå etter medisiner som effektivt kan bremse eller kurere Alzheimers sykdom. – Jo mer vi vet om de molekylære mekanismene bak sykdommen, dess bedre står vi rustet til å behandle den. Da er det viktig å finne ut når sykdommen oppstår: Hva skyldes sviktende DNA-reparasjon? Og hva skyldes sviktende mitokondrieaktivitet? Basert på de foreløpige resultatene våre, er det grunn til å tro at viktige bidrag til Alzheimers sykdom i stor grad skyldes at mitokondriene ikke fungerer som de skal. Hos de ulike undergruppene av pasienter med sykdomme, kan mitokondriedefekter ha mer eller mindre å si; her er det kanskje mer en defekt i DNA-reparasjon, mens der er det mer mitokondriell dysfunksjon. – Det vi vil med framtidens medisin, og ikke minst med personlig medisin, er jo nettopp å forstå hvordan arvematerialet vårt predisponerer oss for å havne i den ene eller den andre undergruppen. (apollon.uio.no 22.8.2016).)

(Anm: Mitochondria (mitokondrie) (mitokondriesykdommer) (mitokondrielle sykdommer). (mintankesmie.no).)

(Anm: PTSD og psykoaktive legemidler knyttet til økt risiko for demens. (PTSD and psychoactive drugs linked to increased risk for dementiaI) (…) I denne studien oppdaget forskerne at det å ta visse antidepressiva, sedativer, beroligende midler eller antipsykotika økte veteranernes risiko for å utvikle demens sammenlignet med risikoen for veteraner som ikke tok slike legemidler. (…) En ny studie, publisert i Journal of the American Geriatrics Society undersøkte denne forbindelsen. (...) Legemidler som betydelig økte risikoen for demens inkluderte: - Selektive serotonin reopptakshemmere (SSRI) - Nye antidepressiva - Atypiske antipsykotika. (news-medical.net 9.5.2017).)

- Alzheimer: Lavt serotoninnivå kan drive utviklingen. En av hypotesene frem til nå har vært at nevrotransmitteren serotonin spiller en nøkkelrolle. (…) Prof. Smith bemerker imidlertid at SSRI-behandling for Alzheimers sykdom ikke har vist seg å være vellykket.

(Anm: Alzheimer: Lavt serotoninnivå kan drive utviklingen. En av hypotesene frem til nå har vært at nevrotransmitteren serotonin spiller en nøkkelrolle. (…) Prof. Smith bemerker imidlertid at SSRI-behandling for Alzheimers sykdom ikke har vist seg å være vellykket. (Alzheimer's: Low serotonin levels may drive development. One of the hypotheses put forth so far has been that the neurotransmitter serotonin plays a key role. In recent years, studies have accumulated evidence that people with Alzheimer's disease have less of this brain chemical, which is known to regulate mood, sleep, appetite, and sexual function, among other things. (…) Prof. Smith notes, however, that SSRI treatment for Alzheimer's disease has not been proven successful. The reason for this, she ventures, might be that SSRIs need to bind to serotonin transporters in order to work, but in patients with Alzheimer's disease, it is precisely these transporters that are missing. She therefore suggests that serotonin receptors - rather than transporters - might be a better therapeutic target. (medicalnewstoday.com 16.8.2017).)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Dementia and low brain serotonin may be linked: Study finds. Johns Hopkins researchers looked into the brain scans of persons with mild loss of thought and memory and have found that they have significantly low levels of serotonin in their brains. Serotonin is a natural brain chemical that is responsible for several functions including mood, sleep and appetite and also is important for several mental health conditions. (…) This new study on persons with early stages of memory decline showed conclusively that serotonin loss was causing the memory loss rather than the other way round. The study is published in the September issue of the journal Neurobiology of Disease. (…) According to Smith, with this idea in mind, researchers have already tried to treat Alzheimer’s disease and other diseases of cognitive decline with SSRIs but have met with limited success. But these drugs need adequate number of serotonin transporters or SERTs in the brain to work, she noted, and that was missing among those with cognitive decline. That is probably why SSRIs do not show as much success as expected. (medicalnewstoday.com 14.8.2017).)

- Mitofagi og mitokondrielle kvalitetskontrollmekanismer i hjertet.

(Anm: Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart. Abstract PURPOSE OF REVIEW: Mitochondrial homeostasis and quality control are essential to maintenance of cardiac function and a disruption of this pathway can lead to deleterious cardiac consequences. RECENT FINDINGS: Mitochondrial quality control has been described as a major homeostatic mechanism in cell. Recent studies highlighted that an impairment of mitochondrial quality control in different cell or mouse models is linked to cardiac dysfunction. Moreover, some conditions as aging, genetic mutations or obesity have been associated with mitochondrial quality control alteration leading to an accumulation of damaged mitochondria responsible for increased production of reactive oxygen species, metabolic inflexibility, and inflammation, all of which can have sustained effects on cardiac cell function and even cell death. SUMMARY: In this review, we describe the major mechanisms of mitochondrial quality control, factors that can impair mitochondrial quality control, and the consequences of disrupted mitochondrial quality control. Curr Pathobiol Rep. 2017 Jun;5(2):161-169.)

- Mitokondriell kvalitetskontroll ved AMD: spiller mitofagi en sentral rolle?

(Anm: Mitochondrial quality control in AMD: does mitophagy play a pivotal role? Abstract Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Mitophagy, a mitochondria-specific type of autophagy, is an essential part of mitochondrial quality control, the collective mechanism responsible for this organelle's homeostasis. The abundance of ROS, DNA damage, and the excessive energy consumption in the ageing retina all contribute to the degeneration of RPE cells and their mitochondria. We discuss the role of mitophagy in the cell and argue that its impairment may play a role in AMD pathogenesis. Thus, mitophagy as a potential therapeutic target in AMD and other degenerative diseases is as well explored. Cell Mol Life Sci. 2018 May 18.)

– Sink forhindrer mitokondriell superoksid-generering ved å indusere myofagi ved settingen for hypoksi/reoksygenering (H/R) i hjerteceller.  (- Sanering av skadede mitokondrier kan forklare årsaken til den hjertebeskyttende effekten av sink på H/R-skade.)

(Anm: Zinc prevents mitochondrial superoxide generation by inducing mitophagy in the setting of hypoxia/reoxygenation in cardiac cells. Abstract Zinc plays a role in autophagy and protects cardiac cells from ischemia/reperfusion injury. This study aimed to test if zinc can induce mitophagy leading to attenuation of mitochondrial superoxide generation in the setting of hypoxia/reoxygenation (H/R) in cardiac cells. (…) In summary, zinc induces mitophagy through PINK1 and Beclin1 via ERK leading to the prevention of mitochondrial superoxide generation in the setting of H/R. Clearance of damaged mitochondria may account for the cardioprotective effect of zinc on H/R injury. Free Radic Res. 2017 Dec 7:1-231.)

- Kokain og ecstasy forårsaker DNA-mutasjon: studie

Cocaine and ecstasy cause DNA mutation: study (Kokain og ecstasy forårsaker DNA-mutasjon: studie)
Reuters Health 5.12.2003
- Cocaine and ecstasy not only cause addiction and raise the risk of cancer but also provoke genetic mutations, Italian scientists said on Friday.

"Cocaine and ecstasy have proved to be more dangerous than we had imagined," said Giorgio Bronzetti, chief scientist at the National Center for Research's (CNR) biotechnology department.

"These drugs, on top of their toxicological effects, attack DNA provoking mutations and altering the hereditary material. This is very worrying for the effects it could have on future generations," he said. (...)

(Anm: Kokainbruk og slagrisiko (nhi.no 18.2.2014).)

(Anm: Ecstasy er i likhet med SSRIer (lykkepiller) en såkalt serotoninreopptakshemmer, dvs. ecstasy og SSRIer har enkelte likhetstrekk mht. mulige bivirkninger, bl.a. antikolinerge skadevirkninger, såkalt serotonin syndrom etc. (mintankesmie.no).)

- Mitochondrial complex I bridges a connection between regulation of carbon flexibility and gastrointestinal commensalism in the human fungal pathogen Candida albicans.

(Anm: Mitochondrial complex I bridges a connection between regulation of carbon flexibility and gastrointestinal commensalism in the human fungal pathogen Candida albicans. Abstract Efficient assimilation of alternative carbon sources in glucose-limited host niches is critical for colonization of Candida albicans, a commensal yeast that frequently causes opportunistic infection in human. C. albicans evolved mechanistically to regulate alternative carbon assimilation for the promotion of fungal growth and commensalism in mammalian hosts. However, this highly adaptive mechanism that C. albicans employs to cope with alternative carbon assimilation has yet to be clearly understood. Here we identified a novel role of C. albicans mitochondrial complex I (CI) in regulating assimilation of alternative carbon sources such as mannitol. Our data demonstrate that CI dysfunction by deleting the subunit Nuo2 decreases the level of NAD+, downregulates the NAD+-dependent mannitol dehydrogenase activity, and consequently inhibits hyphal growth and biofilm formation in conditions when the carbon source is mannitol, but not fermentative sugars like glucose. Mannitol-dependent morphogenesis is controlled by a ROS-induced signaling pathway involving Hog1 activation and Brg1 repression. In vivo studies show that nuo2Δ/Δ mutant cells are severely compromised in gastrointestinal colonization and the defect can be rescued by a glucose-rich diet. Thus, our findings unravel a mechanism by which C. albicans regulates carbon flexibility and commensalism. Alternative carbon assimilation might represent a fitness advantage for commensal fungi in successful colonization of host niches. PLoS Pathog. 2017 Jun 1;13(6):e1006414. eCollection 2017 Jun.)

(Anm: A novel mechanism of fluconazole: fungicidal activity through dose-dependent apoptotic responses in Candida albicans. Abstract Fluconazole (FLC) is a well-known fungistatic agent that inhibits ergosterol biosynthesis. We showed that FLC exhibits dose-dependent fungicidal activity, and investigated the fungicidal mechanism of FLC on Candida albicans. (…) In conclusion, the dose-dependent fungicidal activity of FLC was due to an apoptotic response in C. albicans. Microbiology. 2018 Feb;164(2):194-204.)

(Anm: Allergy Asthma Immunol. Can Controlling Endoplasmic Reticulum Dysfunction Treat Allergic Inflammation in Severe Asthma With Fungal Sensitization? Abstract Severe asthma is a heterogeneous disease entity to which diverse cellular components and pathogenetic mechanisms contribute. (…) Interestingly, a recent study on this issue has suggested that ER stress responses and several associated molecular platforms, including phosphoinositide 3-kinase-δ and mitochondria, may be crucial players in the development of severe allergic inflammation in the SAFS. Defining emerging roles of ER and associated cellular platforms in SAFS may offer promising therapeutic options in the near future. Res. 2018 Mar;10(2):106-120.)

- Antisoppforbindelser mot Candida-infeksjoner fra tradisjonell kinesisk medisin.

(Anm: Antifungal Compounds against Candida Infections from Traditional Chinese Medicine. Abstract Infections caused by Candida albicans, often refractory and with high morbidity and mortality, cause a heavy burden on the public health while the current antifungal drugs are limited and are associated with toxicity and resistance. Many plant-derived molecules including compounds isolated from traditional Chinese medicine (TCM) are reported to have antifungal activity through different targets such as cell membrane, cell wall, mitochondria, and virulence factors. Here, we review the recent progress in the anti-Candida compounds from TCM, as well as their antifungal mechanisms. Considering the diverse targets and structures, compounds from TCM might be a potential library for antifungal drug development. Biomed Res Int. 2017;2017:4614183.)

- Bevis for mitokondriell genommetylering i gjær Candida albicans: En potensiell ny epigenetisk mekanisme som påvirker tilpasning og patogenitet?

(Anm: Evidence for Mitochondrial Genome Methylation in the Yeast Candida albicans: A Potential Novel Epigenetic Mechanism Affecting Adaptation and Pathogenicity? (…) Mitochondria play important roles in fungal energetic metabolism, regulation of nuclear epigenetic mechanisms and pathogenicity. However, the specific impact of inter-strain mitochondrial genome variability and mitochondrial epigenetics in pathogenicity is unclear. Here, we draw attention to this relevant organelle and its potential role in C. albicans pathogenicity and provide preliminary evidence, for the first time, for methylation of the yeast mitochondrial genome. (…) Although intraspecific variation in the nuclear DNA is well-established, the evolutionary rate of C. albicans mitochondrial DNA (mtDNA) and its effect on its fitness and virulence is not clear. Front. Genet., 29 May 2018.)

- Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation

Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation
J Biol Chem. 2014 Jun 3. pii: jbc.M114.560078. [Epub ahead of print]
Abstract To address whether mitochondrial biogenesis is essential for skeletal myogenesis, C2C12 myogenesis was investigated after knockdown of NADH dehydrogenase [ubiquintone] flavoprotein 1 (NDUFV1), which is an oxidative phosphorylation complex I (CI) subunit that is the first subunit to accept electrons from NADH. The NDUFVI knockdown enhanced C2C12 myogenesis by decreasing the NAD+/NADH ratio and subsequently inactivating SIRT1 and SIRT1 activators (pyruvate, SRT1720 and resveratrol) abolished the NDUFV1 knockdown-induced myogenesis enhancement. However, the insulin-elicited activation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) was reduced with an elevated levels of protein tyrosine phosphatase 1B (PTP1B) after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1 knockdown-induced blockage of insulin signaling was released by PTP1B knockdown in C2C12 myotubes and we found that NDUFV1 or SIRT1 knockdown did not affect mitochondria biogenesis during C2C12 myogenesis. Based on these data, we can conclude that CI dysfunction-induced SIRT1 inactivation leads to myogenesis enhancement but blocks insulin signaling without affecting mitochondria biogenesis. (…)

(Anm: In Vivo Assessment of Mitochondrial Dysfunction in Clinical Populations Using Near-Infrared Spectroscopy. (…) Conclusion Recent studies have demonstrated the utility of NIRS in the evaluation of mitochondrial dysfunction in persons with neurological, autoimmune, cardiovascular, and mitochondrial diseases. NIRS provides an affordable, versatile, and noninvasive technique for evaluating mitochondrial oxidative capacity of skeletal muscle in clinical populations. Front. Physiol., 14 September 2017.)

- Suicidalitet og aggresjon under behandling med antidepressiva.

(Anm: Suicidalitet og aggresjon under behandling med antidepressiva. Alkohol og alvorlige skader under behandling med antidepressiva. (Suicidality and aggression during antidepressant treatment. Alcohol and serious harms of antidepressant treatment.) Sharma og kollegers rapport bekrefter at bruk av antidepressiva er assosiert med aggresjon og vold, særlig hos unge mennesker. BMJ 2016;352:i892 (Published 17 February 2016).)

(Anm: Straffesaker (fengselsstraff) (mintankesmie.no).)

- Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking.

(Anm: Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking. (Conclusions SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smokng. BMJ Open 2017;7:e016224.)

Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

- Her behandles piger og kvinder, der lider af svimmelhed, hovedpine eller lammelser, der muligvis skyldes vaccinen. 29 procent af dem, hvilket svarer til næsten hver tredje, havde indløst en recept på medicin mod en psykiatrisk lidelse i løbet af fem år inden vaccinationen.

(Anm: Ny forskning viser igen, at piger og kvinder, der søger hjælp til behandling af formodede bivirkninger efter hpv-vaccinen, har oftere end andre været berørt af angst, depression eller anden psykisk sygdom, inden de blev vaccineret. (…) Undersøgelsen lægger sig op ad en undersøgelse fra Statens Serum Institut fra 2016. Den nye undersøgelse bygger på data fra 1496 kvinder, som i 2015 var henvist til et af regionernes fem hpv-centre. Her behandles piger og kvinder, der lider af svimmelhed, hovedpine eller lammelser, der muligvis skyldes vaccinen. 29 procent af dem, hvilket svarer til næsten hver tredje, havde indløst en recept på medicin mod en psykiatrisk lidelse i løbet af fem år inden vaccinationen. De er sammenlignet med 2240 jævnaldrende kvinder, som også er vaccinerede, men som ikke har søgt behandling.) (jyllands-posten.dk 19.9.2017).)

- En dansk undersøkelse viste at omtrent halvdelen av forskrivninger av selektive serotoninreopptakshemmere (SSRI-preparater) gjelder funksjonsfriske mennesker (4).

(Anm: Selektive serotonin- reopptakshemmere – skade ikke dokumentert? (…) En undersøkelse publisert i 1999 viste at ni av ti allmennpraktiserende leger ikke var oppmerksom på serotonergt syndrom (2).  (…) En dansk undersøkelse viste at omtrent halvdelen av forskrivninger av selektive serotoninreopptakshemmere (SSRI-preparater) gjelder funksjonsfriske mennesker (4). Slike preparater fører muligens til en marginal økning i antall selvmord (5). Tidsskr Nor Legeforen 2002 122:731.)

- Fluoksetin (Prozac; SSRI) og mitokondriene: En gjennomgang av de toksikologiske aspekter. (- Fluoksetin induserer også bivirkninger, som for eksempel angst, seksuell dysfunksjon, søvnforstyrrelser, og gastrointestinale svekkelser. (...) På den annen side har inntak av fluoxetin blitt assosiert med økt risiko for kreft.

(Anm: Fluoksetin (Prozac; SSRI) og mitokondriene: En gjennomgang av de toksikologiske aspekter. (- Fluoksetin induserer også bivirkninger, som for eksempel angst, seksuell dysfunksjon, søvnforstyrrelser, og gastrointestinale svekkelser. (...) På den annen side har inntak av fluoxetin blitt assosiert med økt risiko for kreft. Likevel forblir data motstridende og ingen konklusjoner er trukket.) (Fluoxetine and the mitochondria: A review of the toxicological aspects. (Fluoksetin og mitokondriene: En gjennomgang av de toksikologiske aspekter. (...) On the other hand, fluoxetine intake has been associated with increased cancer risk.) Toxicol Lett. 2016 Jul 5. pii: S0378-4274(16)32264-0.)

(Anm: Dopaminmangel: Hva du trenger å vite. (Dopamine deficiency: What you need to know) (medicalnewstoday.com 17.1.2018).)

- Behandling med antidepressiva og risiko for demens. (- KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva.)

(Anm: Behandling med antidepressiva og risiko for demens: En populasjonsbasert, retrospektiv case-control studie. (…) KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva. (CONCLUSIONS: The incidence of dementia in patients is associated with antidepressant medication use.) J Clin Psychiatry. 2016 Jan;77(1):117-22.)

(Anm: Dopamin i det mediale amygdala-nettverk formidler menneskelige bånd (bindinger) (Dopamine in the medial amygdala network mediates human bonding.) Abstract Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. Proc Natl Acad Sci U S A. 2017 Feb 13. pii: 201612233.)

- Har Mitokondrier et immunsystem?

(Anm: Do Mitochondria Have an Immune System? Abstract The question if mitochondria have some kind of immune system is not trivial. The basis for raising this question is the fact that bacteria, which are progenitors of mitochondria, do have an immune system. The CRISPR system in bacteria based on the principle of RNA interference serves as an organized mechanism for destroying alien nucleic acids, primarily those of viral origin. We have shown that mitochondria are also a target for viral attacks, probably due to a related organization of genomes in these organelles and bacteria. Bioinformatic analysis performed in this study has not given a clear answer if there is a CRISPR-like immune system in mitochondria. However, this does not preclude the possibility of mitochondrial immunity that can be difficult to decipher or that is based on some principles other than those of CRISPR. Biochemistry (Mosc). 2016 Oct;81(10):1229-1236.)

- Mitokondrier: En hovedregulator av makrofag og T-celle-immunitet.

(Anm: Mitochondria: A master regulator in macrophage and T cell immunity. Abstract Orchestrating biological activities of immune cells through metabolic reprogramming reveals a new approach to harnessing immune responses. Increasing evidence reveals that the mitochondrion is a central regulator for modulating metabolic reprogramming and controlling immune cell activation and functions. In addition to supporting bioenergetic demands, the mitochondrion serves as a signaling platform through the generation of reactive oxygen species and metabolites of the tricarboxylic acid cycle to modulate signaling cascades controlling immune cell activation and immune responses. Herein, we discuss the mechanisms through which the mitochondrion acts as a master regulator to fine-tune immune responses elicited by macrophages and T cells. Mitochondrion. 2017 Nov 13. pii: S1567-7249(17)30214-3.)

(Anm: Makrofag, stor «etecelle» (fagocytt) som har viktige renovasjons- og forsvarsfunksjoner i organismen. De dannes fra monocyttene, som er en type hvit blodcelle (se blod). Monocyttene kommer fra benmargen og finnes i blodet. Makrofager finnes i mange organer og vev, men de er særlig tallrike i milt, lever og lunge. De finnes også i bindevevet, spesielt der det pågår en betennelsesprosess. Kilde: Store norske leksikon.)

(Anm: T cells: Mitochondrial shape shifters. Nat Rev Immunol. 2016 Jun 28;16(7):402-3.)

- Mitokondriell metabolisme og kreft. (- I tillegg til å utøve sentrale bioenergetiske funksjoner leverer mitokondrier faktisk byggeklosser for tumoranabolisme, kontroll av redox og kalsiumhomeostase, deltar i transkripsjonsregulering og styrer celledød.)

(Anm: Mitochondrial metabolism and cancer. Abstract Glycolysis has long been considered as the major metabolic process for energy production and anabolic growth in cancer cells. Although such a view has been instrumental for the development of powerful imaging tools that are still used in the clinics, it is now clear that mitochondria play a key role in oncogenesis. Besides exerting central bioenergetic functions, mitochondria provide indeed building blocks for tumor anabolism, control redox and calcium homeostasis, participate in transcriptional regulation, and govern cell death. Thus, mitochondria constitute promising targets for the development of novel anticancer agents. However, tumors arise, progress, and respond to therapy in the context of an intimate crosstalk with the host immune system, and many immunological functions rely on intact mitochondrial metabolism. Here, we review the cancer cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence all steps of oncogenesis, with a focus on the therapeutic potential of targeting mitochondrial metabolism for cancer therapy. Cell Res. 2017 Dec 8.)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

- Mekanismen bak mitokondriell rolle ved induksjon av perifer nevropati ved bruk av kjemoterapi.

(Anm: Role of Mitochondrial Mechanism in Chemotherapy-Induced Peripheral Neuropathy. Abstract BACKGROUND: Even though chemotherapeutic regimens shows considerable importance, it may cause progressive, continuing and sometimes irreversible peripheral neuropathy. Chemotherapy induced peripheral neuropathy (CIPN) comprises of sensory abnormalities that are most distress issues. The mechanism associated with CIPN pathogenesis is not completely revealed and is treatment is still questionable. The purpose of this review was to investigate the role of mitochondria in CIPN. (…) CONCLUSION: The pathophysiology of CIPN is complicated as chemotherapeutic medications often involve combination of drug. With these combinatorial therapies cancer survivors develop continuing effects of CIPN which require rehabilitation strategies for the recovery of patient's condition and quality of life. Curr Drug Metab. 2017 Dec 7.)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

- Perifer nevropati er en vanlig manifestasjon av mitokondrielle sykdommer: et singel senters erfaringer.

(Anm: Peripheral neuropathy is a common manifestation of mitochondrial diseases: a single-centre experience. CONCLUSIONS: In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis. Eur J Neurol. 2016 Jun;23(6):1020-7.)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: nevropati; fellesbetegnelse på organiske nervesykdommer, se nervebetennelse. (...) Kilde: Store norske leksikon.)

(Anm: Immunobiology: The Immune System in Health and Disease. 5th edition. Chapter 8T Cell-Mediated Immunity. Once they have completed their development in the , enter the bloodstream and are carried by the circulation. On reaching a peripheral lymphoid organ they leave the blood again to migrate through the lymphoid tissue, returning to the bloodstream to recirculate between blood and peripheral lymphoid tissue until they encounter their specific . Mature recirculating T cells that have not yet encountered their antigens are known as naive T cells. To participate in an , a naive T cell must first encounter antigen, and then be induced to proliferate and differentiate into cells capable of contributing to the removal of the antigen. We will term such cells because they act very rapidly when they encounter their specific antigen on other cells. The cells on which armed effector T cells act will be referred to as their . Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Chapter 8, T Cell-Mediated Immunity. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10762/.)

- Type 1 diabetes: Kan endrede blodstamceller føre til en kur? (- "Den hellige gral" for forskere som søker en kur for type 1 diabetes er å finne en måte å forebygge eller stoppe immunforsvarets angrep på betacellene.)

(Anm: Type 1 diabetes: Could modified blood stem cells lead to a cure? Increasing levels of a certain protein in blood stem cells so that the immune system stops attacking insulin cells in the pancreas could be a way to halt type 1 diabetes, according to a new study reported in Science Translational Medicine. (…) The "holy grail" of scientists seeking a cure for type 1 diabetes is to find a way to prevent or stop the immune attack on the beta cells. (…) Now, in the new study, the researchers — who were led by senior investigator Paolo Fiorina, an assistant professor of pediatrics at Harvard Medical School's Boston Children's Hospital — might have discovered why treatments that use the person's own blood stem cells may not always work. "We found that in diabetes," explains Prof. Fiorina, "blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease." The defect that they discovered is that the blood stem cells — that is, the progenitor cells that give rise to mature cells — do not produce enough of a protein called PD-L1 that reigns back attack by T cells. (medicalnewstoday.com 17.11.2017).)

(Anm: Type 1 Diabetes: What Are The Symptoms? (medicinenet.com 2.8.2016).)

(Anm: Type 2 Diabetes Overview (webmd 2.2.2016).)

(Anm: Diabetes: Kender du forskel på type 1 og 2? (netdoktor.dk 6.6.2017).)

(Anm: What is the immune system? (medicalnewstoday.com 17.11.2017).)

(Anm: Diabetes (mintankesmie.no).)

- Norsk forskerbragd: Ditt eget immunforsvar kan utløse kronisk sykdom og ta liv. (– Når dette immunapparatet overaktiveres, misforstår og går løs på kroppen selv, så blir det kroppens verste fiende, sier han. Da utløses en betennelsesreaksjon eller en blodforgiftning, og pasienten kan i verste fall dø.)

(Anm: Norsk forskerbragd: Ditt eget immunforsvar kan utløse kronisk sykdom og ta liv. Immunforsvaret kan bli kroppens verste fiende, ifølge ny, norsk forskning. Den norske legen Tom Eirik Mollnes høster internasjonal anerkjennelse for å ha bidratt med ny og skremmende kunnskap om kroppens eget immunforsvar. Udetonert bombe – Det er som en udetonert bombe, sier forskeren som tok sin doktorgrad i Oslo. Siden har han samarbeidet med en rekke medisinske miljøer i Norge og Danmark for å dokumentere sin teori om at kroppens eget immunforsvar i gitte situasjoner kan utløse kronisk sykdom og i verste fall ta liv. – Når dette immunapparatet overaktiveres, misforstår og går løs på kroppen selv, så blir det kroppens verste fiende, sier han. Da utløses en betennelsesreaksjon eller en blodforgiftning, og pasienten kan i verste fall dø. (tv2.no 14.11.2017).)

- Rollen til mitokondriell dysfunksjon i patofysiologien for DNA-reparasjonsforstyrrelser.

(Anm: Role of mitochondrial dysfunction in the pathophysiology of DNA repair disorders. (…) Here we review the recent findings linking mitochondrial impairment and cell death to DNA damage accumulation in the context of DNA repair defects. In addition, the general involvement of DNA damage in cellular dysfunction suggests that these phenomena may be also involved in other human pathologies in which mitochondrial dysfunction and metabolic disruption play causative roles. Cell Biol Int. 2017 Dec 22.)

- En pasient på UNN døde av blodforgiftning som følge av et legemiddel mot psykiske lidelser, opplyser Statens helsetilsyn.

(Anm: En pasient på UNN døde av blodforgiftning som følge av et legemiddel mot psykiske lidelser, opplyser Statens helsetilsyn. (- Pasienten døde etter kort tid, og dødsårsaken var nøytropen sepsis (blodforgiftning), heter det i tilsynets rapport. (nrk.no 12.10.2016).)

(Anm: Multiorgansvikt, svikt eller delvis svikt i funksjonen av mer enn to organer. Pasienter med multiorgansvikt finner man på intensivavdelinger og postoperative avdelinger på sykehus. Kilde: Store norske leksikon.).)

(Anm: Mitochondria-meditated pathways of organ failure upon inflammation. (…) Analysis of the literature suggests that further research should be focused on the impact of mtROS on organ failure induced by inflammation and simultaneously providing a new theoretical basis for a targeted therapy of overwhelmed inflammatory response. Redox Biol. 2017 May 25;13:170-181. [Epub ahead of print].)

(Anm: sepsis; alvorleg smittesjukdom med nærvere av sjukdomsbakteriar eller andre smittekim i blodet; «blodforgiftning», gir feber, frostrier, rask puls og pust, leukocytose, mødd allmenntilstand; kan føra til blodtrykksfall med mjølkesyreacidose, oliguri, uklart sensorium m v pga dårleg organgjennombløding, ev til multiorgansvikt (s d) og sjokk; bakterieendotoksin, TNF, IL-1 og andre cytokin, NO m v er utløysingsfaktorar; kan skuldast ein abscess, sårinfeksjon, kateterinfeksjon e a; jf bakteriemi, septikopyemi, septikemi, TSS, septisk sjokk, DIC, endokarditt, urosepsis. Kilde: Norsk medisinsk ordbok.)

(Anm: Sepsis; grunnleggende kliniske observasjoner (hnt.no 5.11.2013).)

(Anm: Urosepsis er blodforgiftning (sepsis) som utgår fra urinveiene. Dette skyldes at bakterier som har forårsaket urinveisinfeksjon eller en akutt nyrebekkenbetennelse (pyelonefritt), sprer seg til blodbanen. Samme bakterie kan påvises i urinen og blodet. Kilde: Store norske leksikon.)

(Anm: Urosepsis: What to know about UTI complications. Urosepsis is a term used to describe a type of sepsis that is caused by an infection in the urinary tract. It is a complication often caused by urinary tract infections that are not treated quickly or properly. Urosepsis is a serious complication of a urinary tract infection (UTI) that requires immediate medical care to avoid a possible life-threatening event. Anyone experiencing the symptoms of urosepsis should seek emergency medical attention. (medicalnewstoday.com 23.12.2017).)

(Anm: Drug-resistant bacteria in patients' urine or stools raise risk of drug-resistant sepsis (medicalnewstoday.com 26.4.2017).)

(Anm: Autophagy in sepsis: Degradation into exhaustion? Abstract Autophagy is one of the innate immune defense mechanisms against microbial challenges. Previous in vitro and in vivo models of sepsis demonstrated that autophagy was activated initially in sepsis, followed by a subsequent phase of impairment. Autophagy modulation appears to be protective against multiple organ injuries in these murine sepsis models. This is achieved in part by preventing apoptosis, maintaining a balance between the productions of pro- and anti-inflammatory cytokines, and preserving mitochondrial functions. This article aims to discuss the role of autophagy in sepsis and the therapeutic potential of autophagy enhancers. Autophagy. 2016 Jul 2;12(7):1073-822.)

- «Alle» har fått avvik. Ikke ett eneste av akuttmottakene som Helsetilsynet har gjort tilsyn ved, unngikk avvik når det gjelder gjenkjennelse og behandling av sepsis.

(Anm: «Alle» har fått avvik. Ikke ett eneste av akuttmottakene som Helsetilsynet har gjort tilsyn ved, unngikk avvik når det gjelder gjenkjennelse og behandling av sepsis. (…) Rundt 50 prosent av alle pasienter som utvikler sepsis, kommer inn via akuttmottaket. – Pasientene kommer da gjerne med en infeksjon, eller med en uavklart tilstand. (…) Sepsis som oppstår på sengepost ser ikke Fylkesmennene på i dette tilsynet. (sykepleien.no 23.2.2017).)

(Anm: Systemic inflammatory response syndrome (SIRS) is an inflammatory state affecting the whole body, frequently a response of the immune system to infection. (en.wikipedia.org).)

(Anm: Sepsis. Definisjon: SIRS + påvist/mistenkt infeksjon (f. eks. positiv blodkultur). SIRS- kriteriene er: - Feber > 38 ºC eller hypotermi < 36 ºC - Puls > 90/minutt - Respirasjonsfrekvens > 20/minutt eller hypokapni med pCO2 < 4,3 kPa i blodgass - Leukocytose ≥ 12 × 109/l eller leukopeni < 4 × 109/l eller > 10 % umodne leukocytter. (helsebiblioteket.no - Metodebok for indremedisinere, 2012).)

- Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt.

(Anm: Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt. (The role of mitochondrial dysfunction in sepsis-induced multi-organ failure). (Virulence. 2013 Nov 1;5(1).)

- Diagnostisering av sepsis. Sepsis, også kjent som blodforgiftning, er kroppens hyperaktive respons på en infeksjon som kan føre til betennelse, vevskader, organsvikt etc.

(Anm: Diagnosing Sepsis. Sepsis, also known as blood poisoning, is the body’s hyperactive response to an infection that can lead to inflammation, tissue damage, organ failure etc. It is a very dangerous state in which the immune system stops fighting with the invading agents  and turns to itself. Around one-third of patients who are affected with sepsis die every year. (news-medical.net 7.9.2017).)

- Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon.

(Anm: Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon. Recognizing Sepsis as a Global Health Priority — A WHO Resolution. “Some very important clinical issues, some of them affecting life and death, stay largely in a backwater which is inhabited by academics and professionals and enthusiasts, dealt with very well at the clinical and scientific level but not visible to the public, political leaders, leaders of healthcare systems... The public and political space is the space in which [sepsis] needs to be in order for things to change.” NEJM (June 28, 2017).)

(Anm: Sepsis – den dödliga sjukdomen som glöms bort. Trots att infektionssjukdomen sepsis förekommer oftare än de vanligaste formerna av cancer och att upp emot hälften som drabbas av den allvarligaste formen dör, så har många knappt hört talas om sjukdomen. Sepsis som är den medicinska termen på blodförgiftning, drabbar omkring 40 000 svenskar varje år. (netdoktor.se 7.6.2017).)

- Ny innsikt i hvorfor immunforsvaret ikke oppdager kreft. Studien gransker relasjonen mellom hvordan immunforsvaret ser perifert vev og kreft.

(Anm: New insights into why the immune system fails to see cancer. Study explores relationship between how the immune system sees peripheral tissues and cancers. Cancer hides in plain sight of the immune system. The body's natural tumor surveillance programs should be able to detect and attack rogue cancer cells when they arise, and yet when cancer thrives, it does so because these defense systems have failed. A team of investigators led by Niroshana Anandasabapathy, MD, PhD, at Brigham and Women's Hospital have uncovered a critical strategy that some cancers may be using to cloak themselves - they find evidence of this genetic program across 30 human cancers of the peripheral tissue, including melanoma skin cancer. Their results are published in Cell. "Our study reveals a new immunotherapy target and provides an evolutionary basis for why the immune system may fail to detect cancers arising in tissues," said corresponding author Anandasabapathy, of BWH's Department of Dermatology. "The genetic program we report on helps the immune system balance itself. Parts of this program prevent the immune system from destroying healthy organs or tissues, but might also leave a blind spot for detecting and fighting cancer."(medicalnewstoday.com 3.7.2017).)

(Anm: IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment. Cell. 2017 Jun 29;170(1):127-141.e15.)

- Fjerning av senescente celler fra ledd kan reversere progresjon av osteoartritt (betennelse i ledd og tilgrensende knokkel).

(Anm: Removing senescent cells from joints could reverse progression of osteoarthritis. In a preclinical study in mice and human cells, researchers report that selectively removing old or 'senescent' cells from joints could stop and even reverse the progression of osteoarthritis. The findings, published April 24 in Nature Medicine, support growing evidence that senescent cells contribute to age-related diseases and demonstrate that using drug therapies to remove them from the joint not only reduces the development of post-traumatic osteoarthritis but creates an environment for new cartilage to grow and repair joints. (news-medical.net 2.5.2017).)

- Mayo Clinic-studie avslører link mellom senescente celler og benskjørhet (osteoporose) hos mus.

(Anm: Mayo Clinic study reveals link between senescent cells and bone loss in mice. Mayo Clinic researchers have reported a causal link between senescent cells - the cells associated with aging and age-related disease - and bone loss in mice. Targeting these cells led to an increase in bone mass and strength. The findings appear online in Nature Medicine. (news-medical.net 21.8.2017).)

- UCI, Italienske forskere begrenser akselerert cellulær aldring (senescens) forårsaket av bruk av metamfetamin.

(Anm: UCI, Italienske forskere begrenser akselerert cellulær aldring (senescens) forårsaket av bruk av metamfetamin. UCI, Italian scientists limit accelerated cellular aging caused by methamphetamine use. Grasp of underlying molecular mechanisms could improve addiction recovery efforts. The ravaged faces of methamphetamine addicts tell a terrible tale - abusing the drug dramatically accelerates aging. Now scientists from UC Irvine and the Italian Institute of Technology have discovered how this occurs at the cellular level and identified methods to limit the process. (medicalnewstoday.com 14.2.2015).)

- Celledød: Er vår helse i fare? (- Når celler brister og dør, blir deres innhold frigitt og forårsaker betennelse.) (- Hver dag dør mer enn 50 milliarder celler i kroppen vår. Dette er ikke tilfeldige hendelser, men en del av en finjustert biologisk mekanisme som kalles programmert celledød.)

(Anm: Celledød: Er vår helse i fare? (Cell death: Is our health at risk?) Når celler brister og dør, blir deres innhold frigitt og forårsaker betennelse. Livet og døden til cellene i kroppen vår er stramt regulert. Dette er viktig for normal funksjon og begrensning av skader. Men celledød kan ha sideeffekter, og hvis det svikter er vår helse risikoutsatt. Hver dag dør mer enn 50 milliarder celler i kroppen vår. Dette er ikke tilfeldige hendelser, men en del av en finjustert biologisk mekanisme som kalles programmert celledød. Multicellære organismer, inkludert mennesker, må holde nøye kontroll på antall celler i kroppen. Dette ville være enkelt hvis cellene aldri delte seg, men på noen steder - som blod, hud og «lining» av tarmsystemet - produseres stadig nye celler. (Cell death: Is our health at risk? When cells burst and die, their contents are released, causing inflammation. The life and death of the cells in our bodies are tightly regulated. This is essential for normal function and limiting damage. But cell death can have side effects, and if it malfunctions, our health is at stake. Every day, more than 50 billion cells die in our bodies. These are not random events, but part of a finely tuned biological mechanism called programmed cell death. Multicellular organisms, including humans, need to keep a tight lid on the number of cells in their bodies. This would be easy if the cells never divided, but some areas - such as the blood, skin, and lining of the gut - are constantly producing new cells.) (medicalnewstoday.com 11.8.2017).)

(Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

(Anm: Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking. (Conclusions SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smoking. BMJ Open 2017;7:e016224.)

- Eksponering for decabromodiphenyl (BDE-209) gir mitokondriell dysfunksjon i lever hos rotter og celledød.

(Anm: - Eksponering for decabromodiphenyl (BDE-209) gir mitokondriell dysfunksjon i lever hos rotter og celledød. Exposure to decabromodiphenyl ether (BDE-209) produces mitochondrial dysfunction in rat liver and cell death. Abstract Polybrominated diphenyl ethers (PBDE) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunctions, reproductive disorders, and hepatotoxicity. The widespread use of PBDE as flame retardants has culminated in daily exposure of humans and wildlife to these contaminants and resulted in their banned use. J Toxicol Environ Health A. 2017 Sep 7:1-16.)

(Anm: Miljø og helse (mintankesmie.no).)

(Anm: Klima, miljø og globalisering (mintankesmie.no).)

- Den usynlige kloakken.

(Anm: - Den usynlige kloakken. (…) På 25 meters dyp og 100 meter ut i fjorden spyles brunt kloakkvann ut i havet. Slik har det vært i mange år. Men det er umulig å se med det blotte øye fra land. (...) Hver dag havner store mengder med dårlig renset kloakk rett ut i fjordene våre. En rekke store norske kommuner bryter nemlig rensekravene viser NRKs kartlegging. (nrk.no 24.4.2017).)

(Anm: Miljø og legemiddel (Legemidler er farlig avfall). (mintankesmie.no).)

(Anm: Avløp og kloakk på kartet. Statistisk sentralbyrå har laget en enkel visualisering av landets avløpsanlegg på kart. Visualiseringen illustrerer tydelig skillet mellom mye høygradig biologisk og/eller kjemisk rensing på Østlandet og i Trøndelag, og overvekt av mekanisk rensing i de øvrige deler av landet. (ssb.no 19.12.2017).)

- Konklusjoner -Treningsinduserte reduksjoner i glykolytisk aktivitet stimulerer fysiologisk hjertereparasjon, og metabolisk fleksibilitet er viktig for å opprettholde mitokondriell helse i hjertet.

(Anm: Exercise-Induced Changes in Glucose Metabolism Promote Physiologic Cardiac Growth. Conclusions -Exercise-induced decreases in glycolytic activity stimulate physiologic cardiac remodeling, and metabolic flexibility is important for maintaining mitochondrial health in the heart. Circulation. 2017 Aug 31. pii: CIRCULATIONAHA.117.028274.)

(Anm: Orale steroider (glukokortikoider) linket til 10 ganger økt risiko for diabetes. (Oral steriods linked with ten-fold increased risk of diabetes. (pulsetoday.co.uk 5.5.2016).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

(Anm: Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking. (Conclusions SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smoking. BMJ Open 2017;7:e016224.)

- Alvorlig hjertesvikt kan være reversibel. Forskere kan ha oppdaget en måte å reversere hjertesvikt på ved å få hjertemuskler til å regenerere seg selv. De oppdaget at siling av en signalvei i mus som hadde utviklet hjertesvikt etter et hjerteinfarkt aktiverte en tidligere ukjent selvhelbredelsesprosess.

(Anm: Severe heart failure may be reversible. Scientists may have discovered a way of reversing heart failure by getting heart muscle to regenerate itself. They found that silencing a signaling pathway in mice that had developed heart failure following a heart attack activated a previously unrecognized self-healing process. In a paper recently published in the journal Nature, the researchers, led by a team from Baylor College of Medicine in Houston, TX, report their findings about the signaling pathway, which is known as Hippo. (medicalnewstoday.com 5.10.2017).)

- Forskere avslører mekanisme som knytter tarmbakterier til hypertensjon (høyt blodtrykk).

(Anm: Forskere avslører mekanisme som knytter tarmbakterier til hypertensjon (høyt blodtrykk). Scientists unravel mechanism that links gut bacteria to hypertension. (...) In a few studies, when gut bacteria were killed off with antibiotics, patients with hypertension saw a drop in blood pressure. And when gut bacteria were transplanted from hypertensive people into normal mice, they developed high blood pressure. The evidence is compelling, but until now, scientists have not identified a mechanism to explain how bacteria increase blood pressure. (news-medical.net 3.10.2017).)

(Anm: Mitochondrial DNA copy number appears to be predictive of sudden cardiac death, heart attacks. The two studies, one on cardiovascular disease published in JAMA Cardiology on Oct. 11 and the other focused on sudden cardiac death and published in the… (news-medical.net 11.10.2017).)

(Anm: Gut colonization linked to development and progress of heart failure. (…) It has long been known that heart failure and gut health are linked. The gut, thus, has a worse blood supply in instances of heart failure; the intestinal wall is thicker and more permeable, whereby bacteria and bacterial components may find their way into the blood. (news-medical.net 11.7.2017).)

- Betennelser endrer mitokondrier til giftige fabrikker. Å lære hvordan å kontrollere betennelser kan ha store implikasjoner for behandlingen av mange sykdommer.

(Anm: Betennelser endrer mitokondrier til giftige fabrikker. Å lære hvordan å kontrollere betennelser kan ha store implikasjoner for behandlingen av mange sykdommer. Banebrytende forskning oppdager hvordan makrofager endrer mitokondriene til giftige kjemisk-produserende betennelsespromotører. (Inflammation turns mitochondria into toxic factories. Learning how to control inflammation could have huge implications for the treatment of many diseases. Breaking research discovers how macrophages turn mitochondria into toxic chemical-producing inflammation-promoters.) (medicalnewstoday.com 25.9.2016).)

- Forskere gjør overraskende funn om hvordan nevroner kommuniserer med hverandre. (…) Neuroner kommuniserer med hverandre ved å frigjøre kjemikalier kalt neurotransmittere, som dopamin og glutamat inn i det lille rommet mellom to nevroner som er kjent som synaps. (- "Våre funn viser for første gang at nevroner kan forandre hvor mye dopamin de frigjør som en funksjon av deres generelle aktivitet. Når denne mekanismen ikke fungerer som den skal, kan det ha store helseeffekter…

- Nylige estimater av den globale byrden av soppsykdom antyder at deres forekomst har blitt drastisk undervurdert, og at dødeligheten kan konkurrere med malaria eller tuberkulose.

(Anm: Mitochondrial Complex I Is a Global Regulator of Secondary Metabolism, Virulence and Azole Sensitivity in Fungi. Abstract Recent estimates of the global burden of fungal disease suggest that that their incidence has been drastically underestimated and that mortality may rival that of malaria or tuberculosis. (...) Evidence presented in this paper suggests that complex I may play a role in the hypoxic response and that one possible mechanism for cell death during azole treatment is a dysfunctional hypoxic response that may be restored by dysregulation of complex I. Both deletion of the 29.9 KD subunit of complex I and azole treatment alone profoundly change expression of gene clusters involved in secondary metabolism and immunotoxin production raising potential concerns about long term azole therapy. PLoS One. 2016 Jul 20;11(7):e0158724. eCollection 2016.)

- Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes.

(Anm: Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes. (…) Highlights • Pancreatic mitochondrial complex I shows hyperactivity in diabetes. • Complex I hyperactivity is associated with increased NADH/NAD+ redox imbalance. • Complex I hyperactivity is associated with increased oxidative stress and cell death. • Complex I hyperactivity is linked with compromised cellular anti-oxidative stress capacity such as decreased sirt3 and NQO1 expressions. Biochem Biophys Rep. 2017 Sep;11:119-129.)

(Anm: Focus on an unusual rise in pancreatic cancer incidence in France. (…) Conclusion: Pancreatic cancer incidence and mortality exhibited diverging trends. Incidence increased over the last 30 years in France whereas mortality did not vary in men and moderately increased in women. Incidence remained lower than mortality up to 2002. One cannot exclude the possibility that a similar trend may appear in other countries. Etiological studies are required to further explain this increase.Int J Epidemiol. 2017 Dec 1;46(6):1764-1772.)

(Anm: Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring.[1] Use as anti-fungal agents. The search for antifungal agents with acceptable toxicity profiles led first to the discovery of ketoconazole, the first azole-based oral treatment of systemic fungal infections, in the early 1980s. Later, triazoles fluconazole and itraconazole, with a broader spectrum of antifungal activity and improved safety profile were developed. In order to overcome limitations such as sub-optimal spectra of activity, drug-drug interactions, toxicity, development of resistance and unfavorable pharmacokinetics, analogues (en.wikipedia.org).)

(Anm: Sykelighet, sykefravær, uførhet og trygd (mintankesmie.no).)

- Atorvastatin (ATV) som vanligvis brukes til å behandle dyslipidemi rapporteres også å ha effekt mot 6-hydroksydopamin (6-OHDA) indusert nevrotoksisitet. I tillegg kan atorvastatin forstyrre mitokondriell funksjon ved å redusere nivået av Q10. Derfor kan den terapeutiske effekten av atorvastatin (20 mg / kg) bli kompromittert. (- De aktuelle resultater gir bevis på at tilskudd av Q10 til ATV viser synergistisk effekt ved å redusere dopamin toksisitet.) (- Det var signifikant reduksjon i mitokondriell kompleks enzymaktivitet og mitokondrielt membranpotensial (MMP).)

(Anm: Abstract Atorvastatin (ATV) generally used to treat dyslipidemia is also reported to have effect against 6-hydroxydopamine (6-OHDA) induced neurotoxicity. Additionally, atorvastatin can interfere with mitochondrial function by reducing the level of Q10. Therefore, the therapeutic effect of atorvastatin (20 mg/kg) could be compromised. In this context, the present study evaluated the effect of ATV supplemented with Q10. 6-OHDA was unilaterally injected into the right striatum of male rats. On day 8 of 6-OHDA infusion, ATV (20 mg/kg), Q10 (200 mg/kg), and their combination were administered per oral for 14 days. On day 21, there was significant loss of striatal dopamine indicating neurotoxicity. The combination of ATV+Q10 showed significant amelioration of dopamine (DA) toxicity compared to individual treatments. Similarly, ATV+Q10 compared to individual treatment significantly decreased the motor deficits induced by 6-OHDA. Further, 6-OHDA induced mitochondrial dysfunction in the substantia nigra pars compacta (SNpc). There was significant decrease in mitochondrial complex enzyme activities and mitochondrial membrane potential (MMP). Treatment with ATV and ATV+Q10 ameliorated mitochondrial dysfunction by increasing complex enzyme activities; however, only ATV+Q10 were able to stabilize MMP and maintained mitochondrial integrity. Moreover, there was significant induction of oxidative stress as observed from increase in lipid peroxidases (LPO) and nitrite (NO), and decrease in super oxide dismutase (SOD). Treatment with ATV+Q10 significantly altered the above effects indicating antioxidant activity. Furthermore, only combination of ATV and Q10 decreased the 6-OHDA induced expression of cytochrome-C, caspase-9 and caspase-3. Therefore, current results provide evidence that supplementation of Q10 with ATV shows synergistic effect in reducing dopamine toxicity. Neurotox Res. 2017 May;31(4):478-492.)

(Anm: Statiner etc. (mot høyt kolesterol) (mintankesmie.no).)

- Studien identifiserer en ny måte å forhindre at en dødelig soppinfeksjon sprer seg til hjernen.

(Anm: Studien identifiserer en ny måte å forhindre at en dødelig soppinfeksjon sprer seg til hjernen. Study identifies a new way to prevent a deadly fungal infection spreading to the brain. (- Det er mange sykdommer, ikke bare kryptokokker, hvor patogener - bakterier, virus, sopp eller parasitter kan forårsake sykdom - som overlever ved bevisst å kapre immunforsvaret på denne måten. (medicalnewstoday.com 21.8.2017).)

(Anm: Effekter av MPTP på serotonerge nevronale systemer og mitokondrie Complex I aktiviteten i den levende hjernen: En PET-studie på bevisste rhesusaper. (Effects of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys. (Effects of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys.) J Nucl Med. 2017 Mar 9. pii: jnumed.116.189159.)

(Anm: Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes. (…) Highlights • Pancreatic mitochondrial complex I shows hyperactivity in diabetes. • Complex I hyperactivity is associated with increased NADH/NAD+ redox imbalance. • Complex I hyperactivity is associated with increased oxidative stress and cell death. • Complex I hyperactivity is linked with compromised cellular anti-oxidative stress capacity such as decreased sirt3 and NQO1 expressions. Biochem Biophys Rep. 2017 Sep;11:119-129.)

(Anm: Focus on an unusual rise in pancreatic cancer incidence in France. (…) Conclusion: Pancreatic cancer incidence and mortality exhibited diverging trends. Incidence increased over the last 30 years in France whereas mortality did not vary in men and moderately increased in women. Incidence remained lower than mortality up to 2002. One cannot exclude the possibility that a similar trend may appear in other countries. Etiological studies are required to further explain this increase.Int J Epidemiol. 2017 Dec 1;46(6):1764-1772.)

- Kronisk bruk av ketamin har vært knyttet til kognitiv svekkelse og blærebetennelse. En annen bekymring er at ketamin, noen ganger kalt "Special k," er en substans som misbrukes. (- Chronic use of ketamine has been linked to cognitive impairment and bladder inflammation. Another concern is that ketamine, sometimes called “special K,” is a drug of abuse.)

(Anm: The Dangers of Using the Club Drug Ketamine for Depression. Still, ketamine isn’t quite ready to be considered a primetime treatment for depression, concludes an American Psychiatric Association (APA) research task force in a new report published in JAMA Psychiatry. (…) Chronic use of ketamine has been linked to cognitive impairment and bladder inflammation. Another concern is that ketamine, sometimes called “special K,” is a drug of abuse. (time.com 2.3.2017).)

- Akutt inntak av ketamin svekker mitokondriell funksjon og fremmer superoksyd dismutase-aktivitet i rottehjernen. (- KONKLUSJONER: Akutt ketaminadministrasjon svekket funksjonen av mitokondria kompleks I, noe som førte til økt mtNOS-aktivitet, økt generasjon av hydrogenperoksid og NO, noe som resulterte i utløsning av superoksid dismutase og forbedret antioksidantaktivitet.)

(Anm: Acute ketamine impairs mitochondrial function and promotes superoxide dismutase activity in the rat brain. (…) CONCLUSIONS: Acute ketamine administration impaired the function of mitochondrial complex I leading to increased mtNOS activity, increased generation of hydrogen peroxide and NO, resulting in superoxide dismutase triggering, and improved antioxidant activity. The present findings clarify the role of NO modulation in ketamine anesthesia, providing new data on a relevant clinical mechanism. Anesth Analg. 2015 Feb;120(2):320-8.)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

- Modulerende effekt av curcumin på ketamin-indusert toksisitet i rotte-tymocytter: Involvering av reaktive oksygenarter (ROS) og fosfoinositid 3-kinase (PI3K) / proteinkinase B (Akt) bane. (- Våre resultater indikerer at ketamin-indusert toksisitet i rotte-tymocytter hovedsakelig skjer gjennom den mitokondriamedierte apoptotiske bane, og at PI3K / Akt-signalveien er involvert i den anti-apoptotiske effekten av curcumin.)

(Anm: Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Abstract Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. (…) Administration of Wortmannin (a PI3K inhibitor) with curcumin and ketamine significantly decreased the protective effect of curcumin on rat thymocytes. Our results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt signaling pathway is involved in the anti-apoptotic effect of curcumin. Bosn J Basic Med Sci. 2018 Mar 21.)

(Anm: Pasienter behandlet med antipsykotika (nevroleptika) har signifikant senket platelet complex I aktivitet i mitokondrier i likhet med det som er observert ved idiopatisk Parkinsons sykdom. (...) Antipsykotika (nevroleptika) hemmer kompleks I i elektrontransportkjeden. (Neuroleptic medications inhibit complex I of the electron transport chain. (...) Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson’s disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.) Ann Neurol. 1993;33:512-7).)

(Anm: Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes. (…) Highlights • Pancreatic mitochondrial complex I shows hyperactivity in diabetes. • Complex I hyperactivity is associated with increased NADH/NAD+ redox imbalance. • Complex I hyperactivity is associated with increased oxidative stress and cell death. • Complex I hyperactivity is linked with compromised cellular anti-oxidative stress capacity such as decreased sirt3 and NQO1 expressions. Biochem Biophys Rep. 2017 Sep;11:119-129.)

(Anm: Focus on an unusual rise in pancreatic cancer incidence in France. (…) Conclusion: Pancreatic cancer incidence and mortality exhibited diverging trends. Incidence increased over the last 30 years in France whereas mortality did not vary in men and moderately increased in women. Incidence remained lower than mortality up to 2002. One cannot exclude the possibility that a similar trend may appear in other countries. Etiological studies are required to further explain this increase.Int J Epidemiol. 2017 Dec 1;46(6):1764-1772.)

(Anm: Sygdom trækker danskere ned i gæld. (…) En sygdom rammer, og al energi bliver lagt i blodprøver og møder med læger. Imens hober gammel gæld sig op, eller ny kommer til. (...) For mange kommer et svigtende helbred til at betyde begyndelsen på en lang og sej kamp mod renter og minus på kontoen. (…) Her angiver de gældsramte oftest sygdom som det, der startede deres pengeproblemer. (…) »Det er jo hårdt at være syg i sig selv, og det er yderligere hårdt, at man kommer ud i nogle situationer, hvor man risikerer, at huset skal sælges på tvangsauktion, eller man ikke har til huslejen«, siger han. »Så man bliver på en måde dobbelt ramt. (politiken.dk 29.4.2017).)

- Mitokondriell aldring og aldersrelatert mitokondriell dysfunksjon. Alderselaterte endringer i mitokondrier er knyttet til redusert i mitokondriell funksjon. Med fremskyndet aldring reduseres mitokondrielt DNA-volum, integritet og funksjonalitet på grunn av akkumulering av mutasjoner og oksidativ skade fremkalt av reaktive oksygensubstanser (ROS). Hos eldre mennesker er mitokondriene preget av redusert funksjon som redusert oksidativ kapasitet, redusert oksidativ fosforylering, redusert ATP-produksjon, betydelig økning i ROS-generasjon og redusert antioksidantforsvar.

(Anm: Mitokondriell aldring og aldersrelatert mitokondriell dysfunksjon. Abstrakt. Alderselaterte endringer i mitokondrier er knyttet til redusert i mitokondriell funksjon. Med fremskyndet aldring reduseres mitokondrielt DNA-volum, integritet og funksjonalitet på grunn av akkumulering av mutasjoner og oksidativ skade fremkalt av reaktive oksygensubstanser (ROS). Hos eldre mennesker er mitokondriene preget av redusert funksjon som redusert oksidativ kapasitet, redusert oksidativ fosforylering, redusert ATP-produksjon, betydelig økning i ROS-generasjon og redusert antioksidantforsvar. (Abstract Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense.) Biomed Res Int. 2014;2014:238463. Epub 2014 Apr 10.)

(Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

(Anm: Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking. (Conclusions SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smoking. BMJ Open 2017;7:e016224.)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Legemiddelindusert kreft og andre typer celleskader (mintankesmie.no).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

(Anm: Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking. (Conclusions SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smoking. BMJ Open 2017;7:e016224.)

(Anm: SSRI-preparater og antipsykotika har uheldige effekter på mitokondrier (mintankesmie.no).)

(Anm: Legemiddelindusert kreft og andre typer celleskader (mintankesmie.no).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Sovemidler (sovemedisiner) og beroligende midler (mintankesmie.no).)

(Anm: Sovemidler knyttes til dødelighet eller kreft: en matchet kohortstudie. (Hypnotics' association with mortality or cancer: a matched cohort study.)  (...) Målsetting Anslagsvis 6 % -10 % av amerikanske voksne tok et sovemiddel (hypnotika) mot dårlig søvn i 2010. Denne studien underbygger tidligere rapporter som knytter hypnotika (sovemidler) til økt dødelighet. BMJ Open 2012;2:e000850 (27 February).)

(Anm: - Slår sovepiller os ihjel? (- Studiet er det største af sin slags på globalt plan og har også undersøgt sammenhængen mellem brug af antidepressiver og antipsykotika og dødelighed. Også her fandt forskerne en overdødelighed.) (videnskab.dk 21.3.2016).)

- Forskning på cellulær senescens kan føre til nye måter å behandle aldersrelaterte lidelser på.

(Anm: Forskning på cellulær senescens kan føre til nye måter å behandle aldersrelaterte lidelser på. Research into cellular senescence may lead to new ways of treating age-related disorders. (…) In basic research conducted on human cell cultures and on mice, Dr. Krizhanovsky and his team asked, "what, exactly, ties senescent cells to aging?" (medicalnewstoday.com 18.5.2017).)

(Anm: Senescence-associated ultrastructural features of long-term cultures of induced pluripotent stem cells (iPSCs). Aging (Albany NY). 2017 Oct 23.)

(Anm: Senescence promotes chemotherapy side effects and cancer relapse. Standard chemotherapy is a blunt force instrument against cancer - and it's a rare cancer patient who escapes debilitating side effects from systemic treatments that mostly affect dividing cells, both malignant and healthy, throughout the body. Researchers at the Buck Institute and elsewhere now show that chemotherapy triggers a pro-inflammatory stress response termed cellular senescence, promoting the adverse effects of chemotherapy as well as cancer relapse and metastasis. Eliminating the senescent cells in mice prevented the side effects and relapse. The research is published in Cancer Discovery.  (medicalnewstoday.com 18.1.2017).)

(Anm: Mechanisms of Neurotoxic Symptoms as a Result of Breast Cancer and Its Treatment: Considerations on the Contribution of Stress, Inflammation, and Cellular Bioenergetics. (…) SUMMARY: We propose reduced cellular energy (mitochondrial dysfunction) induced by inflammation, oxygen radical production, and stress as a result of cancer and/or cancer treatment as a final mechanism underlying neurotoxic symptoms. Curr Breast Cancer Rep. 2017;9(2):70-81.)

(Anm: Men appear to have worse chemotherapy-induced cardiomyopathy than women, research shows. Men seem to have worse chemotherapy-induced cardiomyopathy than women despite receiving similar cancer treatments, according to research presented today at EuroCMR 2017. (news-medical.net 25.5.2017).)

(Anm: Senescence (/sɪˈnɛsəns/) (from Latin: senescere, meaning "to grow old", from senex) or biological aging (also spelled biological ageing) is the gradual deterioration of function characteristic of most complex lifeforms, arguably found in all biological kingdoms, that on the level of the organism increases mortality after maturation. The word senescence can refer either to cellular senescence or to senescence of the whole organism. It is commonly believed that cellular senescence underlies organismal senescence. The science of biological aging is biogerontology. (en.wikipedia.org).)

(Anm: UCI, Italienske forskere begrenser akselerert cellulær aldring (senescens) forårsaket av bruk av metamfetamin. UCI, Italian scientists limit accelerated cellular aging caused by methamphetamine use. Grasp of underlying molecular mechanisms could improve addiction recovery efforts. The ravaged faces of methamphetamine addicts tell a terrible tale - abusing the drug dramatically accelerates aging. Now scientists from UC Irvine and the Italian Institute of Technology have discovered how this occurs at the cellular level and identified methods to limit the process. (medicalnewstoday.com 14.2.2015).)

- Tre giftige gasser møtes i mitokondriene.

(Anm: Three toxic gases meet in the mitochondria. Front. Physiol. 2015 (20 August 2015).)

(Anm: Toxic formaldehyde is produced inside our own cells, scientists discover. New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment -- it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing cancer therapies, according to research led by scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology. (sciencedaily.com 16.8.2017).)

(Anm: Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature 2017 (Published online 16 August 2017).)

(Anm: Toxic formaldehyde is produced inside our own cells, scientists discover. (…) The research, published in Nature, has uncovered that formaldehyde is a by-product of a key process called the 'one carbon cycle'. This cycle uses a vitamin - folate - to create DNA and essential amino acids, which cells need to function and multiply. (medicalnewstoday.com 17.8.2017).)

- Eksperimentelle bevis støtter en intrikat forbindelse mellom betennelse og mitokondriell dysfunksjon som hovedbidragsyter ved nevrologiske sykdommer. Inflammatoriske mediatorer produsert av aktiverte mikroglia og infiltrerte immunceller utløser intracellulære signaleringskaskader som kan forandre cellulær mitokondriell metabolisme.

(Anm: Inflammation and mitochondrial dysfunction: a vicious circle in neurodegenerative disorders? Abstract Experimental evidence supports an intricate association between inflammation and mitochondrial dysfunction as main contributors of neurological diseases. Inflammatory mediators produced by activated microglia and infiltrated immune cells trigger intracellular signaling cascades that can alter cellular mitochondrial metabolism. Cytokines, particularly tumor necrosis factor-alpha, impede mitochondrial oxidative phosphorylation and associated ATP production and instigate mitochondrial reactive oxygen species production. This culminates in mitochondrial membrane permeabilization, altered mitochondrial dynamics and might ultimately result in cell death. When severely injured mitochondria are not appropriately removed by mitophagy they can release their contents into the cytosol and extracellular environment and thereby amplify the inflammatory process. Here we provide a comprehensive overview on how inflammatory mediators impair mitochondrial metabolism and discuss how defective mitochondria can elicit and potentiate an inflammatory response.Neurosci Lett. 2017 Jun 28. pii: S0304-3940(17)30542-6 [Epub ahead of print].)

(Anm: Bacterial tail anchors can target to the mitochondrial outer membrane. Biol Direct. 2017 Jul 24;12(1):16.)

- Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt.

(Anm: Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt. (The role of mitochondrial dysfunction in sepsis-induced multi-organ failure). (Virulence. 2013 Nov 1;5(1).)

- Diagnostisering av sepsis. Sepsis, også kjent som blodforgiftning, er kroppens hyperaktive respons på en infeksjon som kan føre til betennelse, vevskader, organsvikt etc.

(Anm: Diagnosing Sepsis. Sepsis, also known as blood poisoning, is the body’s hyperactive response to an infection that can lead to inflammation, tissue damage, organ failure etc. It is a very dangerous state in which the immune system stops fighting with the invading agents  and turns to itself. Around one-third of patients who are affected with sepsis die every year. (news-medical.net 7.9.2017).)

- Reparere mitokondriell dysfunksjon ved sykdom.

(Anm: Repairing Mitochondrial Dysfunction in Disease. Abstract Mitochondria are essential organelles for many aspects of cellular homeostasis, including energy harvesting through oxidative phosphorylation. Alterations of mitochondrial function not only impact on cellular metabolism but also critically influence whole-body metabolism, health, and life span. Diseases defined by mitochondrial dysfunction have also expanded from rare monogenic disorders in a strict sense to now also include many common polygenic diseases, including metabolic, cardiovascular, neurodegenerative, and neuromuscular diseases. This has led to an intensive search for new therapeutic and preventive strategies aimed at invigorating mitochondrial function by exploiting key components of mitochondrial biogenesis, redox metabolism, dynamics, mitophagy, and the mitochondrial unfolded protein response. As such, new findings linking mitochondrial function to the progression or outcome of this ever-increasing list of diseases has stimulated the discovery and development of the first true mitochondrial drugs, which are now entering the clinic and are discussed in this review. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 58 is January 6, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. Annu Rev Pharmacol Toxicol. 2017 Sep 27.)

(Anm: Myopathy, Drugs, and Mitochondria. J Korean Med Sci. 2017 Nov;32(11):1732-1733.)

- Effekter av antiepileptiske legemidler (antiepileptika) på mitokondrielle funksjoner, morfologi, kinetikk, biogenese og overlevelse.

(Anm: Effects of antiepileptic drugs on mitochondrial functions, morphology, kinetics, biogenesis, and survival. Abstract OBJECTIVES: Antiepileptic drugs (AEDs) exhibit adverse and beneficial effects on mitochondria, which have a strong impact on the treatment of patients with a mitochondrial disorder (MID) with epilepsy (mitochondrial epilepsy). This review aims at summarizing and discussing recent findings concerning the effect of AEDs on mitochondrial functions and the clinical consequences with regard to therapy of mitochondrial epilepsy and of MIDs in general. (…) CONCLUSIONS: Mitochondrial epilepsy might be initially treated with AEDs with low mitochondrial toxic potential. Only in case mitochondrial epilepsy is refractory to these AEDs, AEDs with higher mitochondrial toxic potential might be tried. In patients carrying POLG1 mutations AEDs with high mitochondrial toxic potential are contraindicated. Epilepsy Res. 2017 Jul 13;136:5-11.)

(Anm: Epilepsi og legemidler (mintankesmie.no).)

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

(Anm: Kan Lupus øke risikoen for demens? Could lupus raise dementia risk? People living with lupus may be at significantly greater risk of developing dementia than those without the autoimmune disease, a new study suggests. (…) Study co-author Daniela Amital, of the Sackler Faculty of Medicine at Tel Aviv University in Israel, and colleagues recently reported their results in the International Journal of Geriatric Psychiatry. (medicalnewstoday.com 9.11.2017).)

(Anm: Antidepressiva ökar risken för benbrott hos äldre. (…) Den förhöjda risken för höftfraktur gällde alla de vanliga antidepressiva läkemedlen, SSRI-preparat, mirtazapin och SNRI-preparat (selektiva serotonin- och noradrenalinåterupptagshämmare. Sambandet gällde även då det kontrollerats för andra faktorer som ålder, annan medicinering som ökar fallrisken, benskörhet, socioekonomisk status, kroniska sjukdomar och psykiatriska diagnoser.) (lakemedelsvarlden.se 12.1.2017).)

- Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon.

(Anm: Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon. Recognizing Sepsis as a Global Health Priority — A WHO Resolution. “Some very important clinical issues, some of them affecting life and death, stay largely in a backwater which is inhabited by academics and professionals and enthusiasts, dealt with very well at the clinical and scientific level but not visible to the public, political leaders, leaders of healthcare systems... The public and political space is the space in which [sepsis] needs to be in order for things to change.” NEJM (June 28, 2017).)

(Anm: Sepsis – den dödliga sjukdomen som glöms bort. Trots att infektionssjukdomen sepsis förekommer oftare än de vanligaste formerna av cancer och att upp emot hälften som drabbas av den allvarligaste formen dör, så har många knappt hört talas om sjukdomen. Sepsis som är den medicinska termen på blodförgiftning, drabbar omkring 40 000 svenskar varje år. (netdoktor.se 7.6.2017).)

- Hurtigtest finner tegn på sepsis i en enkelt dråpe blod.

(Anm: Hurtigtest finner tegn på sepsis i en enkelt dråpe blod. (- Sepsis, en potensielt livstruende komplikasjon av en infeksjon, har den høyeste byrde mht. død og medisinske utgifter på sykehus over hele verden.) (- Quick test finds signs of sepsis in a single drop of blood. (…) Sepsis, a potentially life-threatening complication of an infection, has the highest burden of death and medical expenses in hospitals worldwide. (medicalnewstoday.com 5.7.2017).)

(Anm: Mechanisms of Neurotoxic Symptoms as a Result of Breast Cancer and Its Treatment: Considerations on the Contribution of Stress, Inflammation, and Cellular Bioenergetics. (…) SUMMARY: We propose reduced cellular energy (mitochondrial dysfunction) induced by inflammation, oxygen radical production, and stress as a result of cancer and/or cancer treatment as a final mechanism underlying neurotoxic symptoms. Curr Breast Cancer Rep. 2017;9(2):70-81.)

- Mitokondrier er immunitetens kraftverk

Mitochondria are the powerhouses of immunity
Nat Immunol. 2017 Apr 18;18(5):488-498. doi: 10.1038/ni.3704.
Nylige bevis indikerer at mitokondrier ligger i hjertet av immunitet. Mitokondriell DNA virker som et fareassosiert molekylært mønster (DAMP), og det mitokondrielle ytre membran er en plattform for signalering av molekyler som MAVS i RIG-I-signalering, og for NLRP3- inflammasome. Mitokondriell biogenese, fusjon og fisjon har roller i aspekter ved immun-celle-aktivering. Viktigste Krebs syklus mellomprodukter som succinat, fumarat og citrat involverer prosesser relatert til immunitet og betennelse, i både medfødte og adaptive immunceller. Disse funnene avslører mitokondrielle mål som potensielt kunne utnyttes for terapeutisk gevinst ed betennelse og kreft. (Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells. These discoveries are revealing mitochondrial targets that could potentially be exploited for therapeutic gain in inflammation and cancer.)

(Anm: Krebs Cycle Overview. The Krebs cycle is named after its discoverer, Hans Krebs. It is also known as the citric acid cycle or the tricarboxylic acid cycle. It is a series of chemical reactions required for cellular respiration; it involves  redox, dehydration, hydration, and decarboxylation reactions that produce ATP (adenosine triphosphate), a coenzyme energy carrier for cells.  The waste product, in the form of carbon dioxide, is also produced as well as further sets of reactants used to regenerate the original reaction. (news-medical.net 6.9.2017).)

- Mitokondrier er kroppens livsviktige energifabrikker. Siden mitokondrier finnes i stort sett alle celler i alle vev, kan mitokondriesykdommer ramme hvor som helst. Vi kan ikke leve uten mitokondrier. Når de svikter, kan vi bli alvorlig syke.

(Anm: Mitokondrier er kroppens livsviktige energifabrikker. Siden mitokondrier finnes i stort sett alle celler i alle vev, kan mitokondriesykdommer ramme hvor som helst. Vi kan ikke leve uten mitokondrier. Når de svikter, kan vi bli alvorlig syke. Laurence Bindoff, overlege og leder av NeuroAge, Universitetet i Bergen. (…) Inntil nylig kunne man ikke påvise linken mellom avleiring i hjernen og mitokondrieavvik. Det gjorde vi i fjor. (aftenposten.no 22.2.2017).)

(Anm: Powering the Cell: Mitochondria (ed.ted.com).)

(Anm: Cellular Respiration and the Mighty Mitochondria (ed.ted.com).)

(Anm: Dr. Terry Wahls - Minding Your Mitochondria - TED - Documentary, Lecture, Talk NUTRITION (youtube.com 16.4.2017).)

- Mitokondriell kontroll av immunitet: utover ATP. (- I denne gjennomgangen diskuterer vi hvordan mitokondriell metabolisme varierer over ulike immuncelle-undergrupper, hvordan metabolsk signalering dikterer cellens skjebne og hvordan denne signaleringen potensielt kan målrettes terapeutisk.)

(Anm: Mitochondrial control of immunity: beyond ATP. Abstract Mitochondria are important signalling organelles, and they dictate immunological fate. From T cells to macrophages, mitochondria form the nexus of the various metabolic pathways that define each immune cell subset. In this central position, mitochondria help to control the various metabolic decision points that determine immune cell function. In this Review, we discuss how mitochondrial metabolism varies across different immune cell subsets, how metabolic signalling dictates cell fate and how this signalling could potentially be targeted therapeutically. Nat Rev Immunol. 2017 Jul 3. [Epub ahead of print].)

- Mitokondriell dysfunksjons rolle i kreftprogresjon. (- Vi antyder derfor at mitokondriell dysfunksjon spiller en kritisk rolle i kreftprogresjon, og at målrettet mitokondrieller endringer og mitokondriell retrogradsignalering kan være en lovende strategi for utvikling av selektiv kreftbehandling.)

Role of mitochondrial dysfunction in cancer progression.
Exp Biol Med (Maywood). 2016 Jun;241(12):1281-95. Epub 2016 Mar 27.
Abstract Deregulated cellular energetics was one of the cancer hallmarks. Several underlying mechanisms of deregulated cellular energetics are associated with mitochondrial dysfunction caused by mitochondrial DNA mutations, mitochondrial enzyme defects, or altered oncogenes/tumor suppressors. In this review, we summarize the current understanding about the role of mitochondrial dysfunction in cancer progression. Point mutations and copy number changes are the two most common mitochondrial DNA alterations in cancers, and mitochondrial dysfunction induced by chemical depletion of mitochondrial DNA or impairment of mitochondrial respiratory chain in cancer cells promotes cancer progression to a chemoresistance or invasive phenotype. Moreover, defects in mitochondrial enzymes, such as succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase, are associated with both familial and sporadic forms of cancer. Deregulated mitochondrial deacetylase sirtuin 3 might modulate cancer progression by regulating cellular metabolism and oxidative stress. These mitochondrial defects during oncogenesis and tumor progression activate cytosolic signaling pathways that ultimately alter nuclear gene expression, a process called retrograde signaling. Changes in the intracellular level of reactive oxygen species, Ca(2+), or oncometabolites are important in the mitochondrial retrograde signaling for neoplastic transformation and cancer progression. In addition, altered oncogenes/tumor suppressors including hypoxia-inducible factor 1 and tumor suppressor p53 regulate mitochondrial respiration and cellular metabolism by modulating the expression of their target genes. We thus suggest that mitochondrial dysfunction plays a critical role in cancer progression and that targeting mitochondrial alterations and mitochondrial retrograde signaling might be a promising strategy for the development of selective anticancer therapy. (…)

(Anm: Kreft (mintankesmie.no).)

(Anm: Common cancers hijack powerhouses of cells (medicalnewstoday.com 9.4.2015).)

(Anm: Mitochondria in chronic obstructive pulmonary disease and lung cancer: where are we now? Biomark Med. 2017 Jun 9. [Epub ahead of print].)

(Anm: Signaler fra tarmens mikrobiotika til fjerntliggende organer mht. fysiologi og sykdom. Signals from the gut microbiota to distant organs in physiology and disease. (Nat Med. 2016 Oct 6;22(10):1079-1089.)

- Fatigue etter kreftbehandling. 15-35 % av alle kreftpasienter blir rammet av kronisk fatigue. Dette er i dag en av de vanligste seneffektene etter kreftbehandling.

(Anm: Fatigue etter kreftbehandling. 15-35 % av alle kreftpasienter blir rammet av kronisk fatigue. Dette er i dag en av de vanligste seneffektene etter kreftbehandling. Fatique er en vanlig senfølge etter kreftbehandling. Den som blir rammet opplever plager som vedvarende tretthet, kraftløshet, eventuelt også med konsentrasjonsproblemer og hukommelsessvikt. Hvis trettheten vedvarer etter at behandlingen er avsluttet, og varer mer enn seks måneder, kalles det for kronisk fatigue. For noen kan tilstanden vare i flere år. Sammensatt fenomen Årsaken til at så mange rammes av kronisk tretthet eller fatigue etter kreftbehandling, vet forskerne foreløpig ikke nok om. Men mye tyder på at dette er et sammensatt fenomen som påvirkes av somatiske, demografiske og psykososiale faktorer. - Vi ser at det å bo alene, ha lav inntekt, eller oppleve uro, bekymring og nedsatt stemningsleie, kan gi økt risiko for fatigue. Personer med tilleggs-sykdommer eller andre seneffekter som søvnforstyrrelser, hjerte/lungesykdom, perifere nerveskader og vedvarende smerter kan også ha økt risiko for å utvikle dette, sier Cecilie Essholt Kiserud som er spesialist i onkologi og leder ved Nasjonal kompetansetjeneste for seneffekter etter kreft ved Oslo Universitetssykehus, Radiumhospitalet. (lommelegen.no 14.3.2018).)

(Anm: Kreft (mintankesmie.no).)

(Anm: Kronisk tretthetssyndrom/Myalgisk encefalopati (CFS/ME). (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

- Mitokondriell dysfunksjon som trigger av medfødt immunrespons og betennelse.

(Anm: Mitochondrial Dysfunction as a Trigger of Innate Immune Responses and Inflammation. Abstract A growing literature indicates that mitochondria are key participants in innate immune pathways, functioning as both signaling platforms and contributing to effector responses. In addition to regulating antiviral signaling and antibacterial immunity, mitochondria also are important drivers of inflammation caused by sterile injury. Much research on mitochondrial control of immunity now centers on understanding how mitochondrial constituents released during cellular damage simulate the innate immune system. When mitochondrial integrity is compromised, mitochondrial damage-associated molecular patterns engage pattern recognition receptors, trigger inflammation, and promote pathology in an expanding list of diseases. Here, I review the emerging knowledge of mitochondrial dysfunction in innate immune responses and discuss how environmental exposures may induce mitochondrial damage to potentiate inflammation and human disease. Toxicology. 2017 Jul 29. pii: S0300-483X(17)30215-9.)

- Effekt av antipsykotika på mitokondriell bioenergetikk på rotters ovarie (eggstokk)-teca-celler.

Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells.
Toxicol Lett. 2017 Apr 15;272:94-100. Epub 2017 Mar 18.
Abstract BACKGROUND: Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a possible mechanism of reproductive toxicity.

METHODS: Isolated rat theca interstitial cells (TICs) were treated with two typical (chlorpromazine [CPZ] and haloperidol [HAL]) and two atypical APs (risperidone [RIS] and clozapine [CLZ]). The effects of these APs on TICs bioenergetics (ATP content, mitochondrial complexes I and III activities, oxygen consumption rates (OCRs), mitochondrial membrane potential (MPP) and lactate production) and on steroidogenesis (androstenedione and progesterone synthesis) were investigated.

RESULTS: All APs resulted in a concentration-dependent decrease in the ATP content of TICs. All APs at their estimated IC50s (6μM, 21μM, 35μM and 37μM for CPZ, HAL, CLZ and RIS respectively) significantly decreased TICs OCRs (p<0.0001), MPP (p<0.0001) and significantly (p=0.0003) inhibited mitochondrial complex I activity. Only typical APs inhibited complex III (p=0.005). Also, APs at IC50s increased TICs lactate production to varying degrees. All APs used at their IC50s significantly inhibited progesterone (p=0.0022) and androstenedione (p=0.0027) production. Only CPZ was found to inhibit these hormones at the low concentration (1μM).

KONKLUSJON: Alle fire antipsykotika ser ut til å hemme mitokondriell bioenergetikk og steroidogenese i rotters ovarieceller. Disse funnene støtter hypotesen om at AP-indusert reproduktiv toksisitet kan være gjennom mekanismer som involverer mitokondrielle skader. Videre forskning er nødvendig for å etablere sammenhengen mellom APs-indusert mitokondriell dysfunksjon og forstyrret steroidogenese. (CONCLUSION: All four antipsychotics seem to inhibit mitochondrial bioenergetics and steroidogenesis in rat's ovarian theca cells. These findings support the hypothesis that APs-induced reproductive toxicity may be through mechanisms involving mitochondrial insult. Further research is required to establish the link between APs-induced mitochondrial dysfunction and disordered steroidogenesis.)

(Anm: Antipsykotika (psykofarmaka etc.) (mintankesmie.no).)

(Anm: Lægemiddelstyrelsen opfordrer læger til at være opmærksomme på disse alvorlige bivirkninger hos børn og unge i behandling med aripiprazol (Abilify) (…) Gennemgangen viser også, at børn med ASD (autisme) der behandles med aripiprazol, kan udvikle alvorlige psykiatriske bivirkninger såsom svære kroniske søvnproblemer, aggressiv adfærd og hallucinationer. (…) Hårtab, depression og psykose, Vægtøgning, Hypercholesterolemi, Hypercholesterolemi. (LÆGEMIDDELSTYRELSEN - NYT OM BIVIRKNINGER 2016;7(9).)

(Anm: Variations in ancient mitochondrial DNA may play key role in predisposition to ASD. Wallace and colleagues, including Dimitra Chalkia, Larry Singh and others, published their findings today in JAMA Psychiatry. (news-medical.net 23.8.2017).)

- Studie antyder at kortisol formidler kommunikasjon mellom tarmbakterier og hjernemetabolitter.

(Anm: Cortisol mediates communication between gut bacteria and brain metabolites, study suggests. Gut microbes have been in the news a lot lately. Recent studies show they can influence human health, behavior, and certain neurological disorders, such as autism. But just how do they communicate with the brain? Results from a new University of Illinois study suggest a pathway of communication between certain gut bacteria and brain metabolites, by way of a compound in the blood known as cortisol. And unexpectedly, the finding provides a potential mechanism to explain the characteristics of autism. (news-medical.net 21.8.2017).)

(Anm: «Psykiatrien i Norge har hatt for svak ledelse. På alle nivåer. I alle år». KRONIKK: Helseminister Bent Høie (H). BENT HØIE, Helseminister. (vg.no 23.11.2016).)

(Anm: Antipsykotika øger diabetes-risiko hos børn. En række forskellige antipsykotika har vist sig at medføre op til tre gange så stor en risiko for at udvikle diabetes, hvis børn og unge behandles med dem. Et studie offentliggjort i tidsskriftet JAMA Psychiatry viser ifølge Dagens Medicin, at børn og unge i behandling med antipsykotiske lægemidler har tre gange så stor en risiko for at udvikle diabetes i forhold til lignende personer, der tager andre psykoaktive præparater. (…) Den forøgede risiko indtraf allerede efter blot et års forbrug, og risikoen var fortsat tilstede i mindst et år, efter deltagerne var stoppet med at tage lægemidlerne. (medwatch.dk 9.9.2013).)

- Mitokondriell dysfunksjon (MDF) har blitt identifisert som en viktig faktor i ulike sykdommer som spenner fra nevrologiske lidelser, sykdommer i kardiovaskulærsystemet og metabolske syndromer.

(Anm: Mitochondrial dysfunction and potential anticancer therapy. Abstract Mitochondrial dysfunction (MDF) has been identified as an important factor in various diseases ranging from neurological disorders, to diseases of the cardiovascular system and metabolic syndromes. MDF was also found in cancer as well as in cancer predisposition syndromes with defective DNA damage response (DDR) machinery. Moreover, a recent highlight arises from the detection of MDF in eukaryotic cells upon treatment with antibiotics. In this review, we focus on recent studies of MDF in pathological conditions with a particular emphasis on the effects of various classes of antibiotics on mitochondria. Special attention is given to the role of autophagy/mitophagy in MDF and repurposing antibiotics as anticancer drugs. Med Res Rev. 2017 Jul 6. [Epub ahead of print].)

- Akselerert aldring grunnet legemidlers negative påvirkninger av mitokondrier etc.

(Anm: Editor-in-Chief Henry A. Nasrallah, MD, discusses the possible causes of accelerated aging and premature mortality in younger persons with schizophrenia. Video. Accelerated aging in schizophrenia. Editor-in-Chief Henry A. Nasrallah, MD, discusses the possible causes of accelerated aging and premature mortality in younger persons with schizophrenia. Current Psychiatry. 2017 July;16(7).)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

(Anm: Mitokondriell dysfunksjon ligger bak kognitive defekter som et resultat av nevral stamcelleutarmning og nedsatt neurogenese. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet. 2017 Jun 8.)

(Anm: Behandling av barn og ungdom med antipsykotika er et tveegget sverd. (…) To tilleggsfunn fra Pagsberg og kollegers studie er verdt å understreke. For det første erfarte bare 22 (23 %) av pasientene behandlingsrespons. (…)  For det andre erfarte 111 (98 %) av pasientene uheldige reaksjoner. (For det andre erfarte 111 (98 %) av pasientene uheldige reaksjoner.) Blant de 55 pasienter som tok quetiapine, rapporterte 47 (92 %) økt søvnlengde og 46 (87 %) rapporterte vektøkning. Blant de 58 pasienter som tok aripiprazol, rapporterte 52 (91 %) tremor og 44 (77 %) rapporterte sviktende hukommelse. (Blant de 58 pasienter som tok aripiprazol, rapporterte 52 (91 %) tremor og 44 (77 %) rapporterte sviktende hukommelse.) The Lancet Psychiatry 2017;4(8):576–577 (Published: August, 2017).)

(Anm: Antipsykotika øger diabetes-risiko hos børn. En række forskellige antipsykotika har vist sig at medføre op til tre gange så stor en risiko for at udvikle diabetes, hvis børn og unge behandles med dem. Et studie offentliggjort i tidsskriftet JAMA Psychiatry viser ifølge Dagens Medicin, at børn og unge i behandling med antipsykotiske lægemidler har tre gange så stor en risiko for at udvikle diabetes i forhold til lignende personer, der tager andre psykoaktive præparater. (…) Den forøgede risiko indtraf allerede efter blot et års forbrug, og risikoen var fortsat tilstede i mindst et år, efter deltagerne var stoppet med at tage lægemidlerne. (medwatch.dk 9.9.2013).)

(Anm: Antidepressiva og antipsykotika gir økt risiko for diabetes hos barn og voksne (50 til 700 %) (mintankesmie.no).)

(Anm: Diabetes: Risiko for hjerteinfarkt på grunn av tap av små blodårene rundt hjertet. (Diabetes: Heart attack risk due to loss of small blood vessels around the heart.) (medicalnewstoday.com 24.3.2017).)

(Anm: Alzheimer's disease also affects small blood vessels. A research conducted by the UAB demonstrates that mice suffering from this disease also have substantial malfunctions in small blood vessels, important in nourishing different organs and tissues and in regulating blood pressure, and which mainly affects females. The study also demonstrates a correlation between the state of peripheral blood vessels and different levels of anxious behavior, both in normal aging and in those suffering from Alzheimer's disease.  (news-medical.net 16.3.2018).)

(Anm: Antidepressiva (øyesykdommer). (mintankesmie.no).)

(Anm: Bruk av antidepressiva ble assosiert med et betydelig eldre utseende og forskere fant også ut at vekten spilte en viktig faktor. I de sett med tvillinger som var yngre enn 40 år ble tyngre tvillinger oppfattet som eldre. (…) I tillegg mistenker forskerne at den vedvarende avslapping av ansiktsmuskler som antidepressiva forårsaker kan forklare årsaken til at ansiktet faller sammen (henger). (mintankesmie.no).)

(Anm: Role of mitochondria and energy metabolism in schizophrenia and psychotic disorders. Abstract. Mitochondria are cell organelles that initially had an independent existence as α-proteobacteria. A symbiotic arrangement with either a proto-eukaryote or an archaeon enabled the newly formed organism to generate levels of cellular energy that could sustain metabolic processes of previously impossible complexity (Gray, 2012). In this singular incident, the course of evolution was profoundly changed. Without mitochondria, multicellular organism might not be possible, and there is no doubt that human life depends on them. Schizophr Res. 2017 Jul 10. pii: S0920-9964(17)30408-5. [Epub ahead of print].)

(Anm: From the Editor. Accelerated aging in schizophrenia: Shortened telomeres, mitochondrial dysfunction, inflammation, and oxidative stress. Several lines of evidence are coalescing into a critical scientific insight: Persons with schizophrenia show evidence of accelerated aging.1 This implies early senescence, segmental aging, and, in young adult patients, premature onset of multi-system medical illnesses associated with aging, including cardiovascular disease, cancer, brain atrophy, and cognitive decline. This might be the real reason why persons with schizophrenia die 25 to 30 years too early, not only because of an unhealthy lifestyle and iatrogenic cardio-metabolic adverse effects. Current Psychiatry. 2016 November;15(11):21-23.)

(Anm: Bias [baies] -en, - skjevhet i vitenskapelig undersøkelse el. resultat pga. mangelfull systematikk i innsamlingen av data. Etym.: eng., fr. biais helning, tendens. Kilde: ordnett.no.)

(Anm: Bias; (...) valg og vurderinger som på systematisk måte avviker fra det som er faktisk korrekt. Kilde: Store norske leksikon.)

(Anm: Pasienter behandlet med antipsykotika (nevroleptika) har signifikant senket platelet complex I aktivitet i mitokondrier i likhet med det som er observert ved idiopatisk Parkinsons sykdom. (...) Antipsykotika (nevroleptika) hemmer kompleks I i elektrontransportkjeden. (Neuroleptic medications inhibit complex I of the electron transport chain. (...) Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson’s disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.) Ann Neurol. 1993;33:512-7).)

(Anm: Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes. (…) Highlights • Pancreatic mitochondrial complex I shows hyperactivity in diabetes. • Complex I hyperactivity is associated with increased NADH/NAD+ redox imbalance. • Complex I hyperactivity is associated with increased oxidative stress and cell death. • Complex I hyperactivity is linked with compromised cellular anti-oxidative stress capacity such as decreased sirt3 and NQO1 expressions. Biochem Biophys Rep. 2017 Sep;11:119-129.)

(Anm: Focus on an unusual rise in pancreatic cancer incidence in France. (…) Conclusion: Pancreatic cancer incidence and mortality exhibited diverging trends. Incidence increased over the last 30 years in France whereas mortality did not vary in men and moderately increased in women. Incidence remained lower than mortality up to 2002. One cannot exclude the possibility that a similar trend may appear in other countries. Etiological studies are required to further explain this increase.Int J Epidemiol. 2017 Dec 1;46(6):1764-1772.)

(Anm: A mitochondrial proteomics view of complex I deficiency in Candida. albicans. (…) We hypothesize that the loss of energy production in mutants is compensated by increases in protein levels of glycolysis, gluconeogenesis, and anti-ROS scavengers that at least extend mutant survival. Mitochondrion. 2017 Aug 8. pii: S1567-7249(17)30149-6.)

 - Mitokondrier, bioenergi og eksitotoksisitet: Nye terapeutiske mål i perinatal hjerneskade. Mitokondriene er sterkt Impliserte etter iskemisk skade på grunn av sine roller som drivkraft og hovedenergigeneratorer i cellen, såvel som celledødsprosesser.

(Anm: Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. (…) Mitochondria are the powerhouses of the cell, primarily responsible for the production of adenosine triphosphate (ATP) as well as playing regulatory roles in cell death, including autophagy and apoptosis (Nunnari and Suomalainen, 2012). Advances in genomic and proteomic sequencing have provided irrefutable evidence that these vestiges of bacterial ancestry also perform more diverse roles, particularly in disease (Hagberg et al., 2014). These range from early work showing that mutations in mitochondrial DNA (mtDNA) are implicated in diseases such as Parkinson’s disease (Swerdlow et al., 1996), to research on the epigenetic modulation of mtDNA, including methylation by DNA methyltransferases, which add yet another layer in which mitochondria can influence and contribute to disease (van der Wijst and Rots, 2015). There is thus a growing appreciation that identifying and targeting mitochondrial pathways thought to be responsible for the manifestation of initial injury post asphyxia as well as long-term neurodevelopment holds great promise in the field of perinatal medicine. Front. Cell. Neurosci., 12 July 2017.)

- Enkelte legemidler (substanser) og fysisk attraktivitet.

(Anm: Antipsykotika og fysisk attraktivitet (Antipsychotics and physical attractiveness) (...) Antipsykotika, som gruppe, fører til vektøkning og kan føre til munntørrhet og dårlig ånde, grå stær, hirsutisme (uvanleg sterk eller altfor utbreidd hårvekst (helst hos kvinner)), akne og stemmeendringer; de kan forstyrre symmetri av gangart og øke risikoen for tics og spasmer og inkontinens, og potensielt undergrave en persons attraktivitet. Clin Schizophr Relat Psychoses. 2011 Oct;5(3):142-146.)

(Anm: Medikamentutløst dystoni. (…) Videoen illustrerer ekstrapyramidale bivirkninger med dystoni i tunge og kjeveområdet. Tidsskr Nor Legeforen 2016; 136:1730-1730 (8.11.2016).)

(Anm: Bruk av antidepressiva ble assosiert med et betydelig eldre utseende og forskere fant også ut at vekten spilte en viktig faktor. I de sett med tvillinger som var yngre enn 40 år ble tyngre tvillinger oppfattet som eldre. (…) I tillegg mistenker forskerne at den vedvarende avslapping av ansiktsmuskler som antidepressiva forårsaker kan forklare årsaken til at ansiktet faller sammen (henger). (mintankesmie.no).)

(Anm: Antipsykotika forårsaker ansiktsgrimasering og andre typer mulige varige hjerneskader (mintankesmie.no).)

(Anm: Skrekkbildene som viser hva røyking gjør med kroppen din (dagbladet.no 19.10.2013).)

(Anm: Dödsdrogens sanna ansikte - Detta är bilderna som säger allt. Om livet före och efter. Med drogen crystal meth. (expressen.se 3.3.2006).)

- Søk etter mitokondrielle mekanismer: linking av kjente syndromer til mitokondriell funksjon.

(Anm: Mining for mitochondrial mechanisms: linking known syndromes to mitochondrial function. Abstract Mitochondrial disorders (MDs) are caused by defects in one or multiple complexes of the oxidative phosphorylation (OXPHOS) machinery. MDs are associated with a broad range of clinical signs and symptoms, and have considerable clinical overlap with other neuromuscular syndromes. This overlap might be due to involvement of mitochondrial pathways in some of these non-mitochondrial syndromes. Here, we give an overview of around 25 non-mitochondrial syndromes, diagnosed in patients who were initially suspected to have a MD on the basis of clinical and biochemical parameters. In addition, we highlight the mitochondrial connections of six of these non-mitochondrial syndromes (e.g. Rett syndrome and Dravet syndrome) diagnosed in multiple patients. Further research to unravel the interplay between these genes and mitochondria may help to increase knowledge on these syndromes. Conversely, it may open new avenues for research on pathways interacting with mitochondrial function in order to find new targets for therapeutics to treat MDs. The data presented in this review underline the importance of careful assessment of clinical, genetic, and biochemical data in all patients suspected of a neuromuscular syndrome, and highlights the importance of the role of clinical geneticists, physicians, and clinical biochemists in recognizing the possible mitochondrial connection of non-mitochondrial syndromes. Clin Genet. 2017 Jul 7. [Epub ahead of print].)

- Rollen til mitokondriell dysfunksjon ved utviklingen av Alzheimers sykdom.

(Anm: Rollen til mitokondriell dysfunksjon ved utviklingen av Alzheimers sykdom. The role of mitochondrial dysfunction in the progression of Alzheimer's disease. Curr Med Chem. 2017 Jun 16. [Epub ahead of print] Abstract The current molecular understanding of Alzheimer's disease (AD) has still not resulted in successful interventions. Mitochondrial dysfunction of the AD brain is currently emerging as a hallmark of this disease. One mitochondrial function often affected in AD is oxidative phosphorylation responsible for ATP production, but also for production of reactive oxygen species (ROS) and for the de novo synthesis of pyrimidines. This paper reviews the role of mitochondrial produced ROS and pyrimidines in the aetiology of AD and their proposed role in oxidative degeneration of macromolecules, synthesis of essential phospholipids and maintenance of mitochondrial viability in the AD brain. Curr Med Chem. 2017 Jun 16.)

(Anm: Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt. (The role of mitochondrial dysfunction in sepsis-induced multi-organ failure). (Virulence. 2013 Nov 1;5(1).)

- Diagnostisering av sepsis. Sepsis, også kjent som blodforgiftning, er kroppens hyperaktive respons på en infeksjon som kan føre til betennelse, vevskader, organsvikt etc.

(Anm: Diagnosing Sepsis. Sepsis, also known as blood poisoning, is the body’s hyperactive response to an infection that can lead to inflammation, tissue damage, organ failure etc. It is a very dangerous state in which the immune system stops fighting with the invading agents  and turns to itself. Around one-third of patients who are affected with sepsis die every year. (news-medical.net 7.9.2017).)

- Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon.

(Anm: Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon. Recognizing Sepsis as a Global Health Priority — A WHO Resolution. “Some very important clinical issues, some of them affecting life and death, stay largely in a backwater which is inhabited by academics and professionals and enthusiasts, dealt with very well at the clinical and scientific level but not visible to the public, political leaders, leaders of healthcare systems... The public and political space is the space in which [sepsis] needs to be in order for things to change.” NEJM (June 28, 2017).)

(Anm: Antidepressiva er ifølge ny studie knyttet til mislykkede tannimplantater. (Antidepressants linked to tooth implant failure, new study finds.) (- Forskning viser at bruk av antidepressiva firedobler risikoen for implantat svikt. For hvert år dobler antidepressiva risikoen for svikt.) (medicalnewstoday.com 10.3.2016).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

- Kronisk oksidativ stress, mitokondriell dysfunksjon, Nrf2 aktivering og inflammasjon i Hippocampus-ledsaget av forhøyet systemisk inflammasjon og oksidativ stress i en dyremodell ved GWI (Golfskrigslidelse; engelsk: Gulf War Syndrome).

(Anm: Chronic Oxidative Stress, Mitochondrial Dysfunction, Nrf2 Activation and Inflammation in the Hippocampus Accompany Heightened Systemic Inflammation and Oxidative Stress in an Animal Model of Gulf War Illness. Memory and mood dysfunction are the key symptoms of Gulf war illness (GWI), a lingering multi-symptom ailment afflicting >200,000 veterans who served in the Persian Gulf War-1. Research probing the source of the disease has demonstrated that concomitant exposures to anti-nerve gas agent pyridostigmine bromide (PB), pesticides, and war-related stress are among the chief causes of GWI. Front. Mol. Neurosci., 14 June 2017.)

(Anm: Animal model of Gulf War illness hints at possible ways to mitigate symptoms. (…) To test the effects of such exposure, the researchers must first create an animal model. "We simulate what happened during the war," Shetty said. (…) Additional studies completed recently in Shetty's laboratory have also shown resveratrol as a promising compound for decreasing systemic and brain inflammation, as well as improving cognitive and memory function in animal models of GWI. (medicalnewstoday.com 20.6.2017).)

(Anm: Modeling Gulf War illness: Knowing the cause of brain dysfunction is key to finding a cure. With hundreds of thousands of veterans experiencing long-term side effects of their service, the hunt for a treatment is on. When hundreds of thousands of American troops deployed to the Persian Gulf in 1990 and 1991 in what is now called the First Gulf War, they were exposed to a variety of chemicals. (…) “Together, these findings raise the possibility that hippocampal dysfunction in GWI is one of the adverse outcomes of persistently elevated oxidative stress and inflammation at the systemic level,” he added. (vitalrecord.tamhsc.edu 14.6.2017).)

(Anm: Linking telomere loss and mitochondrial dysfunction in chronic disease. (…) Drawing a mechanistic connection between telomere function and mitochondria biology will provide a broader perspective for understanding the pathophysiology of diseases and their relation to the aging process, and may provide opportunities for new possible treatments. Front Biosci (Landmark Ed). 2017 Jan 1;22:117-127.)

- Kronisk behandling med prebiotika, probiotika og synbiotika redusert hjertedysfunksjon ved å forbedre hjertemittokondriell dysfunksjon hos mannlige overvektige insulinresistente rotter.

(Anm: Chronic treatment with prebiotics, probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats. Abstract PURPOSE: In metabolic syndrome, the composition of gut microbiota has been disrupted, and is associated with left ventricular (LV) dysfunction. Several types of prebiotics, probiotics, and synbiotics have been shown to exert cardioprotection by restoring gut microbiota from dysbiosis and reducing systemic inflammation. However, the effects of prebiotics such as xylooligosaccharides (XOS); probiotics such as Lactobacillus paracasei STII01 HP4, and synbiotics on metabolic and LV function in obese insulin-resistant rats have not been investigated. In this study, we hypothesized that prebiotics and probiotics improve metabolic parameters, heart rate variability (HRV), blood pressure (BP), and LV function by attenuating cardiac mitochondrial dysfunction, systemic inflammation, and oxidative stress, and that synbiotics provide greater efficacy than a single regimen in obese insulin resistance. (…) CONCLUSION: Prebiotics, probiotics, and synbiotics shared similar efficacy in reducing insulin resistance and LV dysfunction in obese insulin-resistant rats. Eur J Nutr. 2017 Jun 12.)

(Anm: Studie linker gastrointestinale forstyrrelser for GWI (Golfskrigslidelse; engelsk: Gulf War Syndrome) med forandringer i mikrobiota (tarmfloraen). (Study links gastrointestinal disturbances of GWI with changes in intestinal microbiota.) (…) "Mennesker og dyr har spesifikke typer bakterier som bidrar til å hjelpe til med forskjellige fysiologiske prosesser, inkludert fordøyelse, absorpsjon, immunitet og tarmintegritet, og når eksterne faktorer endrer den bakterielle sammensetningen i vårt fordøyelsessystem får vi problemer", sier Chatterjee. "Fedme, metabolsk syndrom, inflammatorisk tarmsyndrom og leversykdom er allerede blitt knyttet til endringer i bakteriesammensetningen i tarmen." (news-medical.net.com 23.3.2017).)

(Anm: Antibiotika associeras med högre risk för tarmcancer. (…) Det här är första studien som visar på sambandet mellan antibiotikaanvändning och utveckling av adenom i tjock- och ändtarmen. Studien publiceras i den vetenskapliga tidskriften Gut. (…) Resultatet visade att långvarig antibiotikaanvändning tidigare i livet, i åldern 20 till 59 år, hade samband med diagnostiserade adenom. (lakemedelsvarlden.se 5.4.2017.)

- Er glaukom en mitokondriell neurodegenerativ sykdom.

(Anm: Er glaukom en mitokondriell neurodegenerativ sykdom. [Is glaucoma a mitochondrial neurodegenerative disease]. Abstract. The retinal ganglion cell, due to peculiar structural and energetic constraints, appears acutely susceptible to mitochondrial dysfunction. Emerging evidence suggests that changes in the mitochondrial DNA(mtDNA)and in nuclear DNA genes that encode mitochondrial proteins may influence mitochondrial structure and function and, therefore, contribute to the pathogenesis of primary open angle glaucoma. As the main glaucoma risk factors are elevated intraocular pressure and older age, we discuss their relationship with mitochondrial dysfunction. If the contribution of mitochondrial dysfunction to glaucoma pathogenesis is further established, emerging therapies aiming to optimize mitochondrial function represent potential clinical treatments. (Chin J Ophthalmol, 2016, 52: 714-717).  Zhonghua Yan Ke Za Zhi. 2016 Sep 11;52(9):714-7.)

(Anm: Antidepressiva (øyesykdommer). (mintankesmie.no).)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Ny forskning: Lykkepiller gør mere skade end gavn. Folk med depression får intet ud af at tage antidepressivet SSRI, bedre kendt som lykkepiller, viser nyt dansk studie. (jyllands-posten.dk 13.2.2017).)

(Anm: PTSD og psykoaktive legemidler knyttet til økt risiko for demens. (PTSD and psychoactive drugs linked to increased risk for dementiaI) (…) I denne studien oppdaget forskerne at det å ta visse antidepressiva, sedativer, beroligende midler eller antipsykotika økte veteranernes risiko for å utvikle demens sammenlignet med risikoen for veteraner som ikke tok slike legemidler. (…) En ny studie, publisert i Journal of the American Geriatrics Society undersøkte denne forbindelsen. (...) Legemidler som betydelig økte risikoen for demens inkluderte: - Selektive serotonin reopptakshemmere (SSRI) - Nye antidepressiva - Atypiske antipsykotika. (news-medical.net 9.5.2017).)

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

(Anm: Kan Lupus øke risikoen for demens? Could lupus raise dementia risk? People living with lupus may be at significantly greater risk of developing dementia than those without the autoimmune disease, a new study suggests. (…) Study co-author Daniela Amital, of the Sackler Faculty of Medicine at Tel Aviv University in Israel, and colleagues recently reported their results in the International Journal of Geriatric Psychiatry. (medicalnewstoday.com 9.11.2017).)

(Anm: Antidepressiva ökar risken för benbrott hos äldre. (…) Den förhöjda risken för höftfraktur gällde alla de vanliga antidepressiva läkemedlen, SSRI-preparat, mirtazapin och SNRI-preparat (selektiva serotonin- och noradrenalinåterupptagshämmare. Sambandet gällde även då det kontrollerats för andra faktorer som ålder, annan medicinering som ökar fallrisken, benskörhet, socioekonomisk status, kroniska sjukdomar och psykiatriska diagnoser.) (lakemedelsvarlden.se 12.1.2017).)

(Anm: Tannkjøttsykdom er et tidlig tegn på diabetes, og tap av tenner er forbundet med risiko for demens, ifølge studier. Gum disease is an early sign of diabetes, and tooth loss is associated with risk of dementia, studies find. Patients with periodontitis have higher plasma concentrations of glycated haemoglobin (HbA1c) than people with healthy gums, and those with severe periodontitis have a significantly higher risk of developing diabetes, a Dutch study has found. BMJ 2017;356:j1225 (Published 09 March 2017).)

(Anm: Tannleger og tannhelse (munnhulen er kroppens speil). (mintankesmie.no/).)

(Anm: Diabetes (mintankesmie.no).)

(Anm: Dementia, Alzheimer's, and Aging Brains (medicinenet.com 22.7.2016).)

(Anm: - Kalsiumubalanse i hjerneceller kan utløse Alzheimers sykdom. (- Ingen har noen gang sett på dette før bruken av disse modellsystemene. Det er mulig at endringer i mitokondrienes kalsiumutveksling er driveren av sykdomsprosessen. Tidligere forskning har vist at en overdreven produksjon av kalsium kan føre til at nerveceller dør, derfor linkes en kalsiumubalanse med den nevrodegenerative prosessen involvert i Alzheimers sykdom. (Calcium imbalance within brain cells may trigger Alzheimer's disease.) (medicalnewstoday.com 15.2.2017).)

(Anm: Mitochondrial Dysfunction Triggers Synaptic Deficits via Activation of p38 MAP Kinase Signaling in Differentiated Alzheimer's Disease Trans-Mitochondrial Cybrid Cells. J Alzheimers Dis. 2017 Jun 6. [Epub ahead of print].)

(Anm: Kurerer eller skaper antidepressiva unormale tilstander i hjernen? (mintankesmie.no).)

- Vi konkluderer med at metadon forårsaker svikt i intracellulær Ca (2+) homeostase, og at denne effekten er forbundet med morfologiske og funksjonelle forandringer av mitokondrier. Sannsynligvis bidrar denne mekanismen til degenerative bivirkninger forbundet med metadonbehandling.

(Anm: Vi konkluderer med at metadon forårsaker svikt i intracellulær Ca (2+) homeostase, og at denne effekten er forbundet med morfologiske og funksjonelle forandringer av mitokondrier. Sannsynligvis bidrar denne mekanismen til degenerative bivirkninger forbundet med metadonbehandling. («We conclude that methadone causes failure of intracellular Ca(2+) homeostasis, and this effect is associated with morphological and functional changes of mitochondria. Likely, this mechanism contributes to degenerative side effects associated with methadone treatment.») Int J Cell Biol. 2012;2012:642482. dEpub 2012 Jun 17).

(Anm: 24 år gammel var hun blitt hektet på illegalt metadon. Behandlingen Melissa fikk, var mer metadon. (…) Hun foreller at det ikke er vanskelig å skaffe seg preparater som er skrevet ut til LAR-pasienter. – Det er nok av tilbud på metadon på gaten. Det er et stort marked, og jeg kunne lett solgt dagdosene mine for 200 kroner stykket. Da ville jeg sittet igjen med penger nok til å kjøpe meg en friskmelding, forteller hun og sikter til en dose heroin. (aftenposten.no 31.10.2016).)

- Samspillet mellom betennelse, oksidativt stress, DNA-skade, DNA-reparasjon og mitokondriell dysfunksjon ved depresjon.

(Anm: The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression. Abstract A growing body of evidence suggests that inflammation, mitochondrial dysfunction and oxidant-antioxidant imbalance may play a significant role in the development and progression of depression. Elevated levels of reactive oxygen and nitrogen species - a result of oxidant-antioxidant imbalance - may lead to increased damage of biomolecules, including DNA. This was confirmed in depressed patients in a research study conducted by our team and other scientists. 8-oxoguanine - a marker of oxidative DNA damage - was found in the patients' lymphocytes, urine and serum. These results were confirmed using a comet assay on lymphocytes. Furthermore, it was shown that the patients' cells repaired peroxide-induced DNA damage less efficiently than controls' cells and that some single nucleotide polymorphisms (SNP) of the genes involved in oxidative DNA damage repair may modulate the risk of depression. Lastly, less efficient DNA damage repair observed in the patients can be, at least partly, attributed to the presence of specific SNP variants, as it was revealed through a genotype-phenotype analysis. In conclusion, the available literature shows that both oxidative stress and less efficient DNA damage repair may lead to increased DNA damage in depressed patients. A similar mechanism may result in mitochondrial dysfunction, which is observed in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jun 29. pii: S0278-5846(16)30298-6. [Epub ahead of print].)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

(Anm: Mitokondriell dysfunksjon ligger bak kognitive defekter som et resultat av nevral stamcelleutarmning og nedsatt neurogenese. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet. 2017 Jun 8.)

(Anm: Adenosintrifosfat (ATP) er en energirik kjemisk forbindelse som er involvert i alle energikrevende prosesser i menneskekroppen, som muskelsammentrekning, overføring av signaler i nerver, oppbygging av proteiner, kopiering av arvestoffer med mer. (…) ATP kan oppfattes som en universell energileverandør i alle celler og vev. Livet ville ikke vært mulig uten ATP. Forbindelsen er blitt kalt «livets molekyl». Kilde: Store norske leksikon.)

- Artrose: Forhindring av mangel på nøkkelmolekyl kan forsinke behov for leddproteser. (- Mitokondrier forsyner cellen med energi i form av kjemiske enheter kalt adenosin trifosfat (ATP), adenosin og ATP er et biprodukt av metabolisme.)

Osteoarthritis: Preventing key molecule deficiency may delay need for joint replacements
medicalnewstoday.com 11.5.2017
New research carried out on rodents reveals, for the first time, that preventing the loss of a molecule that is important for cartilage maintenance could delay the onset of osteoarthritis, a disease of the joints that causes disability and affects millions of people in the United States.

Osteoarthritis (OA) - also referred to as degenerative joint disease - is the most common form of arthritis, a general term used to describe a range of conditions that cause pain or disease in the joints.

The new study, led by the NYU Langone Medical Center in New York and published in the journal Nature Communications, shows that injecting the vital cell molecule adenosine into the joints can prevent OA in rat models of the disease.

OA most commonly affects the hips, hands, and knees, and it results from the gradual wear and tear of the cartilage that cushions the ends of the bones in the joint and stops them rubbing against each other. (…)

Adenosine helps healthy chondrocytes maintain cartilage
The researchers investigated the role that adenosine plays in maintaining a healthy supply of chondrocytes.

They note in their study paper that adenosine levels inside and outside cells are "tightly controlled" by cellular stress, oxygen consumption, and the workings of mitochondria - the pockets inside cells that produce the energy for the cell.

Mitochondria supply the cell with energy in the form of chemical units called adenosine triphosphate (ATP), and adenosine is a byproduct of ATP metabolism.

It was already known that aging and inflammation reduces ATP production in chondrocytes, which in turn reduces levels of adenosine. However, until this study, it was not clear how that might relate to OA.

One of the main discoveries of the study is that reduction in chondrocytes, and therefore greater risk for OA, is driven not only by lower levels of adenosine surrounding the cells, but also by loss of signal-receiving proteins called adenosine A2A receptors on the surface of the cells. (…)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

(Anm: Mitokondriell dysfunksjon ligger bak kognitive defekter som et resultat av nevral stamcelleutarmning og nedsatt neurogenese. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet. 2017 Jun 8.)

(Anm: Adenosintrifosfat (ATP) er en energirik kjemisk forbindelse som er involvert i alle energikrevende prosesser i menneskekroppen, som muskelsammentrekning, overføring av signaler i nerver, oppbygging av proteiner, kopiering av arvestoffer med mer. (…) ATP kan oppfattes som en universell energileverandør i alle celler og vev. Livet ville ikke vært mulig uten ATP. Forbindelsen er blitt kalt «livets molekyl». Kilde: Store norske leksikon.)

(Anm: Senescence, apoptosis or autophagy? When a damaged cell must decide its path--a mini-review. Many features of aging result from the incapacity of cells to adapt to stress conditions. When damage accumulates irreversibly, mitotic cells from renewable tissues rely on either of two mechanisms to avoid replication. They can permanently arrest the cell cycle (cellular senescence) or trigger cell death programs. Apoptosis (self-killing) is the best-described form of programmed cell death, but autophagy (self-eating), which is a lysosomal degradation pathway essential for homeostasis, reportedly contributes to cell death as well. Unlike mitotic cells, postmitotic cells like neurons or cardiomyocytes cannot become senescent since they are already terminally differentiated. The fate of these cells entirely depends on their ability to cope with stress. Autophagy then operates as a major homeostatic mechanism to eliminate damaged organelles, long-lived or aberrant proteins and superfluous portions of the cytoplasm. In this mini-review, we briefly summarize the molecular networks that allow damaged cells either to adapt to stress or to engage in programmed-cell-death pathways. Gerontology. 2008;54(2):92-9. Epub 2008 May 2.)

(Anm: ER-Mitochondria signaling regulates autophagy.Autophagy. Abstract. The endoplasmic reticulum (ER) and mitochondria form tight functional contacts that regulate a number of key cellular processes. Finally, our studies revealed that the modulatory effects of ER-mitochondria contacts on autophagy involve their role in mediating ITPR (inositol 1,4,5-trisphosphate receptor) delivery of Ca2+ from ER stores to mitochondria. Autophagy. 2017 May 26:0. [Epub ahead of print].)

(Anm: Control of cell death and mitochondrial fission by ERK1/2 MAP Kinase signalling FEBS J. 2017 May 26. doi: 10.1111/febs.14122. [Epub ahead of print].)

(Anm: Mitochondrial Dysfunction Meets Senescence. Trends Biochem Sci. 2016 Feb 10. pii: S0968-0004(16)00020-7. [Epub ahead of print].)

(Anm: Short Overview. Abstract Mitochondrial autophagy (mitophagy) is a mitochondrial quality control mechanism that selectively removes damaged mitochondria via autophagic degradation. Autophagic adaptor/receptor proteins contribute to the selective degradation of damaged mitochondria by autophagy. A part of them containing both ubiquitin binding domains and Atg8 interacting motif (AIM)/LC3 interacting region (LIR) motifs, which bind to the autophagy-related protein 8 (Atg8) family (LC3 and GABARAP family), lead ubiquitylated (damaged) mitochondria to selective removal. On the other hand, some specific outer mitochondrial membrane-anchored proteins containing AIM/LIR motif function as another type of autophagy adaptor/receptor proteins. Here I briefly summarize mechanisms of mitophagy and its related proteins.) Methods Mol Biol. 2017 May 12. [Epub ahead of print].)

(Anm: Senescence (/sɪˈnɛsəns/) (from Latin: senescere, meaning "to grow old", from senex) or biological aging (also spelled biological ageing) is the gradual deterioration of function characteristic of most complex lifeforms, arguably found in all biological kingdoms, that on the level of the organism increases mortality after maturation. The word senescence can refer either to cellular senescence or to senescence of the whole organism. It is commonly believed that cellular senescence underlies organismal senescence. The science of biological aging is biogerontology. (en.wikipedia.org).)

(Anm: Evig ung. 2. Hvordan bremse det kroppslige forfallet? (…) Episodebeskrivelse For å leve lenge, må vi vedlikeholde kroppen vår. Hjelper det egentlig å trene? Når kroppen blir slitt trenger vi nye deler, forskere mener de nå kan dyrke menneskeorganer inni griser (nrk.no 2.4.2017).)

- Syntetisk forbindelse som leser mitokondrie-DNA kan føre til behandlinger for nerve, muskel sykdommer. For første gang kan en syntetisk fremstilt forbindelse som kan binde seg til DNA i cellenes kraftstasjoner (mitokondrier), undertrykke et gen med tilknytning til nerve og muskelsykdommer.

(Anm: Synthetic compound that reads mitochondrial DNA could lead to treatments for nerve, muscle diseases. For the first time, a synthetic compound has been made that can bind to DNA in the cells' energy powerhouses, suppressing a gene associated with nerve and muscle disease. Pyrrole-imidazole polyamides (PIPs) are compounds that can read specific DNA sequences inside living cells and silence disease-causing genes. They prevent proteins, called transcription factors, from binding to specific parts of the DNA strand, thus suppressing the transcription of DNA into RNA. Most DNA is found in the nucleus. But mitochondria, the cell's powerhouses, also host a small amount of DNA. PIPs are capable of crossing the nuclear membrane to bind to nuclear DNA, but are incapable of crossing the mitochondrial membrane. (news-medical.net 11.7.2017).)

(Anm: Chronic kidney disease induces autophagy leading to dysfunction of mitochondria in skeletal muscle. Am J Physiol Renal Physiol. 2017 Apr 5:ajprenal.00600.2016.)

(Anm: Unclogging the garbage disposal: how exercise may improve mitochondria in ageing skeletal muscle. J Physiol. 2018 Jun 13.)

(Anm: Disrupted mitochondrial function in the Opa3L122P mouse model for Costeff Syndrome impairs skeletal integrity. Thus, mitochondrial function is important for the development and maintenance of skeletal integrity, impaired bone growth and strength, particularly in limb bones, representing a significant new feature of the Costeff syndrome phenotype. Hum Mol Genet. 2016 Jun 15;25(12):2404-2416. Epub 2016 Apr 22.)

(Anm: Linking mitochondrial dysfunction to neurodegeneration in lysosomal storage diseases. (…) Abstract Lysosomal storage diseases (LSD) are inborn errors of metabolism resulting in multisystem disease. Central nervous system involvement, often with progressive neurodegeneration, accounts for a large portion of the morbidity and mortality seen in many LSD. Available treatments fail to prevent or correct neurologic symptoms and decline. J Inherit Metab Dis. 2017 May 5. [Epub ahead of print].)

(Anm: Oxygen’s surprisingly complex journey through your body - Enda Butler. Oxygen forms about 21% of the air around us. In your body, oxygen forms a vital role in the production of energy in most cells. But if gases can only efficiently diffuse across tiny distances, how does oxygen reach the cells deep inside your body? Enda Butler tracks the surprisingly complex journey of oxygen through your body. (ed.ted.com.)

(Anm: From dysfunctional endoplasmic reticulum-mitochondria coupling to neurodegeneration. Neurochem Int. 2017 Apr 4. pii: S0197-0186(17)30081-5.)

(Anm: Chikusetsu (CHI) triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species (ROS) production. (…) Moreover, in vivo study showed that prostate tumor was inhibited by CHI administration through apoptosis induction. Thus, the results illustrated that CHI might be an effective therapeutic strategy for prostate cancer treatment in future.Biomed Pharmacother. 2017 Apr 5;90:446-454.)

- Laktat kan være nøkkelen til kreftutvikling. (- Laktat er et biprodukt av den kjemiske prosess som er kjent som glykolyse - å bryte ned av sukker eller glukose til mindre molekyler med det formål å frembringe energi. Under intens fysisk aktivitet, akkumuleres laktat i vevet og blod, som noen ganger kan føre til dårligere fysisk ytelse og muskelstivhet.)

Lactate may be key for cancer development (Laktat kan være nøkkelen til kreftutvikling.)
medicalnewstoday.com 19.3.2017
Researchers are working hard to understand the mechanism responsible for oncogenesis, the process through which normal cells become cancerous ones. A new study focuses on lactate - a molecule produced during intense exercise - and explains its role in cancer cell formation.

New research, published in the journal Carcinogenesis, analyzes the role of lactate in oncogenesis.

Laktat er et biprodukt av den kjemiske prosess som er kjent som glykolyse - å bryte ned av sukker eller glukose til mindre molekyler med det formål å frembringe energi. Under intens fysisk aktivitet, akkumuleres laktat i vevet og blod, som noen ganger kan føre til dårligere fysisk ytelse og muskelstivhet. (Lactate is a byproduct of the chemical process known as glycolysis - the breaking down of sugar, or glucose, into smaller molecules with the purpose of producing energy. During intense physical activity, lactate accumulates in the tissue and blood, which can sometimes lead to poorer physical performance and muscle stiffness.)

At the beginning of the 20th century, German scientist Otto Warburg noticed that cancer cells consume a lot more glucose than normal cells. The so-called Warburg effect refers to the fact that cancer cells undergo more glycolysis and produce more lactate compared with normal cells.

The new research - led by Inigo San Millan, director of the Sports Performance Department and physiology laboratory at the University of Colorado-Boulder's Sports Medicine and Performance Center - set out to understand why the Warburg effect happens. Since Warburg's time, the focus in cancer research has shifted from cell metabolism to genetics, but the new paper hopes to put lactate back at the center of cancer research. (…)

(Anm: High serum lactate level may predict death within 24 hours. (…) CONCLUSIONS: The significant independent variable that predicted death within 24 hours of admission was arterial blood lactate level on admission. Older age was also an independent variable; low pH affected only males, but was a less dominant variable. We suggest use of arterial blood lactate level on admission as a bio-marker in patients with suspected sepsis admitted to the hospital for risk assessment and prediction of death within 24 hours of admission. Open Med (Wars). 2015 Jun 11;10(1):318-322. eCollection 2015.)

(Anm: The mobility of mitochondria: intercellular trafficking in health and disease. (…) The ability of mitochondria to move between cells appears to be an evolutionarily-conserved phenomenon, relevant to diseases with compromised mitochondrial function including neurodegenerative, neuromuscular and cardiovascular diseases as well as cancer and ageing. Clin Exp Pharmacol Physiol. 2017 Apr 13.)

- Raskt glukoseopptak gir økt risiko for kreft. Menn med raskt glukoseopptak fra blodbanen har betydelig forhøyet risiko for kreft, viser en fersk, norsk studie fra Oslo Universitetssykehus.

(Anm: Raskt glukoseopptak gir økt risiko for kreft. Menn med raskt glukoseopptak fra blodbanen har betydelig forhøyet risiko for kreft, viser en fersk, norsk studie fra Oslo Universitetssykehus. Dersom det sprøytes glukose, også kjent som druesukker, inn i blodbanen, settes det i gang mekanismer som gjør at overskudd av sukker transporteres inn i kroppens celler. En ny studie av norske menn som har blitt fulgt over mange år, viser at raskt opptak av glukose fra blodbanen er forbundet med økt risiko for kreft senere i livet. Studien er nylig publisert i det vitenskapelige tidsskriftet eBioMedicine. (dagensmedisin.no 12.7.2017).)

- The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon.

MDR1 deficiency impairs mitochondrial homeostasis and promotes intestinal inflammation.
Mucosal Immunol. 2017 Apr 12.
Abstract The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon. In mice, loss of MDR1 function results in colitis with similarities to human inflammatory bowel diseases (IBD). Here, we show that MDR1 has an unexpected protective role for the mitochondria where MDR1 deficiency results in mitochondrial dysfunction with increased mitochondrial reactive oxygen species (mROS) driving the development of colitis. Exogenous induction of mROS accelerates, while inhibition attenuates colitis in vivo; these effects are amplified in MDR1 deficiency. In human IBD, MDR1 is negatively correlated to SOD2 gene expression required for mROS detoxification. To provide direct evidential support, we deleted intestinal SOD2 gene in mice and showed an increased susceptibility to colitis. We exploited the genome-wide association data sets and found many (∼5%) of IBD susceptibility genes with direct roles in regulating mitochondria homeostasis. As MDR1 primarily protects against xenotoxins via its efflux function, our findings implicate a distinct mitochondrial toxin+genetic susceptibility interaction leading to mitochondrial dysfunction, a novel pathogenic mechanism that could offer many new therapeutic opportunities for IBD. Mucosal Immunology advance online publication, 12 April 2017; doi:10.1038/mi.2017.31. (…)

(Anm: Problem Drugs. Many different drugs and drug classes have been reported to cause problems in dogs with the MDR1 mutation. The VCPL continues to work to identify drugs that may be dangerous to dogs with the MDR1 mutation and to determine alternative drugs and doses for these dogs. (vcpl.vetmed.wsu.edu (13.4.2017)).)

- Her er den bedste træning til at modvirke, at kroppens celler ældes. (- De yngre testdeltagere havde en forbedret ydelse i cellestrukturernes (mitokondriernes) kapacitet på 49 procent og de ældre på hele 69 procent. Det er meget signifikante tal i forhold til at udsætte cellernes aldring.)

Her er den bedste træning til at modvirke, at kroppens celler ældes
jyllands-posten.dk 8.3.2017
Både unge og ældre opnår overraskende gode resultater på kort tid, viser undersøgelse. (…)

Forskere ved Mayo Clinic i Minnesota i USA lod 72 unge og ældre mennesker udføre forskellige typer fysiske øvelser ved forskellige intensiteter for at måle, hvilke der havde de største fordele i forhold til at udsætte kroppens aldringsproces. Og konklusionen var klar, skriver Daily Mail og New Scientist. (...)

Det handlede ikke om den konkrete, fysiske øvelse. I stedet gælder det om at træne maksimalt i fire minutter ad gangen efterfulgt af tre minutters aktivitet ved lidt lavere niveau 12 gange om ugen. Dette program skal suppleres af i alt 90 minutters gang i en stepmaskine eller en tilsvarende gåtur. Øvelserne kan for eksempel fordeles over 3-4 træningspas i løbet af syv dage.

Og resultatet var overbevisende. Ved at tage biopsier af deltagernes muskler kunne forskerne se, at de yngre testdeltagere havde en forbedret ydelse i cellestrukturernes (mitokondriernes) kapacitet på 49 procent og de ældre på hele 69 procent. Det er meget signifikante tal i forhold til at udsætte cellernes aldring.

Den eneste reelle svaghed ved den kortvarige træningsindsats var en begrænset evne til at opbygge musklerne. Her er styrketræning stadig et godt supplement til intervaltræning. (...)

Motionsstudiet er også beskrevet i magasinet Cell Metabolism. (…)

(Anm: Fysisk trening (aktivitet / løping / jogging). (mintankesmie.no).)

(Anm: Linking telomere loss and mitochondrial dysfunction in chronic disease. (…) Drawing a mechanistic connection between telomere function and mitochondria biology will provide a broader perspective for understanding the pathophysiology of diseases and their relation to the aging process, and may provide opportunities for new possible treatments. Front Biosci (Landmark Ed). 2017 Jan 1;22:117-127.)

(Anm: Extreme short and long telomeres linked to increased cancer risk (news-medical.net 5.4.2017).)

(Anm: Mitochondrial dysfunction-a link between antibiotic use and increased risk of severe mental disorders? Acta Psychiatr Scand. 2017 Mar 23.)

(Anm: Mitokondriell dysfunksjon ved luftveissykdom.  Mitochondrial Dysfunction in Airway Disease. Abstract. There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore non-canonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke and environmental insults important in these diseases, and in turn can respond to such stimuli via altered mitochondrial protein expression, structure, and resultant dysfunction. Chest. 2017 Mar 21. pii: S0012-3692(17)30398-7.)

(Anm: Scientists discover master regulator of cellular aging. (…) "Telomeres represent the clock of a cell," said TSRI Associate Professor Eros Lazzerini Denchi, corresponding author of the new study, published online in the journal Science. "You are born with telomeres of a certain length, and every time a cell divides, it loses a little bit of the telomere. Once the telomere is too short, the cell cannot divide anymore." (medicalnewstoday.com 13.1.2017).)

(Anm: Telomere length and depression: prospective cohort study and Mendelian randomisation study in 67 306 individuals. Background. Depression has been cross-sectionally associated with short telomeres as a measure of biological age. However, the direction and nature of the association is currently unclear. (…) Further, purchase of antidepressant medication was not associated with short telomere length cross-sectionally or prospectively. (…) Conclusions. Short telomeres were not associated with depression in prospective or in causal, genetic analyses. The British Journal of Psychiatry Jan 2017, 210 (1) 31-38.)

(Anm: Harvard Scientists Claim to Reverse Aging in Mice. (…) Mitochondria: Aging in a car takes place mainly in the engine. Similarly, aging in the cell takes place in its "engine," the mitochondria. (bigthink.com 3.1.2011).)

(Anm: Gray matter abnormality predicts neurodevelopmental problems in smaller premature babies (medicalnewstoday.com 8.4.2016).)

(Anm: Gray Matter Abnormalities in the Inhibitory Circuitry of Young Binge Drinkers: A Voxel-Based Morphometry Study. (…) Binge drinking (BD) is defined as a pattern of high alcohol intake in a short time followed by periods of abstinence. Front. Psychol., 13 September 2017.)

(Anm: Antipsykotika kan krympe hjernevolumet (Antipsychotics May Shrink Brain Volume) (medpagetoday.com 8.2.2011).)

– Antipsykotika kan krympe hjernevolum (Antipsychotics May Shrink Brain Volume).

(Anm: Antipsykotika kan krympe hjernevolum (Antipsychotics May Shrink Brain Volume) Forskere rapporterte i februarutgaven av Archives of General Psychiatry at det var tiltagende tap av både grå materie og hvit substans ved økende tid på antipsykotika. En langtidsstudie ved bruk av bildetagning tyder på at hjernevolum hos pasienter med schizofreni gradvis reduseres i takt med varigheten av behandling med antipsykotika. (A long-term imaging study suggests that brain volume in patients with schizophrenia progressively declined with increasing duration of antipsychotic therapy.) (medpagetoday.com 8.2.2011.)

– Konklusjoner Samlet sett viser data fra dyrestudier vår studie at antipsykotika har en snikende, men målbar påvirkning på tap av hjernevev over tid.

(Anm: - Konklusjoner Samlet sett viser data fra dyrestudier vår studie at antipsykotika har en snikende, men målbar påvirkning på tap av hjernevev over tid, noe som tyder på viktigheten av forsiktig, varsom og aktsom risiko-nytte vurdering av dosering og varighet av behandling, samt deres off-label bruk. (Conclusions Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.) Arch Gen Psychiatry. 2011;68(2):128-137 (February 7, 2011).)

(Anm: Mitochondrial DNA: Impacting Central and Peripheral Nervous Systems..Neuron. 2014 Dec 17;84(6):1126-1142.)

(Anm: Synthetic sugar against autoimmune diseases. Researchers are working on an innovative approach to treat a rare autoimmune disease of the peripheral nervous system, using a kind of molecular sponge made of sugar to remove pathogenic antibodies from the bloodstream. Developed to treat anti-MAG neuropathy, the approach also has potential applications in the treatment of other autoimmune diseases. Scientists from the University of Basel and University Hospital Basel have reported their findings in the scientific journal PNAS. (medicalnewstoday.com 18.4.2017).)  

(Anm: Forskere kan have fundet nøgle til sklerosebehandling. Fejl i kommunikationen mellem nerveceller og immunsystemet kan være årsag til sygdommen sklerose. (…) Når personer bliver ramt af sklerose, skyldes det, at immuncellerne i stedet for at beskytte mod sygdomme og vira angriber kroppens egne celler og skaber det, der kaldes en autoimmun sygdom. (jyllands-posten.dk 24.4.2017).)

(Anm: Is Coenzyme Q10 Effective in Statin Myopathy? Atherosclerosis 2015 Feb. - During 8 weeks of treatment, CoQ10 had no effect on muscle symptoms. (NEJM 2017 (January 27, 2015).)

(Anm: Curcumin Protects Mitochondria and Cardiomyocytes from Oxidative Damage and Apoptosis Induced by Hemiscorpius Lepturus Venom. (…) Our findings suggest H. lepturus venom cusses a disruptive effect on mitochondrial respiratory chain, especially on complex II, and IV that predispose cardiomyocytes to ATP depletion and death signaling that could be protected with administration of curcumin. Drug Res (Stuttg). 2017 Oct 10.)

(Anm: Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease. Abstract The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on Aβ and curcumin has revealed that curcumin prevents Aβ aggregation and crosses the blood-brain barrier, reach brain cells, and protect neurons from various toxic insults of aging and Aβ in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin's bioavailability and urgent need for new formulations to increase its brain levels to treat patients with AD. J Alzheimers Dis. 2018;61(3):843-866.)

(Anm: Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae (Danio rerio). Environ Toxicol Pharmacol. 2017 Apr 1;52:150-160.)

(Anm: Is Coenzyme Q10 Effective in Statin Myopathy? Atherosclerosis 2015 Feb. - During 8 weeks of treatment, CoQ10 had no effect on muscle symptoms. (NEJM 2017 (January 27, 2015).)

(Anm: Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae (Danio rerio). Environ Toxicol Pharmacol. 2017 Apr 1;52:150-160.)

(Anm: Neurobiology: Mitochondria make nerves grow. After an injury, some young neurons can regrow their long signalling arms known as axons, but mature cells cannot. Zu-Hang Sheng of the National Institutes of Health in Bethesda, Maryland, and his colleagues… Nature. 2016 Jun 22;534(7608):439.)

(Anm: ATP: The crucial component of secretory vesicles. Abstract. (…) To our knowledge, our data provide the first demonstration that ATP, in addition to serving as an energy source and purinergic transmitter, is an essential element in the concentration of catecholamines in secretory vesicles. In this way, cells can use ATP to accumulate neurotransmitters and other secreted substances at high concentrations, supporting quantal transmission. PNAS (Proceedings of the National Academy of Sciences) 2016 (May 20, 2016).)

(Anm: Adenosintrifosfat (ATP) er en energirik kjemisk forbindelse som er involvert i alle energikrevende prosesser i menneskekroppen, som muskelsammentrekning, overføring av signaler i nerver, oppbygging av proteiner, kopiering av arvestoffer med mer. (…) ATP kan oppfattes som en universell energileverandør i alle celler og vev. Livet ville ikke vært mulig uten ATP. Forbindelsen er blitt kalt «livets molekyl». Kilde: Store norske leksikon.)

(Anm: Proteinstrukturen til ATP-syntase kartlagt. Den komplette strukturen til ATP-syntasen viser det molekylære grunnlaget for mitokondrienes morfologi. ATP-syntasene er lokalisert i mitokondriens indre membran. Disse små molekylære maskinene produserer ATP i cellen og er viktige i utviklingen av nevrodegenerative sykdommer. Kjennskap til proteinets tredimensjonale struktur kan gi informasjon om proteinets mekanismer. (…) En slik modell gir verdifull informasjon om funksjon, molekylær virkningsmekanisme, interaksjon og samspill med andre cellulære komponenter, og ikke minst hvordan enkelte kritiske mutasjoner og defekter i proteiner kan gi patologiske fenotyper. Slike modeller kan være viktige verktøy i design av legemidler, sier Dalhus. Tidsskr Nor Legeforen 2016 (20. desember 2016.)

(Anm: Adenosintrifosfat (ATP). Adenosin-5'-trifosfat (ATP, etter det engelske navnet Adenosine triphosphate) er et multifunksjonelt nukleotid som brukes i celler som et koenzym. ATP blir ofte kalt «molekylær valutaenhet» for intracellulær energioverføring.[1] ATP frakter kjemisk energi i cellene for metabolismen. ATP dannes under fotofosforylering og cellulær respirasjon, og brukes av enzymer og strukturelle proteiner i mange cellulære prosesser, herunder biosyntetiske reaksjoner, motilitet og celledeling.[2] Ett ATP-molekyl inneholder tre fosfatgrupper, og det blir produsert fra uorganisk fosfat og adenosindifosfat (ADP) eller adenosinmonofosfat (AMP) ved hjelp av enzymet ATP-syntase. (no.wikipedia.org).)

(Anm: A high-fat diet may alleviate mitochondrial disease. Salk scientists find that dietary fat, coupled with a natural hormone, can relieve metabolic dysfunction associated with mitochondrial disease in mice (salk.edu 30.6.2015).)

- Kalsiumtransport og signalering i mitokondriene. Calcium Transport and Signaling in Mitochondria. (- Deregulation of either Ca2+ or mitochondrial signaling leads to abnormal function, cell damage or even cell death, thereby contributing to muscle dysfunction or cardiac pathologies. Moreover, altered mitochondrial Ca2+ homeostasis has been linked to metabolic diseases like cancer, obesity, and pulmonary hypertension.)

Calcium Transport and Signaling in Mitochondria. (Kalsiumtransport og signalering i mitokondriene.)
Compr Physiol. 2017 Mar 16;7(2):623-634.
Abstract Calcium (Ca2+) is a key player in the regulation of many cell functions. Just like Ca2+, mitochondria are ubiquitous, versatile, and dynamic players in determining both cell survival and death decisions. Given their ubiquitous nature, the regulation of both is deeply intertwined, whereby Ca2+ regulates mitochondrial functions, while mitochondria shape Ca2+ dynamics. Deregulation of either Ca2+ or mitochondrial signaling leads to abnormal function, cell damage or even cell death, thereby contributing to muscle dysfunction or cardiac pathologies. Moreover, altered mitochondrial Ca2+ homeostasis has been linked to metabolic diseases like cancer, obesity, and pulmonary hypertension. In this review article, we summarize the mechanisms that coordinate mitochondrial and Ca2+ responses and how they affect human health. © 2017 American Physiological Society. Compr Physiol 7:623-634, 2017. (…)

(Anm: Mitochondrial Dysfunction and Neurodegeneration in Lysosomal Storage Disorders. Trends. Abstract Lysosomal storage disorders (LSDs) are rare inherited debilitating and often fatal disorders. Caused by mutations affecting lysosomal proteins, LSDs are characterized by the accumulation of undegraded material in lysosomes and by lysosomal dysfunction. Although LSDs are multisystemic diseases, the majority display neurologic symptoms and neurodegeneration. Only recently has a role emerged for mitochondrial dysfunction in the pathophysiology of LSDs, suggesting an impact of lysosomal dysfunction on mitochondria. Moreover, mitochondrial damage may also cause lysosomal dysfunction, further supporting the activity of common signaling pathways and crosstalk between the two organelles. In this review we explore the mechanisms linking lysosomal and mitochondrial dysfunction to assess whether specific mitochondrial pathways represent a new therapeutic frontier in the management of LSDs. Mol Med. 2017 Jan 19. pii: S1471-4914(16)30188-5. [Epub ahead of print].)

(Anm: Mitochondrial Dysfunction in Lysosomal Storage Disorders. (…) Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs. Diseases. 2016 Oct 11;4(4). pii: E31.)

(Anm: ER-Mitochondria signaling regulates autophagy. Autophagy. Abstract. The endoplasmic reticulum (ER) and mitochondria form tight functional contacts that regulate a number of key cellular processes. Finally, our studies revealed that the modulatory effects of ER-mitochondria contacts on autophagy involve their role in mediating ITPR (inositol 1,4,5-trisphosphate receptor) delivery of Ca2+ from ER stores to mitochondria. Autophagy. 2017 May 26:0. [Epub ahead of print].)

(Anm: Control of cell death and mitochondrial fission by ERK1/2 MAP Kinase signalling FEBS J. 2017 May 26. doi: 10.1111/febs.14122. [Epub ahead of print].)

- Mitokondrier: Sentrale organeller for melatonin-antioksidanter og anti-aldring.

(Anm: Mitochondria: Central Organelles for Melatonin's Antioxidant and Anti-Aging Actions. Abstract Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. (…) A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the "free radical theory of aging", including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age. Molecules. 2018 Feb 24;23(2). pii: E509.)

(Anm: Anti-aging effects of melatonin on the myocardial mitochondria of rats and associated mechanisms. Mol Med Rep. 2016 Dec 7. doi: 10.3892/mmr.2016.6002. [Epub ahead of print].)

(Anm: Melatonin and alcohol: Are they safe to mix? Though many people assume natural sleep supplements, such as melatonin, are always safe, it is essential for anyone who starts taking a supplement to learn about its use, effectiveness, and how to take it safely. (medicalnewstoday.com 28.9.2017).)

Pathogenic mechanisms of acute pancreatitis (Patogene mekanismer ved akutt pankreatitt)
Curr Opin Gastroenterol. 2012 Sep;28(5):507-15
RECENT FINDINGS: Pathologic intra-acinar trypsinogen activation had been hypothesized to be the central mechanism of pancreatitis for over a century. This hypothesis could be explored for the first time with the development of a novel mouse model lacking pathologic intra-acinar trypsinogen activation. It became clear that intra-acinar trypsinogen activation contributes to early acinar injury, but local and systemic inflammation progress independently during pancreatitis. Early intra-acinar nuclear factor kappa B (NFκB) activation, which occurs parallel to but independent of trypsinogen activation, may be crucial in pancreatitis. Although the mechanism of NFκB and trypsinogen activation is not entirely clear, further insights have been made into key pathogenic cellular events such as calcium signaling, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, autophagy and impaired trafficking, and lysosomal and secretory responses. Cellular intrinsic damage-sensing mechanisms that lead to activation of the inflammatory response aimed at repair, but lead to disease when overwhelmed, are beginning to be understood.

SUMMARY: New findings necessitate a paradigm shift in our understanding of acute pancreatitis. Intra-acinar trypsinogen activation leads to early pancreatic injury, but the inflammatory response of acute pancreatitis develops independently, driven by early activation of inflammatory pathways. (...)

(Anm: Impact of Aging on Calcium Signaling and Membrane Potential in Endothelium of Resistance Arteries: A Role for Mitochondria. (…) We conclude that the ability of resistance artery endothelium to release Ca2+ from intracellular stores (ie, ER and mitochondria) and hyperpolarize Vm via SKCa/IKCa activation is augmented as compensation for reduced NO bioavailability during advanced age. J Gerontol A Biol Sci Med Sci. 2017 May 16. [Epub ahead of print].)

- Dine mitokondrier er hva du spiser: en høyfettdiett eller høysukkerdiett eliminerer metabolsk fleksibilitet i isolerte mitokondrier fra rotteskjelettmuskulatur. (- However, it is not known if these diets alter normal interactions of pyruvate and fatty acid oxidation at the level of the mitochondria.)

Your mitochondria are what you eat: a high-fat or a high-sucrose diet eliminates metabolic flexibility in isolated mitochondria from rat skeletal muscle. (Dine mitokondrier er hva du spiser: en høyfettdiett eller høysukkerdiett eliminerer metabolsk fleksibilitet i isolerte mitokondrier fra rotteskjelettmuskulatur.)
Physiol Rep. 2017 Mar;5(6). pii: e13207.
Abstract Extreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate and fatty acid oxidation at the level of the mitochondria. Here, we report that rat muscle mitochondria does show the normal Randle-type fat-carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux-ratio: pyruvate dehydrogenase (PDH)/β-oxidation to suit the actual substrate availability, with the PDH flux as the major point of regulation. We further report that this regulatory mechanism of carbohydrate-fat metabolic interaction surprisingly is lost in mitochondria obtained from animals exposed for 12 weeks to a HF- or a HS diet as compared to rats given a normal chow diet. The mechanism seems to be a loss of the PDH flux decrease seen in controls, when fatty acid is supplied as substrate in addition to pyruvate, and vice versa for the supply of pyruvate as substrate to mitochondria oxidizing fatty acid. Finally, we report that the calculated TCA flux in the isolated mitochondria under these circumstances shows a significant reduction (~50%) after the HF diet and an even larger reduction (~75%) after the HS diet, compared with the chow group. Thus, it appears that obesogenic diets as those applied here have major influence on key metabolic performance of skeletal muscle mitochondria. (…)

(Anm: False alarm from the body may be responsible for acute pancreatitis (medicalnewstoday.com 9.9.2015).)

(Anm: Pancreatic cancer risk linked to changes in mouth bacteria. The presence of certain bacteria in the mouth may indicate a raised risk for pancreatic cancer - a disease that often begins with no symptoms and for which there is no routine screening test. (…) The researchers suggest the finding may lead to earlier, more precise treatments for pancreatic cancer, a disease with a pitifully low survival rate as it often escapes early diagnosis. (medicalnewstoday.com 20.4.2016).)

(Anm: Pancreatitis often caused by gallstones - also statins increase risk. Idiopathic pancreatitis is often caused by small gallstones that are difficult to observe prior to surgery, shows a study from the University of Eastern Finland. Small gallstones were found in surgery from two out of three idiopathic pancreatitis patients. The study also showed that acute pancreatitis was more common in statin users than non-users. (medicalnewstoday.com 7.12.2015).)

- Hemmet enzymaktivitet ved kronisk utmattelsessyndrom? (- Nivåene av de 20 aminosyrene ble undersøkt med massespektometri, der man fant en spesifikk nedgang av aminosyrer hos kvinner. Disse aminosyrene tilhører en gruppe som brytes ned uavhengig av enzymet pyruvatdehydrogenase (PDH).)

Hemmet enzymaktivitet ved kronisk utmattelsessyndrom?
Tidsskr Nor Legeforen 2017; 137:443 (21.3.2017)
Pasienter med kronisk utmattelsessyndrom har svekket enzymfunksjon relatert til energiomsetningen, ifølge en studie ved Haukeland universitetssykehus.

Tidligere studier har vist at pasienter med kronisk utmattelsessyndrom, ofte kalt ME/CSF, har senket nivå av enkelte aminosyrer i serum. Forskningsmiljøer ved Haukeland universitetssykehus har nylig publisert en studie der serum fra 200 pasienter og 100 kontrollpersoner ble undersøkt (1). Pasientene ble utredet for kronisk utmattelsessyndrom i henhold til de kanadiske kriteriene for sykdommen. Nivåene av de 20 aminosyrene ble undersøkt med massespektometri, der man fant en spesifikk nedgang av aminosyrer hos kvinner. Disse aminosyrene tilhører en gruppe som brytes ned uavhengig av enzymet pyruvatdehydrogenase (PDH). I de hvite blodcellene ble mRNA-nivået for ulike regulerende faktorer for dette enzymet undersøkt, og der fant man oppregulert uttrykk av faktorer som virker hemmende på enzymfunksjonen. Disse endringene var til stede i begge kjønn.

– Funksjonell pyruvatdehydrogenase er en av de viktigste faktorene for velfungerende mitokondrier, sier Zhenhe Suo, førsteamanuensis ved Avdeling for patologi ved Universitetet i Oslo.

– Velfungerende mitokondrier vil sørge for normal funksjon av celler og organer. Funnet av unormal energiomsetning ved kronisk utmattelsessyndrom kan forklare flere av de kliniske metabolske manifestasjonene ved sykdommen, sier Suo.

Funnene støttes også av in vitro-studier der pyruvatdehydrogenase er inaktivert med såkalt knockoutgenteknologi (2). – Når pyruvatdehydrogenase blir inaktivert, blir cellene tvunget til aerob glykoslyse, slik at de produserer mindre energi, men gir overskudd av laktat. Disse studiene har nye funn som fremhever den funksjonen pyruvatdehydrogenase har i sykdomsutviklingen ved kronisk utmattelsessyndrom, sier Suo. (…)

- Kronisk utmattelsessyndrom og pyruvat dehydrogenasefunksjon. Les alle innleggene om kronisk utmattelsessyndrom og pyruvat dehydrogenase på våre nettsider.

(Anm: Kronisk utmattelsessyndrom og pyruvat dehydrogenasefunksjon. Les alle innleggene om kronisk utmattelsessyndrom og pyruvat dehydrogenase på våre nettsider. Vi takker for kommentarer fra Yngve Thomas Bliksrud til vår studie (1). Samtidig undres vi hvorfor denne type debatt tas opp i Tidsskriftet og ikke i tidsskriftet som publiserte studien. Bliksrud gir en uriktig fremstilling av funnene med delvis ukritisk bruk av kilder, og et utilstrekkelig bilde av et komplekst forskningsfelt. Vi har fremmet hypotesen om at nedsatt pyruvat dehydrogenase-funksjon kan kobles til kronisk utmattelsessyndrom, uten at det har vært slått fast «uten forbehold». Det er en vitenskapelig begrunnet hypotese som skal testes grundig gjennom videre forskning. Tidsskr Nor Legeforen 2018 Publisert: 8. januar 2018.)

(Anm: Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. 2016 Dec 22;1(21):e89376.)

(Anm: Yngve Thomas Bliksrud er overlege og ph.d. ved Oslo universitetssykehus, Rikshospitalet. Forfatter har fylt ut ICMJE-skjemaet og oppgir følgende interessekonflikter: Han har mottatt honorar for et foredrag i et faglig forum av psykiatere som var støttet av det farmasøytiske selskapet Lundbeck Norge. Svak kobling mellom kronisk utmattelsessyndrom og pyruvat dehydrogenasemangel. Tidsskr Nor Legeforen 2017 Publisert: 28. november 2017.)

(Anm: Antidepressiva (SSRI) Lundbeck (mintankesmie.no).)

(Anm: Vegard Bruun Bratholm Wyller. Ukritisk medieopptreden av ME-forskere. I originalartikkelen som rapporterte endret energiomsetning hos pasienter med kronisk utmattelsessyndrom (CFS/ME) gikk forfatterne langt i å antyde at funnene kunne forklare pasientens symptomer (1). Forfatterne spekulerte altså i årsaksmekanismer, til tross for åpenbare metodologiske begrensninger som studiens tverrsnittsdesign, manglende standardisering av prøvetakning og en ikke-sammenliknbar kontrollgruppe. Tidsskr Nor Legeforen 2018 Publisert: 22. januar 2018.)

- Mitokondriell kvalitetskontroll ved hjertesykdommer. (- Mitokondrier er viktige organeller for vedlikehold av homeostase ved hjerteinfarkt. De spiller en avgjørende rolle i bioenergi, redoksbalanse, ion homeostase, og celledød.)

Mitochondrial Quality Control in Cardiac Diseases.
Front. Physiol., 21 October 2016
Disruption of mitochondrial homeostasis is a hallmark of cardiac diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for cardiomyocyte survival. In this review, we discuss the most recent findings on the central role of mitochondrial quality control processes including regulation of mitochondrial redox balance, aldehyde metabolism, proteostasis, dynamics, and clearance in cardiac diseases, highlighting their potential as therapeutic targets. (…)

Summary and Perspectives
Mitochondria are essential organelles for the maintenance of myocardial homeostasis. They play critical role in bioenergetics, redox balance, ion homeostasis, and cell death. The importance of functional mitochondrial to the heart has been highlighted by the fact that situations that lead to mitochondrial dysfunction are often associated with cardiac diseases. Many of these diseases manifest later in life, where mitochondria seems to be less functional. Therefore, different levels of mechanisms of surveillance and quality control capable of detecting and fixing defects that affect mitochondrial performance are critical for the maintenance of long-lived cells with high energy demand such as cardiomyocytes. The central role of mitochondrial quality control in the health of myocardium has been recently reported. As described above, the machinery regulating mitochondrial quality control including mitochondrial redox balance, aldehyde metabolism, proteostasis, dynamics, and clearance are potential novel therapeutic targets for cardiac diseases. However, future research focusing on the critical molecular events involved in mitochondrial quality control is needed to develop better pharmacological interventions. (…)

(Anm: Homeostase, organismens opprettholdelse av konstante og stabile fysikalsk-kjemiske forhold i det væskemiljøet som omgir de enkelte celler, det såkalte «indre miljø». Både surhetsgrad, temperatur, kjemisk sammensetning med mer i det indre miljø er nøye regulert og varierer meget lite over tid, noe cellene er avhengige av for å funksjonere normalt. En rekke organer som for eksempel hjerte, lunger og nyrer bidrar gjennom kontrollerte justeringer av sin virksomhet til homeostasen. Kilde: Store norske leksikon.)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Laktat er et biprodukt av den kjemiske prosess som er kjent som glykolyse - å bryte ned av sukker eller glukose, til mindre molekyler med det formål å frembringe energi. Under intens fysisk aktivitet, akkumuleres laktat i vevet og blod, som noen ganger kan føre til dårligere fysisk ytelse og muskelstivhet. (Lactate is a byproduct of the chemical process known as glycolysis- the breaking down of sugar, or glucose, into smaller molecules with the purpose of producing energy. During intense physical activity, lactate accumulates in the tissue and blood, which can sometimes lead to poorer physical performance and muscle stiffness.) (medicalnewstoday.com 19.3.2017).)

(Anm: - Kalsiumubalanse i hjerneceller kan utløse Alzheimers sykdom. (- Ingen har noen gang sett på dette før bruken av disse modellsystemene. Det er mulig at endringer i mitokondrienes kalsiumutveksling er driveren av sykdomsprosessen. Tidligere forskning har vist at en overdreven produksjon av kalsium kan føre til at nerveceller dør, derfor linkes en kalsiumubalanse med den nevrodegenerative prosessen involvert i Alzheimers sykdom. (Calcium imbalance within brain cells may trigger Alzheimer's disease.) (medicalnewstoday.com 15.2.2017).)

- Parkinsons er delvis en autoimmun sykdom, ifølge studie. (- Parkinson’s disease-related proteins PINK1 and Parkin repress mitochondrial antigen presentation.)

(Anm: Parkinson’s Is Partly An Autoimmune Disease, Study Finds. First direct evidence that abnormal protein in Parkinson’s disease triggers immune response. New York, NY (June 21, 2017)—Researchers have found the first direct evidence that autoimmunity—in which the immune system attacks the body’s own tissues—plays a role in Parkinson’s disease, the neurodegenerative movement disorder. The findings raise the possibility that the death of neurons in Parkinson’s could be prevented by therapies that dampen the immune response. The study, led by scientists at Columbia University Medical Center (CUMC) and the La Jolla Institute for Allergy and Immunology, was published today in Nature. “The idea that a malfunctioning immune system contributes to Parkinson’s dates back almost 100 years,” said study co-leader David Sulzer, PhD, professor of neurobiology (in psychiatry, neurology, and pharmacology) at CUMC. “But until now, no one has been able to connect the dots. Our findings show that two fragments of alpha-synuclein, a protein that accumulates in the brain cells of people with Parkinson’s, can activate the T cells involved in autoimmune attacks. (cumc.columbia.edu 21.6.2017).)

(Anm: T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature 546, 656–661 (29 June 2017).)

(Anm: Parkinson’s disease-related proteins PINK1 and Parkin repress mitochondrial antigen presentation. Cell 166, 314–327 (2016).)

(Anm: Er Mitokondrier nøkkelen til å finne en løsning på Parkinsons sykdom? Are Mitochondria the Key to Cracking Parkinson’s Disease? European Medical Journal 2017 (Februar 20, 2017).)

- Oppdagelse kan påvirke forståelse, behandling av autoimmune og inflammatoriske sykdommer.

(Anm: Discovery could impact understanding, treatment of autoimmune and inflammatory diseases. Scientists from the Research Institute of the McGill University Health Centre (RI-MUHC) may have cracked the code to understanding the function of special cells called regulatory T Cells. Treg cells, as they are often known, control and regulate our immune system to prevent excessive reactions. The findings, published in Science Immunology, could have a major impact in our understanding and treatment of all autoimmune diseases and most chronic inflammatory diseases such as arthritis, Crohn's disease as well as broader conditions such as asthma, allergies and cancer. Researchers made this discovery by investigating a rare human mutation in a gene called FOXP3. Although the importance of the FOXP3 gene in the proper function of Treg cells has been well documented, its mechanisms were still not fully understood by scientists. (news-medical.net 5.7.2017).)

(Anm: Surprising finding provides more support for Alzheimer's being an autoimmune disease. Brain levels of the lipid ceramide are high in Alzheimer's disease, and now scientists have found increased levels of an antibody to the lipid in their disease model. (medicalnewstoday.com 10.3.2015).)

(Anm: Relationships Between Mitochondria and Neuroinflammation: Implications for Alzheimer's Disease. Curr Top Med Chem. 2015 Aug 26. [Epub ahead of print].)

(Anm: Problems finding your way around may be earliest sign of Alzheimer's disease (medicalnewstoday.com 22.4.2016).)

(Anm: T cell type that promotes damaging immune response discovered. For the first time, researchers have identified a type of T cell that plays a key role in promoting the damaging autoimmune response that inflames and attacks the joints in rheumatoid arthritis. The discovery - made with technologies that help to analyze just a "handful of cells" - offers vital new clues to the biology of the disease and could lead to more powerful, targeted treatments. The study - led by Brigham and Women's Hospital (BWH), a teaching affiliate of Harvard Medical School in Boston, MA - is published in the journal Nature. (medicalnewstoday.com 2.2.2017).)

- Preklinisk studie antyder at Parkinson sykdom kan starte i tarm-endokrine celler. (- Ifølge funnene som er publisert i tidsskriftet JCI Insight hevder forskere og samarbeidspartnere fra University of California, San Francisco, at et stoff i tarmen kan forstyrre alfa-synuclein i endokrine celler i tarmen, og deformere proteinet. Det deformerte eller misfoldede proteinet kan da spre seg via nervesystemet til hjernen som et prion eller infeksjonsprotein, på samme måte som kugalskap.)

(Anm: Pre-clinical study suggests Parkinson's could start in gut endocrine cells. Recent research on Parkinson's disease has focused on the gut-brain connection, examining patients' gut bacteria, and even how severing the vagus nerve connecting the stomach and brain might protect some people from the debilitating disease. But scientists understand little about what's happening in the gut - the ingestion of environmental toxins or germs, perhaps - that leads to brain damage and the hallmarks of Parkinson's such as tremors, stiffness and trouble walking. According to findings published in the journal JCI Insight, Duke researchers and collaborators from the University of California, San Francisco, hypothesize that an agent in the gut might interfere with alpha-synuclein in gut endocrine cells, deforming the protein. The deformed or misfolded protein might then spread via the nervous system to the brain as a prion, or infectious protein, in similar fashion to mad cow disease. (medicalnewstoday.com 19.6.2017).)

(Anm: Two new studies expand understanding of link between PD and gastrointestinal dysfunction. (news-medical.ne 31.7.2017).)

(Anm: Bacterial community in the gut of Parkinson's patients differs from that of healthy people. Parkinson's disease is an insidious disease: by the time it manifests as the typical motor dysfunctions such as tremors or muscle rigidity, portions of the brain have already been irreversibly destroyed. (news-medical.net 29.8.2017).)

(Anm: Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and Cellular Damage Front. Mitochondria are evolutionary endosymbionts derived from bacteria. Thus, they bear molecules, such as mitochondrial DNA (mtDNA) that contains CpG DNA repeats and N-formyl peptides (FPs), found in bacteria. Immunol. 2016 (20 July 2016).)

(Anm: Promise and Pitfalls of Mitochondrial Replacement for Prevention and Cure of Heritable Neurodegenerative Diseases Caused by Deleterious Mutations in Mitochondrial DNA. Front. Cell. Neurosci., 23 September 2016.)

(Anm: Mitophagy is the selective degradation of mitochondria by autophagy. (en.wikipedia.org).)

- Brukere av metamfetamin er tre ganger mer utsatt for å få Parkinsons sykdom enn folk som ikke bruker illegale rusmidler

Meth users 'three times more likely' to develop Parkinson's
medicalnewstoday.com 17.12.2014
Users of methamphetamine are at three times more risk for getting Parkinson's disease than people who do not use illegal drugs, according to new research from the University of Utah and Intermountain Healthcare

A previous study that examined nearly 250,000 California hospital discharge records found that meth users had an increased risk for Parkinson's. The new study - published in the journal Drug and Alcohol Dependence - includes both inpatient and outpatient clinic records, and so draws data from a wider sample of the population. (…)

(Anm: Metamfetamin er et syntetisk sentralstimulerende narkotikum. Det har mye av de samme virkningene og ligner kjemisk på amfetamin. (no.wikipedia.org).)

- Metamfetaminbruk knyttet til økt risiko for hjerneslag hos de unge.

(Anm: Methamphetamine use linked to heightened stroke risk in the young. The stimulant methamphetamine, also popularly known as 'speed,' 'ice' and 'meth,' is linked to a heightened risk of stroke among young people, reveals a review of the available evidence, published online in the Journal of Neurology Neurosurgery & Psychiatry. (medicalnewstoday.com 25.8.2017).)

(Anm: Stroke and methamphetamine use in young adults: a review. Neurology Neurosurgery & Psychiatry 2017 published online 23 August 2017.)

(Anm: International study finds meth messes up brains of youths far more than those of adults (medicalnewstoday.com 16.2.2015).)

- Mitokondriell energimangel fører til hyperproliferasjon av skjelettmuskel-mitokondrier og økt insulinfølsomhet. (...) Vi fremlegger bevis på at mitokondrier bidrar til etiologien (sykdomsårsaken) til metabolsk sykdom. (- Diabetes er assosiert med svekket glukosemetabolisme i nærvær av overskudd av insulin.)

Mitochondrial energy deficiency leads to hyperproliferation of skeletal muscle mitochondria and enhanced insulin sensitivity. (Mitokondriell energimangel fører til hyperproliferasjon av skjelettmuskel-mitokondrier og økt insulinfølsomhet.)
Proceedings of the National Academy of Sciences) 2017;114(10):2705–2710
Significance

Mitochondrial dysfunction is associated with type II diabetes and metabolic syndrome, but whether it is cause or consequence is debated. By showing that increased mitochondrial respiration can impart glucose tolerance, insulin sensitivity, and resistance to high fat diet (HFD) toxicity, we provide evidence that mitochondria contributes to the etiology of metabolic disease. Inactivation of adenine nucleotide translocator isoform 1 (ANT1) results in proliferation of partially uncoupled muscle mitochondrial respiration, creating a sink for excess calories. Although ANT1-deficient muscle induces expression of Fgf21, FGF21 level is not elevated in blood, and FGF21 and UCP1 mRNAs are not increased in liver or brown adipose tissue (BAT). If increased mitochondrial respiration prevents HFD toxicity, then decreased mitochondrial respiration may contribute to metabolic disease.

Abstract
Diabetes is associated with impaired glucose metabolism in the presence of excess insulin. Glucose and fatty acids provide reducing equivalents to mitochondria to generate energy, and studies have reported mitochondrial dysfunction in type II diabetes patients. If mitochondrial dysfunction can cause diabetes, then we hypothesized that increased mitochondrial metabolism should render animals resistant to diabetes. This was confirmed in mice in which the heart–muscle–brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated. ANT1-deficient animals are insulin-hypersensitive, glucose-tolerant, and resistant to high fat diet (HFD)-induced toxicity. In ANT1-deficient skeletal muscle, mitochondrial gene expression is induced in association with the hyperproliferation of mitochondria. The ANT1-deficient muscle mitochondria produce excess reactive oxygen species (ROS) and are partially uncoupled. Hence, the muscle respiration under nonphosphorylating conditions is increased. Muscle transcriptome analysis revealed the induction of mitochondrial biogenesis, down-regulation of diabetes-related genes, and increased expression of the genes encoding the myokines FGF21 and GDF15. However, FGF21 was not elevated in serum, and FGF21 and UCP1 mRNAs were not induced in liver or brown adipose tissue (BAT). Hence, increased oxidation of dietary-reducing equivalents by elevated muscle mitochondrial respiration appears to be the mechanism by which ANT1-deficient mice prevent diabetes, demonstrating that the rate of mitochondrial oxidation of calories is important in the etiology of metabolic disease. (…)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

(Anm: Mitokondriell dysfunksjon ligger bak kognitive defekter som et resultat av nevral stamcelleutarmning og nedsatt neurogenese. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet. 2017 Jun 8.)

(Anm: Adenosintrifosfat (ATP) er en energirik kjemisk forbindelse som er involvert i alle energikrevende prosesser i menneskekroppen, som muskelsammentrekning, overføring av signaler i nerver, oppbygging av proteiner, kopiering av arvestoffer med mer. (…) ATP kan oppfattes som en universell energileverandør i alle celler og vev. Livet ville ikke vært mulig uten ATP. Forbindelsen er blitt kalt «livets molekyl». Kilde: Store norske leksikon.)

(Anm: Antipsykotika øger diabetes-risiko hos børn. En række forskellige antipsykotika har vist sig at medføre op til tre gange så stor en risiko for at udvikle diabetes, hvis børn og unge behandles med dem. Et studie offentliggjort i tidsskriftet JAMA Psychiatry viser ifølge Dagens Medicin, at børn og unge i behandling med antipsykotiske lægemidler har tre gange så stor en risiko for at udvikle diabetes i forhold til lignende personer, der tager andre psykoaktive præparater. (…) Den forøgede risiko indtraf allerede efter blot et års forbrug, og risikoen var fortsat tilstede i mindst et år, efter deltagerne var stoppet med at tage lægemidlerne. (medwatch.dk 9.9.2013).)

(Anm: Antidepressiva og antipsykotika gir økt risiko for diabetes hos barn og voksne (50 til 700 %) (mintankesmie.no).)

(Anm: Diabetes: Risiko for hjerteinfarkt på grunn av tap av små blodårene rundt hjertet. (Diabetes: Heart attack risk due to loss of small blood vessels around the heart.) (medicalnewstoday.com 24.3.2017).)

(Anm: Alzheimer's disease also affects small blood vessels. A research conducted by the UAB demonstrates that mice suffering from this disease also have substantial malfunctions in small blood vessels, important in nourishing different organs and tissues and in regulating blood pressure, and which mainly affects females. The study also demonstrates a correlation between the state of peripheral blood vessels and different levels of anxious behavior, both in normal aging and in those suffering from Alzheimer's disease.  (news-medical.net 16.3.2018).)

(Anm: Orale steroider (glukokortikoider) linket til 10 ganger økt risiko for diabetes. (Oral steriods linked with ten-fold increased risk of diabetes. (pulsetoday.co.uk 5.5.2016).)

(Anm: Bivirkninger (legemiddelinduserte organskader og sykdommer) (mintankesmie.no).)

(Anm: Legemiddelinduserte mitokondrielle skader og sykdom. (Medication-induced mitochondrial damage and disease.) (mintankesmie.no).)

(Anm: Antidepressiva (SSRI-er) kan utløse sentral fatigue (sentral utmattelse) (mintankesmie.no).)

(Anm: Konklusjoner. Bruk av SSRI var assosiert med vektøkning og forekomst av usunn atferd, inkludert vestlig diett, "sedentarisme" (blir stillesittende/inaktiv) og røyking. (Conclusions SSRIs use was associated with weight gain in the presence of unhealthy behaviours including Western diet, sedentarism and smoking. BMJ Open 2017;7:e016224.)

- Effekter av MPTP på serotonerge nevronale systemer og mitokondrie Complex I aktiviteten i den levende hjernen: En PET-studie på bevisste rhesusaper.

Effects of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys. (Effects of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys.)
J Nucl Med. 2017 Mar 9. pii: jnumed.116.189159. [Epub ahead of print]
Abstract The objective of the present positron emission tomography (PET) study was to assess the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on serotonergic neuronal systems and mitochondrial complex-I (MC-I) activity and compare them with those of dopamine in living brains of rhesus monkeys (Macaca mulatta). Methods: A Parkinson's disease (PD) monkey model was prepared by the repeated administration of MPTP. In PET measurements under conscious conditions, 11C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (11C-DASB) for serotonin transporter (SERT), 4-(2'-methoxyphenyl)-1-[2'-(N-2''-pyridinyl)-p-18F-fluorobenzamido]ethylpiperazine (18F-MPPF) for serotonin 1A receptor (5-HT1AR), 11C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl) nortropane (11C-PE2I) for dopamine transporter (DAT), 6-11C-methyl-m-tyrosin (11C-6MemTyr) for dopamine synthesis, 11C-raclopride for dopamine D2 receptor (D2R), or 2-tert-butyl-4-chrolo-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (18F-BCPP-EF) for MC-I was intravenously injected into normal and MPTP-treated monkeys. Serotonin and dopamine parameters were calculated using time activity curves in the cerebellum as input functions. The total distribution volume (VT) of 18F-BCPP-EF was assessed using a Logan plot graphical analysis with the metabolite-corrected plasma input function. Results: MPTP-induced diffuse reductions in MC-I activity was observed throughout the brain, except the cerebellum. Significant reductions in presynaptic dopamine parameters, DAT and synthesis, were detected in the striatum and substantia nigra pars compacta (SNc) of MPTP-treated monkeys, whereas no significant differences were observed in postsynaptic D2R binding. SERT binding was reduced by MPTP not only in the striatal regions, but also in the extra-striatal regions. In contrast, 5-HT1AR binding throughout the brain was not affected by MPTP. The degree of reductions in SERT binding correlated with those in MC-I in the cortex. Conclusion: The results obtained by multiparametric PET measurements demonstrated that chronic MPTP treatments induced reductions not only in the dopaminergic system in the nigrostriatal pathway, but also in SERT in the cortical and sub-cortical regions of PD monkey model. These results suggest that the neurotoxicity of MPTP is not exclusive to the nigrostriatal pathway, as predicted from MC-I damage in the extra-striatal regions of the brain. (…)

(Anm: Pasienter behandlet med antipsykotika (nevroleptika) har signifikant senket platelet complex I aktivitet i mitokondrier i likhet med det som er observert ved idiopatisk Parkinsons sykdom. (...) Antipsykotika (nevroleptika) hemmer kompleks I i elektrontransportkjeden. (Neuroleptic medications inhibit complex I of the electron transport chain. (...) Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson’s disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.) Ann Neurol. 1993;33:512-7).)

(Anm: Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes. (…) Highlights • Pancreatic mitochondrial complex I shows hyperactivity in diabetes. • Complex I hyperactivity is associated with increased NADH/NAD+ redox imbalance. • Complex I hyperactivity is associated with increased oxidative stress and cell death. • Complex I hyperactivity is linked with compromised cellular anti-oxidative stress capacity such as decreased sirt3 and NQO1 expressions. Biochem Biophys Rep. 2017 Sep;11:119-129.)

(Anm: Focus on an unusual rise in pancreatic cancer incidence in France. (…) Conclusion: Pancreatic cancer incidence and mortality exhibited diverging trends. Incidence increased over the last 30 years in France whereas mortality did not vary in men and moderately increased in women. Incidence remained lower than mortality up to 2002. One cannot exclude the possibility that a similar trend may appear in other countries. Etiological studies are required to further explain this increase.Int J Epidemiol. 2017 Dec 1;46(6):1764-1772.)

(Anm: Effekter av MPTP på serotonerge nevronale systemer og mitokondrie Complex I aktiviteten i den levende hjernen: En PET-studie på bevisste rhesusaper. (Effects of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys. (Effects of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys.) J Nucl Med. 2017 Mar 9. pii: jnumed.116.189159.)

(Anm: Antidepressiva (inkl. SSRI-preparater) og antipsykotika har skadelige effekter på mitokondrier (Mol Cell Biochem 1999;199:103-9).)

(Anm: Mitokondriell dysfunksjon ligger bak kognitive defekter som et resultat av nevral stamcelleutarmning og nedsatt neurogenese. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet. 2017 Jun 8.)

(Anm: Mitokondriell dysfunksjon ligger bak kognitive defekter som et resultat av nevral stamcelleutarmning og nedsatt neurogenese. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Hum Mol Genet. 2017 Jun 8.)

(Anm: Adenosintrifosfat (ATP) er en energirik kjemisk forbindelse som er involvert i alle energikrevende prosesser i menneskekroppen, som muskelsammentrekning, overføring av signaler i nerver, oppbygging av proteiner, kopiering av arvestoffer med mer. (…) ATP kan oppfattes som en universell energileverandør i alle celler og vev. Livet ville ikke vært mulig uten ATP. Forbindelsen er blitt kalt «livets molekyl». Kilde: Store norske leksikon.)

(Anm: Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response. PNAS (Proceedings of the National Academy of Sciences) 2017;114(8) (January 6, 2017).)

(Anm: Bruk av annengenerasjons antipsykotiske legemidler øker parametre for metabolsk syndrom. (dgnews.docguide.com 17.3.2016).)

- Konklusjoner: Annengenerasjons antipsykotika forårsaker signifikant flere endringer i metabolske parametere, og øker risikoen for å utvikle metabolsk syndrom og tilhørende lidelser som diabetes mellitus type II og cerebrovaskulære ulykker.

(Anm: Konklusjoner: Annengenerasjons antipsykotika forårsaker signifikant flere endringer i metabolske parametere, og øker sjansene for å utvikle metabolsk syndrom og tilhørende lidelser som diabetes mellitus type II og cerebrovaskulære ulykker. (Conclusions: Second-generation antipsychotics cause significantly more changes in the metabolic parameters, increasing the chances of developing metabolic syndrome and associated disorders like diabetes mellitus type-II and cerebrovascular accidents. Indian J Psychiatry. 2011 Apr-Jun; 53(2): 128–133.)

- Metabolsk syndrom og risiko for kreft. En systematisk gjennomgang og meta-analyse. (- Konklusjoner. Metabolisk syndrom er forbundet med økt risiko for vanlige kreftformer, for enkelte kreftformer er risikoen forskjellig mellom kjønn, populasjoner og definisjoner av metabolsk syndrom.)

(Anm: Metabolic Syndrome and Risk of Cancer. A Systematic Review and Meta-analysis. Abstract Objective—Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites. Conclusions—Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and definitions of metabolic syndrome. Diabetes Care. 2012;35(11):2402-2411.)

(Anm: Dopaminmangel: Hva du trenger å vite. (Dopamine deficiency: What you need to know) (medicalnewstoday.com 17.1.2018).)

- Behandling med antidepressiva og risiko for demens. (- KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva.)

(Anm: Behandling med antidepressiva og risiko for demens: En populasjonsbasert, retrospektiv case-control studie. (…) KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva. (CONCLUSIONS: The incidence of dementia in patients is associated with antidepressant medication use.) J Clin Psychiatry. 2016 Jan;77(1):117-22.)

(Anm: Dopamin i det mediale amygdala-nettverk formidler menneskelige bånd (bindinger) (Dopamine in the medial amygdala network mediates human bonding.) Abstract Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. Proc Natl Acad Sci U S A. 2017 Feb 13. pii: 201612233.)

(Anm: Det allerførste udtryk for liv lever stadig inden i os. En cellemaskine så kraftig, at den lagde grunden til alt liv, kan fortælle os, hvordan det hele begyndte. (jyllands-posten.dk 17.12.2017).)

- Antipsykotika-indusert dopamin supersensitivitetspsykose (SP): Farmakologi, kriterier og terapi. Til slutt beskriver vi 3 antipsykotiske seponeringssyndrom (bivirkninger grunnet nedtrapping av doser), som ligner de som er sett med andre CNS-legemidler, og vi foreslår tilnærminger for å behandle, potensielt forhindre eller midlertidig administrere SP.

(Anm: Antipsykotika-indusert dopamin supersensitivitetspsykose (SP): Farmakologi, kriterier og terapi. Til slutt beskriver vi 3 antipsykotiske seponeringssyndrom (bivirkninger grunnet nedtrapping av doser), som ligner de som er sett med andre CNS-legemidler, og vi foreslår tilnærminger for å behandle, potensielt forhindre eller midlertidig administrere SP. (Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy. Finally, we describe 3 antipsychotic withdrawal syndromes, similar to those seen with other CNS drugs, and we propose approaches to treat, potentially prevent, or temporarily manage SP.) Psychother Psychosom 2017;86:189-219.)

- Studien viser sammenhengen mellom metabolsk syndrom og risiko for kognitive sykdommer.

(Anm: Study shows link between metabolic syndrome and risk of cognitive disorders. A study presented at the European Academy of Neurology Congress in Amsterdam has shown that obesity alone is not a risk factor for cognitive disorders, but commonly associated co-morbidities such as diabetes, high blood pressure, and metabolic disorders are. Dementia diseases in patients who suffer from diabetes are often treated inadequately, a new research paper reveals. It has long been supposed that patients with metabolic syndrome are more likely to suffer from cognitive impairment - and to a greater extent. Reasons are thought to include chronic inflammatory processes which can induce neuroinflammatory and neurodegenerative changes. Whether obese individuals without risk factors such as diabetes mellitus, metabolic disorders and the presence of albumin in the urine have an increased risk of cognitive impairment is still little researched. (news-medical.net 27.6.2017).)

(Anm: Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status. Diabetes Care 2016 (Published online before print March 10, 2016).)

(Anm: Patients With Polyneuropathy Receive Long-Term Opioid Therapy, No Clear Benefit. CHICAGO -- May 23, 2017 -- Polyneuropathy is associated with an increased likelihood of long-term opioid therapy, but therapy does not appear to improve functional status, according to a study published online by JAMA Neurology. Polyneuropathy is a common painful condition, especially among older patients, which can result in functional impairment. (dgnews.docguide.com 23.5.2017).)

(Anm: Prepsychosis links with elevated metabolic syndrome. MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome. (...) He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients. (clinicalpsychiatrynews.com.com 2.4.2016).)

(Anm: Joachim Raese, MD. Metabolic syndrome is defined by the aggregation of hypertriglyceridemia, low high-density lipoprotein (HDL) levels, elevated fasting glucose, hypertension, and increased waist circumference. Metabolic syndrome confers an increased risk of developing diabetes and of dying from coronary artery disease. Cardiovascular disease is the leading cause of death among patients with schizophrenia, who have a life expectancy about 20 years shorter than the general population. (…) For a more detailed discussion, I suggest watching a YouTube video that we have prepared. (cmeinstitute.com 27.4.2016).)

(Anm: Video Lecture 8: Metabolic Syndrome Lectures 1 (By Dr. Joachim Raese) (youtube.com).)

- Ny norsk forskning kan gi Parkinson-svar. (- Nå viser ny forskning fra Universitetet i Bergen at Parkinson kan være forårsaket av at mitokondriene – som er cellenes energifabrikker, ikke klarer å tilpasse segaldringsforandringer i hjernen hos dem som utvikler sykdommen.)

Ny norsk forskning kan gi Parkinson-svar
vg.no 25.11.2016
Mer enn ti millioner personer er på verdensbasis rammet av den hyppig forekommende hjernesykdommen, hvorav cirka 6000 av disse er nordmenn.

Nå viser ny forskning fra Universitetet i Bergen at Parkinson kan være forårsaket av at mitokondriene – som er cellenes energifabrikker, ikke klarer å tilpasse seg aldringsforandringer i hjernen hos dem som utvikler sykdommen.

Den ferske studien ble tirsdag publisert i tidsskriftet Nature Communications, og kaster nytt lys over hva som kan være årsaken til at noen personer er mer utsatt til å utvikle Parkinson sykdom enn andre:

De som rammes av Parkinson sykdom har en sviktende biologisk mekanisme i hjernen, som gjør at de ikke blir beskyttet mot aldringsrelaterte skader på mitokondrienes arvestoff. (…)

(Anm: Yoshinori Ohsumi – a deserving winner of the Nobel Prize for physiology or medicine. am delighted that Yoshinori Ohsumi won this year’s Nobel Prize in physiology or medicine. His pioneering work in yeast led to the discovery of genes and biological processes that are needed for autophagy. Autophagy (from the Greek for “self-eating”) is the mechanism by which cells break down and recycle cellular content. Without this vital housekeeping role we’d be more prone to cancer, Parkinson’s and other age-related disorders. (theconversation.com 3.10.2016).)

(Anm: Autophagy (or autophagocytosis) (from the Greek auto-, "self" and phagein, "to eat"), is the natural, destructive mechanism that disassembles, through a regulated process, unnecessary or dysfunctional cellular components.[1] (en.wikipedia.org).)

(Anm: Communications between Mitochondria, the Nucleus, Vacuoles, Peroxisomes, the Endoplasmic Reticulum, the Plasma Membrane, Lipid Droplets, and the Cytosol during Yeast Chronological Aging. Front. Genet., 27 September 2016.)

(Anm: Cancer cell metabolism and mitochondria: nutrient plasticity for TCA cycle fueling. Abstract Warburg's hypothesis that cancer cells take up a lot of glucose in the presence of ambient oxygen but convert pyruvate into lactate due to impaired mitochondrial function led to the misconception that cancer cells rely on glycolysis as their major source of energy. Most recent 13C-based metabolomic studies, including in cancer patients, indicate that cancer cells may also fully oxidize glucose. In addition to glucose-derived pyruvate, lactate, fatty acids and amino acids supply substrates to the TCA cycle to sustain mitochondrial metabolism. Here, we discuss how the metabolic flexibility afforded by these multiple mitochondrial inputs allows cancer cells to adapt according to the availability of the different fuels and the microenvironmental conditions such as hypoxia and acidosis. In particular, we focused on the role of the TCA cycle in interconnecting numerous metabolic routes in order to highlight metabolic vulnerabilities that represent attractive targets for a new generation of anticancer drugs. Biochim Biophys Acta. 2017 Jan 18. pii: S0304-419X(16)30094-4.)

- Er Mitokondrier nøkkelen til å finne en løsning på Parkinsons sykdom? (- Are Mitochondria the Key to Cracking Parkinson’s Disease?)

- Are Mitochondria the Key to Cracking Parkinson’s Disease? (Er Mitokondrier nøkkelen til å finne en løsning på Parkinsons sykdom?)
European Medical Journal 2017 (Februar 20, 2017)
Mitokondriene av dopaminproduserende celler har vært knyttet til Parkinsons sykdom, med forskere som finner at berørte enkeltpersoner har dopaminceller som i hjernen er mindre i stand til å beskytte sitt mitokondrie-DNA mot aldersrelatert skade, sammenlignet med celler i friske individer. Parkinsons sykdom antas å være en kombinasjon av både genetiske og miljømessige faktorer, den nøyaktige kombinasjon av disse varierer sterkt mellom enkeltpersoner. (THE MITOCHONDRIA of dopamine-producing cells have been linked to Parkinson’s disease, with researchers finding that affected individuals have dopamine cells in their brains less able to protect their mitochondrial DNA against age-related damage, compared with cells in healthy individuals. Parkinson’s disease is believed to be a combination of both genetic and environmental factors, the exact combination of which can vary greatly between individuals.)

Som et hjerne- ødeleggende, progressiv sykdom, påvirker Parkinsons hovedsakelig dopaminproduserende neuroner eller nerveceller i en hjernenstruktur som er kjent som substantia nigra; dette fører til at disse cellene svikter og dør og nivåer av dopamin blir dermed utarmet, noe som resulterer i symptomer som begrenset bevegelse, talefeil, og nedsatt balanse. Studieleder Dr Charalampos Tzoulis, Nevrologisk avdeling, Haukeland universitetssykehus og Institutt for klinisk medisin, Universitetet i Bergen, Bergen, Norge, uttalte at disse problemene blir mer fremtredende med alderen, og uttalte at: "Det er kjent at DNA av mitokondriene er skades under aldring, og forårsaker svikt i kraftgeneratorer, mangel på energi, og sykdom." (Dr Tzoulis and his researchers investigated mitochondrial DNA, comparing the brains of patients with Parkinson’s disease and healthy, older individuals. Their findings suggested that the mitochondrial DNA of healthy dopamine-producing cells in the brain was efficiently protected against aging-induced damage. By contrast, the dopamine-producing cells of individuals with Parkinson’s disease could not replenish their DNA as successfully, which led to a gradual loss of healthy DNA within their mitochondria.)

Disse resultatene antyder eksistensen av en viktig mekanisme som normalt ville forsvare hjernen mot aldringsindusert skade. Men personer som lider av Parkinsons sykdom synes å ha feil, en svakere mekanismer, som forårsaker at deres hjerner blir mer sårbare for virkningene av aldring. Dr. Tzoulis mener at denne forskningen har gjort at de selv og andre forskere bedre forstår utviklingen og patogenesen av Parkinsons sykdom. Han konkluderer at: "Det er generelt veldig lite kunnskap om hvilke mekanismer som forårsaker Parkinsons sykdom. Nå er vi et skritt nærmere å forstå disse mekanismene, og vi kan ha et mål for behandlinger." (…) (These results imply the existence of an important mechanism that would normally defend the brain against aging-induced damage. However, individuals that suffer from Parkinson’s disease seem to have malfunctioning, weaker mechanisms, causing their brains to become more vulnerable to the effects of aging. Dr Tzoulis believes that this research has allowed himself and other researchers to better understand the development and pathogenesis of Parkinson’s disease. Concluding, he stated, “There is generally very little knowledge about the mechanisms causing Parkinson’s disease. Now, we are a step closer to understanding these mechanisms and we may have a target to strike at for therapy.”)

(Anm: Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nat Commun. 2016 Nov 22;7:13548.)

- Multippel sklerose – en mitokondriemediert sykdom? (- Mitokondrieskade sekundært til inflammasjon kombinert med økt energikrav sekundært til demyelinisering kan føre til en kronisk energimangel i sentralnervesystemet. Dette kan igjen føre til nevrodegenerasjon.)

Multippel sklerose – en mitokondriemediert sykdom?
Tidsskr Nor Legeforen 2017; 137:284-7(16.2.2017)
BAKGRUNN Mitokondrier spiller en viktig rolle i patogenesen ved ulike nevrodegenerative lidelser, som for eksempel Parkinson sykdom. Nevrodegenerative forandringer forekommer tidlig i forløpet av multippel sklerose (MS). Formålet med denne artikkelen er å presentere kunnskap om mulig sammenheng mellom mitokondriedysfunksjon og multippel sklerose.

KUNNSKAPSGRUNNLAG Artikkelen er basert på original- og oversiktsartikler valgt ut etter et litteratursøk i PubMed, begrenset til engelskspråklige artikler og avsluttet i mai 2016. Litteratursøket resulterte i totalt 2 276 artikler. Etter en skjønnsmessig vurdering ble 71 artikler lest i sin helhet. Av disse ble 19 brukt som referanser. I tillegg plukket vi ut 15 artikler fra referanselistene og syv fra eget litteraturarkiv.

RESULTATER Mitokondrieforandringer er påvist i affiserte hjerneområder hos pasienter med multippel sklerose. Mens noen av forandringene kan skyldes skade på mitokondrier sekundært til inflammasjon, kan andre være kompensatoriske grunnet økt energikrav i aksoner som er rammet av demyelinisering. Type mitokondrieskade varierer og avhenger av utløsende skade.

FORTOLKNING Mitokondrieskade sekundært til inflammasjon kombinert med økt energikrav sekundært til demyelinisering kan føre til en kronisk energimangel i sentralnervesystemet. Dette kan igjen føre til nevrodegenerasjon. Økt kunnskap om mitokondrienes rolle ved multippel sklerose, både sekundært til inflammasjon og eventuelt som et direkte bidrag til nevrodegenerasjon, kan gi bedre forståelse for patogenesen ved sykdommen og kanskje bidra til nye behandlingsmuligheter. (…)

(Anm: Powering the Cell: Mitochondria (ed.ted.com).)

(Anm: Cellular Respiration and the Mighty Mitochondria (ed.ted.com).)

(Anm: Dr. Terry Wahls - Minding Your Mitochondria - TED - Documentary, Lecture, Talk NUTRITION (youtube.com 16.4.2017).)

- Lundbeck i millionsamarbejde med big pharma om hjernesygdomme. (- Med i alliancen er blandt andet danske Lundbeck, der sammen med en række spillere fra big pharma som eksempelvis Novartis, Eli Lilly og AbbVie nu skal forsøge at løse gåden om de komplicerede hjernesygdomme Alzheimers og Parkinsons sygdom. Det skriver Berlingske.) (- Fokus har meget været på at fjerne proteinerne, når de ikke er i cellerne. Her prøver vi at se, om vi kan fjerne dem, når de er inde i cellerne.)

Lundbeck i millionsamarbejde med big pharma om hjernesygdomme.
medwatch 10.4.2017
Danske Lundbeck har indgået en stor international forskningsaftale med en række topuniversiteter og konkurrenter fra big pharma om at løse gåden om Alzheimers og Parkinsons sygdom.

Et nyt europæisk hjernesamarbejde har set dagens lys. Med i alliancen er blandt andet danske Lundbeck, der sammen med en række spillere fra big pharma som eksempelvis Novartis, Eli Lilly og AbbVie nu skal forsøge at løse gåden om de komplicerede hjernesygdomme Alzheimers og Parkinsons sygdom. Det skriver Berlingske.

Også de to eliteuniversiteter Cambridge og Oxford samt danske Aarhus Universitet er ed i samarbejdet. Formålet med samarbejdet er at finde en metode til at stoppe spredningen af de proteiner - såkaldte toksiske proteiner - der ødelægger hjernecellerne.

"Fokus har meget været på at fjerne proteinerne, når de ikke er i cellerne. Her prøver vi at se, om vi kan fjerne dem, når de er inde i cellerne. Det handler om at få styrket de mekanismer, som nedbryder de toksiske proteiner, så de ikke spreder sig til hele cellen, som dermed dør," siger Jan Egebjerg, underdirektør i Lundbecks afdeling for forskning i neurodegeneration, til Berlingske.

De enkelte virksomheder kan efter projektets afslutning gå videre med udvikling af en egentlig lægemiddelkandidat, hvis der skulle være dukket lovende forskning op undervejs.

Forskningsprojektet er sat til at løbe i fire år med et budget på godt 80 mio. kr. Samarbejdet er støttet af EU med 35 mio. kr. (...)

- Kalsiumubalanse i hjerneceller kan utløse Alzheimers sykdom. (- Ingen har noen gang sett på dette før bruken av disse modellsystemene. Det er mulig at endringer i mitokondrienes kalsiumutveksling er driveren av sykdomsprosessen.)

Calcium imbalance within brain cells may trigger Alzheimer's disease (Kalsium ubalanse i hjerneceller kan utløse Alzheimers sykdom)
medicalnewstoday.com 15.2.2017
Mitokondrier - noen ganger referert til som "cellenes kraftverk" - er små strukturer som omdanner energien fra mat til celledrivstoff. (Mitochondria - sometimes referred to as the "powerhouse of the cell" - are small structures that transform energy from food into cell "fuel.")

I mitokondriene hos en hjernecelle kontrollerer kalsiumioner hvor mye energi som produseres av hjernen for å få hjernen til å fungere. Tidligere forskning har vist at en overdreven produksjon av kalsium kan føre til at nerveceller dør, derfor linkes en kalsiumubalanse med den nevrodegenerative prosessen involvert i Alzheimers sykdom. (In the mitochondria of a brain cell, calcium ions control how much energy is produced for the brain to function. Previous research has shown that an excessive production of calcium can cause neurons to die, therefore linking a calcium imbalance with the neurodegenerative process involved in Alzheimer's disease.)

Until now, however, the exact mechanism that links Alzheimer's-related neurodegeneration and mitochondrial calcium imbalance was unknown. The new research - led by Pooja Jadiya, a postdoctoral fellow at Temple University in Philadelphia, PA - sheds light on this association.

The study was carried out by researchers from the Center for Translational Medicine at Temple University, and the findings were presented at the 61st Meeting of the Biophysical Society in New Orleans, LA. (…)

"Ingen har noen gang sett på dette før bruken av disse modellsystemene. Det er mulig at endringer i mitokondrienes kalsiumutveksling er driveren av sykdomsprosessen." (...) ("No one has ever looked at this before using these model systems. It is possible that alterations in mitochondrial calcium exchange may be driving the disease process.")

"Our hope is that if we can change either the expression level or the activity of this exchanger, it could be a viable therapy to use early on to perhaps impede Alzheimer's disease development - that is the home run," Elrod says. "We are not even close to that, but that would be the idea."

Learn how scientists can stop and reverse Alzheimer's-related brain damage in mice. (…)

(Anm: Study unravels mystery of how nerve cells are damaged in neurodegenerative diseases. A new study has uncovered a molecular mechanism in the prion protein, a protein responsible for neurodegenerative diseases, which may explain why nerve cells degenerate in these disorders. The findings, which appear in the journal eLife, may one day lead to better therapies and treatments for these diseases. (…) Prion diseases are part of larger group of human neurodegenerative disorders, including Alzheimer's, Parkinson's and Huntington's diseases, which are all due to the abnormal accumulation of protein aggregates in the brain. (…) The researchers hope their study will lead to better therapies for neurodegenerative disorders, as well as help clinicians avoid the possible dangerous side-effects of using anti-prion protein antibodies for therapeutic purposes. (news-medical.net 25.5.2017).)

- Miljøets betydning ved multippel sklerose

Miljøets betydning ved multippel sklerose
Tidsskr Nor Legeforen 2015; 135:856-60 (16.2.2017)
BAKGRUNN Epidemiologiske studier tyder på at miljøfaktorer spiller en betydelig rolle for utviklingen av multippel sklerose. Vi gir her en oppdatering om miljøets betydning for sykdomsrisiko og sykdomsforløp.

KUNNSKAPSGRUNNLAG Vi har gjort litteratursøk i PubMed med søkeordet «multiple sclerosis» kombinert med «environment» samt aktuelle miljøfaktorer.

RESULTATER Det er overveiende sannsynlig at et samspill mellom genetiske og miljømessige faktorer avgjør hvem som utvikler multippel sklerose. Epstein-Barr-virusinfeksjon, røyking og lave nivåer av vitamin D er de miljøfaktorene som har vist sterkest og mest konsistent assosiasjon med utvikling av sykdommen. Lavt vitamin D-nivå er også forbundet med høy sykdomsaktivitet. Andre aktuelle risikofaktorer er overvekt og høyt saltinntak.

FORTOLKNING Selv om man i epidemiologiske studier har identifisert en rekke potensielle etiologiske miljøfaktorer og betydningen av disse støttes av eksperimentelle studier, er det fortsatt ikke tilstrekkelige holdepunkter for å fastslå at de spiller en kausal rolle.

Forekomsten av multippel sklerose er økende, og det er beregnet at om lag 10 000 mennesker i Norge har sykdommen (1). Multippel sklerose reduserer livslengden med 5 – 10 år og er en hyppig årsak til nevrologisk invaliditet. Til tross for bedret behandling er det derfor fortsatt behov for kunnskap som kan bidra til å forebygge sykdommen.

Forskning innen epidemiologi, genetikk og immunologi har gitt økt innsikt i hvilke faktorer som kan forårsake multippel sklerose. Målet med denne artikkelen er å drøfte miljøets betydning for sykdomsrisiko og sykdomsprogrediering. (…)

(Anm: Miljø og helse (mintankesmie.no).)

(Anm: Powering the Cell: Mitochondria (ed.ted.com).)

(Anm: Cellular Respiration and the Mighty Mitochondria (ed.ted.com).)

(Anm: Dr. Terry Wahls - Minding Your Mitochondria - TED - Documentary, Lecture, Talk NUTRITION (youtube.com 16.4.2017).)

- Mitokondriell dysfunksjon bidrar til "Hypertensive Target Organ Damage»: Lærdom fra en dyremodell for sykdom hos mennesker.

Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease.
Oxid Med Cell Longev. 2016;2016:1067801. Epub 2016 Aug 9.
Abstract Mechanisms underlying hypertensive target organ damage (TOD) are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2) involved in OXPHOS complex I assembly and activity and the second one (UCP2) involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension. (…)

(Anm: Powering the Cell: Mitochondria (ed.ted.com).)

(Anm: Cellular Respiration and the Mighty Mitochondria (ed.ted.com).)

(Anm: Dr. Terry Wahls - Minding Your Mitochondria - TED - Documentary, Lecture, Talk NUTRITION (youtube.com 16.4.2017).)

- Antibiotika kan utløse mitokondriell dysfunksjon som induserer psykiatriske lidelser.

Antibiotics May Trigger Mitochondrial Dysfunction Inducing Psychiatric Disorders.
Med Sci Monit. 2017 Jan 7;23:101-106.
Abstract Clinical usage of several classes of antibiotics is associated with moderate to severe side effects due to the promotion of mitochondrial dysfunction. We contend that this may be due to perturbation of unique evolutionary relationships that link selective biochemical and molecular aspects of mitochondrial biology to conserved enzymatic processes derived from bacterial progenitors. Operationally, stereo-selective conformational matching between mitochondrial respiratory complexes, cytosolic and nuclear signaling complexes appears to support the conservation of a critically important set of chemical messengers required for existential regulation of homeostatic cellular processes. Accordingly, perturbation of normative mitochondrial function by select classes of antibiotics is certainly reflective of the high degree of evolutionary pressure designed to maintain ongoing bidirectional signaling processes between cellular compartments. These issues are of critical importance in evaluating potentially severe side effects of antibiotics on complex behavioral functions mediated by CNS neuronal groups. The CNS is extremely dependent on delivery of molecular oxygen for maintaining a required level of metabolic activity, as reflected by the high concentration of neuronal mitochondria. Thus, it is not surprising to find several distinct behavioral abnormalities conforming to established psychiatric criteria that are associated with antibiotic usage in humans. The manifestation of acute and/or chronic psychiatric conditions following antibiotic usage may provide unique insights into key etiological factors of major psychiatric syndromes that involve rundown of cellular bioenergetics via mitochondrial dysfunction. Thus, a potential window of opportunity exists for development of novel therapeutic agents targeting diminished mitochondrial function as a factor in severe behavioral disorders. (…)

(Anm: Mitochondrial dysfunction-a link between antibiotic use and increased risk of severe mental disorders? Acta Psychiatr Scand. 2017 Mar 23.)

- Ny studie knytter autisme mutasjoner i mitokondrie-DNA

New study links autism to mutations in mitochondrial DNA
medicalnewstoday.com 31.10.2016
Autism is a developmental disorder affecting over 3.5 million Americans. While there is no known cure for it, there are options for treating some of its associated symptoms. A new study by a team of researchers at Cornell University has found a connection between autism and mutations in mitochondrial DNA. This could eventually lead to developing new and more effective types of treatment. (…)

(Anm: A cannabinoid link between mitochondria and memory. Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB1) can directly alter mitochondrial energetic activity. (…) By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions. Nature. 2016 Nov 9. [Epub ahead of print].)

(Anm: Fakta: Nobelprismodtagere har reddet millioner af liv. Japansk cellebiolog modtager årets nobelpris i medicin. Tidligere modtagere står bag livreddende forskning. (jyllands-posten.dk 3.10.2016).)

(Anm: Mitochondrial Changes in Cancer. (…) This chapter summarizes various changes in mitochondria in relevance to cancer, behavior of mitochondria during tumorigenesis, and the progress on using mitochondria as a therapeutic target for cancer. Handb Exp Pharmacol. 2016 Oct 8. [Epub ahead of print].)

(Anm: Researchers discover a new regulator of mitochondria in invasive cancer growth. Cancer cells' ability to invade and spread is what makes them deadly. In a recent study published in the journal Current Biology, Texas A&M College of Medicine researchers demonstrate that mitochondria, the so-called powerhouses of the cell, play a crucial role in a tumor's ability to grow. With a better understanding of how this process is regulated, new targets for cancer treatments could be identified. (medicalnewstoday.com 28.11.2016).)

(Anm: Kan barneautisme komme av stoffskiftefeil? Det interessante er hvordan Raugland arbeidet for å hjelpe Tim. Forfatteren forteller om de utradisjonelle analysene hun har benyttet seg av: antistoffprøver mot enkelte matvarer, fettsyrebalanse, inflammasjonspanel for eventuell immunologisk dysfunksjon, cøliakiutredning, gentest for eventuelle enzymfeil i stoffskiftet, forhøyede peptider i urin, avføringsanalyse, håranalyse og ortomolekylær utredning. Sentralt er metyleringsreaksjonene. Hans genfeil i stoffskiftet ble omgått ved «genetisk bypass» ved kosttilskudd. Dette behandlingsopplegget kaller hun «Tim-modellen». Forfatteren presiserer at diett og kosttilskudd er individuelt. Tidsskr Nor Legeforen 2017; 137:557 (30.4.2017).)

(Anm: On mitochondrial metabolism in tumor biology. (…) Therapeutic targeting of cancer cell mitochondria remains experimental but promising, and more predictive markers will be needed for metabolism-based treatments and personalized medicine.Curr Opin Oncol. 2016 Oct 26. [Epub ahead of print].)

(Anm: Regulators of mitochondrial dynamics in cancer. (…) This review focuses on key regulators of mitochondrial dynamics and their role in cancer. Curr Opin Cell Biol. 2016 Apr;39:43-52.)

(Anm: Signaler fra tarmens mikrobiotika til fjerntliggende organer mht. fysiologi og sykdom. Signals from the gut microbiota to distant organs in physiology and disease. (Nat Med. 2016 Oct 6;22(10):1079-1089.)

(Anm: Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by Thymidine Phosphorylase Enzyme Deficiency: From Pathogenesis to Emerging Therapeutic Options. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a progressive metabolic disorder caused by thymidine phosphorylase (TP) enzyme deficiency. The lack of TP results in systemic accumulation of deoxyribonucleosides thymidine (dThd) and deoxyuridine (dUrd). In these patients, clinical features include mental regression, ophthalmoplegia, and fatal gastrointestinal complications. Front. Cell. Neurosci., 15 February 2017.)

- Endrede mitokondrier assosiert med økt autisme risiko. Mitokondrier, de små strukturer i cellene våre som genererer energi, kan spille en nøkkelrolle i autisme spektrumforstyrrelser (ASD).

(Anm: Altered mitochondria associated with increased autism risk. Mitochondria, the tiny structures inside our cells that generate energy, may play a key role in autism spectrum disorders (ASD). A provocative new study by Children's Hospital of Philadelphia (CHOP)'s pioneering mitochondrial medicine team suggests that variations in mitochondrial DNA (mtDNA) originating during ancient human migrations may play an important role in predisposition to ASDs. "Our findings show that differences in mitochondrial function are important in ASD," said study leader Douglas C. Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine at CHOP. "Our team demonstrates that a person's vulnerability to ASD varies according to their ancient mitochondrial lineage." Wallace and colleagues, including Dimitra Chalkia, Larry Singh and others, published their findings in JAMA Psychiatry. (…) Mitochondria contain their own DNA, distinct from the more familiar nuclear DNA (nDNA) inside the cell nucleus. The mtDNA codes for essential genes governing cellular energy production, and those genes exchange biological signals with nDNA to affect our physiology and overall health. (medicalnewstoday.com 14.2.2015).)
(Anm: Association Between Mitochondrial DNA Haplogroup Variation and Autism Spectrum Disorders. JAMA Psychiatry 2017 (published online 23 August 2017.).)

(Anm: Mitokondriell dysfunksjon (mitokondriedysfunksjon) indusert av sertraline (Zoloft), et antidepressiva (Mitochondrial dysfunction induced by sertraline, an antidepressant agent) Toxicol Sci. 2012 Jun;127(2):582-91. Epub 2012 Mar 2.)

(Anm: Kan Lupus øke risikoen for demens? Could lupus raise dementia risk? People living with lupus may be at significantly greater risk of developing dementia than those without the autoimmune disease, a new study suggests. (…) Study co-author Daniela Amital, of the Sackler Faculty of Medicine at Tel Aviv University in Israel, and colleagues recently reported their results in the International Journal of Geriatric Psychiatry. (medicalnewstoday.com 9.11.2017).)

- Forandrede mitokondrier assosiert med økt autismerisiko.

(Anm: Altered Mitochondria Associated with Increased Autism Risk. CHOP Scientist: Ancient Mitochondrial DNA Genetic Patterns May Play Role in this Neurodevelopmental Condition. PHILADELPHIA, Aug. 23, 2017 /PRNewswire-USNewswire/ -- Mitochondria, the tiny structures inside our cells that generate energy, may play a key role in autism spectrum disorders (ASDs). A provocative new study by Children's Hospital of Philadelphia (CHOP)'s pioneering mitochondrial medicine team suggests that variations in mitochondrial DNA (mtDNA) originating during ancient human migrations may play an important role in predisposition to ASDs. (prnewswire.com 30.8.2017).)

- Mitokondrielle funksjoner modulerer nevroendokrine, metabolske, inflammatoriske og transkripsjonelle responser på akutt psykologisk stress.

(Anm: Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress. Abstract The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism's multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic-pituitary-adrenal axis, sympathetic adrenal-medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):E6614-23.)

(Anm: Hjernen (mintankesmie.no).)

- Tarmbakterier og hjernen: Er vi styrt av mikrober?

(Anm: Tarmbakterier og hjernen: Er vi styrt av mikrober? (Gut bacteria and the brain: Are we controlled by microbes? Although the interaction between our brain and gut has been studied for years, its complexities run deeper than initially thought. It seems that our minds are, in some part, controlled by the bacteria in our bowels. (…) On the other side of the fence, recent research infers that dysregulation of gut bacteria might be an important factor in inflammatory and autoimmune conditions. The microbiome's role in health and disease is only slowly giving up its secrets. The latest and perhaps most remarkable finding is the ability that gut bacteria have to moderate our brain and behavior.) (medicalnewstoday.com 7.9.2016).)

- Har Mitokondrier et immunsystem?

(Anm: Do Mitochondria Have an Immune System? Abstract The question if mitochondria have some kind of immune system is not trivial. The basis for raising this question is the fact that bacteria, which are progenitors of mitochondria, do have an immune system. The CRISPR system in bacteria based on the principle of RNA interference serves as an organized mechanism for destroying alien nucleic acids, primarily those of viral origin. We have shown that mitochondria are also a target for viral attacks, probably due to a related organization of genomes in these organelles and bacteria. Bioinformatic analysis performed in this study has not given a clear answer if there is a CRISPR-like immune system in mitochondria. However, this does not preclude the possibility of mitochondrial immunity that can be difficult to decipher or that is based on some principles other than those of CRISPR. Biochemistry (Mosc). 2016 Oct;81(10):1229-1236.)

(Anm: Signaler fra tarmens mikrobiotika til fjerntliggende organer mht. fysiologi og sykdom. Signals from the gut microbiota to distant organs in physiology and disease. (Nat Med. 2016 Oct 6;22(10):1079-1089.)

- Rebalansering av mikrobiom i tarmer forlenger overlevelsen i ALS-musemodell. (- Mekanismen for virkningen til butyrat er relatert til fremming av energiforbruk og induksjon av mitokondriefunksjon.)

Rebalancing gut microbiome lengthens survival in mouse model of ALS
medicalnewstoday.com 31.2.2017
sclerosis, or ALS - a progressive, neurodegenerative disease.

Researchers at the University of Illinois at Chicago College of Medicine report that in a mouse model of ALS, the compound butyrate helped correct a gut microbiome imbalance and reduced gut leakiness - both symptoms of ALS. The treated mice lived also longer compared to mice that weren't given butyrate.

The finding is reported in Clinical Therapeutics.

ALS, also known as Lou Gehrig's disease, slowly destroys the motor neurons that control movement. Patients gradually lose the ability to walk, speak and swallow - and eventually, to breathe. Conventional treatments include physical therapy and medications, but researchers have recently started looking to the gut as a new target for intervention.

"The brain and the gut are linked, so it's not too surprising that the health of the gut can impact the functioning of neurons," says Jun Sun, associate professor of gastroenterology and hepatology at UIC and corresponding author of the paper. In March, she and her coworkers were the first to identify a gut component to ALS progression.

The gut microbiome - the myriad bacteria, viruses and other microbes that make the gut their home - when in balance, helps maintain health, starting with the gut lining. Leaky gut in ALS may lead to increased inflammation. Reducing this gut-associated inflammation has been a goal of clinicians and researchers, and rebalancing the gut microbiome has shown promise in small-animal studies.

Sun and her colleagues studied transgenic mice that were engineered to carry human genes known to contribute to certain forms of ALS. The mice were found to have an abnormal microbiome, along with damaged junctions between the cells of the intestinal lining. Poorly functioning junctions can cause the tissue to become leaky, and have been found to be associated with the onset of ALS in humans. (…)

Mekanismen for virkningen til butyrat er relatert til fremming av energiforbruk og induksjon av mitokondriefunksjon. (...) (The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondrial function.)

(Anm: Butyrate (also known as butanoate) is the traditional name for the conjugate base of butyric acid (also known as butanoic acid). The formula of the butyrate ion is C4H7O2−. The name is used as part of the name of esters and salts of butyric acid, a short chain fatty acid. (en.wikipedia.org).)

(Anm: Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. Abstract The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. (…) These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine. World J Gastroenterol. 2011 Mar 28; 17(12): 1519–1528.)

- Mitochondrial Respiratory Chain Dysfunction in Muscle From Patients With Amyotrophic Lateral Sclerosis (ALS) (- In 7 patients, the oxidative defect was severe enough to support the hypothesis that mitochondrial dysfunction must play a role in the pathogenesis of the disease.)

Mitochondrial Respiratory Chain Dysfunction in Muscle From Patients With Amyotrophic Lateral Sclerosis
Arch Neurol. 2010;67(7):849-854 (July)
Background Amyotrophic lateral sclerosis (ALS) is a major cause of neurological disability and its pathogenesis remains elusive despite a multitude of studies. Although defects of the mitochondrial respiratory chain have been described in several ALS patients, their pathogenic significance is unclear.

Objective To review systematically the muscle biopsy specimens from patients with typical sporadic ALS to search for possible mitochondrial oxidative impairment. (...)

Conclusions Our data confirm that the histochemical finding of COX-negative fibers is common in skeletal muscle from patients with sporadic ALS. We did not find a correlation between severity of the oxidative defect and age of the patients or duration of the disease. However, the only patient who underwent a second muscle biopsy did show a correlation between severity of symptoms and worsening of the respiratory chain defect. In 7 patients, the oxidative defect was severe enough to support the hypothesis that mitochondrial dysfunction must play a role in the pathogenesis of the disease. (...)

(Anm: Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients. J Neurol. 2015 Apr 18. [Epub ahead of print].)

- Mitokondrierens rolle i ALS (amyotrofisk lateral sklerose).

(Anm: The Role of Mitochondria in Amyotrophic Lateral Sclerosis. Mitochondria are unique organelles that are essential for a variety of cellular processes including energy metabolism, calcium homeostasis, lipid biosynthesis, and apoptosis. Mitochondrial dysfunction is a prevalent feature of many neurodegenerative diseases including motor neuron disorders such as amyotrophic lateral sclerosis (ALS). Disruption of mitochondrial structure, dynamics, bioenergetics and calcium buffering has been extensively reported in ALS patients and model systems and has been suggested to be directly involved in disease pathogenesis. Here we review the alterations in mitochondrial parameters in ALS and examine the common pathways to dysfunction. Neurosci Lett. 2017 Jun 29. pii: S0304-3940(17)30544-X. [Epub ahead of print].)

- Aspirin øker mitokondriell fettsyreoksidasjon. (- These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders.)

Aspirin increases mitochondrial fatty acid oxidation.
Biochem Biophys Res Commun. 2016 Nov 14. pii: S0006-291X(16)31922-2. [Epub ahead of print]
Abstract The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. (…)

(Anm: Hva er Reyes syndrom? Reyes syndrom er en svært sjelden men alvorlig tilstand, som man mener kan utløses når et barn med virusinfeksjon og feber behandles med acetylsalisylsyre (albyl/globoid). Det typiske forløpet er at man kort tid etter at virusinfeksjonen er over på ny blir syk med forandret bevissthet, etter hvert kramper, bevisstløshet og i mange tilfeller død. Magesmerter og oppkast er også vanlig. Symptomene skyldes alvorlig betennelse i hjerne og lever. Dette er også årsaken til at helsemyndigheter advarer mot bruk av acetylsalisylsyre ved feber hos barn. (nhi.no 28.1.2014).)

- Bupropion (Zyban) er et mye foreskrevet antidepressiva / røykesluttpille. Imidlertid er hepatotoksisitet (levertoksisitet) en av dets bivirkninger som er rapportert hos enkelte brukere.

Mechanistic Approach for Toxic Effects of Bupropion in Primary Rat Hepatocytes.
Drug Res (Stuttg). 2017 Jan 24. doi: 10.1055/s-0042-123034. [Epub ahead of print]
Abstract Bupropion is a widely prescribed antidepressant/smoke cessation drug. However, hepatotoxicity is one of its side effects reported in some recipients. The mechanisms by which bupropion induces hepatotoxicity is not clear yet. This experiment was intended to assess the cytotoxic mechanisms of bupropion toward primary rat hepatocytes. Additionally, the effect of α-tocopherol succinate (ALPHA-TOS) and N-acetyl cysteine (NAC) and mitochondrial permeability transition (MPT) pore sealing agent cyclosporine A (Cs A) on this toxicity was investigated. Cell death, LDH leakage, reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and mitochondrial depolarization were examined as toxicity indicators. Results revealed that bupropion led to a surge in ROS formation, depletion of intracellular glutathione, elevation of LPO, and mitochondrial collapse. ALPHA-TOS, NAC and Cs A administration diminished the intensity of cellular damage caused by bupropion. This experiment suggests the protective role of ALPHA-TOS, NAC and Cs A against bupropion-mediated cytotoxicity possibly through their reactive radical scavenging properties and their impacts on mitochondria. Furthermore, mitochondria might be contributed to the oxidative stress response and subsequent toxicological results observed by bupropion. (…)

(Anm: Cytotoksisk, om et stoff eller påvirkning som skader en celle, eventuelt så alvorlig at cellen dør (i noen tilfeller ved at cellen løses opp; cytolyse). Kilde: Store norske leksikon.)

(Anm: Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (Bitis arietans) or brown recluse spider (Loxosceles reclusa). (en.wikipedia.org).)

- En hurtig mitokondriell toksisitetsanalyse ved anvendelse av skiftende celleenergimetabolisme.

A rapid mitochondrial toxicity assay utilizing rapidly changing cell energy metabolism.
J Toxicol Sci. 2017;42(3):349-358. doi: 10.2131/jts.42.349.
Abstract Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay. Here, we report a rapid version of this method with the same predictability as the original method. We found that replacing the glucose in the medium with galactose resulted in HepG2 cells immediately shifting their energy metabolism from glycolysis to oxidative phosphorylation due to drastic energy starvation; in addition, the intracellular concentration of ATP was reduced by mitotoxicants when glucose in the medium was replaced with galactose. Using our proposed rapid method, mitochondrial dysfunction in HepG2 cells can be evaluated by drug exposure for one hour without a pre-culture step. This rapid assay for mitochondrial toxicity may be more suitable for high-throughput screening than the original method at an early stage of drug development. (…)

(Anm: Statlig legemiddelkontroll (Statens legemiddelverk etc.) (mintankesmie.no).)

(Anm: Statlig hvitvasking av legemiddelinformasjon (Tidsskr Nor Legeforen 2010; 130:368 (25.2.2010).)

- Venlafaksin-indusert cytotoksisitet mot isolerte hepatocytter fra rotter innebærer oksidativt stress og mitokondrie/lysosomal dysfunksjon. (- Venlafaxine-Induced Cytotoxicity Towards Isolated Rat Hepatocytes Involves Oxidative Stress and Mitochondrial/Lysosomal Dysfunction.)

Venlafaxine-Induced Cytotoxicity Towards Isolated Rat Hepatocytes Involves Oxidative Stress and Mitochondrial/Lysosomal Dysfunction.
Adv Pharm Bull. 2016 Dec;6(4):521-530. Epub 2016 Dec 22.
Abstract Purpose: Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine-induced cell death in the model of the freshly isolated rat hepatocytes. Methods: Collagenase-perfused rat hepatocytes were treated with venlafaxine and other agents. Cell damage, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential decline, lysosomal damage, glutathione (GSH) level were analyzed. Moreover, rat liver mitochondria were isolated through differential centrifugation to assess respiratory chain functionality. Results: Our results demonstrated that venlafaxine could induce ROS formation followed by lipid peroxidation, cellular GSH content depletion, elevated GSSG level, loss of lysosmal membrane integrity, MMP collapse and finally cell death in a concentration-dependent manner. N-acetyl cysteine, taurine and quercetine significantly decreased the aforementioned venlafaxine-induced cellular events. Also, radical scavenger (butylatedhydroxytoluene and α-tocopherol), CYP2E1 inhibitor (4-methylpyrazole), lysosomotropic agents (methylamine and chloroquine), ATP generators (L-gluthamine and fructose) and mitochondrial pore sealing agents (trifluoperazine and L-carnitine) considerably reduced cytotoxicity, ROS generation and lysosomal leakage following venlafaxine treatment. Mitochondrion dysfunction was concomitant with the blockade of the electron transfer complexes II and IV of the mitochondrial respiratory system. Conclusion: Therefore, our data indicate that venlafaxine induces oxidative stress towards hepatocytes and our findings provide evidence to propose that mitochondria and lysosomes are of the primary targets in venlafaxine-mediated cell damage. (…)

(Anm: Cytotoksisk, om et stoff eller påvirkning som skader en celle, eventuelt så alvorlig at cellen dør (i noen tilfeller ved at cellen løses opp; cytolyse). Kilde: Store norske leksikon.)

(Anm: Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (Bitis arietans) or brown recluse spider (Loxosceles reclusa). (en.wikipedia.org).)

- Vi har funnet at paroxetine (paroksetin; Seroxat; Paxil etc.) har cytotoksisk aktivitet mot tumorceller, både av murine eller human opprinnelse i det mikromolarer konsentrasjonsområdet.. (- We found that paroxetine has cytotoxic activity against tumor cells, both of murine or human origin in the micromolar concentration range.)

(Anm: Ulike selektive serotonin reopptakshemmeres (SSRI-er) cytotoksisitet mot kreftceller. (Cytotoxicity of different selective serotonin reuptake inhibitors (SSRIs) against cancer cells.) (…) Vi har funnet at paroxetine (paroksetin; Seroxat; Paxil etc.) har cytotoksisk aktivitet mot tumorceller, både av murine eller human opprinnelse i det mikromolarer konsentrasjonsområdet.. (- We found that paroxetine has cytotoxic activity against tumor cells, both of murine or human origin in the micromolar concentration range.) J Exp Ther Oncol. 2006;6(1):23-9.)

(Anm: Cytotoksisk, om et stoff eller påvirkning som skader en celle, eventuelt så alvorlig at cellen dør (i noen tilfeller ved at cellen løses opp; cytolyse). Kilde: Store norske leksikon.)

(Anm: Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (Bitis arietans) or brown recluse spider (Loxosceles reclusa). (en.wikipedia.org).)

(Anm: Efexor / Effexor (venlafaxine) - Pristiq (desvenlafaxine) (mintankesmie.no).)

(Anm: paroksetin (paroxetine); markesføres i Norge under handelsnavn som bl.a. Seroxat; Paxil i USA.)

(Anm: Akutt toksisitet for 8 antidepressiva: hva er deres virkningsmekanismer? (Acute toxicity of 8 antidepressants: what are their modes of action? Currently, the hazard posed by pharmaceutical residues is a major concern of ecotoxicology. Most of the antidepressants belong to a family named the Cationic Amphipathic Drugs known to have specific interactions with cell membranes. The present study assessed the impact of eight antidepressants belonging to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors.) Chemosphere. 2014 Aug;108:314-9. Epub 2014 Feb 14. (PDF).)

(Anm: Cell membranes are way more complicated than you think - Nazzy Pakpour (ed.ted.com).)

(Anm: Cytotoxic immune cell in sick and healthy skin a key to understanding vitiligo. With the aid of thousands of skin biopsies and over a hundred kilograms of skin, researchers at Karolinska Institutet have observed how two subgroups of immune cell behave in healthy skin. This functional dichotomy is preserved in the inflammatory diseases psoriasis and vitiligo. The study, which is published in the journal Immunity, opens the way for more targeted local treatments for patchy inflammatory skin disorders. (medicalnewstoday.com 22.2.2017).)

- Ulike selektive serotonin reopptakshemmeres (SSRI-er) cytotoksisitet mot kreftceller. (- We found that paroxetine has cytotoxic activity against tumor cells, both of murine or human origin in the micromolar concentration range, whereas venlafaxine has not.)

Cytotoxicity of different selective serotonin reuptake inhibitors (SSRIs) against cancer cells.
J Exp Ther Oncol. 2006;6(1):23-9.
Abstract Cell membrane ion transporters expression and activity are altered in cancer cells and these phenotypic alterations offer potential targets for cancer therapies. Among the therapeutic agents affecting cell membrane transporters, serotonin reuptake inhibitors (SSRIs) have been shown to have anticancer potential. In this work, we have compared two SSRIs, one very specific for serotonin reuptake transporters (paroxetine) and another which also inhibit norepinephrine and dopamine transporters (venlafaxine), for their ability to counteract growth of various murine and human cancer cell lines. We found that paroxetine has cytotoxic activity against tumor cells, both of murine or human origin in the micromolar concentration range, whereas venlafaxine has not. A neurotransmitter receptor mediated mechanism of action appears thus unlikely for SSRIs cytotoxicity on cancer cells. With ranges of SSRIs cytotoxicity on cancer cells defined, limits in their possible applicability in cancer therapy is discussed. (…)

(Anm: Cytotoksisk, om et stoff eller påvirkning som skader en celle, eventuelt så alvorlig at cellen dør (i noen tilfeller ved at cellen løses opp; cytolyse). Kilde: Store norske leksikon.)

(Anm: Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (Bitis arietans) or brown recluse spider (Loxosceles reclusa). (en.wikipedia.org).)

- Doserelaterte parestesier med venlafaxin (Venlafaksin; Efexor; Effexor etc.)

Dose-related paresthesias with venlafaxine
J Pharm Pract. 2013 Oct;26(5):514-7. Epub 2013 Jun 13.
INTRODUCTION: Venlafaxine is a serotonin norepinephrine reuptake inhibitor that is used for mood, anxiety, and pain disorders. We report a case of dose-related paresthesias in association with venlafaxine use in a patient with major depressive disorder.

CASE REPORT: A young male patient with major depression started treatment with venlafaxine XR at 37.5 mg/d, and the dose was titrated to 75 mg/d with no significant adverse effects. Upon increasing the dose to 150 mg/d, the patient reported tingling, numbness, and itching in his upper extremities. The dose was reduced to 75 mg/d, at which time, the symptoms disappeared. Since the patient still had target symptoms of depression, the patient was willing to try increasing the dose back to 150 mg/d. Upon rechallenge, the tingling, numbness, and itching reappeared. The dose of venlafaxine was decreased back to 75 mg/d. Per the Naranjo scale, the probability score for the above adverse drug reaction is 5 (probable). We discuss the published evidence of paresthesias associated with antidepressants and clinical implications for recognizing paresthesias during venlafaxine treatment that may be useful for clinicians.

CONCLUSION: Clinicians need to be aware of the possible emergence of paresthesias with venlafaxine treatment, especially at doses of ≥ 150 mg/day. Patients who receive venlafaxine for pain disorders should be closely monitored for worsening of pain symptoms and may require adjustment of their doses. (...)

(Anm: Antidepressiva (nytteverdi) (mintankesmie.no).)

(Anm: Ny forskning: Lykkepiller gør mere skade end gavn. Folk med depression får intet ud af at tage antidepressivet SSRI, bedre kendt som lykkepiller, viser nyt dansk studie. (jyllands-posten.dk 13.2.2017).)

(Anm: Parestesi, hudfornemmelse som ikke skyldes ytre påvirkning. Disse fornemmelsene kan føles som brenning, stikking og prikking, kløe, nummenhet, maurkryping, varme eller kulde. Parestesier kan skyldes sykdom i nerver eller blodårer, som igjen for eksempel kan være utløst av visse former for anemi, diabetes og forgiftninger (for eksempel ved alkoholisme). Behandlingen retter seg mot eventuell underliggende sykdom. Kilde: Store norske leksikon.)

- Konklusjon: Dekonstruksjon av rettsdokumenter avslørte at protokollspesifikke resultater ikke viste statistisk signifikant forskjell mellom citalopram og placebo. Den publiserte artikkelen konkluderte imidlertid med at citalopram var trygt og betydelig mer effektivt enn placebo for barn og ungdom, med mulige bivirkninger mht. pasientsikkerhet.

(Anm: The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance. OBJECTIVE: Deconstruction of a ghostwritten report of a randomized, double-blind, placebo-controlled efficacy and safety trial of citalopram in depressed children and adolescents conducted in the United States. (…) CONCLUSION: Deconstruction of court documents revealed that protocol-specified outcome measures showed no statistically significant difference between citalopram and placebo. However, the published article concluded that citalopram was safe and significantly more efficacious than placebo for children and adolescents, with possible adverse effects on patient safety. Int J Risk Saf Med. 2016 Mar 16;28(1):33-43.)

(Anm: Cipralex (Lexapro) (escitalopram) - Cipramil (Celexa) (cipramil) (citalopram) - H. Lundbeck A/S (mintankesmie.no).)

- Betennelser endrer mitokondrier til giftige fabrikker

Inflammation turns mitochondria into toxic factories (Betennelser endrer mitokondrier til giftige fabrikker)
medicalnewstoday.com 25.9.2016
Å lære hvordan å kontrollere betennelser kan ha store implikasjoner for behandlingen av mange sykdommer. Banebrytende forskning oppdager hvordan makrofager endrer mitokondriene til giftige kjemisk-produserende betennelsespromotører. (Learning how to control inflammation could have huge implications for the treatment of many diseases. Breaking research discovers how macrophages turn mitochondria into toxic chemical-producing inflammation-promoters.)

Inflammation plays a significant role in a number of serious medical conditions. Efforts to understand and control it are ongoing.

Inflammation is the body's attempt to protect itself from harmful stimuli. For instance, after a knock to the knee, inflammation helps prevent further damage; it has evolved to become an essential part of our immune system.

However, during disease, the inflammatory response can go awry and cause damage to healthy tissue; it is a powerful mechanism that must be tightly controlled.

For instance, inflammatory bowel disease, arthritis, and septic shock all involve high levels of poorly controlled inflammation.

In fact, inflammation can actually cause diseases and conditions to occur, such as hay fever, periodontitis, and some cancers. (…)

(Anm: Når cellens kraftverk streiker. Mitokondriesykdom gir energisvikt i cellen, og kan forårsake varierte nevrologiske symptomer som lammelser, epilepsi og anstrengelsesintoleranse. Tidsskr Nor Legeforen 2012; 132:1068 (15.5.2012).)

(Anm: Antibiotika (tarmbakterier, probiotika, mikrobiota etc.) (Dysbiose; dysbiosis (also called dysbacteriosis (dysbakteriose)). (mintankesmie.no).)

(Anm: Signaler fra tarmens mikrobiotika til fjerntliggende organer mht. fysiologi og sykdom. (Signals from the gut microbiota to distant organs in physiology and disease.) (Nat Med. 2016 Oct 6;22(10):1079-1089.)

(Anm: Three toxic gases meet in the mitochondria. Front. Physiol. 2015 (20 August 2015).)

(Anm: Blocking transfer of calcium to cell's powerhouse selectively kills cancer cells. Inhibiting the transfer of calcium ions into the cell's powerhouse is specifically toxic to cancer cells, according to an article published this week in Cell Reports by researchers from the Perelman School of Medicine at the University of Pennsylvania. (medicalnewstoday.com 4.3.2016).)

(Anm: Foods That Fight Inflammation. Inflammation, a response that can affect even the healthiest of bodies, is caused by many factors. One major factor that we can control is the food we eat. Try to incorporate these half a dozen foods to help fight inflammation and keep a balanced diet. (time.com 4.1.2017).)

- Sammenlignet med friske kontrollpersoner hadde suicidale pasienter påfallende økte nivåer av mitokondrie DNA i deres cellefrie blodplasma. (Compared to the healthy control subjects, the suicidal patients had strikingly increased levels of mitochondrial DNA in their cell-free blood plasma.)

New biomarker is higher in suicide attempters and associated with stress response
medicalnewstoday.com 11.12.2016
Researchers at Lund and Malmö universities in Sweden have measured a biomarker in cell-free blood
plasma which can be linked to an overactive stress system in suicidal individuals. This biomarker can
hopefully be used in future psychiatric studies.

"We don't expect the marker to be able to predict who will try to commit suicide, but it may serve as a biological marker indicating greater stress exposure in vulnerable people suffering from various
psychiatric conditions such as anxiety and depression. We would like to test the marker in future
psychiatric studies and see how it is affected by, for example, lifestyle interventions, psychotherapy and pharmacological treatment", says Daniel Lindqvist, associate professor of experimental psychiatry at Lund University and psychiatry resident at Psykiatri Skåne.

The researchers compared 37 patients who had been hospitalised at a psychiatric clinic after attempting suicide with an equal number of healthy control subjects. About 70 per cent of both groups were female, and the average age of the patients was approximately 40. (…)

Compared to the healthy control subjects, the suicidal patients had strikingly increased levels of
mitochondrial DNA in their cell-free blood plasma.

The researchers also found that the large amount of mitochondrial DNA in the plasma was linked to
higher levels of cortisol in the blood. Cortisol is an important hormone in the body's stress system and
high levels of cortisol, which have been found in depressed and suicidal patients in previous studies, are a sign of an overactive stress system.

Previous studies have shown that depressed individuals have an increased level of mitochondrial DNA in their immune cells and that this is linked to stressful life events. Furthermore, studies on animals have shown that increased stress and cortisol levels are linked to higher mitochondrial DNA, but this is the first study to be tested on psychiatric patients.

"We believe the increased levels in suicidal patients are due to their exposure to severe stress for longer periods than the healthy subjects we compared them to. An increased level of cortisol can cause the body's cells to malfunction, which in turn contributes to increased levels of cell-free mitochondrial DNA in the blood", says Lars Ohlsson, senior lecturer at Malmö University. (…)

(Anm: Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters: associations with HPA-axis hyperactivity. Translational Psychiatry (2016) 6, e971 (Published online 6 December 2016).)

(Anm: Valeant’s Siliq approved but suicidal thoughts warning will weigh heavy. Valeant has gained FDA approval for psoriasis drug Siliq – but side effect warnings about suicidal ideation look set to limit sales. (biopharmadive.com 16.2.2017).)

- Celleprotein gir nytt håp i kampen mot effektene av aldring. (- Forskning ved University of Nottingham har vist at et protein funnet i kraftverket (mitokondrie) til en celle kan være nøkkelen til å holde tilbake tidens tann, har vist.)

Cell protein offers new hope in fighting the effects of aging (Celleprotein gir nytt håp i kampen mot effektene av aldring.)
medicalnewstoday.com 12.10.2016
A protein found within the powerhouse of a cell could be the key to holding back the march of time, research by scientists at The University of Nottingham has shown. (…) (Forskning ved University of Nottingham har vist at et protein funnet i kraftverket (mitokondriene) til en celle kan være nøkkelen til å holde tilbake tidens tann, har vist.)

And their research, published in the academic journal Aging, could have special significance for combatting age-related decline and halting the progression of neurodegenerative conditions such as Alzheimer's and Parkinson's Disease.

The work, led by Dr Lisa Chakrabarti and PhD student Amelia Pollard in the University's School of Veterinary Medicine and Science, has centred on a family of proteins called carbonic anhydrase found within mitochondria - the cells' 'batteries' which convert the oxygen we breathe into the energy (ATP) needed to power our body.

Dr Chakrabarti said: "What's really exciting about this development is that we have been able to surmise that the function of this protein is playing a role in the aging process within the cell. (…)

(Anm: Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration. AGING 2016 (published online 10 October 2016).)

(Anm: Legemiddelindusert kreft og andre typer celleskader (mintankesmie.no).)

(Anm: Three toxic gases meet in the mitochondria. Front. Physiol. 2015 (20 August 2015).)

(Anm: Fluoksetin (Prozac; SSRI) og mitokondriene: En gjennomgang av de toksikologiske aspekter. (- Fluoksetin induserer også bivirkninger, som for eksempel angst, seksuell dysfunksjon, søvnforstyrrelser, og gastrointestinale svekkelser. (...) På den annen side har inntak av fluoxetin blitt assosiert med økt risiko for kreft. Likevel forblir data motstridende og ingen konklusjoner er trukket.) (Fluoxetine and the mitochondria: A review of the toxicological aspects. (Fluoksetin og mitokondriene: En gjennomgang av de toksikologiske aspekter. (...) On the other hand, fluoxetine intake has been associated with increased cancer risk.) Toxicol Lett. 2016 Jul 5. pii: S0378-4274(16)32264-0.)

(Anm: Dopaminmangel: Hva du trenger å vite. (Dopamine deficiency: What you need to know) (medicalnewstoday.com 17.1.2018).)

- Behandling med antidepressiva og risiko for demens. (- KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva.)

(Anm: Behandling med antidepressiva og risiko for demens: En populasjonsbasert, retrospektiv case-control studie. (…) KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva. (CONCLUSIONS: The incidence of dementia in patients is associated with antidepressant medication use.) J Clin Psychiatry. 2016 Jan;77(1):117-22.)

(Anm: Dopamin i det mediale amygdala-nettverk formidler menneskelige bånd (bindinger) (Dopamine in the medial amygdala network mediates human bonding.) Abstract Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. Proc Natl Acad Sci U S A. 2017 Feb 13. pii: 201612233.)

(Anm: Translational Identification of Transcriptional Signatures of Major Depression and Antidepressant Response. (…) Of the 13 identified genes that we tested for biomarker validation in human MDE patients, one of the genes HK1 has been previously linked to mood and psychotic disorders. HK1 encodes hexokinase 1, an initial and rate-limiting enzyme of glycolysis (Regenold et al., 2012). It has been known that genes associated with energy production are altered in postmortem brains as well as in peripheral tissues of MDD patients (Sibille et al., 2004; Klempan et al., 2009; Tobe, 2013; Garbett et al., 2015), and that molecular entities that are part of glycolysis pathway and the mitochondria in general serve as biomarkers and potential therapeutic targets for diagnosis and treatment of depression (Gormanns et al., 2011). Therefore, it was not surprising that the biological processes of the mitochondria are shared by the blood and the brain and are differentially regulated by chronic stress and fluoxetine treatment (Figure 3C). Front. Mol. Neurosci., 08 August 2017.)

(Anm: Bruk av annengenerasjons antipsykotiske legemidler øker parametre for metabolsk syndrom. (dgnews.docguide.com 17.3.2016).)

- Konklusjoner: Annengenerasjons antipsykotika forårsaker signifikant flere endringer i metabolske parametere, og øker risikoen for å utvikle metabolsk syndrom og tilhørende lidelser som diabetes mellitus type II og cerebrovaskulære ulykker.

(Anm: Konklusjoner: Annengenerasjons antipsykotika forårsaker signifikant flere endringer i metabolske parametere, og øker sjansene for å utvikle metabolsk syndrom og tilhørende lidelser som diabetes mellitus type II og cerebrovaskulære ulykker. (Conclusions: Second-generation antipsychotics cause significantly more changes in the metabolic parameters, increasing the chances of developing metabolic syndrome and associated disorders like diabetes mellitus type-II and cerebrovascular accidents. Indian J Psychiatry. 2011 Apr-Jun; 53(2): 128–133.)

- Metabolsk syndrom og risiko for kreft. En systematisk gjennomgang og meta-analyse. (- Konklusjoner. Metabolisk syndrom er forbundet med økt risiko for vanlige kreftformer, for enkelte kreftformer er risikoen forskjellig mellom kjønn, populasjoner og definisjoner av metabolsk syndrom.)

(Anm: Metabolic Syndrome and Risk of Cancer. A Systematic Review and Meta-analysis. Abstract Objective—Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites. Conclusions—Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and definitions of metabolic syndrome. Diabetes Care. 2012;35(11):2402-2411.)

(Anm: Dopaminmangel: Hva du trenger å vite. (Dopamine deficiency: What you need to know) (medicalnewstoday.com 17.1.2018).)

- Behandling med antidepressiva og risiko for demens. (- KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva.)

(Anm: Behandling med antidepressiva og risiko for demens: En populasjonsbasert, retrospektiv case-control studie. (…) KONKLUSJON: Forekomsten av demens hos pasienter er assosiert med bruk av antidepressiva. (CONCLUSIONS: The incidence of dementia in patients is associated with antidepressant medication use.) J Clin Psychiatry. 2016 Jan;77(1):117-22.)

(Anm: Dopamin i det mediale amygdala-nettverk formidler menneskelige bånd (bindinger) (Dopamine in the medial amygdala network mediates human bonding.) Abstract Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. Proc Natl Acad Sci U S A. 2017 Feb 13. pii: 201612233.)

(Anm: Det allerførste udtryk for liv lever stadig inden i os. En cellemaskine så kraftig, at den lagde grunden til alt liv, kan fortælle os, hvordan det hele begyndte. (jyllands-posten.dk 17.12.2017).)

- Antipsykotika-indusert dopamin supersensitivitetspsykose (SP): Farmakologi, kriterier og terapi. Til slutt beskriver vi 3 antipsykotiske seponeringssyndrom (bivirkninger grunnet nedtrapping av doser), som ligner de som er sett med andre CNS-legemidler, og vi foreslår tilnærminger for å behandle, potensielt forhindre eller midlertidig administrere SP.

(Anm: Antipsykotika-indusert dopamin supersensitivitetspsykose (SP): Farmakologi, kriterier og terapi. Til slutt beskriver vi 3 antipsykotiske seponeringssyndrom (bivirkninger grunnet nedtrapping av doser), som ligner de som er sett med andre CNS-legemidler, og vi foreslår tilnærminger for å behandle, potensielt forhindre eller midlertidig administrere SP. (Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy. Finally, we describe 3 antipsychotic withdrawal syndromes, similar to those seen with other CNS drugs, and we propose approaches to treat, potentially prevent, or temporarily manage SP.) Psychother Psychosom 2017;86:189-219.)

- Studien viser sammenhengen mellom metabolsk syndrom og risiko for kognitive sykdommer.

(Anm: Study shows link between metabolic syndrome and risk of cognitive disorders. A study presented at the European Academy of Neurology Congress in Amsterdam has shown that obesity alone is not a risk factor for cognitive disorders, but commonly associated co-morbidities such as diabetes, high blood pressure, and metabolic disorders are. Dementia diseases in patients who suffer from diabetes are often treated inadequately, a new research paper reveals. It has long been supposed that patients with metabolic syndrome are more likely to suffer from cognitive impairment - and to a greater extent. Reasons are thought to include chronic inflammatory processes which can induce neuroinflammatory and neurodegenerative changes. Whether obese individuals without risk factors such as diabetes mellitus, metabolic disorders and the presence of albumin in the urine have an increased risk of cognitive impairment is still little researched. (news-medical.net 27.6.2017).)

(Anm: Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status. Diabetes Care 2016 (Published online before print March 10, 2016).)

(Anm: Patients With Polyneuropathy Receive Long-Term Opioid Therapy, No Clear Benefit. CHICAGO -- May 23, 2017 -- Polyneuropathy is associated with an increased likelihood of long-term opioid therapy, but therapy does not appear to improve functional status, according to a study published online by JAMA Neurology. Polyneuropathy is a common painful condition, especially among older patients, which can result in functional impairment. (dgnews.docguide.com 23.5.2017).)

(Anm: Video Lecture 8: Metabolic Syndrome Lectures 1 (By Dr. Joachim Raese) (youtube.com).)

- Mitokondriell dysfunksjon og mitokondrie-dynamikk-Kreft-linken.

Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection.
Biochim Biophys Acta. 2017 Jan 16. pii: S0005-2728(17)30005-1. [Epub ahead of print]
Abstract Mitochondrial dysfunction is a hallmark of many diseases. The retrograde signaling initiated by dysfunctional mitochondria can bring about global changes in gene expression that alters cell morphology and function. Typically, this is attributed to disruption of important mitochondrial functions, such as ATP production, integration of metabolism, calcium homeostasis and regulation of apoptosis. Recent studies showed that in addition to these factors, mitochondrial dynamics might play an important role in stress signaling. Normal mitochondria are highly dynamic organelles whose size, shape and network are controlled by cell physiology. Defective mitochondrial dynamics play important roles in human diseases. Mitochondrial DNA defects and defective mitochondrial function have been reported in many cancers. Recent studies show that increased mitochondrial fission is a pro-tumorigenic phenotype. In this paper, we have explored the current understanding of the role of mitochondrial dynamics in pathologies. We present new data on mitochondrial dynamics and dysfunction to illustrate a causal link between mitochondrial DNA defects, excessive fission, mitochondrial retrograde signaling and cancer progression. This article is part of a Special Issue entitled Respiratory complex I, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. (…)

(Anm: Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice. Abstract. Exercise is known to have numerous beneficial effects. Recent studies indicate that exercise improves mitochondrial energetics not only in skeletal muscle but also in other tissues. (…) Our results suggest that exercise training in old mice can improve brain mitochondrial function through effects on electron transport chain function and mitochondrial dynamics without increasing mitochondrial biogenesis. Exp Gerontol. 2017 Jan 17. pii: S0531-5565(16)30505-8. [Epub ahead of print].)

(Anm: Exercise prevents cellular aging by boosting mitochondria (medicalnewstoday.com 8.3.2017).)

(Anm: Trening er best for å redusere tilbakefall av brystkreft. Exercise is best for reducing breast cancer recurrence. The research was conducted by Dr. Ellen Warner, of the Sunnybrook Health Sciences Centre in Canada, in collaboration with coauthor Dr. Julia Hamer, and the findings were published in the Canadian Medical Association Journal (CMAJ). (medicalnewstoday.com 22.2.2017).)

(Anm: Hyppigheten av kreft var (...) signifikant høyere i undergruppen antipsykotika (p = 0,05) etter enn før medisinering (J Child Adolesc Psychopharmacol. 2013 Apr;23(3):208-13).)

(Anm: Hva er det forskrivere og pasienter ikke vet om bivirkninger av antidepressiva? (What do prescribers and patients not know about the side effects of antidepressant drugs?) (medicalnewstoday.com 15.9.2016).)

(Anm: Forskere: Alvorlige bivirkninger, når antidepressiver droppes. Angst, depression og selvmordstanker er nogle af de bivirkninger, som tit forekommer, når man holder op med at tage antidepressiv medicin. Bivirkningerne kan i nogle tilfælde være langvarige og kroniske, viser et nyt studie. (videnskab.dk 16.3.2015).)

(Anm: Bruk av visse smertestillende midler (og antidepressiva (+ 31 %)) forbundet med økt risiko for drap (Use of certain painkillers linked with increased risk of homicide) Enkelte legemidler som påvirker sentralnervesystemet - som smertestillende og beroligende benzodiazepiner - er assosiert med økt risiko for å begå et drap, finner en ny studie publisert i tidsskriftet World Psychiatry. (medicalnewstoday.com 1.6.2015).)

(Anm: Psykiatriske patienter ender i private botilbud. Drab og vold har de seneste år fyldt debatten om de danske bosteder for patienter med psykiske problemer. (…) Psykiatriske patienter ender i private botilbud. (…) Mens Folketinget kæmper for en løsning på problemet med vold på offentlige bosteder, vælger flere kommuner at sende tunge patienter til private tilbud. (politiken.dk 18.3.2017.)

(Anm: Aggresjon knyttet til økt risiko for substansmisbruk. Aggression disorder linked to greater risk of substance abuse. (…) In the study, published in the Journal of Clinical Psychiatry, Emil Coccaro, MD, and colleagues analyzed data from more than 9,200 subjects in the National Comorbidity Survey, a national survey of mental health in the United States. They found that as the severity of aggressive behavior increased, so did levels of daily and weekly substance use. The findings suggest that a history of frequent, aggressive behavior is a risk factor for later substance abuse, and effective treatment of aggression could delay or even prevent substance abuse in young people. (medicalnewstoday.com 2.3.2017).)

(Anm: Halvparten av norske drap begått av rusede. (…) I 125 av drapene – eller 54 prosent – er det beskrevet i dommen at gjerningspersonen var påvirket av rusmidler under drapet. (nrk.no 13.12.2016).)

- En pasient på UNN døde av blodforgiftning som følge av et legemiddel mot psykiske lidelser, opplyser Statens helsetilsyn.

(Anm: En pasient på UNN døde av blodforgiftning som følge av et legemiddel mot psykiske lidelser, opplyser Statens helsetilsyn. (- Pasienten døde etter kort tid, og dødsårsaken var nøytropen sepsis (blodforgiftning), heter det i tilsynets rapport. (nrk.no 12.10.2016).)

(Anm: Systemic inflammatory response syndrome (SIRS) is an inflammatory state affecting the whole body, frequently a response of the immune system to infection. (en.wikipedia.org).)

(Anm: Sepsis. Definisjon: SIRS + påvist/mistenkt infeksjon (f. eks. positiv blodkultur). SIRS- kriteriene er: - Feber > 38 ºC eller hypotermi < 36 ºC - Puls > 90/minutt - Respirasjonsfrekvens > 20/minutt eller hypokapni med pCO2 < 4,3 kPa i blodgass - Leukocytose ≥ 12 × 109/l eller leukopeni < 4 × 109/l eller > 10 % umodne leukocytter. (helsebiblioteket.no - Metodebok for indremedisinere, 2012).)

(Anm: Rollen til mitokondriell dysfunksjon (mitokondriedysfunksjon) ved sepsis (blodforgiftning)-indusert multiorgansvikt. (The role of mitochondrial dysfunction in sepsis-induced multi-organ failure). (Virulence. 2013 Nov 1;5(1).)

- Diagnostisering av sepsis. Sepsis, også kjent som blodforgiftning, er kroppens hyperaktive respons på en infeksjon som kan føre til betennelse, vevskader, organsvikt etc.

(Anm: Diagnosing Sepsis. Sepsis, also known as blood poisoning, is the body’s hyperactive response to an infection that can lead to inflammation, tissue damage, organ failure etc. It is a very dangerous state in which the immune system stops fighting with the invading agents  and turns to itself. Around one-third of patients who are affected with sepsis die every year. (news-medical.net 7.9.2017).)

- Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon.

(Anm: Å anerkjenne sepsis som en global helseprioritet - En WHO- resolusjon. Recognizing Sepsis as a Global Health Priority — A WHO Resolution. “Some very important clinical issues, some of them affecting life and death, stay largely in a backwater which is inhabited by academics and professionals and enthusiasts, dealt with very well at the clinical and scientific level but not visible to the public, political leaders, leaders of healthcare systems... The public and political space is the space in which [sepsis] needs to be in order for things to change.” NEJM (June 28, 2017).)

(Anm: Sepsis – den dödliga sjukdomen som glöms bort. Trots att infektionssjukdomen sepsis förekommer oftare än de vanligaste formerna av cancer och att upp emot hälften som drabbas av den allvarligaste formen dör, så har många knappt hört talas om sjukdomen. Sepsis som är den medicinska termen på blodförgiftning, drabbar omkring 40 000 svenskar varje år. (netdoktor.se 7.6.2017).)

- Hurtigtest finner tegn på sepsis i en enkelt dråpe blod.

(Anm: Hurtigtest finner tegn på sepsis i en enkelt dråpe blod. (- Sepsis, en potensielt livstruende komplikasjon av en infeksjon, har den høyeste byrde mht. død og medisinske utgifter på sykehus over hele verden.) (- Quick test finds signs of sepsis in a single drop of blood. (…) Sepsis, a potentially life-threatening complication of an infection, has the highest burden of death and medical expenses in hospitals worldwide. (medicalnewstoday.com 5.7.2017).)

(Anm: Nye sepsiskriterier kan føre til forsinket behandling. (…) Sepsis er en svært alvorlig tilstand med høy morbiditet og mortalitet (2). Den totale insidensen er ukjent, men man regner med at sepsis er en av de viktigste årsakene til alvorlig, akutt sykdom på verdensbasis (1). (…) Sepsis har inntil nylig vært definert som mistenkt infeksjon med samtidig tilstedeværelse av to eller flere SIRS-kriterier (1). Endringer i hjertefrekvens, kroppstemperatur, respirasjonsfrekvens og leukocytter er kroppens tegn på inflammasjon, og de indikerer ikke nødvendigvis en livstruende, dysregulert vertsrespons på infeksjon. Tidsskr Nor Legeforen 2017; :609-10 (20.4.2017).)

(Anm: LEGENE FORSTO IKKE AT HAN VAR DØDSSYK: Stian (19) døde etter 18 timer på sykehus uten legetilsyn. (…) Helsetilsynet konkluderer med at sykehusets behandling var uforsvarlig. (…) Fikk ikke beskjed. (…) Fastlegen sendte med dem papirer som foreldrene leverte på Akuttmottaket ved Ahus, der sto det; «Diagnose: Obs sepsis».  (tv2.no 29.4.2017).)

(Anm: Svikt i behandlingen av akutt syk ung mann i akuttmottaket – brudd på helselovgivningen. (…) Pasienten ble lagt på observasjonsposten (Akutt 24) ved akuttmottaket frem til neste morgen. I løpet av tiden på observasjonsposten ble han ikke tilsett av lege. På morgenen var han betydelig verre og han fikk tegn på fullt utviklet blodforgiftning. Behandling med antibiotika ble iverksatt, men han døde kort tid etter som følge av meningokokksepsis og hjerneødem. (helsetilsynet.no 2.5.2017).)

(Anm: Sepsis; grunnleggende kliniske observasjoner. Sepsis= En systemisk inflammatorisk respons (SIRS) pga. en infeksjon Tre alvorlighetsgrader: 1) Sepsis (to eller flere symptomer på SIRS som følge av infeksjon) 2) Alvorlig sepsis (sepsis med akutt organdysfunksjon, hypoperfusjon eller hypotensjon) 3) Septisk sjokk (hypotensjon til tross for adekvat væsketerapi, samt forekomst av perfusjonsforstyrrelser og organdysfunksjon) (hnt.no 5.11.2013).)

- Alle bryt lova i behandling av blodforgifting. Pasientar med alvorleg blodforgifting (sepsis) blir undersøkt av lege for seint.

(Anm: Alle bryt lova i behandling av blodforgifting. Pasientar med alvorleg blodforgifting blir undersøkt av lege for seint. Helsetilsynet fann brot ved 24 akuttmottak over heile landet. – Svært alvorleg. – Dette er svært alvorleg, for det dreier seg om ein alvorleg infeksjonssjukdom som i verste fall kan medføra død dersom behandlinga ikkje blir igangsett til riktig tid, seier avdelingsdirektør i Helsetilsynet, Ragnar Hermstad. OVER EIN TIME: Pasientar som kjem inn med teikn på alvorleg infeksjonssjukdom som blodforgifting skal ifølge nasjonale retningslinjer få anitibiotikabehandling innan maks ein time. Alle dei 24 akuttmottaka hadde svikt på dette området. (nrk.no 16.6.2017).)

(Anm: Lege sier improvisert «kur» for sepsis har hatt bemerkelsesverdige resultater. (…) Spesialist i intensivbehandling Paul Marik sier at enkel behandling med infusjon av vitamin C og steroider har bemerkelsesverdig effekt på pasienter med potensielt dødelig tilstand. (independent.co.uk 24.3.2017).)

(Anm: Bivirkninger underrapporteres i videnskabelige tidsskrifter. (...) Mellem 43 og 100 procent af de bivirkninger, der, ifølge det ikke-publicerede materiale, er fundet ved de testede lægemidler, er ikke lagt frem i de videnskabelige artikler, viser Yoon Loke og kollegernes gennemgang. (videnskab.dk 5.10.2016).)

(Anm: Dødsfall på grunn av nøytropen sepsis (blodforgiftning) etter behandling med legemiddelet klozapin – uforsvarlig oppfølging – mangelfull samhandling og informasjon. (…)  Manglende informasjon fra spesialisthelsetjenesten og mangelfull samhandling mellom kommunehelsetjenesten, fastlegen, pasienten og pårørende bidro til hendelsen. Helseforetaket skal gjennomgå hendelsen for å redusere risikoen ved lignende tilfeller. (helsetilsynet.no 12.10.2016).)

(Anm: Examining mitochondrial DNA may help identify unknown ancestry that influences breast cancer risk (medicalnewstoday.com 23.9.2016).)

(Anm: The rise of mitochondria in medicine. Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential cellular functions beyond energy production, impacting most areas of cell biology and medicine. Mitochondrion. 2016 Jul 13. pii: S1567-7249(16)30098-8. [Epub ahead of print].)

- Teknologi fra hydrogenbiler kan forklare hvorfor livet oppstod. (- I cellene til mennesker og dyr blir energien produsert i det som kalles cellenes kraftverk, mitokondriene. De har et membran, som på mange måter tilsvarer membranet i brenselcellen.)

Teknologi fra hydrogenbiler kan forklare hvorfor livet oppstod
nrk.no 21.3.2014
Brenselceller i hydrogenbiler har noe til felles med levende celler. Undersjøiske varme kilder kan ha skapt naturlige brenselceller, forløperen til stoffskiftet i cellene.

Forskere fra USA og Storbritannia har vist hvordan brenselceller kan oppstå naturlig rundt undersjøiske varme kilder.

Disse brenselcellene kan ha skaffet energien som dyttet livet i gang på jorda for over tre milliarder år siden.

Brenselceller ligner levende celler
- Dette er en original måte å angripe problemet om livets opprinnelse på, sier Tom Kristensen fra Universitet i Oslo.

- Jeg har ingen motforestillinger mot at en slik forløper til stoffskiftet kan ha gitt den energien som må til for å bygge opp større molekyler som RNA og arvestoffet DNA i de første levende celler, fortsetter han. (...)

Elektrolyttmembran
Elektrolytten i en moderne brenselcelle virker på liknende måte. Den skiller hydrogengass fra tanken og oksygen fra lufta, oftest med en membran. Membranen lar de elektrisk ladede hydrogenatomene passere, slik at de kan møte oksygenet. (...)

Rotasjonsmotor i cellene
I cellene til mennesker og dyr blir energien produsert i det som kalles cellenes kraftverk, mitokondriene. De har et membran, som på mange måter tilsvarer membranet i brenselcellen

•Les også: Slik oppsto den moderne cellen

- Spenningsforskjellen over mitokondriets membran pumper ladede hydrogenatomer ut av mitokondriene. Så blir det ført inn igjen når det energibærende stoffet ATP produseres, forteller Tom Kristensen.

Han sammenligner denne mekanismen med en ørliten roterende motor. Slik sett er det enda en morsom sammenheng mellom brenselcellene i en bil og cellene i en levende kropp. (...)

(Anm: Three toxic gases meet in the mitochondria. Front. Physiol. 2015 (20 August 2015).)

(Anm: Feeling Worn Out? PGC1α to the Rescue for Dysfunctional Mitochondria in T Cell Exhaustion. Abstract In chronic viral infections and cancer, T cells acquire a functional state characterized by reduced effector functionality, termed exhaustion. In two related studies by Scharping et al. (2016) and Bengsch et al. (2016) in this issue of Immunity, dysfunctional mitochondria are identified as a key correlate of CD8+ T cell exhaustion. Immunity. 2016 Aug 16;45(2):233-235.)

(Anm: T cell type that promotes damaging immune response discovered. For the first time, researchers have identified a type of T cell that plays a key role in promoting the damaging autoimmune response that inflames and attacks the joints in rheumatoid arthritis. The discovery - made with technologies that help to analyze just a "handful of cells" - offers vital new clues to the biology of the disease and could lead to more powerful, targeted treatments. The study - led by Brigham and Women's Hospital (BWH), a teaching affiliate of Harvard Medical School in Boston, MA - is published in the journal Nature. (medicalnewstoday.com 2.2.2017).)

(Anm: Mitochondrial Cardiomyopathies. Mitochondria are found in all nucleated human cells and perform various essential functions, including the generation of cellular energy.  (…) Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain complexes subunits and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs, ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia. Front Cardiovasc Med. 2016 Jul 25;3:25. eCollection 2016.)

(Anm: Mitochondrial Complex V α Subunit Is Critical for Candida albicans Pathogenicity through Modulating Multiple Virulence Properties. Front. Microbiol., 23 February 2017.)

(Anm: Coenzyme Q10 partially restores pathological alterations in a macrophage model of Gaucher disease. (…) CONCLUSION: These data suggest that targeting mitochondria function and oxidative stress by CoQ can ameliorate the pathological phenotype of Gaucher cells. Chemically-induced Gaucher macrophages provide cellular models that can be used to investigate disease pathogenesis and explore new therapeutics for GD. Orphanet J Rare Dis. 2017 Feb 6;12(1):23.)

(Anm: Study suggests new therapy for Gaucher disease. Scientists propose in Nature blocking a molecule that drives inflammation and organ damage in Gaucher and maybe other lysosomal storage diseases as a possible treatment with fewer risks and lower costs than current therapies. (…) "Current enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of malignancies and Parkinson's disease," says Manoj Pandey, PhD, study first author and a scientist in the Division of Human Genetics at Cincinnati Children's. "We suggest that targeting a molecule called C5aR1 may serve as a viable treatment option for patients with Gaucher disease and possibly other LSDs." (medicalnewstoday.com 24.2.2017).)

(Anm: Magnesium hjelper mot depresjon. (nhi.no 26.7.2017).)

(Anm: High magnesium prevents matrix vesicle-mediated mineralization in human bone marrow-derived mesenchymal stem cells via mitochondrial pathway and autophagy. (…) Our results contribute to the understanding of the role of magnesium homeostasis in osteoporosis and the design of magnesium alloys. Cell Biol Int. 2017 Oct 10.)

(Anm: Magnesium can be key to treat a range of health issues. Magnesium has been hailed as the ‘super supplement’ to give us the boost we need this winter, says experts on BBC Radio Two’s Breakfast Show with Chris Evans. (news-medical.net 23.10.2017).)

(Anm: Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. (…) Conclusions Daily supplementation with 248 mg of elemental magnesium as four 500 mg tablets of magnesium chloride per day leads to a significant decrease in depression and anxiety symptoms regardless of age, gender, baseline severity of depression, or use of antidepressant medications. While the cross over design of this trial is robust in controlling for internal biases, it would be reassuring to see the results replicated in larger clinical trials that test long term efficacy and provide additional data on subgroups. However, this efficacy trial showed magnesium supplements may be a fast, safe, and easily accessible alternative, or adjunct, to starting or increasing the dose of antidepressant medications. PLoS ONE 12(6): e0180067.)

(Anm: Magnesium hjelper mot depresjon. (nhi.no 26.7.2017).)

(Anm: All About Magnesium (webmd.com 22.11.2017).)

(Anm: Magnesium can be key to treat a range of health issues. Magnesium has been hailed as the ‘super supplement’ to give us the boost we need this winter, says experts on BBC Radio Two’s Breakfast Show with Chris Evans. (news-medical.net 23.10.2017).)

(Anm: High magnesium prevents matrix vesicle-mediated mineralization in human bone marrow-derived mesenchymal stem cells via mitochondrial pathway and autophagy. (…) Our results contribute to the understanding of the role of magnesium homeostasis in osteoporosis and the design of magnesium alloys. Cell Biol Int. 2017 Oct 10.)

(Anm: Too much or too little magnesium can raise dementia risk. A new study published in the journal Neurology suggests that both very high and very low levels of magnesium may put people at risk of developing dementia. The first author of the study is Dr. Brenda Kieboom, of the Erasmus University Medical Center in Rotterdam, the Netherlands. (…) Low serum magnesium levels were defined as equal to or lower than 0.79 millimoles per liter, and high magnesium levels were defined as equal to or above 0.90 millimoles per liter. Magnesium levels were divided into quintiles, or fifths; the researchers examined the association between dementia and serum magnesium using the third quintile as a reference. (medicalnewstoday.com 21.9.2017).)

(Anm: Magnesium, terapi. Magnesium er et viktig mineral i kroppen. Hos noen personer kan det oppstå situasjoner med magnesiummangel. (…) Magnesium er det fjerde hyppigst forekommende mineralet i kroppen1. Det er fordelt med ca. halvparten i skjelette