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Can you help? Working on mitochondria page!

Discussion in 'Advocacy Projects' started by JaimeS, Jul 18, 2016.

  1. JaimeS

    JaimeS Senior Member

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    Greetings! We discussed on the thread about MEpedia that we would do a 'meet up and edit' of a single page to improve its quality. If this works out, I would love to do it once a week.

    Here is the page on mitochondria:


    http://me-pedia.org/wiki/Mitochondria

    Right away I can see some edits that can be made in the first section in terms of adding more details, but where I think we can really work together is in gathering studies that discuss mitochondrial dysfunction in ME, ME/CFS, or CFS, always clarifying by what criteria patients were selected.

    These are the 'notable studies' listed:
    And here are the citations of mitochondrial studies discussed, so we don't look up studies that are already mentioned:
    1. Behan, WMH; More, IAR; Behan, PO (1991), "Mitochondrial abnormalities in the postviral fatigue syndrome", Acta Neuropathologica 83 (1): 61–65, PMID 1792865
    2. Vecchiet, L; Montanari, G; Pizzigallo, E; et al. (19 Apr 1996), "Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome", Neuroscience Letters 208 (2): 117–120, PMID 8859904
    3. Zhang, C; Baumer, A; Mackay, IR; et al. (Apr 1995), "Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome", Human Molecular Genetics 4 (4): 751–754, PMID 7633428
    4. Booth, NE; Myhill, S; McLaren-Howard, J (2012), "Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)", Int J Clin Exp Med 5 (3): 208–220, PMID 22837795
    5. Myhill, S; Booth, NE; McLaren-Howard, J (15 Jan 2009), "Chronic fatigue syndrome and mitochondrial dysfunction", Int J Clin Exp Med 2 (1): 1–16, PMID 19436827
    6. Billing-Ross, Paul; Germain, Arnaud; Ye, Kaixiong; et al. (2016), "Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome", Journal of Translational Medicine 14: 19, ISSN 1479-5876, PMID 26791940, doi:10.1186/s12967-016-0771-6, lay summary
    7. Galán, Fernando; de Lavera, Isabel; Cotán, David; Sánchez-Alcázar, José A (24 Sep 2015), "Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome", J Investig Med High Impact Case Rep 3 (3), PMID 26904705, doi:10.1177/2324709615607908
    8. Boles, RG; Zaki, EA; Kerr, JR; et al. (Jul 2015), "Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant?", Mitochondrion 23: 1-6, PMID 25934187, doi:10.1016/j.mito.2015.04.005
    9. Health Rising Forum (19 Mar 2016), End ME/CFS Severe Patient Study Turns to the Mitochondria
      Craig, Courtney (Nov 2015), "Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets", Medical Hypotheses 85 (5): 690-693, PMID 26315446, doi:10.1016/j.mehy.2015.08.013

    Here is a link to PubMed to search for articles: http://www.ncbi.nlm.nih.gov/pubmed

    If there are any suggestions about how to best coordinate, I would love to hear them! I'm thinking we have one person be the editor, and others giving them information that summarizes studies so that they can add this information either now or later on.

    Phoenix Rising often has discussions of a study, so it can be valuable to check out what people here have said to help you in determining the study's quality.

    Finally, please limit your conversations to this page and how it should be altered!
     
    Helen, L'engle, M Paine and 10 others like this.
  2. JaimeS

    JaimeS Senior Member

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    I've got the following from work I've done previously:
    • Disordered glycolysis (Armstrong, McGregor, Lewis, Butt, & Gooley, 2015; Vermeulen, Kurk, Visser, Sluiter, & Scholte, 2010)
    • Coenzyme Q-10 deficiency correlated to cognitive dysfunction (Maes, et al., 2009)
    • Abnormality in the structure of mitochondria, including mitochondrial degeneration, atrophy of type II fibers, and fusion and branching of mitochondrial cristae (Morris & Maes, 2013)
    • Preliminary evidence of disordered citric acid cycle (Davis, 2016)
    • Mito dysfunction implicated in PEM (Morris & Maes, 2014)
    Morris and Maes often do reviews, so I'm going to have to double-check that they weren't simply citing someone else.

    -J

    Ref:

    Armstrong, C.W., McGregor, N.R., Lewis, D.P., Butt, H.L., & Gooley, P.R. (2015, December). Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients. Metabolomics, 11(6): 1626-1639.

    Maes, M., Mihaylova, I., Kubera, M., Uytterhoeven, M., Vrydags, N., & Bosmans, E. (2009). Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mort. Neuro Endocrinol Lett. 2009;30(4):470-6., 30(4), 470-476. Retrieved July 3, 2016, from http://www.ncbi.nlm.nih.gov/pubmed/20010505/

    Morris, G., & Maes, M. (2013). Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. BMC Medicine, 11, 205. http://doi.org/10.1186/1741-7015-11-205

    Morris, G., & Maes, M. (2014). Mitochondrial dysfunctions in Myalgic Encephalomyelitis / chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative, and nitrosative stress pathways [Electronic version]. Metab Brain Dis, 29(19), 19-36.

    Vermeulen, R. C., Kurk, R. M., Visser, F. C., Sluiter, W., & Scholte, H. R. (2010). Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. Journal of Translational Medicine, 8, 93. http://doi.org/10.1186/1479-5876-8-93
     
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  3. olliec

    olliec

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    I'm really keen to hear from others how this page can be improved and there are certainly many studies that have not yet been added. The page has had over 4,000 page views already (including those editing it) so important we improve it, especially in light of the incoming Naviaux studies. I've just added a royalty-free image to the page, a diagram of a mitochondrion.
     
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  4. Silencio

    Silencio Senior Member

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    This is a great page.. I don't feel like I know enough science stuff to contribute much! Although I think another way to contribute is to look at the links off this page, which can also be further fleshed out. So I'll do some googling for those too.
     
    Jennifer J likes this.
  5. Silencio

    Silencio Senior Member

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    Under ME/CFS research. Can editor add after the big data study "led by Dr. Ron Davis at the Open medicine institute" and link to those pages?
     
  6. JaimeS

    JaimeS Senior Member

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    I just added that parasites, too, can alter energy metabolism. I'm sure I could find something saying bacteria as well. It's not just viruses!

    And yes, I initially had something about Ron's preliminary data...
     
  7. Silencio

    Silencio Senior Member

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    Ok I learned how to make a link work! But it made a page for dr Ron Davis, instead if linking to the page for Ronald Davis. How do I rename the Ronald Davis page to be Dr. Ronald Davis?
     
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  8. olliec

    olliec

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    I've tweaked the Davis and OMF links to point to the existing pages for both and added a source to support a statement that a second metabolic study is underway.
     
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  9. JaimeS

    JaimeS Senior Member

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    I might keep it as is -- probably other pages already link to his name as Ronald Davis.
     
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  10. JaimeS

    JaimeS Senior Member

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    One of the things we could really use help with is tracking down some of the references in a Morris & Maes review article:

    Morris, G., & Maes, M. (2014). Mitochondrial dysfunctions in Myalgic Encephalomyelitis / chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative, and nitrosative stress pathways [Electronic version]. Metab Brain Dis, 29(19), 19-36.

    That one!:p

    If someone is willing to take part of that on, please PM me. :)
     
  11. JaimeS

    JaimeS Senior Member

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    Myhill, S., Booth, N. E., & McLaren-Howard, J. (2013). Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit. International Journal of Clinical and Experimental Medicine, 6(1), 1–15.

    Says that:

    We concluded from this audit and a re-analysis of a previous audit of a cohort of 61 patients in the age range of 18-65 years (Cohort 1) and of 53 controls [4], the following features:

    1) All patients of both Cohort 1 (n=61) and Cohort 2 (n=138) had measurable mitochondrial dysfunction.

    2) The degree of mitochondrial dysfunction correlates with illness severity, as demonstrated in our analysis of Cohort 1 [4], and comparison with Cohort 2 [1].

    3) Patients divide into two main groups according to whether oxidative phosphorylation is not already blocked, Group A (NO BLOCK), or is already partially blocked, Group B (BLOCKED or ‘HI Blk’). We further sub-divide Group A into A1 and A2.

    4) For patients in Group A, where there is no prior blocking of oxidative phosphorylation or the reactions leading up to it, cellular metabolism uses increased glycolysis to partially compensate for the dysfunction.

    5) For patients in Group B, where there is partial blocking of oxidative phosphorylation or a reaction leading up to it, there is an alternative route to increased glycolysis which the cells use to partially compensate for the blocking. This route is most likely the adenylate kinase reaction in which two molecules of ADP combine to make one of ATP and one of AMP (Adenosine monophosphate).

    6) Tests on isolated mitochondria (parameters TL OUT and TL IN) show that some of the blocking is due to partial blockages of the translocator proteins, either on the mitochondrial matrix side (TL IN) or the outer membrane (and cytosol) side (TL OUT).

    7) Group A1: ‘no HIs’ patients appear not to suffer from substrate deficiencies in the processes leading to ATP delivery, while those in Group A2: ‘HI TL IN’ have substrate deficiencies. The latter conclusion comes from the measured super-normal values of the parameter TL IN.

    8) Comparisons with some published exercise studies, which also indicate two groups, suggest that the dysfunction that we observe in neutrophils may also occur in other cells such as those of skeletal muscle [1].

    9) The degree of dysfunction in neutrophils correlates with auxiliary measurements of cell-free DNA in blood plasma which indicate levels of tissue damage up to 3.5 times the upper level of the normal reference range. This is clearly demonstrated in figure 6 of our previous paper on the pathophysiology [1]. The cell-free DNA is a measure of non-apoptotic tissue breakdown [5].

    10) The major immediate causes of the mitochondrial dysfunction are: a) lack of substrate, and b) partial blocking of the translocator protein sites and/or oxidative phosphorylation and the reactions leading up to it (link reaction and Krebs cycle).


    Note -- this is based on an ATP test that the researchers are pretty invested in. I'd like a second opinion as to its quality.

    [Edit: yeah, I'm going to pick through this one, I'll get back to you guys.]

    [Edit: phrases like "eating the evolutionary correct stone-age diet" are worrisome. Can anyone else weigh in?]

    -J
     
    Last edited: Jul 18, 2016
  12. JaimeS

    JaimeS Senior Member

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    BTW gotta go, but I'll put in another hour later on in the day. :D

    [I'm back! Meeting cancelled. :) ]
     
    Last edited: Jul 18, 2016
  13. Silencio

    Silencio Senior Member

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    Me too.. Head spinning! Good job team
     
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  14. JaimeS

    JaimeS Senior Member

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    ....just got up to make coffee.

    ....coffee sitting under Keurig, already brewed. :confused:

    Some days I hate having ME more than others. :cry:
     
  15. olliec

    olliec

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    @Silencio The usual format for page names is like "Ronald Davis", so if you search for them and an existing page is there, you know what to link to. He had one already but under Ronald not Ron.

    I've added references to the page for all the studies Jaime mentioned. What other studies are missing?
     
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  16. JaimeS

    JaimeS Senior Member

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    I've fallen down the rabbit hole!

    The following provide evidence that bacteria also affect host mitochondrial function, along with viruses and parasites.

    This one looks especially suitable:
    http://www.ncbi.nlm.nih.gov/pubmed/20818415 <--- Cited! :D

    From that article, above:

    Oooooh. :D

    But there are lots of others to look at:

    Hep C (viral)
    http://www.ncbi.nlm.nih.gov/pubmed/27010100 <---Cited! :D

    E Coli
    http://www.ncbi.nlm.nih.gov/pubmed/15533930
    http://www.ncbi.nlm.nih.gov/pubmed/20618683 <---Cited! :D
    http://www.ncbi.nlm.nih.gov/pubmed/21947777

    Toxoplasmosa
    http://www.ncbi.nlm.nih.gov/pubmed/20618683 <---- Cited! :D
     
    Last edited: Jul 18, 2016
    Silencio likes this.
  17. olliec

    olliec

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  18. JaimeS

    JaimeS Senior Member

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    Huh! I know that author...

    Meeus M, Goubert D, De Backer F, Struyf F, Hermans L, Coppieters I, De Wandele I, Da Silva H, Calders P. (2013, October). Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review. Semin Arthritis Rheum., 43(2):279-87. doi: 10.1016/j.semarthrit.2013.03.004. Epub 2013 Jul 6. Review. PubMed PMID: 23838093.

    Nijs, J., Meeus, M., & De Meirleir, K. (2006, August). Chronic musculoskeletal pain in chronic fatigue syndrome: Recent developments and therapeutic implications. Elsevier Manual Therapy, 11(3), 187-191. doi:10.1016/j.math.2006.03.008

    Nijs, J., Nees, A., Paul, L., De Kooning, M., Ickmans, K., Meeus, M., & Van Oosterwijck, J. (2014). Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: A systematic literature review. Exerc Immunol Rev., 20, 94-116. Retrieved June 30, 2016, from http://www.medizin.uni-tuebingen.de/transfusionsmedizin/institut/eir/content/2014/94/article.pdf

    No earthly idea why I've never seen the one you reference above! <3 Very cool!

    -J
     
  19. JaimeS

    JaimeS Senior Member

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    Found the article -- if anyone wants or needs, PM me and I will send it.
     
  20. JaimeS

    JaimeS Senior Member

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    I'm finishing up in about a half an hour, but I wanted to say the following for next time:

    I discussed hepatitis C as one of the infectious agents that can cause or contribute to mitochondrial dysfunction, and several other pages on MEpedia mention hep C; but there is not a page on hep C on the wiki as of yet.

    Here are several sources that discuss hep C in reference to ME, CFS, or ME/CFS:

    Obv we will need more general info on hep C as well, but I wanted to save these references. Also, this would be a great project for someone to take on as an individual, because it's a blank slate.

    [I added this as a stub, but obv. needs more information!]
     
    Last edited: Jul 18, 2016

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