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In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

Discussion in 'Latest ME/CFS Research' started by A.B., Apr 8, 2015.

  1. Sushi

    Sushi Moderation Resource Albuquerque

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    I am wondering about dosing. I teaspoonful does nothing for me in a crash--even with carnitine and C0-Q-10. Have you tried higher doses?

    And, a big welcome to the forum! :thumbsup:
    Sushi
     
  2. Mij

    Mij Senior Member

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    @Sushi have you tried a tsp with black coffee? A small amount of coffee, of course. I tried d-ribose a few yrs ago but didn't feel any different. I'm still considering trying it with a small amount of black coffee as rec'd by Dr.Myhill.
     
    Last edited: May 2, 2015
  3. Sushi

    Sushi Moderation Resource Albuquerque

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    Yes, I had read Dr. Myhill's recommendation on that but it didn't seem to make any difference.

    Sushi
     
  4. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    You mentioned that the mitochondrial dysfunction probably is secondary, I also find this the most plausible scenario. Do you have any gist of how antibodies may mess it up? In Norway it seems 2/3 of the patiens have an autoimmune/immune dysfunction type of cfs, and PEM disappears when treated with Rituximab. This is also the case to some extent with IVIG, because IVIG reduces the amount of self-antibodies.

    I got sick after a football practice after feeling bad for some months. I guess my energy got all used up!
     
  5. corni

    corni

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    I think it is most likely that the primary cause is somewhere in the immunological response to viruses (like EBV). The following article shows that there seems to be something wrong with the memory B cells for EBV specifically (also from Germany :) , though generally we are quite behind in CFS research):
    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085387
    The immunological response to viruses (INF, TNF and RNase L, Elastase, etc.), which is triggered again and again, then probably causes an impairment of mitochondria (http://circres.ahajournals.org/content/71/5/1268) and an increase of the apoptosis rate (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706398/). This could lead to a vicious cycle which could be maintained even if the virus trigger is not present anymore. But it could also be that there are additional dysfunctions in the response to viruses as indicated by the accumulation of low weight RNase L, usually found in CFS patients.
     
    Last edited: May 3, 2015
    Battery Muncher, MEMum, Sushi and 3 others like this.
  6. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    But does it have to be due to an active infection? I think you are right for the majority of ME/CFS-patients, but there is a subclass without a clear trigger, like me. What viruses can be active but without any sypmtoms?
     
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  7. A.B.

    A.B. Senior Member

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    These cases might be primarily autoimmune.
     
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  8. Wally

    Wally Senior Member

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    @corni,

    Thank you so much for coming to the Forum and sharing your ideas.

    I am not a scientist just a lawyer always searching for answers.

    EBV is the virus that shows up for me as the trouble maker. I have also had some remarkable success using Famciclivor to treat (at least temporarily) many of my symptoms with the most significant being PEM.

    It takes exactly 10 weeks to the day for the dosing with this anti-viral to work for me. I have been able to respond to this drug twice. Currently I am on the second trial with this anti-viral. I take very large doses of the drug and I must take it around the clock on six hour dosing schedules (bioavailabilty of the the drug is approx. 6 hours). The light switch that goes on in my body at 10 weeks is truly remarkable. My energy levels go from 10% to 90% at that 10 week mark. It is almost frightening for those around me to watch. Unfortunately it is difficult to have self-control and not keep my foot on the gas pedal enjoying a reprieve from having all my energy stolen from my body.

    Wally
     
  9. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    A simple but very plausible answer. Thanks! Ive been thinking the same A.B! My only symptoms are debilitating physical and mental fatigue, orthostatic intolerance + fasciculations. So - doesnt really fit the picture with regards to immunulogical responses to viruses, gone haywire.. Im expecting immunoglobulins or rituximab to help my condition..
     
  10. corni

    corni

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    An EBV infection can be as ordinary as a normal flu. In my case, I only knew 3 month later that it was EBV and not just a flu. But there are EBV-unrelated cases, too. Wouldn't it be too simple otherwise? :p
     
  11. Murph

    Murph :)

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    Cort referenced this paper (pdf) in his write up of the recent Tomas Newton paper on cellular bioenergetics.

    I'd never heard of it before. It's a computer simulation "in silico" of what might be happening inside the cells if ATP levels are deficient.

    I found this graph especially evocative: We are the red lines and it takes us an especially long time to recover from moderate exercise. (The trend in the model is even more extreme in me. I can recover from a 30 second burst in under 32 hours, but a repeated 1h exercise regime would probably be more than 60 hours to bounce back from). Screen Shot 2017-11-13 at 12.19.53 PM.png
    (nb this is not experimental data. They set up their model to try to show what kinds of prior conditions would produce cfs-type PEM. If the outputs match reality more or less, we are encouraged to believe the prior conditions that form their assumptions may be correct.)

    "By simulating a reduced mitochondrial ATP synthesis rate for CFS patients the model leads to predictions about the duration of recovery after exertion and demonstrates that long moderate exercises are more exhaustive than short intensive exercises contrary to the results for healthy controls. Furthermore, it was shown that ATP reaches critically low concentrations during high intensity ex- ercise in CFS simulations and the acidification in muscle tissue increases compared to control simulations."

    I'm increasingly taken by the idea of an ATP shortfall. I remain open-minded about how this might happen, whether it is mitochondrial, glycolytic or due to leakage.

    Perhaps loss of ATP via purinergic signalling might be practically equivalent to reduced mitochondrial synthesis. Either way you end up with less ATP to use. @corni what do you think about this?
     
    Last edited: Nov 12, 2017

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