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A Little Poisoning Along the Road to ME/CFS
Looking at my symptoms, many of which are far less these days and some are gone, it would be easy to figure that I'd just been dealing with some heavy-duty menopausal issues.
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XMRV might, just might, explain OI, as well as NMDA activation

Discussion in 'XMRV Research and Replication Studies' started by alex3619, Jan 24, 2011.

  1. alex3619

    alex3619 Senior Member

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    Logan, Queensland, Australia
    Hi everyone, I just wanted to alert people to the following:


    The Journal of Immunology, 1999, 162: 4998-5002.
    Copyright 1999 by The American Association of Immunologists
    Glutamate Augments Retrovirus-Induced Immunodeficiency Through Chronic Stimulation of the Hypothalamic-Pituitary- Adrenal Axis
    Michael Graham Espey1 and Anthony S. Basile
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892

    Abstract
    The mechanisms for activating the hypothalamic-pituitary-adrenal (HPA) axis and the roles glucocorticoids play in the pathogenesis of chronic infectious disease are largely undefined. Using the LP-BM5 model of retrovirus-induced immunodeficiency, we found alterations in HPA axis function, manifested as an increase in circulating levels of adrenocorticotropic hormone and corticosterone, beginning after only 3 mo of infection. These changes occurred contemporaneously with a shift in the profile of circulating cytokines from a Th1-dominant (IFN-γ) to Th2-dominant (IL-4, IL-10) phenotype. No significant changes in either circulating IL-1, IL-6, or TNF-α levels were observed in infected mice. Administering the N-methyl-D-aspartate receptor antagonist MK-801 to infected mice normalized plasma adrenocorticotropic hormone and corticosterone levels, indicating that glutamate was a major activator of the HPA axis. Moreover, MK-801 treatment of late-stage mice also reversed the type 1 to type 2 cytokine shift to a degree comparable or superior to treatment with the glucocorticoid receptor antagonist RU-486. These findings indicate that HPA axis activation during LP-BM5 retrovirus infection is mediated by the chronic hyperactivation of glutamatergic pathways in the hypothalamus. Through this mechanism, the degree of peripheral immunodeficiency observed in the late-stage disease is profoundly augmented.

    http://www.jimmunol.org/content/162/8/4998.long

    Thanks go to garcia for bringing this to my attention.

    This retrovirus in mice induces low nitric oxide status in some parts of the brain, which worsens over time. Low nitric oxide levels mean decreased vasodilation. It is not inconceivable that this could trigger a switch in the brain to try to increase blood flow through vasodilation promoting strategies - one of the consequences of this could be OI. There are other implications too, but since this is highly speculative I thought I would keep it simple.

    Otherwise, this could show that a retrovirus can be a primary inducer of the no/onoo cycle in the body periphery, though maybe less so in the brain (although that point is debatable).

    In any case it provides another potential path to treating ME/CFS.

    Bye,
    Alex
     
  2. WillowJ

    WillowJ Senior Member

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    very interesting, Alex.

    Same Th shift, right?

    But opposite cortisol status. And no change in IL-6, or TNF-α. Then again, it's in mice. :D
     
  3. acer2000

    acer2000 Senior Member

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    Very interesting... makes a lot of sense if you think about it.
     
  4. natasa778

    natasa778 Senior Member

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    another one on glutamate:

    Brain Res. 1999 Aug 21;839(1):153-63.
    Increased blood-brain barrier permeability in LP-BM5 infected mice is mediated by neuroexcitatory mechanisms.

    Kustova Y, Grinberg A, Basile AS.Laboratory of Bio-Organic Chemistry, Building 8, Room 1A15, NIDDK, NICHD, National Institutes of Health, Bethesda, MD 20892-0008, USA.

    Serum protein levels in LP-BM5 infected mouse brains were investigated to gain insight into the contribution of blood-brain barrier (BBB) patency to the pathogenesis of retroviral encephalopathy. Evans blue uptake by the forebrain and cerebellum was significantly increased between 8-12 weeks post inoculation. Immunohistochemistry revealed foci of albumin, transferrin, alpha(2)-macroglobulin and IgG transudation around blood vessels particularly in the cerebral cortex and cerebellar vermis. These leaks were often associated with astrocytosis and apoptotic cells. Unlike the other serum proteins, IgG immunoreactivity extended from the circumventricular organs and disseminated throughout the brain parenchyma, accumulating on the plasma membranes of hippocampal and cortical neurons. Consistent with the chronic elevation of free glutamate levels in LP-BM5 infected mice, the increase in Evans blue uptake into the forebrain was completely reversed following dizocilpine administration. Thus, the chronic increase in free glutamate levels in LP-BM5 infected mouse brain contributes to BBB disruption. Furthermore, the CNS accumulation of serum proteins, particularly IgG, observed in these mice may increase osmotic load, impair neuronal function, and cause white matter pallor. Administration of NMDA receptor antagonists may prove useful in managing BBB permeability in those neuropathologies, such as HIV-associated dementia/cognitive/motor complex, having a glutamatergic component.
     
  5. natasa778

    natasa778 Senior Member

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    and another one on OI

    J Acquir Immune Defic Syndr. 1991;4(1):31-3.
    Orthostatic hypotension in human immunodeficiency virus infection may be the result of generalized autonomic nervous system dysfunction.

    Cohen JA, Miller L, Polish L. Department of Neurology, University of Colorado Health Sciences Center, Denver.

    We used an autonomic nervous system (ANS) testing battery to determine if generalized ANS dysfunction was present in five human immunodeficiency virus-positive (HIV+) patients presenting with severe orthostatic hypotension (OH). All five patients had abnormal ANS testing, which demonstrated both sympathetic and parasympathetic defects, i.e., generalized ANS dysfunction. Treatment with fludrocortisone effectively reversed the OH in four of the five patients. The OH was transient in these four patients. We believe it is important to recognize that OH may be the result of generalized ANS dysfunction in HIV-positive patients and that it can be effectively treated.


    http://en.wikipedia.org/wiki/Fludrocortisone
     
  6. Sasha

    Sasha Fine, thank you

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    This looks interesting - I'm having a discussion with my GP next week about my (currently untreated) OI. I'm curious about the statement that OI was transient but reversible by fludrocortisone in those four patients - does that suggest that their treatment cured it and they could stop taking fludrocortisone?

    I'd like to see the full paper but can't find it - does anyone have a link to the full text?
     
  7. Francelle

    Francelle Senior Member

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    ...or do they mean that OI was only transient ONCE Fludrocortisone treatment was started? It's a bit unclear!
     
  8. Sasha

    Sasha Fine, thank you

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    Yes, it's odd - I am scared of being put on a drug like fludrocortisone because of its potential side effects and would love to think that it might actually fix the problem at source rather than just be a crutch but that isn't how I thought it worked.
     
  9. Sasha

    Sasha Fine, thank you

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    I've just found another organisation's summary (here) of the report which gives a different impression of what was going on:

     
  10. SilverbladeTE

    SilverbladeTE Senior Member

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    oooh, this is interesting! :)
    thanks for posting that
     
  11. bertiedog

    bertiedog Senior Member

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    Just wanted to say that just 1/2 of 0.5 mcg tablet of fludrocortisone plus 20 mg propananol (betablocker) has virtually eliminated my POTS. When I stopped the Fludro for a few days I couldn't even sit up, it was dreadful. I don't get any side effects from either drug but they have made such a difference. I am still aware of a slight strain when standing but it is nothing like it used to be which was completely disabling. Fludro is well worth a try and is very effective even at very low doses.
     
  12. xchocoholic

    xchocoholic Senior Member

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    Thanks for posting this. My CFS/ME/FM started as the result of a virus ... I found this info on Florinef interesting. It seems that according to my labs (low on cortisol and have adrenal fatigue) and the fact that I can't retain sodium or keep my BP up without it, this might just work for me.

    Oh and for some reason, once when I stopped taking Virastop everyday, my OI got so bad that I could barely stand up. I take it every day now but may increase it ... tc ... x

    http://www.drugs.com/pro/fludrocortisone.html

     
  13. August59

    August59 Daughters High School Graduation

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    xchocoholic - Have you ever had your serum levels for "aldosterone" checked? It is the hormone that fludrocortisone replaces and is manufactureded by the adrenal cortex, just as cortisol is. It seems odd that you don't hear fludrocortisone mentioned as much as cortisol with adrenal fatigue. I've seen where some people are supplementing with Florinef and some are using a compounded bio-identical aldosterone from Canada. It is also being used in the treatment of hearing loss which it apparently helps by altering the sodium/potassium levels in the inner ear.
    http://hearinglosshelp.com/weblog/aldosterone%E2%80%94a-new-treatment-for-hearing-loss-and-menieres-disease.php
     

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