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Significance of XMRV Cortisol Receptors

Discussion in 'XMRV Research and Replication Studies' started by Wayne, Oct 22, 2009.

  1. Jimk

    Jimk

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    Prednisone may eventually be part of the treatment for XMVR

    I recall both Mikovits and Peterson saying in interviews about XMVR that since it replicates very slowly it is therefore not a good candidate for some of the HIV drugs that target parts of the retrovirus replication cycle... but that cortisone could possibly be used to stimulate XMVR replication and make it susceptible to these drugs. Mikovits also used this feature of the virus to say how well it matches the symptom pattern we seen in CFS/ME: stress often is a trigger for worsening condition.

    Of course, there is also evidence that cortisol levels not only suppress immune function, but stimulate replication through other mechanisms of various bacteria such as Chlamydia pneumoniae. I'm pretty sure this is true of some other bacteria as well. Some of the speculation in this thread that the common finding in CFS/ME/Fibro of low cortisol levels as a protective response by the body to a cortisol stimulated virus like XMVR could be similar with other invading organisms, and we all know how multiple occult infections are common in our population.

    As to the "what is a monkey wrench?" question earlier: monkeys, although small, are very strong, and can yank your arm producing an injury commonly referred to as a monkey wrench. This was obviously a metaphor by the poster (or is it an analogy, I get these confused) to the small size but powerful effect of a virus like XMVR.;)
  2. Eric Johnson from I&I

    Eric Johnson from I&I Senior Member

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    Athene,
    I'd say the research picture on autoantibodies in CFS is murky. However my judgment is not confident because I havent gotten up close with this issue.

    In addition to the below, see also
    http://www.biomedcentral.com/content/pdf/1740-2557-2-5.pdf

    And (note authorship)
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906448/


    ====================
    Here's a free PDF of a 1997 paper out of Scripps that found low-titer
    anti-nuclear antibodies (and possibly other autoantibodies) in one
    half of CFS cases. The titers are a lot lower than the typical
    autoantibody titers of lupus, etc.

    http://www.jci.org/articles/view/118990/pdf


    The abstract of a 2007 Japanese language article (17561698) refers to
    the work

    "One group in the USA reported that 'nuclear envelope staining
    pattern' was found in more than 50% of the patients with CFS. This
    results, however, have not been confirmed by any other research groups."

    ...possibly referring also to this negative autoantibody study: 12165094 .

    Another positive finding on this topic is 11477286; free text of which
    is found at
    http://rheumatology.oxfordjournals.org/cgi/content/full/40/7/806.
    =====================
  3. Eric Johnson from I&I

    Eric Johnson from I&I Senior Member

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    Them lil numbers are pubmed IDs that refer to a specific paper. Hit up pubmed.com and put those numbers in the search blank, viola.
  4. Sing

    Sing Senior Member

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    XMRV and Cortisol

    Dear Athene,

    I've used Cortef ( one quarter the strength of prednisone) 5 mg twice a day for 10 years to help with my low cortisol level, very low energy and flu like symptoms. It basically helps and balances my system--no complaints. I recommend Dr. William Mc Jeffries book, Safe Uses of Cortisol, if you haven't read it.

    I absolutely agree, however, that too much cortisol, whether made by our own bodies due to stress, or via too much prednisone, etc. is seriously harmful. I expect it could be feeding XMRV too.

    But I have another hypothesis about XMRV and cortisol than I have mostly read here. That is that XMRV somehow sucks it out of our blood so it can use it to reproduce, then we are left, functionally speaking, with hypoadrenia. Maybe the adrenal glands themselves are still fine and the XMRV is getting a lot of the cortisol like a parasite.

    Or maybe XMRV affects the HPA axis to underperform some other way.

    But, "for my money"/body, I believe in having a normal amount of cortisol on board, so I need to take this much extra.

    Cecelia
  5. Samuel

    Samuel Bedbound with NO DOCTOR

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    I am trying various amounts of hydrocortisone, 10-20mg/d in several doses. Concerned about retroviral replication.

    It definitely helps, short term. Sometimes, at least. Stress definitely is bad, short term.

    THEREFORE, there are different processes at work, or a matter of timing. That seems significant. It isn't necessarily the cortisol that is bad short term about stress.

    I'd like this matter to be studied, or comments from knowledgeable people. Perhaps studying viral load at time intervals in people who find cortisol helpful.

    Fogged. I hope this makes sense as a question.
  6. condra

    condra

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    I imagine most ME/CFS patients react badly to stress, much worse than healthy people.

    Since having ME/CFS, stress has always made me feel ill, sometimes quite suddenly and dramatically.

    Emotional turmoil such as heartache or grievance can impact my health very heavily. I actually have to systematically distract myself during such periods so as to subconsciously deal with the stress gradually.

    The effect of stress is magnified during "bad patches", when moderate stress such as traveling on a bus, or entering a busy room can cause symptoms like nausea, weakness and vertigo.

    Despite being similar to a "panic attack" on the surface, and even though remaining calm is important so as not to exasperate the symptoms on such occasions, I've long maintained that it is a mainly physical phenomenon.

    I find it hard to believe that Cortisol could help an ME patient, especially now that we know that cortisone probably helps XMRV to propagate.

    I do hope that liver function and adrenal function is researched further in relation to XMRV.

    ________


    A quick note on Prednisone.

    My mother has autoimmune hepatitis, and my beloved niece has a renal condition. (related to ME/CFS perhaps?) Both conditions require Prednisone as part of treatment.

    I've seen the effects of Prednisone on my niece who puts on weight and gets aggressive and frisky (bless her, shes only 5), but my mother reacted very badly around 2 weeks after starting her course of Prednisone. She developed "steroid psychosis" and had a horrendous psychiatric episode, which lasted about 24 hours at its worst, though she lost touch with reality for about 7 days in total.

    If anyone here really, REALLY, must take Prednisone at any point, please approach it with extreme caution, and be sure to outline your concerns firmly to whatever practitioner proposes the course.
  7. Marco

    Marco Old blackguard

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    Hi all.

    A new member here. I find the suggestion that cortisol stimulates HMRV replication very interesting.

    I've felt for a long time that the stress reponse has played a major role in my own illness and have been coming to similar conclusions to those of Ashok Gupta. Having read Cort's diary on amygdala retraining I'm going to order the AR package as Ashok has had the initiative to research this and put together a practical therapy package.

    However .... the XMRV study finding is the biggest news I've seen in nearly 25 years with ME (sorry but I refuse to legitimise the use of the CFS label) and I've been finding it hard to reconcile the two - even to the extent of wondering If I have ever really had ME and maybe just was unnaturally prone to chronic stress!

    The latter may be the case but a cortisol/XMRV link makes a lot of sense to me and suggests a few possibilities.

    You contract XMRV which remains relatively dormant until the stress reponse is strongly activated (in reponse to emotional, physical, environmental stress etc) causing massive replication of the virus and the wide range of symptoms seen in ME; chicken or egg-like chronic stress may have initially weakened the immune system leaving you open to the XMRV virus.

    This could explain the XMRV findings that those with XMRV and prostate cancer did not develop ME (presumably?) and that 4% of the normal population have ME but are not diagnosed with ME compared to estimates of 1% of the population with ME; i.e. :

    ME results from a combination of carrying the XMRV virus and a stressful trigger event causing viral replication. While 4% of the population may carry the XMRV it does not express as ME unless coupled with an exceptional stress response (or perhaps some have a more robust stress response and are 'immune').

    This would also explain the characteristic post-exercise malaise or frequent collapses/relapses. Any stress including exercise increases cortisol which accelerates XMRV replication causing the cascade of symptoms seen in ME. As for low cortisol in ME it is possible that baseline cortisol is down-regulated but that cortisol 'spikes' produce the crashes.

    If XMRV is confirmed as causal in ME we are stuck with it for life. If however there is this interaction with the stress response then a programme such as Ashok Gupta's, or similar, which allows you to control the stress response, should at least allow us to avoid the worst of the symptoms by maintaining the virus at a low level.

    Just some musings and happy to be here.

    Apologies I now see this was discussed in the necessary but not sufficient thread.
  8. fresh_eyes

    fresh_eyes happy to be here

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    No worries about repetition Marco - I never saw it in the other thread. I agree that therapies like Gupta's might continue to play an important role. I just wish he would tone down his claims (have you seen his piece on Planet Thrive about XMRV?) - he's basically saying some *other* trauma damages the amygdala and makes us vulnerable to XMRV, which undermines his credibility IMO. But I do think techniques like his (and other meditation/yoga based systems) can be extremely helpful, they've done wonders for me. But not made me well. I wish.:)

    Edit: Just to clarify, I haven't done the Gupta program, but I do practice meditation etc.
  9. Alice Band

    Alice Band PWME - ME by Ramsay

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    Marco,

    I don't know if you have read any research but the CFS and Cortisol investigations show that Cortisol is usually normal or more often low in people with the disease.

    That's why I'm sceptical about the claims behind the Gupta program and much of the speculation that is being made of this finding.

    In my own case my cortisol is very low and has been on all tests.

    We don't know why that is (although once again this is lots of speculation).
  10. cfs since 1998

    cfs since 1998 *****

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    My cortisol is low too, I've tested it several times. I actually feel better when my cortisol is higher. I wonder if it is a defense mechanism by the body to suppress XMRV or if it is just a result of the exhaustion. Would be curious to see cortisol levels in people with late stage AIDS or other illnesses that produce severe fatigue.

    I ordered the Gupta Programme but took advantage of the refund offer and sent it back. When I learned the details in the program I felt it did not apply to me. I also think it plays in to the whole "abnormal illness beliefs" notion that is prevalent in the UK. Not surprised Gupta is from Britain.
  11. Alice Band

    Alice Band PWME - ME by Ramsay

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    I've met several people who say that they have benefited from the Gupta program. In all of these cases they describe a terrible anxiety and an "over-hyped" feeling that is uncontrollable and severe.

    This is either on top of CFS or is there main symptom.

    This type of anxiety or sensation is serious and Gupta's program doesn't seem to be helping them.

    But for the rest of us who do not have these particular symptoms I have not met anyone who has been helped. I live in London.
  12. Marco

    Marco Old blackguard

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    Hello again.

    First let me say that I have no intention of trying to promote the Gupta programme specifically or similar approaches but that over a long period of time and study its basic premise resonates with my own personal experience of this illness.

    I can also appreciate resistance to any paradigm which appears to support the discredited notion that it is "all in the mind" however what the Gupta programme describes is most definitely NOT about "belief systems" - just the opposite in fact.

    Its also not helpful in my view to continue with the conception of a mind/body dichotomy with regard to illness. Modern theories of cognition such as the Santiago Theory state that congnition in its broadest sense is how the whole living organism reacts dynamically to its environment. The immune and autonomic nervous systems are as much part of cognition as the conscious brain. In fact our perception of emotions starts with our unconscious bodily sensations - literally the 'gut feeling' preceeds any conscious experience of emotion.

    What Gupta (and others) propose is that the (unconsious) brain structures that deal with perception of threat and the stress response - specifically the Amygdala - become chronically over aroused initiating and sustaining the stress response and producing the wide range of symptoms seen in ME. These symptoms are then subconsiously perceived by the amygdala as threatening and feedback into maintaining the hyperarousal state or in the terms of the Santiago theory - the symptoms become part of the threatening environment.

    If all this sounds a little too 'psychological' what we are talking about is physical changes in brain structures through neural plasticity as chronic arousal of the amygdala and association of threat with the symptoms creates ans strengthens the neural connections creating a web of connections conditioned to stimulate the stress response. None of this process is conscious or involves 'beliefs'.

    The other side is that feedback mechanisms exist between the conscious frontal areas of the brain and sub-cortical areas such as the amygdala. In normal circumstances the stress response is triggered in response to an external threat and conscious perception that that threat has gone has an inhibitary effect on the amygdala reducing the stress response. In ME the conditioned stress response has got caught in a maladaptive loop operating outside of consciousness therefore no amount of adaptive or maladaptive consious beliefs or 'talk therapy' will have any effect. However it may be possible that the web of neural connections can be extinguished by consious effort. I assume the Gupta programme uses some variation of mindfulness meditation to moderate the degree to which the various symptoms are subconsiously interpreted as threatening - thereby extinguishing the neural connections over time and breaking up the maladaptive neural web.

    I appreciate that not everyone with ME feels that they suffer from chronic anxiety - I didn't at the earlier stages of the illness - or at least not to the same extent. It may be that 'anxiety' is not perceived consiously or that ME is expressed in different ways depending on an individual's 'preferred' mode of expressing physical illness (in the same way I believe that ME and FMS are just different expressions of the same underlying pathology rather than distinct illnesses).

    As I said however, this resonates with me and I can see how such processes could interact with a chronic retroviral infection to produce the experienced ups and downs and frequent relapses.

    As for cortisol levels in ME, the research I've seen over the last 20 years or so is mixed with reports of both low and high levels in ME patients. This may depend on when the measurements are taken or the duration of the illness. That's why I said that baseline cortisol may be down-regulated. Cortisol levels may start high in response to a viral infection or other stressor but over time become exhausted or are down-regulated by feedback mechanisms either from the ANS or immune system. My own subjective experience is that my stress hormone levels start low but build throughout the day, plus I'm aware that any exercise or excitement (pleasurable or not) creates a 'spike' and triggers a magnification of all the other symptoms.

    So I'm happy to give this programme a try - if all else fails I might just end up a little calmer and accepting of my situation. I also appreciate that if the Gupta programme was universally successful, the distinctions discussed above would be quickly ignored and the psychological lobby would claim it as proof positive of a psychological origin.
  13. gracenote

    gracenote All shall be well . . .

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    mind/body dichotomy

    Hi Marco,

    I really appreciate this post. I too could say, "over a long period of time and study its basic premise resonates with my own personal experience of this illness" to a point. I would like to respond to a couple of comments you made in it.

    I have been studying the nervous system response in illness for my MA thesis for (too many) years. However, due to my significant cognitive symptoms and profound fatigue, I'm having trouble recalling what I've read and even more difficulty connecting the dots. So rather than a technical response, this is my take on all this.

    I think you have expressed very well what can be found in the literature coming out of many disciplines including psychology, neurobiology, medicine, and a new separate field of trauma studies. It is really an exciting time to be studying the brain and the confluence of these latest studies will prove to be very enlightening for all of us, hopefully one day soon. I think those of us who are ill can benefit greatly by this new brain science.

    However . . .

    I don't think you are trying to say that you think ME/CFS is ONLY a brain over-reacting to a threat that is no longer there. But some people ARE saying that. Some people ARE using this latest research to support the notion that ME/CFS is all maladaptive responses of the brain and can be fixed through the brain (I apologize for the oversimplification of this but it's the best I can do right now). Just one example of this is the book The Body Has a Mind of Its Own by Sandra Blakeslee. It is a fascinating, revelatory book. I was thoroughly enjoying reading it until I got to the chapter on CFS and FM (I can't find my copy of it at the moment so this is just from memory), which basically reduces these illnesses to our brains and their wiring.

    This is unhelpful in my opinion as it may leave unaddressed a continuing "external threat" which may or may not turn out to be XMRV. Even though this is not "external" in a sense of outside our body, it is external in the sense that it may be continuing to ignite the "stress response," continuing to send out signals of danger because there is actually ongoing danger there! Until this ongoing threat is dealt with, I am wondering if only limited or temporary progress can be made with breaking the "feedback" loop.

    I would love to hear that these approaches, which I think are profound in their own way, also include the possibility (and what I really think as probability), of not just an original trigger, but an ongoing agent that will continue to wreck havoc if not dealt with adequately. There is too much it's ALL "maladaptive responses" OR bacterial/viral/retroviral infection and not enough "lets get at this thing from all angles." So much so, that trying to use these approaches (and there continue to be more being offered every day), while believing that one may also have an active ongoing infectious trigger makes one feel defensive. At least it makes ME feel very defensive.

    It makes me feel all scrinchy.

    And then there is the other very real problem of where our research dollars are going, what kinds of treatments will be developed etc.

    I value this new research, I really do. But if we treat the maladaptive responses without treating an ongoing trigger we may not have long term healing. At the same time, it is probably also true that if we treat the virus (or whatever it turns out to be) and do not work with the responses our brains have made, we may end up not totally well.

    I want both.

    I don't think I am necessarily disagreeing with anything you are saying, Marco. And I commend you on saying it so well. If you try the Gupta program, please report back. I would love to hear all about it.

    And Marco, if I had a portion of your brain right now I could finish up my thesis and move on with my life. Just the time I've spent writing this post leaves me with the feeling that my brain has been sucked out of my head. And that is probably the most clarifying thing I have said so far.

    I would love to continue this dialog with you.

    Gracenote
  14. Jenny

    Jenny Senior Member

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    Hi Athene

    That 'crushed into a pulp' feeling sounds awful.

    My experience is a bit different. I've had this 27 years, so not in early stages ....

    I've only managed to get my cortisol tested twice - both times in the early morning. The first time it was way over the top of the normal range - so much so that doc suspected Cushing's disease. The second time, a few weekls late, it had come down a bit to just inside the range.

    Now, when in a bad relapse I'm mostly in the 'tired but wired' state. And it doesn't take much to make me anxious. But when I was first ill I don't think I often felt like that - it was more like your crushed feeling - leaden all over.

    Jenny
  15. Marco

    Marco Old blackguard

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    Don't know about anyone else Athene but the "tired but wired" expression is as good as any although tired doesn't come close to describing it.

    My experience is literally dragging myself through the day unable to do anything of consequence but also not able to just sit still and rest; needing to sleep for a few hours immediately after lunch or everything goes haywire, back to tired and wired afterwards and dragging on until I feel so exhausted I take myself off to bed at 9 or 10 o'clock only to be completely unable to sleep (note the nighttime insomnia preceeded the need to sleep during the day). Hardly a reason for jealousy.

    I've been ill since 1986 and had always tried to carry on with normal life until unable to - certainly not getting myself into a stew in anticipation - but when you have had, for example, IBS every day for nearly 25 years its hard to avoid the likelihood that the next day will be the same.
  16. Alice Band

    Alice Band PWME - ME by Ramsay

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    I don't get hyped up and I don't suffer from anxiety on a regular basis (and just in case anyone reads this the "wrong way", I'm not trying to be derogatory to those who do).

    Although I do have a normal range of emotions and if something big is happening I'll feel sad, angry, upset, frightened, worried as we all do.

    My illness started at the beginning of 1984 and was an acute onset viral one with no extra stress in my life.

    The "tired by wired" doesn't relate to me. Can quite understand how people feel that way, after all many of us are trapped at home and frustrated.
  17. Jenny

    Jenny Senior Member

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    Hi Alice

    Nothing to do with being trapped at home and frustrated I'm afraid. The agitated and wired feelings come and go randomly with rapid heart beat and sweating. They happen only when I'm in a bad relapse, when I'm feeling so terribly ill and poisoned that I feel very glad and fortunate that I'm able to stay in bed for months with someone to look after me.

    Jenny
  18. Jenny

    Jenny Senior Member

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    Hi Athene

    Not sure if it's me you're asking about the heart arrhythmia - I haven't had a holter monitor but have had several other standard heart rhythm checks. All normal.

    But I've also had extensive autonomic testing which showed abnormally low vagal tone and tachycardia, cardio accelerator failure, and reduced venous return to the heart. None of this led to any suggested treatments though!

    Jenny
  19. Sing

    Sing Senior Member

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    Dear Athene,

    I feel compassion for you--what you have been through!

    Here is more of the puzzle, perhaps. I'm like you with low adrenal functioning and digestive problems--not as bad off but in the same neck of the woods. Not only do I have low cortisol, for which I am prescribed low-dose Cortef, but I also lack the fight or flight/adrenaline and the salt conserving functions of the adrenal glands.

    If I get into a situation calling for adrenaline or respond that way, my body can only do a weak, ineffective buzz, which is unable to mobilize resources. The buzz is followed by a deep fatigue. Similarly I can't effectively raise and sustain sexual energy or cry either. My eyes can leak a few tears but I can't actually weep and sob. Sometimes I wish I could! I can then feel "constipated" with grief.

    Without salt conservation, I pee out my bodily fluids and need to drink 3X what a normal person might. Dr. Byron Hyde wrote about this as a feature of ME, how we can be wrongly diagnosed with Central Diabetes Insipidus when the cause is different. Of course I have to drink a lot of water and take in extra salt.

    And if I don't eat extra salt, my orthostatic intolerance is decidedly worse. I feel weak, like fainting when I try to walk and stand. If I persist in moving forward, then my heart will beat fast, trying to compensate--that is what is happening, according to a doctor--it is a compensatory feedback mechanism in order to try to keep some blood going up to the brain and to allow for movement. Then I have to rest quietly for some time, exhausted. It would be hard to speak, either during the heart racing or in its aftermath.

    So this kind of speediness is quite different from that of the speed that comes with high functioning, coordinated power--and it is also doesn't share the same cause as someone with a primary heart defect.

    The neurological, endocrine and vascular systems are not working well. This also affects the digestive track through the vagus nerve in particular which is supposed to coordinate that orchestra. An uncoordinated digestive system doesn't secrete enzymes, etc. as needed so allows undigested food to pass, causing problems down the line, or it stops digestion when it ought to be moving forward, which can result in the backup mechanism of nausea and vomiting. The elements aren't coordinated, things get out of balance and backup sytems are called into action with dysfunctional results!

    I'm riding in the same boat!

    Cecelia
  20. gracenote

    gracenote All shall be well . . .

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    brakes and revved-up engines

    Hi Athene,

    I could describe the first twenty years or so of my illness as you have, kind of like trying to drive with the emergency brake on just struggling to push forward and push through only to be left depleted and almost comatose. (There were some times of feeling wired but tired but not that I would describe as hyped or anxious.) That changed five or so years ago. Now it's like the brake is on but my engine is revving and won't calm itself down. There is a hyped-up quality to it even when I spend my whole day resting.

    Neither state has left me more able to engage with the environment or my life. I think I also suffer from a mood disorder (notice I said also!) and I have to cultivate my ability to experience pleasure and passion. Days that my awareness is either feeling crushed by fatigue, or hyped up with anxiety, or feeling inflamed by viral activation are tough. There seems to be no energy left over to feel anything other than sick.

    I see this part of it (cultivating my ability to experience pleasure) as my spiritual practice while I'm also trying to fix the physiological cause(s) to this nervous system gone wacky.

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