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A defect in cortisol production in rheumatoid arthritis: why are we still looking?

Discussion in 'Other Health News and Research' started by Snow Leopard, Oct 12, 2012.

  1. beaverfury

    beaverfury beaverfury

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    Simon, jimells, August59 and 2 others like this.
  2. natasa778

    natasa778 Senior Member

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    Absolutely, I have always felt that to be the case... in terms of 'evidence' for this I feel we can only push it as far as taking it from animal studies, like the one that currer posted.

    I don't see how we could ever prove that beyond doubt in humans (short of unethical experimenting on healthy people, to see what happens :) because in real humans with developed/established health conditions we would get forever entangled in chicken-or-egg situation and 'NEVER COME TO ANY REAL CONCLUSIONS'.
     
  3. Snow Leopard

    Snow Leopard Senior Member

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    Here is one prepared earlier (by Broderick and colleagues):
    http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000273

    The problem is that the assumption of increased GC receptor expression or activity has not shown to be the case when CFS patients have been tested. So the statements in the Seckl/Yahuda about increased GC receptor density paper don't actually apply to CFS cases.

    The model does not consider suppression due to the effect of the immune system (which is a logical consequence of the feedback systems, but wasn't actually mentioned in the previous articles I cited - I apologise to currer if there was any misunderstanding)
     
  4. beaverfury

    beaverfury beaverfury

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    Ok. Phew! I can comprehend 50% of the text, none of the math. Ive got some learning to do.

    Interesting that they propose a treatment plan of lowering cortisol levels rather than raising as you would expect.
    Wonder how that goes??

    Now i have to read about HPA axis stable steady states and GC receptors.
     
  5. Snow Leopard

    Snow Leopard Senior Member

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    I bet it doesn't work. ;)
     
  6. caledonia

    caledonia

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    According to Rich Vank, the HPA axis problem is caused by lack of glutathione in the hypothalmus and pituitary. This results in them no longer being able to make the proper signals to the adrenals and thyroid, so they lose functioning. The treatment would be to do a methylation protocol to raise glutathione, thus restoring function.
     
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  7. jimells

    jimells Senior Member

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    Well, actually the studies do come to conclusions: "We conclude we need more grant money to keep publishing useless papers" ;)
     
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  8. beaverfury

    beaverfury beaverfury

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    "We conclude that....OH, MY GOD!.. WHAT'S THAT?.........We've never even seen ONE of those before!!!!!"

    "Thats my lunch, Dr Bob. Youre looking through the wrong end of the microscope!"
     
  9. beaverfury

    beaverfury beaverfury

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    'A number of chronic diseases have been characterized by abnormalities in HPA axis regulation. These include major depression and its subtypes, anxiety disorders such as post-traumatic stress disorder, panic disorder and cognitive disorders such as Alzheimer's disease and minimal cognitive impairment of aging [3]. Dysregulation of the HPA axis has also been linked to the pathophysiology of Gulf War illness [4], post-infective fatigue [5], and chronic fatigue syndrome (CFS) [6],[7]. It is not clear what causes this dysregulation, but it is manifested in many HPA axis disorders as a hypercortisol or hypocortisol state. The existence of these separate and stable states is not surprising when one considers the multiple feedforward and feedback mechanisms that regulate the HPA axis. Systems such as this often display complex dynamics that readily accommodate multiple stable steady states which are known as attractors because the system is naturally drawn back to these resting states after perturbation. However, if the perturbation is of sufficient strength and duration, the system can be pushed away from a given resting state and into the basin of new attractor.'

    I like this bit:)
    'We propose that a well-directed push given at the right moment may encourage the axis to reset under its own volition.'

    Yeah, just give it a shove! Thats my sort of science.

    They propose this
    'A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels.'

    Theres a discussion on this at http://forums.phoenixrising.me/index.php?threads/hpa-axis-reboot.17879/
    But be sure and come back here
     
  10. Snow Leopard

    Snow Leopard Senior Member

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    Here is an interesting one for you guys, a paper that turns things on its head. I am surprised it took me this long to find this paper as I have been hinting towards results like this.


    Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome
    http://cfids-cab.org/cfs-inform/Cytokines/gaab.etal04.pdf

    The authors also discuss the previous studies which did not find increased Glucocorticoid receptor density or activity. (therefore the typical explanation is likely false and something more interesting is at play)

    Actually, I feel the sensitization could be on a cellular level rather than a brain level, mediated by other biochemical deficiencies.

    In conclusion, you should try increasing your psychosocial stress levels. ;)
     
  11. beaverfury

    beaverfury beaverfury

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    'Actually, I feel the sensitization could be on a cellular level rather than a brain level, mediated by other biochemical deficiencies.' snowleopard


    The plot thickens, as my brain dissolves.
    Ive just been reading cort's article on cellular ion channel malfunctionshttp://phoenixrising.me/research-2/...chronic-fatigue-syndrome-mecfs/comment-page-1.

    Potential causes of channel dysfunction The natural history of CFS suggests that an early pathogenic or toxic insult often occurs. Several viruses, including HIV and the picornaviruses are able to alter ion channel flow. Toxins can be key ion channels disrupters because they often attack the membrane surrounding the cell. Some toxins can even create new channels that cause severe ionic imbalances through the leakage of ions out of the cell.

    Is this the sort of thing you might be alluding to? (fishing). I guess theres a thousand things can go wrong in a cell.
    I wonder how this ties in with varying cortisol levels? Beyond me.
     
  12. lansbergen

    lansbergen Senior Member

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    http://www.me-cvs.nl/index.php?pageid=4817&printlink=true&highlight=ebv

    LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome
    patients is increased but supersensitive to inhibition by dexamethasone

    Abstract

    Several causes have been held responsible for the chronic fatigue syndrome
    (CFS), including an altered hypothalamus-pituitary-adrenal gland (HPA)-axis
    activity, viral infections and a reduced Th1 activity. Therefore, it was
    investigated whether the regulation of IL-10 is different in CFS. LPS-induced
    cytokine secretion in whole blood cultures showed a significant increase in
    IL-10 and a trend towards a decrease in IL-12 as compared with healthy
    controls. In patients and controls, IL-12 secretion was equally sensitive to
    suppression by dexamethasone, whereas IL-10 secretion appeared more sensitive
    in CFS-patients. In controls, IL-10 and IL-12 secretion were inversely
    correlated with free serum cortisol (r=-0.492, p<0.02 and r=-0.434, p<0.05,
    respectively). In CFS, such an inverse correlation was found for IL-12
    (r=-0.611, p<0.02) but not for IL-10 (r=-0.341, ns). These data are
    suggestive for a disturbed glucocorticoid regulation of IL-10 in CFS.
     
  13. Snow Leopard

    Snow Leopard Senior Member

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    One more.

    http://www.ncbi.nlm.nih.gov/pubmed/10690878

    J Clin Endocrinol Metab. 2000 Feb;85(2):692-6.
    Disturbed neuroendocrine-immune interactions in chronic fatigue syndrome.

    Kavelaars A, Kuis W, Knook L, Sinnema G, Heijnen CJ.
    Source

    Department of Pediatric Immunology, Wilhelmina Children's Hospital of the University Medical Center Utrecht, The Netherlands. a.kavelaars@wkz.azu.nl
    Abstract

    The present study was designed to investigate the interaction between neuroendocrine mediators and the immune system in chronic fatigue syndrome (CFS). We examined the sensitivity of the immune system to the glucocorticoid agonist dexamethasone and the beta2-adrenergic agonist terbutaline in 15 adolescent girls with CFS and 14 age- and sex-matched controls. Dexamethasone inhibits T-cell proliferation in healthy controls and in CFS patients. However, the maximal effect of dexamethasone on T-cell proliferation is significantly reduced in CFS patients as compared with controls. The beta2-adrenergic receptor agonist terbutaline inhibits tumor necrosis factor-alpha production and enhances interleukin-10 production by monocytes. Our data demonstrate that the capacity of a beta2-adrenergic agonist to regulate the production of these two cytokines is also reduced in CFS patients. We did not observe differences in baseline or CRH-induced cortisol and ACTH between CFS patients and controls. Baseline noradrenaline was similar in CFS and controls, whereas baseline adrenaline levels were significantly higher in CFS patients. We conclude that CFS is accompanied by a relative resistance of the immune system to regulation by the neuroendocrine system. Based on these data, we suggest CFS should be viewed as a disease of deficient neuroendocrine-immune communication.
     
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  14. August59

    August59 Daughters High School Graduation

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    This sure would make a good new name for us to use in association with our disease:

    Neuroendocrine-Immune Encephalomyelitis or NIE or NIEM, we could drop the Encephalo and then it would be Neuroendocrine-Immune Myelitis or NIM for short. Nah, we better leave the Encephalo in it.

    I'm just playing around with names as the sooner CFS is gone the happier I will be!

    Thanks Snow Leopard for a great thread. It is sort of interesting that there were several threads starting with somewhat similar subjects at he same time. So, it must be on peoples minds and I think it is a very plausible subject for discussion and research if it can start where they left off and move on. I don't care to see some of this research repeated as it is just wasting funding.
     
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  15. Hip

    Hip Senior Member

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    This is a good point, Nanonug, and one which I have often pondered on myself.

    To restate your point: there is a distinct division in physics: there are the experimental physicists, who set up laboratory experiments (sometimes with billion dollar budgets) in order to make specific observations, measurements and tests on the laws of nature, and on the behaviors of physical world; and then there are the theoretical physicists who, with nothing more costly than a pencil and paper, sit down at their desks trying to develop theories that explain how the physical world actually works (with of course the help of the data derived from experimental physics).

    The experimentalists are doers that are at home in the lab. The theoreticians are the thinkers that are at home in a library or any place they are left alone to engage in deep thinking. These are quite different personalty types, and each prefers their own domain.

    In the medical, biochemical and microbiology fields, there does not seem to be this distinction between the doers and the thinkers, as far as I am aware. I personally don't have any direct experience of this academic area, but from what I can work out, in the biological sciences, most people are primarily experimentalists that work in labs, with some of these guys moonlighting as theoreticians.

    Because there seem to be few dedicated theoreticians in the biological sciences, this means there are not enough people sitting down with pencil and paper, devising new theoretical models that explain biochemical mechanisms and disease etiologies.

    Though it has to be said that biology is a different beast to physics. In the history physics, time and time again, very complex looking phenomena are often eventually boiled down to a startlingly simple and beautiful mathematical equation that, remarkably, captures all the facets of the phenomenon. In physics, complex phenomena arise out of a underlying substrate of beautifully simple laws.

    However, in the biological sciences, even the underlying substrate itself seems complex. You don't seem to get many occasions in the history biology where a complex phenomenon is boiled down to a simple equation or law that you can print on a T-shirt. In fact, often the reverse: when you try to understand a simple concept in biology, like say that of heredity, instead of boiling down to a simple equation, it explodes into something extremely detailed and convoluted, like the complex science of genetics.
     
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  16. beaverfury

    beaverfury beaverfury

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    Since getting cfs i have found the, 'shit happens' T-shirt has a new resonance for me.

    I dont like Freud's 'anatomy is destiny'.
     
  17. beaverfury

    beaverfury beaverfury

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    Those are hell better names than what we've got. Cant wait till they finally pull the trigger on this name change.
    If something generalised like 'Neuroendocrine immune dysfunction' doesnt serve in the long term, it is still a more workable solution than 'chronic fatigue syndrome' in the medium term, and would give us some breathing space.
    I know science has to tread lightly for fear of mistep, but politically.....
     
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  18. beaverfury

    beaverfury beaverfury

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    Theres not enough philosophical debunking of mainstream beliefs concerning current scientific research either.
    The conflation of 'in vitro' theory with 'in vivo' effectiveness is an example.(Mea culpa. Maybe i am only thinking of my own idealistic gullibilty).
    The latest antioxidant, the great new supplement, anti-aging strategies, brain enhancing nootropics, medications can all be rendered worthless if the right person doesnt take the right chemical- at the right dose- at the right time.
    Drinking enough water, getting enough sleep, getting maximum nutrition and enough aerobic exersise(we're screwed there) could be by far more effective than any particular chemical i'm putting into my recalcitrant system.

    The explosion of new research, its desemination in fitness magazines, forums, soundbites in the media are not offset
    by cold reality. This is not the fault of scientists themselves, who by profession are the most cautious of creatures.

    I'm guilty of swallowing all these idealistic narratives, along with a ton of supplements. I keep searching for a dopaminergic holy grail, hoping for inreased energy, motivation, libido! Confusing these with success in career, enhanced sexual relationships and freedom from illness. So far, i'm alone, ill, sleep deprived... and i've got a headache.

    The results that these industrious lab moles put down on paper are grasped by people of divergent motivations.
    Mainly, healthy people that have commercial interests, and commercially vulnerable folk who have health interests!

    I'm going off subject probably. Suffice to say there are a few gaps in the market.
     
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