Alpha-MSH protein, a potential biomarker for CFS - Japan

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DysautonomiaXMRV

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Source: Daily Yomiuri Online (Japan)
Date: January 11, 2010
URL: http://www.yomiuri.co.jp/dy/national/20100111TDY03103.htm


Breakthrough made in diagnosing chronic fatigue syndrome

Researchers have discovered a protein in blood that can be used to diagnose chronic fatigue syndrome, a breakthrough that could help detect the ailment during physical checkups.

There are diagnostic criteria for chronic fatigue syndrome - a disorder involving extreme fatigue of unknown cause that continues for at least six months--that rely primarily on subjective symptoms, but there have been no objective markers such as blood tests. The research team led by Hiroshi Kiyama, a professor of anatomy at Osaka City University, examined the intermediate lobes of the pituitary glands of rats in which they induced extreme fatigue by making them exercise for five consecutive days. They found that the lobes excreted extraordinarily high amounts of a protein called alpha-MSH and that alpha-MSH levels in the animals' blood also increased. The neurotransmitter dopamine inhibits the secretion of alpha-MSH, but the rats' ability to produce dopamine declined as their fatigue grew.

The group also tested the levels of alpha-MSH in the blood of 57 people diagnosed with chronic fatigue syndrome and the blood of 30 healthy people. The average level among the 37 people who had been diagnosed with chronic fatigue syndrome less than five years before was about 50 percent higher than the healthy people.
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Source: Journal of Neurochemistry
Vol. 109, #5, pp 1389-1399
Date: March 23, 2009
URL:
http://www3.interscience.wiley.com/journal/122270951/abstract?CRETRY=1&SRETRY=0
Ref: All Hiroshi Kiyama papers,
http://www.ncbi.nlm.nih.gov/pubmed?term="Kiyama H"[Author]
All Hiroshi Kiyama papers on alpha-MSH,

http://www.ncbi.nlm.nih.gov/pubmed?term="Kiyama H"[Author] alpha-MSH
Rem: Please note that this might not be the research reported in
todays press release.

Chronic stress elicits prolonged activation of alpha-MSH secretion and subsequent degeneration of melanotroph.
------------------------------------------------------------------
Ogawa(*,**), Nobue Shishioh-Ikejima(*,**), Hiroyuki Konishi(*,**),
Tetsuya Makino(*,**), Hiroyoshi Sei(***), Sumiko Kiryu-Seo*,**),
Masaaki Tanaka(**,****), Yasuyoshi Watanabe(**,****), and Hiroshi
Kiyama(*,**,+)
* Department of Anatomy & Neurobiology, Graduate School of Medicine,
Osaka City University, Osaka, Japan
** The 21st Century COE Program 'Base to Overcome Fatigue', Graduate
School of Medicine, Osaka City University, Osaka, Japan
*** Department of Integrative Physiology, Institute of Health
Biosciences, The University of Tokushima Graduate School, Tokushima,
Japan
**** Department of Physiology, Graduate School of Medicine, Osaka
City University, Osaka, Japan
+ Address correspondence and reprint requests to Hiroshi Kiyama,
Department of Anatomy and Neurobiology, Graduate School of Medicine,
Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585
Japan. E-mail: kiyama@...


Abstract

Prolonged stress affects homeostasis in various organs and induces stress-associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up-regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of alpha-melanocyte stimulating hormone (alpha-MSH), a major product of proopiomelanocortin in IL were increased. The alpha-MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus-derived dopamine release in IL, which elicited over-secretion of alpha-MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration.
 
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Katie

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Abstract

Prolonged stress affects homeostasis in various organs and induces stress-associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up-regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of alpha-melanocyte stimulating hormone (alpha-MSH), a major product of proopiomelanocortin in IL were increased. The alpha-MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus-derived dopamine release in IL, which elicited over-secretion of alpha-MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration.

I'm no scientist but this is my take.

Firstly, this study seems to focus on short term stress as the rats in the study were placed in a five-day discomfort/stress situation. Unless you theorise that we remain in a constant 'stress' state which would suggest a psychological factor as the stress factor on the rats was external, not an internal virus/neurological issue etc. Although outside stress situations can and do cause internal issues, this study seems to posit that it is our reaction to outside stressors that create the upregulation. They do talk about continued stress but I would find this study more relevant to those suffering from PTSD than myself. I know I'm writing like I know what I'm talking about, but this is my first true bash at critiquing a study so I'm totally open to someone telling me that I should reinstate my tagline of Bovine Scatology Phd. :)

While I am open to stress studies, I've certainly seen variable deterioration in my health under stress but my emotional stress is not necessarily separate from pushing too hard and running on adrenaline which I can do for an impressively long time before spectacularly crashing like a forklift driver in a vodka storage facility ;) I'm concerned that this study supports a neuropsychiatric basis rather than a purely neurological one. Anyone want to correct me on that? What it could mean is that some cases of ME/Cfs are triggered by high stress situations which leads to hyperactivation of endocrine cells. I have in my time seen at least two cases of ME which turned out to have a psychological basis. I do not think of them any differently from anyone else with ME as they experienced the same symptoms as I did, but for different reasons. It makes not a jot of difference to me personally, but the more we organise the wastebasket the better for future studies and cohorts.
 

fresh_eyes

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Interesting take, Katie. I read it as saying that the fatigue of CFS sufferers is chemically the same as fatigue caused by extreme exertion, and can be tested for.

But you may be right - I do get a red flag from "stress-associated disorders".
 

acer2000

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The curious thing about this study is that it seems to be reporting the opposite of what Dr. Shoemaker claims. Although things may change over time with the illness... ie high MSH to begin with and then over time it falls. Interesting though...
 

lostinthedesert

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When I crashed hard almost 20 years after I first got sick, I had very low MSH. Don't know where I am now...waiting for results. I have heard of some people who had low MSH who were still sick after it came back up. I also know of some mold patients who said they have tried MSH analogs like melanotan2 with no improvement.

Peace,
S
 

Nina

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I'm pretty sure that whatever they measured there is not what we are experiencing.

Haven't you all had the situation where you needed to explain what your exhaustion and weakness feels like?

My reply to that is often that it's very much like wanting to explain the colour yellow to someone who has been blind since birth. There has been nothing in my life before this disease that felt even remotely close to what I am feeling now. Not even runnning a marathon after not having slept for 3 nights... it's just not like anything a healthy person would ever feel like.

Just my 2 cents.
 

Tammie

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Interesting take, Katie. I read it as saying that the fatigue of CFS sufferers is chemically the same as fatigue caused by extreme exertion, and can be tested for.

But you may be right - I do get a red flag from "stress-associated disorders".
I'm not quite sure of my understanding overall of the study bc it does seem to contradict other findings, and bc it does seem focused on short term exertion (and only how that impacts fatigue levels, and as we know CFS is much more than just fatigue)....however, just considering the above quote, if your take is correct, it immediately brings to mind my own experiences (pre-CFS) with running 26.2 mile marathons. I would say those qualify as extreme exertion, and I can honestly say that I felt substantially better in the minutes, hours, and days following running marathons than I do on a regular basis after a full night's (admittedly very fitful) sleep with CFS. So, even if the body's response appears similar, there is still something significantly different between the two things they are measuring.
 

Tammie

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I'm pretty sure that whatever they measured there is not what we are experiencing.

Haven't you all had the situation where you needed to explain what your exhaustion and weakness feels like?

My reply to that is often that it's very much like wanting to explain the colour yellow to someone who has been blind since birth. There has been nothing in my life before this disease that felt even remotely close to what I am feeling now. Not even runnning a marathon after not having slept for 3 nights... it's just not like anything a healthy person would ever feel like.

Just my 2 cents.
Interesting - I had not read this response when I posted my first response to this thread (I mentioned marathons in it)

anyway, just wanted to comment that the comparison to explaining the color yellow is a great way to put it
 
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I have been injecting a-MSH (1mg per day) for about 2 weeks now and the benefits have been tremendous so far. My sensitivity to mold has gone down considerably and I haven't gotten PEM from walking lately. I am doing some other things too but I think the MSH has played a big part.
 

Hip

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I have been injecting a-MSH (1mg per day) for about 2 weeks now and the benefits have been tremendous so far. My sensitivity to mold has gone down considerably and I haven't gotten PEM from walking lately. I am doing some other things too but I think the MSH has played a big part.
That's very interesting, I was looking at the possibility of trying alpha-melanocyte-stimulating hormone (alpha-MSH) a few years ago, on account of its anti-inflammatory effects.

Although alpha-MSH appears to be elevated in ME/CFS patients, as the above paper indicates, so it's not clear that it would help ME/CFS.

If you have mold sensitivity thought, its possible you may have chronic inflammatory response syndrome (CIRS) rather than ME/CFS, and in CIRS, alpha-MSH is low.

Dr Ritchie Shoemaker's treatment protocol for CIRS includes raising alpha melanocyte-stimulating hormone by eliminating the MARCoN infections in the nose and sinuses. MARCoNs he says lower α-MSH, and he considers such low α-MSH to be part of the problem in mold and biotoxin illness.
 

perrier

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That's very interesting, I was looking at the possibility of trying alpha-melanocyte-stimulating hormone (alpha-MSH) a few years ago, on account of its anti-inflammatory effects.

Although alpha-MSH appears to be elevated in ME/CFS patients, as the above paper indicates, so it's not clear that it would help ME/CFS.

If you have mold sensitivity thought, its possible you may have chronic inflammatory response syndrome (CIRS) rather than ME/CFS, and in CIRS, alpha-MSH is low.

Dr Ritchie Shoemaker's treatment protocol for CIRS includes raising alpha melanocyte-stimulating hormone by eliminating the MARCoN infections in the nose and sinuses. MARCoNs he says lower α-MSH, and he considers such low α-MSH to be part of the problem in mold and biotoxin illness.
Hip,
But haven't studies also shown that CFS patients can also have mold infection? Or in your mind, does having Marcons rule out ME? I'm finding all this very entangled and thus difficult to sort out.

PS. I want to answer your other question on the other thread about Canadian enterovirus testing later.
 

Hip

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But haven't studies also shown that CFS patients can also have mold infection?
The difference between CIRS (caused by mold or other biotoxins) and ME/CFS (usually triggered by viral infection) does seem hard to pin down, because as you say, ME/CFS patients also appear to harbor mold infections (in their nasal cavities according to Dr Brewer's ideas).


But the reason @stolpioni may do well to consider the possibility of having chronic inflammatory response syndrome is because if you have CIRS and are misdiagnosed as an ME/CFS patient, you are going to get the wrong treatments. CIRS appears to be more treatable that ME/CFS, and if you have CIRS and get the right treatments, you may make major improvements.

There was a recent thread on Health Rising by Ryan who was misdiagnosed with ME/CFS for 10 years, but really had CIRS. Once he got the correct diagnosis and got the correct CIRS treatment, he attained near full remission in a matter of five months. It would be tragic to see other patients miss out on a curative treatment due to misdiagnosing CIRS as ME/CFS.

More details of Ryan's story and the differences between ME/CFS and CIRS in this post.
 
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That's very interesting, I was looking at the possibility of trying alpha-melanocyte-stimulating hormone (alpha-MSH) a few years ago, on account of its anti-inflammatory effects.

Although alpha-MSH appears to be elevated in ME/CFS patients, as the above paper indicates, so it's not clear that it would help ME/CFS.

If you have mold sensitivity thought, its possible you may have chronic inflammatory response syndrome (CIRS) rather than ME/CFS, and in CIRS, alpha-MSH is low.

Dr Ritchie Shoemaker's treatment protocol for CIRS includes raising alpha melanocyte-stimulating hormone by eliminating the MARCoN infections in the nose and sinuses. MARCoNs he says lower α-MSH, and he considers such low α-MSH to be part of the problem in mold and biotoxin illness.
Yes, I have CIRS and very low (undetectable levels) of MSH. So it would be a good idea to test your own levels before using it. I also used BEG Spray to remove MARCoNs but it didn't seem to help raising my MSH levels.
 

perrier

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The difference between CIRS (caused by mold or other biotoxins) and ME/CFS (usually triggered by viral infection) does seem hard to pin down, because as you say, ME/CFS patients also appear to harbor mold infections (in their nasal cavities according to Dr Brewer's ideas).


But the reason @stolpioni may do well to consider the possibility of having chronic inflammatory response syndrome is because if you have CIRS and are misdiagnosed as an ME/CFS patient, you are going to get the wrong treatments. CIRS appears to be more treatable that ME/CFS, and if you have CIRS and get the right treatments, you may make major improvements.

There was a recent thread on Health Rising by Ryan who was misdiagnosed with ME/CFS for 10 years, but really had CIRS. Once he got the correct diagnosis and got the correct CIRS treatment, he attained near full remission in a matter of five months. It would be tragic to see other patients miss out on a curative treatment due to misdiagnosing CIRS as ME/CFS.

More details of Ryan's story and the differences between ME/CFS and CIRS in this post.
You are absolutely right to make this point. But I would like to know how many ME patients also have Marcons, and how common this might be.
 

perrier

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Yes, I have CIRS and very low (undetectable levels) of MSH. So it would be a good idea to test your own levels before using it. I also used BEG Spray to remove MARCoNs but it didn't seem to help raising my MSH levels.
Were you able to eliminate the Marcons. What would you recommend?
 

Hip

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I also used BEG Spray to remove MARCoNs but it didn't seem to help raising my MSH levels.
I recently came across this paper which demonstrated that chlorine dioxide at 100 ppm completely killed all MRSA (methicillin-resistant Staphylococcus aureus) strains in 15 seconds. I should imagine that chlorine dioxide will kill MARCoNs (multiple antibiotic resistant coagulase negative staphylococci) with similar efficacy.

So it occurred to me that a nasal spray of chlorine dioxide might be much more effective at eliminating MARCoNs than the regular BEG spray devised by Dr Shoemaker (BEG contains Bactroban, EDTA and gentamicin).

100 ppm of chlorine dioxide I think should be safe as a nasal spray, since chlorine dioxide mouthwashes like Freshen contain 1,000 ppm of chlorine dioxide.


One quite easy to obtain source of chlorine dioxide is the "miracle mineral supplement" (MMS), which creates a solution of chlorine dioxide by reacting together a 28% sodium chlorite solution with a 10% citric acid solution. I know there is great controversy about the possible dangers of taking MMS internally; but here we are only talking about spraying chlorine dioxide onto the nasal mucous membranes, in order to kill MARCoNs.

By my calculation, one drop of MMS added to 50 ml of water will create a solution of around 160 ppm of chlorine dioxide (since each drop of MMS contains around 8 mg of chlorine dioxide, and 50 ml of water weighs 50,000 mg).

I am not sure if I have MARCoNs (I don't have any known mold issues), but I did a brief experiment a while ago spraying a homemade 160 ppm solution of chlorine dioxide into my nose, and this seemed to be well tolerated (there was no discomfort or nasal irritation or stinging).



Chlorine dioxide is a good mold killer too, so a chlorine dioxide nasal spray might also be effective for treating the chronic mold infections that Dr Brewer thinks ME/CFS patients have in their nasal cavities (Dr Brewer usually prescribes a nasal spray based on the antifungal amphotericin B for destroying nasal mold infections).
 
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I recently came across this paper which demonstrated that chlorine dioxide at 100 ppm completely killed all MRSA (methicillin-resistant Staphylococcus aureus) strains in 15 seconds. I should imagine that chlorine dioxide will kill MARCoNs (multiple antibiotic resistant coagulase negative staphylococci) with similar efficacy.

So it occurred to me that a nasal spray of chlorine dioxide might be much more effective at eliminating MARCoNs than the regular BEG spray devised by Dr Shoemaker (BEG contains Bactroban, EDTA and gentamicin).

Chlorine dioxide is a good mold killer too, so a chlorine dioxide nasal spray might also be effective for treating the chronic mold infections that Dr Brewer thinks ME/CFS patients have in their nasal cavities (Dr Brewer usually prescribes a nasal spray based on the antifungal amphotericin B for destroying nasal mold infections).
Very cool, you've given me a lot to read up on! Did you only use the spray once? The problem with Marcons is that they are covered in biofilm. Is this true for MRSA as well?

Were you able to eliminate the Marcons. What would you recommend?
I don't know actually, I haven't retested. But I did feel that the BEG Spray helped clear my sinuses quite a bit. I am also hoping that by raising MSH, that should help the body naturally get rid of the Marcons.