Theoretical Immunology

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Leonard
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Re: I think I found it: This Is MS

Post by Leonard »

http://www.thelancet.com/journals/laneu ... =Neurology

I think the article under the link above is not without merit. In fact, many neuro-degenerative diseases could be caused primarily by poor nutrition at micro-cellular level due to vascular problems. MS is no exception as this thread shows.
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MS as a 2-stage disease

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this is also an interesting article, it is reference [9] from the above article about coffee, wine, fish consumption and MS progression [see posting 19 Mar 12:57pm]. it is from 2008.
http://www.ncbi.nlm.nih.gov/pubmed/18632772

neurologists / researchers see some ingredients here for a 2-stage disease but they are still in the dark about the why or what happens. Well, this thread explains... :-D
They better take it and move on from there, there are millions of people waiting every day...
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Mediterranean Diet and White Matter

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On Mediterranean Diet and White Matter

This article takes a different slant on things.
It is not about MS as such but the overlap is remarkable...

http://www.natap.org/2012/HIV/251.pdf

quote:
Conclusions:AMeDi was associated with a lowerWMHV
burden, a marker of small vessel damage in the brain.
However, white matter hyperintensities are etiologically
heterogenous and can include neurodegeneration.
Replication by other population-based studies is needed.

The MeDi has been associated
with improved endothelial function,23 adiposity,
24 and lower levels of inflammatory markers, includingC-
reactive protein25 and interleukin 6,26 and these may
be mechanisms underlying the observed association between
the MeDi and WMHV.

In summary, the current study suggests a possible protective
association between increased consumption of a
MeDi and small vessel disease
. The MeDi emphasizes a high
consumption of olive oil, plant proteins, whole grain, and
fish; a moderate consumption of alcohol; and a low consumption
of red meat, refined grains, and sweets.
unquote
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Leonard
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Chronic immune system disease based on wrong presumptions?

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The previous posting stressed the importance of a good health of the small vessels.

After many years of CCSVI, a lot of damage will have been caused to the small vessel walls in parts of the brain and spinal column. There can be no doubts anymore about the relationship. This recent publication by the US Society of Interventional Radiologists (SIRs) shows that 95 percent of the individuals evaluated had venous obstructions http://www.cisionwire.com/society-of-in ... s,c9232953

In the affected areas, endothelial functioning will be considerably weakened. Infection with a bacteria or virus may then further impair the endothelial functioning (by receptor blocking or dysfunctioning) to a point where inflammation and acute relapses occur. If severe enough, one will be diagnosed with RR MS.

In the second progressive stage, experience has shown that progression can be stopped through diet, even to a point where the disease may be somewhat reversed. This is most clearly demonstrated by the positive effects of the Swank low-fat diet (140 patients over 34 years) and other diets (Terry Walsch etc). The Mediterenean diet (see above posting) shows a large overlap with the Swank diet and will help to preserve endothelial health in those already weakened small vessels. Hence, in the second progressive stage, maintaining vessel wall functioning is critical while further aggravated endothelial conditions would lead to further disease progression.

We may now ask what mechanism is underlying demyelination and axonopathy in this second progressive stage. One mechanism that I can see is a further receptor dysfunctioning that aggravates micro-cellular feeding conditions and natural transcription processes (for generating oligodendrocytes that then compete). This mechanism will then further weaken the already vulnerable myeline and axons.

A possible second mechanism involves the immune system. I can see that the weakened myeline and axons will cause a low grade inflammation; I am sure that the metabolism counts many (neuro-)signalling pathways and some of them will get excited to signal that there are things going wrong.

[As a side step in the reasoning, I am convinced that vitamin C, vitamin D and cortisol do not work inflammation suppressive but rather improve the micro-cellular nutritional conditions such that (neuro-)signalling pathways calm down. It looks then as if things work suppressive but the real underlying mechanism at work here works the other way around, in fact not to suppress but to enhance… dogma1].

Now going back to the main line of reasoning: The fact that MS patients who strictly adhere to a Swank low-fat diet stabilise provides a clear indication that through diet you can change the course of the disease. Possibly, this happens by keeping key receptors healthy by improving conditions and the endothelial functioning in the smallest vessels.

I am convinced that sugar and/or for instance wheat flour are a factor here. Anything that pushes the blood sugar high up is bad; high insulin peaks are bad as they reduce insulin sensitivity. See e.g. http://www.wheatbellyblog.com/about-the-author/ And possibly the super-sticky MGmin LDL cholesterol (that grows on sugar and saturated fats) is further sealing vessel walls. Here the common diabetes medication Metformin may help break down this ultrabad cholesterol, and arguably also help keep insulin peaks down...

But the diet also works on the gut. See http://www.vitamindandms.org/ and http://web.inter.nl.net/users/vitaminda ... -in-ms.pdf An unbalanced gut flora arguably manipulates T/B cells that then migrate through the liver to the brain. These bad T/B cells would then cause further damage to the already vulnerable and low-level inflammated myeline. These bad T/B are also understood to be the cause of many 'chronic immune' system diseases' as diabetes, asthma and rheumatic disorders.

This latter is what the neurologists have always believed is causing the MS. This latter is also what is common believe in the medical world for what causes many chronic diseases. But if one looks at the total picture from the outside, one really starts to wonder whether that concept is correct... And whether one should really speak here of an 'immune system disease' or, alternatively, whether what one sees is really the consequence of other things such as impaired micro-cellular feeding and receptor dysfunctioning as the following cases would seem to hint at.

The above articles on Mediterenean diet and on the wheat flour, returning people from pre-diabetic to non-prediabetic with marked improvements or total relief from arthritis or improvement in asthma, a relief of acid reflux and irritable bowel syndrome, disappeance of numbness etc would suggest that perhaps here lies the origin/etiology of many chronic diseases while the excited immune system is in fact nothing else than a perfectly normal re-action.

All blood from the gut passes through the liver. Hence, the liver may serve as an important gateway to stop bad things from the gut from proliferating through the body. For us, the case of the Caucasian women with MS is an interesting case. When this women got a new liver, she saw her MS reverse. I believe that her new liver changed the type of cholesterol being produced and that it is precisely that what caused her MS improvement. I can not imagine her new liver being a better gate for bad T/B cells.

THIS WOULD SUGGEST THAT THE DOGMATIC BELIEVE WIDELY HELD IN THE MEDICAL WORLD OF A CHRONIC IMMUNE SYSTEM DISEASE IS BASED ON WRONG PRESUMPTIONS.
And for us, it would suggest that the fact that we have not yet found a solution for arresting MS progression is caused by a completely wrong understanding of underlying disease mechanisms.
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MS in summary

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Taking things further from the previous posting:

The immune system involvement is secondary where irritation may be promoted by an imbalance in the intestine and the associated LSP production.

The primary mechanism is that of oligodendrocytes that are not well or not sufficiently maintained. It is a transcription process that is activated from the vessel walls that goes wrong.

Many years of venous obstruction (CCSVI) will have weakened the important tissue of the vessel walls, in particular the receptors that control various processes (transcription / nutrition) in the finest capillaries.

A virus or bacterial infection further blocking receptors than is enough for an inflammation (the immune system signals that there is something going wrong) and an acute relapse is the result. If severe enough, you get RR MS.

In the secondary stage, it is a different mechanism. The bad things then come up from the intestine through the liver (all part of the endocrine system). This mechanism is going to play from mid age.

All blood from the intestine passes through the liver. The LSP production in the gut may stir up the immune system somewhat. But what particularly matters is the related cholesterol production (LDL cholesterol MGmin etc.), the primary process, that further blocks receptors in the vascular walls especially in the finest capillaries. And then, as receptor functioning is weakened, the transcription will be further undermined. The myelin/axons condition will slowly disintegrate and SP / PP MS is the result.

Finally the immune system comes around again to clean up the mess (in a re-active mode) ...

The new liver in the case of the Caucasian woman reversed her MS. There is also experience with gut (flora) transplantation in MS where the disease process reversed and people after 15 years remain asymptomatic... And of course the beneficial effects of the diet are known..

This strengthens the case that the etiology of MS rests in the gut possibly in combination with the liver.
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Re: I think I found it: This Is MS

Post by elliberato »

ms in the raw...my friend feels your grief...
www.thegreekfromdetroit.com
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Leonard
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are we at the outset of a "Medical Spring" ?

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elliberato wrote:ms in the raw...my friend feels your grief...
http://www.thegreekfromdetroit.com
thank you, I feel touched by your words...

Your story under the link carries some fine emotions.
We easily resign to pessimism, in my darkest dreams I am no different..
Yet, as you say, we are strong at the same time coping with our every day situation sometimes doing things even normal people can't do..

What I consider worst is the psychological dessert we have been forced to enter,
more in particular when placed in a situation where emotions easily take over from common sense..
leaving us with the idea that we got stuck in this dessert, that we can never go home, that we are doomed forever..
It is like seeing a Fata Morgana with, at the horizon, the great illusion of no-hope.

I am convinced now this is a false no-hope.
It is a message of no-hope that served a professional system, that was maintained through the enormous weight of the status quo.
It is not to put the blame on anyone, it is a system that lacks the incentives to change ..

But it won't be for long... the public can conceptualise very well..
Just look how the debates in the public / patient fora have shifted emphasis over recent months,
look what new issues are introduced e.g on the role of the gut etc...
Or look at the role of public fora in disseminating patients' informed views raising the anger ...
http://dl.dropbox.com/u/66292082/Prof%2 ... 0final.pdf
http://www.lemonde.fr/sciences/article/ ... 50684.html
http://www.lemonde.fr/cgi-bin/ACHATS/ac ... ts&xtcr=96

I could get at least 3 major dogma's out of this thread that have dictated believes in the medical world for decades..
Wrongly...
Paradoxically, it is the success of the health care system that developed in the 20st century that impedes progress now..

Fortunately, the new insights are gaining traction and momentum..
Continued pressure from our side will help organising for the world of the 21st century,
it will help ensuring the new visions can land and
it will help speed the development of an international self-confidence among care givers..

I am sure we are in here for a "Medical Spring" (MS)..
It is a new wave of democratisation that will replace the message of false no-hope with one of hope for a better life for all...
Last edited by Leonard on Wed May 02, 2012 4:18 am, edited 2 times in total.
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is it the astrocytes or is it the mechanism before?

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http://www.smh.com.au/national/research ... 15sfw.html

Quote: Their work, which suggests the past 40 years of MS research has been looking at the wrong parts of the central nervous system, could eventually lead to new treatments.

"Astrocytes are very common and important cells … their role in the central nervous system is basically to look after everything else," Professor Prineas, from the University of Sydney, said. unquote

http://www.sciencedaily.com/releases/20 ... 170439.htm

Quote: Scientists have long known that that's a job for astrocytes -- sopping up excess potassium, ending the nerve pulse, and restoring the cells so they can fire again immediately. unquote

If the astrocytes don't do their work properly, the equilibrium of our ion pump will not be sufficiently maintained and our motor function will go down slowly (and recover slowly with the typical time delays we see).

The maintenance of our nervous system then is a complex process that involves both astrocytes (ion pump, motor functions) and oligodendrocytes (maintenance of myeline and axons)....

I think that the vessel walls in the finest capilarries and more in particular key nuclear receptors play an essential role here for ensuring proper feeding and transcription... and that if these receptors get blocked or dysfunction for whatever reason, the stage is set for developing MS...

Therefore, researchers should not waste another 40 years of MS research on the astrocytes. It is not the astrocytes or the oligodendrocytes as such which are the problem. I think they are just fine. But it is the disconnect in the vessel walls between the bloodflow (for us with RBC carrying a very high ATP because of impaired transfer; incidently for diabetics patients who have their diabetes under control, the RBC carry a low ATP) and these important support cells, in particular in the finest capilarries. It is the process of nuclear receptor interaction that fails, probably for "environmental" reasons (plaques?, super sticky mGmin LDL cholesterol?); and it is not one or the other intrinsic genetic defect of brain cells or immune system defect [dogma2].

I can just hope that future research and treatment plans will look at this broader horizon.
Last edited by Leonard on Mon Apr 09, 2012 2:36 am, edited 2 times in total.
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Re: I think I found it: This Is MS

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LEONARD,
you need to start a blog...your words are profound, intelligent, and inspiring. You are definately a leader of the revolt! Awesome!
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Leonard
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Re: I think I found it: This Is MS

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we don't have to fight this alone.
this matter needs a political engagement.

the political discussion should have the right balance from the outset.
that is to say it should not be dominated by neurologists or the field of neurology..

I am sure through our participation to these fora we will be able to deepen and strengthen our representative democracy.
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Re: I think I found it: This Is MS

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I am convinced that the etiology of many chronic diseases that have been earmarked as "autoimmune diseases" rests in the gut (possibly in combination with liver and pancreas). I find these links rather inspiring:
http://www.purenewyou.com/shop/index.ph ... &cPath=162
http://www.kruidenvrouwtje.nl/zozitdat/schimmel.htm (in Dutch but Google Translate does a good job)

Whether it is a generally low vitamin B12, a magnesium deficiency (muscle pain and spasms), a zinc deficiency (control on insulin) or copper deficiency (high blood cholesterol), a mycose nail or athlete's foot or tinea cruris in the groin, or yeast and candidiasis, these "symptoms" typically seen with MS patients are essentially caused by an unhealthy / unbalanced gut flora.
http://biochemie.web.med.uni-muenchen.d ... 0Fungi.pdf
http://www.thisisms.com/forum/general-d ... 19653.html

The bad gut flora results in an intestinal lining which is more permeable (porous) than normal, a "leaky" gut, where the bloodstream can be invaded by bacteria and fungi. These may then colonize almost any body tissue or organ. So our mycose nail comes from within... The porous gastrointestinal tract will cause allergic or "autoimmune" diseases because the immune system starts to make antibodies to larger molecules in the tract because it recognises them as foreign. whow, read this:
http://www.mold-survivor.com/leaky_gut_syndrome.html

A related question is whether you could benefit from special "manipulated" bacteria to treat the situation (as suggested by the news feed under the link below) or, alternatively, whether it would not be good enough if you would restore the normal intestinal flora by gut flora transplant. The latter is what they do in Amsterdam and in other places around the world for diabetes, and also what is being practised for MS with good results that have shown to be sustainable over the years.
http://www.medicalnewstoday.com/releases/243917.php

It seems ever more important that a bigger holistic picture of "altered immunity" diseases is developed as a matter of urgency.
I believe it will show that many of these chronic diseases including MS and diabetes are pathogenic relatives, or forms of immune dysfunction, with a common underlying cause in the gut [rather than being a range of different autoimmune diseases - dogma3]


I have just updated the raw sketch of a new concept for MS in the first posting accordingly.
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Re: I think I found it: This Is MS

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quote from http://www.neuropenews.org/?p=609

Conclusion and recommendations: Based on these extensive, scientifically solid data obtained from investigators outside of Ferrara, we see no rationale to support CCSVI as a key pathogenetic factor in MS.
Furthermore an ongoing large multi-center Italian epidemiological study recruiting more than 1000 MS patients and about 1000 healthy controls and patients with other neurodegenerative diseases, promoted by the Italian Foundation of Multiple Sclerosis and endorsed by the Italian Society of Neurology will greatly augment our scientific knowledge about the relationship between CCSVI and MS.
There is the theoretical possibility that the venous drainage of autoimmune lymphocytes from the brain may cause some endothelial changes during the longstanding disease course of MS, maybe in combination with immunosuppressive therapies. Yet even if this were the case, this is insufficient to justify invasive, costly and potentially dangerous manipulations of the deep cervical venous system in MS patients.
Therefore, both the EFNS and the ENS Multiple Sclerosis Scientist Panel and ECTRIMS Executive Committee emphasize the high risk and absence of a scientific basis for “liberation procedures” in MS patients. All societies are in full accord with the Multiple Sclerosis International Federation statement on CCSVI.

unquote

These neurologists from Europe are not very honest with us. The truth is of course that many years CCSVI will damage the endothelium. To link this with patients who had "immunosuppressive therapies" is tendentious and misleading...

Essential processes that are controlled from there will then slow down or fail, including nutrition and transcription. This in combination with a 'leaky gut' eventually gives rise to MS.

So strictly speaking, CCSVI is not MS, MS is different and more complex. But CCSVI does prepare for the condition; and this is a whole lot more than just "a theoretical possibility". The first posting on pg 1 explains further.
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Re: I think I found it: This Is MS

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quote from http://www.ncbi.nlm.nih.gov/pubmed/22252237

Characterizing brain oxygen metabolism in patients with multiple sclerosis with T2-relaxation-under-spin-tagging MRI.

Our results of significant underutilization of oxygen in MS raise important questions regarding mitochondrial respiratory dysfunction and neurodegeneration of the disease.
unquote


you may find numerous links to poor oxygen usage in diabetes by just Googling on diabetes and oxygen.
sometimes the slant on things is the right one, sometimes the low oxygen level is suggested to be a causal factor for diabetes..

of course, we know about the "diabetes dimension" in multiple sclerosis, many postings above refer (e.g. of Russian tomographic study on glucose usage in MS).
we know that glucose uptake and oxygen uptake of the cells are related, not one without the other.
and we know that our body and in particular the vessel walls have some difficulty to transport the glucose from the bloodstream to the cells.
and we know that dysfunctioning or slowly functioning receptors in the vessel walls causes us the trouble.
and we know that our astrocytes and oligodendrocytes suffer because of that (and that there is nothing wrong with the astrocytes and oligodendrocytes as such).
and we know the result...

I find it really amazing to see how a whole sector is struggling with this matter while it is right under their nose..
in any event, this study is yet another strong confirmation of the concept that is sketched here.
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ECTRIMS 2012

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http://www.congrex.ch/fileadmin/files/2 ... index.html

Under the above link, you find the preliminary programme for ECTRIMS 2012, that is the European Committee for Treatment and Research Into Multiple Sclerosis. Last year they met in Amsterdam in a joint conference with ACTRIMS, their American sister organisation. The scene is set by the neurology, what else would you expect...

I had a quick look at the programme. Last year or the year before, I remember that was difficult for me but I guess I am learning to find my way...

The programme is still pretty much neurology focussed, almost as if there is no world outside while MS is a neurological disease of unknown origin... But I also sense some more emphasis on studying the underlying causes of our disease and less so on immune suppressive therapies and the like, so perhaps there is some change in the air..

It gets interesting on page 16 of the programme. Here, you find a session on controversies in the natural history of multiple sclerosis. The text reads: "Several concepts have emerged from the recent analyses of the natural history of MS in representative cohorts of patients. Dr1... will focus on the lack of a clear association between relapses and long term disability accumulation, the MS onset being exacerbating-remitting or progressive. Dr2... will discuss the association between the patients' age and the MS clinical course and disability milestones. Dr3... will merge these observations with the concept of MS being one disease with different clinical phenotypes, infer about pathophysiology and treatments, and discuss the need for a revised classification of MS. "

Well, of course we know how it all fits together, that it is a two-stage disease, about the relationship with age and why we see what we see, and a whole lot more for instance on the relation with the gut.... The first posting with the raw sketch of a new concept for MS explains.

Again, but now I start repeating myself, I find it really amazing to see the neurology sector struggling with this matter while it is right under their nose..
If there are people of the ECTRIMS programme committee reading here or people who have connections, - if you promise not to tear me apart - I offer to come to Lyon to present the raw sketch of concept that has been developed here. Just send me a pm. Waiting until 2013 is far too late..
Last edited by Leonard on Wed Apr 18, 2012 6:46 am, edited 1 time in total.
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the role of vitamin D

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with reference to this discussion on the role of vitamin D http://www.thisisms.com/forum/general-d ... 19729.html

Vitamin D can help produce a natural antibiotics, cathelicidin, to help restore a healthy gut flora. See for instance http://web.inter.nl.net/users/vitaminda ... -in-ms.pdf

This seems to explain the fact that most MS diagnoses are made in the Spring. The gut flora detoriated during the Winter time, and a faulty brain-bowel connection (porous gut, compromised BBB) then caused the uprise of MS. [Vitamin D and the immune system will be involved here but not necessarily in/as the primary path]

Of course supplementation of vitamin D may help to keep a healthy gut flora in Winter time. I do not exclude the possibility that 7 x 3000 I.E. (daily intake) is better than 25,000 I.E. once per week. This was also suggested in one of the postings under the first link of this posting..

To complicate things further, the vitamin D concept then is one with vitamin D content on both sides of the intestinal lining i.e. in the gut flora and in the bloodstream. They are not necessarily the same, they do not necessarily work the same..

Besides the gut, there is another relationship to Vitamin D and that is at the intra-cellular level. When the mother is pregnant or during the adolecence, the body grows and new cells are formed. The body then takes the building blocks that are available at that moment, from the blood of the mother or the own blood stream.

What I found most striking is that all players of the Canadian national ice-hockey team were born in February. Ice-hockey is one of the physically most demanding sports. I am not joking here.. What is the case? When their mothers were pregnant (going through the first say 4-5 months), it was Summer. And the vitamin D level of the mother may be assumed to have been high(er). As the fetus was growing, it took the available building blocks and you might thus expect the cells to have more vitamin D gates and less 'calcified' gates. And these players to have a better glucose metabolism...

The same is true for young people. If there is more vitamin D available during their adolecence, newly formed cells will have more vitamin D gates, the conditions for cellular feeding later on in life will improve, and as a consequence one has less risk to develop MS later on. The story of the identical twins where one moved further South in his/her childhood and has less risk of developing MS later on than his or her twin brother or sister is almost anecdotal... Again, because the former have more active gates and nutrition works better...

This seems to be fully confirmed by the fact that the risk of developing MS depends somewhat on the month of birth
http://multiple-sclerosis-research.blog ... birth.html
http://www.webmd.com/multiple-sclerosis ... rosis-risk
http://www.bmj.com/content/330/7483/120
There is suggested a relation to the genes and epigenic factors but obviously we know better..

There is definitely a role for vitamin D in MS, and in fact through several working mechanisms (gut, micro-cellular feeding, cell composition, see my posting of 17 Aug 2012 on http://www.thisisms.com/forum/general-d ... 00-15.html ), but on the whole I think it is an influence, one of the many... anyhow, this to complete the picture...
Last edited by Leonard on Fri Aug 31, 2012 12:07 am, edited 2 times in total.
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