Theoretical Immunology

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Leonard
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Nerve conduction, sugar and fat..

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MS patients have a bad nerve conduction of signals from the brains to the periphery and vice-versa. The problem of conduction is serial: there is a problem with the conduction in the CerebroSpinal (due to the scleroses) and in addition conduction may degrade because of pre-diabetic conditions. For diabetes patients, the neurological symptoms are similar to ours like numbness of the hands etc. For them, these symptoms show up when the diabetes diagnosis is made but then the process is already underway for many years. For us, these symptoms show up much earlier because we already have an impaired conduction of the signals. Therefore, we are much more vulnerable to diabetes-like nerve degeneration.

Besides demyelination, I believe the degradation is mainly caused by an undernourishment of the cells, including nerve cells with the result that the ion pump is not sufficiently charged to maintain its equilibrium necessary for passing nerve signals and ultimately - if undernourished for a long time - the death of the cell. In this context, I believe that the combination of (thick) saturated fats and high sugar consuption is devastating. I also believe that it is no so much the arteriosclerose or hardening of the veins, but rather that it is the GLUTS (the glucose transporters on the cells at micro-cellular level) that are blocked-off that is the problem. This would explain why the Swank diet works and also why the no-sugar diet (as the old wise neurologist said) works to turn away from the MS disease. I think the GLUT problem really applies to us because we have a problem with the power of the cells. And what we have left, we must keep alive.

I think that MGmin cholesterol that grows on sugar and thick saturated fats and that "seals" the GLUTS of the cells is somewhere somehow part of the picture. As well as Metformin that seems to be able to break down the ultra-bad and super-sticky MGmin cholesterol. I have seen many working mechanisms for Metformin suggested including stabilising the blood sugar level/glucose level and working on the liver to produce lower peaks in the blood sugar. I think the medical sector has to leave behind another dogma here. And accept that it is the cells (at micro-cellular level) that open up and absorb the glucose better due to the medication. Thereby it will look as if the blood sugar is regulated down but probably that is conceptually wrong.

This pre-diabetic condition (which is causing the progressive phase of MS) is more likely to happen at mid-age because of the skin (lower Vitamin D production), veins (hardening) and intestinal flora unbalances (Western diet and lack of Vitamin D). I think this is a wonderful article http://www.healingmatters.com/diabetes.htm describing the important role of the GLUTs.
Last edited by Leonard on Mon Nov 14, 2011 8:07 am, edited 2 times in total.
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Leonard
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Re: I think I found it: This Is MS

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I will try to recapitulate:

What is Multiple Sclerosis?

Multiple Sclerosis (MS) is caused by a faulty immune system that reacts to problems in the intestine (faulty brain-bowel connection). If the gut flora is unbalanced, bad T-cells induced by the gut start to spread in our body through the bloodstream. Here, the over-presence of the segmented filamentous bacteria (SFB) in the gut flora is suspect.

The immune system response to the bowel infection is believed to be the cause of many diseases including diabetes, rheumatic disorders and late-onset asthma. For people with MS, after many years of CCSVI (venous insufficiency in the draining part of the brain) the blood-brain-barrier (BBB) will be compromised causing the protective tissue to become permeable. Bad T-cells can then enter the brain and do their destructive work. In particular, undernourished weakened cells of the eco-system that got infected are targetted. Besides neurological damage in the CerebroSpinal, people with an unhealthy intestinal flora may develop a diabetes-related peripheral neuropathy aggravating the neurological symptoms.

While the unbalance of the gut is mainly responsible for the secondary degenerative phase, in the early Relapse Remitting phase of MS, the immune system may react to virus infection (e.g. Bar-Eppstein) or a periodic reactivation of the Chlamydia bacteria.

refs:
1. http://www.congrex.ch/fileadmin/files/2 ... harcot.pdf, see page 2;
2. http://www.mscare.org/cmsc/images/pdf/MSE_Nov_03.pdf ; the results of epidemiological research are very strong!


What about our kids? Speed is of the essence

A related question is: what if our kids would turn out to have CCSVI – the genetic component in MS is known. But have no symptoms of MS yet. Is it dangerous for them to have CCSVI? Because the BBB could get under stress with the risk that it finally breaks? After which T-cells can do their destructive work and they would eventually develop MS.

MS patients may certainly benefit from the new insights. But it may be our children that are the real winners of this breakthrough. If they get liberated in good time (assuming they have vascular constrictions of their neck veins draining the brain) they will never develop MS.

With good screening programmes through relatively simple and inexpensive echo-Doppler examination, in the time of a generation, MS may be of the past.


The systemic problem

Neurologists believe that CCSVI is a strange term. A vascular specialist knows very well what is CVI, CCSVI is nothing more than CVI (Chronic Venous Insufficiency) for the Cerebro Spinal.

This shows the problem. MS is a disease that transcends beyond the boundaries of the different medical disciplines. MS is caused by a complex of issues; there is not one single cause. It involves neurology, vascular, endocrinology, and diabetology.

Cooperation across the boundaries is easy and automatic for some diseases like cancer, but for MS it is not. The patterns for cross-discipline communication in the field of MS are virtually non-existent. The current division of work and the strict protocols of medical specialists create an important cultural barrier to change.

In addition, the power of the system presents a significant problem. Firstly, so many institutions and so many people from health professionals, science, commerce and government have so much invested in the current system, and therefore have so much to loose by change. Secondly, the public, politicians and patients are almost all conditioned by history to think about health and health care in particular ways. The very things that helped us make such excellent progress in the twentieth century have, paradoxically, now become a major part of the problem.

ref:
3. http://www.amazon.com/Turning-World-Ups ... 89&sr=1-1


The challenge is to graduate the system

As there are powerful opposing forces to change, there is risk of developing confrontational positions between medical disciplines. The challenge is to manage a real-life transition as smooth as possible and to fend off the risk of stagnation of the whole system.

This will need to involve another way of approaching MS as a disease. The medical system is deeply entrenched in research, and the research culture is dominant. But as it looks now, MS is more a scientific combinatorial problem than a deep research area that could possibly be unravelled by applying and connecting to each other existing scientific results more vigorously.

As the potential ramifications of current findings are so huge, the medical sector may have lost its fixed Archimedean points from which to exert leverage. Outside help may help accelerate the change process.

ref:
4. http://www.thelancet.com/journals/lance ... 1/fulltext
Last edited by Leonard on Thu Nov 17, 2011 12:43 am, edited 1 time in total.
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Leonard
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The role of Vitamin D: something to think about

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Under the link you find a beautiful video on Vitamin D:


A few remarks made:
= careful when we use the animal model these days; may explain why the mouse model is wrong for humans..
= careful with Vitamin D supplementation as after some time it may give the inverse effect; also to note comment in question round
= 14:30 in the subtitle of the slide: explanation for the high prevalence of "auto-immune" in women
= 17:00 immune suppression encourages chronic diseases...
= the body regulates down the concentration of Vitamine D as a protective measure against immune disease..
= towards the end, supplementation in the food supply may be counterproductive


This is another video on Vitamin D, clearly arriving at different conclusions:


= explains where the fobia for Vitamin D poisoning came from;
= enzyme introduces its own break
= body adapts, important is how Vitamin D fluctuates

I guess the future will tell who is right or wrong :sad:
It would be interesting to confront Trevor Marshall with the views of Reinhold Vieth and vice versa.
Personally, I like the first presentation better because it is not on Vitamin D itself but on its role on the root of the innate immune system.
Last edited by Leonard on Tue Nov 15, 2011 7:59 am, edited 4 times in total.
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Re: I think I found it: This Is MS

Post by BERNARD »

thanks to speak about other possibilities ( sorry for my bad english ).
I was doctor in France , in deperate countryside and was estonished by old veterinary ttt wich stimulate the immune system in animals ( mainly horses and cows) : immune arthritis, viral and microbian deseases , etc
Further , in North india ( I spend many missions in desperate villages where ther had no medecine , no doctor)) i hear and saw same thing on ... humans ! It seems to give good results on many chronic deseases , specially immune arthritis and chronical or acute infections ( they had no antibiotics).
The medecine was combination of essential oil, phytotherapy and somme kind of salts ; farmers put that "mixture" on skin injuries that they made in this aim or sub cutaneous injections.
We had in europe , before actual and moderns medecines such treatments for veterinary and medical uses, but the probleme was dolor +++; its seems the Indan "mixture" (sorry) had not that default and is well tolered without any side effect. It seems be employed in non official way , actually in India by some "Ayurvedic doctors "
Sorry , I know you have to face many strange treatments ; I want only to give you that information on what I saw
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Leonard
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Is Vitamin D supply healthy?

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I am referring to the Youtube presentations from Marshall and Vieth in my earlier posting of today.

I think that Marshall has a good story.
The presentation is strong because the workings of Vitamin D are presented in a microcellular environment on the roots of the innate immune system.
And he uses much results and evidences from recent papers and research.
Towards the end in the Q & A session, he sounds very confident of his own right, particularly through his experiences with patients.

The story from Vieth has more focus on Vitamin D, per se.
Where, because it is not framed in a broader context, it lacks something.

By the end of the story of Marshall, he says that the metabolism regulates the vitamin D down to protect...
And that supplementation of vitamin D in the food supply may work counterproductive, and could give rise to more cases of "autoimmune" diseases.
That's big!!
If it is true what Marshall is saying here, then here again, we are running into a big dogma, almost a doctrine, which now proves to be wrong...
And again, like with auto-immunity for MS, experts that may have for years advised their governments and patients, will have to change.. and that is not easy...
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Leonard
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Is the Vitamin D nuclear receptor the culprit?

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I think that the VDR (vitamin D receptor) is the culprit;

contamination of the receptor by enzymes from bacteria leads to a dysfunction of the Vitamin D;

the innate immune system (the first line of defence of the metabolism) is turned on: see my posting immediately below explaining the immune response to the unhealthy gut flora (bacteria);

this then gives rise to what is called "autoimmune" diseases; a doctor once told me that the word "auto" means that they just did not know where it came from; she had her training 35 years ago and at the time that was perhaps so, but then the concept has changed over time..

we have a compromised BBB through many years of CCSVI; those T-cells penetrate our brains and do their destructive work attacking weakened and infected cells; on top of that there is a (serial) effect because also in the periphery nerve conduction may be affected.

I can see a cure along two different paths, which may possibly be combined:

1. get the bacterial-load down:
- By low fat / low sugar diets such as diabetics do; by fasting etc [to note: 3 weeks on a 600 kcal diet heals you from diabetics)
- By anti-biotics e.g. Marshall protocol, minocycline trials, daptomycin etc

2. do something with the VDR:
- By cleaning it with olmesartan
- By blocking it e.g. by Metformin

I find these article easy to understand:
http://bacteriality.com/about-the-mp/
http://www.townsendletter.com/Jan2009/vitaminD0109.htm
http://autoimmunityresearch.org/preprin ... eprint.pdf

for tara97, I note that the FDA is involved in this. it would interesting to find out more...
Last edited by Leonard on Tue Nov 22, 2011 9:07 am, edited 2 times in total.
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Leonard
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Re: I think I found it: This Is MS

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Vitamin D has apparently several functions: it is a building block of the cells during pregnancy and childhood, and helps to nourish the cells by interaction with the insulin. But it also does something in the intestine.

The link between MS and the bowel is increasingly stressed where the intestine induces a reaction of the immune system, see for example http://www.ncbi.nlm.nih.gov/pubmed/19833089

It appears there is a direct link between vitamin D in the intestine and triggering the immune system in the intestine. Where a dysfunction of the Vitamin D nuclear receptor (VDR) would mean that it is no longer able to effectively control the NF-Kappa B. And at that point the immune system would turn on.

Quote from the link below: Also Sun's team discovered thats the vitamin D receptor plays a key role in defending the body from assault by Salmonella and squelching inflammation. The receptor stops a molecule known as NF-Kappa B, a well-known master player in the world of inflammation, by binding to it and Preventing it from activating other inflammatory molecules. While scientists have known thats the receptor inter-acts with NF-Kappa B, details of the interaction modulated by bacteria in the colon are new.
The scientists found that Salmonella was much more virulent and aggressive in mice in which the vitamin D receptor had been turned off. These mice showed higher levels of activity of inflammatory molecules..
http://www.sciencecentric.com/news/1007 ... layer.html

the nuclear vitamin D receptor (VDR) is directly Involved in the regulation of NF-kappaB activation
These data suggest an inhibitory role That VDR plays in the regulation of NF-kappaB activation.
http://www.ncbi.nlm.nih.gov/pubmed/17298882

Incorrect regulation of NF-kB Has Been linked to cancer, inflammatory and autoimmune diseases
http://en.wikipedia.org/wiki/NF-kappa_B
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Re: I think I found it: This Is MS

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There is a new free website that offers the same clinical articles used by professional neurologists to the general public. It has the most extensive MS coverage of any online resource. Note that the articles are written for physicians and not dumbed down for general consumption, but they are of considerable depth and quite up to date. The site is available here:

http://www.medmerits.com
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Re: I think I found it: This Is MS

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I find this discussion of significant interest.
Anyone considered renal function and posture? Denser solutes, be it sugar or salts migrate in accordance with the direction of gravity through the vessels! Renal function improves on IBT. Could sleeping inclined (IBT) help to resolve excess sugars in the blood? See experiment:
Inclined Bed Therapy (IBT) | http://www.inclinedbedtherapy.com
Sleeping Inclined To Restore and Support Your Health For Free. Fascinating Science, Discovery, History and Medical Research In Circulation And Posture.
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Leonard
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Re: I think I found it: This Is MS

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This article explains it all:
http://autoimmunityresearch.org/preprin ... eprint.pdf
http://www.ncbi.nlm.nih.gov/pubmed/19758226
including the "contagion factor" of partners: see http://www.ncbi.nlm.nih.gov/pubmed/21883098

and this is also relevant:
http://autoimmunityresearch.org/preprin ... eprint.pdf
http://autoimmunityresearch.org/preprin ... eprint.pdf

is all this nonsense? or coincidence? Of course not. The simple fact that my body's vitamin D was down-regulated as the disease progressed - probably for self-protection - is for me a very strong signal...

A few extracts from the article:
"This suppression would lead to short-term improvements in patients taking higher levels of vitamin D by slowing bacterial death and subsequent immunopathological reactions. Therefore, studies that evaluate the role of vitamin D supplementation in chronic inflammatory diseases should take into account the potential for short-term symptom reduction, but exacerbation of the disease process over the long-term due to pathogen increase."

"Problems with many studies on vitamin D include failure to adequately consider confounding factors, failure to measure the active metabolite (1,25-D), inadequate study lengths, overreliance on in vitro and animal studies, lack of randomization7 and a failure to consider the alternative hypothesis for low vitamin D levels."

"As mentioned previously, the majority of studies inferring vitamin D deficiency plays a role in causing disease are epidemiological studies that are just as consistent with the alternative hypothesis that low vitamin D levels are a result of the disease process, rather than a cause."

and this: "A divergence in response in different populations might even be an explanation for the mixed, inconclusive results in vitamin D studies."

There are many important leads in the article, and I ask myself whether and to what extent these have been taken into account in the Vitamin D studies that we see. If not, as far as I am concerned, they can be filed on the board immediately (shelfware).

The discussion yesterday about olmesartan shows a possible link of a VDR dysfunction with the glucose metabolism. I think that the glucose metabolism indeed plays a role here, alongside the "activation" of NP-KappaB and the immune response from dysfunctioning VDR (is not necessarily the same as non-functioning ..). Improving the glucose metabolism would first improve the nutrition of the cells (like Metformin) and possibly regulatory pathways of the immune system calm down because this feeding improves.

Hence, there may be a direct (via NP-KappaB) and an indirect effect (via the glucose metabolism). I do not exclude the possibility that if you look differently conceptually, there is a common underlying mechanism ... but that is still in the dark ...
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Leonard
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Re: I think I found it: This Is MS

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I am convinced that there is a multiplicity of factors that contribute to the development of MS... and that share a joint diagnostic profile (you have MS). Have a look at Figure 1 of http://autoimmunityresearch.org/preprin ... eprint.pdf to see how all these 'autoimmune' diseases overlap .. and it tells you enough ..

Therefore, urgent action is needed to establish measurable key indicators to bring some order into this diversity. For example the measured 1.25D could be a good indication for... or when diabetes2 is in the family for... etc etc. And I honestly believe that you will end up with maybe 5 to 10 profiles that cover the whole spectrum .. and then from there you may start the most promising treatment ...
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Re: I think I found it: This Is MS

Post by Leonard »

MacksJ wrote:There is a new free website that offers the same clinical articles used by professional neurologists to the general public. It has the most extensive MS coverage of any online resource. Note that the articles are written for physicians and not dumbed down for general consumption, but they are of considerable depth and quite up to date. The site is available here:

http://www.medmerits.com
Thank you!

I had a quick look at MS and note a rather neuro-centric view of things.
Take for instance the Vitamin D study at http://www.medmerits.com/index.php/arti ... treating_m
This very neuro-centric view makes it less useful... but it seems that that is the problem in general with this disease.
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Leonard
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Re: I think I found it: This Is MS

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AndrewKFletcher wrote:I find this discussion of significant interest.
Thank you!

I feel that I am not in the best place to comment on the IBT.
The only thing I could usefully say is that, if you have serious strictures in your neck veins, anything that helps to relief the blood flow from your brain is good. IBT seems part of that..
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Leonard
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Vitamin D and seasonal effects

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It is known that many flares occur in the spring, when vitamin D is low. It has therefore been suggested and this is obvious that there is a direct relationship between the Vitamin D levels and the worsening of the disease. I think that notion is conceptually very wrong. I will explain.

After the summer, the level of the vitamin D precursor form, called 25-D, is the highest. Beyond mid-age that level and the volatility will become somewhat less (probably a protective effect of the body).

The half life of vitamin D in the blood is approximately half a year. So after a half year, a portion of the vitamin D precursor (25-D) will have been converted into the active form of vitamin D 1,25-D. I would think that the peak of the 1.25-D occurs somewhere from 3 to 4 months after the peak of the 25-D.

When the 1.25-D becomes [too] high, it binds a set of key receptors and displaces the metabolites that are supposed to activate from these receptors [re: Marshall]. Since these receptor transcribe natural anti-biotics created by the body called anti-microbial peptides (e.g. in the gut flora), the high 1,25-D (and its effect on the nuclear receptors) will cause the production of anti-microbial peptides to slow.

Besides the effect described, the high 1,25-D will displace cortisol, T3 and other metabolites from their target nuclear receptors, causing havoc on the body's hormonal pathways. Thus, we have difficulty tolerating stress, changes in temperature, and a variety of other hormone-related issues (just like diabetes patients, and patients with other chronic disease).

Well, as anti-microbial peptides work less (and also the innate immune system works less), all kinds of bacteria are far more likely to grow. The VDR receptor will get further blocked (by enzymes from these bacteria), and then finally the immune system will turn on with its proliferation of T cells. And because our BBB is broken (re: CCVSI), we all know the consequences ...

When does that happen? I think a few months after the 1,25-D peak, so in total somewhere 6-8 months after the D-25 peak. While in the winter or immediately after the system should work optimal...

Conclusions:
= There is an indirect and inverse effect of vitamin D on [gut] bacteria growth;
= There is a time lag of about six months between vitamin D increase and its effect on the metabolism where bacteria cause dysfunction of the VDR and turn the immune system on ..


MS thus is composed of three major components:
= the vascular strictures in the neck (CCSVI) that after many years cause the BBB to break;
= a "faulty" brain-bowel connection where a bowel-induced immune system response causes T-cell attacks on our (infected) brain cells;
= a deficient Vitamin D metabolism that weakens the innate immune system and causes bacterial growth (e.g. in the gut) that then induces T-cell action.
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Leonard
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For the non-believers...

Post by Leonard »

further evidence that a VDR dysfunction is the culprit:

http://www.ncbi.nlm.nih.gov/pubmed/19758177
http://www.ncbi.nlm.nih.gov/pubmed/19758226
http://www.ncbi.nlm.nih.gov/pubmed/16886667
http://www.ncbi.nlm.nih.gov/pubmed/19758159 (very strong! explains why women are in the majority)
http://www.ncbi.nlm.nih.gov/pubmed/20593215 (also very strong: explains the relationship to Eppstein-Bar)
http://www.jofem.org/index.php/jofem/ar ... icle/23/32 (from the Journal of Encocrinology: A unique feature of 1,25(OH)2D3 is that not only does it interact with T cells, but also targets the antigen-presenting cell, the central cell in the immune cascade; interesting to note here: India and other countries emerge, our system from the 20th century gets blocked or is stagnating, see Nigel Crisp...)
http://www.sciencedaily.com/releases/20 ... 223302.htm
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