Theoretical Immunology

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Scott1
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Re: A new concept and treatment options for MS

Post by Scott1 »

Hi Leo
I just pulled this from my "Beyond Avonex and Valtrex" pages but if you do a quick hunt there are numerous references and it comes up in the body of a number of articles.
“Epstein-Barr virus (EBV)-transformed cell lines derived from normal B lymphocytes and some B cell lines also possessed cytochrome b558 and two cytosolic proteins. Isolated human peripheral B lymphocytes generated the superoxide anion upon cross-linking of surface antigens such as IgM, IgD, IgG, HLA-DR, and CD19. EBV-transformants derived from normal peripheral B lymphocytes and B lymphoid cell lines also generated the superoxide anion when stimulated with various antibodies against surface antigens. These results indicate that peripheral B lymphocytes have substantial amounts of a superoxide-generating system identical to that in phagocytes and that the system is stimulated to generate the superoxide anion by the cross-linking of clonally expressed surface immunoglobulins or of certain surface antigens”. ( http://www.ncbi.nlm.nih.gov/pubmed/7592536 .)

I think its important to note our interest should lie in the excess production as all those radicals occur normally in a healthy system.
I get the short term stressors view but they wont explain other factors all astray at the same time, in particular shortages of vit D, B12 and a leaky gut from shortages of vit A which need to be persistent problems rather than transitory to always be an issue. That takes me back to where they are processed in the renal proximal tube. I don't think a viral issue is always at work there yet if they are deficient we will be more susceptible to stressors or viral problems.
The approach I take has left me with no fatigue or cognitive issues (I got tested) but a bit of damage to my spine from demyelination. I'm now fairly sure we have two pathways at work against us; an EBV/peroxynitite path for fatigue and many issues and a Th1 activated path for demylination. I'm having a really good look at peptidoglycans as a catalyst for Th1.

Regards
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Re: A new concept and treatment options for MS

Post by Leonard »

Scott,

Thank you for the information, very useful, shows EBV immune complexes have the same superoxygen generating capability than phagocytes, in fact it is explicitly mentioned…

As regards vitamin D and B12, they are scavengers of the peroxynitrite, their depletion may just demonstrate that we have this high level of peroxynitrite and oxidative stress. My tensed up shoulder is probably related.

My gut was tested and is not leaky. The test is reliable and based on metabolites that leak from the 'tennis court' into the circulation and then are filtered out by the kidney. Also to consider that if the HPA axis is affected, the endocrine system will suffer, including the cortisol production necessary for good gut function. In general, I tend to see the deficiencies of endocrine markers as collateral damage.

[As a side step on the tensed up shoulder:
I have never been very stress resistant. But I remember in 2005 – 1 year after being diagnosed with MS – I organised an international conference, 17 speakers from all over the world, over 250 people attending from as far down as Australia. Incidently and I am not trying to be ironic here, this was on the old world vs the new world in telecoms, very similar to what is going on in healthcare today. I was still in a reasonably good shape, only the gait was affected a bit by the flare up one year earlier.
With hindsight, this did not cause me any noticeable stress. I must admit, the full system was in place for organising these sort of events, things went just fine, debates were some times vigorous, you can still find traces on the Internet today. But if I would have to organise an event like this today, I could not, I would be burned up completely and immediately, the stress on my shoulders would be unbearable.
Did I change psychologically? May be, but I do not think so. I think it is the physiological mechanism, the biochemical cycle, that has eroded my metabolism. The parallel comes to mind of the Chronic Fatigue Syndrome attributed to psychological factors. This is not the case either, its origins lie in the same biochemical cycle, it just works the other way around and starts from the physiology.
After thought: Notwithstanding that the primary path is from physiology to psychology, there may be a secondary path - a much thinner line - back from the psychology to the physiology. This is the factor stress. That is why many MS therapies have yoga or other meditation elements. In a broader sense, I think this is all part of how we stand in life. This website captures the essence: https://www.bluezonesproject.com/power9
I was taken out of my "natural habitat" / blue zone 35 years ago after my studies when I started my international career. I think this is now true for many people as our society has changed from agricultural religious/reflective local communities to a modern global real-time/instantaneous information society.
George Jelinek writes in his book 'Taking control of Multiple Sclerosis': "A long time ago, I realised that our spirits reflect what we put into ourselves, what we think, and what we are exposed to. If we put trash into our spirits, we will have trashy spirits." The changing anatomy of the spirit, as George refers to, where we are increasingly consumed by poring over issues that have come up during the day may help explain - besides the weakened immune system due to poor diet and lack of immune training - the current scourge of immune diseases.

Now back to the main line of argument]

I agree with you that we have two pathways to work against us. And I would add to that that our problems may locate in different places, that is in the brains with demyelination (I think my problem with the gait in 2005 can be attributed to this - and the active lesions in the head) and that is in the peripheral nerves / muscles (I think this explains the main part of my current progressive problems).

For sure the EBV/peroxynitrite path is for fatigue and many issues. In my view, the other path is paved by the high load of EBV immune complexes that cross-reacts with transgenic OPCs causing the typical MS plaques (the viral tolerance theory underlies - see earlier posting). The OPCs stop and myeline is not maintained. During this cross-reaction, many mediators will be released by the infiltrating T-cells. This will increase angiogenesis and cause hyperproliferation of surrounding tissue cells in the CNS which in turn causes the pathological lesions (sclerotic plaques) typical for MS. In parallel, Th1 activation for demyelination may occur as an extension of the EBV/peroxynitrite path. The NF-KB is triggered by the biochemical cycle mechanism, causing elevated cytokines that contribute to raising the inflammation and Th activity. And in some way it becomes all convolved.

Leo
Last edited by Leonard on Thu Nov 13, 2014 1:23 am, edited 25 times in total.
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Re: A new concept and treatment options for MS

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Hi Leo,

I think in the main we are in vigorous agreement.
I wish I could lend you my Pilates teacher. She is like a physio on steroids. I've just come back from a two hour session. Like you I had troubles with a limp but she fixed it up.
What really made a difference was I would lie on a bench with my hips just on the edge. One leg would be down and the other up but resting on her. She would apply weight to my quads so the hip flexor is stretched. Then she would put her thumb on pressure points in my groin and in the area just inside my hip bone. Both refer to the soas muscle which in my case was super tight. The pressure point work is excruciating and I did a lot of swearing ( she's my friend) but suddenly the leg releases and it drops. By stretching the soas you will get power back into the leg. The other part was spasticity in the left calf. Really little movements to flex the foot, right down practicing pick up things with my toes worked wonders (and rapidly). Tiny movements like practicing scrunching up a theraband under my foot using my toes and little jumps on trampoline really are useful. You don't have to be Baryshnikov for it to make a huge difference. If your tight its worth trying. Its not exhausting.
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Re: A new concept and treatment options for MS

Post by Luvsadonut »

Hi Scott1
Rather than hijack the thread could I PM you about the psoas muscle release?

Thanks
Darren
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Re: A new concept and treatment options for MS

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Of course
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Re: A new concept and treatment options for MS

Post by Leonard »

MS is caused by the herpes family of viruses (along with other factors such as CCSVI).
There is a potentially very promising anti-viral medication, its name is Letermovir.

Letermovir has been designated orphan drug status by the European Medicine Agency (EMA) and the FDA.
see e.g. http://www.ema.europa.eu/ema/index.jsp? ... 058001d12b
http://www.ema.europa.eu/docs/en_GB/doc ... 129449.pdf
It has a completely new working mechanism.
It has very few side effects, very good tolerability and safety profile while no toxicity was observed even in the highest concentrations.
I think it might perhaps be compared with the anti-biotics for bacteria.

The orphan designation for Letermovir was granted for treatment of the cytomegalo virus (CMV), a member of the herpes family.
The CMV often arises in post-transplantation patients because their immunity needs to be surpressed.
EMA now asks what other diseases could be treated with Letermovir.
In fact, the medication works much broader than only CMV, for all herpes viruses.
See for instance the last pages of http://www.informedhorizons.com/hivdart ... chaeff.pdf
saying literally "Letermovir offers attractive options for the treatment of additional patients."
The pesentation also shows the superiority of the Letermovir over Valtrex/acyclovir.
And also Table 3 of http://aac.asm.org/content/56/2/1135.full on the antiviral activity of Letermovir against alpha-, beta-, and gammaherpesviruses.

But in parallel to the EMA action, a subtle game may be played by pharmaceuticals which could imply that Letermovir would be made available exclusively for the treatment of CMV in post-transplantation patients.
Is the pharmaceutical industry afraid here that the medication will cannibalise their existing billion dollars portfolio for MS medication? THAT WOULD BE UNACCEPTABLE.
As we live in an open and informed society where new information and knowledge circulates very quickly among patients and citizens, exclusive availability of Letermovir for CMV would no doubt result in a lot of off-label use and patients experimenting with the drug on their own. IS THAT WHAT WE WANT?
If EMA asks what other diseases could potentially be treated with Letermovir, could pharmaceuticals just cut off the path unilaterally where contract law supersedes the general public interest? THAT WOULD BE UNACCEPTABLE AND MAKE THE MATTER HIGHLY POLITICAL.

The viral dimension of MS is getting clearer every day. More and more studies are brought to my attention, every day again.
We also know that anti-HIV medication also works for MS with statistically very convincing data.
We must make sure that what appears a very promising path for effective MS treatment namely Letermovir is not cut off.

Therefore, I recommend to all of you who read here to ask your neurologist about the herpes virus as the cause for MS and Letermovir as a potential medication for the effective treatment of MS.
The time has come to mobilise the power of the crowds.
Last edited by Leonard on Sat Nov 01, 2014 12:54 am, edited 5 times in total.
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Re: A new concept and treatment options for MS

Post by vesta »

Hello Leonard: Since 95% of the population has the latent herpes family of viruses, how can you say MS is caused by the herpes (or EBV) virus? Maybe in MS the virus damaged the veins but once they've been damaged, treating the virus won't matter much.
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Re: A new concept and treatment options for MS

Post by Leonard »

Vesta,

Patients with MS have a low grade inflammation by herpes/EBV, probably also VZV, due to a weakened immune system (poor diet, poor food quality, hygiene, indoor life, lack of immune training, stress in a broad sense). According to prof. Pender, MS patients have decreased immunity to the Epstein Barr Virus which causes glandular fever. I think the intestine might also play a role in decreased immunity and low grade EBV inflammation, the intestine being the major immune system organ of the size of a 'tennis court' that separates body own from the 2 kg of foreign bacteria, fungi, viruses. When I started to take Valtrex, the spot that developed in the groin provides an indication of the relationship with the gut.

The immune system produces immune complexes that are infected themselves and don't work. So the immune system produces more. The concentration of both herpes simplex and EBV immune complexes in my blood was very high, about 20 x max. VZV was not measured. According to a later test, I don't have the cytomegalo virus but there much is determined by the 'band' that is measured.

The immune complexes are very damaging. They cross react with transgenic cells from earlier infections in periods of immune deficiency, when no immune memory is established. That explains the auto-immunity. T-cells are drawn in, mediators released and this gives the typical MS plaques. I think CCSVI is a factor here too that damages the BBB tissue.

Over time, this may cause an HPA dysfunction which in turn may cause low cortisol. http://hormonerestoration.com/Cortisol.html Thus, this situation would not refer to an adrenal fatigue but to an insufficiency in control of the adrenal gland (and ACTH production). And because cortisol can lower iNOS induction, low cortisol may have the effect of increasing NO synthesis systematically. And lower cortisol worsens gut function. And it may also affect the thyroid and impact on thyroid hormones and hence mitochondrial function.

Women have a higher NO synthase than men. The higher NO may explain the higher prevalence of MS (and autoimmune diseases in general) in women. But during pregnancy, the cortisol production is up, and MS comes to a halt. Probably because the higher cortisol production lowers the NO synthesis. Adding to the plausibility of the NO link. whow..

But the immune complexes also release superoxide. This superoxide reacts with the NO in our veins. We have various forms of NO synthase. Stress can act to increase NO levels. And, as we have just seen, low cortisol may also increase the NO systematically. The product is peroxynitrite which is by far the worst antioxidant. This peroxynitrite jams the cells, inhibits the ADP to ATP conversion and thus the energy metabolism, causes mitochondrial failure, directly affects the ion-pump etc etc. See for instance the book by Martin Pall titled Explaining Unexplained Illnesses. This explains why I am eating my own muscles. Their sensitivity for neuro stimulation (by the signals from the brain) will go down.

A therapy would need to start with getting the low grade inflammation under control, possibly by Letermovir. I think that once you get rid of the virus, the immune system will calm down and the MS will evaporate.
http://www.informedhorizons.com/hivdart ... chaeff.pdf

The paradigm change that we need is one where traditional medical disciplines are complemented by a new model based on virology and biochemistry and the NO/peroxynitrite vicious cycle paradigm (see also chapter 14 Pall on "A Major New Paradigm of Human Disease?").

Leo
Last edited by Leonard on Wed Nov 19, 2014 10:35 pm, edited 12 times in total.
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THE PROTOCOL

Post by Leonard »

I think a therapy for MS should look a bit like this (not necessarily in the order of importance, e.g. Terry Wahls recovered by steps 5 and 6 only):

1. Kick the virus down, by Letermovir
http://www.informedhorizons.com/hivdart ... chaeff.pdf

or possibly by Raltegravir http://en.wikipedia.org/wiki/Raltegravir
the statistics of recovery of MS patients who get anti-HIV treatment are impressive.

2. Get the superoxide down, therefore get the immune complexes down, by Rituxan, at least for a short while.
https://en.wikipedia.org/wiki/Rituximab

or improve the virus-fighting capability of immune cells http://www.couriermail.com.au/news/quee ... 6817970065

3. Get the NO down, therefore get the NO Synthesis down, by increasing cortisol; on how cortisol is interwoven with MS, for misconceptions about cortisol and on balanced hormone restoration i.e. cortisol supplementation accompanied by DHEA, see: http://hormonerestoration.com/Cortisol.html

4. Help the immune system get up by eg. IgG3 (and possibly IgG4); this will also help proper gut function and increase of cortisol level
on IgG4 see e.g. http://www.clinicaltherapeutics.com/art ... 0649-2/pdf
on improving virus-fighting capability: http://www.couriermail.com.au/news/quee ... 6817970065
The gut function/immune system will strengthen with more soil grown vegetables/antioxidants/flavonoids, less bread and pasta; improved immune system training; reduction of over-all stress level.

5. Capture free radicals (vit B and D, CoQ10, MitoQ, more vegetables/antioxidants/flavonoids)
see e.g. pg 14 - 17 of: http://www.ms-uk.org/files/npwm_2009_0053.pdf

6. Stimulate muscle strength (exercise, NMES)
see e.g. pg 14 - 17 of: http://www.ms-uk.org/files/npwm_2009_0053.pdf

And add to that a good dose of hope.
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Re: A new concept and treatment options for MS

Post by Leonard »

Scott1 wrote:Hi Leo,

I think in the main we are in vigorous agreement.
I wish I could lend you my Pilates teacher. She is like a physio on steroids. I've just come back from a two hour session. Like you I had troubles with a limp but she fixed it up.
What really made a difference was I would lie on a bench with my hips just on the edge. One leg would be down and the other up but resting on her. She would apply weight to my quads so the hip flexor is stretched. Then she would put her thumb on pressure points in my groin and in the area just inside my hip bone. Both refer to the soas muscle which in my case was super tight. The pressure point work is excruciating and I did a lot of swearing ( she's my friend) but suddenly the leg releases and it drops. By stretching the soas you will get power back into the leg. The other part was spasticity in the left calf. Really little movements to flex the foot, right down practicing pick up things with my toes worked wonders (and rapidly). Tiny movements like practicing scrunching up a theraband under my foot using my toes and little jumps on trampoline really are useful. You don't have to be Baryshnikov for it to make a huge difference. If your tight its worth trying. Its not exhausting.
Hi Scott,

My physiotherapist tried release of the SOA muscle by putting pressure on the pressure points in the groin but for me it has little effect (other than that it was painful). He thinks that my problem with the SOA muscle is not a muscle spasm but an overall weakening. I think this is generally true for other muscles in the leg too.

BR, Leo
Last edited by Leonard on Fri Nov 28, 2014 2:52 am, edited 2 times in total.
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Re: A new concept and treatment options for MS

Post by Leonard »

This study suggests that the gut microbiota is a critical factor in BBB permeability.
http://stm.sciencemag.org/content/6/263 ... ign=buffer

I think that the immune system is inextricably linked to that gut microbiota and is convolved in many ways with other things that are not (yet) fully understood. While the communication gut microbiota-BBB might well be via the virus! Where a normal healthy gut microbiota i.e. a balanced bacterial content is the enemy of the virus (to note: here we have the virus again).

For sure, my own gut function went bad many years before MS diagnosis (although inevitably there were already things happening long time before pointing to CIS and autoimmunity condition, in fact from 14 years of age when I had loss of control of my left hand).

I know that neurologists and researchers are trying to deny CCSVI as a factor. Despite, I think this finding does not exclude the possibility that vascular insufficiency (I think you should read truncation here, narrowing may have a different cause) and hypoperfusion are a factor in MS too. The statistics of MS of people living in the shadow of the heavy metal industry (Beverwijk, Glasgow, Boston, Texas) as compared to the general population and the statistics of Zivadinov provide - to me - a case in point.
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Re: A new concept and treatment options for MS

Post by Leonard »

Hi Scott,

You will find this study very interesting.
Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial, The Lancet, Vol 383, June 28, 2014
article 2213 of http://www.thelancet.com/journals/lance ... %29X6090-3

The interesting part for us comes towards the end of the paper. Quote: The mechanism by which the brain penetrant simvastatin causes a significant reduction in the annualized rate of whole-brain atrophy and the improvement in two major disability outcomes in this study therefore remains to be elucidated. Accumulating evidence shows that statins have cell protective properties. For example, inhibition of inducible nitric oxide synthase, thus reducing release of free radicals from activated microglia and astrocytes [Leonard added: we know it is a product of the superoxide and the NO] and exerting a neuroprotective effect by prevention of glutamate-mediated excitotoxic effects. An alternative or additional mechanism could be through an effect on vascular function. Statins acting through endothelial nitric oxide synthase can result in improved cerebral vasomotor reactivity protecting against long-term hypoxic damage. Finally, since vascular comorbidity is associated with substantial risk of disability in multiple sclerosis [Leonard added: I think this is caused by the VZV, re: papers Maria Nagel], the noted benefit might be directly due to the reduction in total cholesterol achieved in this study. unquote

The viral connection is obvious (to note: here we have the virus again).

I am secondary progressive. For me the study findings are sufficiently positive to consider using simvastatin to help slow the progression.

Cortisol supplementation could help the gut function. And cortisol also lowers the NOS. I wonder whether there could be any relationship between the the cortisol production and ad-renal; and the kidney renal system and ADMA; and cholesterol. I wonder whether you have ideas in this regard.

Leo
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Re: THE PROTOCOL

Post by PointsNorth »

Leonard wrote:I think a therapy for MS should look a bit like this (not necessarily in the order of importance, e.g. Terry Wahls recovered by steps 5 and 6 only):

5. Capture free radicals (vit B and D, CoQ10, MitoQ, more vegetables/antioxidants/flavonoids)
see e.g. pg 14 - 17 of: http://www.ms-uk.org/files/npwm_2009_0053.pdf

6. Stimulate muscle strength (exercise, NMES)
see e.g. pg 14 - 17 of: http://www.ms-uk.org/files/npwm_2009_0053.pdf

And add to that a good dose of hope.
Thanks Leo - a nice (much needed) summary of the Whals Regimen. I am on a hybrid regimen involving:
High Dose vit D 60Kiu day
Magnesium w. B6
CoQ10 300mg
Some Zinc & Omega3
Transdermal B12 (thinking that formulation with MultiBs could be best)
Extra B2
Soon to add Lecithan
Albany 2010. Brooklyn 2011
Hayes inspired Calcitriol+D3 2013-2014
Coimbra Protocol 2014-16
DrG B12 Transdermal Spray 2014-16
Progesterone 2015-16
Low-Dose Immunotherapy 2015-16
My Current Regimen http://www.thisisms.com/forum/regimens-f22/topic25634.html
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Re: A new concept and treatment options for MS

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Hi Leo,
I admire your tenacity. Since my big attack I wondered if I was starting on a progressive path but I think I may have skipped a bullet. I have been reading a number of different books to broaden my thinking. As I felt the attack was doing something different than I was used to, I looked more closely at coinfections. In particular I found a book by Stephen Harrod Buhner on Lyme disease was enlightening as he goes into detail on how Mycoplasmas affect ATP and the neural system. I read Terri Wahls book but I think it was not aimed at readers who love detail (like us). The basic idea was interesting but not well enough explained for me. The most important book I have read is called "The Sinatra solution- Metabolic Cardiology" by Stephen T Sinatra. Chapter 3 is called ATP:The miracle of life. I have read it twice now and I think it contains many interesting points for us. Lets just jump all preliminaries and lets assume ATP is affected by peroxynitrite and we have a problem.
Cardiac problems often lead to a total energy collapse and ATP failure is central to Sinatras view. In the cell there really isn't much ATP relative to the demand for it so it's the recycling of ADP back into ATP that is critical. The ATP has three bits to it;3 phosphates, a ring of sugar called D-ribose and Adenine (a purine). When 1 phosphate is broken free it goes on to make energy.
ATP can move freely around the cell but to become ATP the ADP largely returns to the mitochondria. It can rebuild outside that mechanism but it is very slow. As Sinatra says "the fire starts in the Mitochondria"
Mitochondria have two sets of membranes. The transport agent between the membranes is L-Carnitine. Without using it the membrane barrier is closed. 90% of all energy comes from Mitochondria. ADP from the cytosol must be moved into the mitochondria to make ATP and that ATP must move back to the cytosol to activate the sodium potassium pump. Sinatras explanation of this involves fatty acids and B group vitamins but I need to read it again to follow it. Nonetheless it makes sense of Wahls focus on saturated fats. Three molecules of ATP are formed from each molecule of glucose metabolized by glycogen. Only two are formed by glucose alone. Both are poor rewards for the input. In the mitochondria, 129 molecules of ATP can be formed from palmitate (a 16 carbon fatty acid). We need the fats to burn in the mitochondria but we need L-Carnitine to cross an otherwise impenetrable barrier.If we don't maintain ATP we end up with a net loss of Purines and the remaining ATP degrades and is lost.
On cortisol, he draws a relationship between chronic cortisol overload leading to magnesium depletion as physical and emotional stress causes it to be secreted by the adrenals. Sinatras view is all reactions involving ATP have a need for magnesium. So I'm not sure supplementing with cortisol will do what you want it to do.
On statins, he acknowledges they may be anti-inflammatory but they interfere with Q10 producing a negative effect on cellular energy. The benefit for patients with systolic function problems was slight and exercise tolerance was 50% lower in the group taking stains for the diastolic issues.
I am leaning towards his view that supplementing with Q10, magnesium, D-ribose and L-carnitine might be better for us.
On the Psoas- You should find the Thomas stretch with pressure points painful because the muscle is tight. If it's unable to contract and release properly then something else has to do the work and that's hard. When I had my recent attack and had to learn how to walk again it was all about overcoming weakness overlaying tightness. That means you need to exercise it as well as release it. It takes a while and my stomach still feels sore but I'm pretty good now.
I don't know how your ATP levels are holding up as the work you need to do is tiring.
What I did at the start for strength was basic. I had to learn how to walk upstairs one step at a time and come down one step at a time. Then I progressed to up two at a time and down one at a time. Then up steps facing backwards. I also did a lot of an exercise called Jumping. To do that you lie down on something like a Pilates reformer and jump up like ballet dancer controlling both the jump and the landing. A good Pilates instructor will know what to do.
The other exercise is to stand up, holding onto a bar, quickly bring one knee high up in front you then lower it down to the floor and kick it back like a horse kick. A good physio should know that one. The issue for you will be how well your ATP holds up while you do it. Just being prodded isn't enough. You need to exercise the muscles. I know that's a clumsy description. In Australia, I haven't found physios to be anywhere near as useful as good Pilates people. Where ever you start doesn't matter. You need to do some strength work but you need to make ATP or the exercise will exhaust you.
Boost the production of ATP and some of these other issues might be lessened.

Regards
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Re: A new concept and treatment options for MS

Post by Leonard »

Thank you Scott, there is a lot of information in your last posting, I need to study this and take advice.

I am sure now that the cell machinery is central to MS. My disability was most definitely progressing long before I was diagnosed with MS. There are several signs: when jogging 10 km’s, I had to walk after 5 km’s and for several minutes to let the ion pump recharge. When skiing downhill, I had to pause every now and then, with increasing frequency, to let the pump recharge. Again, all ranges went down slowly, year after year. This slow demobilizing course just continued after diagnosis with MS. The gut was bad many years before diagnosis which probably allowed EBV growth and infection, including of the bone marrow, which over time immortalized the B-cells.

For this same reason, others may get ALS, or mitochondrial energy failure or type 2 diabetes, or arthritis, or post-herpetic neuralgia or... In MS, there are the specific plaques and lesions which have something to do CCSVI or hypo-perfusion or blood flow changes in the brains. For that reason, things happen in the vessel walls at specific places in the brains, it may that bacteria are involved, with the result of increased BBB permeability. Then, the virus gets its chance to anchor itself (in the early days) which then, many decades later on when the immune complexes start circulate (immortalized EBV infected B-cells), leads to autoimmunity and the MS plaques. I also do not rule out that exactly because subsequent mechanisms played there role, MS extinguishes after 60.

The following facts seems to confirm a dysfunction of the cellular gates responsible for cellular respiration. I know that if I eat rice (easy carb) with sweets, and then start bicycling or do other physical activity, I have to pee twice per hour, in big quantities, almost clear water. A medical specialist who checked me on diabetes believes my metabolism will respond because it asks for energy and produces the necessary fuel but then the cells don’t open or at least open too slow. And the kidneys filters out the excess glucose.

The enormous heat effect that patients with MS experience would seem to be yet another confirmation of the central role of the cell machinery. On a warm day, people in general want to take a swim or jump in the water, to cool down. This makes them feel better. Our body has an enormous heat sensitivity, that is if the outside temperature gets above a certain threshold, things run down quickly and people automatically slow down. This must be an evolutionary mechanism for self-protection of the species. In case of MS or diabetes, the effect is more pronounced. Because they have fewer working/active gates in the vessel walls. For that reason, cellular nutrition is impaired which also causes effects on the ion pump. On a hot day, I go difficult, but after I take a jump in the swimming pool, I walk like a well-oiled machine. Because of low temperature, the gates function again and the pump is recharged much better and faster. Demonstrating the central role of the cell machinery.

Also the vitamin D relationship is important here and provides a further indication that the cell machinery is involved. The risk to develop MS is different for identical twins who get separated before adolecence. Presumably, the person that moves south has more sun exposure and thus more vitamin D in his/her blood during the main phase of cellular growth. As the number of gates on a cell is between 1500 and 3000 and directly proportional to the vitamin D level the blood when the cell was formed, a high level of vitamin D during the main phase of cellular growth would seem to provide a higher density of gates per cell and therefore it will just last longer before the cell is immobilised by the virus/peroxynitrite for the south going twin.

I am confident that a virus related angiopathy is causal, the virus being the Varicella Zoster Virus (a herpes virus). The virus causes inflammation/receptor blocking and is known to damage the vessel walls (papers Maria Nagel). Here our problem starts. Where drugs such Metformin (presumably has effects on the functioning of the gates) and Glimperid (extra insulin) which are the most common drugs for diabetes 2 patients will help to improve the cellular feeding conditions. Gradually, the bone marrow gets EBV infected (another herpes virus), B-cells get infected and stop work, the immune system produces more causing autoimmune reaction with transgenic cells and further damage. I am sure, thse different mechanisms explain the double peak in the graph of the age of onset.

Leo
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