Peglem Faith All

[kim]

Peglem,

 

I though your post here contained amazing info http://www.latitudes.org/forums/index.php?showtopic=3411. I read the post, but didn't read the Megson paper until later. I was posting on another thread about some of the same stuff (sort of)!

I will be going back through it, (probably in the wee hours of the morning). If we both have time, I would love to try to take that post apart with you. There are so many questions that I have regarding strep and the sulfur system that Carolyn N. and I have really been getting acquainted with. I'm going to leave that alone for now, but I might have lots of questions for you.

 

I'm thinking of the MTHFR mutation that we have touched on several times recently, antiphospholipid syndome, the children who have had severe muscle symptoms in relationship to illness, injury....even those slow head turning tics (muscle contraction, or tightness as described by my youngest son) and finally, has anyone wondered why a blood pressure med (clonidine) helps tics in some cases?

 

These were the excerpts that really caught my eye. Faith the fat metabolism (family history of lipoma) The info on B12 and folate, your son's symptom increase with strep althought not clear cut PANDAS, well your son popped to mind here. Just seemed like info others might be looking at too.

 

http://en.wikipedia.org/wiki/Choline

 

Choline as a supplement

It is well established that supplements of methyl group transfer vitamins B6, B12, folic acid reduce the blood titer of homocysteine and prevent heart disease. Choline is a necessary source of methyl groups for methyl group transfer. Supplements of lecithin/choline by Central Soya scientists reduced heart disease in laboratory studies

 

and

 

Due to its role in lipid metabolism, choline has also found its way into nutritional supplements which claim to reduce body fat; but there is little or no evidence to prove that it has any effect on reducing excess body fat or that taking high amounts of choline will increase the rate at which fat is metabolised.

 

 

Acetylcholine

 

http://en.wikipedia.org/wiki/Acetylcholine

 

 

Acetylcholine has functions both in the peripheral nervous system (PNS) and in the central nervous system (CNS) as a neuromodulator.

 

In the PNS, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system.

 

In the CNS, acetylcholine and the associated neurons form a neurotransmitter system, the cholinergic system, which tends to cause excitatory actions.

 

and

 

 

In PNS

In the peripheral nervous system, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system. . When acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it opens ligand gated sodium channels in the cell membrane. Sodium ions then enter the muscle cell, stimulating muscle contraction. Acetylcholine, while inducing contraction of skeletal muscles, instead induces decreased contraction in cardiac muscle fibers. This distinction is attributed to differences in receptor structure between skeletal and cardiac fibers.

 

 

http://www.ncbi.nlm.nih.gov/pubmed/11406107 bolding mine

 

Transport of choline and its relationship to the expression of the organic cation transporters in a rat brain microvessel endothelial cell line (RBE4).Friedrich A, George RL, Bridges CC, Prasad PD, Ganapathy V.

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912, USA.

 

The present study was undertaken to elucidate the functional characteristics of choline uptake and deduce the relationship between choline uptake and the expression of organic cation transporters in the rat brain microvessel endothelial cell line RBE4. Confluent RBE4 cells were found to express a high affinity choline uptake system. The system is Na(+)-independent and shows a Michaelis-Menten constant of approx. 20 microM for choline. The choline analogue hemicholinium-3 inhibits choline uptake in these cells with an inhibition constant of approx. 50 microM. The uptake system is also susceptible for inhibition by various organic cations, including 1-methyl-4-phenylpyridinium, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, clonidine, procainamide, and tetramethylammonium

 

 

Does antiphospholipid syndrome play a part here? I didn't read the whole page or the studies that he usually cites.

 

 

http://www.raysahelian.com/choline.html

 

THE MEMORY NUTRIENTS—CHOLINE AND PHOSPHOLIPIDS

from the book Mind Boosters by Ray Sahelian, M.D.

 

Like omega-3 fatty acids, phospholipids are also important for optimal brain health. As the name implies, phospholipids are made of the combination of lipids (fats) and the mineral phosphorus. Phospholipids are found in high concentrations in the lining of practically every cell of the body, including brain cells. They help brain cells communicate and influence how well receptors function. Although present in many foods, phospholipids are found in higher concentrations in soy, eggs and the brain tissue of animals. There may actually be a biochemical rational for the folk wisdom that says eating brain makes one smarter. The two most common phospholipid supplements sold over the counter are phosphatidylcholine and phosphatidylserine. Phosphatidylcholine is also known as lecithin. This chapter explains the role and function of phospholipids, their clinical effects, and practical recommendations for or against supplementation.

 

In addition to these phospholipids, I will also discuss choline, a nutrient that helps form phosphatidylcholine. Choline is the precursor to acetylcholine, the brain chemical involved with memory. Choline has been sold over the counter for many years. A new and more activated form of choline, called CDP-choline, became available in the US in 1998.

[Chemar]

Kim I confess I have barely skimmed your post ...... but wanted to mention that in the original treatment protocol for my son (see my siggie link) we supplemented phosphatidylcholine in the form of lecithin. He was getting 1200mg lecithin a day which equated to just over 400mg phosphatidylcholine per day.

[peglem]

I used to be one avid little researcher...the intensity has worn off over the last few years. But, the cholinergic sytem, as it pertains to especially the parasympathetic nervous system (PNS) is something that I'm still pretty up on.

 

Here's the thing (and it still confuses me a bit) even though acetylcholine is acetylcholine, there are 2 different kinds of cholinergic receptors, nicotinic and muscarinic. It seems to me that the muscarinic cholinergic system tends to be more regulatory than the nicotinic. The nicotinic cholinergic system seems to have more direct action. (nerve to mucle stimulation). Also, acetylcholine (Ach) is so pervasive in the body, really seems to have some effect on all body systems- really makes it hard to study and figure out.

 

In anycase, its a bit different than most neurotransmitters because its not a matter of a nerve cell containing Ach and secreting it into the synapse. Instead, the cell contains the components to make acetylcholine (acetic acid and choline) and requires acetyltransferase to synthesize Ach from the components. (can't remember anymore if that happens in the cell or in the synapse-not sure how important that is.) Then, instead of "reuptake into the secreting cell (like most neurotransmitters), an enzyme, acetylcholinesterase, is required to break it back down into the 2 components, which are then recycled and stored for reuse. This is what makes supplementation a bit iffy...just having enough choline and enough acetic acid does not mean that they'll form a happy union and start neurotransmitting for you...If you don't have the catalyst (acetyltransferase), they don't mix. Or there may be a toxin blocking the receptor. Its like anything, the more moving parts, the greater the chance that something will break.

 

Now, the medication my daughter is taking, bethanecol, only works on the muscarinic receptors (as far as they know) and supposedly does not cross the BBB (as far as they know). Yet it does seem to help with fine motor control (which is supposed to be nicotinic). However, I seem to recall reading somewhere that while the end of the neurotransmission chain (nerve to muscle) is nicotinic, muscarinic receptors are further up in the chain-so do have an influence.

 

One last thing, on the Megson paper: I really, really wish she hadn't included her theory on vaccinations causing the G-alpha protein problem...whether its true or not, it makes it hard to bring this to doctors for consideration because for many, that makes the whole paper suspect. The paper would be perfectly valid w/o her proferring her theory on causation. I'm not saying she's wrong (I really don't want to debate the whole vaccine issue-gets us nowhere), just that it really doesn't matter as it pertains to logis of a solution.

 

I'll have to come back later- gotta take care of the kiddo.

[faith]

Thank you Kim, this is way interesting. Especially because recently I am really trying to look at these pathways where the B12,folic acid are concerned. Even though we are doing the B12 supplementation to hopefully correct this, I can't help but feel something else is missing here for us, for it is not exactly "doing the trick" if you know what I mean. So because this is one of my son's glitches, I think concentrating on this and how it relates to the rest of the pathway ending in detox is very intriguing to me. Somehow I feel the important parts are "right here", as in "these pathways". If anyone has anything to add to this, please continue on this thread. I have asked CarolynN to help me out here too, as it relates to the info she is concentrating on and has put out there for us. I can't help but feel this is an important part of it for most of us.

 

Kim or peglem, or anyone, what do you get from the "choline" information? Is it saying that it is needed to get the methlyation going? Anyone here using that (or lecithin)?

 

I have a little studying (understatement) to do here, and will come back again with questions (or a major breakthrough!! ) Again, there is "something" here to be learned, I just feel it. The methylation and transulpheration (sp.) pathways is what I desperately want to understand more about. I need to before I am comfortable with giving the supplements on any kind of long term basis, especially the aminos. Heaven forbid there was a doctor or medical professional readily available out there that could simplify this for us all.

 

 

When I was a little girl, I wanted to be a model (too short), a ballet dancer (mom said it was too expensive for lessons and I was not the type ) or a flight attendant (we said stewardess back then!) in that order ........ but NEVER ever did I even entertain the idea of being a "scientist" (too nerdy? ) but dang, here we are!........ and at MY tender age!? ...

 

Faith

[CSP]

All,

 

My son's methylation markers indecate, no adnormality found. So does this mean his sulfer system is fine???

 

On the other hand his energy markers shows he needs lipoic acid (compound containing sulfer) for his energy metabolism.

 

And to add... he shows no signs of abnormality in his dexoxification indicators.

 

WHAT GIVES???

 

C.P.

[peglem]

I love Wickipedia-it so helps me make better sense of it all:

 

http://en.wikipedia.org/wiki/Acetylcholine

 

and from the bottom of that page:

 

Synthesis inhibitors

Organic mercurial compounds have a high affinity for sulfhydryl groups, which causes dysfunction of the enzyme choline acetyltransferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function.

 

That's a nice little connection that deserves a little more study!

[bmom]

CSP, What test did your son do? Is your sons doc. recommending Alpha Lipoic Acid? I believe this does help with the detox although it doesn't show he needs it. If it is any comfort, I believe it was Claire's son that showed Alpha Lipoic Acid was deficient and Cysteine and she said the supplements were a big help. Also the book "Victory over Tourette Syndrome" talks about Alpha Lipoic Acid as a good supplement. I have bought it, but not used it. Too many supplements, not enough info. I have finally decided that I need to have my son tested to see his specific needs. I am now trying to decide what doc. to guide me through. I am thinking Dr. Demio or Dr. Mullan (who uses Amy Yasko's protocal). I want to get it right the first time as I am not going to be able to pay out of pocket for multiple DAN docs. Any thoughts anyone? So much that we are talking about seems to fit in line with Amy Yasko's approach.

Faith- How funny, I think those were the professions I wanted to be too.

[kim]

bmom, more and more my vote is the Yasko approach. I'm not saying ALL of the answers are there, but I think she sure is on the right track.

 

Quickly, I was looking for something that I came across for CP. It seems I had read about a mutation on 1p36 that had to do with potassium and chloride (?). That area of that chromosome seems to come up quite a bit. I know there is an EXTL (the L stands for "like") gene, located on 1p36. The EXT genes are what are implicated in my son's bony growth and what shows a problem with heparan sulfate sythesis. I think the MTHFR gene is there, can't remember what else, but I listed some of them on the genetics thread.

 

You can probably see by the highlights in this article what i searched. This was interesting. Peglem, I'm not interested in debating vaccines anymore either. I carefully reseached all I needed to know, awhile back. I think the current vax schedule is recklessly dangerous PERIOD. There may be a case for some vaccines, but they need to be given with a GREAT DEAL MORE CARE than they are now, IMO, with careful consideration to family history, the overall health of the child etc.

Anyway this popped up. Sorry CP, i just don't have anymore time right now. One other thing, I was search pub med regarding Crohn's today. Some of the current research seems to be looking at vessel involvement and coagulation factors.

 

 

http://64.233.167.104/search?q=cache:qjxuR...cd=11&gl=us

 

Peglem have you ever used Pant. acid?

 

http://www.raysahelian.com/bvitamin.html

 

Pantothenic acid (B5) is essential for biological reactions involving acetylation and energy production. This vitamin helps in the formation of acetylcholine, the metabolism of fatty acids, and the incorporation of fatty acids into cell membrane phospholipids. Pantothenic acid is also involved in making steroid hormones, vitamin A, vitamin D, and cholesterol. Good sources are egg yolk and fresh vegetables. The recommended daily intake is about 5 mg. Pantothenic acid is sold over the counter in dosages ranging from 5 to 250 mg.

 

My patients report that pantothenic acid helps improve their mood and energy. Personally, I notice an improvement in alertness, concentration, energy, and visual clarity with dosages ranging from 100 to 250 mg. I do experience insomnia, though, when I take more than 250 mg, even if I take it in the morning. Benita von Klingspor, a nutritionist in Marina Del Rey, California, says, "Pantothenic acid is one of my favorite nutrients. I know the effects of this nutrient extremely well since I’ve been taking 100 to 250 mg most mornings for more than thirty years. I often recommend it to many clients with low energy. Pantothenic acid increases their alertness and focus, improves their mood, and enhances their joy in life. They begin to have more interest in whatever they’re doing. However, if people take too much pantothenic acid, they can become overstimulated, wired, and easily aggravated."

 

Pantothenic acid is available in its activated form known as pantethine. Pantethine, itself, is part of coenzyme A, a very important substance that participates in the metabolism of carbohydrates, amino acids, fatty acids and dozens of other important chemical reactions. Cognitive effects of oral pantethine administration to humans have not been published. Pantethene is sold over the counter in dosages ranging from 5 to 50 mg. In my experience, a lower dosage of pantethine provides similar effects as a higher dosage of pantothenic acid.

[CSP]

bmom,

 

This was from his OAT report. Done by Metametrix. He had two intreventions for the energy markers Arginine and Lipoic acid It does not say alpha, does that make a difference? The cause is listed as Retal ammonia loading. (I have googled that and don't get any of what I read so far.)

 

Thanks, bmom, I'll look up Claire's info on that.

C.P.

[kim]

Peglem,

 

Once again, we are looking at similar issues.

 

In anycase, its a bit different than most neurotransmitters because its not a matter of a nerve cell containing Ach and secreting it into the synapse. Instead, the cell contains the components to make acetylcholine (acetic acid and choline) and requires acetyltransferase to synthesize Ach from the components. (can't remember anymore if that happens in the cell or in the synapse-not sure how important that is.)

 

From the reseach that I'm assuming is likely to be part of our issue (althou, I think we have a less severe problem with lack of transferase than what they are studying which is a multiple hereditary thing) the lack of heperan sulfate, would be due to lack of an enzyme which catalyzes it to the cell surface too, missing components.

 

http://www.researchcrossroads.com/index.ph...rant_id=3210354

 

Now the really interesting thing is that the GluR1 subunit of AMPA-type glutamate receptors, that they say is drastically reduced, is stimulated, if I'm understanding what I'm reading by (edit. I thought acetylcholine was implicated here too, but when I went back to cite the article that I took it from, looks like I better do some more reading) nicotine. It looks like the GluR1's of AMPA glutamate receptors, play an inhibitory role.

 

So, I'm wondering the same thing. By supplementing sulfur, there is no evidence that it is going to link up with heparan and change the situation, however, I do think there would be benefit. They may have found a lack of surface heparan sulfate when studying this disorder, but what about the other GAGS that need sulfation? chondroitin sulfate (cartilage), keratin sulfate (cartilage, bone, and cornea), dermatan sulfate (skin, tendons, lungs, blood vessels). I copied that last part from this site, which I didn't even read, just looking for something that spelled out the GAGS. The "hyaluronic" they reference there, is a GAG also, but it isn't sulfated. I think that is one of the things that they look for cross reactivity in an autoimmune situation with PANDAS. It is found in the host and in the strep bacteria as is N acetylglucosime. Again, if anyone follows up on any of this, and finds where i'm interpreting something dead wrong, PLEASE correct me. Some of this info is found on the Anti Basil Ganglia testing thread.

 

http://www.wellnessresources.com/products/...uronic_acid.php

 

http://www.ihop-net.org/UniPub/iHOP/pm/124...p;pmid=17898222

The same nicotine treatment increased the levels of the AMPA glutamate receptor subunit GluR1

[kim]

Peglem/All,

 

Faith's question on another thread caused me to re evaluate a hypothesis of sorts, based on the research that is being done on people with multiple ostero tumors (which I have been trying to figure out how much relates to our situtation ). Anyway, it led me to this article. Is any of this familiar to you. Do you have any knowledge of the Cog's mentioned here?

 

http://hmg.oxfordjournals.org/cgi/reprint/ddl476v1.pdf

 

 

Because of her occasional coagulation problems, bleeding or thrombosis, and the

fluctuation of the coagulation parameters through out development (protein C and protein S

deficiency, decreased prothrombin time and coagulation factors), a wide study for

“increased risk of thrombosis” was performed. While homocysteine, vitamin B12 and folic

acid levels were normal, a heterozygous C677T mutation in the methylenetetrahydrofolate

reductase (MTHFR) gene was found. The factor V Leiden and factor II mutations were

absent.

Her father also has a very high level of plasma homocysteine, undetectable vitamin B12

levels, antibodies against intrinsic factor and incipient macrocitic anemia. He was

diagnosed with a pernicious anemia. The mother is heterozygous for the C677T mutation in

the MTHFR gene. Other basal laboratory analyses, coagulation studies, creatin kinase,

lipids, thyroid hormones and levels of CDT in serum were normal in both parents. A

summary of the clinical features is presented in table 1.

[peglem]

Peglem/All,

 

Faith's question on another thread caused me to re evaluate a hypothesis of sorts, based on the research that is being done on people with multiple ostero tumors (which I have been trying to figure out how much relates to our situtation ). Anyway, it led me to this article. Is any of this familiar to you. Do you have any knowledge of the Cog's mentioned here?

 

http://hmg.oxfordjournals.org/cgi/reprint/ddl476v1.pdf

 

 

Because of her occasional coagulation problems, bleeding or thrombosis, and the

fluctuation of the coagulation parameters through out development (protein C and protein S

deficiency, decreased prothrombin time and coagulation factors), a wide study for

“increased risk of thrombosis” was performed. While homocysteine, vitamin B12 and folic

acid levels were normal, a heterozygous C677T mutation in the methylenetetrahydrofolate

reductase (MTHFR) gene was found. The factor V Leiden and factor II mutations were

absent.

Her father also has a very high level of plasma homocysteine, undetectable vitamin B12

levels, antibodies against intrinsic factor and incipient macrocitic anemia. He was

diagnosed with a pernicious anemia. The mother is heterozygous for the C677T mutation in

the MTHFR gene. Other basal laboratory analyses, coagulation studies, creatin kinase,

lipids, thyroid hormones and levels of CDT in serum were normal in both parents. A

summary of the clinical features is presented in table 1.

 

Sorry, Kim, I really don't. The area that I've studied the most is in the cholinergic system, and that's so complicated I can't fully comprehend it. Medical science doesn't fully understand it, either. And the thing is...the solutions I've found for my child seem to be working, so unless my dream of med school comes to fruition (heehee), or things start to go downhill for her, I'm not doing much research these days. I used to make myself crazy trying to understand all this stuff-everything leads to connections to something else. Now I just seek enough understanding to figure out what to try out, solutionwise. I feel great right now, because we had 5 days w/o an anticholinergic meltdown here, and though that streek has come to an end, I think I know what to do now.