N acetylglucosamine

[kim]

Just wanted to make it clear that I'm not suggesting that anyone give this to their child. I'm only hoping that those with access to Dr.s working on this, will ask if they think that this might a safe or effective treatment.

 

http://www.google.com/products?q=source+na...ved=0CCMQrQQwAA

 

Source Naturals NAG N-Acetyl Glucosamine

 

Remarks from another thread

 

http://www.medicalnewstoday.com/articles/70952.php

 

In studies on mice, Dr. Michael Demetriou and colleagues with the UC Irvine Center for Immunology found that N-acetylglucosamine (GlcNAc), which is similar but more effective than the widely available glucosamine, inhibited the growth and function of abnormal T-cells that incorrectly direct the immune system to attack specific tissues in the body, such as brain myelin in MS and insulin-producing cells of the pancreas in diabetes. Study results appear on the online version of the Journal of Biological Chemistry.

 

"This finding shows the potential of using a dietary supplement to help treat autoimmune diseases," said Demetriou, an assistant professor of neurology, and microbiology and molecular genetics. "Most importantly, we understand how this sugar-based supplement inhibits the cells that attack the body, making metabolic therapy a rational approach to prevent or treat these debilitating diseases."

 

The UC Irvine study defines how metabolic therapy with the sugar GlcNAc and other related nutrients modifies the growth and autoimmune activitiy of T-cells. Virtually all proteins on the surface of cells, including T-cells, are modified with complex sugars of variable lengths and composition. Recent studies have shown that changes in these sugars are often associated with T-cell hyperactivity and autoimmune disease.

Mommd and anyone with good Drs!

 

I wonder if anyone could get Doc's feedback on this concept. I have felt for a long time that something is affecting the way these sugar chains are assembled in some people with autoimmune problems. If it's genetic response to environmental factors (strep and other ....viral/metals etc)seems this may be one of the best/safest ways available now in some instances for damage control. My biggest concern is regarding long term use, and insulin resistance. From what I've been able to find on it, seems there is some uncertainty about that and i think there is definitely a predisposition here. Also, since there is at least a mild immune suppression (or does it only suppress abnormal t cells?), for people with known immune deficiency this might not be a good option.

 

 

What an interesting thought regarding GlcNAc. There's a very recent John Hopkins study by Dias at http://www.jbc.org/content/284/32/21327.abstract where they found direct correlation between GlcNAc and CamKinaseIV activation.

 

While it is dangerous to connect the three dots, it sure seems like the following is a good working hypothesis:

 

1) T-cells are producing monoclonal antibodies with epitype GlcNAc

2) The monoclonal antibodies are bonding with GlcNAc and thereby inactivating the ability of GlcNAc to bond with cAMP

3) The lack of available GlcNAc inhibits the suppression of CaM Kinase activations (II and IV)

 

So perhaps what Kirvan and Cunningham are measuring with elevated Cam Kinase II is that the available GlcNAc is abnormally low in the blood serum.

 

It appears that Kirvan and Cunningham are pursuing the direction that the antibodies bind directly to dopamine receptors, but I think the direction you raise in your post is equally interesting and seems to fit the model (i.e., that there's a decline in available GlcNAc). Hmm....

[kim]

Buster,

 

Was quite excited to read your hypothesis and it's stated much more eloquently than what I usually come up with!

 

This is has a filing date of 11/89, so not sure if newer research refutes any of this. Seems to me that these NAG containing chains have a negative charge. They should repel bacteria in some instance, so if a deficiency is present, could account for more frequent infections i.e. bladder, throat, sinus, lung etc. the "mucousy" membranes? The tone of this suggests that the GAGS are deficient subsequent to infection, bit i wonder if these findings are present to some degree, prior to the infection.

 

http://www.freepatentsonline.com/EP0372730.html

 

The inventor has discovered that sufferers of Crohn's disease have a reduced level of NAG in their system. The inventor has also discovered unexpectedly that an intake of a pharmacologically acceptable amount of NAG stimulates the synthesis of protective substances, improves tissue integrity and restores tissue function in the direction of normal. Administration of NAG in therapeutic quantities has been found to be helpful in the treatment of Crohn's disease. In IBD, specifically, the conversion of glucosamine to NAG has been found to be much slower than normal. This invention, in one aspect, is directed to overcoming IBD to at least a certain extent by supplementing the sufferer's (patient's) diet with NAG.

I also found this statement from the same article really interesting. Some kids who have been taking huge amts of probiotics are still found to have reduced levels of some of the supposed beneficial bacteria's.

 

 

It is known that NAG is secreted into mother's milk and stimulates the establishment of lactobacilli in the intestine of newborn infants who are breast-fed. Such flora tends to prevent establishment of less favourable bacteria and has certain advantages in the digestion of milk and in proper bowel function. A similar situation exists in vaginitis, where the prevalence of lactobacilli has a similar protective effect. However, establishment of this organism has not heretofore been successful, probably because of the lack of the "growth factor", NAG, which is required by this organism to enable synthesis of the cell wall. Consequently, providing NAG as a dietary supplement represents a physiological means of encouraging the establishment of lactobacilli in the vagina, with the attendant benefits.

[kim]

Here is a pubmed abstract regarding the reseach reported by Demetriou

 

excerpt

http://www.ncbi.nlm.nih.gov/pubmed/1959464...Pubmed_RVDocSum

 

Galectins bind surface glycoproteins in proportion to the branching and number of N-glycans per protein, the latter an encoded feature of protein sequence. N-glycan branching is conditional to the activity of Golgi N-acetylglucosaminyl transferases I, II, IV and V (Mgat1, 2, 4, and 5) and metabolic supply of their donor substrate UDP-GlcNAc. Genetic and metabolic control of N-glycan branching co-regulate homeostatic set-points for basal, activation, and arrest signaling in T cells and, when disturbed, result in T-cell hyperactivity and autoimmunity.

[kim]

Very good info regarding N acetylglucosamine (and glycobiology in general) on this site

 

http://www.ultimateglucosamine.com/consume...cobiology.shtml

[kim]

well, I learned something this morning. White spots on fingernails are commonly assoc. with low zinc. That has appeared to be the case in my youngest son but this abstract has me thinking....

Also, I think I remember horsetail being a supplement that was used by some for strep clearance on the Yasko forum. Chitosan (glucosamine), horsetail and sulfur, very interesting!

 

These are some pretty extreme picture

 

Leukonychia Photos

http://www.dermnet.com/Leukonychia

 

 

New abstract PubM bolding mine

 

http://www.ncbi.nlm.nih.gov/pubmed/1947004...mp;ordinalpos=1

 

Improvement of psoriatic onychodystrophy by a water-soluble nail lacquer

 

BACKGROUND: There is a strong need for effective products, simple to use and safe for a chronic use in the management of nail psoriasis. Recently, a non-drug, water-soluble nail lacquer became available, containing hydroxypropyl chitosan (HPCH), horsetail extract (Equisetum arvense) and methylsulphonyl-methane (DMSO(2)). This product was effective in strengthening the nails and reducing fragility and roughness in brittle nails.

 

and

 

66% reduction in leukonychia, 63% reduction in onycholysis and a reduction of 65% in NAPSI score compared to baseline, respectively. No changes were observed in the untreated nails. Patients' treatment evaluation was classified as very satisfying or good by 78.6% of patients. The acceptability of the treatment was excellent in all patients both for the easiness and for the organoleptic characteristics of the product and 75% of them decided to continue the application after the end of the study. No adverse reactions were reported.

 

 

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

chitosan=linear polysaccharide composed of randomly distributed β-(1-4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit).

[kim]

http://ard.bmj.com/cgi/content/abstract/57/4/220

 

Annals of the Rheumatic Diseases 1998;57:220-225; doi:10.1136/ard.57.4.220

Copyright © 1998 BMJ Publishing Group Ltd & European League Against Rheumatism.

Ann Rheum Dis 1998;57:220-225 ( April )

 

Extended reports

 

The p68 autoantigen characteristic of rheumatoid arthritis is reactive with carbohydrate epitope specific autoantibodies

 

CONCLUSIONS Autoimmunity to p68 during RA is carried by anti-carbohydrate autoantibodies. The carbohydrate modification of p68 appears to be N-acetylglucosamine, which may reflect the regulation of intracellular localisation of the antigen. It is hypothesised that a shift in glycosylation pattern accompanied by an unphysiological localisation of the antigen could trigger antigenicity of p68 during the pathogenesis of RA.

 

 

Does "unphysiological localisation" mean that the antigen wouldn't normally be found intracellularly?

[bronxmom2]

Hi Kim, I've been giving my son NAG since his Plasma exchange.

[kim]

bronxsmom,

 

Do you have any opinion on it's effect? Curious if you ran it by your immuno? Thanks for sharing that you're trying it! Oh yea, how much are you dosing?

[bronxmom2]

I really can't say. I was fascinated by the idea that it could suppress the bad T Cells, since PEX does nothing to address that.

It's not hurting, and my instinct is to include it every day in our routine. We are over a month past-PEX and still doing fine.

I did run it by the immunologist, who said it wasn't dangerous but probably wouldn't help. (He wants to do IVIG to retrain those TCells.)

 

If you want, I can pass along specific studies to him about what it really does. (I was a little vague in my explanation.) I'm seeing him next week.

[LNN]

Just to ditto. I saw the same UC Irvine research and thought there may be some benefit to trying it. We're stuck with glucosamine, not NAG, because my son won't swallow pills and we need something in a liquid. We found liquid glucosamine at CVS and it has a vanilla taste that blends well with Fuze coconut banana drink. We're not religious about it, but my son takes it when he complains about muscle soreness and whether its a placebo effect or it actually helps, he seems to feel better an our or so after taking it. It gives us an alternative to dosing with Mortin every night.

[kim]

I really can't say. I was fascinated by the idea that it could suppress the bad T Cells, since PEX does nothing to address that.

It's not hurting, and my instinct is to include it every day in our routine. We are over a month past-PEX and still doing fine.

I did run it by the immunologist, who said it wasn't dangerous but probably wouldn't help. (He wants to do IVIG to retrain those TCells.)

 

If you want, I can pass along specific studies to him about what it really does. (I was a little vague in my explanation.) I'm seeing him next week.

 

bronxsmom,

 

Maybe you could just email him? These would be two articles that would be helpful, and personally I would be delighted if you would at least introduce him to the idea that this may be something important.

 

http://today.uci.edu/iframe.php?p=/news/re...me.asp?key=1666

 

http://www.newscientist.com/article/mg1942...ne-disease.html

 

Also, the PANDAS papers showing GlcNAc as being the apparent cross reactive antigen

 

My suspicion is that GlcNac isn't only deficient in the Tcell, but also in some host tissue. It's involved in the sythesis of heparan/heparan sulfate (?) too. Look at this

 

http://www.ncbi.nlm.nih.gov/pubmed/37168?dopt=Abstract

 

Antibacterial activity of bladder surface mucin duplicated by exogenous glycosaminoglycan (heparin).

Parsons CL, Mulholland SG, Anwar H.

 

We have previously shown that the transitional cells lining the urinary bladder are capable of producing glycosaminoglycan (GAG). By use of a quantitative in vivo method of measuring bacterial adherence, we demonstrated that bacterial adherence to the mucosal cells is diminished in the presence of this GAG, rises when it is removed (by acid), and returns to normal when the GAG is resynthesized (in less than 24 h). We also found that this much layer could be removed (with a corresponding rise in bacterial adherence) and that addition of exogenous GAG (heparin) to the bladder prevented the expected rise in bacterial adherence. This study analyzed in depth the manner by which heparin prevents the rise in adherence seen when the mucin is removed. Pretreatment of bacteria with heparin had no effect on adherence, whereas pretreatment of the bladder with heparin inhibited adherence. To corroborate our impression that the heparin was coating the transitional cells, [3H]heparin was added to bladders after removal of mucin. Autoradiography revealed the heparin to be adherent to the surface of the transitional cells.

 

I thought you might be interested in some of these articles too. Boy, some of this is OLD. Why hasn't there been more progress in these areas?

 

http://www.ultimateglucosamine.com/consume...reastmilk.shtml

 

Oligosaccharides (small sugar chains larger than lactose) are unique to human breast milk. These small sugar chains are present in amounts as high as 18 grams per litre of breast milk which is much higher than protein at 10 to 12 gram per litre. The most common sugars making up these short chains are N-acetyl-D-glucosamine, sialic acid (a 9 carbon amino sugar) and fucose. Fifteen percent of the sugar content is protein bound and 85% is free in the form of oligosaccharides, with chain lengths varying from 3 to 11 units1.

 

 

http://pubs.acs.org/cen/coverstory/86/8639cover.html

 

Unraveling Breast Milk

Analytical scrutiny reveals how complex fluid nourishes infants and protects them from disease

Jyllian Kemsley

WHEN IT COMES to feeding infants, the mantra is "breast is best." A diet of breast milk for babies is correlated with benefits including less diarrhea as well as lower incidence of diabetes or asthma when compared to formula-fed babies. But precisely how breast milk confers those advantages is unclear. Scientists know the basic ingredients of breast milk but don't fully understand how exactly they work to provide optimum nutrition for infants and protect against disease.

[kim]

http://aac.asm.org/cgi/reprint/51/9/3056.pdf

 

Chitosan Malate Inhibits Growth and Exotoxin Production of

Toxic Shock Syndrome-Inducing Staphylococcus aureus

Strains and Group A Streptococci

 

The present study has shown that chitosan malate has the

ability to inhibit exotoxin production by gram-positive bacteria

at chitosan malate concentrations that are not overtly toxic to

rabbits, and in vivo the compound has the ability to prevent

serious staphylococcal and streptococcal illnesses. Further

studies are required to assess the human safety of chitosan

malate use, but these studies suggest the compound may be

useful as an additive to wound dressings for the management

of infections.

[matis_mom]

So... how much NAG do you give??? I am currently giving my ds "Gastrothera" (from ProThera, Inc.), which is supposed to help heal the gut (I suspect he has a bit of a leaky gut). NAG is one of the main ingredients, I wonder how much is needed to make a difference in the immune system...

 

Isabel

[kim]

mati's mom,

 

I think it would depend on why you're giving it. In the one small study that was done in children with Crohn's/IBS they were using 3 to 6 grams.

 

If you are using it to try to prevent autoimmune attack, it may require much less (or maybe not).

 

I have a sneaking suspicion that no pharma company is going to put up big reseach bucks to give us an answer here any time soon. NAG is too cheap and is not under FDA control (this may have a down side too tho). I think the dose in most supplements is designed to aid in connective tissue repair (if speaking of glucosamine, not NAG which acts differently..and I think NAG is required for what we're speaking of) so again, I don't know what dose it would take to accomplish autoimmune supression, without an undo increase infection risk. Maybe mom2pandas will have some thoughts for us.

 

It appears around 80% of chitan (pronounced kite- in ...don't want anyone talking to their Dr about chi tan. like I had been reading it) is manufactored in china, possibly under less than ideal circumstances. Also, it is not a very "pure" product to begin with. I have a healthy respect for contaminants and metals, which can be found in the shells from which this stuff is made. If I were going to give my kids (or myself) any substantial amt or over a long period of time, I'd like a product that met 'Good manufacturing practice' which appears some US companies comply with voluntarily, but I can't find a retail supplier.

 

I might be over reacting here. Many older people with probably less than optimal immune systems take these products, but who knows the long term effects on a child. Dr.s can obtain a pharmaceutical grade product, i believe, but I'm not optimistic about getting someone to order it for me any time soon. I just wish we had some input from someone (Dr.s) involved in PANDAS research.

 

bronxsmom, Is your son still doing well? I don't see anything in the allergy research link to suggest that they aren't importing their product. Just remember, I'm hyper cautious now.

 

http://www.faqs.org/patents/app/20080248508

 

http://www.allergyresearchgroup.com/N-Acet...Caps-p-159.html

 

http://www.allergyresearchgroup.com/prodde...Sheet060705.pdf

 

http://organicpharmacy.org/products/Extra....ate/SKU:3223NOW

 

How is glucosamine manufactured?

 

Glucosamine is supplied mostly by China. The shells of shrimp and crabs have their proteins and minerals removed producing Chitin or poly N-acetylglucosamine. Manufacturers use acid with a depolymerizing and deacetylating process to produce glucosamine hydrochloride or glucosamine sulfate.

[matis_mom]

Thanks for the reply Kim. I am currently giving it to him as part of a product called "Gastrothera" from ProThera, which is a reputable company. My thinking is his gut is probably a mess, he has some food sensitivities he did not have before, and constipation/diahrrea off and on. So along with probiotics, I am giving him this supplement that is designed for leaky gut. So far he seems to be doing well on it, and his stomach/bathroom issues are better too (well, that may have to do with other things).

 

Isabel