N-acetylglucosamine (GlcNAc)

[kim]

N-acetylglucosamine (GlcNAc) bolding mine

 

http://today.uci.edu/news/release_detail.asp?key=1666

 

In tests on mice, Demetriou found that genetic deficiencies in a process called protein glycosylation led to a spontaneous disease very similar to MS, including paralysis associated with inflammatory damage to the protective myelin coating on nerve cells and degeneration of axons and neurons. Protein glycosylation refers to the addition of specific sugars to proteins; virtually all cell-surface and secreted proteins have complex sugars attached to them.

and

 

“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.”

http://www.msrc.co.uk/index.cfm?fuseaction...CFTOKEN=5729539

 

 

Urinary excretion of silicon, the 'natural' antagonist to the potential toxicity of aluminium, was decreased in MS and particularly so in secondary progressive form of the disease.

The research suggests that individuals with MS have a higher body burden of aluminium and that their urinary excretion of aluminium is linked to changes taking place during the relapsing-remitting stage of the disease.

 

 

edit...sorry about the link, corrected now

[kim]

I know you are always on the lookout for Azith articles. Don't know if you have this one, or if it's something that would be useful to take to your Dr? That "acetylcarnitine" seems to pop up in more than one place too.

 

http://www.pubmedcentral.nih.gov/articlere...i?artid=1562448

Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data

Thanks for the good article highlighting Azithwith chronic fatigue. I just wish they would write one specific to PANDAS. I know every Dr. I've seen has been against it in the NE because of resistance. Do you think showing this article would help convince them to try it for our kids immune issues? You think it should react in a similar way for our PANDAS cases?

 

Original article regarding NAG and autoimmune issues http://today.uci.edu/news/release_detail.asp?key=1666

 

Michelle,

 

I didn't want to clutter up Mack5moms thread about azith, but did want to respond to you.

 

I think that article is a good case for the immune modulating effect. I don't think it says anything about it's use prophylatically? That would probably be the arguement that you would get.

 

Quite honestly, I would want to discusee the info on the use of N acetyl glucosamine with the nearest DAN, myself. It might be worth your while to join this group and read the thread regarding it. Not a lot of indepth info, but a few discussing it's use in regards to PANDAS

http://health.groups.yahoo.com/group/Autism-Immune/

 

I'm having a hard time thinking that the bony tumor study referring to a lack of GlcNAc and glucuronic acid (not gluconic which I have been referring to it as)and a suspected relationship to autistic like symptoms and this new info regarding GlcNAc is just a coincidence. A friend of mine knows that I have an interest in it, and sent me the link to that group. I am becoming more than just a little curious about just how many of us may be dealing with malfunction regarding one, the other or both.

 

I have thought of you and your son, so often when wading through all of this. When you mentioned his nails, I wasn't surprised at all. Sure don't have all of the answers, but it feels like there's important correlations here.

 

You might want to read thru a few articles here as well, Michelle.

http://www.google.com/search?hl=en&rls...ion&spell=1

[kim]

I noticed where glucosamine was being discussed on another thread, and sure didn't want to miss the opportunity to discuss that one!

 

 

A defect in glycosylation is being researched in relationship to a condition that my oldest son has...the ole bony tumor (osteochondroma).

 

So, Dr Demetriou's team found

 

http://today.uci.edu/news/release_detail.asp?key=1666

 

In tests on mice, Demetriou found that genetic deficiencies in a process called protein glycosylation led to a spontaneous disease very similar to MS, including paralysis associated with inflammatory damage to the protective myelin coating on nerve cells and degeneration of axons and neurons. Protein glycosylation refers to the addition of specific sugars to proteins; virtually all cell-surface and secreted proteins have complex sugars attached to them.

 

AND this statement

 

http://www.newscientist.com/channel/health...=mg19426074.500

 

A large number of proteins in the body are modified by the attachment of sugar molecules to their surface through a process called glycosylation, and altered glycosylation has been implicated in some autoimmune diseases. Demetriou's team found that naturally occurring GlcNAc molecules attach to T-cell receptors and these GlcNAc "branches" form a lattice on the cell surface that prevents the receptors from clustering near where the antigens are located (see Diagram). Less clustering means less antigen binding, and less activation of Th1 cells, reducing the autoimmune reaction.

 

 

 

 

There are a couple of studies that seem to contradict the "less activation of TH1 cells" but first, my understanding of Chitin....

 

http://cat.inist.fr/?aModele=afficheN&cpsidt=16658782

 

The biophysical properties of fungal cell walls are determined by the composition, level and structural arrangement of their polysaccharides. A small amount of glucosamine in the cell wall (1-3%) forms chitin, which is a ß(1 ? 4) linear homopolymer of N-acetylglucosamine (GlcNAc). Chitin synthetase activity is often analysed by radioactivity using [14C] GlcNAc.

 

 

Chitin is the substance that gives snails, oysters, lobster and shrimp their hard shell. Wiki says that it is also involved in pain pathways. I bought a Glucosamine supplement (hydrochloride) which contains chitin from the above mentioned sources.....not snail, but the other 3. I have not tried (kids) the N acetylglucosamine which I did find online here. http://www.iherb.com/ProductDetails.aspx?c...d=1295&at=0

 

So, GlcNAc is naturally occuring in our bodies AND in the cell wall of some bacteria (including strep) and fungus. Glucosamine supplements provide chitin which is a linear homopolymer of GLcNAc, so I'm sure hoping that means "the same." We have not even used the glucosamine up to this point. My oldest son had new blood work done Mon. We have been using minimal supplements leading up to that. I did give him one this morning. What really makes me curious, is if N acetyl glucosamine is part of a bigger picture or link btwn PANDAS related conditions and more of what would be thought to be TS in some cases.

 

 

 

These are the studies that I wondered about being a contradiction?

 

Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse.Shibata Y, Foster LA, Bradfield JF, Myrvik QN.

Department of Physiology, East Carolina University School of Medicine, Greenville, NC 27858, USA.

 

Previous studies showed that local macrophages phagocytose nonantigenic chitin particles (1-10 micrometer polymers of N-acetyl-<cmd SC>d<cmd /SC> -glucosamine) through mannose receptors and produce IL-12, IL-18, and TNF-alpha. These cytokines lead to the production of IFN-gamma by NK cells. To determine whether chitin could down-regulate Th2 responses, chitin was given orally (8 mg/day for 3 days before and 13 days during ragweed allergen immunization) in BALB/c and C57BL/6 mice. These ragweed-immunized mice were given ragweed intratracheally on day 11. Three days after the challenge, the immunized mice with saline (controls) showed increases in serum IgE levels and lung eosinophil numbers. The chitin treatment resulted in decreases of these events in both strains. To dissect the inhibitory mechanisms of Th2 responses, spleen cells (4 x 106 cells/ml) isolated from the ragweed-immunized mice (controls) were cultured in the presence of ragweed and/or chitin for 3 days (recall responses). Ragweed alone stimulated the production of IL-4 (0.6 ng/ml), IL-5 (20 U/ml), and IL-10 (3.2 ng/ml), but not IFN-gamma. Ragweed/chitin stimulation resulted in significant decreases of IL-4, IL-5, and IL-10 levels and the production of IFN-gamma (48 U/ml). Moreover, spleen cells isolated from the chitin-treated mice showed ragweed-stimulated IFN-gamma production (15 U/ml) and significantly lower levels of the Th2 cytokines, suggesting that the immune responses were redirected toward a Th1 response. Collectively, these results indicate that chitin-induced innate immune responses down-regulate Th2-facilitated IgE production and lung eosinophilia in the allergic mouse.

 

 

http://www.ncbi.nlm.nih.gov/pubmed/1155355...ogdbfrom=pubmed

 

Infect Immun. 2001 Oct;69(10):6123-30. Links

Th1 adjuvant N-acetyl-D-glucosamine polymer up-regulates Th1 immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice.Shibata Y, Honda I, Justice JP, Van Scott MR, Nakamura RM, Myrvik QN.

Department of Physiology, East Carolina University Brody School of Medicine, Greenville, North Carolina 27858, USA. shibatay@mail.ecu.edu

 

Treatment of mice with heat-killed (HK) Mycobacterium bovis BCG or 1- to 10-microm chitin particles (nonantigenic N-acetyl-D-glucosamine polymers) is known to induce innate immune responses, including gamma interferon (IFN-gamma) production, which plays a Th1 adjuvant role. However, HK BCG further induces prostaglandin E2-releasing spleen macrophages (Mphi) (PGE2-Mphi), which potentially inhibit Th1 adjuvant activities. We found that chitin particles did not induce PGE2-Mphi formation. To further assess whether chitin has Th1 adjuvant effects, interleukin-10 (IL-10)-knockout (KO) mice and their wild-type (WT, C57BL/6) controls were immunized with a 30-kDa MPB-59 mycobacterial protein mixed with chitin. Immunization with MPB-59 alone induced Th2 responses, characterized by increases in total serum immunoglobulin E (IgE) and specific serum IgG1 levels and spleen Th2 cells producing IL-4, IL-5, and IL-10. No IFN-gamma-producing spleen Th1 cells, specific serum IgG2a, or delayed-type hypersensitivity (DTH) footpad reactions were detected. On the other hand, chitin-MPB-59 immunization significantly increased spleen Th1 responses, DTH reaction, and serum IgG2a levels along with decreases of Th2 responses. The magnitude of these Th1 adjuvant effects was greater in IL-10-KO mice than in WT mice. In contrast, immunization with HK BCG-MPB-59 showed little or no Th1 adjuvant effect. These data indicate that chitin has a unique Th1 adjuvant effect on the development of Th1 immunity against a mycobacterial antigen. IL-10 down-regulates the adjuvant effect of chitin.

[Chemar]

lol ms Kim you speaking a foreign language again!

 

I will spend some time trying to digest all this (as you know my brain turns to jello with most of these research papers that use many formulae or numerals) but it is of much interest to me as the auto-immune link sure seems evident in both mine and hubby's family trees

 

just wanted to thank you again for the time you spend sharing this info here. I think there are many golden keys that could unlock doors to healing in much of what you detect.

[Buster]

Hi Kim,

 

I was really delighted to see your post. I think there is something very significant here with the GlcNAc. Dr. Kirvan in her paper with Dr. Swedo isolated the antibody idiotype to one targeting the GlcNAc (i.e., the streptococcal carbohydrate). The problem was that this antibody seemed to react with neuronal tissue. This was Kirvan's paper in 2006 "Antibody-mediated neuronal cell signaling in behavior and movement disorders"

 

http://www.csus.edu/bios/faculty/Kirvan/Ki...JNI_article.pdf

 

She later went on to isolate reactions to Tubulin in her 2007 paper, "Tubulin Is a Neuronal Target of Autoantibodies in Sydenham’s Chorea."

 

http://www.csus.edu/bios/faculty/Kirvan/JI_paper_2007.pdf

 

What is so fascinating here is whether there are anti-idiotype antibodies that supress the GlcNAc antibody and that for some reason these anti-antibodies aren't doing the supressing they are supposed to.

 

To me, this explains why IVIG might work... it is adding in this anti-anti-body that supresses the immune response.

 

Regards,

 

Buster

[kim]

Thank you Cheri and Buster!

 

Cheri, you are such a sweetie with your vote of confidence.

 

Buster, I was trying to figure out the GlcNAc connection from the link you posted (http://www.csus.edu/bios/faculty/Kirvan/Ki...JNI_article.pdf) back in March.

 

It's on this thread.

 

http://www.latitudes.org/forums/index.php?...l=basal+ganglia

 

 

I have so many thoughts on this, its hard to know where to start, BUT I'm so glad you see the possible correlation here. I have been trying to get a post out on this all morning, and just don't have the time but I'll be back!

[Buster]

Hi Kim,

 

Interesting string of posts on your other thread. I liked the graphical image of the lattice network. However, protecting cells with the lattice network seems at best a short term/temporary mechanism to reduce binding rather than a cure.

 

There is a really interesting Sept 2008 article on regulatory B cells by Matsushita at Duke U. http://content.jci.org/articles/view/36030 and there is Tedder's work on C19 and regulatory B cells http://www.biochemsoctrans.org/bst/030/0807/0300807.pdf

 

What this got me wondering is whether IVIG is adding back in these regulatory B cells in the IgG and whether these B cells are supressing the replication of the GlcNAc attacking antibody. Essentially, if the PANDAS kids have a lot of the GlcNAc antibodies and these GlcNAc antibodies cross react with neuronal tissue, then do people who don't have PANDAS have better regulation of these GlcNAc antibodies (i.e., kill them off or suppress their expansion). This seems to explain why steroid burst would work, why azithromycin might work (immunomodulates and controls inflammatory response), why plasma exchange would work (because it removed the GlcNAc antibodies) and IVIG would work (adds the anti-anti-bodies that get rid of the GlcNAc antibodies).

 

Anyway, just a theory, but awfully interesting....

 

Thanks,

 

Buster

[kim]

Buster,

 

Is the D8/17 test helpful in determining that theory?

 

The proposed auto immune reaction is btwn GlcNAc and brain-derived lysoganglioside GM1, correct? I'm only asking because I'm really not all that "up" on all the PANDAS info and how IVIG actually works. I'm not sure if there are other elements that are thought to be the cross reactive?

 

 

 

However, protecting cells with the lattice network seems at best a short term/temporary mechanism to reduce binding rather than a cure

.

 

What if you were not producing the amt. of GlcNAc that a person normally does, due to a genetics or damaged DNA?

[kim]

deleted... double post again

[Buster]

Is the D8/17 test helpful in determining that theory?

 

I wish I knew too! At this point, I've been tracking the papers on D8/17 and it has been mixed. It is at least an anomoly in the B Lymphocyte and seems the show up in PANDAS, SC and ARF patients. How this marker corresponds with activation on B cells or whether there is some flaw in binding due to this and the MyD88 TLR is just unknown.

 

I'll keep digging though.

 

What if you were not producing the amt. of GlcNAc that a person normally does, due to a genetics or damaged DNA?

 

I'll go back and re-read Kirvan's paper again, but my understanding was that the antibody was attacking GlcNAc (i.e., that was the idiotype) and thus causing the attack on host self. It is not known how the antibody is crossing the blood brain barrier.

 

I ran into a very interesting paper on epinephrine affecting BBB and allowing antibodies and drugs to pass. Perhaps there has to be a very frightening event/stress marker that lines up with the strep allowing the antibodies to cross. Just don't know....

 

Thanks,

 

Buster

[kim]

Buster,

 

I ran into a very interesting paper on epinephrine affecting BBB and allowing antibodies and drugs to pass. Perhaps there has to be a very frightening event/stress marker that lines up with the strep allowing the antibodies to cross. Just don't know....

 

Epinephrine can be problematic in non PANDAS too. Wonder if there is an overlap there.

 

This info on chitin/chitosin/N acetyl glucosamine is getting more and more interesting! Probblem is, I have no idea how much of this info an be extrapolated to a deficiency in O linked N acetyl glucosamine and glucuronic acid . Bolding mine

 

http://nano.cancer.gov/news_center/2007/ja...2007-01-22c.asp

 

Nanoparticles made of chitosan, a naturally occuring polymer isolated from crab and shrimp shells, have shown promise as carriers of anticancer drugs, antitumor genes, and other novel therapeutic agents (click here for earlier news stories). In addition, chitosan nanoparticles by themselves appear toxic to various types of malignant cells. To better understand this latter observation, Lifeng Qi, Ph.D., at West Virginia University, working with colleagues at Zhejiang University in Hangzhou, China, has conducted a detailed study evaluating the effect of chitosan nanoparticles on human liver cancer cells.

 

http://www.yourdictionary.com/chitosan

 

chitosan Definition

chi·to·san (kīt′ə san′)

 

noun

 

a polysaccharide derived from chitin, that absorbs heavy metals while in solution: it is used in industry, esp. to purify waste water

 

http://www.ncbi.nlm.nih.gov/pubmed/1757683...Pubmed_RVDocSum

 

Chitosan malate inhibits growth and exotoxin production of toxic shock syndrome-inducing Staphylococcus aureus strains and group A streptococci.

 

http://www.ncbi.nlm.nih.gov/pubmed/1711246...Pubmed_RVDocSum

 

Chewing chitosan-containing gum effectively inhibits the growth of cariogenic bacteria.

 

 

http://www.ncbi.nlm.nih.gov/pubmed/1754780...ogdbfrom=pubmed

 

[Anti-Helicobacter pylori effect and regulation of T helper response of chitosan]

 

CONCLUSIONS: Chitosan has anti-Hp effect and synergism with amoxicillin in

vivo. Chitosan can up-regulate Th1 and Th2 response

[P_Mom]

yeah!! Kim.....I bet you are glad someone is on board who finally understands your posts and can engage in good "conversation" with you!

 

I enjoy reading the discussions between you guys! Keep at it...maybe you guys can figure out this whole thing....I bet you are doing more research on it than many of the docs out there!

 

Thanks for taking the time!

 

kelly