IMPORTANT:Carnosine Nitric Oxide Oxidative Stress and AS

Post Reply New Topic

Who said THAT? Apparently, a lot of aspies/autistics LIKE the cold!

Steve

Yeah I read that just now!

Any way have a look at this

Grants Funded - 2002
Studies of a serotonin transporter (5HTT) mutation associates with Asperger's syndrome
Matthew Beckman, University of Alabama at Birmingham (Young Investigator)
The search for genes associated with autism has been the focus of much attention by researchers in the past few years. Recently this search has led to the discovery of a mutation in the human serotonin transporter (SERT) coding sequence from patients with the following neuropsychiatric triad: Asperger's syndrome, obsessive-compulsive disorder, and anorexia. The function of a cloned serotonin transporter with this mutation (SERT-AS) has been characterized using [3H]5Ht uptake assays, binding assays employing a high affinity SERT ligand, ?-CIT, and immunocytochemical methods. When compared to the wild type SERT, mutant SERT-AS exhibits a roughly 1.5 fold increase in both maximum transporter velocity (Vmax) and binding sites (Bmax) and an increase in affinity (lower Kd) for ?-CIT, a high affinity ligand. Serotonin transporters have been shown to be highly regulated by various intracellular signal transduction pathways and direct phosphorylation of the transporter. Treatment of cells expressing the wild-type SERT with a nitric oxide donor S-Nitroso-N-acetylpenicillamine (SNAP) suggest a role for nitric oxide in the regulation of wild-type SERT, but the mutant SERT-AS is refractory to this stimulus. This work aims at characterizing the differences between the wild type SERT and the mutant SERT-AS using pharmacological, biochemical, and electrophysiological methods. Further, we hope to delineate the mechanism by which nitric oxide upregulates wild-type SERT with the goal of understanding why SERT-AS is constitutively upregulated. These studies offer the possibility for new insight into the pathogenesis and treatment of autism.

fMRI of perceptual gating

My hands and feet do get cold often.

Not all AS can have low NO and high BP. Because I am AS and have low BP (but my Dr says it is in a healthy range).

Okay this is really just a guess but I think in your case it's possible something else has gone wrong (or else we'd all have high BP right?) meaning that instead of producing too much NO you produce to much something else instead and the end result is that some of the same whaste products are formed (or else NO production is just a symptom of oxidative damage in which case still take the same anti-oxidants but not because they scavenge NO [even if this theory is wrong the treatment is seems is still correct: see carnosine study vit C study etc] ). Here's one way how this can happen in mice and how to fix it. tetrahydrobiopterin so if you had exactly this issue (unlikely) then after taking this drug in theory you would have high NO again still have AS but not have low blood pressure. Oxidative molecules in general would not have changed since NO is never synthasised but some of the whaste products of NO are still created.

Did you always have low no and hypertension?

Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
Ulf Landmesser1, Sergey Dikalov1, S. Russ Price2, Louise McCann1, Tohru Fukai1, Steven M. Holland3, William E. Mitch4 and David G. Harrison1
1 Division of Cardiology, and
2 Division of Nephrology, Emory University School of Medicine and Atlanta Veterans Administration Hospital, Atlanta, Georgia, USA
3 Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
4 Department of Medicine, University of Texas, Galveston, Galveston, Texas, USA

Address correspondence to: David G. Harrison, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Drive, 319 WMB, Atlanta, Georgia 30322, USA. Phone: (404) 727-8386; Fax: (404) 727-3585; E-mail: dharr02@emory.edu.

Received for publication September 7, 2001, and accepted in revised form February 18, 2003.

Tetrahydrobiopterin is a critical cofactor for the NO synthases, and in its absence these enzymes become "uncoupled," producing reactive oxygen species (ROSs) rather than NO. In aortas of mice with deoxycorticosterone acetate–salt (DOCA-salt) hypertension, ROS production from NO synthase is markedly increased, and tetrahydrobiopterin oxidation is evident. Using mice deficient in the NADPH oxidase subunit p47phox and mice lacking either the endothelial or neuronal NO synthase, we obtained evidence that hypertension produces a cascade involving production of ROSs from the NADPH oxidase leading to oxidation of tetrahydrobiopterin and uncoupling of endothelial NO synthase (eNOS). This decreases NO production and increases ROS production from eNOS. Treatment of mice with oral tetrahydrobiopterin reduces vascular ROS production, increases NO production as determined by electron spin resonance measurements of nitrosyl hemoglobin, and blunts the increase in blood pressure due to DOCA-salt hypertension. Endothelium-dependent vasodilation is only minimally altered in vessels of mice with DOCA-salt hypertension but seems to be mediated by hydrogen peroxide released from uncoupled eNOS, since it is inhibited by catalase. Tetrahydrobiopterin oxidation may represent an important abnormality in hypertension. Treatment strategies that increase tetrahydrobiopterin or prevent its oxidation may prove useful in preventing vascular complications of this common disease.

So in short supplementation with Nitric potentiators would probably be more harmful to these mice than healthy ones and similarly no scavengers would be of more benefit to them than to healthy ones! Even though they test low NO (depending on what test you use) and have high BP.

Which explains why BSN contraindicate the use of it's nitric supplement NO-Xplode for people with hypertension and do not market it as a treatment for the same thing! Actually the contraindication in hypertensive peeps had me confused before now.

Yeah I'm sure my blood pressure level is not due to just my NO levels. I guess at age 26 was the first time the doctors said my pressure was high. I put on weight over the next 8 years and got little exercise. About 2 years ago I began noticing signs of high blood pressure such as erectile problems. So I began exercising and lost weight and that got my pressure very close to normal.

Thats from the abstract you quoted. It suggest that its ROS thats the problem(negative side effects) not NO. And tetrahydbiopterin reduce ROS production (but boosted NO) and that reduce blood pressure in the mice.

http://atvb.ahajournals.org/cgi/content/full/24/3/397



So is it the superoxide anions (which is the same as ROS I think) that is the real toxic
byproduct?



Vitamin C boost tetrahydrobiopterin levels and its allready been mentioned that tetrahydrobiopterin boost NO levels.

http://www.ebmonline.org/cgi/content/full/228/11/1291



Ascorbate = Vitamin C

Oh I re-read the first post and the poster did mention it NO break down products that he is concern with. So the focus should be on preventing its break down not reducing
NO levels. So far Vitamin C seems a good idea.



That mention garlic benifits in boosting NO levels but at the same time increasing vitamin levels.

A lot of that is interesting, doesn't sound too believable about Nitric Oxide levels being high in Autistic Spectrum Disorders though

Is anyone here involved in neurobiochemistry research? Vitamin B12 does help autism though I am investigating its role via another biochemical pathway.

Sublingual vitamin B12 [or parenteral methylated vitamin B12] has been shown to help in some cases. Zinc may help improve behavioural aspects and cutting out any allergies in the diet may help people with autism think clearer. Thats basically what I have gathered so far. I have looked at some of the pathways involved and researched these in more detail.

I think there is a connection involving eczema which may show itself in autistics with unresolved food allergies.

regarding vitamin B6, it comes in 3 forms and the form in most supplements is pyridoxine [because its cheap], the form that is most bioactive is pyridoxal-5'-phosphate. This form is sometimes [perhaps rarely] used in paediatric epilepsy, though it is an unlicensed medicine in Britain,

Need to investigate this pathway, find out more about the possible mutations that could exist in the genome in ASD and also about kainate ?receptors [not looked at that in years] and epilepsy.

Arnolds aspirations, business dealings, and history tend to indicate that he is NOT AS. He is fairly social, studious, and likes social events, etc... HECK, he married into the kennedy family! Rumor has it that he actually DID plan to win mister America, become a US citizen, star in movies, and get into politics. He once tried laying bricks, but didn't do well, and he told his customer it was a european style! SHE BOUGHT IT!