uric acid

[bernie100]

Hi everyone

Can anyone tell me if there is any conection between uric acid and nitric oxide or if they are completely different things and do different things

Thanks in advance

[CureOrBust]

At the following URL, they say

Uric Acid is a scavenger of Peroxynitrite, which is the product of Nitric Oxide (NO) and Superoxide.

http://www.geocities.com/HotSprings/346 ... 2g5.html#6

The following URL also has a lot on Nitric Oxide
http://www.geocities.com/HotSprings/346 ... eta.html#1

I wont pretend to understand all of the stuff at these URL's, but the first talks of a connection.

[rulerulz]

u shud try searching for the definitions in the dictionary or on the net, they wil be more precise and you will be able to differentiate in clear terms.

[jimmylegs]

someone else probably has posted this before but it's new to me thanks to a recent heads up from another site member. i just can't stand to bury this kind of stuff down in the 'natural approach' forum...

Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease
Authors: Spitsin S.1; Hooper D.C.1; Leist T.2; Streletz L.J.2; Mikheeva T.1; Koprowski H.1, *
Source: Multiple Sclerosis, Volume 7, Number 5, October 2001, pp. 313-319(7)
Publisher: Hodder Arnold Journals

Abstract:
Peroxynitrite has been implicated in the pathogenesis of multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Previously, we have shown that administration of uric acid (UA), a peroxynitrite scavenger, is therapeutic in EAE. We have also shown that MS patients have lower levels of serum uric acid than healthy individuals or those with other neurological diseases. The aim of this investigation was therefore to raise serum UA levels in MS patients. Oral administration of UA failed to increase low serum UA levels, evidently due to its degradation by gastrointestinal bacteria. However, serum UA could be raised and maintained at elevated levels for a year and more without reported side-effects by oral administration of its precursor inosine. Three of 11 patients given inosine showed some evidence of clinical improvement and there was no sign of disease progression in the remaining patients. Gadolinium-enhanced lesions, observed in two patients before receiving inosine, could not be detected after either 10 or 15 months inosine treatment. These data provide evidence that serum UA levels can be readily manipulated and that the benefit of higher levels to individuals with MS should be studied further in greater number of patients.

[jimmylegs]

i could not find inosine on the natural factors site or at my usual store - nutrition house - but found it here: http://www.sourcenaturals.com/products/?id=GP1157 and will see if my store can order it in quick before i leave.

*update: glad i never got my hands on inosine. correcting a deficiency of essential zinc corrected the uric acid levels without attempting to use a non-essential ua precursor like inosine*

[jimmylegs]

bernie check this out, first abstract is nitric oxide/peroxynitrite, second is inosine(uric acid)/peroxynitrite

Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37.
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly.
Beckman JS, Koppenol WH.
Department of Anesthesiology, University of Alabama at Birmingham 35233, USA.

Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.

Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease
Authors: Spitsin S.1; Hooper D.C.1; Leist T.2; Streletz L.J.2; Mikheeva T.1; Koprowski H.1, *
Source: Multiple Sclerosis, Volume 7, Number 5, October 2001, pp. 313-319(7)
Publisher: Hodder Arnold Journals

Abstract:
Peroxynitrite has been implicated in the pathogenesis of multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis (EAE). Previously, we have shown that administration of uric acid (UA), a peroxynitrite scavenger, is therapeutic in EAE. We have also shown that MS patients have lower levels of serum uric acid than healthy individuals or those with other neurological diseases. The aim of this investigation was therefore to raise serum UA levels in MS patients. Oral administration of UA failed to increase low serum UA levels, evidently due to its degradation by gastrointestinal bacteria. However, serum UA could be raised and maintained at elevated levels for a year and more without reported side-effects by oral administration of its precursor inosine. Three of 11 patients given inosine showed some evidence of clinical improvement and there was no sign of disease progression in the remaining patients. Gadolinium-enhanced lesions, observed in two patients before receiving inosine, could not be detected after either 10 or 15 months inosine treatment. These data provide evidence that serum UA levels can be readily manipulated and that the benefit of higher levels to individuals with MS should be studied further in greater number of patients.

[bromley]

Jimmy,

I could send you a hundred similar research papers and you would have to get another job to pay for all the different supplements and potions. This was a very small study and the benefits look a bit inconclusive to me. This disease is a researchers dream and if you are not careful, you could be spending all your money on bee stings, LDN, uric acid, abx, vit D tablets, live yogurts etc etc. And don't forget to cut out artifical sweetners, red meat etc etc. And read your bible everday. Science will work this disease out (eventually) and come up with ways to stops it etc. In the meantime, it's a snakeskin oil saleman's paradise - coming up with potions to sell to desperate people like us.

Ian

[jimmylegs]

it's true i try a lot of stuff. and notice improvement. at this point, my daily regimen includes:

personalized b-complex,
E,
C,
selenium,
turmeric,
calcium/magnesium/d liquid (with extra D by prescription),
multi-acidophilus,
multi-mineral, and
ginkgo biloba. oh and right now, some extra
iron. and soon, some
inosine.

i stage it so that the C goes with the iron, but not at the same time as the B vitamins, to help with absorption.

when i stick with it bromley, honestly, i get into really good shape. the only lingering problem is my sensory impairment in my hands. (i think that's because i actually physically damaged my neck right at C7/C8 a day before this attack started.) when i get off the program, i start to have issues again.

[HarryZ]

Hi Ian,

This disease is a researchers dream and if you are not careful, you could be spending all your money on bee stings, LDN, uric acid, abx, vit D tablets, live yogurts etc etc.

I'm not so sure that the thousands of MS patients using LDN and gaining some benefit would like you lumping this very inexpensive drug into the pot of worthless spending.

Take care.

Harry

[SarahLonglands]

Yes, Bromley,

I don't think you can really dump bee stings in with antibiotics or live yoghurt, which is good for everyone, either

I probably wouldn't be here today without antibiotics.

Sarah

[bromley]

Harry / Sarah / Jimmy,

The point I was making was that every week there is some new "cure" which is promoted and people head down to their health shops and come back with bags of supplements etc. Many swore by bee stings but recent research has shown that they had no effect. On LDN, some report good results but other say did nothing for them and there have been no proper trials. ABX has worked for Sarah and some others, but I would place a bet that it hasn't worked for everyone who has taken them.

It was just a gentle warning to Jimmy that you can end up spending lots of money on supplements which may have little effect. Recent research in the UK concluded that eating a balanced diet was the best quarantee of getting all the vitamins and minerals required.

Ian


PS Harry - I see that you have moved your profits from your Biogen share sale to promote LDN.

PSS Sarah - you should take BeatMS's advice 'abx are bad for you'. And don't forget to read your bible tonight, I know you are a god-fearing woman underneath.

I probably wouldn't be here today without antibiotics.

Yes, the inventors of anti-biotics have got a lot to answer for!

[jimmylegs]

lol re god-fearing brom. and thank you for the gentle warning.

yep i agree about balanced diet. however, i do not pretend that mine is perfect and therefore supplement. since i have recently given up veganism, i have to build up stores of nutrients seriously depleted over close to 15 years. i now eat fish and eggs and some tiny amount of dairy... but i just don't think i'll be having steak and kidney pie any time soon, to get the inosine. guess i'll be making sushi more often, and taking that supplement!

[HarryZ]

Ian,

PS Harry - I see that you have moved your profits from your Biogen share sale to promote LDN.

Oh heavens no....I would never take my millions out of Biogen at the moment...they just raised the price of Tysabri by 22% so I'm counting my money before they even start using the drug again And nobody is going to make any money on LDN...no patent!! But there ARE a lot of LDN users out there who appear to be gaining some benefit.

Harry

[lyndacarol]

My Summer 2006 issue of MSQR (Multiple Sclerosis Quarterly Report), arrived this week. In the section entitled, "Current Clinical Trials in MS," is the entry, "Treatment of MS Using Over-the-Counter Inosine."

Location: Hospital of the University of Pennsylvania, Philadelphia, PA.
Purpose: The purpose of this study is to determine whether raising low levels of the natural antioxidant uric acid by the administration of a precursor, inosine, has any therapeutic effect of the progression of RRMS and secondary progressive MS.
Eligibility: Males and females, 18 to 60 years of age. Non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test result within 60 days before the first dose of study material. Males and females must practice adequate contraception, in the judgment of the investigator, during the course of the study. Subjects must have a diagnosis of clinically definite relapsing-remitting MS based on medical history, physical examination, laboratory test results, and neurologic examination, and have had one clinical relapse in the last year. Alternatively, subjects may have clinically probable MS characterized by one attack and the presence of at least four lesions on MRI within 12 months before the initial baseline evaluation. Subjects must have an EDSS test result of less than or equal to 5.0 within 60 days before the first dose of study material. Subjects will have serum uric acid levels less than 5 mg/dl. There are also several exclusion criteria. For information contact Vanessa Zimmerman by phone at 215-349-5162, or via e-mail "vanessa.zimmerman@uphs.upenn.edu".

[jimmylegs]

another older study for review.

Ther Umsch. 2004 Sep;61(9):553-5.
[Uric acid and multiple sclerosis]
Mattle HP, Lienert C, Greeve I.
Neurologische Klinik und Poliklinik, Universitatsspital Bern, Inselspital, Bern.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.