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Increased serum uric acid levels predict longer survival in men with ALS
Fafut_1
Posted: Tuesday, February 21, 2012 6:33:49 AM
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its more about lipids and sugar that get into the blood....
Olly
Posted: Tuesday, February 21, 2012 1:15:31 PM

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Ben,
some more info on uric acid that may be of use?


How Can We Cure NO/ONOO− Cycle Diseases?
Approaches to Curing Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Fibromyalgia, Multiple Chemical Sensitivity, Gulf War Syndrome and Possibly Many Others by Martin L. Pall, PhD


Uric acid levels in the blood are often about 4 to 5 times those of ascorbate, although there is quite a bit of variation around those figures. However the effectiveness of uric acid in scavenging peroxynitrite and its products, per mole, is roughly similar to that of ascorbate.31


Consequently, even though it is possible to raise ascorbate levels by much higher percentages than uric acid levels in vivo, it seems likely that raising uric acid levels will produce a substantial effect on peroxynitrite-mediated oxidations in vivo and therefore should be considered well worth pursuing in lowering the central couplet.

Uric acid has a half-life of about 20 hours in humans, so it should not take very long to increase its levels by increasing the availability of purine-containing compounds in the body, such that when an increase in purine degradation is obtained, it will be sustained substantially longer than any high-level ascorbate elevation.53

Consequently, it makes sense to consider each of these three supplements – inosine, RNA, and D-ribose – as possible agents to raise uric acid levels.

A second, related issue is that very high uric acid levels may produce hypertension, and while direct measurements suggest that uric acid lowers nitric oxide synthase uncoupling, rather than raising it, this also suggests that we should limit the rise in uric acid levels in these treatments.

With these two caveats in mind, a substantial rise in uric acid levels into the mid-to upper-normal range may be very helpful to people suffering from NO/ONOO− cycle diseases.


http://www.townsendletter.com/FebMarch2010/cureNO0210.html



Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
Olly
Posted: Tuesday, February 21, 2012 1:27:28 PM

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Uric Acid again:-but for MS


Moreover, UA treatment suppresses the enhanced blood–CNS barrier permeability characteristic of EAE.

We postulate that UA acts at two levels in EAE:

1) by protecting the integrity of the blood–CNS barrier from ONOO--induced permeability changes such that cell invasion and the resulting pathology is minimized; and

2) through a compromised blood–CNS barrier, by scavenging the ONOO- directly responsible for CNS tissue damage and death.—Hooper, D. C., Scott, G. S., Zborek, A., Mikheeva, T., Kean, R. B., Koprowski, H., Spitsin, S. V. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood–CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis.

http://www.fasebj.org/content/14/5/691.abstract

Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
Mercury
Posted: Tuesday, February 21, 2012 2:59:35 PM
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Hello Olly

This link may be worth looking into.

http://www.iub.edu/~sengelab/research/spinal_motoneuron.shtml

I am currently experimenting with testosterone depo and nandrolone but don't have sufficient data to submit yet.

Merc
Olly
Posted: Tuesday, February 21, 2012 4:57:22 PM

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Hi Merc,
thanks for that.

It's interesting in the there seems to be sex differences in some possible beneficial substances/drugs and oestrogen is believed to be involved in the differences in numbers of female/males ALS

Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
Fafut_1
Posted: Tuesday, February 21, 2012 5:00:25 PM
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maybe Meaghers theory needs further investigation. I cannot find anything more about it but Olly you seem to be inquisitive online seeker, maybe you will? He claimed mnd to be sex hormones imbalance
Olly
Posted: Tuesday, February 21, 2012 5:26:48 PM

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This may point you in the right direction:

The serum level of free testosterone is reduced in amyotrophic lateral sclerosis.

Militello A, Vitello G, Lunetta C, Toscano A, Maiorana G, Piccoli T, La Bella V.


Source

ALS Clinical Research Center, Institute of Neuropsychiatry, University of Palermo, Via G. La Loggia, 1, 90129, Palermo, Italy.


Abstract

Sporadic amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motoneurons. There is an approximately 2:1 higher incidence of ALS in men compared to women, and this has raised the hypothesis of an involvement of sex hormones in the etiopathogenesis of the disorder. In this work, the serum levels of dehydroepiandrosterone sulphate (DHEAS), 17-betaestradiol, free and total testosterone were measured in 35 patients with defined or probable ALS, according to the El-Escorial/WFN revisited criteria, and compared to those obtained from 57 disease controls, matched for age and gender to the ALS group. We found no differences between ALS cases and disease controls in the serum levels of DHEAS, 17-betaestradiol and total testosterone.

Conversely, free testosterone was significantly decreased in the ALS group.

Given that testosterone crosses the blood-brain barrier only as unbound form, we suggest a possible involvement of this sex hormone in the pathophysiology of this severe motor neuron disease.


PMID: 11867076 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/11867076


Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
Fafut_1
Posted: Tuesday, February 21, 2012 5:46:07 PM
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meagher was underlying its not only testosterone but also FSH and LH. He treated himself with pergonal and somethin else, but I dont remember exacly and cant find. There was another guy who pursued this trace and supported his observation
sunsmile
Posted: Wednesday, February 22, 2012 6:49:20 AM
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Fafut here:

http://web.archive.org/web/20100511022211/http://tpals.org/meagher1.htm
Fafut_1
Posted: Wednesday, February 22, 2012 6:36:49 PM
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To summarize Meagher's faulty assumptions and conclusion:
1. Testosterone is necessary for the life of motor neurons.
2. FSH is necessary to transport testosterone into motor neurons.
3. Therefore pituitary failure causes low FSH, which in turn causes an insufficient amount of testosterone to reach the motor neurons, which then causes their death.
HappyPhysicist
Posted: Friday, February 24, 2012 2:52:28 PM
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Got my new toy today, a uric acid meter, and 5 bottles on inosine. I'll post soon my baseline uric acid level and start on about 6 g /day of inosine.

If it is done in secret, it is done in vain.
HappyPhysicist
Posted: Friday, February 24, 2012 3:54:17 PM
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My first reading is 5.4 mg/dL

If it is done in secret, it is done in vain.
Olly
Posted: Friday, February 24, 2012 4:17:11 PM

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In human blood plasma, the reference range of uric acid is between 3.6 mg/dL (~214 µmol/L) and 8.3 mg/dL (~494 µmol/L) (1 mg/dL=59.48 µmol/L).

This range is considered normal by the American Medical Association Manual of Style.

Ben when are you going to start dosing - on or off OSC dosing time?

Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
HappyPhysicist
Posted: Friday, February 24, 2012 4:41:32 PM
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Those guys at PLM are awesome. I asked them to add Uric Acid to their list of "labs" and the responded quickly. We can now report our Uric Acid levels. I strongly urge all PALS to request a uric acid test order from their physician.


If it is done in secret, it is done in vain.
Nemesis
Posted: Saturday, February 25, 2012 5:55:21 AM

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On the subject of low serum testosterone I would like to note that this aspect of ALS (which is common also in Type II diabetes) is indicative of cellular hypoxia.

I'm working off an old PC and don't have the energy to format references, but here are a couple of links:

Serum testosterone depression associated with hypoxia in respiratory failure

Hypoxia, depression of testosterone, and impotence in pickwickian syndrome reversed by weight reduction

Effect of hypoxia on the release of vascular endothelial growth factor and testosterone in mouse TM3 Leydig cells

Testosterone-stimulated growth of the rat prostate may be driven by tissue hypoxia and hypoxia-inducible factor-1alpha


Since Olly have been looking at the LRX-β null mutant he might have noted that reduced feundicity and pathology of the Leydig cells is an aspect of that phenotype. Reduced feundicity is btw also noted in male carriers of the SOD1 mediated FALS.

The connection between tissue hypoxia leading to the induction of Hif-1α and increased vascularization (i.e. tissue reoxygenation) by VEGF as a prerequisite for testosterone synthesis is obviously very important in ALS.

It should also be noted that testosterone synthesis is not unique to Leydig cells, but can occur also in (Type II) muscles and neurons, but it can't happen anywhere in the absence of a sufficient oxygen supply.

As noted in one of the links above, this is really bad news for motor neurons, since they are completely dependent on testosterone (androgens) for their survival. This is reflected for example by the order of inactivation of facial muscles in ALS, which is directly proportional to their respective levels of androgen receptors.

However, supplying androgens alone won't cut it, since trophic growth of neurons as well as muscles is dependent also on the supply of oxygen and other nutrients that must be supplied via blood.

This in turn requires appropriate vascularization, but this process has failed in ALS, since the hypoxic response after the VEGF event horizon is well known to become paradoxical in CSF of patients with ALS.

Hence, to treat ALS one must first of all address the inflammation caused by the insufficient oxygenation and thereafter (or preferably simultaneously) restore the supply of oxygen, plus restore the supply of nutrients, preferably by restoring the hypoxic response and thereby enabling for a normal (micro-) vascularization.




Don't just ask what scientists can do to speed up the solution for ALS or when they will do it, instead ask yourself what you can do right now to solve ALS asap.
De Laval
Posted: Saturday, February 25, 2012 11:51:26 AM
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HP.
Normal values of Uric acid are from 0.20-0,42 mmol/l in male and in female 0,12-0,34 mmol/l

Jan
HappyPhysicist
Posted: Monday, March 05, 2012 9:33:25 AM
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Good news. I am able to increase my Uric Acid (UA) levels by taking Inosine supplements and adding Brewer's yeast to my diet. My current level is 9.9 mg/dL up from 5.4 mg/dL.

As far as the study that Persevering referenced earlier that would put me in the highest "quartile" category, i.e > 6.35 mg/dL

Now IF, and this is a very big IF, there is a causal relationship between uric acid levels and survival, then this increased UA level should slow my progression.

Inosine is a pretty cheap supplement. I am taking 6 g/day and I can probably lower that if I want and still maintain a high UA level. I would estimate that if anyone wanted to join this study it would cost at most $50/month.

PaitentsLikeMe has added UA levels to their 'labs' section so it will be relatively straightforward to track our UA levels and find out if there is a correlation between it and our rates of progression.

Thanks,

Ben


If it is done in secret, it is done in vain.
sceptic
Posted: Monday, March 05, 2012 10:35:28 AM
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That's good news. Keep us abreast of changes both good and bad. I will trade gout for this crapfest disease any day of the week
Olly
Posted: Wednesday, March 07, 2012 7:48:48 PM

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Protection of midbrain dopaminergic neurons by the end-product of purine metabolism uric acid: potentiation by low-level depolarization

Abstract

High plasma levels of the end product of purine metabolism uric acid (UA) predict a reduced risk of developing Parkinson’s disease suggesting that UA may operate as a protective factor for midbrain dopaminergic neurons.

Consistent with this view, UA exerted partial but long-term protection in a culture model in which these neurons die spontaneously.

The rescued neurons were functional as they accumulated dopamine, efficiently. The use of the fluorescent probe dihydrorhodamine-123 revealed that UA operated by an antioxidant mechanism.

The iron chelating agent desferrioxamine, the H2O2 scavenger enzyme catalase and the inhibitor of lipid peroxidation Trolox mimicked the effects of UA, suggesting that UA neutralized reactive oxygen species produced via a Fenton-type chemical reaction.

UA was, however, not significantly accumulated into neurons, which indicates that the antioxidant effect occurred probably extracellularly.

Structure – activity relationships among purine derivatives revealed that the antioxidant properties of UA resulted from the presence of a 8-one substituent in its chemical structure.

Of interest, the stimulation of L-type Ca2+ channels by high K+-induced depolarization and the ensuing activation of extracellular signal-regulated kinases 1/2 strongly improved the neuroprotective effect of UA whereas the depolarizing signal alone had no effect.
In summary, our data indicate that UA may interfere directly with the disease’s pathomechanism.

http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2009.06040.x/full

Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again
De Laval
Posted: Friday, March 09, 2012 11:18:04 AM
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Members..
For your information the lab check my uric acid level and it is 0,23 mmol/l

Jan
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