Hi John,

I'm sorry to hear this. My thoughts are with you and your family.

Mary

Ron and a few other have said that they have lost there sense of taste after starting OSC.

I wonder if somehow OSC has an affect on the gluamate receptors?

Glutamate receptor


From Wikipedia, the free encyclopedia

Excitotoxicity

Overstimulation of glutamate receptors causes neurodegeneration and neuronal damage through a process called excitotoxicity. Excessive glutamate, or excitotoxins acting on the same glutamate receptors, overactivate glutamate receptors (specifically NMDARs), causing high levels of calcium ions (Ca2+) to influx into the postsynaptic cell.[32]


Effects outside the central nervous system

Glutamate receptors are thought to be responsible for the reception and transduction of umami taste stimuli.

Taste receptors of the T1R family, belonging to the same class of GPCR as metabotropic glutamate receptors are involved.
Additionally, the mGluRs, as well as ionotropic glutamate receptors in neural cells, have been found in taste buds and may contribute to the umami taste

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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

Don't go by what Ron says. I can only speak for myself.

The old about glutamate is that it was not the most "druggable" or optimal target as originally thought. But glutamate exitotoxicity is still a very significant adverse consequence of ALS.

Note that the discussion above was not related to the possible negative effects of ingesting glutamate.

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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.

I am rather excited now...

After listening to the update on the NP001 trial that Rob provided a link to, it looks like they will finish the trial in 2012.

If the "first aid" treatment provided by oral sodium chlorite keeps helping, you may have something beyond the "incredible anecdotal blog-o-sphere" stories that we now have.

Sometimes you have to dig a little to find progress, but it appears that it is there...

Tom

Hello Ron,

That is very interesting. I have a theory that a heavy dose helps at first, then you can cut back to a lower dose and still hold on to the benefits.

If chlorite is dealing with inflammation, the large amount may be needed to get things under control, then lower amounts may keep things in control.

This is a wild guess on my part, but a few people have observed the same thing.

Your taste "thing" is interesting. That is not a common side effect outside of the ALS community. My initial thought is to agree with Nemesis in that you may have a vitamin, or mineral, or electrolyte imbalance that is aggravated by oxidation.

By the time the NP001 phase III trials are done, we may have oral sodium chlorite dialed in... :)

Tom

Tom/Ron,
the taste effect, if it is caused by fluctuating glutamate levels may indicate that:

1. OSC has an unknown action on glutamate levels - maybe not directly on the mechanism of glutamate prodution but through some other knock on mechanism

2. OSC at lower doses would probably better because if item 1 is true then higher doses of OSC, as reported by Ron, cause loss of taste (higher glutamate levels) and reduction in OSC reversed the taste effect and decreases glutamate levels.

Or OSC may impact taste buds by some unknow, as yet, mechanism?

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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

DTA reported taste loss too, along with a few others. Can't remember who. I cut back to 14 ml SC instead of 17 ml. In my mix. I have 75% taste now. Still on two tablespoons a day. Still have strong legs and arms. Eat fine. Drive car, cut grass. Chase women, and drink whiskey.

Looking further at taurine chloramine as it is has been proposed that it is increased when taking OSC what does tau-Cl actually do?

...........................................

IkappaB is a sensitive target for oxidation by cell-permeable chloramines: inhibition of NF-kappaB activity by glycine chloramine through methionine oxidation.

Abstract
Hypochlorous acid (HOCl) is produced by the neutrophil enzyme, myeloperoxidase, and reacts with amines to generate chloramines.
These oxidants react readily with thiols and methionine and can affect cell-regulatory pathways.
In the present study, we have investigated the ability of HOCl, glycine chloramine (Gly-Cl) and taurine chloramine (Tau-Cl) to oxidize IkappaBalpha, the inhibitor of NF-kappaB (nuclear factor kappaB), and to prevent activation of the NF-kappaB pathway in Jurkat cells.
Glycine chloramine (Gly-Cl) and HOCl were permeable to the cells as determined by oxidation of intracellular GSH and inactivation of glyceraldehyde-3-phosphate dehydrogenase, whereas Tau-Cl showed no detectable cell permeability.
Both Gly-Cl (20-200 muM) and HOCl (50 microM) caused oxidation of IkappaBalpha methionine, measured by a shift in electrophoretic mobility, when added to the cells in Hanks buffer.
In contrast, a high concentration of Tau-Cl (1 mM) in Hanks buffer had no effect.
However, Tau-Cl in full medium did modify IkappaBalpha.
This we attribute to chlorine exchange with other amines in the medium to form more permeable chloramines.
Oxidation by Gly-Cl prevented IkappaBalpha degradation in cells treated with TNFalpha (tumour necrosis factor alpha) and inhibited nuclear translocation of NF-kappaB. IkappaBalpha modification was reversed by methionine sulphoxide reductase, with both A and B forms required for complete reduction. Oxidized IkappaBalpha persisted intracellularly for up to 6 h. Reversion occurred in the presence of cycloheximide, but was prevented if thioredoxin reductase was inhibited, suggesting that it was due to endogenous methionine sulphoxide reductase activity.
These results show that cell-permeable chloramines, either directly or when formed in medium, could regulate NF-kappaB activation via reversible IkappaBalpha oxidation

http://www.ncbi.nlm.nih.gov/pubmed/16405428
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If I'm reading the above right Tau-Cl modifies or oxidises IkappaBalpha the inhibitor of NF-kappaB (nuclear factor kappaB), and to prevent activation of the NF-kappaB pathway in Jurkat cells.

In other word it prevents activation of the NF-kappaB pathway in Jurkat cells.
...................................................

The following shows another substance that also blocks of the NF-kappaB pathway in Jurkat cells and gives an indication of action on the immune system.

Maybe another candidate with the same action as chlorite?
....................................................


Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression.
.
Leflunomide is a novel immunosuppressive and antiinflammatory agent currently being tested for treatment of autoimmune diseases and transplant rejection.

NF-kappa B is a transcription factor activated in response to a wide variety of inflammatory stimuli, including TNF, but whether leflunomide blocks NF-kappa B activation is not known.
In the present report we demonstrate that treatment of a human T cell line (Jurkat) with leflunomide blocks TNF-mediated NF-kappa B activation in a dose- and time-dependent manner, with maximum inhibition at 5-10 microM.

Inhibition was not restricted to TNF-induced activation, because leflunomide also inhibited NF-kappa B activation induced by other inflammatory agents, including phorbol ester, LPS, H2O2, okadaic acid, and ceramide. Leflunomide blocked the degradation of I kappa B alpha and subsequent nuclear translocation of the p65 subunit, steps essential for NF-kappa B activation.

This correlated with inhibition of dual specificity-mitogen-activated protein kinase kinase as well as an Src protein tyrosine kinase, p56lck, by leflunomide. Reducing agents did not reverse the effect of leflunomide.

Leflunomide also suppressed the TNF-activated NF-kappa B-dependent reporter gene expression.
Our results thus indicate that leflunomide is a potent inhibitor of NF-kappa B activation induced by a wide variety of inflammatory stimuli, and this provides the molecular basis for its anti-inflammatory and immunosuppressive effects.

http://lib.bioinfo.pl/pmid:9973483

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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

Hello Ron,

If you went to "store bought" whiskey instead of brewing your own, your sense of taste would probably return... :)

Glad to hear that you are doing reasonably well.

Tom