Patent filing for the use of nitric oxide with or without B-cell depletion in CFS

[aimossy]

Mady Hornig found us to have significantly reduced ADMA asymmetric dimethylarginine in the first 3 years. Could this be related to the breakdown of synthesis with NO at all. She said this could cause oxidative stress. This was reported from the last IiME conference regarding a study on 180 metabolites that I presume is still to be published.

 

[NK17]

I am not the right person to answer that

I think this one is good in explaining it: http://spo.escardio.org/eslides/view.aspx?eevtid=40&fp=1939

Wow @deleder2k once again you are our greatest informant and Prof. Mella and Dr. Fluge our true heroes!
They're really looking and working hard to find the treasure trove of treatments that might work for us.

 

[Snow Leopard]

If everyone else is doing that it makes sense to do the same. I think it is a pity, but it may mean that money comes back to hospitals and universities rather than just going to drug company shareholders.

Yes, the answer is that someone is going to patent the ideas. I'd rather it be the Mellas and Fluges of the world, rather than patent trolls or certain drug companies...

 

[Snow Leopard]

This is not in line with Fluga and Mella who use products to raise the NO level and dilated the bloodvessels even more. I don't understand this, anyone?

This was my question too...

OI does suggest endothelial dysregulation, but towards vasodilation and elevated NO, rather than vasoconstriction.

There is of course a balance between the various NO synthases and perhaps one may be upregulated, whereas the others are downnregulated, this could contribute to symptoms in some way?

The hypothesis still needs a lot of work...

 

[adreno]

OI does suggest endothelial dysregulation, but towards vasodilation and elevated NO, rather than vasoconstriction.

There are likely several types of OI/POTS. Low NO was reported as a mechanism of low flow POTS ten years ago:

Decreased Microvascular Nitric Oxide–Dependent Vasodilation in Postural Tachycardia Syndrome

 

[alex3619]

Could this be related to the breakdown of synthesis with NO at all. She said this could cause oxidative stress.

I am unsure about this. Does anyone know why it will cause increased oxidative stress? It seems to me there may be additional things going on, either empirically or theoretically, and used to infer this.

High ADMA may impact NO synthesis resulting in vasoconstriction. Low ADMA seems under-researched.

One possibility, if ADMA is not low or is high in long term patients, is that this is part of the switch between short and long term.

ADMA is linked to methylation issues too. I have not fully investigated this.

 

[Sidereal]

This was my question too...

OI does suggest endothelial dysregulation, but towards vasodilation and elevated NO, rather than vasoconstriction.

I vaguely recall it being proposed that the problem could be regional - excessive vasodilation of the large blood vessels and too much constriction in the periphery.

 

[alex3619]

Let me point out that low ADMA is consistent with very high NOS activity whether or not it produces NO. The alternative product is peroxynitrite, ONOO, according to one hypothesis. There are too many unknowns at present for us to be sure of anything. It might be that our nitric oxide synthesis is pumping out toxic peroxynitrite. So we could be pushing NO synthesis but still vasoconstricted and with a side of oxidative stress. Yummy.

 

[alex3619]

I vaguely recall it being proposed that the problem could be regional - excessive vasodilation of the large blood vessels and too much constriction in the periphery.

Which would imply regulatory failure, and maybe neurological. Other alternatives involving the extensive gut vasculature have also been proposed.

PS Guess where enteroviruses love to hang out?

 

[MeSci]

I vaguely recall it being proposed that the problem could be regional - excessive vasodilation of the large blood vessels and too much constriction in the periphery.

I really do recommend that anyone who hasn't yet read the 2 Phoenix Rising nitric oxide articles I linked to do so, as they provide explanations - or at least hypotheses - for many of the issues being discussed here.

For example, the second article says:

If eNOS is inhibited, nitric oxide cannot act to dilate the blood vessels in muscle tissue. The lower supply of blood to the peripheral circulation and muscles means that the supply of oxygen and removal of waste materials cannot occur at a sufficient rate in respiring tissues.

This means that when the muscles are used in ME/CFS patients, there is a much lower ability to produce ATP through aerobic respiration. Therefore anaerobic respiration has to 'pick up the slack' to provide the vital ATP required for voluntary muscle contraction.

 

[MeSci]

I first encountered it in neuroscience lectures. You don't form memory properly if you are deficient.

I seem to form memories OK except during brain fog (unless that is more a matter of retrieval). So could PEM reduce NO levels? Ah - the diagram @melihtas posted suggests that it's the other way round, so exertion in the presence of insufficient endothelial NO leads to premature anaerobic ATP production and consequent PEM, and the inadequate synthesis of endothelial NO is hypothesised as being due to autoimmune activity (reducing or inhibiting eNOS?).

 

[gregh286]

What about nitric oxide supplements.

 

[Hip]

What about nitric oxide supplements.

Nitric oxide is a gas, and although inhalation of this gas can be used medically, it's vasodilatory effects never travel much further than the lungs.† This is because the half life of NO in the blood is incredibly short: around 1 second. So NO breaks down extremely quickly in the blood, and needs to be made on the spot where and when it is needed. In the body, NO is manufactured by nitric oxide synthase enzymes (NOS). There are three such NOS enzymes: iNOS, eNOS and nNOS.

 

[Jonathan Edwards]

Nitric oxide is a gas, and although inhalation of this gas can be used medically, it's vasodilatory effects never travel much further than the lungs.† This is because the half life of NO in the blood is incredibly short: around 1 second. So NO breaks down extremely quickly in the blood, and needs to be made on the spot where and when it is needed. In the body, NO is manufactured by nitric oxide synthase enzymes (NOS). There are three such NOS enzymes: iNOS, eNOS and nNOS.

The inhaled anaesthetic gas is nitrous oxide N2O, which is stable. Nitric oxide NO mixed with air forms nitrogen dioxide before you can breathe it in and choke on the nasty brown NO2 gas if I remember rightly.

 

[Hip]

The inhaled anaesthetic gas is nitrous oxide N2O, which is stable. Nitric oxide NO mixed with air forms nitrogen dioxide before you can breathe it in and choke on the nasty brown NO2 gas if I remember rightly.

Perhaps that happens at higher NO concentrations? In this paper they talk about inhaling NO at concentrations of 20 ppm for medical purposes.


Apparently dietary nitrates raise NO levels. High levels of nitrates can be found in beetroot juice. A few years ago I tried taking potassium nitrate 2 grams daily, but did not notice much in the way of symptom improvements.

 

[anne_likes_red]

Recently I discovered beetroot juice makes me feel significantly better. OI symptoms improve most but I experienced cognitive improvement too.
When I had a look online to see what could be happening with the juice I found sports blogs discussing benefits relating to muscle recovery and stamina.

(I juiced organic beets at home myself but I suppose bottled stuff might have the same effect.)

 

[Hip]

Recently I discovered beetroot juice makes me feel significantly better. OI symptoms improve most but I experienced cognitive improvement too.
When I had a look online to see what could be happening with the juice I found sports blogs discussing benefits relating to muscle recovery and stamina.

You might like this article on a study on the effects of nitrates / beetroot juice on blood pressure:

Beetroot juice and blood pressure - Health news - NHS Choices


The actual study is here:

Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans

 

[anne_likes_red]

...So I wonder if beetroot juice could have a 'normalizing' effect on BP rather than exclusively lowering it?
My BP overall at the time was lower than normal. ...The result, I think, of increased exposure to LPS.

 

[Sushi]

I juiced organic beets at home myself

Good idea. I'll drag out my juicer and see what happens.

You might like this article on a study on the effects of nitrates / beetroot juice on blood pressure:

We might be touching again on the difference that many of us have between the levels of vasodialation in large and small blood vessels. It isn't clear what the effect of NO is in these cases--is it?

So I wonder if beetroot juice could have a 'normalizing' effect on BP rather than exclusively lowering it?

I am wondering that too. The "public" is only concerned with reducing high blood pressure.

Sushi

 

[Sidereal]

...So I wonder if beetroot juice could have a 'normalizing' effect on BP rather than exclusively lowering it?
My BP overall at the time was lower than normal. ...The result, I think, of increased exposure to LPS.

Beet raises my BP from 90/60 to 110/70.