Author Topic: Information about Cytokines and other biological substances  (Read 11899 times)

Nas

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Re: Information about Cytokines and other biological substances
« Reply #40 on: March 13, 2019, 05:34:11 PM »
So do you guys think Quinolinic acid serum level have any meaning in POIS? When should this be measured?
https://drive.google.com/file/d/1nLgk-A7TpkU1k7Z3GTeH9kPrR3siqKcW/view
Actually B3 levels after orgasm would be a very good indicator of the validity of this theory.
Isn't it crazy that no one actually tested their B3 levels in this form, yet?

Nas

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Re: Information about Cytokines and other biological substances
« Reply #41 on: March 14, 2019, 03:50:01 PM »
Quoted from Nanna on the topic of kynurenic acid:


Here is some background information that might help you with the kynurenine pathway:
  Glutamate (excitation) and GABA (inhibition) act as on/off switches for neurons. When the neuron is on (glutamate-NMDA) there is increased energy consumption and NAD+/NADH cycling. When the neuron is turned off (GABA) energy is conserved and there is very little cellular activity.

  The main purpose of the kynurenine pathway is to produce niacin and ultimately NADH and NADPH (Ref). NADH and NADPH are a key energy redox antioxidants that allow the body to used calories as energy (ATP). NAD+ is also a required cofactor along with poly(ADP-ribose) polymerase-1 (PARP-1) for DNA repair. But if there is too much DNA damage then PARP-1 will consume and deplete NAD+, which depletes the energy of the cell/neuron and kills it. For example:
Blockade of PARP activity attenuates poly(ADP-ribosyl)ation but offers only partial neuroprotection against NMDA-induced cell death in the rat retina.

  As long as everything is normal in a neuron/cell, then the kynurenine pathway is only producing niacin/NAD as the end-product. However, there are several ways that the neuron can detect DNA damage. If a small amount of DNA damage occurs then NAD+ is consumed by PARP-1 to repair DNA. But if a large amount of DNA damage is suddenly detected, the cell goes into safe-mode by shutting down cellular activity (block NMDA, reduce PARP-1 activity, and increase GABA). This is partially accomplished by diverting kynurenine metabolism away from niacin production and into kynurenic acid. Kynurenic acid then blocks cellular activity by blocking glutamate receptors (NMDA, AMPA, etc...) (Ref). The increase in kynurenic acid prevents further DNA damage and stress induced toxicity.

  Kynurenic acid production is a safety-switch in the kynurenine pathway to prevent DNA damage and cell death. The side-effect of this is that it prevents DNA damage by shutting down the neuron (inhibiting glutamate receptors) so that it is no longer excited/firing (brain fog). Kynurenic acid prevents excitotoxicity at the expense of cognition. If you want to decrease kynurenic acid and brain fog, you should answer the question, "Why is there an increase in DNA damage?" Different stressors (cancer, infection, poison, emotional stress) can cause DNA damage. So I do not consider kynurenic acid a cause of anything, but rather it is a safety-reaction to a cause.

  The true cause of brain fog is likely something that has nothing to do with the kynurenine pathway, but the body uses changes in the kynurenine pathway to prevent irreversible DNA damage. You can always recover from kynurenic acid induced brain fog, but you cannot recover from neuron loss (brain cell death) due to DNA damage.

In terms of autoimmune diseases, "N-acetylcysteine (NAC) treatment significantly reduced kynurenine levels relative to placebo in vivo" -Comprehensive metabolome analyses reveal N-acetylcysteine-responsive accumulation of kynurenine in systemic lupus erythematosus: implications for activation of the mechanistic target of rapamycin

Sure you can share that explanation. If you do, you may also want to share this quote:
"Kynurenic acid shows neuroprotective properties. (Ref12) Some researchers have posited that the increased levels found in cases of neurological degradation is due to a failed attempt to protect the cells. (Ref13)" -Kynurenic acid: Role in disease

Muon

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Re: Information about Cytokines and other biological substances
« Reply #42 on: March 15, 2019, 09:20:15 AM »
Some of us do feel better on a ketogenic diet:
https://en.wikipedia.org/wiki/Kynurenic_acid#Link_to_ketogenic_diet

Nas

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Re: Information about Cytokines and other biological substances
« Reply #43 on: March 18, 2019, 09:41:34 PM »
From wiki:

KYNA has been proposed to act on four targets:

As an antagonist at ionotropic AMPA, NMDA and Kainate glutamate receptors in the concentration range of 0.1-2.5 mM.[2]

As a noncompetitive antagonist at the glycine site of the NMDA receptor.

As an antagonist of the α7 nicotinic acetylcholine receptor.[3] However, recently (2011) direct recording of α7 nicotinic acetylcholine receptor currents in adult (noncultured) hippocampal interneurons by the Cooper laboratory [4] validated a 2009 study [5] that failed to find any blocking effect of kynurenic acid across a wide range of concentrations, thus suggesting that in noncultured, intact preparations from adult animals there is no effect of kynurenic acid on α7 nicotinic acetylcholine receptor currents.[4][5]

As a ligand for the orphan G protein-coupled receptor GPR35.[6] Another tryptophan metabolite, 5-hydroxyindoleacetic acid exerts its effects via the orphan G protein-coupled receptor GPR35.[7]

It seems that Glycine is only going to work on agonising the NMDA receptor from the Glycine site, but what about the ionotropic site? Or the AMPA and kainate receptors?

b_jim

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Re: Information about Cytokines and other biological substances
« Reply #44 on: March 19, 2019, 10:46:34 AM »
I think we are VERY CLOSE of the Pois secret.
it's hard for me to understand all these elements. I need some hours to work on this.
Taurine + Choline = Anti-Pois
Lyme disease "cured" in 2020.

Nas

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Re: Information about Cytokines and other biological substances
« Reply #45 on: March 19, 2019, 10:53:00 AM »
I think we are VERY CLOSE of the Pois secret.
it's hard for me to understand all these elements. I need some hours to work on this.
I wouldn't be that optimistic b_jim, but hey, maybe we can hit some sort of Jackpot and accidentally find a universal solution? or even a bio-marker?

demografx

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Re: Information about Cytokines and other biological substances
« Reply #46 on: March 19, 2019, 11:18:40 AM »
I think we are VERY CLOSE of the Pois secret.
it's hard for me to understand all these elements. I need some hours to work on this.
I wouldn't be that optimistic b_jim, but hey, maybe we can hit some sort of Jackpot and accidentally find a universal solution? or even a bio-marker?

Nas, I’m hoping for the Jackpot, even after 12 years of this forum work.

b_jim, I love your Spirit!

Demo
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

Nas

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Re: Information about Cytokines and other biological substances
« Reply #47 on: March 19, 2019, 12:11:58 PM »
I think we are VERY CLOSE of the Pois secret.
it's hard for me to understand all these elements. I need some hours to work on this.
I wouldn't be that optimistic b_jim, but hey, maybe we can hit some sort of Jackpot and accidentally find a universal solution? or even a bio-marker?

Nas, I’m hoping for the Jackpot, even after 12 years of this forum work.

b_jim, I love your Spirit!

Demo
I've been recently going into an emotional spiral where I just keep thinking of all the relationships that I could've had and that was getting me horny which made me relapse alot these recent days, so I've also been taking cigarettes after orgasm, cigarettes if you don't know, give me POIS. This I think was too much of a load on my metabolic mechanism of POIS and I think that gave me some sort of anemia ( general weakness, pain in the kidneys, my throat feels rigid, dizziness, tiredness, etc.) Perhaps if I can figure out what type of anemia I'm suffering from I can trace it back to its metabolic cycle. According to this thread, it could b3 deficiency however I don't have pellagra symptoms, I think it's more similar to D3 deficiency. Maybe I'll do general serum vitamins in the future. We'll see.

b_jim

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Re: Information about Cytokines and other biological substances
« Reply #48 on: March 19, 2019, 03:16:21 PM »
Some guys spoke about Anti-NMDA receptor encephalitis. Clearly, the symptoms are the same that Pois : flu-lik, memory, speech/cummonication, insomnia, vision, muscular....

Taurine + Choline = Anti-Pois
Lyme disease "cured" in 2020.

b_jim

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Re: Information about Cytokines and other biological substances
« Reply #49 on: March 19, 2019, 03:29:39 PM »
It's like if we lose controle of NMDA's after ejaculation.
The elements keeping controle of sex homeostasis (testosterone level, semen regeneration) might be the same keeping controle of the NMDA.

So we can keep the one the system in balance, but not both in the same time because some element might be missing (mg in my case).

Taurine + Choline = Anti-Pois
Lyme disease "cured" in 2020.

Nas

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Re: Information about Cytokines and other biological substances
« Reply #50 on: March 19, 2019, 05:30:12 PM »
It's like if we lose controle of NMDA's after ejaculation.
The elements keeping controle of sex homeostasis (testosterone level, semen regeneration) might be the same keeping controle of the NMDA.

So we can keep the one the system in balance, but not both in the same time because some element might be missing (mg in my case).
Can be a good explanation but it has to be proven.

Nas

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Re: Information about Cytokines and other biological substances
« Reply #51 on: March 20, 2019, 01:11:58 PM »
It's like if we lose controle of NMDA's after ejaculation.
The elements keeping controle of sex homeostasis (testosterone level, semen regeneration) might be the same keeping controle of the NMDA.

So we can keep the one the system in balance, but not both in the same time because some element might be missing (mg in my case).
Quote from Nanna:
"  Kynurenic acid (KA) prevents any activation of the NMDA receptor (NMDAR). This is how it turns off the neuron. So not even glutamate can activate NMDAR once KA blocks the glycine site. Herbs like Tribulus or Wormwood may be able to overcome this block of the NMDA receptor, but playing with NMDAR is a dangerous game due to excitotoxicity. Niacinamide is known to prevent glutamate induced excitotoxicity. So while you are trying to excite this receptor, you may want to take Niacinamide as a safety. You can look in the literature for the appropriate Niacinamide. I personally, do not think Kynurenic acid or the NMDAR is the problem in POIS. Something that might be safer to try is beta-alanine (see post)."

Nas

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Re: Information about Cytokines and other biological substances
« Reply #52 on: March 22, 2019, 06:07:01 PM »
Where does the KYNA metabolic activation primarily occur? Is it only in the CNS, or the peripheral nervous system, or anywhere ? 

Nas

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Re: Information about Cytokines and other biological substances
« Reply #53 on: March 23, 2019, 04:45:18 PM »
"COX-2 inhibitors down-regulate indoleamine 2,3-dioxygenase, leading to a reduction in kynurenine levels as well as reducing proinflammatory cytokine activity." from wiki
I tried celebrex many times and many different NSAID's but with no success. Should this be a sign that this theory is false in my case?

Nas

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Re: Information about Cytokines and other biological substances
« Reply #54 on: March 29, 2019, 11:54:46 AM »
Just tested Glycine powder. I took about ~2000mg dissolved in water after orgasm and no significant effect was observed.