Blood Clots & Strokes In COVID-19; ACE-2 Receptor; Oxidative Stress

[Drareg]

I’m not sure if this is posted already but it’s a decent mainstream view. You’ll never guess who’s right again, right on the money as it unfolds, it’s like the saga is hitting all the markers he mentioned.



Same channel on famotidine

 

[RealNeat]

Funny you posted this I was watching these last nights and just thinking the whole time, "if only people knew that, Ray Peat is right again... months ago."

 

[Drareg]

Funny you posted this I was watching these last nights and just thinking the whole time, "if only people knew that, Ray Peat is right again... months ago."

You know tragically at this point I firmly believe he’s right about the realization of how toxic the system is only coming to the general public once their health has deteriorated to base mammal like functioning.

This whole covid-19 saga and the behavior of many is an example of how sick the general public are, the mental incoherency is a good sign.

 

[Diokine]

The supple clockwork

The clots are caused by lack of sufficient oxidation status in the vascular network, one of the major causes is sequestration of superoxide anion by indoleamine and tryptophan dioxygenase.

edit: this is worded wrong. It's not necessarily a lack of oxidation status, in general oxidative stress is elevated. But the effects of oxidation on vascular competence are significantly attenuated. This can be catastrophic.

Blood clotting is induced by difference in potential
- Exposure to a gradient significantly different from bulk (i.e. injured environment, release of prostaglandins, COX, oxidative species,) initiates cascade of coagulation
- Coagulation cascade timed very intimately and specifically to direct repair

We can examine this potential as a difference in temporal gradients. High levels of oxidants indicate "high frequency" lability, this reduces the viscosity and "stickiness" of fibrin and reduces tendency towards embolism. Imagine how rubber reacts to manipulation as a function of temperature. Cold rubber is more "dead," less reactive, hot rubber is more "alive." So cold rubber is reduced, hot rubber oxidized. Don't get your rubber too hot or it burns. Coagulation is similar. So reduction-oxidation in the vascular network tunes viscosity and tendency towards clotting.

One of the other factors in the manifestation of this gradient is calcium flux. So arachidonic acid complexes, like prostaglandins, serve to create an electrical "injury potential" or voltage to draw the required high frequency components to prevent significant clotting. Of course this is timed exquisitely and fatigue in this system (PGD2 excess vs PGE2 or prostacyclin) manifests in the capacity of the products of COX and AA to encourage clotting, which is how they are typically interpreted.

Chloroquine works in essence by "toning" the blood or increasing the high frequency component of its temporal spectral decomposition (what the hell does that even mean?) Hypochlorite and other radicals act in a similar fashion. They are the high frequency reference standard in time that allows events to evolve in a continuous fashion, temporally and spatially.

So how is Kawasaki disease related? Why are children expressing with severe arteritis and vascular inflammation, with vascular injury, while grown peoples exhibit thrombus and coagulation? It's complicated but I think that children in general express greater capacity for oxidation, their tendency towards expression of high frequency quenchers like TDO and IDO is reduced. So they express the other end of the oxidative-reductive spectrum, not usually exhibiting clotting but gross endothelial and vascular damage from excessive oxidative stress. How covid toes play into this? What is chilblains? How can we explain it in the context of vascular decompensation? How does a virus contribute to these cascades?

How does tryptophan play?
What about serotonin?
Can you simultaneously have too much serotonin and too little?
What about iron?

If you're a nerd;

A Putative Metabolite of Serotonin, tryptamine-4,5-dione, Is an Irreversible Inhibitor of Tryptophan Hydroxylase: Possible Relevance to the Serotonergic Neurotoxicity of Methamphetamine

Tryptamine-4,5-dione (T-4,5-D) is formed as a result of oxidation of 5-hydroxytryptamine by superoxide (O(2)(-)(*), nitric oxide (NO*), and peroxynitrite (ONOO(-)). T-4,5-D rapidly inactivates tryptophan hydroxylase (TPH), derived from rat brain, probably as a result of covalent modification of active site cysteine residues. The activity of TPH exposed to T-4,5-D cannot be restored by anaerobic reduction with dithiothreitol (DTT) and ferrous iron (Fe(2+)) indicating that the inactivation is irreversible. 7-S-Glutathionyl-tryptamine-4,5-dione, formed by the rapid reaction between T-4,5-D and glutathione, also inhibits TPH but in this case the activity is restored by anaerobic reduction with DTT/Fe(2+). The results of this investigation may be relevant to the initial reversible and subsequent irreversible inactivation of TPH evoked by methamphetamine and 3,4-methylenedioxymethamphetamine.

Serotonin as a Physiological Substrate for Myeloperoxidase and Its Superoxide-Dependent Oxidation to Cytotoxic tryptamine-4,5-dione

During inflammatory events, neutrophils and platelets interact to release a variety of mediators. Neutrophils generate superoxide and hydrogen peroxide, and also discharge the haem enzyme myeloperoxidase. Among numerous other mediators, platelets liberate serotonin (5-hydroxytryptamine), which is a classical neurotransmitter and vasoactive amine that has significant effects on inflammation and immunity. In the present study, we show that serotonin is a favoured substrate for myeloperoxidase because other physiological substrates for this enzyme, including chloride, did not affect its rate of oxidation. At low micromolar concentrations, serotonin enhanced hypochlorous acid production by both purified myeloperoxidase and neutrophils. At higher concentrations, it almost completely blocked the formation of hypochlorous acid. Serotonin was oxidized to a dimer by myeloperoxidase and hydrogen peroxide. It was also converted into tryptamine-4,5-dione, especially in the presence of superoxide. This toxic quinone was produced by stimulated neutrophils in a reaction that required myeloperoxidase. In plasma, stimulated human neutrophils oxidized serotonin to its dimer using the NADPH oxidase and myeloperoxidase. We propose that myeloperoxidase will oxidize serotonin at sites of inflammation. In doing so, it will impair its physiological functions and generate a toxic metabolite that will exacerbate inflammatory tissue damage. Consequently, oxidation of serotonin by myeloperoxidase may profoundly influence inflammatory processes.

Involvement of Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphisms in Susceptibility to Coronary Artery Lesions in Korean Children With Kawasaki Disease

Kawasaki disease (KD) is an acute vasculitis of childhood that predominantly affects the coronary arteries. We investigated single nucleotide polymorphisms (SNPs) of the tryptophan hydroxylase 2 (TPH2) gene as risk factors for KD with coronary artery lesions (CALs) in Korean children. We genotyped two SNPs [rs7305115 (exon 7) and rs4290270 (exon 9)] using direct sequencing in 101 KD and 256 control subjects. To analyze the genetic data, SNPStats, SNPAnalyzer, and Helixtree programs were used. The genotype analysis of rs7305115 and rs4290270 showed no significant differences between KD and control groups. However, we found a statistically significant association between the two SNPs and the development of CALs in KD (p < 0.05). The minor homozygous genotype (rs7305115, AA genotype and rs42901270, AA genotype) of each SNP showed increased susceptibility to risk of CALs in KD patients. These results suggest that TPH2 may be associated with the development of KD with CALs in Korean children.

Myeloperoxidase Genetic Polymorphisms and Susceptibility to Kawasaki Disease in Taiwanese Children



Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation

Enhanced Prostacyclin Generation by Phenolic Compounds Acting as a Tryptophan-Like Cofactor of PG Hydroperoxidase

Serotonin Receptor-Mediated Stimulation of Bovine Smooth Muscle Cell Prostacyclin Synthesis and Its Modulation by Platelet-Derived Growth Factor

Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice

Inhibition and subsequent enhancement of platelet responsiveness by prostacyclin in the rabbit. Relationship to platelet adenosine 3' ,5'- cyclic monophosphate.


While chloroquine may be effective therapy for the vascular pathology, I think intermittent whole body UV irradiation may be safer. Or maybe irradiation of the blood? Supplementing melatonin and 5-MTP would probably be advised also. Anyways I hope some of the symbols fit otherwise we're just spinning wheels.

Also would you say that the statement "a virus is causing this disease," is accurate? Like are the viral particles actually causing the problems we are seeing here? Or are they impacting subtle aspects of physiology that lead to serious disruption? God knows.

 

[Drareg]

The supple clockwork

The clots are caused by lack of sufficient oxidation status in the vascular network, one of the major causes is sequestration of superoxide anion by indoleamine and tryptophan dioxygenase.

edit: this is worded wrong. It's not necessarily a lack of oxidation status, in general oxidative stress is elevated. But the effects of oxidation on vascular competence are significantly attenuated. This can be catastrophic.

Blood clotting is induced by difference in potential
- Exposure to a gradient significantly different from bulk (i.e. injured environment, release of prostaglandins, COX, oxidative species,) initiates cascade of coagulation
- Coagulation cascade timed very intimately and specifically to direct repair

We can examine this potential as a difference in temporal gradients. High levels of oxidants indicate "high frequency" lability, this reduces the viscosity and "stickiness" of fibrin and reduces tendency towards embolism. Imagine how rubber reacts to manipulation as a function of temperature. Cold rubber is more "dead," less reactive, hot rubber is more "alive." So cold rubber is reduced, hot rubber oxidized. Don't get your rubber too hot or it burns. Coagulation is similar. So reduction-oxidation in the vascular network tunes viscosity and tendency towards clotting.

One of the other factors in the manifestation of this gradient is calcium flux. So arachidonic acid complexes, like prostaglandins, serve to create an electrical "injury potential" or voltage to draw the required high frequency components to prevent significant clotting. Of course this is timed exquisitely and fatigue in this system (PGD2 excess vs PGE2 or prostacyclin) manifests in the capacity of the products of COX and AA to encourage clotting, which is how they are typically interpreted.

Chloroquine works in essence by "toning" the blood or increasing the high frequency component of its temporal spectral decomposition (what the hell does that even mean?) Hypochlorite and other radicals act in a similar fashion. They are the high frequency reference standard in time that allows events to evolve in a continuous fashion, temporally and spatially.

So how is Kawasaki disease related? Why are children expressing with severe arteritis and vascular inflammation, with vascular injury, while grown peoples exhibit thrombus and coagulation? It's complicated but I think that children in general express greater capacity for oxidation, their tendency towards expression of high frequency quenchers like TDO and IDO is reduced. So they express the other end of the oxidative-reductive spectrum, not usually exhibiting clotting but gross endothelial and vascular damage from excessive oxidative stress. How covid toes play into this? What is chilblains? How can we explain it in the context of vascular decompensation? How does a virus contribute to these cascades?

How does tryptophan play?
What about serotonin?
Can you simultaneously have too much serotonin and too little?
What about iron?

If you're a nerd;

A Putative Metabolite of Serotonin, tryptamine-4,5-dione, Is an Irreversible Inhibitor of Tryptophan Hydroxylase: Possible Relevance to the Serotonergic Neurotoxicity of Methamphetamine


Serotonin as a Physiological Substrate for Myeloperoxidase and Its Superoxide-Dependent Oxidation to Cytotoxic tryptamine-4,5-dione


Involvement of Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphisms in Susceptibility to Coronary Artery Lesions in Korean Children With Kawasaki Disease



Myeloperoxidase Genetic Polymorphisms and Susceptibility to Kawasaki Disease in Taiwanese Children



Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation

Enhanced Prostacyclin Generation by Phenolic Compounds Acting as a Tryptophan-Like Cofactor of PG Hydroperoxidase

Serotonin Receptor-Mediated Stimulation of Bovine Smooth Muscle Cell Prostacyclin Synthesis and Its Modulation by Platelet-Derived Growth Factor

Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice

Inhibition and subsequent enhancement of platelet responsiveness by prostacyclin in the rabbit. Relationship to platelet adenosine 3' ,5'- cyclic monophosphate.


While chloroquine may be effective therapy for the vascular pathology, I think intermittent whole body UV irradiation may be safer. Or maybe irradiation of the blood? Supplementing melatonin and 5-MTP would probably be advised also. Anyways I hope some of the symbols fit otherwise we're just spinning wheels.

Also would you say that the statement "a virus is causing this disease," is accurate? Like are the viral particles actually causing the problems we are seeing here? Or are they impacting subtle aspects of physiology that lead to serious disruption? God knows.

Thanks this is really good.

What do think about the potential of a vitamin K dump of sorts? pure oxygen displacing CO2 on proteins from the associative induction hypothesis point of view.
Almost like serotonin syndrome.

"Also would you say that the statement "a virus is causing this disease," is accurate? Like are the viral particles actually causing the problems we are seeing here? Or are they impacting subtle aspects of physiology that lead to serious disruption? God knows."

The above is interesting when we think about viral load ,signal and noise. Maybe the main signal is your metabolic rate,a signal is something that has a coherent consistent pattern relative to the noise around it, there can be patterns in the noise but not enough coherency relative to the metabolic rate. The virus at lower levels is just noise until it increases its coherency and becomes the alpha signal.

 

[RealNeat]

The supple clockwork

The clots are caused by lack of sufficient oxidation status in the vascular network, one of the major causes is sequestration of superoxide anion by indoleamine and tryptophan dioxygenase.

edit: this is worded wrong. It's not necessarily a lack of oxidation status, in general oxidative stress is elevated. But the effects of oxidation on vascular competence are significantly attenuated. This can be catastrophic.

Blood clotting is induced by difference in potential
- Exposure to a gradient significantly different from bulk (i.e. injured environment, release of prostaglandins, COX, oxidative species,) initiates cascade of coagulation
- Coagulation cascade timed very intimately and specifically to direct repair

We can examine this potential as a difference in temporal gradients. High levels of oxidants indicate "high frequency" lability, this reduces the viscosity and "stickiness" of fibrin and reduces tendency towards embolism. Imagine how rubber reacts to manipulation as a function of temperature. Cold rubber is more "dead," less reactive, hot rubber is more "alive." So cold rubber is reduced, hot rubber oxidized. Don't get your rubber too hot or it burns. Coagulation is similar. So reduction-oxidation in the vascular network tunes viscosity and tendency towards clotting.

One of the other factors in the manifestation of this gradient is calcium flux. So arachidonic acid complexes, like prostaglandins, serve to create an electrical "injury potential" or voltage to draw the required high frequency components to prevent significant clotting. Of course this is timed exquisitely and fatigue in this system (PGD2 excess vs PGE2 or prostacyclin) manifests in the capacity of the products of COX and AA to encourage clotting, which is how they are typically interpreted.

Chloroquine works in essence by "toning" the blood or increasing the high frequency component of its temporal spectral decomposition (what the hell does that even mean?) Hypochlorite and other radicals act in a similar fashion. They are the high frequency reference standard in time that allows events to evolve in a continuous fashion, temporally and spatially.

So how is Kawasaki disease related? Why are children expressing with severe arteritis and vascular inflammation, with vascular injury, while grown peoples exhibit thrombus and coagulation? It's complicated but I think that children in general express greater capacity for oxidation, their tendency towards expression of high frequency quenchers like TDO and IDO is reduced. So they express the other end of the oxidative-reductive spectrum, not usually exhibiting clotting but gross endothelial and vascular damage from excessive oxidative stress. How covid toes play into this? What is chilblains? How can we explain it in the context of vascular decompensation? How does a virus contribute to these cascades?

How does tryptophan play?
What about serotonin?
Can you simultaneously have too much serotonin and too little?
What about iron?

If you're a nerd;

A Putative Metabolite of Serotonin, tryptamine-4,5-dione, Is an Irreversible Inhibitor of Tryptophan Hydroxylase: Possible Relevance to the Serotonergic Neurotoxicity of Methamphetamine


Serotonin as a Physiological Substrate for Myeloperoxidase and Its Superoxide-Dependent Oxidation to Cytotoxic tryptamine-4,5-dione


Involvement of Tryptophan Hydroxylase 2 (TPH2) Gene Polymorphisms in Susceptibility to Coronary Artery Lesions in Korean Children With Kawasaki Disease



Myeloperoxidase Genetic Polymorphisms and Susceptibility to Kawasaki Disease in Taiwanese Children



Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation

Enhanced Prostacyclin Generation by Phenolic Compounds Acting as a Tryptophan-Like Cofactor of PG Hydroperoxidase

Serotonin Receptor-Mediated Stimulation of Bovine Smooth Muscle Cell Prostacyclin Synthesis and Its Modulation by Platelet-Derived Growth Factor

Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice

Inhibition and subsequent enhancement of platelet responsiveness by prostacyclin in the rabbit. Relationship to platelet adenosine 3' ,5'- cyclic monophosphate.


While chloroquine may be effective therapy for the vascular pathology, I think intermittent whole body UV irradiation may be safer. Or maybe irradiation of the blood? Supplementing melatonin and 5-MTP would probably be advised also. Anyways I hope some of the symbols fit otherwise we're just spinning wheels.

Also would you say that the statement "a virus is causing this disease," is accurate? Like are the viral particles actually causing the problems we are seeing here? Or are they impacting subtle aspects of physiology that lead to serious disruption? God knows.

not to over simply your well written thought but I think if we analyze everything Ray has said happens to people and the physiological effects/ cascade that is produced in a low energy state, hypothyroidism etc... and follow that, there is almost no room for disruption. Once any further disruption occurs like in ACE2 we are looking for order in a building that's actively collapsing.

 

[RealNeat]

Thanks this is really good.

What do think about the potential of a vitamin K dump of sorts? pure oxygen displacing CO2 on proteins from the associative induction hypothesis point of view.
Almost like serotonin syndrome.

"Also would you say that the statement "a virus is causing this disease," is accurate? Like are the viral particles actually causing the problems we are seeing here? Or are they impacting subtle aspects of physiology that lead to serious disruption? God knows."

The above is interesting when we think about viral load ,signal and noise. Maybe the main signal is your metabolic rate,a signal is something that has a coherent consistent pattern relative to the noise around it, there can be patterns in the noise but not enough coherency relative to the metabolic rate. The virus at lower levels is just noise until it increases its coherency and becomes the alpha signal.

Also have you read this yet? I think this is the second phase if the body has been compromised and not recovered after the virus, https://osf.io/usztn/

 

[Diokine]

What do think about the potential of a vitamin K dump of sorts? pure oxygen displacing CO2 on proteins from the associative induction hypothesis point of view.
Almost like serotonin syndrome.

Yes this is probably a very competent frame, thanks. Carboxylation probably interfaces "holonomically" with respect to the idea of temporal decomposition. CO2 feels like the gold standard reference clock in this system, a product directly yoked to the output of the watch maker mitochrons.

looking for order in a building that's actively collapsing.

Tricky business.

 

[LeeLemonoil]

Anthony Fauci right again .... wait, no, this other guy.

 

[Drareg]

Anthony Fauci right again .... wait, no, this other guy.

Is trump protecting fauci at the moment by not allowing him to questioned ? I’m following the euro story more at the moment so don’t have time to pick through the mega drama that is American politics.

 

[Drareg]

Also have you read this yet? I think this is the second phase if the body has been compromised and not recovered after the virus, https://osf.io/usztn/

It’s interesting and an additional burden ,normal metabolism doesn’t allow the growth, hydrogen peroxide should take care of them before they multiply maybe.

 

[HLP]

I’m not sure if this is posted already but it’s a decent mainstream view. You’ll never guess who’s right again, right on the money as it unfolds, it’s like the saga is hitting all the markers he mentioned.



Same channel on famotidine

I unsubscribed to this. Too religiously motivated.

 

[Drareg]

I unsubscribed to this. Too religiously motivated.

Oh really I didn’t know that, thanks.

 

[Peatness]

Flavonoid compound can prevent blood clots — Harvard Gazette

Harvard researchers have shown that a compound called rutin, commonly found in fruits and vegetables and sold over the counter as a dietary supplement, inhibits the formation of blood clots in an animal model of thrombosis.

news.harvard.edu

 

[BRMarshall]

Yes this is probably a very competent frame, thanks. Carboxylation probably interfaces "holonomically" with respect to the idea of temporal decomposition. CO2 feels like the gold standard reference clock in this system, a product directly yoked to the output of the watch maker mitochrons.



Tricky business.

please more of your haiku and a follow up at some point to your amazing long puzzle of intrigue that seems to have synchronized with reent discussion in the familly as concers serotonin syndrome, and now a discussion of these vax clotts that some are saying is some sort of amoloidosis, which maybe a hypothesis or hype, but was enough to do a search an find this thread i think will evolve as the crisis continues...