Key: "The observed pulmonary vascular dilation might be due to relative failure of normal, physiological hypoxic pulmonary vasoconstriction in the setting of overactivation of a regional vasodilatation cascade as part of a dysfunctional and diffuse inflammatory process." 2/
This leads me to hypothesize this is the site of viral injury, where #COVID binds #ACE2R's - where mito demands are the greatest - where #HIF proteins and assoc. cascades they initiate are in play - including #vasodialiation #angiogenesis and excessive #inflammation 3/
Key points:
HIF-a subunit stability is posttranscriptionally regulated by o2 availability through the iron-dependent enzymes prolylhydroxylases (PHDs). When O2 is available, PHDs are active and hydroxylate HIF-a, 5/
HIF-a subunit stability is posttranscriptionally regulated by o2 availability through the iron-dependent enzymes prolylhydroxylases (PHDs). When O2 is available, PHDs are active and hydroxylate HIF-a, 5/
marking it for proteasomal degradation... If O2 drops, PHDs become inactive, resulting in HIF-a accumulation. Factor inhibiting HIF (FIH) provides another layer of regulation by hydroxylating asparaginyl residues in HIF1-α and HIF-2α, 6/
blocking protein interactions between the HIF-α transactivation domain (CAD) and coactivators like P300 that form an effective transcriptional complex. 7/
Apart from O2 as a cofactor, both PHDs and FIH require a-ketoglutarate (2-oxoglutarate) as a limiting electron donor cosubstrate, which is oxidized and decarboxylated to succinate. Ferrous iron and ascorbate serve as cofactors for these hydroxylation reactions 8/
Poor iron - management - hmm. See a pattern? The much ballyhooed mechanism of the suspected success of #hydroxychloroquine (and no, I am not advocating for HCQ, it is a horrible drug, just pointing out a pattern). What this and other articles fail to realize is 9/
Indeed, thiamine insufficiency by itself, absent any other potentially hypoxia inducing variables, induces hypoxia and stabilizes the HIF cascades mentioned above. ncbi.nlm.nih.gov/pubmed/24846908 12/
And here - just for kicks and giggles - this lab does a lot of great work on thiamine deficiency. ncbi.nlm.nih.gov/pmc/articles/P… 13/
So why do I keep harping on #thiaminedeficiency and mitochondrial fitness or lack thereof relative to #COVID? 14/
It's bc it is critical to mitochondrial function and thus for survival. Everything about #COVID speaks to #mitochondrialcollapse -we just have to get beyond the laundry list of suspected covid symptoms, the vain attempts to create an equally long laundry list of new diagnoses 15/
and ask what could potentially cause all of these seemingly disparate symptoms? The answer is failing mitochondria. 16/
Certainly, #COVID is a nasty virus and as the initial article posted above shows, it does attack the lungs in some new and unique ways, but that may be more an expression of mitochondrial damage than of the virus itself. 17/
Damage that is magnified by pre-existing conditions, medications and of course the #virus itself, but mitochondrial damage nevertheless. Viruses usurp several mito pathways after all. ncbi.nlm.nih.gov/pmc/articles/P… 18/
And whenever we are talking about #mitochondria, we have to talk about #thiamine.
Serious illness is a drain on the mitochondria. Serious illness requires thiamine (and other nutrients) to survive. It is so simple and yet we make it so complex. 19/
Serious illness is a drain on the mitochondria. Serious illness requires thiamine (and other nutrients) to survive. It is so simple and yet we make it so complex. 19/
But here we are, requiring infinite proof to provide an essential vitamin to patients while we simultaneously sling any number of untested and dangerous drugs at them. 20/
Please, please, please consider IV thiamine in the treatment of COVID (a Wernicke's protocol) and if you're feeling particularly rambunctious, throw in a banana bag for some other much needed nutrients (daily, 2x daily, not just once).
End of sermon. 21/
End of sermon. 21/
