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Are astrocytes suppressed by corticosteroids as well? Also, how effective would corticosteroids if the inflammation is getting worse at the same time as the treatment is given, ie, say DAMPS are increasing in concentration and leading to more inflammation

Could PEM be, when neuron action potential fires, use of atp, atp require mitochondria and defective mitochondria generates more ROS, and then ROS causes DAMPS release from within the cell itself that the mitochondria is in, and that DAMPS released then activate glial cells which causes...

Yes but, you can ask to try it, in a similar way that ampligen is available I think. It's a matter of convincing a doctor and then convincing somebody at the Pharma comoany. Given that a phase 3 trial has been done, although failed, it seems reasonable to say it's safe to try once, though long...

Wait sorry if this is wrong place for me to ask, but who the heck should I target to see if I were to try to obtain tak 242? I'm a fibro patient with PEM, which complicates things because when doctors see me they think I'm another chronic pain patient. I asked a rheumatologist I was seeing but...

I had a thought, are we going to attribute pain in cfs due to fibromyalgia or pain in cfs due to cfs? And, if we attribute to fibromyalgia does that mean cfs experiences fatigue both from fibromyalgia and from cfs?

Do most CFS with pain find it beneficial in the same way fibromyalgia patients do? Ie at least does it help as a pain killer?

About narcan vs naltrexone I had the same thought, wondering what the difference was. There are 3 opioid receptors, mu kappa beta or something like that, narcan binds strongly to all 3 I was told, while naltrexone strongly binds 2 weakly binds the third The metabolism study u link states :By...

Naltrexone IC50 for LPS NO at 2microM Naltrexone IC50 for LPS NO at 100microM Why the huge discrpency? They used different cell lines? https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-9-32 https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.13394 Tak242 IC50 FOR X...

Just had another thought, although naltrexone has tlr 7,8,9 antagonism, these are located within the cell, and therefore ligand must be able to cross... Cell membrane...? So unless your ligand is a virus... Hmmm. No nvm, rna DAMPS can cross cell membrane so naltrexone could still be working via...

Ah damn I've misunderstood LDN for a long time, I saw that it inhibited tlr4, so I thought it was a competitive antagonist. No it's non competitive and therefore changing the amount of tlr4 agonist won't change the inhibition. So high doses of naltrexone will only help little bc saturation but...

I'm starting to doubt the TLR4 hypothesis Dr Younger has, since LDN is only a LPS tlr4 antagonist at the md2 site, there are other ways to bind tlr4 without md2. So how would naltrexone be of help there. Unless there are DAMPS that need md2 as well. But naltrexone has other tlr antagonisms so...

Does anybody understand how Naltrexone inhibits TLR4? If I get this right, naltrexone competitively binds for md2, a protein needed by lps to dimerise whatever that means, but naltrexone only inhibits in a biased fashion, the trif pathway. The other pathway is the myd88 pathway. So naltrexone...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634939/ 75x more powerful than dextro naltrexone tlr4 antagonist, based on naltrexone Why would naltrexone reduce cell viability? Why would it be cytotoxic? polymyxin b tlr4. Another tlr4 antagonist

When they LDN has properties different to Naltrexone, due to dosage, do they mean chemical/biological properties or do they mean different drug effects? Eg dextro-naltrexone only seems to have TLR4, 7,8,9? activity and maybe NOX? activity, does that mean at a higher dose it doesn't? And instead...

We need a foundation like this. https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.alzdiscovery.org/uploads/cognitive_vitality_media/TLR4_Inhibitors.pdf&ved=2ahUKEwiT272vlvb9AhXl4TgGHdUhCTMQFnoECCcQAQ&usg=AOvVaw2z-WT9GLfZ01LIuttzZpHj Alz drug discovery. Though we're still looking...

Merged thread Naltrexone TLR9 Antagonist? https://www.frontiersin.org/articles/10.3389/fimmu.2017.00809/full This paper says naltrexone has tlr9 antagonism but not tlr4... Contradiction so I haven't seen this paper mentioned anywhere in regards to ldn, so ig it was wrong? Or... 'we...

Hmmm on this note, researchers were trialling tlr4 antagonists for sepsis. They failed though bc there were other pathways

Merged thread TBI Jeff Wood wrote something on health rising about maybe CFS being a mini tbi with exertion. Is this possible at a cellular level? Could neurons firing act like a mini tbi? Activating glia? I thought his idea was novel but he didn't provide any explanation as to what it might...

https://www.takeda.com/what-we-do/access-to-medicines/pre-approval-access Either can get through this, or buy from dodgy research only supplier. Hmm Woah hold on there are a lot of tlr4 antagonists. Amitriptyline and thalidomide apparently are tlr4 inhibitors! Oh my god there are a lot of tlr4...

Merged thread TAK242, resatorvid, a tlr4 antagonist Is a non competitive tlr4 antagonist. LDN slows my pem down by a factor of 10, if its working via tlr4 inhibition I assume its because agonist conc is still going up. But tak242 is no competitive, meaning even if agonist goes up blocking...