"Menthol's [agonism of] the cold-sensitive Transient Receptor Potential cation channel subfamily M (melastatin) member 8 or TRPM8 receptors is responsible for the well-known cooling sensation it provokes.
Menthol's analgesic properties are mediated through a selective activation of κ-opioid receptors. Menthol blocks calcium channels and voltage-sensitive sodium channels, reducing neural activity that may stimulate muscles.
Some studies show that menthol acts as a GABAᴀ receptor positive allosteric modulator and increases GABAergic transmission in PAG neurons."
…and! Check this out:
"Menthol has anesthetic properties similar to though less potent than propofol, interacting with the same sites on the GABAᴀ receptor."
Propofol. PROPOFOL. The -ol in propofol is the -ol in menthol, haha.
"Menthol may also enhance the activity of glycine receptors and negatively modulate 5-HT3 receptors and nAChRs."
Aaaaand:
"Menthol also lowers blood pressure and antagonizes vasoconstriction through TRPM8 activation."
Peppermint is even more wild becasue while Menthol is a TRPM8 agonist (cold sensation), ECGC, also very high in peppermint, is a TRPV1 agonist (warm sensation), which has the opposite effect of TRPM8.
The EGCG is probably what is reducing the blood pressure.
Transient receptor potential vanilloid type 1 is vital for (−)-epigallocatechin-3-gallate mediated activation of endothelial nitric oxide synthase
Anything with EGCG in it causes me extreme bladder pain, even peppermint tea. While taking tons of Ricola cough drops (high in mentol) once when I had covid I found my bladder pain vanished. I then learned how the TRPV1 receptor is involved in my bladder pain.
Hard disagree on number 4. Open-ended questions that facilitate conversation are ideal. (They are an art form in themselves.) Since we're being analytical, you need a scaffold for the conversation, and questions are a better way to build it.
Maybe I’m misinterpreting "early on." I guess their point holds for the first 500 words or so.
Thank you. That is insightful and well written. And corresponds with academic literature as far as I have read.
I find it extremely interesting that GLP-1 agonists and GLP-1 receptors are highly pulmonary.
(There seems to be a persistent correlation between detailed pulmonary mechanisms, biology, responses… and neuroinflammation. Which does make sense when we consider the metabolic demands of the brain,
which can be highly localized and sensitive to fine variances in supporting system capacity.)
My from-the hip take – from the hip!, no judging pls; It's a hunch, working to falsify it – is that… everything that makes humans aggressive to someone. Every feature someone can present that increases the odds of aggression… is a heuristic for neuroinflammation.
It's a lot of things, but neuroinflammation is a pretty consistent good match as core heuristic.
As in: GLP-1 agonists do reduce neuroinflammation. And then the hunch: This generally and ubiquitously reduces the aggression-induced features thereof.
(This take is somewhere between riffing on concepts and a surprisingly earnest and mechanistic theoretical perspective. Started as jokey banter but it's kinda hard to unsee it. not sure where else to place it, haha.)
(I'm kidding when I say this, and it's also concretely true.)
Been working on realtime DSP and ad-hoc A/V integration and sync.
Audio DACs are a solved problem. Pristine D/A conversion is a ubiquitous low-cost commodity. It's fun to buy a bunch of cheap "chi-fi" DACs – quality is excellent – and ad-hoc merge them into one big audio interface and do per-channel DSP. Toss in some TPA3255 amplifiers. Bodge together a crossover and room correction monstrosity in Reaper or Logic. Run system audio through that. It's easy to get super arcane. My home stereo is frightening. The interesting part is thinking about how to get a human interface on top of it. How to get it to assemble and stay assembled and present human-comprehensible knobs – or not.
Also had an extended family health crisis. About 9 years non-stop of extremely unlikely convergences of life-threatening conditions. (My close family has dissolved due to trauma and stress. (It's okay.)) And I haven't been working a programming or computer-science job since 2020… but I have very serious and significant work experience in things that are… how to even put it. It's not immediately clear how to add the past few years to my resumé?
Did an invisible PhD in mitochondrial neuroimmunobiology at the School of Hard Knocks? Stint of off-piste biomedical engineering? Amateur placental biotechnologist? Independent researcher?, or just… faceplanted into some PDFs on Google Scholar and accidentally read some out-of-my-lane stuff and it turns out it's actionable. Results from molecular biology are actionable.
It is said that there's a 15 year gap before something reaches clinical practice. Between having in one hand some concrete scientific results. On how to treat something in the body. And on the other hand… to clinical practice. A 15 year gap.
What's that 15 year gap made out of?, and can we cross it earlier?
We can.
Trying to figure out how to get this into words, and what to do with it.
And then when I've got the realtime-DSP-ed-to-the-hilt home-computer workstation going, I'm going to work on Idris 2 because we need dependent types.
I'm sorry to hear about your family's health and relationship issues. I would be interested in hearing more about your audio projects. Your health research sounds like it could be very beneficial to society--please keep pushing forward there. Anything that can help reduce the cycle time on new research has to be valuable.
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