I think the role of nystatin in the study you quoted is to permeate the cells, like amphotericin B (very similar to nystatin) in these studies (i did a “amphotericin anandamide” search) ncbi.nlm.nih.gov/pmc/articles/PMC140203/ ncbi.nlm.nih.gov/pmc/articles/PMC1572286/
(I quote “In these experiments, amphotericin B was used to gain access to the cell”)
I’m still very interested by this normast “drug” since it seems to be useful in chronic abacterial prostatitis, which is what I seem to have (yeah, i still have prostatitis, confirmed by my symptoms and the DRE, the four glass meares-stamey test , and other capable radiologists via TRUS in a reputated health center in Paris. Can’t isolate a known pathogen from the prostatic fluid though, hence “abacterial”. Maybe I don’t have PFS, or don’t have it any more, or never had it…)
Maybe you guys are onto something here (I’m more convinced by this than any convoluted androgen insensitivity theory, but that’s because I respond very well to exogenous androgens)
My interpretation of the first two studies is they are talking about Physiological levels/normal circulating levels of progesterone.
So all you would have to do is add Nystatin.
EDIT: i see you were talking about the studies i posted
I dont understand how “simply adding nystatin” would be enough when the study you quted says
Is 10ug/ml progesterone equivalent to normal circulating levels?
normal serum progesterone level in males : less than 1 ng/mL (1ug=1000ng)
Also since oral nystatin is not absorbed systemically (and you dont want it to, its extremely toxic administered IV), it would only effect the lining of the intestines… Maybe that’s enough to affect the nearby prostate? Anyway that’s an angle that real scientists should investigate. I wish awor put his team on this instead of being obsessed with the androgen receptors. Good job anyway, tim. (although I still think deducing “Nystatin reduces AEA levels.” from the studies you quoted is fallacious, and biaised, reasoning)
Btw, have you received your normast? Wouldnt you consider using it in conjunction with nystatin?
OK but, really, I like how this theory seems to be able to explain all the symptoms, but I’m still not comfortable with phrases such as “Now if you add that to the above information about how Nystatin inhibits the metabolism Anandamide (AEA), (…)” , you’re really taking big jumps from small tiny hints and distorting the datas with this one… I understand how you want to make a “good” recovery fit in with you theory but… Well, I understand you anyway, we all tend to do this.
Let me share some of my own quick pseudo-scientific, most probably huge BS, ideas : you probably bought the sublingual normast… This formulation gets directly into the bloodstream, what if the best way would be to take it orally, or even as an enema, for it to reach the prostate region (an organ very poorly vascularized and which drugs difficultly can reach, but which fin is designed to affect specifically)? Nystatin gets all the way through the digestive system without ever getting into the bloodstream (or only an infinitesimal amount, in theory). Maybe that’s how it could somehow “permeate” the prostatic cells (from the end of the colon) to the AEA-inhibiting properties of a very small amount of progesterone (10 000 less than in your quoted study, but now Icant seem to beleive my own BS anymore). I didnt plan to write this sarcastically, but if it definitely sound like it, it’s probably that this simply is too complicated and unlikely to be what’s happening (who talked about Occam’s razor here?)
Anyway…
Do you plan to try a fast before/during normast administration?
Really? Well I do think that PFS can possibly be linked (indirectly, by a disturbance of the immune system) to a fungal infection.
I also think that your theory is interesting.
I dont know anything. NOBODY here does.
I will post here if I feel like it wether you like it or not.
I also think you writing this is absolutely ridiculous and you should feel ashamed of yourself if you think twice about it. This is not the way things will go any further and this kind of pathetically bitter/narrow-minded attitude is what brings this forum down.
[Size=4]Androgens rapidly increase the cytosolic calcium concentration in Sertoli cells.
Gorczynska E, Handelsman DJ.
[/size]
Department of Obstetrics and Gynecology, University of Sydney, New South Wales, Australia.
Abstract
We demonstrate that androgens rapidly and specifically increase intracellular calcium in Sertoli cells, investigate the mechanism, and suggest the unifying hypothesis that calcium might be a common intracellular molecular effector to explain the known synergism between FSH and testosterone (T) action on Sertoli cells in support of spermatogenesis. In freshly isolated Sertoli cells, T and its 5 alpha-reduced metabolite dihydrotestosterone increased intracellular calcium from 83 +/- 4 to 147 +/- 8 and 167 +/- 29 nM, respectively, whereas estradiol had minor (117 +/- 9 nM) and progesterone no (80 +/- 6 nM) effect. The effect of T was rapid (20-40 sec) and inhibited by 1) preincubation with either a pure nonsteroidal antiandrogen (hydroxyflutamide) or a 5 alpha-reductase inhibitor (finasteride) or 2) removal of extracellular calcium (47 +/- 4 nM) or pharmacological blockade of voltage-activated (62 +/- 5 nM) or voltage-independent (55 +/- 14 nM) membrane calcium channels. These findings suggest that the T-induced rise in Sertoli cell cytosolic calcium involves sequential 5 alpha-reduction, binding to a classical androgen receptor, and activation of transmembrane influx of extracellular calcium. Immobilization of T by conjugation to a large carrier molecule (BSA) to prevent steroid entry into Sertoli cells also resulted in a rapid increase in cytosolic calcium to a similar magnitude as unconjugated T, consistent with a plasma membrane site of action. This finding together with the rapid cytosolic calcium rise caused by T argues for the possible existence of a short term, nongenomic effects in hormonal regulation of Sertoli cell function in addition to the well known, slower genomic response.
So possibly when DHT returned it drove the anandamide level way to high, before Palmitoylethanolamide could recover off setting the balance of N-acylethanolamides.
And on the other hand while on finasteride, high T levels could have driven anadamide levels high while Palmitoylethanolamide was being partially inhibited causing a catastrophic unbalance there.
(PPAR-a) is a transcription factor and a major regulator of lipid metabolism in the liver. And it turns out that it is activated under nutrient-deficient conditions, such as fasting.
Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.
The types of lipids involved include:
Its a good idea tim. Thanks for your research. I think the people who show androgen responsiveness with a prostatitis/pelvic pain syndrome should be interested in this.
I look forward to see how you respond to normast.
Btw i passed my medical finals so until graduation i am unofficially a doctor.
Capsaicin, a component of red peppers, induces expression of androgen receptor via PI3K and MAPK pathways in prostate LNCaP cells.
Malagarie-Cazenave S, Olea-Herrero N, Vara D, Díaz-Laviada I.
Source
Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, Madrid, Spain. sophie.malagarie@uah.es
Abstract
In this study, capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) induced an increase in the cell viability of the androgen-responsive prostate cancer LNCaP cells, which was reversed by the use of the TRPV1 antagonists capsazepine, I-RTX and SB 366791. In further studies we observed that capsaicin induced a decrease in ceramide levels as well as Akt and Erk activation. To investigate the mechanism of capsaicin action we measured androgen (AR) receptor levels. Capsaicin induced an increase in the AR expression that was reverted by the three TRPV1 antagonists. AR silencing by the use of siRNA, as well as blocking the AR receptor with bicalutamide, inhibited the proliferative effect of capsaicin.
By partially inhibiting Palmitoylethanolamide (PEA) an enhancer of anandamides (AEA) effect on the TRPV1 as cited here,
Or could capsaicin also have the same effect as finasterride or saw?
“American Association for Cancer Research reports studies suggesting capsaicin is able to kill prostate cancer cells by causing them to undergo apoptosis.[44][45] The studies were performed on tumors formed by human prostate cancer cell cultures grown in mouse models, and showed tumors treated with capsaicin were about one-fifth the size of the untreated tumors”.
