Also found a place that does procaine i.v.
aeskulap-klinik.ch/index.php?option=com_content&view=article&id=392&Itemid=433&lang=en
What they give it for is nonsense but they at least do it.
You still think this will work even though Awor didnât have success? I know this is different, but I injected about 6 ccâs daily per Shippen with no results either. I still have a ton of procaine sittin in my fridge. I think your reasoning is sound with what we know at this time. Obviously this is all a shot in the dark until we can get the interest of a research lab.
I.V. procaine is the only procaine option that could work. Injecting will do nothing due to its half life apart from give a placebo effect.
Now awor had success at first especially mentally. Over time it did wear off but maybe also with repeated treatments the effect will become more pronounced. Also it takes about 72 hrs before demethylation takes place. Awor had a shorter treatment. So short treatments will only start the process. Also remethlyation is a problem which it is possible is what awor experienced.
You need to hit it hard to get results. Having said that the degree of silencing is likely to vary in all of us so different people will need different depths of treatment. So its worth a shot.
Even if there is only a minor improvement it will show promise!
Another member here is having methylation testing done. That should tell us something. I think his results are due back in a few weeks. Would love to see a sample of 20 or so of us have testing done.
where is Awor? I hope he would come out with some happy news.
Does anyone else find it worrisome regarding how long heâs been away (Awor, I mean)? I hope he is OK.
Aworâs last login was March 24th, At least we know he didnât jump off a bridge or anything. Iâve been wondering how heâs been doing too. Kinda disappointing that he hasnât had much to say recently, most of his posts are very interesting/relevant.
Good luck with whatever youâre doing awor.
Ditto.
Where did he have the methylation testing done? What did it cost? I think many of us would like to have this done but we donât know how.
Ask Frustrated. Seems to be through Dr Jacobs.
Said those labs will take a few months. Hopefully will hear something soon. Technically I think his father ordered the lab as either a result of his own research or per discussions w/Jacobs or both. Anyway, those of us who are patients of Jacobs I would think the results will play a big role in future treatment options.
Just to clarify, a family friend offered to run some methylation tests after she briefly learned about my condition. The doctor has been extremely busy and the tests are complex so it is going to take a while to get results. There is a chance that the tests are never executed so I probably shouldnât have mentioned this so early on. To my knowledge, this type of assessment is not currently available commercially. Iâll try to keep pressure on the situation, but I donât really have much control over the situation. Iâve been instructed to keep my expectations low for these tests and I apologize if I prematurely got you guys excited.
The doctor currently has my blood sample that may be used to test for methylation. It might make more sense to draw a tissue biopsy to check the androgen reception in the related organs.
Recent article discussing finasteride inducing hypersensitivity of the androgen receptor during treatment.
Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: Implications for chemoprevention of prostate cancer
RESULTS
Immunohistochemical study revealed significant upregulation of ARs by finasteride treatment for 30â180 days. In cell line study, quantitative real-time reverse transcription polymerase chain reaction revealed significant upregulation of ARs treated by finasteride.
Very interesting and very relevant. Good find mariobros. Hope all is well with you.
Frustrated, i think you should really push for these tests to be done, this could be the key to finding out what is actually going on inside us.
Tell your friend how important this could be for thousands of men out there, and how many lives they may help if this testing reveals something.
Yes this test is very important. Please if you can try and persuade them.
endo.endojournals.org/cgi/content/abstract/137/4/1385
Testosterone up-regulates androgen receptors and decreases differentiation of porcine myogenic satellite cells in vitro
Accumulation of DNA is essential for muscle growth, yet mechanisms of androgen-induced DNA accretion in skeletal muscle are unclear. The purpose of this study was to determine whether androgen receptors (AR) are present in cultured skeletal muscle satellite cells and myotubes and examine the effects of testosterone on satellite cell proliferation and differentiation. Immunoblot analysis using polyclonal AR antibodies (PG-21) revealed an immunoreactive AR protein of approximately 107 kDa in porcine satellite cells and myotubes. Immunocytochemical AR staining was confined to the nuclei of satellite cells, myotubes, and muscle- derived fibroblasts. Administration of 10(-7) M testosterone to satellite cells, myotubes, and muscle-derived fibroblasts increased immunoreactive AR. In satellite cells and myotubes, AR increased incrementally after 6, 12, and 24 h of exposure to testosterone. Testosterone (10(-10) - 10(-6) M), alone or in combination with insulin- like growth factor I, basic fibroblast growth factor, or platelet- derived growth factor-BB, had no effect (P > 0.01) on porcine satellite cell proliferation, and testosterone pretreatment for 24 h did not alter the subsequent responsiveness of cells to these growth factors. Satellite cell differentiation was depressed (20-30%) on days 2-4 of treatment with 10(-7) M testosterone. This effect was not reversible within 48 h after treatment withdrawal and replacement with control medium. These data indicate that satellite cells are direct targets for androgen action, and testosterone administration increases immunoreactive AR protein
and reduces differentiation of porcine satellite cells in vitro.
onlinelibrary.wiley.com/doi/10.1111/j.1365-2605.1992.tb01125.x/abstract
Effect of testosterone deprivation on expression of the androgen receptor in rat prostate, epididymis and testis
Adult rats were treated with ethane dimethane sulphonate (EDS) to eliminate the Leydig cells. This treatment resulted in very low levels of testosterone in the blood and in the testis. Furthermore, histological evaluation of spermatogenesis showed no marked differences between control and EDS-treated animals.
In the ventral prostate, 5 days after EDS-treatment, a 4.0 ± 0.3âfold up-regulation of androgen receptor (AR) mRNA was observed, together with a 2.2 ± 0.2âfold increase in actin mRNA. In the epididymis, a 2.0 ± 0.5âfold increase in AR mRNA level was observed, without a change in actin mRNA level. In the testes of EDS-treated rats, the AR mRNA level was not changed (1.02 ± 0.17âfold of controls), and there was also no change in actin mRNA level at 5 days after EDS-treatment. These results indicate that AR mRNA expression in the ventral prostate and epididymis is regulated differentially by testosterone when compared to regulation in the testis.
Testicular androgen binding sites were assayed by Scatchard analysis of the binding of 3H-R1881 to a nuclear fraction, that was isolated by a method which involved the use of liquid nitrogen and high sucrose buffer. The number of specific binding sites per testis in EDS-treated rats with testosterone-implants, remained unaltered compared to control rats (9.1 ± 1.4 pmol/testis). In these rats, 20% of the normal testicular testosterone level was sufficient to maintain the androgen receptor in a tight nuclear binding (transformed) form. In testes from EDS-treated rats without testosterone-implants, the AR did not fractionate into the nuclear fraction; however, the total testicular AR content in these animals was close to control levels, as measured by nuclear 3H-R1881 binding after receptor transformation through injection of a high dose of testosterone (10 mg) 2 h before killing the rats (testosterone pulse). In the different experimental groups, FSH was not required to maintain the total testicular AR content (ligand binding).
toxsci.oxfordjournals.org/content/early/2011/03/21/toxsci.kfr063.abstract
Pharmacological doses of testosterone up-regulated androgen receptor (AR) and 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase (3ÎČHSD) and impaired Leydig cells steroidogenesis in adult rat
Anabolic androgenic steroids (AAS) are testosterone derivatives originally designed to enhance muscular mass and used for the treatment of many clinical conditions as well as in contraception. Despite popular interest and abuse, we still lack a broad understanding of effects of AAS on synthesis of steroid hormones on the molecular level. This study was designed to systematically analyze the effects of pharmacological/high doses of testosterone on steroidogenic machinery in Leydig cells. Two different experimental approaches were used: (1) In vivo experiment on groups of adult male rats treated with testosterone for one day, two weeks, and two months; (2) Direct in vitro testosterone treatment of Leydig cells isolated from intact rats. Result showed that prolonged in vivo treatment with testosterone decreased the expression of Scarb1 (Scavenger receptor class B type 1), Tspo (Translocator protein), Star (Steroidogenic Acute Regulatory protein), Cyp11a1 (Cholesterol side-chain cleavage enzyme); Cyp17a1 (17α-hydroxylase/17, 20 lyase) in Leydig cells. Oppositely, the expression of Hsd3b (3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase), Ar (androgen receptor) and Pde4a/b (cAMP-dependent phosphodiesterases) was increased. Androgenization for two weeks inhibited Cyp19 (aromatase) transcription, while two months exposure caused opposite effect. Direct in vitro testosterone treatment also decreased the expression of Cyp11a1, Cyp17a1 and Cyp19a1, while Hsd3b was up-regulated. The results of expression analysis were supported by declined steroidogenic capacity and activity of Leydig cells, while conversion of pregnenolone to progesterone was stimulated. The up-regulation of AR and 3ÎČHSD in testosterone-impaired Leydig cells steroidogenesis could be the possible mechanism that maintain and prevent loss of steroidogenic function.
If the problem was downregulation of androgen expression increasing testosterone would help in all of us.
The problem must therefore lie after testosterone binds to the androgen receptor - aka the AR signal.
To everyone having green tea - STOP!!! - its actually bad for us.
Yes it is can change DNA methylation but not in a way beneficial to us. In fact it helps more with estrogen silencing:
ncbi.nlm.nih.gov/pmc/articles/PMC2967543/
ncbi.nlm.nih.gov/pubmed/21177307
Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer.
Androgen deprivation therapy is the major treatment for advanced prostate cancer (PCa). However, it is a temporary remission, and the patients almost inevitably develop hormone refractory prostate cancer (HRPC). HRPC is almost incurable, although most HRPC cells still express androgen receptor (AR) and depend on the AR for growth, making AR a prime drug target. Here, we provide evidence that epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, is a direct antagonist of androgen action. In silico modeling and FRET-based competition assay showed that EGCG physically interacts with the ligand-binding domain of AR by replacing a high-affinity labeled ligand (IC(50) 0.4 ÎŒM). The functional consequence of this interaction was a decrease in AR-mediated transcriptional activation, which was due to EGCG mediated inhibition of interdomain N-C termini interaction of AR. Treatment with EGCG also repressed the transcriptional activation by a hotspot mutant AR (T877A) expressed ectopically as well as the endogenous AR mutant. As the physiological consequence of AR antagonism, EGCG repressed R1881-induced PCa cell growth. In a xenograft model, EGCG was found to inhibit AR nuclear translocation and protein expression. We also observed a significant down-regulation of androgen-regulated miRNA-21 and up-regulation of a tumor suppressor, miRNA-330, in tumors of mice treated with EGCG. Taken together, we provide evidence that EGCG functionally antagonizes androgen action at multiple levels, resulting in inhibition of PCa growth.-Siddiqui, I. A., Asim, M., Hafeez, B. B., Adhami, V. M., Tarapore, R. S., Mukhtar, H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer.
nature.com/onc/journal/v19/n15/full/1203511a.html
Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells
Androgens via their cognate receptor may be involved in the development and progression of prostate cancer. The aim of this study was to determine whether tea polyphenols have inhibitory effects on androgen action in an androgen-responsive, prostate cancer cell line, LNCaP. The tea polyphenol, EGCG, inhibited LNCaP cell growth and the expression of androgen regulated PSA and hK2 genes. Moreover, EGCG had a significant inhibitory effect on the androgenic inducibility of the PSA promoter. Immunoblotting detected a decrease in androgen receptor protein with treatments of the tea polyphenols EGCG, GCG and theaflavins. Northern blot analysis showed decreased levels of androgen receptor mRNA by EGCG. Transient transfections demonstrated that EGCG and theaflavins could repress the transcriptional activities of the androgen receptor promoter region. An Sp1 binding site in the androgen receptor gene promoter is an important regulatory component for its expression. This study suggests Sp1 is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Sp1 protein. In conclusion, we have described a new property of tea polyphenols that inhibits androgen action by repressing the transcription of the androgen receptor
So STOP green tea - if you are hoping to nudge the silencing off into the right direction green tea is interfering with any recovery.
Based on these studies I donât think you can say Green Tea is bad for us. Here are some things that theanine, an amino acid in green tea does that are beneficial:
en.wikipedia.org/wiki/Theanine
This article also claims that green tea increases dht and testosterone, at least in mice
Interesting point.
In the prostate, testosterone is rapidly and irreversibly converted to a more biologically active metabolite, DHT, by catalysis of 5α-reductase. EGCG has been shown to inhibit the growth of prostate cancer cells in vitro (36 ) and in vivo (37 ) through mechanisms that might involve inhibition of type I 5α-reductase (37 ). In this study, black tea reduced serum levels of DHT (Fig. 2 D), suggesting that black tea may have bioactive components that inhibit the conversion of testosterone to DHT, presumably via inhibition of 5α-reductase in this SCID-LNCaP animal model. It is unclear whether black tea theaflavins, EGCG and/or other components are responsible for this function in vivo.
On the other hand, green tea did not reduce the serum level of DHT, but instead tended to increase it (P = 0.076) (Fig. 2 D), and we found that green tea treatment did not inhibit tumor growth (Fig. 1 A). Green tea contained more EGCG than black tea (Table 1) , and studies have shown that EGCG inhibits the activity of 5α-reductase (38 ). These results derived from our animal model suggest that, although EGCG may be a potent antitumor agent in green tea and inhibit 5α-reducatase activity, green tea contains other constituents that may counteract EGCGâs antitumor activity, in part by counteracting its modulation of 5α-reducatase activity. Further research is required to identify these constituents and study their effects and/or their interactions with other components on prostate cancer. Our results demonstrate the importance of evaluating the benefit of whole tea products, rather than just isolated tea catechins or EGCG, on prostate cancer prevention because other tea constituents may play important roles.
The way i see it green tea and tea can interact with androgen action by repressing transcription of the androgen receptor. It can boost testosterone and DHT but since I believe the problem is not our hormonal levels but the the AR receptor and signal inhibiting this component will have worse effects than the benefits a slight increase in DHT can give.