PROPECIAHELP: Persistent Finasteride Propecia Proscar side effects info & discussion forum

Forum for men with PERSISTENT sexual, mental & physical side effects which CONTINUE DESPITE QUITTING Finasteride (Propecia, Proscar), a 5AR inhibitor drug for hair loss, prostate enlargement & prostate cancer.
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PostPosted: Fri Jun 25, 2010 9:59 pm 
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For all those that can follow on the line of thought, that some form of silencing of the AR signal is at the root of our problem, there might be some hope. The main molecular mechanism behind persistent epigenetic changes in gene expression is DNA methylation. As methylation is also implied in cancer, much research attention is going into the question of reversing this process through demethylation via demethylating agents.

I would like to dedicate this thread to the subject of such demethylating agents. If anyone finds interesting information on the subject, please post it here.

A real “here and now” treatment option is Procaine (Novocaine):

http://cancerres.aacrjournals.org/conte ... /4984.full
http://en.wikipedia.org/wiki/Gerovital_H3

If anything promising has come along my way recently, this is it. I am going to try to get my doc to shoot me up with this stuff.


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PostPosted: Fri Jun 25, 2010 10:11 pm 
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Nice Awor! Worth a shot bro....We can't import this though right? There is a FDA ban I believe...


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PostPosted: Fri Jun 25, 2010 10:53 pm 
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What exactly does this have to do with the androgen receptor, specifically? Not asking this sarcastically...


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PostPosted: Fri Jun 25, 2010 10:58 pm 
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looks like you can buy injections from overseas...http://www.zalmo.com/4.html


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PostPosted: Sat Jun 26, 2010 3:12 am 
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Is the Procaine (Novocaine) the same as the dentist uses to numb your mouth? The link you provided states:

Quote:
As of 2004[update], the FDA's 1982 automatic detention alert is still in effect and bans the import of Gerovital H3 into the U.S. as "a new drug within the meaning of 201(p), without an approved new drug application [Unapproved New Drug, Section 505(a)]."[7]

Since Novocaine is not banned (I assume) what is the difference between Gerovital H3 and Novocaine? There are some other demethylating agents listed on wikipedia:

http://en.wikipedia.org/wiki/Demethylating_agent

Quote:
Cytidine analogs such as 5-azacytidine (azacitidine) and 5-azadeoxycytidine (decitabine) are the most commonly used demethylating agents .

This article claims that ECGC in green tea can be used as a demethylating agent for one specific gene (how do we find the right demethylating agent for the genes that fin has methylated?) I'm totally ignorant on this so excuse me if I'm rambling.
http://ar.iiarjournals.org/content/29/6/2025.full
Quote:
Conclusion: These results suggest the potential therapeutic use of EGCG for the reversal of WIF-1 promoter methylation.

This is a pretty decent article on demethyating agent and cancer:
http://anti-agingfirewalls.com/2009/11/ ... t-cancers/


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PostPosted: Sat Jun 26, 2010 9:45 am 
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How would this work in practice? Just simply shooting novocaine to reconnect with androgen response?

http://www.youtube.com/watch?v=V2yy141q8HQ

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PostPosted: Sat Jun 26, 2010 7:35 pm 
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Awor, the epigenetic changes argument is a very interesting one. I spent several days reading about it some months ago. It was interesting to take away a very different understanding of genetics and the way DNA operates over generations, as most of us grew up believing that these things were immutable, and they are not.

From what I remember, there were studies that showed the ineffectiveness of some of the more common "demethylating" treatments... but then again, I suppose most treatments have "studies" that contradict each other on effectiveness. If you find a treatment that doesn't appear to present a health risk for you, and you are willing to try it, I say go for it, and keep us posted. I find the topic fascinating.


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PostPosted: Tue Jun 29, 2010 11:03 pm 
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Turns out some of those trans fats may be good for you.
Quote:
We show here that CP-4200, an elaidic acid derivative of azacytidine, has strong epigenetic modulatory potency in human cancer cell lines, as evidenced by efficient depletion of DNA methyltransferase protein, genome-wide DNA demethylation, and robust reactivation of epigenetically silenced tumor suppressor genes.

http://mct.aacrjournals.org/content/9/5/1256.abstract
Quote:
Elaidic acid is the principal trans unsaturated fatty acid often found in partially hydrogenated vegetable oils

http://en.wikipedia.org/wiki/Trans_fat
Fry your dinner in some vegetable oil and have some green tea (EGCg) with it.


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PostPosted: Fri Jul 02, 2010 10:42 pm 
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golf17331 wrote:
What exactly does this have to do with the androgen receptor, specifically? Not asking this sarcastically...

This has to do with silencing of AR signal, which is the basis of the androgen insensitivity theory. It has been proposed by scientists that drug induced persistent side effects are due to epigenetic changes in gene expression levels, specifically by DNA methylation. Note that this paper specifically talks about isotretinoin (Accutane, also a 5ARI class drug) as causing such problems. I had contact with the author of this paper and he also suspects finasteride as causing such problems.

Hence the idea about reversing this with a demethylating agent. Fortunately for us, many cancer forms are associated with hypermethylation of certain DNA segments. As most research $$ go into cancer research these days, we can hope that therapy options coming out of there could be useful to us.

My thoughts on this: Perhaps the root-root cause of our problem is an overactive Methyltransferase enzyme, which goes about hypermethylating DNA more actively than it should. Proof of this would be an unusual high incidence of cancer cases with persons in our blood line (parents, brother, sister, grandparents, cousins). Does that fit anyone?

Following quote gives the link with AR silencing further credence:
Quote:
methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells. The demethylating agent 5-aza-2′ deoxycytidine induced a re-expression of AR RNA (http://www.ncbi.nlm.nih.gov/sites/pubmed/9850055).


5-aza-2 is a commercially available under the brand name Dacogen: http://www.cancer.gov/cancertopics/drug ... decitabine
http://en.wikipedia.org/wiki/Decitabine


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PostPosted: Fri Jul 02, 2010 11:12 pm 
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Thanks for the explination - are you attempting to find a doc to try a demethylating drug? I see it is iv admin only. Also, is there a way to test for hypermethylation? I very much admire the fact that you wrote the researcher btw, kudos.


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PostPosted: Sat Jul 03, 2010 7:07 am 
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golf17331 wrote:
Thanks for the explination - are you attempting to find a doc to try a demethylating drug? I see it is iv admin only. Also, is there a way to test for hypermethylation?
Yes, and I have already found a medical center near my home that offers this (IV) on the basis of Novocaine. Will investigate this for August, but want I to discuss this treatment option with another scientist first.

golf17331 wrote:
I very much admire the fact that you wrote the researcher btw, kudos.
Sure. You're new here I think, so let me tell you that there is a lot of effort going on behind the scenes to get science more involved. I am part of this effort. It is very long term and slow progressing work though, so there unfortunately is not something to report every month. Research also eventually requires patient groups to participate in studies. We're getting to a point where we will need to know who we can count on to participate in such studies. The amount of effort it took to get people to register for a simple telephone interview with Dr. Irwig was disconcerting. There is going to be an announcement about this soon.


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PostPosted: Sat Jul 03, 2010 9:07 am 
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My thoughts on this: Perhaps the root-root cause of our problem is an overactive Methyltransferase enzyme, which goes about hypermethylating DNA more actively than it should. Proof of this would be an unusual high incidence of cancer cases with persons in our blood line (parents, brother, sister, grandparents, cousins). Does that fit anyone?





No one in my family has had cancer. I was pretty healthy and probably destined for a long life before this crap, always tried to eat well and exercise reasonably well.


If novocaine did help how would it relieve symptoms?

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http://www.pfsfoundation.org/donate/


Last edited by Luckfax on Sat Jul 03, 2010 1:02 pm, edited 1 time in total.

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PostPosted: Sat Jul 03, 2010 11:45 am 
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Have you also considered methylation testing prior to the novicaine treatment? I saw a methylation pathways test is available for 300 online.

I have also seen through some googling that low histamine is a common factor on the overmethylated - perhaps it's worth testing


Last edited by golf on Sat Jul 03, 2010 6:00 pm, edited 2 times in total.

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PostPosted: Sat Jul 03, 2010 2:24 pm 
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Awor,

You can count on me to participate in any study. I will respond very quickly.

Thanks for all of your efforts, it's appreciated.


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PostPosted: Tue Jul 06, 2010 3:31 pm 
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.


Last edited by solonjk on Sun Jul 10, 2011 4:02 pm, edited 1 time in total.

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PostPosted: Tue Jul 06, 2010 3:48 pm 
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I think a lot of people attempted to participate in irwigs survey but were intelligible, like myself, due to strict restraints such as not being on any other pharmaceuticals. Im sure we will all participate in any promising treatment options in the future.


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PostPosted: Wed Jul 07, 2010 3:15 pm 
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Does anyone have access to the full paper here?

http://www.sciencedirect.com/science?_o ... ee88858cc6


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PostPosted: Thu Jul 08, 2010 12:38 am 
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Perhaps valproic acid, a commonly prescribed pharmaceutical for epilepsy, is another option for demethylation:

http://www.medscape.com/viewarticle/538458


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PostPosted: Thu Jul 08, 2010 3:45 pm 
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maybe folate levels should also be tested, it looks like that in excess folate has the potential to hypermethylate:

http://www.researchprofiles.collexis.co ... 8&o_id=55&


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PostPosted: Mon Jul 12, 2010 7:04 pm 
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It looks like valproate and 5-aza-2'-deoxycytidine both have an effect on reversing leukemia via demethylation as well. It includes some valuable information on effective use of a demethylation agent in re-expression of a gene (at least in the leukemia context) which, perhaps, may enhance the effectiveness of any treatments which we may try in the future.


Quote:
There are several limitations to our study. The first one is the choice of the HDAC inhibitor. A number of new HDAC inhibitors are currently being investigated.30 In vitro, VPA is the least effective HDAC inhibitor, and its clinical use at higher doses is limited by its toxicity profile. The combination of either decitabine or 5-azacytidine with other more effective and less toxic HDAC inhibitors may improve the results.30,31 Second, the optimal schedule of decitabine is currently being evaluated. Data from ongoing studies at our institution suggest that shorter schedules (20 mg/m2 by IV for 5 days)32 may be better. Third, maximal effect on gene reactivation has been observed when administering the hypomethylation agent followed by the HDAC inhibitor. In our in vitro model,18 the use of the sequence had no effect on cell kill, hence our choice of the schedule. That said, it is possible that a schedule using a sequence in which the hypomethylating agent is administered before the HDAC inhibitor may be more active clinically.


http://bloodjournal.hematologylibrary.o ... 08/10/3271


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