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Why gains slow!

Fibrosis-The Problem

Below is a study that illustrates some major points. Priapism causes fibrosis. Our Uli type exercises mimic priapism. The types of exercises we are doing a causing a buildup of fibrin. Fibrin deposition follows microvascular injury, the types of injuries we give ourselves while we squeeze our penis to the point where we see red dots, or perhaps even before that. As in Peyronies, which is caused by trauma of excessive bending of your erect penis, we are causing microtears with our exercises. These tears stimulate an immune response in which TGF-beta is recruited. At this point, lots of changes take place including the formation of dense collagenous connective tissues with fragmented elastic fibers. These fibers are quite strong and unless you employ the most herculean of forces after they have developed, YOU WILL CONTINUE TO GAIN NOTHING!!!!!! Forget about newbie gains until this crap is cleared from your penis. In the next post I will tell you how to do so.

Take a look at how they induced Priapism. They used a vacuum to inflate the penis and then the clamped it off with a rubber band. Is this sounding familiar yet? Guys, we need to hit the literature.

Int J Impot Res. 2004 Jul 29 [Epub ahead of print] Related Articles, Links


TGF-beta(1) neutralizing antibodies decrease the fibrotic effects of ischemic priapism.

Sanli O, Armagan A, Kandirali E, Ozerman B, Ahmedov I, Solakoglu S, Nurten A, Tunc M, Uysal V, Kadioglu A.

1Istanbul Faculty of Medicine, University of Istanbul, Istanbul, Turkey.

The objective of this study was to evaluate the possible role of transforming growth factor beta 1 (TGF-beta(1)) antibodies (ab) for the prevention of fibrotic effects of priapism in a rat model. In total, 30 adult Sprague-Dawley rats were divided into five groups. Priapism with 6 h (group 1), priapism with 6 h+ab (group 2), priapism with 24 h (group 3), priapism with 24 h+ab (group 4) and control (group 5). Priapism was induced with a vacuum erection device and a rubber band was placed at the base of the erect penis. At 1 h after the initiation of priapism, TGF-beta1 antibodies were given intracavernosaly. All rats underwent electrical stimulation of the cavernous nerve after 8 weeks. Intracavernous and systemic blood pressures were measured during the procedure. Rats in group 1 showed significantly higher (intracavernosal pressure (ICP) pressures to cavernous nerve stimulation and had higher ICP/BP ratios when compared to other groups. Similarly, histopathologic examination revealed less fibrosis in group 2, compared with the other groups. Consequently, TGF-beta1 antibodies antagonise the fibrotic effects of TGF-beta1, especially in cases with duration of priapism less than 6 h.International Journal of Impotence Research advance online publication, 29 July 2004; doi:10.1038/sj.ijir.3901261

PMID: 15284835 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/…t_uids=15284835

Inormation in this post has also been obtained at:
http://www.ncbi.nlm.nih.gov/entrez/…t_uids=12629334

Fibrosis-A Solution

In the following article they review Peyronie’s disease. Although we are not causing Peyronie’s with our exercises, the tissue changes in this disease are similar to those in Priapism at the site of fibrous build up(see the post preceding this one in this thread).

They list effective treatments. I will list a few that are accessible to us.

Acetyl L-carnitine
1 gram twice daily. No side effects were recorded in the study and plaques size was reduced.

Vitamin E
200-300 Mg. daily. Again, no side effects and plaque sizes was reduced.

There are other treatments as well but they are more dangerous and I will not list them for that reason.

So there it is folks, a simple and safe way to potentially restart those newbie gains.

All the information is here:

J Urol. 2003 Apr;169(4):1234-41. Related Articles, Links


Peyronie’s disease: a review.

Gholami SS, Gonzalez-Cadavid NF, Lin CS, Rajfer J, Lue TF.

Knupps Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, 94143, USA.

PURPOSE: We provide a current review of Peyronie’s disease. MATERIALS AND METHODS: We reviewed the world peer reviewed literature on the pathology, pathogenesis, diagnosis and treatment of Peyronie’s disease. RESULTS: The incidence of Peyronie’s disease has continuously increased during the last 30 years. However, fewer patients need prosthesis surgery as the sole treatment option because of earlier diagnosis, improved medical therapy, refinement in surgical technique and better understanding of the basic sciences of the disease. CONCLUSIONS: Currently patients with Peyronie’s disease have had improvements in prognosis and experienced an expansion of the available therapeutic options.

Publication Types:
Review
Review Literature

PMID: 12629334 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/…t_uids=12629334

Maybe I don’t understand completely, but I think you’re saying that Ulis and clamping cause priapism and if we get priapism we will not gain. Naturally this makes me wonder, how is it that many people who do Ulis and clampwork have gained so well? And, if you believe that clamping and Ulis are not the answer to gaining (I guess we are mainly talking girth here), what do you suggest we use to gain?

I don’t think he’s saying that by clamping and doing Uli’s you will not gain. I think he’s saying that by doing them, as well as gains you will be setting an environment that could slow future gains.

I believe this is an inevitable consequence of PE (at this time), and that we should be looking for ways to prevent pro stasis adaptations whilst doing these exercises in order to see a more linear growth curve, rather than the current diminishing returns.

Thanks Shiver, that is what I meant.

Also, thanks for this great thread on the same subject:

For Science minded PE’ers

For those who want the origional Acetyl-L-carnitine study:

1: BJU Int. 2001 Jul;88(1):63-7. Related Articles, Links


Acetyl-L-carnitine vs tamoxifen in the oral therapy of Peyronie’s disease: a preliminary report.

Biagiotti G, Cavallini G.

Andros-Italia, Perugia, Italy.

OBJECTIVE: To detect whether oral acetyl-L-carnitine might be useful in the acute and early chronic phases of Peyronie’s disease, compared with tamoxifen, a drug currently in use. PATIENTS AND METHODS: The study included 48 patients with Peyronie’s disease (15 acute and 33 initial chronic), randomized equally into two groups. The first group used tamoxifen 20 mg twice daily for 3 months and the second acetyl-L-carnitine 1 g twice daily for 3 months. The disease and stages were diagnosed and identified using a history, objective examination, pharmacologically induced erection, autophotography during erection, and basic and dynamic colour Doppler ultrasonography. Penile curvature, plaque size, pain and disease progression were assessed. The differences between the groups or between the variables before and after therapy were compared using analysis of variance or the chi-squared test. RESULTS: Acetyl-L-carnitine was significantly more effective than tamoxifen in reducing pain and in inhibiting disease progression. Acetyl-L-carnitine reduced penile curvature significantly, while tamoxifen did not; both drugs significantly reduced plaque size. Tamoxifen induced significantly more side-effects than acetyl-L-carnitine. CONCLUSIONS: These results suggest that acetyl-L-carnitine is significantly more effective and safe than tamoxifen in the therapy of acute and early chronic Peyronie’s disease.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11446848 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/…t_uids=11446848

The fibrosis angle is certainly interesting and should be pursued further. But isn’t it a bit of a leap to equate any possibly PE-induced fibrotic changes to alterations caused by Peyronie’s disease? And then from there assume treatments for Peyronie’s may reduce any fibrosis caused by PE?

I realize everyone here is brainstorming and speculating, which is great and can eventually lead to new discoveries. However, as I read this I can’t help but notice some assumptions and associations are being made that don’t necessarily follow.

I only mention this because I foresee a stampede of newbies racing to stock up on L-Carnitine to prevent their gains from stalling.

This ends the PSA. Now back to the regularly scheduled discussion…

I haven’t studied Peyronies very much, but my undertanding is that it is a calcification of part of the penis. If this is the case, then I can’t help but wonder what you would find underneath if you could remove that calcium. Could it be a tunical breach? If it is (and that’s a *huge* assumtion on my part), then it may be very relevant indeed.

I’ll stick that on the long list of things to explore some day soon, but I think we need more pseudo-scientist researchers (who’s going to front the group to ask for more funding? :) )

The problem is that I read a lot of studies in their entirety but can only post the abstracts. Everything I have said this week are substantiated by the three references I listed this week, the Peyronie’s disease reference in particular.

They state that trauma is believed to be the initiating factor in Peyronies’s. This trauma is thought to result in bleeding into the subtunical spaces. Fibrin deposition is one of the initial consequences of microvascular injury. Fibrin deposition is known to form in Peyronie’s plaques not in normal or scarred tunica. “Plaques consist of dense collagenous connective tissue with reduced and fragmented elastic fibers.” Calcification is present but only in 30% of patients.

TGF-beta expression is detected in 86% of Peyronie’s cases.

“Intra-tunical injection of TGF-Beta1 or its analog, cytomedulin, produced histological alterations such as chronic cellular infiltration, focal and diffuse elastosis, thickening, disorganization and clumping of the collagen bundles.”

It is all here in this study, I really wish I could post the whole thing. I just changed the wording a little. There is so much more in there as well, but I can’t spend all night paraphrasing it.

Now re-read this abstract:

The objective of this study was to evaluate the possible role of transforming growth factor beta 1 (TGF-beta(1)) antibodies (ab) for the prevention of fibrotic effects of priapism in a rat model. In total, 30 adult Sprague-Dawley rats were divided into five groups. Priapism with 6 h (group 1), priapism with 6 h+ab (group 2), priapism with 24 h (group 3), priapism with 24 h+ab (group 4) and control (group 5). Priapism was induced with a vacuum erection device and a rubber band was placed at the base of the erect penis. At 1 h after the initiation of priapism, TGF-beta1 antibodies were given intracavernosaly. All rats underwent electrical stimulation of the cavernous nerve after 8 weeks. Intracavernous and systemic blood pressures were measured during the procedure. Rats in group 1 showed significantly higher (intracavernosal pressure (ICP) pressures to cavernous nerve stimulation and had higher ICP/BP ratios when compared to other groups. Similarly, histopathologic examination revealed less fibrosis in group 2, compared with the other groups. Consequently, TGF-beta1 antibodies antagonise the fibrotic effects of TGF-beta1, especially in cases with duration of priapism less than 6 h.International Journal of Impotence Research advance online publication, 29 July 2004; doi:10.1038/sj.ijir.3901261

PMID: 15284835 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/…t_uids=15284835

We are dealing with TGF-beta1 and fibrosis with both Priapism and Peyronie’s. The link is there, it is microvascular injury and the resulting fibrosis and collagen buid up via TGF-beta1. Again, notice how they induced Priapism.

“Priapism was induced with a vacuum erection device and a rubber band was placed at the base of the erect penis. At 1 h after the initiation of priapism, TGF-beta1 antibodies were given intracavernosaly.”

This results in TGF-beta1 production in this study! We are doing simular things to our penis and are likely getting simular results, TGF-beta1 production. We know what TGF-beta1 does, it results in fibrosis and extensive collegen build up. In the treatment of Peyronie’s with Vit E or Acetyl-L-Carnitine results in the reducion of the build up of these “Plaques (which) consist of dense collagenous connective tissue with reduced and fragmented elastic fibers.”

Any questions?

Penismith,

Is there any mention in the literature of how long it takes once a state of priapism is reached for the TGF-beta1 production to begin?

What I am trying to get at, is that would it be beneficial to cut down the time for each set of clamping/uli’s but include more sets to try and get around the TGF production?

I have found personally (and I doubt it has anything to do with what we are talking about here as I have yet to pleateau on my current routine) that I get better results from extreme Uli’s if I do 4 five minute sets rather than 2, 10 minute sets.

It may be possible that breaking the sets up could help extend the “training time” before fibrosis halts our progress if it in fact does limit TGF production and it could well explain why some people gain so well on so little (like myself), because the short routines negate the TGF production. Thoughts on this?

Originally Posted by penismith
Acetyl L-carnitine
1 gram twice daily. No side effects were recorded in the study and plaques size was reduced.

Vitamin E
200-300 Mg. daily. Again, no side effects and plaque sizes was reduced.

I’ve taken vitamin E occasionally, but am currently out. I’ve taken Acetyl L- carnitine, but it’s been quite a while back. Both of these supplements are healthy to take for other reasons anyway, and just in case they could aid in PE, I’m going tomorrow and pick both up and take regularly.


Last edited by beenthere : 09-18-2004 at .

L-Arginine/nitric oxide to fight fibrosis

Guys,
I found this while trying to find some free papers for you to read:

http://www.biolreprod.org/cgi/rapid…04.030833v1.pdf

Read this carefully and you will better understand the connection I ab making between Peyronie’s, fibrosis and vascular injury.

It also looks like nitric oxide and L-Arginine might also be benificial.

“Peyronie’s disease (PD) is a localized fibrosis of the tunica albuginea (TA) of the penis
affecting about 2-4% of the male population (1). This fibrosis is assumed to be triggered by
trauma to the erect penis (2,3), followed by vascular damage, fibrin extravasation, recruitment of
inflammatory cells, and release of pro-fibrotic factors like transforming growth factor (TGF-β1)
and other cytokines, as well as reactive oxygen species (ROS), leading to cellular infiltration,
proliferation and differentiation. These processes cause chronic inflammation, excessive
collagen deposition and disorganization, and elastin fragmentation. This can be recognized
clinically as a palpable plaque and/or penile curvature during tumescence (2-4). Although
spontaneous regression of the plaque and the resulting curvature may occur in about 15% of
these cases (1), and some reports suggest that the injection of certain agents like verapamil
may improve the clinical condition, the majority of cases of PD seem to be refractory to
pharmacological therapy.
The recent description of a new rat animal model for PD whereby the injection of fibrin
into the TA produces a lesion indistinguishable histologically from the human condition allows us
to test pharmacological regimens in an attempt to cure or diminish the fibrosis. One approach
was based on the recently recognized antifibrotic effect of nitric oxide (NO), that reduces
collagen deposition and inhibits fibroblast differentiation into myofibroblasts, cells whose
persistence in abnormal wound healing may lead to fibrosis (5). NO was also a potent quencher
of ROS, one of the presumed agents in PD that induce fibrosis. Furthermore, when iNOS
activity was inhibited in a rat model of PD, tissue fibrosis is exacerbated and leads to an
increase in oxidative stress, whereas administration of the NOS substrate L-arginine and certain
phosphodiesterase (PDE) inhibitors exerts an antifibrotic effect (6-8).”

Via Pubmed in case the link dies:

http://www.ncbi.nlm.nih.gov/entrez/…t_uids=15240426

Andrew,
I think you are a lot better off with the shorter sets.

That is a fantastic find! It’s “cialis to go” for me. There is mounting evidence to suggest that short sets (if total duration is same) with plenty of fresh blood/massage inbetween would be more productive (and also much healthier).

Thanks guys.
I found, by accident (nearly got busted three days in a row by my kids while doing extreme Uli’s!), that I had a far better response to the exercises if I kept the total time the same, but made it up with more shorter sets.

I guess it shows that the guys who do these PE marathons each day are setting themselves up for heartache.Less really is more.

Great, great work Penismith and Shiver!!

Thanks for a great read! I really appreciate your efforts!

PS Now it’s time to stop thinking and use some energy on some jelqs ;-)

Just another quick thought - topical verapamil might be a good addition to maintain healthy tissues and keep growth potential. It’s currently off label prescription only though, with a couple of contraindications.

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