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pey ron

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group buys for self-medication?
« on: March 24, 2019, 05:11:01 PM »

I am an engineer. We often are a weird bunch of crazy, curious and impatient people that do not take a 'NO' for an answer and have a bias for action. I personally am tired of waiting for something ground-breaking to be approved for our condition. I am under the impression that new antifibrotic treatments are gonna take over a decade in the best case, likely longer. And then it's only gonna be for other conditions. They'll only get to be prescribed off-label for Peyronies Disease much later, and only if some urologist is enlightened enough to be willing to experiment.

I see a number of like-minded people also happen to be engineers. I'm thinking of people like Cacogen and Whyisthishappening, for example. There may be more folks and hopefully with different backgrounds -- in medicine or biochemistry if we are lucky -- that can balance us out.

It would be awesome if we could band together to figure out what experimental drug we could try, that is promising and reasonably safe and risk-free. Or displaying a good compromise of benefits/risks. All skepticism is very welcome. We need it. So, if you don't feel like being a guinea pig yourself, feel free to share your concerns with us.

Then we could perhaps do a group buy and leverage the economy of scale. All while getting the drug tested at a reputable lab.

I am ready to contribute money, time and my "subject" to an experiment that has a high likelihood of success. If you don't feel the same, you can still contribute a lot by helping us research pros and cons, and then just wait for our experience and results if you prefer to stay on the sidelines and watch.

What do you guys all think?
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Whyisthishappening

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Re: group buys for self-medication?
« Reply #1 on: March 24, 2019, 06:03:53 PM »

great idea my friend ron ,you will have my support
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pey ron

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Re: group buys for self-medication?
« Reply #2 on: March 25, 2019, 10:54:43 PM »

who else is interested? I think the top and most promising candidates at the moment would be:

(1) Dasatinib
(2) FOXO4
(3) Vactosertib (TEW-7197)

Any other one?
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Whyisthishappening

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Re: group buys for self-medication?
« Reply #3 on: March 26, 2019, 07:13:20 AM »

also the korean studies with hdac are very promising i wish we could contact the scientists
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Jack1909

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Re: group buys for self-medication?
« Reply #4 on: March 26, 2019, 09:44:55 AM »

There are some antifibrotic drugs on their way out to the market..phase 2 or more advanced, I would start from them..

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pey ron

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Re: group buys for self-medication?
« Reply #5 on: March 26, 2019, 12:22:01 PM »

@Jack1909, @Whyisthishappening: please list the compounds!
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Whyisthishappening

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Re: group buys for self-medication?
« Reply #6 on: March 26, 2019, 06:16:22 PM »

Inhibition of histone deacetylase 2 mitigates profibrotic TGF-β1 responses in fibroblasts derived from Peyronie's plaque
Author information 2013
National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 400-711, Korea
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881653/
Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie's Plaque.2018
Author information
1National Research Center for Sexual Medicine, Inha University School of Medicine, Incheon, Korea.
2Department of Urology, Inha University School of Medicine, Incheon, Korea.
3Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, Korea. jksuh@inha.ac.kr.
4Department of Urology, Inha University School of Medicine, Incheon, Korea. rjk0929@inha.ac.kr.

https://www.ncbi.nlm.nih.gov/pubmed/29706035
 
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Whyisthishappening

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Re: group buys for self-medication?
« Reply #7 on: March 26, 2019, 06:18:04 PM »

also these guys do state of the art research
Simvastatin and the Rho-kinase inhibitor Y-27632 prevent myofibroblast transformation in Peyronie's disease-derived fibroblasts via inhibition of YAP/TAZ nuclear translocation.
Author information
1Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
2Department of Urology, University Hospitals Leuven, Leuven, Belgium.
3Faculty of Health, Education, Medicine and Social Care, Medical Technology Research Centre, Anglia Ruskin University, Chelmsford, UK.
4Faculty of Medicine and Surgery, University of Padua, Padua, Italy.
5Department of Pediatric Nephrology and Growth and Regeneration, University Hospitals Leuven and KU Leuven, Leuven, Belgium
https://www.ncbi.nlm.nih.gov/pubmed/30536599
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Whyisthishappening

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Re: group buys for self-medication?
« Reply #8 on: March 26, 2019, 06:21:53 PM »

but i believe another problem is that scientists want to find compounds for patents we want to know the mechanism of activation and shut it down but only nestor gonzalez cadavid is interested about that and researched it for a long time
 also coffee at least in theory in right doses and time in combination with fasting seems promising,but no clinical evidence for something like Peyronies Disease,i cannot understand how something so devastating  and  common 3% best estimates 9% worst and 22% of corpses with penile fibrosis,is not studied that much and does not get the  attention of big pharma
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pey ron

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Re: group buys for self-medication?
« Reply #9 on: March 26, 2019, 11:19:27 PM »

any links/references on coffee?
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Whyisthishappening

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Re: group buys for self-medication?
« Reply #10 on: March 27, 2019, 06:15:59 AM »


 whyisthishappening coffee thread
https://www.peyroniesforum.net/index.php/topic,11576.msg108610.html?PHPSESSID=u8ubohu3oa1vufj1clg2f8hv55#new
Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801884/
Impact of Alcohol and Coffee Intake on the Risk of Advanced Liver Fibrosis: A Longitudinal Analysis in HIV-HCV Coinfected Patients (ANRS https://www.ncbi.nlm.nih.gov/pubmed/29857547HEPAVIH CO-13 Cohort).
Food components with antifibrotic activity and implications in prevention of liver disease.
https://www.ncbi.nlm.nih.gov/pubmed/29268106
Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes.
https://www.ncbi.nlm.nih.gov/pubmed/29167102
Autophagy mediated by endoplasmic reticulum stress enhances the caffeine-induced apoptosis of hepatic stellate cells.
https://www.ncbi.nlm.nih.gov/pubmed/28949381
Molecular Bases Underlying the Hepatoprotective Effects of Coffee.
https://www.ncbi.nlm.nih.gov/pubmed/28124992
Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.
https://www.ncbi.nlm.nih.gov/pubmed/28075394
 
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Whyisthishappening

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Re: group buys for self-medication?
« Reply #11 on: March 27, 2019, 06:25:15 AM »

neov caffeine thread
https://www.peyroniesforum.net/index.php/topic,7300.0.html?PHPSESSID=u8ubohu3oa1vufj1clg2f8hv55
TGf-beta and fibrosis
2016- Caffeine inhibits TGFβ activation in epithelial cells, interrupts fibroblast responses to TGFβ, and reduces established fibrosis in ex vivo precision-cut lung slices -- Tatler et al. -- Thorax
2014 - Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β. - PubMed - NCBI
2008 - Pharmacological application of caffeine inhibits TGF-beta-stimulated connective tissue growth factor expression in hepatocytes via
2009 - Identification of paraxanthine as the most potent caffeine-derived inhibitor of connective tissue growth factor expression in liver
2009 - Less Smad2 is good for you! A scientific update on coffee's liver benefits - Gressner - 2009 - Hepatology - Wiley Online Library
2009 - About coffee, cappuccino and connective tissue growth factor-Or how to protect your liver!? - PubMed - NCBI
2008 - Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases. - PubMed - NCBI

Penis and erection
2012 - Caffeine relaxes smooth muscle through actin depolymerization. - PubMed - NCBI
2008 - Effect of caffeine on erectile function via up-regulating cavernous cyclic guanosine monophosphate in diabetic rats. - PubMed - NCBI
2004 - Effect of caffeine on response of rabbit isolated corpus cavernosum to high K+ solution, noradrenaline and transmural electrical

Inflammation in general
2013 - Effects of caffeine on the inflammatory response induced by a 15-km run competition. - PubMed - NCBI
2004 - Associations between coffee consumption and inflammatory markers in healthy persons: the ATTICA study | The American Journal of Clinical Nutrition | Oxford Academic
Caffeine inhibits TGFβ activation in epithelial cells, interrupts fibroblast responses to TGFβ, and reduces established fibrosis in ex vivo precision-cut lung slices -- Tatler et al. -- Thorax
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popopo

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Re: group buys for self-medication?
« Reply #12 on: March 28, 2019, 08:41:46 AM »

I would be interested in group buys and testing some drugs, but we would have to find out which compounds hel first.
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Date of onset: 17
Symptoms: sharp pains, numbness, change in shape/size, hourglassing and discolaration from jelqing/VED usage as a teen. Diagnosed with a venous leak and possible scarring.
Treatments tried: cialis, pentox and VED didnt help

Crooked_Stick

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Re: group buys for self-medication?
« Reply #13 on: March 28, 2019, 01:19:25 PM »

The problem I see with most of the above mentioned drugs is that they would only work in the active phase of the disease. Most of us are long past that with established fibrosis that is 'irreversible'. Like many I continue to watch current research and unfortunately there really isn't anything on the horizon that looks that promising. Mediwound's MWPC003 had me excited for awhile as they had started some research with an injectable that was shown to dissolve the plaque while not harming other tissue or blood vessels (unlike Xiaflex). They are years from even getting back to research with MWPC003 as they are trying to get two other products to market.

 https://www.mediwound.com/pipe-line/

A cancer immunotherapy drug being developed at Stanford was shown to reverse fibrosis but you would never be able to get your hands on that.

https://medicalxpress.com/news/2017-04-fibrosis-reversed-dont-blocked-stanford.html
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Re: group buys for self-medication?
« Reply #14 on: March 28, 2019, 07:36:34 PM »

I am unable to leave active phase for 3 years now. Count me in.
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Never out of Active phase, painful erections.

Werther

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Re: group buys for self-medication?
« Reply #15 on: March 30, 2019, 01:32:13 PM »

The problem I see with most of the above mentioned drugs is that they would only work in the active phase of the disease. Most of us are long past that with established fibrosis that is 'irreversible'.

I completely agree with this. The only things I saw that have been developed and marketed so far aim to target inflammation (i.e. the acute phase) but there's currently nothing for estabilished fibrosis. I'm thinking of H-100 for example, which is one of the latest drugs developed for peyronie's: it could be maybe helpful for people in the early stages of disease as stated by the manufacters themselves.

It looks like long-standing peyronie's sufferers with stable scars have no choice except for Xiaflex (if they're eligible) or surgery.

Quote
A cancer immunotherapy drug being developed at Stanford was shown to reverse fibrosis but you would never be able to get your hands on that.

https://medicalxpress.com/news/2017-04-fibrosis-reversed-dont-blocked-stanford.html

This is really interesting and I came to know about it on this forum (thanks to a thread of yours: CD47 antibody phase-1 clinical trial - Peyronies Society Forums).

Anyhow I doubt that any laboratory could actually develop something like this in order for people to experiment with it.

I really wish I could be proven wrong on this and I'd like to hear people's results with something like this.
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pey ron

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Re: group buys for self-medication?
« Reply #16 on: March 31, 2019, 12:11:06 AM »

dr. Paulis says the active phase lasts several years. There are patients that thanks to his multimodal approach healed completely within 10 years. I am in touch with several of them via Telegram. But, I don't want to wait for 10 years, I want something quicker. But I believe cures can be effective even after the first 18 months.
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pey ron

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Re: group buys for self-medication?
« Reply #17 on: March 31, 2019, 02:13:34 AM »

Also, according to this DS+QC are effective against fibrosis established since over a year:

Quote
The team then tested the in vivo effectiveness of quercetin in resolving fibrosis in an aged (older than 12 months) bleomycin-induced lung injury mouse model. Seven days after bleomycin administration (the inflammatory phase), mice received quercetin (30 mg/kg) every other day over a period of one or three weeks, until day 14 or 28 after bleomycin administration.

Quercetin was found to reverse the established bleomycin-induced pulmonary fibrosis in these animals. Moreover, the therapy restored the animals’ body weight loss and increased their survival, compared with bleomycin-treated control mice.

from: https://pulmonaryfibrosisnews.com/2018/08/21/quercetin-treatment-reduces-pulmonary-fibrosis-mouse-model-study/

it is my understanding that you should read Dasatinib+Quercetin wherever they refer to Quercetin.
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Werther

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Re: group buys for self-medication?
« Reply #18 on: March 31, 2019, 12:31:52 PM »

dr. Paulis says the active phase lasts several years. There are patients that thanks to his multimodal approach healed completely within 10 years. I am in touch with several of them via Telegram.

I know about Paulis' BS but I don't buy it dude. As a matter of fact "his multimodal approach" is nothing more than what is already suggested on this forum (Peyronies Survival Guide - Information for New Members - Peyronies Society Forums) with the only difference that pentox is injected right into the dick, traction and/or VED aren't recommended and some other supplements besides coq10 and l-arginine are suggested. He made a business out of desperate people by telling them that even if they've been suffering for years they're still eligible for his "treatment" because - as you say - the active phase can last up to 10 years so they can empty their wallet for him for years and years to come; then he tricks his patients by telling them that the ultrasounds showed plaques' reductions after his magical treatment even if their dicks didn't change a single bit (no changes in curvature, deformities, etc.) so they keep coming back to his office.

This guy is smart btw because he gets tons of mild cases so nobody ever complain about the fact that his treatment isn't working because they blindly rely on what he tells them after the ultrasounds.


With regards to the paper on quercetin I have to say that I found it contradictory; there's a part where's stated that "To assess the ability of quercetin to induce apoptosis, researchers treated normal, stable IPF and rapid IPF fibroblasts with quercetin for 24 hours. Results showed that quercetin led to increased expression of the FAS receptor, which induces apoptosis when bound to its ligand, FasL, and two other death receptors called death receptor (DR) 4 and 5. No differences were observed in normal fibroblasts".



Back on topic anyhow I'd like to know a full list of what you're willing to purchase as of today.
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popopo

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Re: group buys for self-medication?
« Reply #19 on: April 02, 2019, 01:12:54 PM »

Me too, I’m willing to experiment, just need to know what substances could actually work. Wish there was a way to speed up research.
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Date of onset: 17
Symptoms: sharp pains, numbness, change in shape/size, hourglassing and discolaration from jelqing/VED usage as a teen. Diagnosed with a venous leak and possible scarring.
Treatments tried: cialis, pentox and VED didnt help

Whyisthishappening

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Re: group buys for self-medication?
« Reply #20 on: April 02, 2019, 01:50:23 PM »

popopo you live in holland there is a team in groningen doing state of the art research do you believe you can contact them in person
Verteporfin as a Medical Treatment in Peyronie's Disease.
Mohede DCJ1, de Jong IJ2, Bank RA3, van Driel MF2.
Author information
1
Department of Urology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands. Electronic address: d.c.j.mohede@umcg.nl.
2
Department of Urology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
3
Department of Pathology & Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
https://www.ncbi.nlm.nih.gov/pubmed/30274909
 
and their forthcoming
Medical Treatments of Peyronie's Disease: Past, Present, and Future.
https://www.ncbi.nlm.nih.gov/pubmed/30634029
i also believe we should find a way to approach the korean scientists with hdac research
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pey ron

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Re: group buys for self-medication?
« Reply #21 on: April 02, 2019, 04:52:21 PM »

Do we know the polarity of verteporfin? IIRC it's only available as a solution for injection, but since I have the idrobrea [ion(t)ophoresis & hydrophoresis machine], it would be easy for me to deliver it transdermally where I need it the most...
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pey ron

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Re: group buys for self-medication?
« Reply #22 on: April 02, 2019, 04:53:18 PM »

wait, verteporfin has a molecular weight of 718.794 dalton, I guess it has to be injected...
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popopo

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Re: group buys for self-medication?
« Reply #23 on: April 03, 2019, 08:36:32 AM »

I'm gonna talk with my GP soon. Maybe he'll send me to Groningen, but I'm not sure. I'll let you know.
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Age: 24
Date of onset: 17
Symptoms: sharp pains, numbness, change in shape/size, hourglassing and discolaration from jelqing/VED usage as a teen. Diagnosed with a venous leak and possible scarring.
Treatments tried: cialis, pentox and VED didnt help

Whyisthishappening

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Re: group buys for self-medication?
« Reply #24 on: April 10, 2019, 10:06:23 AM »

Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment
 This paper introduces the concept that the molecular stages of healing involve the sequential activation of 3 different stages of the cell danger response (CDR). Progress through the healing process is regulated by MITOCHONDRIA and METABOLITES that act as signaling molecules. These are called “metabokines”. If progress through the healing cycle is interrupted, chronic disease can result. An important prediction of this new model is that a handful of new drugs and devices that act to unblock the healing cycle may be effective against hundreds of chronic diseases
 http://naviauxlab.ucsd.edu/wp-content/uploads/2018/10/NaviauxHealingCycle_2018_v2.pdf
on page 4  CDR2 disorders(proliferative) mentions fibrosis ,keloids,mTOR,diabetes,dyslipidemia(all Peyronies Disease related)
   this man is working on mitochondrial disease and chronic illness like CFS and gulf war syndrome
 anyboby of us leaving in san diego?
do you believe we can do a group test?

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Whyisthishappening

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Re: group buys for self-medication?
« Reply #25 on: April 16, 2019, 01:25:16 PM »

THE TRANSCRIPTIONAL SIGNATURES OF CELLS FROM THE HUMAN PEYRONIE'S DISEASE PLAQUE AND THE ABILITY OF THESE CELLS TO GENERATE A PLAQUE IN A RAT MODEL SUGGEST POTENTIAL THERAPEUTIC TARGETS
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339076/

"We assumed that the Peyronies Disease cells in addition to stimulate FIBROSIS have a HIGHLY PROLIFERATIVE phenotype, since we had shown previously that STEM CELLS were present in the Peyronies Disease plaque and the Peyronies Disease cell cultures, and that these Peyronies Disease cells, but not the TA cells, had the ability to display anchorage independence [19] and OVEREXPRESS IGF-1 and other cell growth-related genes."
 

  "The STEM CELLS in human Peyronies Disease cultures, previously reported by our group [19] and confirmed in the current results, may be RESPONSIBLE, at least in part, for the GENERATION of MYOFIBROBLASTS and for the in vivo INDUCTION of the Peyronies Disease like PLAQUE that we have observed after their implantation in the rat tunica albuginea. The role of the STEM CELL in the Peyronies Disease cultures as supportive of plaque growth can also be speculated from our previously reported anchorage-independence of Peyronies Disease− cells in soft agar [19], an indicator of INDEFINATE REPLICATION shared with TUMOR CELLS. MYOFIBROBLAST generation in the Peyronies Disease plaque may be INHIBITED by TARGETING STEM CELLS in the tunica albuginea or by interfering with early myogenic differentiation of fibroblasts by blocking ACTG2, MYF5 or ACTC1. Therapeutically, specific shRNAs [26], endogenous microRNAs that are inhibitors of these genes [24], or pharmacological blockers if available, may be a good strategy because of the easy local administration into the Peyronies Disease plaque"
 

"The recent report that STEM CELLS implanted into the tunica albuginea of the TGFβ1 rat model of Peyronies Disease increased MMP and reduced TIMP expression in this tissue [44] does not contradict our hypothesis that UNKNOWN FACTORS within the milieu of the Peyronies Disease plaque stimulate ENDOGENOUS Stem Cells to undergo MYOFIBROBLAST and/or osteoblast DIFFERENTATION, thus contributing to FIBROSIS and OSSIFICATION, respectively, within the Tunica Albuginea."


 "Peyronies Disease cells display INCREASED CELL GROWTH and S-phase on flow cytometry, STABILIZATION and INACTIVATION of p53, consistent morphologic transformation, and induction of subcutaneous nodules at 2-3 MONTHS following injection into immunodeficient mice [45], suggesting that these CELLS are BIOLOGICALLY TRANSFORMED. The most relevant of our findings illustrating the ability of Peyronies Disease CELLS to PROLIFERATE, and SPECIFICALLLY their STEM CELLS, to drive PLAQUE GROWTH , and implicitly to undergo UNCONTROLLED REPLICATION outside the tunica albuginea, is the UPREGULATION of EDNRB, EGR2, and SerpinB10, key GENES for PROLIFERATION and APOPTOSIS not just IN NORMAL but also MALIGNANT GROWTH, as well as in STEM CELLS"

"The previously postulated role of genes involved in osteogenesis, such as OSF-1 and OSF-2 in the Peyronies Disease plaque [11-13], and PSTN in the Peyronies Disease+ cells [27], has now been confirmed This agrees with the differentiation into MYOFIBROBLASTS of STEM CELLS in the Peyronies Disease cultures and their CONVERSION into OSTEOBLASTS in either NORMAL or OSTEOGENIC medium, as previously shown. PSTN [30,31,37,38] is perhaps the MOST potentially INTERESTING target for THERAPY, as a member of the matri-cellular protein family that regulates cell functions and cell–matrix interactions and is involved in the structure and organization of the extracellular matrix."





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