Peyronie's Disease: Gene transfer of Inducible nitric oxide synthase (iNOS) reverses fibrosis

Therapeutic Efforts
#1

biolreprod.org/cgi/content/full/71/5/1568

Gene Transfer of Inducible Nitric Oxide Synthase Complementary
DNA Regresses the Fibriotic Plaque in an Animal Model of
Peyronie’s Disease.

Davila HH, Magee TR, Vernet D, Rajfer J,
Gonzalez-Cadavid NF.

To investigate the antifibrotic role of inducible
nitric oxide synthase (iNOS) in Peyronie’s disease
(PD), by determining whether a plasmid expressing
inducible nitric oxide synthase (piNOS) injected into
a PD-like plaque can induce regression of the plaque.

A PD like plaque was induced with fibrin in the penile
tunica albuginea (TA) of mice, and then injected with
a luciferase-expressing plasmid (pLuc), either alone
or with piNOS, following luciferase expression in vivo
by bioluminescence imaging.

Rats were treated with either piNOS, an empty control plasmid (pC), or
saline. Other groups were treated with pC or piNOS, in
the absence of fibrin. Tissue sections were stained
for collagen, transforming growth factor (TGF-beta1)
and plasminogen activator inhibitor (PAI-1) as
pro-fibrotic factors, CuZn superoxide dismutase (SOD)
and nitrotyrosine to detect NO reaction with reactive
oxygen species (ROS).

Quantitative image analysis was applied. iNOS and xanthine oxido-reductase (XOR) (oxidative stress) were estimated by western blot.
Luciferase reporter expression was restricted to the
penis and peaked at 3 days after injection but
continued for at least 3 weeks. In rats receiving
piNOS, iNOS expression also peaked at 3 days, but
decreased at the end of treatment when a considerable
reduction of plaque size occurred.

Protein nitrotyrosine, XOR, and SOD increased, and TGF-beta1
and PAI-1, decreased.

piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in
PD is defense mechanism by the tissue against fibrosis.

PMID: 15240426 [PubMed - as supplied by publisher]

#2

I am getting checked by a uroglolist on Thursday for PD. My penis is bending to the left, no doubt about it and I also have a nodule that has developed on the left side. Are there any natural or pharmiceutical treatments I can try to beat this thing? Does anyone know? Does Dr Lue have an email address or any contact information?

#3

Supplements:

  • Vitamin E: 200iu - 400iu/day
  • acetyl-l-carnitine
  • bromelain (enzyme found in pineapple)
  • quercetin

… visit peyronies-disease-help.com and mouse over “Treatment Options” for more.

From urologychannel.com/peyronies … thic.shtml :

Naturopathic Treatment

Peyronie’s disease is a condition in which the fibrous connective tissue in the penis thickens. The disease is not fully understood and many cases spontaneously resolve within a year or two. For those cases requiring medical or surgical intervention, treatment may be frustrating and ineffective. Naturopathic treatment may be used in conjunction with conventional treatments.

Nutrition

Proper nutrition and supplements may be helpful. The appropriate diet can improve overall health, boost the immune system, and help the body heal.

Eat, fresh, unrefined, and unprocessed foods. Include fruits, vegetables, whole grains, soy, beans, seeds, nuts, olive oil, and cold-water fish (salmon, tuna, sardines, halibut, and mackerel). Eating organic food helps reduce exposure to pesticides, herbicides, and hormones.

Avoid sugar, dairy products, refined carbohydrates, fried foods, junk foods, and caffeine.

Eliminate food sensitivities. Use an elimination and challenge diet to to determine food sensitivities.

Drink 50% of your body weight in ounces of water daily (e.g., if you weigh 150 lbs, drink 75 oz of water daily).

Supplements

Bromelain (proteolytic enzymes)- Take 750 mg, 3 times daily, on a empty stomach. Bromelain is a pineapple enzyme that can digest proteins (as can all proteolytic enzymes). It helps prevent the deposition of fibrin, which is believed to cause the connective tissue to thicken.

Herbal Medicine

Gotu kola (Centella asiatica)-Supports healing and normal development of connective tissue.
Note: It may be up to 6 weeks of using bromelain and gotu kola before results are noticed.

Bromelain - cautions…

From spineuniverse.com/displayart … le982.html :

Bromelain should not be taken for more than a week to 10 days. Listed below are guidelines for taking Bromelain.

Cardio/Vascular disease 500-mg to 750-mg 3 times/day on an empty stomach
Gastrointestinal (digestion) 500-mg with meals
Trauma 500-mg 4 times/day on an empty stomach
Inflammation 500-mg to 2,000-mg per day divided into two doses
Tumor Defense 1,000-mg daily

Consult with a medical professional prior to taking Bromelain, especially if any of the following conditions exist: blood-clotting disorder, pregnancy, allergy to pineapples, high blood pressure (hypertension), liver disease, kidney disease. Bromelain can increase the effects of antibiotics (tetracycline) and may increase the risk of bleeding if taken with anticoagulants (i.e. Warfin, Heparin). Seek the advice of a medical professional if taking prescription medication.

This enzyme may cause vomiting, diarrhea, nausea, and heavy menstrual bleeding. If allergic to pineapples, a reaction may occur.

#4

Thanks Mew,

A question. Its says not to take Bromelain for more than a week to 10 days. What does this mean? Aslo I am allergic to pineapple, so how good is this stuff? Is it worth the risk compared to other stuff?

I am already on 400 Vit E and ALC. Will add Quercitin. How does the Quercitin fit in to all this?

#5

Actually I’m not sure how beneficical Quercetin might be for PD, I do recall seeing it as a treatment option before…

However, googling Quercetin + Prostate seems to show that Quercetin helps “shrink” the prostate in certain cases… not something we want to do since that is what Finasteride did.

Bromelain, if you’re allergic to pineapples I dunno if I’d risk trying it. Depends how serious of an allergy you have I guess.

#6

Thanks Mew but I still dont get the “dont take Bromelain for more than a week to 10 days” bit???

#7

I went to a urologis the other day and its confirmed - im in the early stages of Peyronies Disease. He said "thats odd considering your not even 30 years old yet. I am not a happy camper.

#8

Damn, sorry to hear this… how did he confirm this? What tests did he do? And what treatment options did he suggest?

Did you tell him about your use of Propecia?

It sucks, I have a feeling I am also in the same boat… 400-800IU Vitamin E may be a good thing to try for now… and Bromelain intermittently if you can handle it.

#9

He told me there is nothing you can do to treat PD. So i am now seeing a different urologist. He knows about the finasteride use and see the link between the two in my case, but is very passive about the whole thing.

This is also after he told me 3 times that my ED was in my head and it was caused by sitting on internet chatrooms reading about ED. What a joke. He gave me all the ED prescriptions, none of which work because I have no libido. I need TRT. Hopefully with TRT, my erections and T and DHT will bring back my penis so its straight again.

#10

Sorry to hear that J89. How did he confirm your PD? You should have a penile doppler ultrasound just to see the extent of the fibrosis. How old are you currently? Did you feel anything directly that gave you an indication you had PD? Such as pain, shrinkage, etc

#11

I rarely have pain with it. Its more just that ive got nodules. 3 that i can count. And it bends to left. Im in my late 20’s. Far too young for this crap. Ive had shrinkage ever since i stopped finasteride.

#12

Hey RK…how is your treatment with Melman so far? Have things improved for you? Can you tell us what PD treatments u r currently using?

#13

I’ve been on colchicine for a while now. My PD had gotten a lot better for a months - less pain, less curve, fuller, not as dense. Recently (maybe 2 weeks ago) it started acting up again. Curve, pain, etc. Don’t know what caused it. Melman said to continue with the colchicine. I’m having a doppler the monday after next. I didn’t know dopplers can see PD, just blood flow. I’m going to stress that he take a look.

I’m not sure about the shrinkage issue. I can tell that the left side must be shrinking, hence the curve. I sure hope I haven’t lost any size. Have you been measuring? I also don’t know about nodules. I don’t feel any lumps however I do have a kind of crevice like line in the area where I get pain.

#14

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#15

Going to up this…

I too have two nodules on my penis and the base has thinned conciderably. No pain or weird feeling downstairs anymore (in addition to my scrotum and balls feeling cold, any ideas on that one?). Keeping an erection is almost impossible though.

Has bromelain, VIT E or gotu kola helped?

#16

i d like to understand what nodules feel like…i mean,you understand to have them by touching your penis? are they on the surface of the penis or are they difficult to find if you have?