Peyronie's, Venous Leakage: Physiology, scar tissue, collagen, metabolism, etc.

Previous topic - Next topic

0 Members and 1 Guest are viewing this topic.

BillyBob2

I don't see anywhere else on the forum to put this but there may be a few people here who want to understand our problem on a much deeper level so that we can understand what's going on and possibly find the solution that works for each individual.
 
I'm pasting a post that I made on another topic which is related to ED and testosterone as it gives information on how the penis "works".  I'm also going to post other articles along these lines that are related to scaring, how collage and scars develop and how the body modifies or removes the scars.  I'll try to add to these as I find other related information. Comments/discussion welcome!
--------------------------------------------------------------------------------------------------------------------------------------

I ran across this article while doing some research.  It may already be on this forum somewhere but I thought I'd throw it out there.  It certainly helped me understand how things work.  ED does not seem to be part of my problem but the knowledge and process is closely associated with Peyronies Disease.  There are little seeds of information here that may help me understand and possibly find a solution for my Peyronies Disease.  For me, this journey to find a cure for myself is a myriad of avenues of thought and brain storming.

Since links on the internet may be here today and gone tomorrow I'm pasting the article as well as providing the link for reference.
Venous Leakage


Venous Leakage

"Venous leakage."  Sounds nasty, doesn't it?  Kind of like a hemorrhage or something, eh?  Well, most guys would probably rather have a little hemorrhaging than venous leakage, because it leads to weak and/or rapidly disappearing erections.

Venous leakage describes the condition where the blood escapes from the penis and thus a good erection cannot be achieved.  An erection begins when penile smooth muscle relaxes enabling blood to infill the corpus Cavernosum, two cylindrical "caverns" of spongy tissue running within the penis. Stage two of the erection process occurs with this infilling of the corpus cavernosum.  The inflow of blood expands the spongy tissue, which begins to pinch off the emissary veins of the penis, decreasing outflow and - voila! - the erection begins to build.

NOTE:  Venous leakage should not be confused with venous insufficiency, which is a condition in which the valves in the lower legs go out due to varicose veins, deep vein thrombosis, etc.  There is some evidence that grape seed extract can help with this condition. [4]


Do you know the foods and drinks that increase erection-boosting Nitric Oxide? Check out the Peak Erectile Strength Diet where I show you how to dramatically and naturally improve your erectile strength.

Venous leakage occurs when this second stage fails and bloods leaks out as fast as it infills. The "pinching off" of the outflow veins never occurs adequately and, basically, you're sailing in a leaking boat. Again, though, it's not really that the veins are leaking but rather that the veins are not receiving proper compression.

The causes for venous leakage can be summarized to several basic underlying conditions: 1) smooth muscle insufficiency and 2) structural changes of the corpus cavernosum.  Now what condition can lead to both of these erection killers?  Low testosterone, a.k.a. hypogonadism.

That's correct - low testosterone is a freight train ride to venous leakage and we're going to look at why below.  Here's the good news:  it doesn't have to be a one-way train ride - you can get off the train.

1) Smooth Muscle Dysfunction. Researchers now know that testosterone both maintains smooth muscle and the nerves the fire them in the corpus cavernosum. [1][5] For example, researchers have noted that in castrated animals, the nerve fibers and myelin sheaths around them actually shrink and "wither". And they have also noted that smooth muscle content in the corpus cavernosum decreased as well. [2] Yes, testosterone affects everything in a male!

Your doctor won't give you testosterone? Show him What Low T Does.
Combine supplements for max erectile strength? Go with This Approach.

2) Corpus Cavernosum Integrity. The research points to the fact that low testosterone can actually affect the connective tissue within the corpus cavernosum.  While you are losing smooth muscle, you are also likely gaining more connective tissue, i.e. collagen. [1][2][5] The ECM (extracellelular matrix) changes for the worse, another structure implicated in erectile dysfunction. [6]  This is a sort of "hardening" similar to what causes problems throughout your body. You need for the corpus cavernosum to be flexible and expandable in order to properly compress the outflow.

The bottom line is that researchers have found that in a low testosterone environment, the inside of the penis literally atrophies and is replaced with inelastic, fibrous tissue.

For some of you that have discovered that you lived in a hypogonadal state for years without knowing it, this may be a scary prospect.  "Did it do permanent damage?" is the natural question to ask yourself.

The answer is probably 'yes' to some degree.  However, the good news is that studies show that if testosterone is restored, normal erectile function usually goes with it.  This means that the damage could not have been too severe from a long term low testosterone environment and indicates that a significant reversal is possible.

By the way, some of you who may not respond well to PDE5 Inhibitors, such as Viagra or Cialis, may find that restoring your testosterone restores your erections for the above reasons. One study looked at hypogonadal males who did not respond to Viagra and found a significant restoration of erectile function after HRT (Testosterone Therarpy). [3] Very similar results were found in a study of Cialis non-responders as well. [5] In other words, sometimes the problem is nitric oxide and sometimes it is low testosterone (or both).

So the bottom line is that many of you need to either Increase Your Testosterone Naturally or discuss with your doctor Hormone Replacement Therapy if you want your erections back.  And, yes, Sex is Good For You.


REFERENCES:

1) J Sex Med, 2005, 2:759–770, "The Physiological Role of Androgens in Penile Erection: Regulation of Corpus Cavernosum Structure and Function"

2) Endocrinology, Apr 1 1999, 140(4)1861-1868, "Effects of Castration and Androgen Replacement on Erectile Function in a Rabbit Model"

3) J Urol, 2004 Aug, 172(2):658-63, "Randomized study of testosterone gel as adjunctive therapy to sildena?l in hypogonadal men with erectile dysfunction who do not respond to sildena?l alone"

4) Grape seed

5) Andrologia, 2006, 38:61–68, "Testosterone and erectile function in hypogonadal men unresponsive to tadala?l: results from an open-label uncontrolled study"

6) Braz. J. Morphol. Sci., 2008, 25(1-4):35-10, "Stereological study of extracellular matrix of penile body in felis domestica: experimental model applied to erectile dysfunction"
 
#1 Ranked Book in Amazon Kindle Store for Erectile Dysfunction!
Testosterone Herbs
LATEST BOOK:
WHAT LOW T DOES:
ERECTION "TRICK":

BillyBob2

Collagen metabolism:

Medscape: Medscape Access
Wounds
Collagen Metabolism

Robert F. Diegelmann, PhD, From the Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
Disclosures

Wounds. 2001;13(5)


   Print

   References

The biosynthetic pathway responsible for collagen production is a very complex one.[4,8] Each specific collagen type is encoded by a specific gene; the genes for all of the collagen types are found on a variety of chromosomes. As the messenger RNA (mRNA) for each collagen type is transcribed from the gene, or DNA "blueprint," it undergoes many processing steps to produce a final code for that specific collagen type. This step is called mRNA processing. Once the final pro-alpha chain mRNA is produced, it attaches to the site of actual protein synthesis. This step of the synthesis is called translation. This site of pro-alpha chain mRNA translation is found on the membrane-bound ribosomes also called the rough endoplasmic reticulum or rER. Like most other proteins that are destined for function in the extracellular environment, collagen is also synthesized on the rER (Figure 2, step 1).

Click to zoom
(Enlarge Image)

Figure 2.

The intracellular and extracellular events involved in the formation of a collagen fibril. Copyright 1994 from Molecular Biology of the Cell, Third Edition , by Alberts, Bray, Lewis, Raff, Roberts, Watson (eds). Reproduced by permission of Routledge, Inc., part of The Taylor & Francis Group.

A precursor form of collagen called procollagen is produced initially.[9] Procollagen contains extension proteins on each end called amino and carboxy procollagen extension propeptides. These nonhelical portions of the procollagen molecule make it very soluble and therefore easy to move within the cell as it undergoes further modifications. As the collagen molecule is produced, it undergoes many changes, termed post-translational modifications.[4,8] These modifications take place in the Golgi compartment of the ER.

Collagen, like most proteins that are destined for transport to the extracellular spaces for their function or activity, is produced initially as a larger precursor molecule called procollagen.[9] Procollagen contains additional peptides at both ends that are unlike collagen. On one end of the molecule, called the amino terminal end, special bonds called disulfide bonds are formed among three procollagen chains and insure that the chains line up in the proper alignment. This step is called registration. Once registration occurs, the three chains wrap around each other forming a string-like structure.

One of the first modifications to take place is the very critical step of hydroxylation of selected proline and lysine amino acids in the newly synthesized procollagen protein (Figure 2, step 2). Specific enzymes called hydroxylases are responsible for these important reactions needed to form hydroxyproline and hydroxylysine. The hydroxylase enzymes require Vitamin C and Iron as cofactors.[10] If a patient is Vitamin C deficient, then this reaction will not occur. In the absence of hydroxyproline, the collagen chains cannot form a proper helical structure, and the resultant molecule is weak and quickly destroyed.[11] The end result is poor wound healing, and the clinical condition is called scurvy.[12] The current recommended daily allowance for Vitamin C is 60mg; however, 200mg may be optimal.[13,14]

Some of the newly formed hydroxylysine amino acids are glycosylated by the addition of sugars, such as galactose and glucose.[15] The enzymes that catalyze the glycosylation step, galactosyl and glucosyl transferases, require the trace metal manganese (Mn+2). The glycosylation step imparts unique chemical and structural characteristics to the newly formed collagen molecule and may influence fibril size.[16] It is of interest to note that the glycosylation enzymes are found with the highest activities in the very young and decrease as we age.[17]

While inside the cell and when the procollagen peptides are intact, the molecule is about 1,000 times more soluble than it is at a latter stage when the extension peptides are removed.[18] This high degree of solubility allows the procollagen molecule to be transported easily within the cell where it is moved by means of specialized structures called microtubules to the cell surface where it is secreted into the extracellular spaces.[19]

As the procollagen is secreted from the cell, it is acted upon by specialized enzymes called procollagen proteinases that remove both of the extension peptides from the ends of the molecule.[20] Portions of these digested end pieces are thought to re-enter the cell and regulate the amount of collagen synthesis by a feed-back type of mechanism.[21,22] The processed molecule is referred to as collagen and now begins to be involved in the important process of fiber formation.

In the extracellular spaces, another post-translational modification takes place as the triple helical collagen molecules (Figure 1) line up and begin to form fibrils and then fibers. This step is called crosslink formation and is promoted by another specialized enzyme called lysyl oxidase (Figure 3).[23] This reaction places stable crosslinks within (intramolecular crosslinks) and between the molecules (intermolecular crosslinks). This is the critical step that gives the collagen fibers such tremendous strength. On a per weight basis, the strength of collagen approaches the tensile strength of steel!

Click to zoom
(Enlarge Image)

Figure 3.

The intramolecular and intermolecular cross-links formed within a collagen fibril. Copyright 1994 from Molecular Biology of the Cell, Third Edition , by Alberts, Bray, Lewis, Raff, Roberts, Watson (eds). Reproduced by permission of Routledge, Inc., part of The Taylor & Francis Group.

One can visualize the ultrastructure of collagen by thinking of the individual molecules as a piece of sewing thread. Many of these threads are wrapped around one another to form a string (fibrils). These strings then form cords; the cords associate to form a rope, and the ropes interact to form cables. The structure is just like the steel rope cables on the Golden Gate bridge. This highly organized structure is what is responsible for the strength of tendons, ligaments, bones, and dermis.

When the normal collagen in our tissues is injured and replaced by scar collagen, the connective tissue does not regain this highly organized structure. That is why scar collagen is always weaker than the original collagen. The maximum regain in tensile strength of scar collagen is about 70 to 80 percent of the original.[24] Collagen synthesis and remolding (see below) continue at the wound site long after the injury. The body is constantly trying to remodel the scar collagen to achieve the original collagen ultrastructure that was present before the injury. This remodeling involves ongoing collagen synthesis and collagen degradation. Anything that interferes with protein synthesis will cause the equilibrium to shift, and collagen degradation will be greater than collagen synthesis. For example, patients who are malnourished or patients receiving chemotherapy may experience wound dehiscence, because the wound site will become weak due to a shift in the balance toward collagen degradation. It is of interest to note that when wounds in the fetus heal, they do so in such a manner that the original collagen ultrastructure is achieved.[25] If only we understood more about the biology and mechanisms responsible for the rapid and optimal wound healing response seen in the fetus, we would have greater insight into the management of adult wounds.[26]
 

MattFoley

Great info.

So far I've restored my testosterone and now I'm going after boosting my HGH.

It's not over till the fat lady moans.  ;)

Got Testosterone?

BillyBob2

Mechanism of in vivo DNA transport into cells by ... [J Gene Med. 2006] - PubMed - NCBI

J Gene Med. 2006 Mar;8(3):353-61.
Mechanism of in vivo DNA transport into cells by electroporation: electrophoresis across the plasma membrane may not be involved.
Liu F, Heston S, Shollenberger LM, Sun B, Mickle M, Lovell M, Huang L.
Source

School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. fliu@email.unc.edu
Erratum in

   J Gene Med. 2006 Sep;8(9):1192.

Abstract
BACKGROUND:

Recently, in vivo gene transfer with electroporation (electro-gene transfer) has emerged as a leading technology for developing nonviral gene therapies and nucleic acid vaccines. The widely hypothesized mechanism is that electroporation induces structural defects in the membrane and provides an electrophoretic force to facilitate DNA crossing the permeabilized membrane. In this study, we have designed a device and experiments to test the hypothesis.
METHODS:

In this study, we have designed a device that alternates the polarity of the applied electric field to elucidate the mechanism of in vivo electro-gene transfer. We also designed experiments to challenge the theory that the low-voltage (LV) pulses cannot permeabilize the membrane and are only involved in DNA electrophoresis, and answer the arguments that (1) the reversed polarity pulses can cause opposing sides of the cell membrane to become permeabilized and provide the electrophoresis for DNA entry; or (2) once DNA enters cytoplasmic/endosomal compartments after electroporation, it may bind to cellular entities and might not be reversibly extracted. Thus a gradual buildup of the DNA in the cell still seems quite possible even under the condition of the rapid reversal of polarity.
RESULTS:

Our results indicate that electrophoresis does not play an important role in in vivo electro-gene transfer.
CONCLUSIONS:

This study provides new insights into the mechanism of electro-gene transfer, and may allow the definition of newer and more efficient conditions for in vivo electroporation.

BillyBob2

Regulation of energy metabolism by inflammation: A feedback response in obesity and calorie restriction

Regulation of energy metabolism by inflammation: A feedback response in obesity and calorie restriction - AGING Journal

This is copied from a post by Littlemacca in Causes of Peyronie's Disease

Discovery on how body controls inflammation and wound healing
Study gives new insight on inflammation

Gardner

1st - a big thank you to BillyBob2 for showing this article.  I read this right after I posted my story and question in this thread entitled 'Methods of strengthing cellular strenth of Penis.'  

The venous leakeage issue is a "shrug the shoulders, nothing to do issue" with my uroligist.  I do not agree.  I also have a deformaty still weaking the area of my 90% bend after 1.5 years post surgery.   The body is made up of cells, I cannot believe that cells cannot be naturelly replaced in any part of the body.   The article posted by Billybob2 is far more than any info I received from my urologis.   He also sells penile pump implants which is a concern about confilct of interest.

emo_boy17

HI all,

I wonder if the scar tissue diminishes over time....will venous leak improve as well?

james1947

emo_boy17

Yes, the scat may diminish during time, with or without treatment (rarely without).
But if the venous leakage will improve, I don't know. Maybe yes, maybe no. We can just hope that it will be yes.

James
Age 71, Peyronies from Jan 2009 following penis fracture during sex. Severe ED.
Lost 2" length and a lot of girth. Late start, still VED, Cialis & Pentox helped. Prostate surgery 2014.
Got amazing support on the forum