Ideas on Endothelial Dysfunction

[Nas]

If you categorize and divide the Genitourinary system into two parts, organs where organic material is being stored/produced and transport tubes. I think POIS reactions take place on the inside of transport tubes. I do get symptoms when pre-ejaculate is dripping out so that's why I suspect tissue which transport fluids.

Now if you compare storage tissue with transport tissue you may find differences in their structure and this will eliminate layers which are the same for both. You may focus on what they do not have in common.

I do get reactions from food as well upon contact with the oral cavity. I suspect there is something wrong with mucous membranes in general.   

But there are also people who suffer from prostate pain and premature ejaculation as a result of POIS, which again is confusing cause this only happen during ejaculation and not before.
Also I believe that the component that is being attacked here is sperm and not some other component in the semen.
Sperm are germ cells that are quite auto-immunogenic, and pre-cum can be explained by sperms that are left over in the transport tubes, which is why pre-cum POIS is weaker than ejaculation POIS.

[Nas]

If pois related to an endothelial dysfunction this could be an easy test.  It has Glisodin, SOD molecules protected through GI degradation and other compounds for endothelium regulation?

http://www.lifeextension.com/Vitamins-Supplements/item01997/Endothelial-Defense-with-Full-Spectrum-Pomegranate-and-Cordiart

Hmmm, I wonder if that Endothelial protection would be useful at all in our case, maybe should order it and see what.

Also does this supplement support a leaky Endothelium? Because many products can actually increase permeability for cases of hypertension for example.

[Muon]

But pre-ejaculate comes free before ejaculation/orgasm and it also lacks sperm. Some men produce pre-ejaculate with sperm but the presence of sperm in this fluid is very low. Symptoms only seem to arise when fluids are moving around (transported). Anyway, everyone has a theory but where do we go from here?

[Nas]

But pre-ejaculate comes free before ejaculation/orgasm and it also lacks sperm. Some men produce pre-ejaculate with sperm but the presence of sperm in this fluid is very low. Symptoms only seem to arise when fluids are moving around (transported). Anyway, everyone has a theory but where do we go from here?

The point that I am trying to make is how to pinpoint the Enndothlial leak that causes the immune system to attack. I do not think that it is in the BTB rather in the transport tube, possibly the utethra.
For me it seems that sperms are the most logical component in the semen as a suspect for being attacked by the immune system.
The way to move forward is to do tests and possible treatments for this problem.
I wish I had expertise when it comes to this matter, I think with the help of a sexologist we can test for the place of the leak, or let's say the place where the immune system becomes active.

[Muon]

There are people who have developed POIS after undergoing a vasectomy procedure. I suspect this is more like a wall integrity problem of transporter tubes or a mast cell activation disorder where mast cells are being activated upon contact with semen/sperm/cowper's fluid and triggering a cascade.

I wish I had expertise when it comes to this matter, I think with the help of a sexologist we can test for the place of the leak, or let's say the place where the immune system becomes active.

Yes that's the issue for this forum, the complete absence of any specialist that will join the discussion and share their expertise.

[Nas]

Also sorry for bombarding the forum with posts recently.
But one thing I also like to share is that there is a possibility we can reduce Endothelial permeability using vasoconstrictor drugs.
I'm not sure which vasoconstrictor drugs to be used as most of them are either Nose drops or shots. But increasing the integrity of the vascular walls can be a way forward in inhibiting Endothelial permeability.

[Hopeoneday]

https://en.wikipedia.org/wiki/Endothelial_dysfunction#Nitric_oxide

Testing diagnosis etc.

[Nas]

https://en.wikipedia.org/wiki/Endothelial_dysfunction#Nitric_oxide

Testing diagnosis etc.

Hmmmm, can't believe all I had to do is look into a Wikipedia page haha.
I will see if any of these tests are available in my country, we really need to seek professional help to guide us forward with this one as it really comes down to connecting loose dots using someone who has knowledge in the subject.

[Muon]

https://en.wikipedia.org/wiki/Endothelial_dysfunction#Nitric_oxide

Thank you Dr. POIS!

Here are some testing details they have used in POTS research Nas:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511496/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511487/

[Hopeoneday]

If someody on the streat ask me what arae you think why you hawe POTS? I would tell him that i hawe POTS because of POIS( i get pots from pois). And maybe i will be wrong there, because mybe i hawe POIS because of hawing POTS.

[swell]

I get POIS only on ejaculation and have absolute 0 POIS on pre-ejaculate fluid.  I read that pre-ejaculate fluid composition is similar to the ejaculation composition EXCEPT the following:
1. pre-ejaculate has absence of: Gamma-glutamyltransferase
2. is highly alkaline to neutralize acidic environment of urethra (to protect the passage of live sperm later)
3. for some males, it can include dead sperm. 

The ejaculation fluid, is comprised of following properties:
Property   Per 100mL   In average volume (3.4 mL)
Calcium (mg)   27.6   0.938
Chloride (mg)   142   4.83
Citrate (mg)   528   18.0
Fructose (mg)   272   9.25
Glucose (mg)   102   3.47
Lactic acid (mg)   62   2.11
Magnesium (mg)   11   0.374
Potassium (mg)   109   3.71
Protein (g)   5.04   0.171
Sodium (mg)   300   10.2
Urea (mg)   45   1.53
Zinc (mg)   16.5   0.561
Buffering capacity (β)   25
Osmolarity (mOsm)   354
pH   7.7
Viscosity (cP)   3?7
Volume (mL)   3.4
Ref: Wikipedia, search 'semen'

This brings to: what is  Gamma-glutamyltransferase (GGT)
GGT is present in the cell membranes of many tissues, including the kidneys, bile duct, pancreas, gallbladder, spleen, heart, brain, and seminal vesicles.[7] It is involved in the transfer of amino acids across the cellular membrane[8] and leukotriene metabolism.[9] It is also involved in glutathione metabolism by transferring the glutamyl moiety to a variety of acceptor molecules including water, certain L-amino acids, and peptides, leaving the cysteine product to preserve intracellular homeostasis of oxidative stress.
GGT is predominantly used as a diagnostic marker for liver disease. Latent elevations in GGT are typically seen in patients with chronic viral hepatitis infections often taking 12 months or more to present.
Ref: Wikipedia, search 'Gamma-glutamyltransferase'

Could possibly GGT be the culprit?

But pre-ejaculate comes free before ejaculation/orgasm and it also lacks sperm. Some men produce pre-ejaculate with sperm but the presence of sperm in this fluid is very low. Symptoms only seem to arise when fluids are moving around (transported). Anyway, everyone has a theory but where do we go from here?

The point that I am trying to make is how to pinpoint the Enndothlial leak that causes the immune system to attack. I do not think that it is in the BTB rather in the transport tube, possibly the utethra.
For me it seems that sperms are the most logical component in the semen as a suspect for being attacked by the immune system.
The way to move forward is to do tests and possible treatments for this problem.
I wish I had expertise when it comes to this matter, I think with the help of a sexologist we can test for the place of the leak, or let's say the place where the immune system becomes active.

[Nas]

I get POIS only on ejaculation and have absolute 0 POIS on pre-ejaculate fluid.  I read that pre-ejaculate fluid composition is similar to the ejaculation composition EXCEPT the following:
1. pre-ejaculate has absence of: Gamma-glutamyltransferase
2. is highly alkaline to neutralize acidic environment of urethra (to protect the passage of live sperm later)
3. for some males, it can include dead sperm. 

The ejaculation fluid, is comprised of following properties:
Property   Per 100mL   In average volume (3.4 mL)
Calcium (mg)   27.6   0.938
Chloride (mg)   142   4.83
Citrate (mg)   528   18.0
Fructose (mg)   272   9.25
Glucose (mg)   102   3.47
Lactic acid (mg)   62   2.11
Magnesium (mg)   11   0.374
Potassium (mg)   109   3.71
Protein (g)   5.04   0.171
Sodium (mg)   300   10.2
Urea (mg)   45   1.53
Zinc (mg)   16.5   0.561
Buffering capacity (β)   25
Osmolarity (mOsm)   354
pH   7.7
Viscosity (cP)   3?7
Volume (mL)   3.4
Ref: Wikipedia, search 'semen'

This brings to: what is  Gamma-glutamyltransferase (GGT)
GGT is present in the cell membranes of many tissues, including the kidneys, bile duct, pancreas, gallbladder, spleen, heart, brain, and seminal vesicles.[7] It is involved in the transfer of amino acids across the cellular membrane[8] and leukotriene metabolism.[9] It is also involved in glutathione metabolism by transferring the glutamyl moiety to a variety of acceptor molecules including water, certain L-amino acids, and peptides, leaving the cysteine product to preserve intracellular homeostasis of oxidative stress.
GGT is predominantly used as a diagnostic marker for liver disease. Latent elevations in GGT are typically seen in patients with chronic viral hepatitis infections often taking 12 months or more to present.
Ref: Wikipedia, search 'Gamma-glutamyltransferase'

Could possibly GGT be the culprit?

But pre-ejaculate comes free before ejaculation/orgasm and it also lacks sperm. Some men produce pre-ejaculate with sperm but the presence of sperm in this fluid is very low. Symptoms only seem to arise when fluids are moving around (transported). Anyway, everyone has a theory but where do we go from here?

The point that I am trying to make is how to pinpoint the Enndothlial leak that causes the immune system to attack. I do not think that it is in the BTB rather in the transport tube, possibly the utethra.
For me it seems that sperms are the most logical component in the semen as a suspect for being attacked by the immune system.
The way to move forward is to do tests and possible treatments for this problem.
I wish I had expertise when it comes to this matter, I think with the help of a sexologist we can test for the place of the leak, or let's say the place where the immune system becomes active.

Good point swell, I personally believe that it can just be the sperms that are being attacked because it doesn't require a case of Auto-immune syndrom for it to be possible. Sperms are naturally auto-immunogenic and without the protection of Endothelial cells they are most likely going to be attacked.

[nanna1]

If you want to test permeability, zinc increases endothelial permeability through regulation of matrix metalloproteinases (MMP-2, MMP-9, etc...).

[Muon]

Urethra epithelium related ideas:

- Increased epithelial permeability (does IL-17 play a role in this? https://www.ncbi.nlm.nih.gov/pubmed/26431948)
- Was reading about this https://www.ncbi.nlm.nih.gov/pubmed/17722022
and wondered if some sort of hormone controlled binding reaction could happen in the male urinary tract between sperm and the epithelium.
- Epithelial dysfunction
- Scarring of epithelium
- Infiltrated (by chemotaxis) epithelium
- Chronic epithelial inflammation

[FernandoPOIS]

My GGT blood test is normal, well below the level = 16.
But I have endothelial dysfunction. Whenever I take a weak stroke I already have a huge purple spot (black bruise) and I have a vascular problem. I already had 2 surgeries to remove varicose veins and I have low blood pressure, always 10/6.
I think my microcirculation is problematic. I have astigmatism and myopia, muscular tension, and in the cerebral part I have problems to easily forget things.
In my case what improves a lot is the physical activity, mainly running and swimming.

[swell]

Physical activity for me also help in particular swimming.  I know some fellows say it aggravates POIS.  I think trick is, that certain kinds of physical activities help POIS while certain kinds make it worse.  I realized that after ejaculations I turned very pale.  So I used to cure my POIS almost 100% by diving from the highest altitude diving board and on purpose landing at an angle so water made a very big splash on my head/neck/upper body.  That big impact used to turn my face specially but the entire body very very red.  And that redness, which now I think is basically forced circulation, used to do the trick.  I no longer have access to a high-diving bigger pool.  To test the hypothesis I tried microdermabrasion treatment 3-4 times.  If you want to try make sure, it is a medical grade equipment based on high velocity suction.  It basically forces your blood to come to the surface of skin and helps circulation.  You become very red immediately after but then redness subsides.  The treatment is expensive so I have not done it but it also is bit too much invasive so I dont like getting it.

In past I tried homeopathic tinctures for circulation that didn't help.  I have tried Niacin flushes that also dont help me.   Would you know which is the most powerful compound (and yet not harmful) supplement that can increase circulation to same extend that high-altitude diving into swimming pool would do?

My GGT blood test is normal, well below the level = 16.
But I have endothelial dysfunction. Whenever I take a weak stroke I already have a huge purple spot (black bruise) and I have a vascular problem. I already had 2 surgeries to remove varicose veins and I have low blood pressure, always 10/6.
I think my microcirculation is problematic. I have astigmatism and myopia, muscular tension, and in the cerebral part I have problems to easily forget things.
In my case what improves a lot is the physical activity, mainly running and swimming.

[Muon]

I had this posted inside another thread but perhaps it fits this thread better. The main idea is that mast cell activation triggers endothelial activation/degranulation or inflammation. Copy:
Hi nanna,

If (vascular/lymphatic) endothelial cells are being activated in this process then you could check for Weibel-Palade bodies in serum like IL-8, vWF, P-selectin etc. If you have high levels of these you could check for VEGF next: https://www.ncbi.nlm.nih.gov/pubmed/15345585

If there is mast cell activation present then endothelial cells will probably be affected, high concentrations are close to the endothelium.
This could explain (see figure 3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217344/  )
-Your low neutrophil levels due to extravasation.
-My low CD57 NK cells due to the same mechanism.
-Decreased levels of leukocytes levels seen in members of my family
Activation of endothelial cells due to VEGF release by mast cells, could explain my IL-8
This could also explain elevated Lp-PLA2 levels seen in my brother http://circ.ahajournals.org/content/108/17/2041.full

So the point I want to make is that mast cells may be responsible for vascular problems. A Negative tryptase result does not rule out mast cell activation, it does rule out mastocytosis.
Suggestions for future testing:

• Endothelial inflammation markers
• Weibel-Palade bodies
• Mast cell activation markers other than tryptase
• Adhesion molecules like selectins and CAMs

Again guys, check figure 3 of the second link. It's an interesting picture.

[Nas]

Hi guys,
So I previously mentioned in this thread that Vasoconstrictor drugs could possibly decrease Endothelial permeability by increasing vascular walls' integrity.

So I did by the suggestion of Nanna on his thread: http://poiscenter.com/forums/index.php?topic=2502.msg24507#msg24507

Where he mentioned:
"Taken 45 minutes prior to sexual activity (prepack):
Vasoconstrictors:
---Excedrin (acetaminophen 250mg, aspirin 250mg, caffeine 65mg)"
"The below supplements were not taken in the above trial, but can be stacked. However, consult your doctor before stacking multiple vasoconstricting agents as they can increase the risk of heart attack or stroke.
Enhancements:
---Trimethylglycine/TMG (methyl-donor) (2g)
---Indomethacin (COX inhibitor/antioxidant) (75mg)
---propranolol (beta2-blocker, blocks PGE2 induced vasodilation) (see personal doctor for details)"

So I did try a vasoconstrictor based on his suggestion yesterday, and after consulting a doctor, he suggested taking: Propanolol 10mg, Indomethacin 25mg, Paracetamol 250mg and Aspirin 100mg, all before orgasm.

The results were positive, I noticed a clear reduction in many of the Cognitive POIS symptoms I usually suffered from; there were still some symptoms that I felt, like social anxiety, brain fog and fatigue. But overall dare I say that I had about 80% success rate?. I even masturbated two more times after the first session, after about an hour, and I still was able to talk to people after that! That's an insane result for some one who suffers from POIS.

So this trial and the Dexamethasone trial both gave good results, so I can not dismiss the effect these medications had on the Enndothlium and thus I can not disprove the role of the Endothelium and Epithelium on POIS.

I highly advise you people to try one of these suggested treatments after consulting a doctor to prove a consistency in results. And perhaps be able to look more accurately for suitable tests and predict more accurate theories for the future.

[FernandoPOIS]

NAS

Propranolol as a daily medicine may be a good option.
But I do not agree with the idea of ??taking analgesics or anti-inflammatories every time it's going to have an orgasm. Relieves the symptom but does not address the cause of the problem.

[Nas]

NAS

Propranolol as a daily medicine may be a good option.
But I do not agree with the idea of ??taking analgesics or anti-inflammatories every time it's going to have an orgasm. Relieves the symptom but does not address the cause of the problem.

Fernando it's not about anti-inflammatory or analgesics. It's the vasoconstrictor property of this stack; by constricting vascular walls we can increase integrity and thus reduce vascular wall's permeability.
This stack was constructed by Nanna, if you have questions about their exact mechanism ask him cause I'm not sure tbh.
Perhaps it's their anti-inflammatory property but I highly doubt it since I've taken many anti-inflammatory medication before but I never really got any benefit from them.