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POIS Cause/Treatment Discussions => General Alternative Causes and Treatments of POIS => Topic started by: Nas on June 26, 2018, 06:02:22 PM

Title: Ideas on Endothelial Dysfunction
Post by: Nas on June 26, 2018, 06:02:22 PM
Hi guys,
So following a discussion last month on this forum about the Blood brain barrier and the testicle blood barrier and how their dysfunction could be the reason why an action that happens in the reproductive system, ejaculation that is, is connected with symptoms in the brain.
Personally I do not know how to theorize about this subject - as I am not really experienced in the medical field, but I have been searching on the possible treatments for Endothelial Dysfunction.
What caught my eyes though was many of the treatments suggested decrease blood pressure even though POIS sufferers experience low blood pressure as a POIS symptoms including me.
Here is the article: https://www.jstage.jst.go.jp/article/ihj/51/1/51_1_1/_article
So I wonder how does that correlate with POIS? ff there is a correlation at all,
and if Endothelial Dysfunction treatment is not suited for POISers since it decreased blood pressure.
Asking the many experts here, since I'm not really suited for this kind of research. lol
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on June 26, 2018, 06:27:18 PM
I was thinking lately that perhaps the redness in skin prick tests are related to endothelial dysfunction. Skin redness by these test is mainly due to molecules pouring through artery walls and causing reactions (someone should correct me if I'm wrong). What if a vascular endothelial dysfunction causes hyperpermeabilty of the artery walls and stimulates this reaction?

Also if the source of my elevated IL-8 is the endothelial cell then it can create an IL-8 gradient near the endothelium lining attracting neutrophils and/or lymphocytes. Maybe these could migrate through this lining and disrupt it. And what if this happens in the genitourinary system? Does this leads to POIS due to diffusion of semen/sperm/pre-ejaculate?

Anyway I stumbled upon an article just before you posted this thread and could be of interest for treatment purposes:

Angiopoietin‐1 inhibits endothelial permeability, neutrophil adherence and IL‐8 production
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0705259

Here is another one:
Angiopoietin-1 Regulates Brain Endothelial Permeability through PTPN-2 Mediated Tyrosine Dephosphorylation of Occludin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474807/
Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on June 26, 2018, 06:32:30 PM
I think it has a relationship. I have varicose veins and low blood pressure.

People with mutations in the MTHFR gene exhibit enzymatic deficiency that leads to homocysteine accumulation and this alters the function of nitric oxide.

I do not know whether the treatment goes through the way of correcting endothelial dysfunction but something might help maybe for the symptoms phase.

I believe that the enzymatic deficiency, genetic characteristic of little connective tissue and problem in the vagus nerve to respond to the mental and physical stresses form a condition that the majority here in the forum suffer.

Again I will mention that I was very impressed with the typical physical characteristics that I saw in the members of the Facebook group. Deficiency of postural musculature, Low muscle mass and large legs compared to torso size It may be that this is a cause of low blood pressure (thinking of the implied physical issue).

Let s discuss about it. This idea may lead us to somewhere.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on June 26, 2018, 06:53:07 PM
Hi Fernando,

Yes perhaps plasma leaks through walls and causes low blood pressure. The body could compensate for this effect by raising heart rate (POTS?). I wonder if this can lead to hypovolemia which can also be seen in POTS patients. I have the same low muscle mass.

So Ang-1 could inhibit IL-8 production, that is what the first link I have posted states. So my IL-8 is elevated and could make a case for getting this substance. I don't know if there is a medicine containing Ang-1 or indirect releases it in the body. I'm tired at the moment, if someone could look into this matter and search what receptors are at play here and what medicine can simulate the effect of Ang-1 in the first paper then please post it in this thread, It's late I'm going to bed.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on June 26, 2018, 07:35:51 PM
Hi Fernando,

Yes perhaps plasma leaks through walls and causes low blood pressure. The body could compensate for this effect by raising heart rate (POTS?). I wonder if this can lead to hypovolemia which can also be seen in POTS patients. I have the same low muscle mass.

So Ang-1 could inhibit IL-8 production, that is what the first link I have posted states. So my IL-8 is elevated and could make a case for getting this substance. I don't know if there is a medicine containing Ang-1 or indirect releases it in the body. I'm tired at the moment, if someone could look into this matter and search what receptors are at play here and what medicine can simulate the effect of Ang-1 in the first paper then please post it in this thread, It's late I'm going to bed.

It's ok Muon I think I found an article that suggests a treatment method: https://www.sciencedirect.com/topics/medicine-and-dentistry/angiopoietin-1
This article suggests: "Dexamethasone in doses of 8 to 40 mg per day upregulates angiopoietin 1 to stabilize the blood-brain barrier and downregulates VEGF"
What do you think? I'm not explicitly thrilled at trying a chorticosteriod but maybe worth a try?
Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on June 26, 2018, 08:24:19 PM
Hi All,

  I think histamine is the key that the immune system uses to open the blood vessels and allow large molecules (chemokines) and cells (neutrophils) to pass through. The H1-histamine receptor functions as the keyhole that unlocks/opens the blood vessel. I posted about this here (http://poiscenter.com/forums/index.php?topic=2683.msg24197#msg24197). When histamine binds to the H1 receptor, it activates phospholipase A2 and produces prostaglandins through the arachidonic acid cascade. Ultimately, prostaglandins produced from the arachidonic acid cascade control the blood-brain-barrier.

"One of the most striking actions of prostaglandins of the E and A series is their capacity to dilate peripheral blood vessels and thereby to lower arterial pressure. This vasodilating effect of prostaglandins may be mediated by alterations in circulating blood levels of the hormone(s) or by changes in concentration of prostaglandins in blood vessel walls. Prostaglandins also have been implicated in the regulation of the renin-angiotensin-aldosterone system."
-Prostaglandins: Effects on blood pressure, renal blood flow, sodium and water excretion (https://www.sciencedirect.com/science/article/pii/S0085253815316550)

"...mechanistic studies of how NO switches on/off the PG/COX pathway have been undertaken and additional pathways through which NO modulates prostaglandin production unraveled."
-Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors. (https://www.ncbi.nlm.nih.gov/pubmed/15914468)

  The easiest/cheapest way to close the blood-brain-barrier is to take the H1-receptor antiagonist Zyrtec (or Xyzal). Dexamethasone (and all other corticosteroids) function as phospholipase inhibitors (Ref (https://www.ncbi.nlm.nih.gov/pubmed/3103170)), meaning that they block the release of aracidonic acid. But in general, it seems anything that stops the arachidonic acid cascade will close the BBB and reduce inflammation.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on June 26, 2018, 08:52:05 PM
Very interesting Nanna,
I wonder though what would be the cause of H1-histamine activity in the blood ? According to your theory it could be the dormant virus' activity. But what I suggest is that in a case of a dysfunctional Endothelium, the ejaculation process can cause a diffusion of Semen components through the testicles blood barrier which initiates the immune response. Here, there could be two possible cases: 1) The immune system attacks the Semen component increasing the levels of histamine in the blood causing the dysfunction in the Endothelium. 2) We have a general Endothelial dysfunction that makes these Semen components not only get passed the Testicles Blood Barrier but also get passed the BBB.
Although I would like to note that I already tryed different anti-histamines including cetrizine but they didn't do much unfortunately.
Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on June 26, 2018, 11:10:49 PM
Hi Nas,

You may be on to something. I do think blood vessel health is part of the POIS equation.
Very interesting Nanna,
I wonder though what would be the cause of H1-histamine activity in the blood ? According to your theory it could be the dormant virus' activity. But what I suggest is that in a case of a dysfunctional Endothelium, the ejaculation process can cause a diffusion of Semen components through the testicles blood barrier which initiates the immune response. Here, there could be two possible cases: 1) The immune system attacks the Semen component increasing the levels of histamine in the blood causing the dysfunction in the Endothelium.
(1) is a genetic autoimmune mechanism for POIS. My test results suggest that I do not have genetic autoimmunity (see "Autoimmunity blood test: (http://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039)" section). So for me, (1) would not be the cause of my POIS symptoms. My immune system does not attack healthy cells in my body. However, semen is generally high in prostaglandins (prostate-gland-in, in the prostate gland). Also, you might find this article interesting (Seminal plasma components stimulate interleukin-8 and interleukin-10 release (https://www.ncbi.nlm.nih.gov/pubmed/10333355)).
Quote
2) We have a general Endothelial dysfunction that makes these Semen components not only get passed the Testicles Blood Barrier but also get passed the BBB.
In my test results, I posted the doctors notes from my MRI angiogram (MRA). The doctor found what he believed to be a small bulge (aneurysm) in a blood vessel in my brain on the left side (see "Brain scan: (http://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039)" section). In the doctor's notes, he says "There is no evidence for vessel irregularity, stenosis or other aneurysm formation." In other words, the angiogram did not find anything generally wrong with my blood vessels. They only found a blood vessel abnormality in this small location in the left hemisphere of my brain. However, MRAs are not detailed enough to diagnose endothelial dysfunction. And like others here, I also have relatively low blood pressure (110/70). So you could be right about this blood vessel dysfunction. But what would be the cause of Generalized Endothelial Dysfunction?
Quote
Although I would like to note that I already tryed different anti-histamines including cetrizine but they didn't do much unfortunately.
  I'm not trying to suggest endothelial dysfunction is the cause of POIS. I was just suggesting that Zyrtec is a way of testing the theory of endothelial dysfunction. If cetirizine does not work, that may be evidence that the source of the problem is not mast cells opening the BBB. However, it takes a while for an injured or inflamed blood vessel to heal, similar to if you have a skin cut. It could take a week or more of consistent use to heal the injury. There are receptors other than H1 that can release arachidonic acid. So a better test might be using a general phospholipase inhibitor like the corticosteroid you suggested, Dexamethasone.

  I currently believe that the aneurysm in my brain is caused by white blood cell (lymphocyte, neutrophil) chemotaxis (http://www.gluegrant.org/chemotaxis.htm). And if there is a good reason for that chemotaxis, I don't want to interfere with it since my stack, though cumbersome, works for me.

  I know sometimes you refer to the herpes virus theory of POIS as my theory, but many people on this forum have suggested herpes as the cause of POIS even before I became a member. So I don't consider it my theory. Most of what I have been doing recently is summarizing the many ideas surrounding immunity and infection so that it is easy for us see the common points of agreements. Thanks for challenging the ideas and offering new ideas. We all beat POIS together!  ;)
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on June 27, 2018, 03:58:14 AM
  I know sometimes you refer to the herpes virus theory of POIS as my theory, but many people on this forum have suggested herpes as the cause of POIS even before I became a member. So I don't consider it my theory. Most of what I have been doing recently is summarizing the many ideas surrounding immunity and infection so that it is easy for us see the common points of agreements. Thanks for challenging the ideas and offering new ideas. We all beat POIS together!  ;)

No Nanna people 'hypothesized' about Herpes virus as a possible cause, on the other hand, you're the one who drew the the theory, and thus it is "your theory".
Same with me, I do not claim that I have an Endothelial theory. I claim to have a hypothesis that Endothelial dysfunction can be a possible cause and I'm asking members here to help me draw the theory.
Anyways full credit for your time and effort on the theory is where it's due.
Anyways I'm not challenging anything really I'm just too desperate to do nothing. Lol
Title: Re: Ideas on Endothelial Dysfunction
Post by: Quantum on June 27, 2018, 09:17:30 AM
Hi Nas, and Nanni,

Just to add to this discussion, I would like to point out the role of cartilage/collagen in vascular integrity.   When there is a genetic problem with collagen quality/collagen metabolism in the body, veins are one of the structures that can be affected, because a blood vessel need a good and elastic wall in order to undergo dilatation, and than be able to contract back.   Varicose veins, as you may know, are veins in which the venous wall has been chronically enlarged and twisted, their wall have lost elasticity, and they do not go back to original size, leading to many physiological problems ( https://en.wikipedia.org/wiki/Varicose_veins).  However, I do not know if varicose veins can worsen endothelial dysfunction, but I figure out that it would.  The endothelium is lining the interior of the venous wall, so if the later is dilated, it automatically stretches the endothelium.  I suppose that stretching the endothelium can have a worsening effect on permeability problems.


In my own case, I clearly have a defect in collagen/cartilage genetic, as shown by a rib cage birth defect linked to a cartilage malformation.   Women in my family also have a high occurrence of varicose veins in the legs, and both my parents had severe hemorrhoids, which is also a problem of chronic venous dilatation.  I had hemorrhoids problems in the past, but I have learned to manage this, and no longer have them ( in particular, my ultra-healthy diet allows for soft stools and easy bowel movements, constipation being a main aggravating factor for hemorrhoids).   I also have some varicose veins on my body, mainly telangiectasis stage.  I have some dilated veins on the scrotum, in particular ( I work standing for many hours, and this may be the cause)   

Anybody here who had genetic test found has found defect for cartilage metabolism?

Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on June 27, 2018, 10:05:28 AM
Below is a screen shot from the paper ( eminal plasma components stimulate interleukin-8 and interleukin-10 release (https://academic.oup.com/molehr/article/5/3/220/1404473)) that might be useful for looking into endothelial dysfunction. I talks about what happens when semen makes contact with certain cells in the blood and other tissues. And it also discusses the inflammatory and anti-inflammatory cytokines IL-8/IL-10.
(https://i.imgur.com/hj3wdKT.png)

  I do not have varicose. Neither my mom nor my dad has varicose veins. My aunts on my mom's side of the family do not have varicose veins. My veins are quite healthy looking. But I do have relatively low body weight, which allows me to see my veins more than people who have a higher percentage of fat. Also, my blood pressure is relatively low (110 systolic and 70 diastolic) like most athletes, but I am also physically active.

  I just wanted to suggest one thing to consider. If multiple people in the same family have POIS symptoms, is it possible that the cause of POIS is contagious? For example, if the cause of POIS can be transferred through saliva, then shouldn't the mother be able to pass it to a child who's immune system has not fully formed yet.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on June 27, 2018, 10:25:58 AM
This article suggests: "Dexamethasone in doses of 8 to 40 mg per day upregulates angiopoietin 1 to stabilize the blood-brain barrier and downregulates VEGF" . What do you think? I'm not explicitly thrilled at trying a chorticosteriod but maybe worth a try?
Thanks for bringing this up Nas. It goes on my things to try list. I have no idea whether it may be worth it, I don't have the medical background to say anything useful about it in general. In my case however it could be of interest if the IL-8 production is of EC origin. At the end of the day it's a matter of experimentation. VEGF is by the way an interesting parameter to test in this context, there could be an overexpression of it. If you are going to use it Nas be careful not to suddenly abort intake schedules, ask your doctor.

My brother has elevated Lp-PLA2 outside of POIS episode. The immunologist made a comment next to it (it's in german):
''Erhohte Lipoprotein-assoziierte Phospholipase A2 (Lp-PLA2) Aktivitat. Dieses spricht fur eine erhohte endotheliale Entzundung''.
This could be an indication of endothelial inflammation. (the above sentence needs umlaut symbols but dunno how to insert them)

Quote from: nanna1
I currently believe that the aneurysm in my brain is caused by white blood cell (lymphocyte, neutrophil) chemotaxis.
Now to think of it, I had a conversation with Disaster about Sjogren's syndrome and IgG antibodies. He said he had an focus score of 1.0 which is a borderline criteria for lymphocyte infiltration near salivary glands in sjogren's. There could be chemotaxis at work here.
http://poiscenter.com/forums/index.php?topic=305.15

Quote from: Quantum
Just to add to this discussion, I would like to point out the role of cartilage/collagen in vascular integrity.
Good point. There are also indications of a link between mast cell disorders and cartilage/collagen disorders.

Quote from: Quantum
In my own case, I clearly have a defect in collagen/cartilage genetic, as shown by a rib cage birth defect linked to a cartilage malformation.
You mean like this: http://pectusexcavatumfix.com/wp-content/uploads/2015/06/My-Flared-Ribs-Case.jpg
My brother has this malformation, do you have something similar like this?
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on June 27, 2018, 12:40:01 PM
Just an update on Dexamethasone,
The article suggested that Dexamethasone would be taken from doses of 8 to 40, this can only achieved by taking injections and I can not really take injections personally, because I do not know how to inject my self, so that is not possible unfortunately.
I will be taking 1mg of oral Dexamethasone tablets though until I find a way to up the dosage safely.
Any suggestions on a safe chorticosteroid that has the same effectiveness as Dexamethasone?
Especially when it comes to angiopoietin 1 upregulation.
Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on June 27, 2018, 02:59:32 PM
Quote
Quote from: nanna1
I currently believe that the aneurysm in my brain is caused by white blood cell (lymphocyte, neutrophil) chemotaxis.
Now to think of it, I had a conversation with Disaster about Sjogren's syndrome and IgG antibodies. He said he had an focus score of 1.0 which is a borderline criteria for lymphocyte infiltration near salivary glands in sjogren's. There could be chemotaxis at work here.
http://poiscenter.com/forums/index.php?topic=305.15
Thanks Muon for sharing, I think my autoimmune test (http://poiscenter.com/forums/index.php?topic=2683.msg24039#msg24039) rule out Sjogren's syndrome for me. But I am thinking of getting more blood test. So it has been interesting to read about those immunoglobulins.

Hi Nas, I put a list of phospholipase A2 inhibitors here (see "cytosolic phospholipase A2 (cPLA2) inhibitors:" section) (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773). The corticosteroid phospholipase A2 inhibitors are listed at the bottom of "Anti-herpes therapuedics (http://poiscenter.com/forums/index.php?topic=2683.msg23773#msg23773)".
Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on June 27, 2018, 03:29:01 PM
Quote
Hi Nas, and Nanni,

Just to add to this discussion, I would like to point out the role of cartilage/collagen in vascular integrity.   When there is a genetic problem with collagen quality/collagen metabolism in the body, veins are one of the structures that can be affected, because a blood vessel need a good and elastic wall in order to undergo dilatation, and than be able to contract back.   Varicose veins, as you may know, are veins in which the venous wall has been chronically enlarged and twisted, their wall have lost elasticity, and they do not go back to original size, leading to many physiological problems ( https://en.wikipedia.org/wiki/Varicose_veins).  However, I do not know if varicose veins can worsen endothelial dysfunction, but I figure out that it would.  The endothelium is lining the interior of the venous wall, so if the later is dilated, it automatically stretches the endothelium.  I suppose that stretching the endothelium can have a worsening effect on permeability problems.
That's interesting Quantum! I heard about UC-II collagen (https://www.amazon.com/s/?ie=UTF8&keywords=uc-ii+collagen&tag=googhydr-20&index=aps&hvadid=153722604928&hvpos=1t2&hvnetw=g&hvrand=5264449278886249167&hvpone=&hvptwo=&hvqmt=e&hvdev=c&hvdvcmdl=&hvlocint=&hvlocphy=9027891&hvtargid=kwd-3146389657&ref=pd_sl_4jb3kzhtej_e) and I was thinking of trying it for my bad knees. Also, I used to have arthritis in graduate school. I think B vitamins and vitamin D3 fixed the arthritis. Not sure if that has anything to do with collagen defects.

There was a clinical trial for UC-II collagen:Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764342/)
Title: Re: Ideas on Endothelial Dysfunction
Post by: Quantum on June 28, 2018, 06:42:21 AM
Quote from: Quantum
Just to add to this discussion, I would like to point out the role of cartilage/collagen in vascular integrity.
Good point. There are also indications of a link between mast cell disorders and cartilage/collagen disorders.

Quote from: Quantum
In my own case, I clearly have a defect in collagen/cartilage genetic, as shown by a rib cage birth defect linked to a cartilage malformation.
You mean like this: http://pectusexcavatumfix.com/wp-content/uploads/2015/06/My-Flared-Ribs-Case.jpg
My brother has this malformation, do you have something similar like this?

Yes, I have a pectus excavatum.  The link with POIS is not clear, if one at all, except if endothelial dysfunction may be linked to a collagen defect, and linked to a mast cell activation syndrome. But, it is clear that all those with a pectus excavatum do not have POIS, and it is also very clear that all those with POIS do not have a pectus excavatum.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on June 28, 2018, 09:47:44 AM
Indeed Quantum the link isn't clear but it's supsicious nonetheless. I have kyphosis+POIS, my brother has pectus excavatum plus POIS like you do. Bone malformations can be seen in mast cell disorders, if you look up papers you won't find group studies (except for osteoporosis) of them but they can be found in case reports.

Storage granules of endothelial cells (Weibel-palade bodies) might be of interest in testing:
https://en.wikipedia.org/wiki/Weibel%E2%80%93Palade_body

Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways.
https://www.ncbi.nlm.nih.gov/pubmed/23609797

VEGF:
Vascular permeability factor: a unique regulator of blood vessel function.
https://www.ncbi.nlm.nih.gov/pubmed/1791186

VEGF induces hyperpermeability by a direct action on endothelial cells.
https://www.ncbi.nlm.nih.gov/pubmed/9612282

Endothelial cell inflammation:
https://www.ncbi.nlm.nih.gov/pubmed/25022461
https://www.ncbi.nlm.nih.gov/pubmed/29549630

Background info on endothelial cell functions, lining and gaps:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289273/

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcp.10333
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on June 29, 2018, 12:44:06 AM
Hey guys,
So it really hasn't been three days since I tried 1mg Dexamethasone. But tbh I'm a little bit worried for many things.

1) To start off I'm really worried that 1mg is not really enough of a dosage especially when the article suggested a dosage of 8 to 40 mg. I'm not sure if a 1mg will take longer to show effectiveness or not show any at all because it's not enough.
2) I'm also worried about the many side effects of Dexamethasone, especially for increased chance of infection, and it's effect on natural steroid hormones expression in the body long term.
3) I would like to test for Dexamethasone effectiveness as soon as possible to know weather it is effective against POIS or not. Yet I need professional help to administer that. This professional help unfortunately is hard to get, since I have to explain to him what is POIS first before delving into his administration of the dosage. So what is your suggestion? I'm thinking of trying 20mg Dexamethasone for a week but I can not inject my self. Perhaps drinking the injection solution can be an alternative?
Perhaps there is a less dangerous alternative to dexamethason that can still upregulate angiopoietin 1?
I'm looking for your suggtion and advise here guys, I really just want to test the angiopietin 1 upregulation but I can't really debunk it with certainty without professional administration.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Quantum on June 29, 2018, 07:02:00 AM
Hi Nas,

20mg of dexamethasone is a very high dose. You should find a doctor to guide you in that.  In addition, I am not sure a doctor would go with injections rather than with oral tablets of dexamethasone.

There is a report on the old NS forum about a member who had relief ( less severity and less duration of symptoms) with oral dexamethasone, in the range of a few mg, taken at the onset of POIS symptoms.

Also, here on the forum, you can find the report of a member who had some success with low dose of oral prednisone:  http://poiscenter.com/forums/index.php?topic=2488.msg21324#msg21324

Coricosteroids on a current basis are not good for the body.  A as needed dosage like those mention above are far more safe on the long run.   I hope you will discuss that with a health professional.


Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on June 29, 2018, 07:21:25 AM
Hi guys,
I agree that the amount of 20 mg is very high. Perhaps prednisolone may help, and there are still other corticosteroids with less potency and fewer side effects. According to my knowledge the cost benefit I will never try corticosteroids and benzodiazepines. I think we have other ways.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on June 29, 2018, 10:45:14 AM
*sigh*
It's going to be really hard to convince a health professional that I have POIS, nonetheless that I suffer from Endothelial dysfunction, nonetheless that I need dexamethason to test for angiopoietin 1 upregulation. He'll just think that I'm being delusional. I'm really stuck here.
I guess I'll just continue 1mg dexamethasone  for the rest of the week and then terminate it, I doubt any benefit would come from such a low dose anyways.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Bulbo on June 29, 2018, 08:33:43 PM
Hi Nas
Dont take any steroids continuously for more than 5 days... it can reduce immunity, central obeisity, hypertension and many other side effects... also after taking steroids for a few days continuously u cannot stop steroids abruptly... u hv to taper the dose and stop... for ecammple if u hv been tkking 8 mg for five days resuce the dose to 4 mg for 2 more days and then stop
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on June 29, 2018, 09:57:26 PM
Hi Bulbo,
I'm only taking 1mg plus I'm using 4 more days than I'll stop.
I realize the consequences of this medication but I want to hit a week to perhaps give a chance for the medication to prove it self.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 01, 2018, 10:41:35 PM
Hey guys,
So after about 5 days of trying 1mg dexamethason, I'm terminating this method.

So here is my conclusion:
1- The medication really accelerates your recovery from POIS, I was more social, clear headed, motivated and focused in three days of dexamethason after orgasm than an entire week of normal POIS recovery.
2- Unfortunately, Dexamethason comes with side effects, which unfortunately bit my ass on the fifth day. As someone who deals with pure OCD and depression as a POIS symptom, at first dexamethason seemed great for those two until yesterday I was watching a video on YouTube, then suddenly I started experiencing soul crushing pure OCD thoughts that put me in a state of panic and anxiety; I couldn't even sleep that day and until right now I'm feeling some of the effects of OCD. So definitely I do not recommend Dexamethason if you suffer from psychological issues.

Yet I also would like to remind everybody, that for someone who tried so many of the treatments that have been tested on this forum and got a 30% improvement max. This was still a great experience. Dexamethason definitely works for me but It's not a safe method of treatment at all.

When it comes to the theory of Endothelial dysfunction this is still not a proof that Dexamethason healed my Endothelium, because there is an equal chance that Dexamethason healed my brain inflammation that I suffer from. I never usually find success with NSAID's nor with Histamine blockers though so I'm not sure about that.

Thus, to properly test weather the vascular permeability factor is the driving reason for POIS symptoms I need to use much safer methods and treatments for Endothelial Dysfunction. There are many methods that I found articles about, but most of them focus on Endothelial function when it comes to elevated blood pressure related illnesses. Hence the blood pressure lowering treatment methods suggested by many articles. So I wonder is it a good idea to try ACE inhibitors or Beta blockers even though POIS causes us lower blood pressure? Looking forward for your suggestions.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 02, 2018, 12:47:28 AM
I dont find info on this maybe someone here has.  My body is strange with abnormaly small torso and abnormaly long legs.   10 years ago I thought I will grow into a normal body like others but that never materialized.  I never been able to run for too long and have to catch breadth.  I have speech issues I think as I run out of air while talking.  Is there a condition that relates to abnormal small torso size for male?
Title: Re: Ideas on Endothelial Dysfunction
Post by: aswinpras06 on July 02, 2018, 10:03:32 AM
Hi  Swell

Even I have a small built torso and feel out of breath while talking and this exists from my childhood days.   I've reached 40 years now and still have the same problem.  Doctors I have consulted  have attributed this to my allergic rhinitis and sinus issues, but  don't have a solution for it.  This may be due to chronic inflammation in our airway.  But till now I could not find out the exact reason because the doctors are not that helpful and they usually send for speech therapy which I tried for six months, with no improvement.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 02, 2018, 11:01:43 AM
I too same, allergic rhinitus and sinus issues.  I got tested for every allergy substance I could but all tests came negative.  Doc even injected into bloodstream still came  negative.  Good to know not that I want people to suffer but that others have same issue.  I get too much nasal discharge all times which cause more problems like affects the tone/pitch of my voice - which hate it.  I am trying NAC and Alpha Lipoic both in sustained release twice daily.  NAC is supposed to clear airways, but to me it does very little.  The only thing that really helps is 'guaifaniscene'.  But for some reason I dont like taking it daily. 
Title: Re: Ideas on Endothelial Dysfunction
Post by: Quantum on July 02, 2018, 08:04:04 PM
Hey guys,
So after about 5 days of trying 1mg dexamethason, I'm terminating this method.

So here is my conclusion:
1- The medication really accelerates your recovery from POIS, I was more social, clear headed, motivated and focused in three days of dexamethason after orgasm than an entire week of normal POIS recovery.
2- Unfortunately, Dexamethason comes with side effects, which unfortunately bit my ass on the fifth day. As someone who deals with pure OCD and depression as a POIS symptom, at first dexamethason seemed great for those two until yesterday I was watching a video on YouTube, then suddenly I started experiencing soul crushing pure OCD thoughts that put me in a state of panic and anxiety; I couldn't even sleep that day and until right now I'm feeling some of the effects of OCD. So definitely I do not recommend Dexamethason if you suffer from psychological issues.

Yet I also would like to remind everybody, that for someone who tried so many of the treatments that have been tested on this forum and got a 30% improvement max. This was still a great experience. Dexamethason definitely works for me but It's not a safe method of treatment at all.

When it comes to the theory of Endothelial dysfunction this is still not a proof that Dexamethason healed my Endothelium, because there is an equal chance that Dexamethason healed my brain inflammation that I suffer from. I never usually find success with NSAID's nor with Histamine blockers though so I'm not sure about that.

Thus, to properly test weather the vascular permeability factor is the driving reason for POIS symptoms I need to use much safer methods and treatments for Endothelial Dysfunction. There are many methods that I found articles about, but most of them focus on Endothelial function when it comes to elevated blood pressure related illnesses. Hence the blood pressure lowering treatment methods suggested by many articles. So I wonder is it a good idea to try ACE inhibitors or Beta blockers even though POIS causes us lower blood pressure? Looking forward for your suggestions.


Hi Nas,

Corticosteroids are the "fight or flight" hormones, so they surely not calm down.  But they are very strong to stop the immune response, and therefore, to lower inflammation.

As with any medication that has significant side effects, it is often to find to lowest efficient dosage. Another POIS sufferer have reported that a single low dose of corticosteroids, just before or after O, was helpful.     


Hopefully, I am glad you decided not to try the 20mg dose   :)

Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on July 02, 2018, 08:33:33 PM
Hi Swell

On this feature of presenting the small torso:
As I mentioned on my topic on causes and treatments for POIS (http://poiscenter.com/forums/index.php?topic=2714.0), I noticed that members of the Facebook group (POIS) presented small trunk relative to the legs, thin neck, small jaw and prominent cheeks. The men I've seen in the group who have white skin, the cheeks are red as well. Physical characteristics just like mine.

Regarding the possible metabolic alterations, I highlight the mutation in the MTHFR gene as a probable cause of these physical characteristics in most of the men who suffer from this disease. There may also be problems with other enzymes. Each one has to do a genetic test to see what enzymatic changes it has.

I joined a Facebook group about MTHFR and the people in the group are very much like the men I saw in the Facebook POIS group.

After gathering the information I found in the following places: This forum (POISCENTER), Facebook Groups and Google searches I strongly believe that men who suffer from POIS have a deficiency in the general development of the body with much evidence like little muscle mass in the trunk and problems related to connective tissue (colagen).

In my specific case, I have a very small trunk, long neck. Since I was 14, I'm too ashamed to take off my shirt. My body looks like a 12-year-old boy despite my height (1.90). All of my photos I took on the beach when I was 14 or 15 were burned. I'm very ashamed. I believed that this would change when I arrived at the age of twenty years or more. But this never happened. I'm still very thin. I managed to improve this condition a little with a few years of bodybuilding, but after the beginning of POIS, I had to stop the exercises.

In parallel to this, I trained soccer since I was a child and maybe because I dedicated a lot I excelled in this sport and almost became a professional. But it had many physical limitations. Had large bruises after someone beat my leg. Always have vascular problems. I already had 2 varicose veins surgery. The first with 29 years old and the other this year (36 years old)

The main question is:

If we have this characteristic and there is no way to change, we must take care to try to improve this condition.

How to:
Correct feeding and supplementation to correct enzymatic deficiencies.
Correct physical exercises to improve posture, muscle condition, and vagus nerve work.
Title: Re: Ideas on Endothelial Dysfunction
Post by: aswinpras06 on July 03, 2018, 01:49:59 AM
You're are an excellent observer Fernando.  The thin body which many of us have may be due to fat malabsorption which inturn is most likely caused by enzymatic deficiency.  Good and correct nutrition is the key factor in overcoming this.  So far I have little success in increasing my body weight.  But good sleep helps a lot.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 03, 2018, 11:15:37 AM
Hi Nas,

With such low dosage and having good effects could indicate you are affecting the right system. What that system is, is a big question mark. ACE inhibitors and beta blockers work via different mechanisms though. Yes most of the endothelial related papers are focussing on abnormal blood pressure as the central problem instead of tackling endothelial dysfunction/inflammation regardless of blood pressure or cholesterol problems.

Off-topic:
Some ideas about low muscle mass; Metabolism problems by POIS, malabsorption in general, Gastrointestinal motility problems by autonomic dysfunction or decreased blood supply to muscles.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 05, 2018, 02:38:06 AM
Hi guys,
So I stumbled upon an online article about repairing a leaky Blood Brain Barrier:https://www.optimallivingdynamics.com/blog/how-to-repair-a-leaky-blood-brain-barrier-ways-heal-fix-supplements-mental-health-neuroinflammation-treatments-causes-gaba-injury-hyperpermeability (https://www.optimallivingdynamics.com/blog/how-to-repair-a-leaky-blood-brain-barrier-ways-heal-fix-supplements-mental-health-neuroinflammation-treatments-causes-gaba-injury-hyperpermeability)

What's interesting is that this article suggests ?in his book Why Isn?t My Brain Working, Dr. Datis Kharrazian explains that the blood-brain barrier can break down and become ?leaky?. This allows harmful substances to enter your brain, contributing to brain inflammation, which has been shown to cause cognitive problems and mental illness"

And many of the treatment methods have been discussed in this forum such as: Omega-3, gluten free diet, healing the gut, B-vitamines, Curcumin, Vitamin D-3, etc.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Quantum on July 05, 2018, 10:14:52 AM
Hi guys,
So I stumbled upon an online article about repairing a leaky Blood Brain Barrier:https://www.optimallivingdynamics.com/blog/how-to-repair-a-leaky-blood-brain-barrier-ways-heal-fix-supplements-mental-health-neuroinflammation-treatments-causes-gaba-injury-hyperpermeability (https://www.optimallivingdynamics.com/blog/how-to-repair-a-leaky-blood-brain-barrier-ways-heal-fix-supplements-mental-health-neuroinflammation-treatments-causes-gaba-injury-hyperpermeability)

What's interesting is that this article suggests ?in his book Why Isn?t My Brain Working, Dr. Datis Kharrazian explains that the blood-brain barrier can break down and become ?leaky?. This allows harmful substances to enter your brain, contributing to brain inflammation, which has been shown to cause cognitive problems and mental illness"

And many of the treatment methods have been discussed in this forum such as: Omega-3, gluten free diet, healing the gut, B-vitamines, Curcumin, Vitamin D-3, etc.

Hi Nas,

Good article, from my point of view. Many of my favorite supplements are talked about in it.  Broccoli is in each of my green smoothies, I take omega-3 every day, 1000ui of vit D every day too ( not much sun in my part of the world), curcumin with black pepper in my breakfast cereals every morning.  All these are good for inflammation in general, and if they also help eliminate a leaky blood-brain barrier, that's great.    Stress management, through meditation, yoga, brain wave entrainment, are also part of my life for years.


I am in far more better condition than when I was younger.   It's the results of those many healthy choices over the years.  But we have to begin somewhere.  This article is a very good starter, I think.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 09, 2018, 12:34:04 AM
Hello guys,

So I stumbled recently on an article discussing the BBB permeability that also discussed how to test for a leaky BBB. Here is the link: ( https://www.selfhacked.com/blog/blood-brain-barrier-causes-tests-leaky-brain/#Health_Tools_I_Wish_I_Had_When_I_Was_Sick ).

One of the testing methods was testing for MMP-9 enzyme levels in the blood as an indicator:

"Matrix metalloproteinases (MMPs) play a role in the disruption of the blood-brain barrier (BBB), especially MMP9. MMPs are endopeptidases (enzymes that break down peptide bonds) that degrade the extracellular matrix.

Disruption of the BBB occurs after a stroke, and worsens brain injuries. Many animal and postmortem studies of brain tissues from stroke patients have shown an increase in MMP9 levels following a stroke.

In one study, researchers studied the effect of MMP9 on rat brains with traumatic brain injuries. After the brain injury, MMP9 levels significantly increased, as did BBB disruption. Additionally, treatment with an MMP inhibitor reduced BBB disruption
"

Testing for these can be a huge step in confirming our high BBB permeability problem and it can also confirm a case of chronic inflammation or Auto-immune disease potentially. 
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 09, 2018, 01:28:50 AM
I also stumbled on another article concerning the role of the Blood-Testis-Barrier (BTB) and the Sertoli cells on protecting auto-antigenic germ cells. Here is the link: ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043859/ )

" The focus of this manuscript is to review the evidence that the Blood-Testis-Barrier (BTB)/Sertoli cell (SC) barrier along with the SCs ability to modulate the immune response is vital for protecting auto-antigenic germ cells. In normal testis, the BTB/SC barrier protects the majority of the auto-antigenic germ cells by limiting access by the immune system and sequestering these ?new antigens?. SCs also modulate testis immune cells (induce regulatory immune cells) by expressing several immunoregulatory factors, thereby creating a local tolerogenic environment optimal for survival of nonsequesetred auto-antigenic germ cells. Collectively, the fortress created by the BTB/SC barrier along with modulation of the immune response is pivotal for completion of spermatogenesis and species survival."

Highlights:
"
1- Appearance of germ cells, expressing novel cell surface and intracellular proteins, after induction of the systemic tolerance makes them auto-immunogenic.
2- Sertoli cells (SCs) protect germ cells by forming the Blood-Testis-Barrier (BTB)/SC barrier, includes the tight junctions between Sertoli cells along with the body of the SCs, and modulating the local environment of the testis.
3- The BTB/SC barrier sequesters the majority of auto-antigenic germ cells and prevents the immune cells from gaining access to these developing germ cells.
4- Immunomodulatory factors expressed by SCs protect the nonsequesetred auto-antigenic germ cells by inducing regulatory cells either directly and/or indirectly.
"

The only problem I am confused by though, is that the BTB is situated between the testicles and the blood vessels, yet POIS only occurs during ejaculation? So if anything this can be supposedly explained as that the endothelial cells in the urethra are the ones that are leaky and not the BTB. This kind of confuses me so I am looking forward for your response. If we have an endothelial dysfunction in the reproductive system, where will it be? in the BTB, the prostate or the urethra?     
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 09, 2018, 11:47:18 AM
Perhaps we should map all the layers of tissue making up the 'walls' within the entire Genitourinary system first. Like what is the order of layers or cells within walls of the https://en.wikipedia.org/wiki/Seminal_vesicle or https://en.wikipedia.org/wiki/Urethra . I still don't have a clear picture in front of me.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 09, 2018, 02:13:41 PM
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
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 09, 2018, 02:45:49 PM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 09, 2018, 02:49:23 PM
Perhaps we should map all the layers of tissue making up the 'walls' within the entire Genitourinary system first. Like what is the order of layers or cells within walls of the https://en.wikipedia.org/wiki/Seminal_vesicle or https://en.wikipedia.org/wiki/Urethra . I still don't have a clear picture in front of me.

Yeah this part is quite confusing.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 09, 2018, 03:27:46 PM
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.     
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 10, 2018, 12:20:09 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 10, 2018, 08:52:57 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 10, 2018, 09:03:14 AM
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?
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 10, 2018, 09:15:26 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 10, 2018, 09:41:02 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 10, 2018, 09:59:41 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Hopeoneday on July 10, 2018, 10:17:02 AM
https://en.wikipedia.org/wiki/Endothelial_dysfunction#Nitric_oxide

Testing diagnosis etc.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 10, 2018, 10:32:07 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 10, 2018, 11:49:39 AM
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/
Title: Re: Ideas on Endothelial Dysfunction
Post by: Hopeoneday on July 10, 2018, 03:01:11 PM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 11, 2018, 01:16:18 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 11, 2018, 02:38:27 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on July 11, 2018, 04:01:04 AM
If you want to test permeability, zinc increases endothelial permeability through regulation of matrix metalloproteinases (MMP-2, MMP-9, etc...).
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 11, 2018, 05:40:50 AM
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
Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on July 11, 2018, 08:19:33 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 11, 2018, 01:17:15 PM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 11, 2018, 05:48:22 PM
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:
Again guys, check figure 3 of the second link. It's an interesting picture.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 13, 2018, 06:53:29 AM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on July 13, 2018, 03:59:27 PM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 13, 2018, 04:18:19 PM
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.
Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on July 14, 2018, 08:43:22 AM
Nas

I believe then that the stimulators of the central nervous system are capable of contracting the blood vessels. In this case we have several options that seem to help a lot as reported here in the forum: Caffeine, pseudoephedrine, green tea....
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 14, 2018, 10:30:44 AM
I take Adderall one of most potent stimulators of CNS known.  It is also a vasoconstrictor.  Its a fact and not my opinion.  It lifts your mood like a rocket by increasing helpful neurotransmitters (dopamine, norepinephrine, serotonin).  Whether you are in POIS or not in POIS it will lift you up.  I consider it helping pois 0%.  I say because it only temporary camouflages  your mental fog with this alert feeling.  Its temporary and it follows with a crash.  These meds do nothing to therapeutically cure or help treat your POIS.  In fact it worsens your POIS.  It marshals blood flow and all your energies towards your brain so yes mental fog temporary is gone but at direct factual expense of your other vital organs and your peripherals like skin effect of POIS.  Most POIS sufferers I think have Raynauds syndrome too, and these CNS stimulators make you swell up due to less blood flow reaching furthest organs.  By the way I got Berberine I start eating it today will let all know.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 14, 2018, 11:58:11 AM
I've uploaded my brother's data, check the second link: http://poiscenter.com/forums/index.php?topic=2545.0
Check the elevated Lp-PLA2 activity. I don't know how this is defined compared to Lp-PLA2 levels. The order form @ #73: https://www.imd-berlin.de/fileadmin/user_upload/Anforderungsscheine/SI_Anforderung_IGEL.pdf  emphasizes endothelial origin?

Check the discussion section: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377521/
There are more references to other papers in the above article.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Quantum on July 14, 2018, 04:13:01 PM
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.

Hi Nas,

I am very happy for you, that you have finally found an effective method to relieve your POIS symptoms. You have been very patient, and tried many methods, and now it pays up for you. 

Please keep us updated in the coming months about how it goes for you.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 16, 2018, 09:37:48 AM
Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 16, 2018, 09:59:19 AM
Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

I will try to give a more accurate prescription of symptoms using Muon's symptoms from his Muon's case post: http://poiscenter.com/forums/index.php?topic=2545.msg24545#msg24545

1= positive result ( had relief )
0= negative result ( did not have relief )
%= about 50% decrease
X= Do not suffer from this symptom

- Extreme fatigue = 1
- Muscle ache = 1
- Joint pain = X
- Exercise/motion intolerance = %
- Heavy body = 1
- Feeling cold/warm, feeling cold happens far more often than warm = 1
- Decreased endurance, especially with the duration of standing and sitting straight = 1
- Sensitive teeth = X
- Stinging pain at liver area = X
- Yellowing of facial skin = X
- Pale skin and facial skin becomes like a babyskin = X
- Decreased vocabulary = 0
- Articulation problems = %
- Poor concentration = %
- Grammar problems (constructing sentences suddenly becomes a puzzle) = 1
- Short term memory loss (temporary) = %
- Motivation in general is being lowered and often completely wiped out = %
- I become someone without personality = %
- Accelerated Bowel movement, loose stools and sometimes diarrhea = X
- It amplifies my food intolerance/sensitivity = X
- Decreased digestion = X
- A sense of being full (digestion) = X
- Fasciculations = X
- Itching = X
- Soar Throat = X
- Decreased accuracy of handwriting ,also problems with controlling videogames like aiming in FPS = 1
- Faster spreading of local fungal skin infection at feet in POIS = X

So there are two points that are interesting here:
1- It seems that I do not suffer from Physical symptoms, or let's say that they are not really that extreme, possible explanation? Perhaps endothelial leaks vary from person to person?
2- I still suffer from cognitive symptoms, which can mean that this treatment is not enough to reduce Endothelial permeability enough so that an inflammatory response doesn't happen in the brain. Any suggestions for better cognitive relief? Also what do you guys think of all of this?
Title: Re: Ideas on Endothelial Dysfunction
Post by: dizzy on July 16, 2018, 12:19:21 PM
Do you have tension in the jaw (clenching/bruxism)? I'm getting some good results in the speech/articulation department by simply keeping my jaw relaxed during the day. (I say "simply", but it's not that simple actually, and really requires and effort. But for me the effect is remarkable.)
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 16, 2018, 12:46:05 PM
Do you have tension in the jaw (clenching/bruxism)? I'm getting some good results in the speech/articulation department by simply keeping my jaw relaxed during the day. (I say "simply", but it's not that simple actually, and really requires and effort. But for me the effect is remarkable.)
No, and probably it's not that simple in my case lol.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 16, 2018, 01:39:55 PM
What strategies you use dizzy?  I clench my teeth only when I am real angry so I say once every day I clench my teeth and fist, is that same as bruxism?

Do you have tension in the jaw (clenching/bruxism)? I'm getting some good results in the speech/articulation department by simply keeping my jaw relaxed during the day. (I say "simply", but it's not that simple actually, and really requires and effort. But for me the effect is remarkable.)
Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on July 16, 2018, 03:19:19 PM
Look at this:

Bioflavonoids, the diosmin with hesperidin, promote increased resistance of the vascular wall of the vein, with decreased capillary permeability. Clinical and experimental studies suggest that the association of diosmin with hesperidin potentiates the action of noradrenaline in the cellular receptors of the veins, potentiating vasoconstricting action (1), acting as a phlebotropic agent and vascular protector, improving venous tone and lymphatic drainage, reducing the capillary permeability and protecting the microcirculation of inflammatory processes (2,3,4). By reducing the expression of some molecules of endothelial adhesion (5), they inhibit the activation, migration and adhesion of leukocytes at the capillary level (6,7). This causes a reduction in the release of inflammatory mediators, such as free radicals of oxygen, prostaglandins and thromboxane, resulting in reduction in capillary permeability (6,8).

1. Araújo, M.:”Farmacoterapia das Doenças Vasculares Periféricas” Angiologia e Cirurgia Vascular: guia ilustrado pgs 1-13 2003 disponível em www.lava.med.br/livro .

2. Struckmann JR, Nicolaides AN. Flavonoids: a review of the pharmacology and therapeutic efficacy of MPFF 500 mg in patients with chronic venous insufficiency and related disorders. Angiology 1994 Jun 45 (6): 419-28.

3. Daftary SN, Irani JS, Tsouderos Y: “The Therapeutic Activity of Micronized Flavonoid Fraction in IUCD-induced bleeding” Drugs of Today vol 31 (suppl. E) 41-45 1995

4. Bouskela E, Cyrino FZGA, Lerond L. Leukocyte adhesion after oxidant challenge in the hamster cheek pouch microcirculation. J Vasc Res 1999 36 Suppl. 1: 11-4.

5. Korthuis RJ, Gute DC. Adhesion molecule expression in postischemic microvascular dysfunction: activity of a micronized purified flavonoid fraction. J Vasc Res 1999 36 Suppl. 1: 15-23.

6. Damon M, Flandre O, Michael F, et al. Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in the rat: study of prostaglandin E2 and F2a and thromboxane B2 release and histological changes, Arzneimittelforschung 1987 Oct 37 (10): 1149-53

7. Lonchampt M, Guardiola B, Sicot N, et al. Protective effect of a purified flavonoid fraction against-reactive oxygen radicals: in vivo and in vitro study. Arzneimittelforschung 1989 Aug 39 (8): 882-5.

8. Boccalon, H., et al.: “Therapeutic Equivalence of Two Dosage Forms of a Micronized Flavonoid Fraction in Patients with Chronic Venous Insufficiency” Current Therapeutic Research vol 57 (10) 1996.

Jean T, Bodinier MC. Mediators involved in inflammation: effects of MPFF 500 mg on their release. Angiology 1994 Jun 45 (6 Pt 2): 554-9
Title: Re: Ideas on Endothelial Dysfunction
Post by: Quantum on July 16, 2018, 04:11:50 PM
Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

Hi Nas,

20mg of propranolol is a high a dose for someone who has a normal blood pressure and normal heart rate to begin with, and therefore, hypotension and bradychardia are quite possible outcome to watch for.  Two of the main effects of propranolol is that it lowers blood pressure, and, it slows down the heart rate  ( it his an antihypertensive drug, as well as a beta-blocker, which all slow down the heart rhythm in a very significant way).

With prescription drugs, more is not necessarily better.  The usual aim is to find the lower efficient dosage.

Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 16, 2018, 04:42:26 PM
Thank you Fernando for this suggestion,
I don't think Hesperidin is available in my country and Diosmin is hard to find.
But overall that's exactly the drug I'm looking for; a drug that can in crease the resistance of the vascular wall and thus reduce permeability.
The thing is there is really isn't that many medications that are readily available for this job, I've searched many times but I still can't pin point one readily available drug. If you guys find any please share it with us.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 16, 2018, 04:45:13 PM
Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

Hi Nas,

20mg of propranolol is a high a dose for someone who has a normal blood pressure and normal heart rate to begin with, and therefore, hypotension and bradychardia are quite possible outcome to watch for.  Two of the main effects of propranolol is that it lowers blood pressure, and, it slows down the heart rate  ( it his an antihypertensive drug, as well as a beta-blocker, which all slow down the heart rhythm in a very significant way).

With prescription drugs, more is not necessarily better.  The usual aim is to find the lower efficient dosage.

Yes, that's where I messed up thank you for pointing it out Quantum.
Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on July 17, 2018, 09:22:03 AM
Nas

I do not believe that Hesperidin with Diosmin is such a powerful remedy. Here in Brazil it is sold under the names of Flavonid, Daflon and Diosmin. But it is also possible to get in pharmacy handling. It is a remedy used for varicose veins.
I believe that potent vasoconstriction we get with caffeine and pseudoephedrine.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 19, 2018, 04:45:40 PM
Fernando you have any solution for Voice fatigue?   I wake up in morning with a perfect crisp voice and people can hear me even at lower volume.  But then middle of day something happen and my voice gets muffled as if someone stuffed something in my mouth and people have hard time hearing me and I have to speak very loud and I feel if I am straining or shouting.   Sleep is very important and it does something because as experiment if I dont sleep my voice stays muffled through morning.
Title: Re: Ideas on Endothelial Dysfunction
Post by: FernandoPOIS on July 20, 2018, 07:39:42 AM
I'm a physiotherapist and I do not have much knowledge about voice problems.

But we can imagine something related to the functioning of the vagus nerve and inflammation. It is known that singing stimulates the vagus nerve. You may have chronic inflammation of the vocal cords. I had a similar problem a few years ago and had to take antibiotics and anti inflammatory (corticoid).

The sure thing is you consult an otolaryngologist who is an ear, nose and throat specialist. This doctor will be able to tell you what happens to your voice.
Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on July 20, 2018, 06:21:52 PM
Ok so I have tried a second round of Vasoconstrictor stack with an increase in some of the doses; I've taken 50mg Indomthacin, 20mg propanolol, 100mg Aspirin and 250 paracetamol, waited 45 minutes as usual and had an O. The result was different, in that while I believe there was a reduction, I'd say about 40%, I still suffered from usual symptoms like brain fog and speech issues. There were less fatigue and pain in the urethra and the genitals region and slightly clearer mind. Still, I was still annoyed from POIS symptoms so I decided to take another 25mg Indomethacin pill to see if it can clear my head a bit more, and it did, but at the same time it caused a huge decrease in blood pressure. I tested it and it was about 116/61 with a 55 heart beat rate, I took it on an empty stomach which is probably why there was a huge decrease in blood pressure. I stabilized my self later after breakfast and drinking salt water.
Overall I'd say that it still caused me POIS, with decreased symptoms.

I will try to give a more accurate prescription of symptoms using Muon's symptoms from his Muon's case post: http://poiscenter.com/forums/index.php?topic=2545.msg24545#msg24545

1= positive result ( had relief )
0= negative result ( did not have relief )
%= about 50% decrease
X= Do not suffer from this symptom

- Extreme fatigue = 1
- Muscle ache = 1
- Joint pain = X
- Exercise/motion intolerance = %
- Heavy body = 1
- Feeling cold/warm, feeling cold happens far more often than warm = 1
- Decreased endurance, especially with the duration of standing and sitting straight = 1
- Sensitive teeth = X
- Stinging pain at liver area = X
- Yellowing of facial skin = X
- Pale skin and facial skin becomes like a babyskin = X
- Decreased vocabulary = 0
- Articulation problems = %
- Poor concentration = %
- Grammar problems (constructing sentences suddenly becomes a puzzle) = 1
- Short term memory loss (temporary) = %
- Motivation in general is being lowered and often completely wiped out = %
- I become someone without personality = %
- Accelerated Bowel movement, loose stools and sometimes diarrhea = X
- It amplifies my food intolerance/sensitivity = X
- Decreased digestion = X
- A sense of being full (digestion) = X
- Fasciculations = X
- Itching = X
- Soar Throat = X
- Decreased accuracy of handwriting ,also problems with controlling videogames like aiming in FPS = 1
- Faster spreading of local fungal skin infection at feet in POIS = X

So there are two points that are interesting here:
1- It seems that I do not suffer from Physical symptoms, or let's say that they are not really that extreme, possible explanation? Perhaps endothelial leaks vary from person to person?
2- I still suffer from cognitive symptoms, which can mean that this treatment is not enough to reduce Endothelial permeability enough so that an inflammatory response doesn't happen in the brain. Any suggestions for better cognitive relief? Also what do you guys think of all of this?
Hi Nas,
 You might be interested in this article on anti-oxidants.
Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide (http://www.pnas.org/content/103/1/218)
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 20, 2018, 11:17:35 PM
nanna1, fernando or anyone on this forum, do you anyone here has a white film like thing in the inside of your mouth, inner part of the lips?.   This is rare, but I am thinking maybe we poisers have this white film called epithelial hyperplasia or hyperkeratosis?.  Background:  My vocal cords are always inflamed and red from time immemorial.  I also have had sore throat that gets worse during POIS since childhood.  I spent close to $15,000 with Gastro and Otolaryngologist they did some studies and procedures few years back and came to conclusions (no acid reflux, no GERD, no LPR, no H. Pylori, no barretts esophaegal cancer they initially all suspected) and lol referred me to psychiatrist for depression.   I dont have a good insurance at moment.  My dentist today is still concerned and points me to this white film I have.  She says it is epithelial hyperplasia and hyperkeratosis which could be due to a virus or some immune reaction.  My first inclination is its HPV since I do have 2-3 warts on my feet sole since last 10 yrs.

I looked up Wikepedia and it says:
The causative agent implicated is Epstein-Barr virus, the same virus that causes infectious mononucleosis (glandular fever). After the primary EBV infection has been overcome, the virus will persist for the rest of the host's life and "hides" from the immune system by latent infection of B lymphocytes.[5] The virus also causes lytic infection in the oropharynx, but is kept in check by a normal, functioning immune system. Uncontrolled lytic infection is manifested as Oral Hairy Leukoplakia (OHL) in immunocompromised hosts. OHL usually arises where the immunocompromise is secondary to HIV/AIDS.[4] Rarely are other causes of immunocompromise associated with OHL, but it has been reported in people who have received transplants and are taking immunosuppressive medication. OHL may also accompany chronic graft versus host disease.[6] Even more rare are reports of OHL in persons with competent immune systems

The white lesion cannot be wiped away,[6] unlike some other common oral white lesions, e.g. pseudomembranous candidiasis, and this may aid in the diagnosis. Diagnosis of OHL is mainly clinical, but can be supported by proof of EBV in the lesion (achieved by in situ hybridization, polymerase chain reaction, immunohistochemistry, Southern blotting, or electron microscopy) and HIV serotesting.[6] When clinical appearance alone is used to diagnose OHL, there is a false positive rate of 17% compared to more objective methods.[7] The appearance of OHL in a person who is known to be infected with HIV does not usually require further diagnostic tests as the association is well known. OHL in persons with no known cause of immunocompromise usually triggers investigations to look for an underlying cause. If tissue biopsy is carried out, the histopathologic appearance is of hyperplastic and parakeratinized epithelium, with "balloon cells" (lightly staining cells) in the upper stratum spinosum and "nuclear beading" in the superficial layers (scattered cells with peripheral margination of chromatin and clear nuclei, created by displacement of chromatin to the peripheral nucleus by EBV replication). Candida usually is seen growing in the parakeratin layer.   I dont have HIV, I was tested.

Another article points me to: "Focal epithelial hyperplasia is a rare contagious disease caused by human papilloma virus".  https://www.hindawi.com/journals/crid/2013/871306/

To simply postulate, I might have EBV, HPV and maybe also Candida in my throat despite fact Otolor.  didn't do anything about it and wrote biopsies are normal.   I suspect they didn't test for these viruses as they were focused on Barrets and GERD etc.  I am currently taking Berberine 1000mg daily since last 3 days and since this morning in POIS.   I dont believe Berberine has helped though I would continue it for 3-4 weeks.  I am in full-blown POIS currently minus some relief that I get from supplement protocol.  But my point is, wouldn't Berberine be taking care in the event this white film is indeed Candida?  What there be a supplement for this HPV, EBV and Candida in general or this requires Rx med?  I currently take daily:  Adderall, Multi-vitamin with Minerals, Liposomal Glutathione and Vitamin C.  And few days prior to POIS I start:  NAC, ALA, B-Vitamins, Vit-D3, Vit-E, Olive Leaf Extract (for Luteolin) and now Berberine.

Update: I was hopeful on Berberine, since Echinicea and Goldenseal do provide me some relief and Berberine is a constituent of Goldenseal.  The longest anything that has worked on me is Liposomol Glutathione and Vit C for 6-7 times with a 100% relief but then stopped working.  Mineral supplementation to 100% DV like Zn, Cu  has not changed much, maybe I need higher values?     
Title: Re: Ideas on Endothelial Dysfunction
Post by: dizzy on July 22, 2018, 10:59:35 AM
@Swell,

I think I had the same problem as you, Swell, with the voice fatigue. I traced it back to a tight jaw. I'm using these techniques:

1. I relax the jaw as often as I can.

2. I'm doing the Wim Hof breathing exercise several times a day (lookup FloppyBanana's post about this on this forum).

3. When speaking, I'm making the upper back wider (this is a singing technique).

4. Magnesium glycinate and vitamin B2 help me with tension headache, and this also makes it easier for me to do the relaxation of the jaw.

5. While at it, I'm also relaxing the cranium, because this makes me feel overall more relaxed. Also helpful while speaking.

6. You may want to do sit-ups and look for exercises on youtube to strengthen the scalene and sternocleidomastoid muscles.

7. Watch out for forward-head posture, it kills the voice.

8. Don't overdo any strength-exercises, as they may create tension which you want to avoid for a good voice.

It takes a real effort, but in my case these rules have been very helpful so far.

By the way, also make sure you don't have (silent) stomach acid reflux, because it may cause vocal chord problems. An ENT doctor can tell easily by using a scope.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 22, 2018, 01:46:48 PM
HPV replicates in the epithelium. Might be interesting to test these for the oral epithelium.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 23, 2018, 03:34:41 PM
Thank you Dizzy.  Thank you Muon.  Muon would you know if HPV can be treated in the oral epithelium.  Since I dont have access to testing maybe I can try a supplement to see if my throat/vocal cord symptom improve
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on July 23, 2018, 03:45:54 PM
I have no idea, haven't looked into it though. Try to google it. But the first step should be to check if HPV plays a role. Someone should explore this option to rule out HPV involvement.
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 23, 2018, 08:43:34 PM
Was just messing.  With medical docs there is no effective treatment for epithelial HPV etc.  There are vaccines that are still being 'researched' (pun intended) and they are not effective for over 21 anyway.   There are adjunct treatments laser that cuts through HPV affected tissue growths etc, but they are all localised treatments not useful unless cancerous, so nothing that can benefit a systemic problem acrossbody like POIS.  I dont think our POIS solution lies with docs its really chemistry, biomolecular practitioners that will if provide any breakthrough.


I have no idea, haven't looked into it though. Try to google it. But the first step should be to check if HPV plays a role. Someone should explore this option to rule out HPV involvement.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 24, 2018, 04:31:19 PM
Hello guys,
Sorry for being absent from this forum, Iraq had been experiencing heavy protests and our "democratic government" decided to shut down internet access completely ( Thanks America! ) and not until lately have we had the chance of accessing internet through VPN.
So meanwhile I've been thinking about POIS and this theory, and one of the things that still baffle me is how are the brain and the reproductive system correlate to get us to have symptoms in both of those regions.
My theory comes down to that there are Epithelial leaks in the Urethra that causes the semen to leak into blood, then the immune system starts attacking the sperm component.
My only question remaining is: What's next? How do symptoms form? Does these sperm cells ( Or what ever is causing this auto-immune response ) inter the brain through the BBB? Do they enter other endotheliums and epitheliums causing the rest of the Physical symptoms?
So in order to confirm all of these suspicions, the following questions need to be answered:
1- Do you guys experience chronic Urethral inflammation? Pain or difficulty in peeing?
2- If semen or a semen components enters the blood stream, doesn't that mean that they are testable or observable in blood samples? Have you guys ever looked for semen or sperms in your blood right after ejaculation?
I think question 2 is very important when it comes to confirming this theory, if we do not find any traces then this theory is most likely incorrect, if anyone is able to make this test please let us know your results.
Thank you. 
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 25, 2018, 04:44:35 PM

Acetylcholine released by endothelial cells facilitates flow‐mediated dilatation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157078/):

"Circulating blood generates frictional forces (shear stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow‐mediated dilatation."

"we show that the endothelium responds to flow by releasing ACh. Once liberated, ACh acts to trigger calcium release from the internal store in endothelial cells, nitric oxide production and artery relaxation."

Memeber ThisType Said that he did a genetic test and found mutations in these regions:
rs16969968 Nicotinic Acetylcholine Receptors
rs1051730 Nicotinic Acetylcholine Receptors
rs1824024 Muscarinic Acetylcholine Receptors. Ref (http://poiscenter.com/forums/index.php?topic=2684.msg23944#msg23944)

Hmmm, perhaps the Acetylcholine deficiency causes problems in Endothelial signaling?
Title: Re: Ideas on Endothelial Dysfunction
Post by: b_jim on July 27, 2018, 02:51:03 PM
Brilliant. But why the delay ? I feel 50% muscular energy loss on day 2, not just after orgasm. Is choline loss with semen causing Ach defiency 24h later ?
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 27, 2018, 07:01:54 PM
Brilliant. But why the delay ? I feel 50% muscular energy loss on day 2, not just after orgasm. Is choline loss with semen causing Ach defiency 24h later ?
I don't know man, this illness is so confusing and nothing works for me and I just keep theorizing but reaching nothing, I so feel done with this crap.
Title: Re: Ideas on Endothelial Dysfunction
Post by: dizzy on July 28, 2018, 02:56:07 PM
Quote
I don't know man, this illness is so confusing and nothing works for me and I just keep theorizing but reaching nothing, I so feel done with this crap.

I've been theorizing about my own situation, and perhaps there is a connection with (sex/porn) addiction, where the urge is delayed until day 2, because that's sort of when libido fully restores. The urge may cause the muscle problems. (?)

Not sure how that would be explained in terms of biochemistry though.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 28, 2018, 04:21:01 PM
Quote
I don't know man, this illness is so confusing and nothing works for me and I just keep theorizing but reaching nothing, I so feel done with this crap.

I've been theorizing about my own situation, and perhaps there is a connection with (sex/porn) addiction, where the urge is delayed until day 2, because that's sort of when libido fully restores. The urge may cause the muscle problems. (?)

Not sure how that would be explained in terms of biochemistry though.

 Nah I don't think so, there are alot of people suffering from sex/porn addiction without having their genitals on flames after they done ejaculating. It's clearly and immune response to what ever is immunogenic. 
Title: Re: Ideas on Endothelial Dysfunction
Post by: swell on July 28, 2018, 06:01:46 PM
My problems also show at right about the 24th hour.  Its creepy why the heck symptoms dont begin right away.  My 7th day will be tomorrow I am already celebrating for tomorrow to come.   So much relief is on the way.   

Brilliant. But why the delay ? I feel 50% muscular energy loss on day 2, not just after orgasm. Is choline loss with semen causing Ach defiency 24h later ?
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on July 28, 2018, 06:41:23 PM
My problems also show at right about the 24th hour.  Its creepy why the heck symptoms dont begin right away.  My 7th day will be tomorrow I am already celebrating for tomorrow to come.   So much relief is on the way.   

Brilliant. But why the delay ? I feel 50% muscular energy loss on day 2, not just after orgasm. Is choline loss with semen causing Ach defiency 24h later ?

In my case my cognitive symptoms start immediately and they build up for full hour. Then there are other symptoms that take time to appear, they are usually psychological and emotional; at about day 2 of POIS I start feeling down and I start getting attacked by pure OCD thoughts that either make me panic or more depressed. I think this has to do with how neurotransmitters are effected by brain inflammation.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on August 30, 2018, 06:26:47 PM
So one of the things we need to investigate is, what happens at the Urethra during ejaculation? Does the body attack semen that is stuck to the walls of the urethra and cause a sensitive reaction? Or is there a leak that causes semen to diffuse through the urethra and spread into blood and pass through multiple organs causing an either: 1) Allergic reaction 2) The body tries to get rid of this diffused semen but it faces difficulties and thus it gets stuck in a sarcoidosis like state 3) an auto-immune response ( I don't know because I can't tell from Muon's tests what he actually has, I wish his doctors would figure it out but apparently Muon seems to be meeting one of the worst doctors out there lol, ok that's not fair since non of them know about POIS but perhaps if they knew some stuff about POIS they would be able to tell? ).

What I also like to mention that it could be a case where every person who suffers from POIS can a have a totally different type of immune response to leaked out semen. This would explain why different treatment methods work specifically for some while it completely fails for others.

So any creative ideas to see if we can test for that? I would really appreciate your suggestions.

Thanks!
Title: Re: Ideas on Endothelial Dysfunction
Post by: Vandemolen on August 30, 2018, 08:49:04 PM
I have a small cyst near my testicles. My theory was that after ejaculation a small amount of semen stays there and that’s the cause of my UTI or/and my POIS. But my urologist doesn’t think so. He said the cyst is small.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on August 30, 2018, 10:37:38 PM
I have a small cyst near my testicles. My theory was that after ejaculation a small amount of semen stays there and that’s the cause of my UTI or/and my POIS. But my urologist doesn’t think so. He said the cyst is small.

Which is most likely correct. I don't speculate POIS occurs in the testicles region rather at the urethra.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on January 11, 2019, 10:14:47 AM
Low Testosterone Level Is an Independent Determinant of Endothelial Dysfunction in Men (https://www.nature.com/articles/hr2007144)

''In conclusion, a low plasma testosterone level was associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium.''

Since we have a bunch of members with low testosterone, there is a chance they could have an endothelial dysfunction as well.
People using TRT could be modulating their endothelial function. If this is the case and POIS symptoms improve then could POIS be related to an endothelial dysfunction? More food for thought.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on January 11, 2019, 10:32:43 AM
Low Testosterone Level Is an Independent Determinant of Endothelial Dysfunction in Men (https://www.nature.com/articles/hr2007144)

''In conclusion, a low plasma testosterone level was associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium.''

Since we have a bunch of members with low testosterone, there is a chance they could have an endothelial dysfunction as well.
People using TRT could be modulating their endothelial function. If this is the case and POIS symptoms improve then could POIS be related to an endothelial dysfunction? More food for thought.
Could NO dysfunction = weak pelvic muscles, thus = PE ?
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on January 11, 2019, 10:51:38 AM
Could NO dysfunction = weak pelvic muscles, thus = PE ?
NO dysfunction could be responsible for hyperexcitatory disturbances of ejaculation (premature ejaculation). Here is a paper my POIS doctor gave me a long time ago: https://www.ncbi.nlm.nih.gov/pubmed/12597985 These kind of drugs may have an effect on PE.
Endothelial dysfunction could indicate problems relating to NO/acetylcholine cycles. We need FMD testing and if these are positive then this could be an indication to look further into NO and/or acetylcholine.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on January 11, 2019, 11:35:24 AM
Could NO dysfunction = weak pelvic muscles, thus = PE ?
NO dysfunction could be responsible for hyperexcitatory disturbances of ejaculation (premature ejaculation). Here is a paper my POIS doctor gave me a long time ago: https://www.ncbi.nlm.nih.gov/pubmed/12597985 These kind of drugs may have an effect on PE.
Endothelial dysfunction could indicate problems relating to NO/acetylcholine cycles. We need FMD testing and if these are positive then this could be an indication to look further into NO and/or acetylcholine.
Nitric-oxide donating drugs could be a good way of testing the role of NO on POIS. My deduction of its role, is probably related to our PE problems, the question is whether it is a fundamental issue in POIS, or just another symptom of the hyperactive immune-response in POIS.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Vandemolen on January 11, 2019, 11:42:10 AM
Could NO dysfunction = weak pelvic muscles, thus = PE ?
NO dysfunction could be responsible for hyperexcitatory disturbances of ejaculation (premature ejaculation). Here is a paper my POIS doctor gave me a long time ago: https://www.ncbi.nlm.nih.gov/pubmed/12597985 These kind of drugs may have an effect on PE.
Endothelial dysfunction could indicate problems relating to NO/acetylcholine cycles. We need FMD testing and if these are positive then this could be an indication to look further into NO and/or acetylcholine.
Nitric-oxide donating drugs could be a good way of testing the role of NO on POIS. My deduction of its role, is probably related to our PE problems, the question is whether it is a fundamental issue in POIS, or just another symptom of the hyperactive immune-response in POIS.
The question is why some POIS-patients have PE and others do not. I can last for hours. One time more than 4 hours. And is PE connected to POIS? We think so because the majority of the POIS-patients in the first Waldinger-paper have PE. When I came to this forum and before on the Naked Scientist Forum I discovered there are a lot of other men who do not have PE. The same for prostate/bladder problems. I have that problem. So I thought it was connected with POIS. But a lot of members here do not have those problems.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on January 11, 2019, 11:55:58 AM
Guys, the bottom line is; We will need testing/research, these will give us answers. Without research, we will continue to speculate in circles for years here on this forum.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on January 11, 2019, 11:58:26 AM
Guys, the bottom line is; We will need testing/research, these will give us answers. Without research, we will continue to speculate in circles for years here on this forum.
I'm getting NO supplements soon, that'll be my part.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on January 11, 2019, 12:08:13 PM
Guys, the bottom line is; We will need testing/research, these will give us answers. Without research, we will continue to speculate in circles for years here on this forum.
I'm getting NO supplements soon, that'll be my part.
I have read something about it that it's not known whether taking them in supplement form can also have an impact on NO synthesis. The drugs stated in the paper are different than the 'NO' supplements which you can buy in store.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on January 11, 2019, 12:51:07 PM
So one of the biggest mysteries about POIS that I just simply cannot decipher, is the type of immune response that is suggested to cause the symptoms. On one hand, Waldinger tested positive for semen prick tests, but is this an indication of auto-immune disease? In that I question, whether normal people also can test positive for semen prick test without having POIS? Then I ask about the type of immune response in POIS, if it is MCAS related, then why does usual MCAS treatment which comprises of anti-histamine treatment not work for me? When I try to think about possible reasons I can not find any other explanation to MCAS. Yet when I ask MCAS sufferers who suffer from Neuropsychiatric symptoms about what they take as remedy they say that usual MCAS treatment gave them back their brain, yet it clearly fails in my case. In fact I question if there was an immune response at all?
I know that Muon always suggests doing tests but where have tests lead us so far? We need a better theoretical frame to base our tests on. Currently I find the Mast Cell theory to be the most testable of the other theories. But I find that the lack of effect the MCAS treatment regiment had on me is starting to give me doubts. This illness is nothing less than a curse, one that is more seen in the world of the metaphysical. Sigh.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on January 22, 2019, 10:28:22 AM
Nebivolol: The Somewhat-Different β-Adrenergic Receptor Blocker (https://www.sciencedirect.com/science/article/pii/S0735109709024310?via%3Dihub)

Comparison of Beta blockers on endothelial function (https://www.sciencedirect.com/science/article/pii/S0735109709024310?via%3Dihub#tbl2)

''In conclusion, nebivolol has beneficial effects on endothelial function mainly by increasing NO bioavailability.''
Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of β‐Blockers? (https://onlinelibrary.wiley.com/doi/full/10.1111/jch.12856)
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on January 22, 2019, 10:34:39 AM
Nebivolol: The Somewhat-Different β-Adrenergic Receptor Blocker (https://www.sciencedirect.com/science/article/pii/S0735109709024310?via%3Dihub)

Comparison of Beta blockers on endothelial function (https://www.sciencedirect.com/science/article/pii/S0735109709024310?via%3Dihub#tbl2)

''In conclusion, nebivolol has beneficial effects on endothelial function mainly by increasing NO bioavailability.''
Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of β‐Blockers? (https://onlinelibrary.wiley.com/doi/full/10.1111/jch.12856)
Again, I'm not really sure about this, wouldn't lowering the blood pressure be bad for POTS? If not it would also be bad for inflammation? Since more vasodilation means more penetration?
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on January 22, 2019, 10:47:24 AM
Again, I'm not really sure about this, wouldn't lowering the blood pressure be bad for POTS? If not it would also be bad for inflammation? Since more vasodilation means more penetration?

Nebivolol has beneficial effects on endothelial function so I will place this here. There are always side effects involved with medicine. The point is whether these benefits are outweighing the negative side effects. This might be useful for people who want to increase NO bioavailability as well.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on January 22, 2019, 10:54:33 AM
Again, I'm not really sure about this, wouldn't lowering the blood pressure be bad for POTS? If not it would also be bad for inflammation? Since more vasodilation means more penetration?

Nebivolol has beneficial effects on endothelial function so I will place this here. There are always side effects involved with medicine. The point is whether these benefits are outweighing the negative side effects. This might be useful for people who want to increase NO bioavailability as well.
Good point, I might give it a try.
Title: Re: Ideas on Endothelial Dysfunction
Post by: nanna1 on January 25, 2019, 12:02:04 AM
"This study shows that CMV-seropositive individuals have endothelial dysfunction and impaired responses to nitric oxide (NO). This association was independent of conventional risk factors and may be associated with increased atherosclerosis burden." -Human cytomegalovirus seropositivity is associated with impaired vascular function (2003) (https://www.ncbi.nlm.nih.gov/pubmed/12900349)
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on November 20, 2019, 12:01:06 PM
I am still annoyed that this has not been tested on me. NO defects can play a role in POTS and premature ejaculation. I got both but this has never been tested.  Endothelial dysfunction can be an indication for NO related issues. Nothing is being done.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Nas on November 20, 2019, 12:29:56 PM
I am still annoyed that this has not been tested on me. NO defects can play a role in POTS and premature ejaculation. I got both but this has never been tested.  Endothelial dysfunction can be an indication for NO related issues. Nothing is being done.
Can't you do tests your self?
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on November 20, 2019, 12:33:54 PM
I am still annoyed that this has not been tested on me. NO defects can play a role in POTS and premature ejaculation. I got both but this has never been tested.  Endothelial dysfunction can be an indication for NO related issues. Nothing is being done.
Can't you do tests your self?
Can't find any labs that offer these kind of FMD tests.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Hopeoneday on November 25, 2019, 01:48:29 PM
What obout epithelial in gen..uri trackt?

The epithelial lining of the male urethra changes from transitional epithelium at the bladder end to pseudostratified epithelium through prostatic, membranous and most of penile urethra, eventually changing to nonkeratinizing stratified squamous epithelium distally.

Connected to Muons post about b-defensin-2

b-defensin-2 concetons with poisers:

Defensins are a family of antimicrobial peptides that form part of the innate and adaptive immune system and constitute the first line of host defense against microorganisms. It has shown the broad antimicrobial activity spectrum against bacteria, fungi and viruses [1, 24].


Expression and regulation of b-defensin-2
https://www.intechopen.com/books/immune-response-activation-and-immunomodulation/multifunctional-activity-of-the-defensin-2-during-respiratory-infections

HBD2 is expressed mainly in all the epithelia of human body (respiratory, digestive, UROGENITAL, conjunctive epithelium), mucous, peripheral blood and skin.

Vit D , activation tru vit D receptors (vit D helped a lot poisers)
https://www.intechopen.com/books/immune-response-activation-and-immunomodulation/multifunctional-activity-of-the-defensin-2-during-respiratory-infections


Multifunctional activities of b-defensin-2

Antimicrobial activities
https://www.intechopen.com/books/immune-response-activation-and-immunomodulation/multifunctional-activity-of-the-defensin-2-during-respiratory-infections


Innate and adaptive immunity (Nana1 mentioned)
https://www.intechopen.com/books/immune-response-activation-and-immunomodulation/multifunctional-activity-of-the-defensin-2-during-respiratory-infections

Neutrophils(low in poisers), dexamethasone(helped Nas),
isoleucine(helped Swell-growt factor , isoleucin is cruciall for epithelium..)
https://www.intechopen.com/books/immune-response-activation-and-immunomodulation/multifunctional-activity-of-the-defensin-2-during-respiratory-infections

Cytokines and chemokines tru IL6
https://www.intechopen.com/books/immune-response-activation-and-immunomodulation/multifunctional-activity-of-the-defensin-2-during-respiratory-infections




Inflamation and antiinflamatory activity -imunomdulatory...
https://www.intechopen.com/books/immune-response-activation-and-immunomodulation/multifunctional-activity-of-the-defensin-2-during-respiratory-infections




Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on November 25, 2019, 02:00:56 PM
Yes we need more people testing this. Me and my brother's IL-8 can stem from the same source as BD-2. BD-2 can downregulate some cytokines which are needed for anti-fungal actions like IL-17 and upregulate IFN-g. These fungals can deplete tryptophan via Kyn. Leading to a depletion of serotonin. In theory it could affect brain neurotransmitters. People suspecting gut inflammation should consider this.
Title: Re: Ideas on Endothelial Dysfunction
Post by: Muon on December 19, 2020, 04:28:08 PM
Nebivolol: The Somewhat-Different ?-Adrenergic Receptor Blocker (https://www.sciencedirect.com/science/article/pii/S0735109709024310?via%3Dihub)

Comparison of Beta blockers on endothelial function (https://www.sciencedirect.com/science/article/pii/S0735109709024310?via%3Dihub#tbl2)

''In conclusion, nebivolol has beneficial effects on endothelial function mainly by increasing NO bioavailability.''
Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of ??Blockers? (https://onlinelibrary.wiley.com/doi/full/10.1111/jch.12856)

https://www.thenakedscientists.com/forum/index.php?topic=6576.msg364692#msg364692

"Great! That should be helpful. However, metropolol can cause erectile dysfuntion, while nebivolol doesn't: http://www.ncbi.nlm.nih.gov/pubmed/17324145

I think both Nebivolol (B1 receptor blocker) and carvedilol (B1,B2 and Alpha1 blocker) are very good at Nitric Oxide Release, specially Nebivolol:

http://circ.ahajournals.org/content/107/21/2747.short
http://www.sciencedirect.com/science/article/pii/S1089860308000426
"

"Both, Valsartan and Nebivolol seem to improve Nitric Oxide, and have fewer side effects than others."