POISCENTER
POIS Cause/Treatment Discussions => Auto-Immune Causes and Treatments => Topic started by: Muon on February 17, 2019, 01:55:22 PM
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Discussion about hypersensitivity in POIS. https://en.wikipedia.org/wiki/Hypersensitivity
A quote from Waldinger's paper: ''The combination of allergic and systemic flu-like reactions post-ejaculation together with a positive skin-prick test in the majority of males underscores the hypothesis of an "immunogenic" etiology of POIS, e.g., that POIS is caused by Type-1 and Type-IV allergy to the males' own semen, as soon it is triggered by ejaculation.'' https://www.ncbi.nlm.nih.gov/pubmed/21241453
Didn't he mean a type I hypersensitivity, which is an allergy, and type IV hypersensitivty (which is not an allergy)? A type IV hypersensitivity reaction takes place over the course of days and is of the delayed type and is not mediated by antibodies. Type IV hypersensitivity is mediated by T-cells. Th1 cells and interferon gamma are involved in such reactions. Macrophages could produce hydrolytic enzymes like, for example, acetylcholinesterase: https://en.wikipedia.org/wiki/Type_IV_hypersensitivity
Now when you look at my case you will notice the following:
1) IFN-g decreases after orgasm
2) IFN-g has increased 24 hours after orgasm if you compare the value before orgasm and 24h after
I do think point 1 might be a natural process which is related to orgasm and competes with the tendency of IFN-g to increase due to POIS. On short term after orgasm point 1 may dominate point 2, meaning a decreasing trend. As time goes by this may switch up and be reversed, meaning a dominant increasing trend. Orgasm itself might interfere with type IV Hypersensitivity measurements shortly after orgasm.
09-07-2015 (https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+1-1+Th1Th2%2BInflammation+markers+9%2610-07-2015.pdf): IFN-g (Th1) 1806 pg/ml RR: 374 - 1660 pg/ml (just before orgasm)
10-07-2015 (https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+1-1+Th1Th2%2BInflammation+markers+9%2610-07-2015.pdf): IFN-g (Th1) 1965 pg/ml RR: 374 - 1660 pg/ml (24h later relative to the 09-07-2015 data point, after orgasm)
13-08-2015 (https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+2-1+Th1Th2+part2-1%2BIL-8%2BIgGsub%2BIgE+13-08-2015.pdf): IFN-g (Th1) 1315 pg/ml RR: 374 - 1660 pg/ml (just before orgasm)
14-08-2015 (https://www.dropbox.com/sh/nc2dt6pcwd5xpmu/AACyyDE6uhY1DHn1fAuxw86Ja?dl=0&preview=Muon+3-6+Th1Th2+part2-4%2BIL4gen+14-08-2015.pdf): IFN-g (Th1) 3053 pg/ml RR: 374 - 1660 pg/ml (24h later relative to the 13-08-2015 data point, after orgasm)
When looking at the data, it's possible IFN-g is still rising >24h after orgasm meaning it should be measured longer than I have done. My brother has measured Interferon gamma only once, which doesn't tell us anything about its dynamics in time. Suggestion for POIS research: IFN-g measurements during an interval of just before orgasm up to a few days after orgasm. Different subtypes can be distinguished, see below.
Subtype IVa: with Th1 and monocyte directed and cytokines: IFNgamma, IL-1, IL-2.
Subtype IVb: with Th2 and eosinophils directed and cytokines: L-5, IL-4, IL-13.
Subtype IVc: with T CD8+ directed and cytokines: perforin, granzyme B, Fas Ligand.
Subtype IVd: with T CD4+, CD8+ and neutrophil directed and cytokines: IL8, GM-CSF.
Source: [Type IV of hypersensitivity and its subtypes] (https://europepmc.org/abstract/med/18409354)
LTT and seminal fluid
The lymphocyte transformation test might be a method for measuring a cellular T-cell response to seminal fluid. Even more interesting is to combine this with gel electrophoresis.
https://www.imd-berlin.de/en/special-areas-of-competence/lymphocyte-transformation-test-ltt.html
https://en.wikipedia.org/wiki/Gel_electrophoresis
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That is interesting. Interferon-beta is a medicine that is used for MS-patients. But in your case your Interferon-gamma has rised after sex. So maybe it is not usefull? But if Interferon-beta brings the IFN-g down...
And Interferon-alfa is used against hepatitis.
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That is interesting. Interferon-bèta is a medicine that is used for MS-patients. But in your case your Interferon-gamma has rised after sex. So maybe it is not usefull? But if Interferon-bèta brings the IFN-g down...
And Interferon-alfa is used against hepatitis.
I don't understand a word of what you have said. Do you mean I can lower my IFN-g by injecting myself with another IFN type? Do you mean that MS is related to type IV by increased IFN-g so medicine used for MS might help against POIS? IFN-gamma has risen because my assumption in this thread is that POIS is a type IV hypersensitivity reaction. Btw I can't read those symbols you have typed after the word interferon, it doesn't show up for me, maybe you could use the words alpha, beta, gamma etc.
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Never mind. I just wanted to say that there are medicines with Interferon. But as I said it is useless because your level rised. And taking Interferon will only make the level higher.
But when I read Wikipedia I think Waldinger means type-4 hypersensitivity.
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Perfume allergy is also a type 4 allergy reaction. I have perfume allergy. It got it exactly at the same time I got POIS. I wonder if there are more POIS-patients who have a perfume allergy.
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Perfume allergy is also a type 4 allergy reaction. I have perfume allergy. It got it exactly at the same time I got POIS. I wonder if there are more POIS-patients who have a perfume allergy.
From my understanding a type IV hypersensitivity is not an allergy (someone should correct me if I'm wrong about that). I can react to parfums as well.
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Yes you are right. Perfume allergy is not the correct term, but a lot of people use this term. It is just a sensitivity to perfume. I also have this sensitivity to cigarette smoke. Before the smoke ban in The Netherlands I used to have red eyes and a runny nose after I visited a bar or a restaurant. So when Waldinger used type 4 in his paper then he meant that POiS-patients have a sensitivity to their own semen?
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Vandemolen, yes I do think Waldinger made a mistake for calling it a type 4 allergy in his paper instead of a type 4 hypersensitivity. An allergy assumes allergic mechanism where antibodies are involved, check the first wikipedia link for the distinction. The weird thing is that I can react to cigarette smoke as well but not consistently, it's quite variable.
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Check the Dutch Wikipedia about the term allergy. There are two kinds in type 4: one where T helper is involved and the delayed kind (perfume sensitivity).
https://nl.m.wikipedia.org/wiki/Allergie
In English (Google Translate):
https://translate.google.com/translate?hl=nl&sl=nl&tl=en&u=https%3A%2F%2Fnl.m.wikipedia.org%2Fwiki%2FAllergie
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I'm confused, so the dutch page tells us there are two type 4 hypersensitivity mechanisms, an allergic one and non-allergic one. The english page just calls it type 4 hypersensitivity and doesn't mention this. The Dutch wiki pages aren't always that accurate compared to the english versions though. I could be wrong about the terminology. What we can say is that there is no evidence for his type I allergy claim because there hasn't been a group study showing positive IgE results (a lot of patients have been tested for this outside of studies). Cytokines haven't been explored yet, these are playing a role in type 4 HS, so his type 4 claim could still be true. My data supports that possibility. Read the chapter about history: https://en.wikipedia.org/wiki/Allergy#History
Cytokines from mast cells and/or T-helper cells could be explored. Eosinophils could play a role in delayed phase reactions as well, so unique mediators from that cell type is something to think about in further POIS research.
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We shouldn't assume that POIS is type 4 hypersensitivity just by Wladinger's skin prick test; semen in the body is usually protected by many epithelial cells which is a different environment than a skin prick test's environment.
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We shouldn't assume that POIS is type 4 hypersensitivity just by Wladinger's skin prick test; semen in the body is usually protected by many epithelial cells which is a different environment than a skin prick test's environment.
You got to start somewhere. The duration of symptoms are in line with type 4 HS and some of them are 'allergic-like'. Aside from that my data could be an indication for this assumption. In my opinion this should be explored by a group study (cytokines), if this will give negative results we can scratch it of our list. I don't see a reason why you shouldn't explore this.
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You got to start somewhere. The duration of symptoms are in line with type 4 HS and some of them are 'allergic-like'. Aside from that my data could be an indication for this assumption. In my opinion this should be explored by a group study (cytokines), if this will give negative results we can scratch it of our list. I don't see a reason why you shouldn't explore this.
What intrigues me is the cause of the brain symptoms? If we have type 4 hypersensitivity, how does that lead to brain fog and cognitive issues? I think that's the main part of POIS that I'm trying to explore. Because I pretty much believe that the auto-immune part of POIS is close to unsolvable.
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Perfume allergy is also a type 4 allergy reaction. I have perfume allergy. It got it exactly at the same time I got POIS. I wonder if there are more POIS-patients who have a perfume allergy.
Yes, I have perfume allergy. but only in POIS out of POIS the perfume smells good!!!
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What intrigues me is the cause of the brain symptoms? If we have type 4 hypersensitivity, how does that lead to brain fog and cognitive issues?
Th1 activation ---> interferon gamma release ---> increased macrophage activity ---> release of hydrolytic enzymes ---> affecting neurotransmitter metabolism ---> cognitive dysfunction
Perhaps POIS symptoms are being caused by the release of a bunch of enzymes damaging tissue which mimicks inflammation or altering enzyme activity in general.
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Perhaps POIS symptoms are being caused by the release of a bunch of enzymes damaging tissue which mimicks inflammation or altering enzyme activity in general.
Any idea on which possible enzymes? What do you think about cortisol?
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Perhaps POIS symptoms are being caused by the release of a bunch of enzymes damaging tissue which mimicks inflammation or altering enzyme activity in general.
Any idea on which possible enzymes? What do you think about cortisol?
I haven't looked into what types of enzymes macrophages are able to produce. As far as cognitive symptoms acetylcholinesterase. For joint pain, eye floaters, blood vessel wall integrity and neuroinflammation: https://en.m.wikipedia.org/wiki/Matrix_metalloproteinase
They can also produce Lp-PLA2 leading to cardiovascular problems. I haven't looked into cortisol related stuff. My aunt got elevated cortisol btw, she told me years ago that this was tested multiple times and always elevated. She has health problems as well.
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I have tried many Acetylcholine medications but they don't seem to work. About macrophages, you should also consider that this only happens in POIS; not when you have any other illness. I think that this is a crucial point if we want to figure out the cause of brain symptoms. I don't think it's brain inflammation since NSAID do little to nothing. It must be either neurotransmitters imbalance or potentially brain damage. I've read that cortisol can stimulate the production of white matter between neurons; hindering communication. I don't know if it applies to the almost instant reaction we get when we orgasm
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I have tried many Acetylcholine medications but they don't seem to work.
Like what?
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I have tried many Acetylcholine medications but they don't seem to work.
Like what?
Mestinon for example.
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Ok then it probably does not play a role in pois.
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Ok then it probably does not play a role in pois.
I've also tried L-Dopa and it seems to be good but it's not fundamental. I don't what we're missing or what what's happening to the brain but I think we can prevent it if we figure it out.
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I don't what we're missing or what what's happening to the brain but I think we can prevent it if we figure it out.
Good luck with that
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I don't what we're missing or what what's happening to the brain but I think we can prevent it if we figure it out.
Good luck with that
Why?
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I wished you good luck for trying to figure it out. I'm disengaging from this discussion because it's not leading to anything and I'm out of ideas. You may ask other people for their ideas on causes of brain related symptoms in pois.
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I wished you good luck for trying to figure it out. I'm disengaging from this discussion because it's not leading to anything and I'm out of ideas. You may ask other people for their ideas on causes of brain related symptoms in pois.
Oh, sorry I thought you were sarcastic lol.
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I think Muon is in the right direction. I got POIS in 2000. At the same time I developped a sensitivity for perfume and cigarette smoke. A lot of symptoms are the same: red itchy eyes, runny nose, irritation in the throat. Of course there are more POIS-symptoms. But I think POIS is a multiheaded monster. One of the causes could be hypersensitivity. And in my case my POIS is even worse when I have a sexual activity without ejaculation. If I only get POIS after ejaculation then you could say it is a hormone thing. And there are other members who also get POIS even without orgasm. But I am not saying hormones are not involved, because there are POIS-patients who get relief by testosterone. And maybe there is not only 1 type of POIS.
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Hi Vandemolen,
There are actually more than two subtypes of type IV hypersensitivity. I have added these to the first post, just scroll down: https://poiscenter.com/forums/index.php?topic=2925.msg27479#msg27479
They are mentioning the possibility of patients having multiple subtypes where one is dominant over the other. Perhaps different poisers have different type IV subtypes. I also got IL-8 elevated, if I test positive for GM-CSF then there might be a chance I got subtype IVd. Increase in Interferon gamma could already be an indication for type IV HS in general though.
I remember that Nanna once mentioned that I should be tested for GM-CSF. A delayed type VI HS does exist as well but haven't read about that yet, they also propose a seventh type in a paper.
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Maybe you should post it in the blood test discussion topic. If some guys do blood tests they can check also if they might have type IV HS. At short time I can not do blood tests. But I hope to able to do it about a few weeks or months.
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The lymphocyte transformation test might be a method for measuring a cellular T-cell response to seminal fluid. Even more interesting is to combine this with gel electrophoresis.
https://www.imd-berlin.de/en/special-areas-of-competence/lymphocyte-transformation-test-ltt.html
https://en.wikipedia.org/wiki/Gel_electrophoresis
I might ask the medlab in Berlin whether it's possible to use this test in combination with my seminal fluid. So what you can do is using this test on a pois group and compare it with healthy controls. You could repeat the test with gel electrophoresis to explore properties of the molecule like size.
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Th1 activation ---> interferon gamma release ---> increased macrophage activity ---> release of hydrolytic enzymes ---> affecting neurotransmitter metabolism ---> cognitive dysfunction
Perhaps POIS symptoms are being caused by the release of a bunch of enzymes damaging tissue which mimicks inflammation or altering enzyme activity in general.
I've read somewhere that certain Cytokines can mess with the kynurenine pathway leading to psychological issues. If anyone can find these papers you'd make me a favor. Maybe type 4 hypersensitivity leads to production of certain Cytokines that mess with neurotransmitters production.
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Maybe poisers show different cytokine profiles Nas, these could affect parts of the brain. We need to take this step by step. The first step is to prove whether this is a type IV HS by using the LTT. Waldinger mentioned in his paper that a flu-like state could be caused by cytokines. I think it's possible that different symptom clusters might be caused by different cytokine profiles. I will send an email to the lab and ask whether it's possible to use my seminal fluid for LTT.
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Again I'm more focused on the cognitive side of things. Let's assume that these brain effecting Cytokines are elevated in POIS. What would be the mechanism? If anyone has an idea please share.
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I'm more focused on trying to prove T-cell mediated hypersensitivity in pois, this is what the thread is about. You are getting two steps ahead. You could search for papers which related cognitive symptoms to cytokines. I've mentioned a few cytokines for the subtypes in the first post of this thread, you can look up if they play a role in cognitive dysfunction. Just to let you know, I'm not going into all of that, not in the mood for that (at least for now).
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I'm more focused on trying to prove T-cell mediated hypersensitivity in pois, this is what the thread is about. You are getting two steps ahead. You could search for papers which related cognitive symptoms to cytokines. I've mentioned a few cytokines for the subtypes in the first post of this thread, you can look up if they play a role in cognitive dysfunction. Just to let you know, I'm not going into all of that, not in the mood for that (at least for now).
Not trying to interfere with this thread Muon. But one last point I like to make, is that by knowing which Cytokines interfere with brain metabolism I can narrow down the possible subtypes. So again if anyone has any knowledge of these Cytokines please tell.
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I'm more focused on trying to prove T-cell mediated hypersensitivity in pois, this is what the thread is about. You are getting two steps ahead. You could search for papers which related cognitive symptoms to cytokines. I've mentioned a few cytokines for the subtypes in the first post of this thread, you can look up if they play a role in cognitive dysfunction. Just to let you know, I'm not going into all of that, not in the mood for that (at least for now).
Not trying to interfere with this thread Muon. But one last point I like to make, is that by knowing which Cytokines interfere with brain metabolism I can narrow down the possible subtypes. So again if anyone has any knowledge of these Cytokines please tell.
Quantum did a write up on cytokines on this thread: https://poiscenter.com/forums/index.php?topic=2350.msg19559#msg19559
It will also be a good place to continue cytokine discussion
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Delayed hypersensitivity and negative PGE feedback loop:
Regulation of allergic responses by prostaglandins: a review (https://journals.sagepub.com/doi/pdf/10.1177/014107688007300610)
Antigen--->sensitized lymphocytes--->lymphokines--->stimulation of macrophages--->macrophage activation--->PGE--->lymphocyte inhibition.
''This negative feedback system has been suggested as a device for regulating the extent and duration of lymphocyte activation in delayed hypersensitivity reactions''
https://en.wikipedia.org/wiki/Lymphokine
From that list IL-3,5 and GM-CSF haven't been measured. IFN-g rises this could activate macrophages which could release PGE molecules on their turn inhibiting lymphocytes and causing a delayed reaction. The PGE series could be explored.
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All those speculations in papers about hypersenstivities and potential involvement of cytokines and not a single doctor measuring cytokines...mind blowing!
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Human Lymphocyte Migration as a Parameter of Hypersensitivity (https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.0954-6820.1967.tb07255.x)
So does that mean we have to block T-lymphocyte migration?
Symptom localization in POIS = higher density of T-lymphocytes to inflammatory sites by migration?
Some quick examples:
Astilbin suppresses delayed‐type hypersensitivity by inhibiting lymphocyte migration (https://onlinelibrary.wiley.com/doi/abs/10.1211/002235703765344612)
''Repertaxin also selectively blocked CXCL8-induced T lymphocyte and natural killer (NK) cell migration.''
Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2 (https://www.sciencedirect.com/science/article/abs/pii/S0006295204007282)
Idea for POIS: Look for medicine that can block T-lymphocyte migration and adhesion or block lymphokine production.
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Human Lymphocyte Migration as a Parameter of Hypersensitivity (https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.0954-6820.1967.tb07255.x)
So does that mean we have to block T-lymphocyte migration?
Symptom localization in POIS = higher density of T-lymphocytes to inflammatory sites by migration?
Some quick examples:
Astilbin suppresses delayed‐type hypersensitivity by inhibiting lymphocyte migration (https://onlinelibrary.wiley.com/doi/abs/10.1211/002235703765344612)
''Repertaxin also selectively blocked CXCL8-induced T lymphocyte and natural killer (NK) cell migration.''
Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2 (https://www.sciencedirect.com/science/article/abs/pii/S0006295204007282)
Idea for POIS: Look for medicine that can block T-lymphocyte migration and adhesion or block lymphokine production.
Good find
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Some quick examples:
Astilbin suppresses delayed‐type hypersensitivity by inhibiting lymphocyte migration
From this site (https://www.ulprospector.com/en/asia/Food/Detail/17797/459373/Astilbin)
"Astilbin can be found in St John's wort, in Dimorphandra mollis, in the leaves of Harungana madagascariensis (Hypericaceae), in the rhizome of Astilbe thunbergii, in the root of Astilbe odontophylla(Saxifragaceae), in the rhizone of Smilax glabra(Chinaroot, Smilacaceae) and in the bark of Hymenaea martiana. It can also be isolated from Kohki tea processed from Engelhardtia chrysolepis (huang-qui). Astilbin is used in traditional Chinese medicine and can be used in supplements."
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Perhaps slightly off-topic but I find this interesting:
''When the innervation to substance P nerve terminals is lost, post-synaptic cells compensate for the loss of adequate neurotransmitter by increasing the expression of post-synaptic receptors. This, ultimately, leads to a condition known as denervation supersensitivity as the post-synaptic nerves will become hypersensitive to any release of substance P into the synaptic cleft.''
https://en.wikipedia.org/wiki/Substance_P#Denervation_supersensitivity
''Denervation supersensitivity is the sharp increase of sensitivity of post-synaptic membranes to a chemical transmitter after denervation.[1][2] It is a compensatory change.[3]''
https://en.wikipedia.org/wiki/Denervation_supersensitivity
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Perhaps slightly off-topic but I find this interesting:
''When the innervation to substance P nerve terminals is lost, post-synaptic cells compensate for the loss of adequate neurotransmitter by increasing the expression of post-synaptic receptors. This, ultimately, leads to a condition known as denervation supersensitivity as the post-synaptic nerves will become hypersensitive to any release of substance P into the synaptic cleft.''
https://en.wikipedia.org/wiki/Substance_P#Denervation_supersensitivity
''Denervation supersensitivity is the sharp increase of sensitivity of post-synaptic membranes to a chemical transmitter after denervation.[1][2] It is a compensatory change.[3]''
https://en.wikipedia.org/wiki/Denervation_supersensitivity
I think this needs it's own topic, I have no idea how anyone would understand this without getting a bit of background on substance P
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I think it fits more into a topic about neurotransmitters. What if there is denervation supersensitivity in the genitourinary tract and POIS is actually a supersensitivity to neuropeptides? These can interact with nerve endings right?
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I think it fits more into a topic about neurotransmitters. What if there is denervation supersensitivity in the genitourinary tract and POIS is actually a supersensitivity to neuropeptides? These can interact with nerve endings right?
Again I think you should make a post giving us a background on this subject, cause here other than Nanna I don't think people will understand this topic.
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I think it fits more into a topic about neurotransmitters. What if there is denervation supersensitivity in the genitourinary tract and POIS is actually a supersensitivity to neuropeptides? These can interact with nerve endings right?
Definitely could be , i can fell that something damaging our nerves.
And i have syptomes that prove that to me.
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I think it fits more into a topic about neurotransmitters. What if there is denervation supersensitivity in the genitourinary tract and POIS is actually a supersensitivity to neuropeptides? These can interact with nerve endings right?
Definitely could be , i can fell that something damaging our nerves.
And i have syptomes that prove that to me.
Yes I have symptoms that led me to believe there is neurogenic inflammation involved. I suspect something is going on with the nerves whether it's inflammation, neurotransmission, abnormal conduction, I don't know. Like pain in inside of arms, burning sensation, muscle spasms. Neuropeptides play a role in neurogenic inflammation:
https://en.wikipedia.org/wiki/Neurogenic_inflammation
https://en.wikipedia.org/wiki/Neuropeptide#Examples
They can cause inflammation in your brain, spine or even joints. I have no knowledge about these systems though so I will refrain from discussing it further, but this is something that is in the back of my mind.
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"A recent (2010) study of the treatment of migraine with CGRP blockers shows promise.[24] In early trials, the first oral nonpeptide CGRP antagonist, MK-0974 (Telcagepant), was shown effective in the treatment of migraine attacks" Neurogenic inflammation wiki (https://en.wikipedia.org/wiki/Neurogenic_inflammation#treatment)
If anyone has access to these drugs, it could be a good way to test the Neurogenic inflammation theory.
''Denervation supersensitivity is the sharp increase of sensitivity of post-synaptic membranes to a chemical transmitter after denervation.[1][2] It is a compensatory change.[3]''
https://en.wikipedia.org/wiki/Denervation_supersensitivity
Denervation reaction in the genitourinary tract could actually be the cause of premature ejaculation due to hypersensitivity in the penis neural endings.
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''Denervation supersensitivity is the sharp increase of sensitivity of post-synaptic membranes to a chemical transmitter after denervation.[1][2] It is a compensatory change.[3]''
https://en.wikipedia.org/wiki/Denervation_supersensitivity
Denervation reaction in the genitourinary tract could actually be the cause of premature ejaculation due to hypersensitivity in the penis neural endings.
Maybe. Waldinger has a background on this matter, he should know something about this.
These antagonists are experimental, which means they are not available to the public. Another one might be a NK1 blocker, those are used in cancer and very expensive, statins is an option. Are there free nerve endings in the mucosal layer of the lower urinary tract? It could be denervation of these nerves interacting with molecules in sperm or there is something wrong with signal transduction. When using the terms denervation and premature ejaculation I stumbled upon this paper, which is again off-topic (LOL):
The hormonal control of ejaculation (https://www.nature.com/articles/nrurol.2012.147)
''Evidence shows that oxytocin is actively involved in regulating orgasm and ejaculation via peripheral, central and spinal mechanisms''
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The link you gave me about neurogenic inflammation mentions Botox. They used this for my Bell's Palsy. There was a problem with recovery. When I contract 1 facial muscle one other facial muscle contracted as well and vice versa. The neurologist told me the same signal probably were shared between two nerves which were intertwined in the repair phase and he proposed to use Botox to destroy the end plates which then had a chance to regrow properly, this helped somewhat but not much. So could my Bell's palsy be caused by neurogenic inflammation?
Edit: Or there is demyelination where two nerves were making contact. Could this make the signal jump over like in an electrical circuit?
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These antagonists are experimental, which means they are not available to the public. Another one might be a NK1 blocker, those are used in cancer and very expensive, statins is an option.
erenumab
fremanezumab
galcanezumab
Are all FDA approved. They are probably rare and expensive, yet if anyone has access to them, trying them would be a good experiment when it comes to this theory.
When using the terms denervation and premature ejaculation I stumbled upon this paper, which is again off-topic (LOL):
The hormonal control of ejaculation (https://www.nature.com/articles/nrurol.2012.147)
''Evidence shows that oxytocin is actively involved in regulating orgasm and ejaculation via peripheral, central and spinal mechanisms''
What are the coexisting peptides of oxytocin? If we consider that ejaculation is the trigger for POIS then knowing the neurotransmitter that gets expressed right in that moment would let us pinpoint coexisting neuropeptides that are potentially auto-immunogenic.
So could my Bell's palsy be caused by neurogenic inflammation?
Given your situation, you definitely seem to have some sort of nerve issue. And neuro-inflammation us highly likely.
We should totally open up a lab Muon, we have such great theories but no means of testing for their validity lol
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Tell me when the ‘Muon and Nas on the road show' comes to my city.
I assume you offer Senior discounts!
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Cytokine Targets in the Brain: Impact on Neurotransmitters and Neurocircuits (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141874/)
"In human studies, increases in kynurenine and decreases in tryptophan have been associated with major depression and depressive symptom severity in patients administered IFN-alpha for cancer or infectious disease.[58,59] Of note, kynurenine can be converted to kynurenic acid (KYNA) in astrocytes and quinolinic acid (QUIN) in microglia, and patients treated with IFN-alpha has been found to exhibit increased KYNA and QUIN in the CSF, indicating that kynurenine can access the brain and be converted to its neuroactive metabolites"
Really recommend this article, it talks alot about the potential ways certain cytokines effect the nervous system. From what it written their, it seems that IFN-alpha is a recurring cytokine in many of these metabolic disruptions.
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IFN alpha doesn't play a role in hypersensitivity as far as I know.
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IFN alpha doesn't play a role in hypersensitivity as far as I know.
Hmmmm, so completely irrelevant?
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IFN alpha doesn't play a role in hypersensitivity as far as I know.
Hmmmm, so completely irrelevant?
Irrelevant if the hypersensitivity theory is true, which is a big IF.
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Irrelevant if the hypersensitivity theory is true, which is a big IF.
Is IFN-alpha related to auto-immunity though? Cause auto-immunity is technically a type v hypersensitivity.
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I went through a lot of papers considering hypersensitvity but have never seen involvement of IFN-alpha. You can share papers if you find any.
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Tell me when the ‘Muon and Nas on the road show' comes to my city.
I assume you offer Senior discounts!
Yes and we will reserve a special chair for you as our VIP:
(https://encrypted-tbn0.gstatic.com/images?q=tbn%3AANd9GcRbUTls3nDBdXIlGdA-9mh1D-Yy3nqSRwOCv4m2kc7vvboBx01Y)
As a bonus we will serve premium quality caviar!
Thank you, Muon!!
Demo
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Hahah good one demo.
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Concept: Altered stress state/response(Neuroendocrine dysregulations)--->Immune function---->Delayed-type hypersensitivity?
Enhancing versus suppressive effects of stress hormones on skin immune function.
Abstract
Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoimmunity) aspects of immune function. Contrary to the idea that stress suppresses immunity, we have reported that short-duration stressors significantly enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin may mediate this immunoenhancement.
Here, we identify the hormonal mediators of a stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed skin DTH.
These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.
https://www.ncbi.nlm.nih.gov/pubmed/9927693
Is CRH worth investigating? (HPA/CRH hyperactivity?)
Brain-immune interactions and disease susceptibility (https://www.nature.com/articles/4001643)
(https://media.nature.com/lw926/nature-assets/mp/journal/v10/n3/images/4001643f1.jpg)
Schematic illustration of neural immune connections. The figure shows immune signaling of the CNS via systemic routes and the vagus nerve (Vagus n.) and CNS regulation of immunity via the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-gonadal (HPG) axes, and the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS). Cytokine expression within the CNS is represented by asterisks within the brain. Dotted lines represent negative regulatory pathways, and solid lines represent positive regulatory pathways. CRH, corticotrophin-releasing hormone; AVP, arginine vasopressin; TRH, thyrotropin-releasing hormone; GnRH, gonadotropin-releasing hormone; ACTH, adrenocorticotrophin hormone; TSH, thyroid-stimulating hormone; T4, thyroxine; T3, triiodothyronine; LH, luteinizing hormone; FSH, follicle-stimulating hormone; SNS, sympathetic nervous system; PNS, parasympathetic nervous system; LC, locus ceruleus; A1, C1, A2, C2, brainstem adrenergic nuclei.
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''Although IgE and IgG1 are central to the induction of immediate hypersensitivity reactions, our results show that IgLCs have similar activity. IgLCs may therefore be a novel factor in the humoral immune response to antigen exposure. Our findings open new avenues in investigating the pathogenesis of autoimmune diseases and their treatments.''
Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses (https://www.nature.com/articles/nm722)
Has anyone checked this parameter in their serum?
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Has anyone checked this parameter in their serum?
Yes Simon66 did, all normal:
https://poiscenter.com/forums/index.php?topic=2684.msg24995#msg24995
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Would a lymphocyte transformation test be useful for POIS? Might there be other substances present in sperm that could stimulate or suppress lymphocyte proliferation naturally? If overwhelmingly positive, could this antigen-specific memory T cell be isolated and characterized? What receptors are involved?
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Would a lymphocyte transformation test be useful for POIS? Might there be other substances present in sperm that could stimulate or suppress lymphocyte proliferation naturally? If overwhelmingly positive, could this antigen-specific memory T cell be isolated and characterized? What receptors are involved?
I like this idea
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You can read up on the basics here: https://www.imd-berlin.de/en/special-areas-of-competence/lymphocyte-transformation-test-ltt.html
They use it as a diagnostic tool for type IV hypersensitivity aside from skin testing. It makes much sense. You add the (self)-antigen to your own bunch of cells and watch how they grow compared to your control sample. Antigen specific memory T cells make up the for the difference in numbers.
The problem is that, there are 1000's of different molecules in sperm. Perhaps these could affect lymphocyte division. You will need healthy controls to compare results. Some papers seem to prefer LTT over skin pricks.
You could try to filter out the semen and do the testing with seminal fluid. Proteins can be fractioned by mass or size and these fractions can be used again in LTT. Or you can investigate the speciic memory T cell, if there is one involved.
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Hmm it seems that the same lab also offers in-vitro antigen induced th1/th2 cytokine profile testing. What about doing this kind of test with seminal fluid? I already did this test without induction with a potential antigen. You could distinguish orgasmic and ejaculatory effects from eachother.
Link (https://www.google.com/url?sa=t&source=web&rct=j&url=https://www.imd-berlin.de/fileadmin/user_upload/Diag_Info_Englisch/172_In_vitro_induced_cytokine_secretion_to_characterise.pdf&ved=2ahUKEwibmtOivtrkAhVB4qQKHbbxDscQFjABegQIAhAB&usg=AOvVaw3TqXsOFzMDa1JYrBz9Irym)