Author Topic: POIS Theory Master List  (Read 18126 times)

Muon

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POIS Theory Master List
« on: March 13, 2021, 04:07:11 PM »
Post theories/ideas regarding the Pathophysiology of POIS. This thread can function as a central hub. You may dump links to threads from other members in the comment section.

Rudimentary version
Or a combination of more than one of the above.

What else?

Comorbidities:

Premature Ejaculation:

Increased APP, AB42 in seminal plasma. Abnormal PSSR (lifelong PE)
Low Serotonin
Low serotonin + High Interferon gamma
Low serum BDNF
High Leptin/5-HT ratio
Low seminal plasma magnesium
Low NO
Imbalance between excitatory and inhibitory signals in the brain
Altered serotonin receptor activity
Hyperexcitability of penile sensory receptors
Changes in the neural processing of sensory signals
PIEZO2
H3R
ANS dysfunction (lifelong PE)
TRP ion channels
weakened connectivity between the inner brain regions in the dopamine system and strengthened connectivity between the dopamine system and other brain areas
Decreased TPH2 expression in brain.
Altered ALFF of frontal, parietal cortex, and putamen
Caudate nucleus volume
Dopamine autoreceptors
DAT1 polymorphism
Increased Norepinephrine firing? Low Norepinephrine?
Medial preoptic area in the rostral hypothalamus and nucleus paragigantocellularis in the ventral medulla
Increased nerve fibers (NGF?)
Dynamic changes of brain activity (Lifelong PE)

Hormonal Risk factors: High Testosterone, High Estradiol, Low Prolactin, High oxytocin, High FT3, High FT4, High Leptin.

Exercise intolerance

Histamine depletion
Histamine response
MCAS
Natural Killer cell response
Post-exertional Malaise
PSN/SNS tone
Gut and plasma microbiome
S100B compromised
Testosterone and Heat shock protein response
Impaired microcirculation/deficient action of NO
Defective Growth Hormone response
Elevated Cytokines
Decreased rate of ammonia clearance: Amino acids: Aspartic acid deficiency
Dysfunctional increase in WASF3 protein

Headache inducers

CGRP
Histamine
TNF-alpha
Serotonin

Non-IgE mediated food hypersensitivity

Central sensitization
MCAS
Eosinophil/ECP (ECP is a better marker for allergic activation than IgE, need source)
Type IV hypersensitivity
MRGPRX2 mediated pseudo-allergy
Intestinal B cell activating factor
Tregs
Intestinal epithelial barrier disruption

Weakness

Muscle hypoperfusion

Ocular itch

Gastrin-releasing peptide receptors in trigeminal sensory system
« Last Edit: March 28, 2024, 03:17:53 PM by Muon »

Muon

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Re: POIS Theory Master List
« Reply #1 on: March 13, 2021, 04:07:56 PM »
Reminder: Some ideas might be left inside other threads like POIS paper treatment summary etc.
« Last Edit: April 22, 2021, 06:35:23 AM by Muon »

Muon

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Re: POIS Theory Master List
« Reply #2 on: March 13, 2021, 04:09:02 PM »
Reserved 2

Muon

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Re: POIS Theory Master List
« Reply #3 on: March 13, 2021, 04:10:24 PM »
Reserved final

Muon

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Re: POIS Theory Master List
« Reply #4 on: March 19, 2021, 07:42:34 AM »

Muon

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Re: POIS Theory Master List
« Reply #5 on: April 20, 2021, 07:23:55 AM »
Running nose and nasal congestion can be related to vasomotor dysfunction (ANS, endothelial dysfunction?) which is unrelated to allergy, people might not be aware of this:

Vasomotor rhinitis

https://en.wikipedia.org/wiki/Nonallergic_rhinitis

Muon

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Re: POIS Theory Master List
« Reply #6 on: April 22, 2021, 06:51:26 AM »
Fox:
Gluten sensitivity
Improves on Niacin rich food
Slight blood pooling upon standing (Sympathetic activation? Vasomotor function?)

I do remember that a certain subset of Tregs plays a role in gluten sensitivity, it was the CD39 subset if I'm not mistaken (paper needed for confirmation). Now throw Niacin into the mix and combine it with the following post, see pic: https://poiscenter.com/forums/index.php?topic=3765.msg40413#msg40413

Could Niacin intake affect Tryp/5HT pathway and improves vasomotor function, thus blood pooling?

What does Testosterone therapy have to do with this?---> T is able to increase Treg population directly. POISers who improved on antibiotics could have altered Treg populations. Treg increase can also be seen in some individuals who have done allergic desensitization therapy with succesful outcome (generally speaking that is, but could play a role in desensitized POISers). These points can be used to support MCAS theory as well. Tramadol--->Tregs?
« Last Edit: April 22, 2021, 09:43:32 AM by Muon »

Muon

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Re: POIS Theory Master List
« Reply #7 on: June 03, 2021, 02:20:20 PM »
An Overview of Seminal Plasma Hypersensitivity and Approach to Treatment

Can’t copy stuff from tablet. Read part about: PAR2 and dust mite. Possible protease-activated receptor-mediated epithelial barrier dysfunction.

Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics

Proteases constitute more than 8% of all SPPs in WSP8 and can augment IgE-independent inflammatory responses by disrupting the epithelial permeability barrier and activating protease-activated receptors (PARs) on epithelial cells.9 PAR-2 activation, which has been demonstrated in response to proteases from dust mite and cockroach and in seafood workers exposed to high aerosolized levels of proteases, can augment epithelial barrier dysfunction and localized mucosal inflammation independent of specific IgE responses.9,  10 Moreover, it has been demonstrated that semen proteases such as PSA can activate PAR-2 on spermatozoa cell membranes.11 We have recently confirmed the presence of PAR-2 receptors on vaginal keratinocytes by using western blotting and flow cytometry as well as calcium influx in SPP-stimulated vaginal keratinocytes using confocal microscopy, which was blocked by a protease inhibitor (unpublished data; Ghosh D and Bernstein JA, 2014, manuscript in preparation).

Thus, PAR-2 activation in vaginal epithelium might contribute to localized SPH, although other possible mechanisms such as IgE-independent mast cell activation and neurogenic responses involving bradykinin-mediated inflammatory/pain pathways should be investigated. In addition, prostaglandins (present in a considerable amount in WSP), which can cause antigen presenting cells to release proinflammatory cytokines, may also contribute to localized vaginal inflammation, as we have observed in some cases of women with localized SPH who experience attenuation of their symptoms if they take a nonsteroidal anti-inflammatory agent before unprotected intercourse (unpublished data). Thus, these mechanisms, summarized in Fig E2 in this article's Online Repository at www.jacionline.org, could potentially explain reactions observed in women with localized SPH in which specific IgE does not play a critical role. To conclude, our data demonstrate that although women with systemic and localized SPH have similar clinical outcomes, the mechanism(s) of action for these responses is distinctly different. Further investigation of the mechanism(s) related to localized SPH is warranted.



Fig E2Postulated mechanisms for localized SPH: Although women with systemic SPH sensitized to PSA can induce a specific serum IgE response through the classical TH2 pathway, women with localized SPH may exhibit symptoms as a result of seminal plasma proteases causing degradation of mucosal tight junctions, leading to the activation of PAR-2 receptors on epithelial cells that results in the release of proinflammatory cytokines and localized inflammation. Seminal plasma also contains high levels of prostaglandin E2 (PGE2), which can activate antigen-presenting cells (APCs) lining the inner face of the vaginal epithelium, leading to the release of proinflammatory cytokines, causing localized mucosal inflammation.

Table 2:
https://sci-hub.se/10.1111/jsm.12813#

HDM, cockroach allergens or seminal protease—>PAR2–>leakage of PGE2 and other stuff. MCA is another possibility.
« Last Edit: June 03, 2021, 02:51:32 PM by Muon »


Muon

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Re: POIS Theory Master List
« Reply #9 on: March 28, 2022, 12:49:50 PM »
https://twitter.com/scubatropin/status/1319398186708942848
" Its a class 6 allergy to semen. Precoital prednisone is pretty effective when given sufficient time to affect the multiple areas where the immune system attack. Avoiding omega-6 and other inflammatory fats is crucial to tx. "

Antibody Dependant Cell Mediated Cytotoxicity (ADCC) Type VI Hypersensitivity
« Last Edit: June 13, 2022, 08:12:42 AM by Muon »

Muon

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Re: POIS Theory Master List
« Reply #10 on: April 07, 2022, 07:00:43 AM »
Also in most cases I don't think the cause of POIS is mast cell related, its mainly neurotransmitter dysfunctions: imbalanced Glutamate/Gaba ratio causing excitotoxicity, low dopamine, low DBH activity, low BH4, high epinephrine, low norepinephrine, any mast cell symptoms are secondary to the neurotransmitter issues. Correcting gut microbiome imabalances/gut infections, mineral imbalances, methylation impairments, removing heavy metals you will see the neurotransmitter issues correct themselves.

Improving dopamine synthesis, normalising DBH, correcting an imbalanced gaba glutmate ratio will all also help.

This Post from an ME/CFS researcher has a lot of useful information.

https://bornfree.life/experimental-treatment-methodology/7/blood-ph-ion-channel-disturbances-neurotransmitters-and-mineral-deficiencies/37/

A preferred approach (after confirming noradrenaline is low and/or vanillylmandelic acid is low on urine tests), is to normalise DBH, thereby correcting the downstream cascade. This would be best mediated by removing any/all "low-hanging fruit", such as:

1. Quantifying and remediating deficiencies of vitamin C, copper, manganese, magnesium, zinc, lithium, riboflavin and potassium. (PQQ may also be helpful.)
2. Quantifying and remediating interstitial and blood pH. Confirming by blood smear that red blood cell morphology is normal. Any clumping or rouleaux may act to limit other interventions.
3. Quantifying and remediating pulmonary respiration function.
4. Antagonising a2-adrenergic receptors, using a suitable intervention. (At this time, appropriate a2-antagonists may include small doses of yohimbe / yohimbine, rauwolscine and phenoxybenzamine. This is a WIP)
5. Further reducing NLRP-3 using eg. hesperidin.
6. Removing / remediating any detected pathogens that impair DBH - this can be a long process.
7. Investigating a BH4 deficiency - this is difficult to measure directly. This may appear as low levels of neurotransmitters, low ferritin, low intracellular riboflavin, low 5-MTHF / folinic acid, low citrulline.

Muon

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Re: POIS Theory Master List
« Reply #11 on: June 13, 2022, 06:11:49 AM »
Silodosin could be used for research to make a distinction between subgroups by blocking ejaculation.

Muon

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Re: POIS Theory Master List
« Reply #12 on: June 13, 2022, 10:00:37 AM »
Silodosin could be used for research to make a distinction between subgroups by blocking ejaculation.
Good idea. And Rapaflo?
Anything that fully blocks ejaculation. You could end up with 4 groups if the block is successfull:
1) POIS free
2) Diminished symptoms
3) Increased symptoms
4) No effect in symptoms

Group 1 and 4 could be isolated and investigated further.

Muon

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Re: POIS Theory Master List
« Reply #13 on: June 13, 2022, 05:38:14 PM »
Type IV of hypersensitivity and its subtypes

Classification of hypersensitivity reactions

"It should be noted that some disorders are caused by IgE-independent, nonspecific activation of mast cells, which could be considered to be a subset of type I hypersensitivity reactions."

Perspective of Delayed Hypersensitivity: A review

"There is an increase in  leukocyte  concentration  in  tissues  where  immunological  and  inflammatory  responses  are occurring  in  response to  external  antigens  because  of  the  upregulation  of  endothelial  cell adhesion  molecule  expression."

Why haven't these Type IV subtypes been explored already? The mediators are shown for each subtype.
« Last Edit: June 14, 2022, 02:22:16 PM by Muon »

dylanmurphy

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Re: POIS Theory Master List
« Reply #14 on: June 14, 2022, 01:56:35 AM »
Pulsatilla 200c works well so far for me for stopping Ne's (touch wood) !!

Muon

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Re: POIS Theory Master List
« Reply #15 on: September 15, 2022, 08:24:49 PM »
Men versus women on sexual brain function: Prominent differences during tactile genital stimulation, but not during orgasm

"The only prominent gender difference during orgasm was male-biased activation of the periaqueductal gray matter."

Periaqueductal Gray

Muon

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Re: POIS Theory Master List
« Reply #16 on: April 23, 2023, 06:06:08 AM »
Are we dealing with inflammatory exosomes (20-100 nm) in POIS? Crossing all kinds of biological barriers?

Exosomes in inflammation and role as biomarkers

The advantage of using exosomes as a biomarker vehicle consists of their ease of collection from body fluids such as urine and saliva as they may represent a non-invasive means for screening human pathology.

Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), blood-lymph barrier (BlyB), blood-air barrier (BAB), stromal barrier (SB), blood-labyrinth barrier (BLaB), blood-retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform.

Progecitor

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Re: POIS Theory Master List
« Reply #17 on: April 23, 2023, 02:04:06 PM »
Are we dealing with inflammatory exosomes (20-100 nm) in POIS? Crossing all kinds of biological barriers?

Exosomes in inflammation and role as biomarkers

The advantage of using exosomes as a biomarker vehicle consists of their ease of collection from body fluids such as urine and saliva as they may represent a non-invasive means for screening human pathology.

Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), blood-lymph barrier (BlyB), blood-air barrier (BAB), stromal barrier (SB), blood-labyrinth barrier (BLaB), blood-retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform.

Exosomes are also involved in SASP signaling.

Additionally, small exosome-like extracellular vesicles have recently emerged as key components of the senescent cell secretome to enable more distal functions, such as enhancing cancer cell proliferation, an intriguing topic requiring further investigation.
Senescent cells can communicate with the surroundings through juxtacrine NOTCH/JAG1 signaling or ROS secretion or cargo transfer by formation of cytoplasmic bridges or release of extracellular vesicles such exosomes.

https://www.frontiersin.org/articles/10.3389/fcell.2021.645593/full
The cause is probably the senescence of sexual organs and resultant inducible SASP, which also acts as a kind of non-diabetic metabolic syndrome.

Muon

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Re: POIS Theory Master List
« Reply #18 on: May 31, 2023, 06:55:07 PM »
Input from nurse Claire is appreciated. She tries to describe the cause of POIS with an autoimmune approach.

May 19, 2023
Equal Parts Derogatory Dismissal and Powerless Exasperation

May 26, 2023
Find the Antigen(s), Define the Disease

Reminder to incorporate it into the list.

demografx

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Re: POIS Theory Master List
« Reply #19 on: June 01, 2023, 09:09:07 AM »

Input from nurse Claire is appreciated. She tries to describe the cause of POIS with an autoimmune approach.

May 19, 2023
Equal Parts Derogatory Dismissal and Powerless Exasperation

May 26, 2023
Find the Antigen(s), Define the Disease

Reminder to incorporate it into the list.

Sent to POIS Research Team. Thanks.
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business