Muon's Case

[Muon]

https://www.thenakedscientists.com/forum/index.php?topic=6576.msg369612#msg369612

"Alexander is an active participant of russian Syndrom X blog. Recently he wrote a post where he explains that there are huge similarities in symptoms of POIS and Anaphylactic Shock. He also mentions that his mother had an allergic reaction to the sperm of his father.

The post of Alexander in russian is located here:"
http://syndrom-x.blogspot.com/2011/10/blog-post.html

Similar to my mother (no anaphylaxis, just burning)...

[Muon]

https://www.thenakedscientists.com/forum/index.php?topic=6576.msg225842#msg225842

POIS catecholamines theory

The theory that I have about POIS, is that the symptoms may be caused by a deficiency of one or more of the catecholamines of which noradrenaline may be of most significance.

There are several points that may lead into this direction.

Possible links between POIS and catecholamines:

- During sexual activity noradrenaline levels increase and afterwards they decrease. (1)
- Having a shower with alternating hot and cold water and the sauna including cooling down with a cold water bath / shower both help reducing the symptoms. Noradrenaline and adrenaline levels rise significantly when the body is subjected to cold stress. (2) (3)
- During a period in which POIS symptoms occur, I can have an enlarged / swollen penis. Continuous release of noradrenaline is necessary to keep the penis in a non-erectile state. (4)
- Human semen contains high levels of catecholamines. (5)
- The symptoms of a depletion of catecholamines are similar to many symptoms related to POIS. In the scientific research linked as reference a depletion of dopamine is induced, though this is likely to cause a depletion of noradrenaline and adrenaline besides dopamine alone, as a consequence. Since noradrenaline and adrenaline are produced from dopamine in the body. (6)
- PDE4 inhibits the cyclic AMP (cAMP), which has an inhibition of noradrenaline and adrenaline as a consequence. Therefore, a PDE4-inhibitor has the opposite effect, an increase of cAMP and noradrenaline levels. (7) (
- Among other areas in the body, PDE4 has also been found in male and female sexual organs. I'm not sure if this is relevant. (9) (10)
- Sceletium Tortuosum helps reducing POIS symptoms. It's a herb of which the main active alkaloid is mesembrine, which is a PDE4 inhibitor with a mechanism in a way similar to rolipram (11) that raises levels of noradrenaline. (7) (
- Thinking back about it, I remember that recreational use of amphetamines (speed) in the past showed a reduction of symptoms and after the effects wore off, an increase of the severity of the symptoms was noticed for up until about a week, possibly because of a depletion of noradrenaline. I already had POIS long before I had used any amphetamines, by the way. Amphetamines are known to increase levels of noradrenaline and a temporary depletion of noradrenaline after use is possible.
- Garlic has been reported to help reducing POIS symptoms. Garlic can increase noradrenaline and adrenaline levels. (12)
- Fenugreek has been reported to help reducing POIS symptoms. Fenugreek contains diosgenin, which can produce an oxytocin-like effect. Oxytocin can increase noradrenaline levels. (13)
- Celtic salt has been reported to help reducing POIS symptoms. That person might be sensitive to salt-induced hypertension, which can cause an increase in plasma noradrenaline and adrenaline levels. (14) Another possibility is that the level of oxytocin increases by the salt. (15) Oxytocin can increase noradrenaline levels. (13)
- Heavy physical exercise can reduce POIS symptoms. Heavy physical exercise can increase catecholamines. (16)
- The combination of testosterone and Levitra (vardenafil) has been reported to reduce POIS symptoms. Testosterone may increase noradrenaline. (17) Vardenafil also inhibits PDE4 besides PDE5, although relatively weak. (18) Vardenafil also increases nitric oxide. Nitric oxide can increase dopamine. (19) (20) An increase of dopamine may lead to an increase of the other catecholamines as well. Testosterone and vardenafil can have a synergistic effect. (21)

- Blood test results showed a deficiency of noradrenaline and adrenaline. During the collection of blood for the tests, only mild POIS symptoms were experienced, during a period of more severe symptoms there may be an even greater deficiency. (22)


(1) Plasma noradrenaline and dopamine-beta-hydroxylase during sexual activity Link to full text (PDF) is also available at that website.
(2) The Influence of Cold Stress on Catecholamine Excretion and Oxygen Uptake of Normal Person
(3) Interrelations between Sympathoadrenal System and Hypothalamo-Pituitary-Adrenocortical/Thyroid Systems in Rats Exposed to Cold Stress
(4) Physiological significance of nitrergic transmission in human penile erection
(5) High levels of catecholamines in human semen: a preliminary study
(6) Subjective Experiences During Dopamine Depletion
(7) Rolipram, an Antidepressant That Increases the Availability of cAMP, Transiently Enhances Wakefulness in Rats
( The antidepressant and antiinflammatory effects of rolipram in the central nervous system
(9) Immunohistochemical Distribution of cAMP- and cGMP-Phosphodiesterase (PDE) Isoenzymes in the Human Prostate
(10) Immunohistochemical Description of Cyclic Nucleotide Phosphodiesterase (PDE) Isoenzymes in the Human Labia Minora
(11) Mesembrine is an inhibitor of PDE4 that follows structure-activity relationship of rolipram
(12) Allyl-Containing Sulfides in Garlic Increase Uncoupling Protein Content in Brown Adipose Tissue, and Noradrenaline and Adrenaline Secretion in Rats  ("Administration of diallyldisulfide, diallyltrisulfide and alliin, organosulfur compounds present in garlic, significantly increased plasma noradrenaline and adrenaline concentrations")
(13) Facilitative role of endogenous oxytocin in noradrenaline release in the rat supraoptic nucleus
(14) Genetic influence on brain catecholamines: high brain noradrenaline in salt-sensitive rats
(15) Release of oxytocin induced by salt loading and its influence on renal excretion in the male rat
(16) FREE AND CONJUGATED CATECHOLAMINES IN HUMAN PLASMA DURING PHYSICAL EXERCISE
(17) Effects of testosterone and ethinyloestradiol on the synthesis and uptake of noradrenaline and 5-hydroxytryptamine in rat hindbrain: evidence for a presynaptic regulation of monoamine synthesis?
(18) The inhibitory selectivity of vardenafil on bovine and human recombinant phosphodiesterase isoenzymes
(19) Nitric oxide inhibits [3H]dopamine uptake
(20) Effect of Nitroprusside (Nitric Oxide) on Endogenous Dopamine Release from Rat Striatal Slices
(21) Hypogonadism and erectile dysfunction: the role for testosterone therapy
(22) Test results of neurotransmitters, hormones, etc.

[Muon]

Colder environmental temperatures affect me big time, in a positive way. It seems to synergize with diurnal rythm. I'm getting energy when I approach midnight. Temperature approaches zero degrees celsius. Reminder to write more about symptoms.

Dumping for later:

Thermoregulatory disorders and illness related to heat and cold stress

Effect of cold stress on immunity in rats

https://scholar.google.com/scholar?hl=nl&as_sdt=0%2C5&q=autoimmune+disease+cold+stress&btnG=

https://forums.phoenixrising.me/threads/why-do-we-feel-better-at-night.52204/page-3#post-2294949

[Muon]

Started two days ago with pyridostigmine 30 mg/day. I'm now on 2x30 mg/day. Will titrate it up in ~10 days. I get more sensitive to my environment (air molecules-->nose, lungs) immediately. Yesterday had an flare of itching in my left eye, never had this symptom before. The scent of the tablets alone makes my nose sensitive, it's the same type of smell I encountered in other type of tablets. I can't find a notification of the fillers involved. They only had 10mg tablets available, so I have to take quite a few.

[Igy78]

1 question, did you check your liver and bile production?

[Muon]

1 question, did you check your liver and bile production?

I have no idea, there are some liver related measurements in here. I do experience flares of liver pain.

[Igy78]

You can have fatty liver even with in range results. Read my post, maybe it helps, i got better when dealing with bile production and fatty liver. But fatty liver is not mandatory to have low bile production, it can be hereditary.

https://poiscenter.com/forums/index.php?topic=3203.105

[BoneBroth]

It's strange. We have technique to send a human 384 400 km to the moon and and back and watch galaxies billions of light years away. But to know the condition of one of your most important organs, your intestines, that lies only two centimeters behind the skins surface - should be nearly impossible! No doctor would do that unless your not in severe pain. That makes you think about how we humans makes priorities...

[Muon]

Muon:

1) Should anal contractions always happen during orgasm?

2) What does it mean if anal contractions are absent during orgasm?

Dr. Nicole Prause via demo's email:

Hi,

1) Contractions are the main way we define orgasm physiologically, but contractions do not need to be present to experience pleasure and have fulfilling sexuality.

2) We don't know. I'm working on it.

Nicole Prause, Ph.D.

[Muon]

There are plenty of particles that do not show up in blood tests like, for example, mast cell-derived exosomes or the one below:

New particle discovered in the bloodstream of patients with sepsis

"ENDS are not normal – they are not detectable in healthy people or mice,” says Klaus Ley, senior author of the study. “But ENDS are very high in sepsis, and I would not be surprised if they were high in other inflammatory diseases."

Elongated neutrophil-derived structures are blood-borne microparticles formed by rolling neutrophils during sepsis

Abstract:
Rolling neutrophils form tethers with submicron diameters. Here, we report that these tethers detach, forming elongated neutrophil-derived structures (ENDS) in the vessel lumen. We studied ENDS formation in mice and humans in vitro and in vivo. ENDS do not contain mitochondria, endoplasmic reticulum, or DNA, but are enriched for S100A8, S100A9, and 57 other proteins. Within hours of formation, ENDS round up, and some of them begin to present phosphatidylserine on their surface (detected by annexin-5 binding) and release S100A8–S100A9 complex, a damage-associated molecular pattern protein that is a known biomarker of neutrophilic inflammation. ENDS appear in blood plasma of mice upon induction of septic shock. Compared with healthy donors, ENDS are 10–100-fold elevated in blood plasma of septic patients. Unlike neutrophil-derived extracellular vesicles, most ENDS are negative for the tetraspanins CD9, CD63, and CD81. We conclude that ENDS are a new class of bloodborne submicron particles with a formation mechanism linked to neutrophil rolling on the vessel wall.

[Muon]

I keep getting surprised how well I fare outside during winter times when ambient temperatures are near 0 degrees celsius. I have posted a few papers in this thread about Cold effects. I should collect them. Saw these papers on the CFS forum:

Possible use of repeated cold stress for reducing fatigue in chronic fatigue syndrome: a hypothesis
Adapted cold shower as a potential treatment for depression
Hydrotherapy as a possible neuroleptic and sedative treatment

My metabolism speeds up. Better and quicker digestion. Muscles feel different, lighter and stronger. Quicker muscle repair (or is it reduced muscle fatigue?). Brain fog and cognitive function can improve as well. I get the impression that local soft tissue partially 'clears up'. I need to adapt/acclimate to cold otherwise it's too stressful though.

Low opioid tone....hmmm...HOD fared better during winter and gets relief of POIS symptoms by benzodiazepines. My brother same story heat intolerance, feels much better during cold and also gets relief of POIS symptoms by benzodiazepines.

Before I forget: My mother took a walk outside for about 10 min during a summer day, last summer and felt nauseous from the heat of the sun.

[Muon]

You can have fatty liver even with in range results. Read my post, maybe it helps, i got better when dealing with bile production and fatty liver. But fatty liver is not mandatory to have low bile production, it can be hereditary.

https://poiscenter.com/forums/index.php?topic=3203.105

I also have diagnosed fatty liver.

...it's like these pills are helping liver to detox and to produce bile and clean toxic stuff from blood.

Probably a molecule(s) that isn't part of standard lab test. In the past my facial skin and eyes would turn yellow from POIS. My liver still reacts (especially to stress). Aside from detox overload there could be inflammation present damaging hepatic cells which leads to leakage of liver enzymes.

One guy in literature with a fatty liver and elevated liver enzymes. See table 1 https://f1000research.com/articles/2-113

SIBO and non-alcoholic fatty liver disease (I have placed this link in the SIBO poll thread as well)

[Muon]

https://forums.phoenixrising.me/threads/rapid-complete-recovery-from-an-autism-spectrum-disorder-after-treatment-of-aspergillus-with-the-antifungal-drugs-itraconazole-and-sporanox.82345/

Dysbiotic microbiota in autistic children and their mothers: persistence of fungal and bacterial wall-deficient L-form variants in blood

"In conclusion, cell wall-deficient variants of opportunistic bacteria and fungi were recovered from blood of autistic children and their mothers. CWD converted under appropriate conditions of cultivation into detectable bacteria and fungi. The unifying finding for autistic children and their mothers was the presence in blood of wall-free variants from life-cycle of Aspergillus fumigatus, a phenomenon of fungal “colonization” or “silent infection”. It can be assumed that autistic children may be born with fungal colonization acquired from mothers by transplacental pathway. “Silent aspergillosis” may strongly influence development of immune and nervous systems in the early childhood and be a leading cause for neurodevelopmental disorders."

[Muon]

Bile regulates good/bad bacteria, it prevents SIBO, if the colon has bad bacteria i get POIS due to undigested food get to colon and bad bacteria making gasses like methane and hydrogen sulfide, which is getting to blood and into brain and then i get POIS symptoms.

If I eat a big meal and digestion is off whether it is due to low stomach acid, POIS, blood flow problems (I get the impression it's rather a decrease in blood supply), POTS, then I feel a lump of food traveling through my intestines. I'm more sensitive to friction at one area (same area where I had exploding pain once due to hot weather condition). Stool is never well shaped or colored when this happens. Sometimes it smells like cow manure instead of human feces.

[Hopeoneday]

Indigestion, specualy in pois cascade, nerwes do not work properly,
if nerwes do not work as they should, digestion and guts is stucked.

[Muon]

I had an orgasm. I get the impression that the fatigue originates inside my brain, a small focal area, somewhere near the center. It warped me into a state that is similar when I'm trying to exercise and go over a threshold. Another impression I get is that something is depleted, like I'm missing some kind of juice. Very vague but wanted to throw this out there.

[Muon]

IL-8 serum: 89.8 pg/ml

Comparative evaluation of Inflammatory cells and Interleukins in Irritable Bowel Syndrome subtypes

"On correlating Interleukins with mast cells and IELs,  significant positive correlation was seen only between IL-8 and mast cells"

"But our observation is supported by the paper of Patrixet al who have stated that IBS patients have increased serum concentration of IL-8 which is the main cytokine responsible for attraction of mast cells and granulocytes."

Didn't know IL-8 was an attractor of mast cells...if epithelial cells in the GI tract release this chronically then IL-8 gradients may lead to infiltrates of MCs. IL-8 is the main cytokine in MCs (MCs attracting MCs via IL-8?)

Scoping of my stomach revealed a patch of redness, this could be a macroscopic sign of inflammation.

https://youtu.be/lrKqlv6VK_w?t=320

Healthcare doesn't investigate these things, GI biopsy + staining for CD117.

[Muon]

Altered peripheral toll-like receptor responses in the irritable bowel syndrome

Potential increased activity of peripheral TLR3 or TLR7.

[Muon]

Plasma Endothelin Level in the Acute Stage of Bell Palsy

wow I never read this thread till today and was frozen while reading.  Moun's your symptom match mine.  Thank you for sharing these links.  Not to badger you, but the link you posted: Impairment of microcirculation of the facial nerves catches my attention, talks about: Endothelin, which has potent vasoconstrictive effects, may contribute to the pathogenesis of the microcirculatory impairment that occurs in patients with Bell palsy, mainly by promoting secondary ischemia.  I dont follow since we POISers have low BP and Endothelin constrict vessels raising BP.  During POIS, I get severe burning in my Palsy areas, as if nerves are trying to fire up but unable to.  When I take vasodilatory things (specially a med, gabapentin) that burning sensation stops but I dont know if vasodilatory is the key or its something else the key that helps.  But I know that POIS creates a burning sensation also across all distal peripherals, like ankles, wrists, exact symptoms of Raynaud syndrome.

In tuning the brain, when looking at the chapter about RESPIRATORY RHYTHM REGULATION (which I can have problems with) endothelin is mentioned.

"Respiratory rhythm is generated in and around the pre-Botzinger complex, a morphologically defined region in the lower brainstem. The network is regulated by various neuromodulators, all of which are important in neurosomatic disorders (Figure 7), especially SP acting at the neurokinin-1R."

"Many, if not most, of the symptoms related to neurosomatic disorders are caused by autonomic dysfunction which may be a result of inappropriate endothelin secretion. Blocking endothelin receptors may be an important way to treat neurosomatic disorders in the future"

"Endothelin, being one of the most vasoconstrictive substances known, could account for the increased global cerebral hypoperfusion seen after fatiguing stimuli, notably exercise but also after mental tasks."

"A considerable amount of experimental evidence indicates that endothelin plays a role in neurosomatic disorders. It stimulates NGF secretion (high in FMS CSF) and activates phospholipase A2."

"Most sympathetic ganglionic neurons can express considerable quantities of both endothelin-3 and endothelin-1 and have been suggested to rapidly release the former into the circulation during exercise"

"All neurosomatic patients who respond to treatment reduce their global cerebral blood flow"

Edit: and NGF can selectively increase IgG4. Swell had a Bell's palsy as well if I'm not mistaken. Regarding use of Gabapentin:

"The effects of endothelin on sensory gating have not been studied, but activation of the endothelin A receptor (there are A and B receptors that work quite differently) caused reduction in a potassium K_ATP channel response produced by activation of the muopioid receptor (done also by morphine-like drugs, gabapentin, minoxidil, and clonidine). Because these agents are often beneficial for neurosomatic disorders, endothelin’s blocking of K_ATP channels makes it even more implicated in neurosomatic pathophysiology."

"Both adenosine and gabapentin decrease pain in many patients with FMS by decreasing hyperactive neuronal activity. Gabapentin selectively opens K_ATP channels."

It also mentions that if pain is induced by endothelin, that NSAIDs will not work but benzodiazepines do.

[Muon]

Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis

T84 intestinal epithelial cell line (+involvement of PI3K pathway? PTEN, mTOR)

Studying permeability in a commonly used epithelial cell line: T84 intestinal epithelial cells

Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation

Opposing regulation of the tight junction protein claudin-2 by interferon-gamma and interleukin-4

Active and passive involvement of claudins in the pathophysiology of intestinal inflammatory diseases

Claudin-2: Roles beyond Permeability Functions

Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry.