Mast Cell Activation Syndrome

[Muon]

Mast cells and the CNS:

An Overview of the Physiological and Pathological Role of Mast Cells in the Central Nervous System

"Clemastine, for instance, is associated with reduced microgliosis, modulation of microglia-related inflammatory genes and enhanced motor neuron survival."

Clemastine is the only antihistamine that had a minor effect on my POIS. Microglia involvement? Microglia as IL-8 source?

Mast cells and liver disease:

The emerging role of mast cells in liver disease

Random stuff:

Cromolyn Inhibits the Secretion of Inammatory Cytokines by Human Microglia (HMC3)

Propolis suppresses cytokine production in activated basophils and basophil-mediated skin and intestinal allergic inflammation in mice

Propolis (bee glue)

[Hopeoneday]

What benzodiazepines have you tried HOD?

Apaurine 2mg
Xanax 0.25mg

Tested bee propolis in a lot of version, even cro patent native propolis,
god for imunyty colds etc, nothing for pois.
I will see active ingre.. in clemastin an test for pois in future...
Liver is crucial for "ewrything in body" main detox factory...

[Muon]

So which of those two are you using for POIS? Which one is more effective? What is the timing. I can add that info to the treatment thread.

"MCAS has been estimated to affect as many as 17% of the population with a severity ranging from mild to life-threatening." Ref

[Muon]

Yes, I share the non-O POIS symptoms from all of the items you've mentioned as well as sometimes defecating also triggering some symptoms. have skin sensitivity as well, head, scalp, legs. Almost as if the hair follicles get inflamed.

Friction can trigger mast cells. Mast cell numbers per unit surface area are roughly twice as high in the GI tract compared to the skin.

Note: Clicking just above the quote can launch you to the original post.

[Muon]

I think we had 1 or 2 POISers with aspirin intolerance:
Cellular interactions in aspirin-exacerbated respiratory disease

Willem did sublingual hyposensitization therapy with autologous semen, similar mechanism?:
Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy.

[Hopeoneday]

www.frontiersin.org/articles/10.3389/fimmu.2012.00147/full
Mast cells are important modifiers of autoimmune disease: with so much evidence, why is there still controversy?

[Hopeoneday]

https://www.jimmunol.org/content/163/2/947
Neutrophil Defensins Induce Histamine Secretion from Mast Cells: Mechanisms of Action

[EnriqueM075]

Many people with these symptoms are diagnosed with anxiety, and are medicated with antidepressants or anxiolytics without knowing the real cause, some improve, others do not, the illogical thing is that currently there are millions of people taking these drugs for life, when before they were only for days in the case of anxiolytics or benzodiazepines or months in the case of antidepressants. I took clonazepam for 13 years for a supposed cerebral dysrhythmia, when leaving them abruptly it generated anxiety and after months POIS

[Journey]

Many people with these symptoms are diagnosed with anxiety, and are medicated with antidepressants or anxiolytics without knowing the real cause, some improve, others do not, the illogical thing is that currently there are millions of people taking these drugs for life, when before they were only for days in the case of anxiolytics or benzodiazepines or months in the case of antidepressants. I took clonazepam for 13 years for a supposed cerebral dysrhythmia, when leaving them abruptly it generated anxiety and after months POIS

That clonazepam gave you POIS after discontinuing the usage of that?

[Muon]

That clonazepam gave you POIS after discontinuing the usage of that?

Click on his profile name and go to 'show posts' for post history.

[Journey]

That clonazepam gave you POIS after discontinuing the usage of that?

Click on his profile name and go to 'show posts' for post history.

I have seen already his original post about that.

[Muon]

I spent 4 months with colitis and lost half of my weight until thankfully my mother deduced that soy was the culprit.

Hmm, I don't think I expell any liquid, apart from normal natural lubrication (which I produce a lot of).

I came across this by chance:

"VIP seems to be an important neuropeptide during inflammatory bowel diseases since the communication between mast cells and VIP in colitis, as in Crohn's disease, is upregulated."

"VIP provokes vaginal lubrication in normal women, doubling the total volume of lubrication produced."

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

Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats:
https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.12127

Mast cell number, substance P and vasoactive intestinal peptide in irritable bowel syndrome with diarrhea:
https://www.tandfonline.com/doi/abs/10.3109/00365521.2013.857712

I feel irritated and sometimes downright angry for no apparent reason.

"The production and release of the neuropeptide VIP is centralized in the hypothalamic and extrahypothalamic regions of the brain and from there it is able to modulate the release of prolactin secretion.[24] Once secreted from the pituitary gland, prolactin can increase many behaviors such as parental care and aggression."

My GI tract reacts easily to stress (and food):

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.

This is ruining my life, and the symptoms have been consistently getting worse and worse every time, to the point that I fear dying during one of these "POIS attacks". And lately my neck gets so stiff and hurts so much that I can't even takes notes properly in class. It's a nightmare.

Something else, I had painfully stiff muscles due to POIS a week ago. The higher part of the back, shoulders and part of the upper arms were affected, the weird thing was it kept getting stiffer and stiffer up to the point I could barely move my right arm, it was that painful (there was only pain present during movement, not in rest). Moving my arm/shoulder, was like the feeling of almost tearing some muscles. I slept one night with clothes on because undressing was too painful. Quite a weird event, I have never experienced this intensity of stiffness before.

My symptoms were getting worse in a trending motion as well (Dr. Afrin mentioned this somewhere that he sees this in MCAS patients, can happen more than once in a lifetime, building up to escalations). I wonder whether mast cells were infiltrating somewhere, like in the GI tract or just getting more reactive over time.

She developed the same type of exercise intolerance after exposure to bleach (MC trigger?). https://poiscenter.com/forums/index.php?topic=3609.0

[Muon]

Well...good luck reaching a proper diagnosis without a proper diagnostic workup.

Well, beggars can't be choosers unfortunately. We have an extensive healthcare system over here, but the competency around chronic (and especially rare) disorders seems to be a real wasteland. I've heard from the University hospital that we basically had a single MCAD expert and she retired last year. So I have to work with this guy and see what I can do.

From the book tuning the brain:
"My patients from Australia described the medical environment for CFS as a "vast wasteland," although some progress was being made in educating individual physicians."

Seems there has been made little progress 20/30 years later...

[Muon]

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration



Figure 1. Mast cells in inflammatory diseases. Mast cells play a crucial role in the pathogenesis of many inflammatory diseases of various organs. Certain systemic inflammatory conditions could affect and augment neuroinflammation and neurodegeneration. Therefore, targeting mast cells represents a potentially novel approach to developing the next generation of precision guided therapeutic strategies for the treatment of inflammatory diseases. IBD, inflammatory bowel disease; CAD, coronary artery disease; BBB, blood-brain barrier.



Figure 2. Schematic diagram showing peripheral inflammatory factors and cells on neuroinflammation and neurodegeneration. Peripheral mast cell activation releases proinflammatory and neurotoxic mediators such as histamine, glia maturation factor (GMF), ?-synuclein, corticotropin-releasing hormone (CRH), proteases, cytokines and chemokines. These mediators can induce neuroinflammation by inducing BBB breakdown, entering into the brain and activating glia and neurons to secrete various additional inflammatory mediators. Peripheral mast cells and T-cells enter into the brain, proliferate and secrete proinflammatory mediators that activate glia and neurons to secrete more inflammatory mediators, reduce uncoupling protein (UCP) expression, and induce neurodegeneration. Further, glia and mast cells reactivate each other in the brain through co-stimulatory molecules CD40/CD154 or inflammatory mediators such as TNF-?, IL-1? or IL-33. Mast cell tryptase acts on the neurons through PAR2.

Mast cells can reactivate by their own mediators in an autocrine and paracrine manner to exacerbate inflammatory mechanisms. ?-synuclein or MPP+ from glia/neuron or extracellular A?1–42 can further activate mast cells to release neuroinflammatory mediators in Alzheimer’s disease (AD) or Parkinson’s disease (PD). Additionally several inflammatory mediators from the peripheral system can alter BBB, enter the brain and activate the neuroinflammatory pathways. Inflammatory mediators released from activated microglia and astrocytes can enter into peripheral system through defective BBB; then, they can activate and recruit immune and inflammatory cells towards the inflammatory site in the brain. MC, mast cell; MCP, mast cell progenitor; TC, T-cell; PAR2, protease activated receptor-2.

[Hopeoneday]

ME connection to  MCAS
https://me-pedia.org/wiki/Mast_cell_activation_syndrome

[Muon]

Postorgasmic Illness Syndrome: Two Cases

"A 43-year-old male visited our department without any referral. His medical history was unremarkable, apart from lifelong hyperhydrosis on mild exertion, spontaneous ejaculations, lifelong premature ejaculation, stuttering, and allergy to penicillin. His symptoms consisted of flulike symptoms the onset of which coincided with the moment of ejaculation and included extreme fatigue and exhaustion; feelings of extreme warmth inside the body ("like an exploding fire-ball" in the lower abdominal region)"

From the book 'Never bet against occam: mast cell activation disease and the modern epidemics of chronic illness and medical complexity':

"Ironically, only two months after I first met Mark, I heard of yet another case of spontaneous human combustion covered by the popular media. A man in a porn shop in San Francisco reportedly had suddenly erupted in flames and had run out of the shop into the street before collapsing. He was taken to the burn unit of a local hospital. Police investigation found no source of combustion. Given my hypothesis by that point that spontaneous human combustion might be the consequence of an acute stress causing enough release of norepinephrine by adipose tissue mast cells to raise the temperature of such tissue to the ignition point, I wondered whether it might have been the stress of sexual excitement that could have caused the event in this victim.

Through news reports and Google, I tracked down the San Francisco medical examiner and the chief of the burn unit at the hospital to which the patient had been taken. I e-mailed them regarding my theory and suggested that a work-up for MCAS would not be unreasonable, but, unsurprisingly ( ? ), I never heard anything from either of them. I am convinced spontaneous human combustion is real, though it obviously will be difficult to prove my hypothesis as to its etiology. To this day, though, I haven't come across any evidence proving my hypothesis can't hold water."

[Muon]

Targeting Siglec-8 for POIS?

Discovery, Function, and Therapeutic Targeting of Siglec-8

Mast Cell Effects on Esophageal Smooth Muscle and their Potential Role in Eosinophilic Esophagitis and Achalasia

[Muon]

Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis (2019)

[Muon]

Mast Cells Down-Regulate CD4+CD25+ T Regulatory Cell Suppressor Function via Histamine H1 Receptor Interaction

[Muon]

Dr Nicole Prause - Advancing Research In Sexual Psychophysiology, Sexual Biotechnology, And Sex-Tech

"Given increasing appreciation of a great menagerie of mutations in MC regulatory elements in mastocytosis and MCAS, the great heterogeneity of MCAD’s clinical presentation is unsurprising. Most MCAD patients present with decades of chronic multisystem polymorbidity generally of an inflammatory?±?allergic theme. Preliminary epidemiologic investigation suggests MCAD, while often misrecognized, may be substantially prevalent, making it increasingly important that practitioners of all stripes learn how to recognize its more common forms such as MCAS." Ref