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General
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"Beneficial effects of LDN on MCAS may include regulating overall T-lymphocyte production and decreasing cytokine mediators from T cells which directly cause MC activation, blocking Toll receptors which stimulate MC activity and reducing neuroinflammatory pain via microglia.

Endorphins produced by LDN may improve intestinal dysmotility in POTS by directly increasing the migrating motor complex which prevents small intestinal stasis and subsequent bacterial overgrowth.

We theorise that neuropathic POTS with an immune mechanism may also be improved by LDN via reduction of autoimmune antibody production by B-lymphocyte regulation."

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Cromolyn Sodium May Attenuate Covid-19 SARS and Systemic Complications and May Be Useful Prophylactically.

"Fatalities due to SARS-COV2 (COVID 19) infection continue rising worldwide. The need exists for additional treatment options addressing antiviral replication, Severe acute respiratory syndrome (SARS) and the cytokine storm (1-4).
In the most recent article by Tao Chen et al (2), it is noted that interferon treatment has more recovered patients than deceased. Modulation of the host immune response may be an important strategy to improve patient survival. Interferon b 1a trial is underway in the U.K. (1).

Severe acute respiratory syndrome (SARS) and the cytokine storm account for a large part of the high mortality in intensive care units (2).

The NF-ÎşB pathway is often targeted by viral pathogens to enhance viral replication, host cell survival and host immune evasion. Viruses may activate or suppress NF-kB. (5). There have many studies on SARS-COV since 2002-2003 SARS epidemic. SARS-COV2 (COVID-19) belongs to the same family of corona viruses and shares many similarities (3)"

"Cromolyn may be proposed as an adjunct treatment.

Cromolyn has been found to have broader anti-inflammatory and anti-tumor mechanisms than what has been described historically as an antiallergy and mast cell stabilizer (12).

Cromolyn has been identified to inhibit of S100P activation of RAGE and inhibited elevated basal activity of NF-kB pathway in pancreatic cancer cells in vitro and in vivo in (13).

S100P proteins as therapeutic targets has been reviewed elswhere (14). Cromolyn binds S100P in a stable complex (15 ). Cromolyn has been found to be effective in reducing inflammation pathways in several other diseases (16 - 22).

Another reported mechanism of Cromolyn sodium is that it acts as a chloride channel inhibitor (Reviewed in reference 12, 28). Viral infections and replication depend on host cell membrane chloride channels (29, 30, 31, 32, 33, 34), . Viruses posses ion channels called viroporins (30, 31). Cromolyn may also directly affect these channels.

Furthermore, Cromolyn may attenuate innate immune responses that are influenced by chloride ion channels (35).

Some of deaths due to COVID 19 are due to cardiac involvement (2). Cromolyn may also act on NF-kB mediated remodeling in the inflamed heart in acute viral myocarditis (36).

Inhaled Cromolyn has a favorable safety profile and having been used for asthma treament for several decades since the sixties, including children and pregnant women, and with renewed interest in for repurposing in other diseases, has well-studied pharmacokinetics (37).

In summary, Cromolyn may be effective in decreasing inflammation, ARDS, and cytokine storm in COVID 19 patients.

It may also reduce viral replication and systemic inflammation, in particular cardiac inflammation. It may be administerd in a variety of ways. It may be administered as a nebulized therapy, oral, nasal and IV. Nebulized therapy may achieve better penetration of the inflammed tissues of the lung of progressively worsening patients.

Cromolyn sodium may be included as part of the treatment of COVID 19 patient at different stages in their infection, mild, moderate or severe. Cromolyn may work synergistically with interferon therapy.
Exploration of using Cromolyn prophylactically intranasal, inhaled or oral cromolyn sodium may also be feasible.

https://www.bmj.com/content/368/bmj.m1252/rr-1

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Wearing masks over and over isn’t a good idea. Handling after use risks contamination.

Even storing in a paper bag and handling by straps risks cross infection.

Doing Counter Biowarfare research a few years ago our researchers found Microwave Generated Steam MGS was effective in decontaminating masks with all sorts of nasties. 70C for 5 minutes (158°F) will clean up most any thing.

We had a complicated fixture. Veggie steamer from New Zealand works just as good as our $1/2 M fixture. 4 minutes with 1000 Watt Microwave got it to over 175°F. And then let it set for 5 minutes.

Just remove the metal strips before nuking. Wear gloves handling the ‘dirty’ mask and wash hands.

https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30003-3/fulltext

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The Circadian Clock Drives Mast Cell Functions in Allergic Reactions

Pia Christ, Anna Sergeevna Sowa, […], and Axel Lorentz
Additional article information

Abstract

Allergic diseases are known to vary in the severity of their symptoms throughout the day/night cycle. This rhythmicity is also observed in mast cell function and responsiveness. Mast cells are key effector cells of allergic reactions and release cytokines, chemokines, and important inflammatory mediators such as histamine, which have been shown to display diurnal variation.

Recent research clarified that mast cells are controlled by their internal clock—which is regulated by a specific set of clock genes—as well as external factors such as light sensed by the suprachiasmatic nuclei, hormonal status, or diet.

Here, we give an overview of the connections between circadian clock, mast cells, and allergic disease. Further work aimed at studying the role of chronotherapy/chronomedicine should take into account this rhythmic nature of not only mast cells but also the immune responses generated by mast cell signaling.

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I prefer Community Normal Saline, Or Ringer’s Lactate of Dunkin’ Donuts Dark roast.

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Some good news

Detailed analysis of immune response to SARS-CoV-2 bodes well for COVID-19 vaccine
MedicalXpress Breaking News-and-Events
May 15, 2020

Published in today’s online edition of Cell, the study documents a robust antiviral immune response to SARS-CoV-2 in a group of 20 adults who had recovered from COVID-19. The findings show that the body’s immune system is able to recognize SARS-CoV-2 in many ways, dispelling fears that the virus may elude ongoing efforts to create an effective vaccine.

“If we had seen only marginal immune responses, we would have been concerned,” says Sette, a professor in the Center for Infectious Disease and Vaccine Research, and adds, “but what we see is a very robust T cell response against the spike protein, which is the target of most ongoing COVID-19 efforts, as well as other viral proteins. These findings are really good news for vaccine development.”

“All efforts to predict the best vaccine candidates and fine-tune pandemic control measures hinge on understanding the immune response to the virus,” says Crotty, also a professor in the Center for Infectious Disease and Vaccine Research. “People were really worried that COVID-19 doesn’t induce immunity, and reports about people getting re-infected reinforced these concerns, but knowing now that the average person makes a solid immune response should largely put those concerns to rest.”

“We specifically chose to study people who had a normal disease course and didn’t require hospitalization to provide a solid benchmark for what a normal immune response looks like, since the virus can do some very unusual things in some people,” says Sette.

The researchers found that all COVID-19 patients had a solid CD4, or “helper,” T cell response, which helps antibody production. Almost all patients had produced virus-specific CD8, or “killer,” T cells, which eliminate virus-infected cells. “Our data show that the virus induces what you would expect from a typical, successful antiviral response,” says Crotty.

https://www.mdlinx.com/news/6xT8scxTd9WADfnWXSmA6U

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Fibrinolysis Shutdown Correlates to Thromboembolic Events in Severe COVID-19 Infection

Wright FL, Vogler TO, Moore EE, Moore HB, Wohlauer MV, Urban S, Nydam TL, Moore PK, McIntyre Jr RC,

Journal of the American College of Surgeons (2020)

Patients who are critically ill regardless of cause can develop a condition known as disseminated intravascular coagulation (DIC). The blood of these patients initially forms many clots in small blood vessels. The body’s natural clotting factors can form too much clot or eventually not be able to effectively form any clot leading to issues of both excessive clotting and excessive bleeding.

However, in patients with COVID-19 the clotting appears to be particularly severe and—as evidenced by case studies in China and elsewhere—clots in COVID-19 patients do not appear to dissipate, explained Dr. Wright.

The researchers evaluated outcomes for all patients who had a TEG assay as part of their treatment for COVID-19 infection as well as other conventional coagulation assays, including ones that measure D-dimer levels. D-dimer is a protein fragment that is produced when a blood clot dissolves. D-dimer levels are elevated when large numbers of clots are breaking down.

The research team is now participating in a randomized clinical trial of a drug that breaks down blood clots in COVID-19-infected patients. “This is an early step on the road to discovering treatments to prevent some of the complications that come with this disease,” said Franklin Wright, MD, FACS, lead author of the research article and an assistant professor of surgery at the University of Colorado School of Medicine.

Their research is published as an “article in press” on the Journal of the American College of Surgeons

doi: Fibrinolysis Shutdown Correlation with Thromboembolic Events... : Journal of the American College of Surgeons.

https://linkinghub.elsevier.com/retrieve/pii/S1072751520304002

https://www.mdlinx.com/news/Rvd0KFvgDBwNrDD1VMTuo

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Should have used Muskrats. Muskrat Suzie and Muskrat Sam. Admit it you had to sing it…:rofl::rofl::rofl:

Hamster tests show masks reduce coronavirus spread

Led by Professor Yuen Kwok-yung, one of the world’s top coronavirus experts, the team placed hamsters that were artificially infected with the disease next to healthy animals.

Surgical masks were placed between the two cages with air flow travelling from the infected animals to the healthy ones. The researchers found non-contact transmission of the virus could be reduced by more than 60 percent when the masks were used. Two thirds of the healthy hamsters were infected within a week if no masks were applied.

The infection rate plunged to just over 15 percent when surgical masks were put on the cage of the infected animals and by about 35 percent when placed on the cage with the healthy hamsters.

Those that did become infected were also found to have less of the virus within their bodies than those infected without a mask.

https://www.google.com/amp/s/medicalxpress.com/news/2020-05-hamster-masks-coronavirus-scientists.amp

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Is 8 to 11 years study and residency past your degree worth it?

https://www.medscape.com/slideshow/2020-compensation-overview-6012684

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From Jennifer

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A daily dose of sunshine can actually help fight against a wide range of chronic illnesses.

But, before we get to that, you might be wondering whether the health benefits of sunlight can be obtained through the convenience of vitamin D supplements.

Sadly, according to current research, the answer is no. In a review article published in Lancet Diabetes Endocrinology, for instance, researchers noted that although prospective studies support an association between serum levels of 25-hydroxyvitamin D (25[OH]D)—the principal type of vitamin D circulating in the blood—and various types of chronic disease, interventional studies involving vitamin D supplements do not corroborate such findings.

On the bright side, a little fun in the sun can be a free, stress-relieving way to help defend against these ten common chronic conditions.

https://www.mdlinx.com/article/a-daily-dose-of-this-can-help-fight-chronic-conditions/P5i9BWT7H9W1VJGPntebl?utm_source=alert&utm_medium=email&utm_campaign=ajm_49895

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https://www.annallergy.org/article/S1081-1206(19)30613-1/fulltext

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Masks so incredibly comfortable, I think everyone will be wearing them in the future. Mask 101.

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Persistent postural perceptual dizziness is on a spectrum in the general population

Preprint

Persistent postural perceptual dizziness (PPPD) is a chronic functional condition that describes dizziness and nonspinning vertigo induced by self-movement, challenging visual environments, and upright posture.1,2

PPPD was recently defined in order to unite a range of related conditions previously known as supermarket syndrome,3 visual vertigo,4 chronic subjective dizziness,5 space and motion discomfort,6 and phobic postural vertigo.7

Common triggers include situations of vestibulo-visual conflict, such as cinemas, and intense visual environments, such as supermarkets.

Patients often develop functional gait abnormalities and an excessive vigilance about balance sensations.8–10 PPPD is the second most common condition reported in dizziness clinics and is particularly prevalent in middle age.

https://www.google.com/url?sa=t&source=web&rct=j&url=https://n.neurology.org/content/neurology/early/2020/04/16/WNL.0000000000009373.full.pdf&ved=2ahUKEwiq-ubOqMHpAhVBeawKHeZgCf4QFjABegQICRAB&usg=AOvVaw2W-h0JyRXjE-ZrIdKpwsrK

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Miss Ranitidine? Take Action! Send and Share!

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Novel Identified Receptors on Mast Cells

Helena Migalovich-Sheikhet, Sheli Friedman, […], and Francesca Levi-Schaffer

Abstract

Mast cells (MC) are major participants in the allergic reaction. In addition they possess immunomodulatory roles in the innate and adaptive immune reactions.

Their functions are modulated through a number of activating and inhibitory receptors expressed on their surface.

This review deals with some of the most recently described receptors, their expression patterns, ligand(s), signal transduction mechanisms, possible cross-talk with other receptors and, last but not least, regulatory functions that the MC can perform based on their receptor expression in health or in disease.

Where the receptor role on MC is still not clear, evidences from other hematopoietic cells expressing them is provided as a possible insight for their function on MC.

Suggested strategies to modulate these receptors’ activity for the purpose of therapeutic intervention are also discussed.

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Beyond IgE: Alternative Mast Cell Activation Across Different Disease States David O. Lyons and Nicholas A. Pullen * School of Biological Sciences, University of Northern Colorado, Greeley, CO 80639, USA;

Published: 22 February 2020

Abstract:

Mast cells are.often regarded throughthe lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to.

After the characterization of the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis of mast cell activation—a pathway that is independent of the adaptive immune system—researchers are revisiting other stimuli to induce mast cell activation and/or subsequent degranulation independent of IgE.

This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease.

Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues aswell.

This variety in receptor expression suggests mast cells.respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-β1 (TGF-β1) can enhance mast cell IL-6 production.

Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro.

Given mast cells’ ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response.

Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies and autoimmune disorders of the gut.

In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.

Keywords: mast cell; innate immunity; NLRP3; MRGPRX2; inflammatory bowel disease; cancer; food allergy; trained immunity; TGF-β1; IL-10