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1652

A cross-sectional study of provider and patient characteristics associated with outpatient disclosures of dietary supplement use

Derjung M Tarn et al. Patient Educ Couns. 2015 Jul.

…

A supplement-drug interaction occurs when a supplement competes with a drug for the same mechanism of absorption, distribution, metabolism, or excretion (ADME).

If the supplement elbows out the prescription medication, it can lead to a different concentration of the drug at the site of action.

So, the drug may not work as intended or result in unexpected adverse effects.

More than 1,000 enzymes are involved in ADME mechanisms, and they’re categorized into four basic families:

CYP - cytochrome P450 (CYP) drug metabolism enzymes

UGT - uridine diphosphate-glucuronosyltransferase (UGT) conjugating enzymes

ABC - adenosine triphosphate-binding cassette (ABC) drug uptake/efflux transporters

OATP - organic anion-transporting polypeptide (OATP) drug transporters

Importantly, six CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4) metabolize nearly 80% of all prescribed drugs.

Other important ADME enzymes in supplement-drug interactions are OATP1A1, OATP1A2, OATP2B1, and the ABC transporter P-glycoprotein (P-gp).
…

Seventy-nine percent of 603 patients reported on a post-visit survey that they took a total of 2107 dietary supplements. Of those taking supplements, 232 patients (48.6%) discussed at least one supplement with their provider on the day of their office visit.

However, patients disclosed only 714 (33.9%) of the 2107 supplements they were taking. Patients more frequently disclosed supplement use when they saw providers who attributed greater importance to asking about supplements.

Patient characteristics such as patient activation, number of medical conditions, and use of prescription medications were not associated with disclosure of supplement use.

1653

If cromolyn sodium and other mast cell stabilizers predominately affect the GI system, how do we treat the rest?

Mast cells are the great communicator of the immune system. Various sources quote that ablut 70 percent of your immune system resides in the vascular rich tissues of your GI system.

Your gut mast cells through cytokines, neuromodulators, and other mediators communicates with your brain, endrocrine, and othernorgan systems.

So when you quiet down the mast cells in your GI tract, you turn the alarm bells all over your body.

"The widespread tissue distribution of mast cells and their versatility allow them to respond to harmful situations as a first-response and respond to environmental changes through the interactions with other cells implicated in physiological and immunological responses.

Their ubiquitous distribution places mast cells in a privileged position to act not only as guardians of the immune system, but to also participate in many biological processes and in the maintenance of homeostasis.

Mast cells have both immunomodulatory as well as physiological functions. It is currently acknowledged that mast cells modulate innate and adaptive immune responses, both directly and indirectly, through communication with other immune cells.

Moreover, mast cells are able to modulate immune responses through their array of mediators, surface molecules, and co-stimulatory molecules."

1654

Mast Cells in Gut and Brain and Their Potential Role as an Emerging Therapeutic Target for Neural Diseases

Giovanna Traina

Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy

The mast cells (MCs) are the leader cells of inflammation. They are well known for their involvement on allergic reactions through degranulation and release of vasoactive, inflammatory, and nociceptive mediators.

Upon encountering potential danger signal, MCs are true sensors of the environment, the first to respond in rapid and selective manner.

The MC activates the algic response and modulates the evolution of nociceptive pain, typical of acute inflammation, to neuropathic pain, typical not only of chronic inflammation but also of the dysregulation of the pain system.

Yet, MC may contribute to modulate intensity of the associated depressive and anxiogenic component on the neuronal and microglial biological front. Chronic inflammation is a common mediator of these co-morbidities.

In parallel to the removal of the etiological factors of tissue damage, the modulation of MC hyperactivity and the reduction of the release of inflammatory factors may constitute a new frontier of pharmacological intervention

1655

A Role for Mast Cells in Alcohol-Induced Tissue Damage and Remodeling

Brittany Law1, Charity Fix2, Blair Barton2,3 and Wayne Carver2*

1Department of Biochemistry and Molecular Biology, Medical University of South Carolina Charleston, USA

2Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Colombia

3 Department of Otolaryngology, School of Medicine, Tulane University, New Orleans, USA

J Clin Exp Pathol 2015, Vol 5(2): 218
DOI: 10.4172/2161-0681.1000218

Abstract

Introduction: Alcohol continues to be one of the most frequently abused drugs in the world. While low levels of alcohol consumption may have health benefits, chronic abuse of alcohol deleteriously impacts most body systems and contributes to or exacerbates over sixty disease conditions. The mechanisms of organ and tissue damage in response to alcohol abuse include altered metabolic pathways, accumulation of reactive oxygen species and depressed immune function.

Mast cells are multi-functional cells that have been classically described for their role in hypersensitivity reactions. More recently, roles for these cells have been elucidated in innate immunity and tissue remodeling.

Mast cells perform these functions primarily through the secretion of a plethora of mediators that include histamine, heparin, serine proteases, cytokines and others. The specific factors that are produced and secreted at any time by mast cells depend in part on the tissue microenvironment providing the basis for extensive plasticity of these cells.

Recent studies are beginning to define the role of mast cells in mediating the deleterious effects of chronic alcohol abuse. For instance, alcohol-induced damage to the gastrointestinal mucosa is at least in part mediated by activation of mast cells.

Pharmacological inhibition of mast cell degranulation attenuates the increased permeability of the gastrointestinal epithelium associated with alcohol abuse.

Conclusion: Mast cells and their secretory products have been implicated in promoting a number of disease conditions. Recent studies have suggested an important role for these cells in alcohol-induced tissue remodeling. These cells and their specific secretory mediators may provide novel therapeutic targets in prevention or reversal of alcohol-induced tissue damage.

https://www.omicsonline.org/open-access/a-role-for-mast-cells-in-alcoholinduced-tissue-damage-and-remodeling-2161-0681-1000218.php?aid=51580#:~:text=Pharmacological%20inhibition%20of%20mast%20cell,a%20number%20of%20disease%20conditions.

1656

When your synapses could do the Kessel run in Eleven Parsecs…

1657

Epigenetic and transcriptional control of mast cell responses

Silvia Monticelli, et al.

Version 1. F1000Res. 2017; 6: 2064.
doi: 10.12688/f1000research.12384.1
PMCID: PMC5710380
PMID: 29225792

Mast cells are tissue-resident, innate immune cells present in most tissues of the body and are important effector and immunomodulatory cells.

Differentiated mast cells typically are characterized by the surface expression of the receptors KIT and FcεRI, the latter especially being important for stimulation through IgE antibodies, although these cells have the ability to respond to a wide variety of environmental signals, to which they can variably react by releasing pre-stored or de novo–synthesized mediators or both.

Since mast cells terminate their differentiation in their tissue of residence in response to specific microenvironmental cues, each tissue may comprise unique mast cell subtypes, and responses are tailored to the danger signals that are likely to be encountered in each anatomical location.

From a transcriptional point of view, these cells therefore must be endowed with epigenetic and transcriptional programs that allow them to maintain a stable identity and at the same time allow sufficient plasticity to adapt to different environmental challenges.

In this commentary, we highlight some of the recent findings that advanced our understanding of the transcriptional and epigenetic programs regulating mast cell functions.

Keywords: mast cell response, transcription factors, epigenetic control

1658

Mask up fashion statement for Covid 19 protection, Hey it’s not just for Mast Cell Chemical and Perfume Sensitivity anymore.:crazy_face::rofl::rofl::mask:

1659

Podcast with Dr Theo

Episode 51: All things Mast Cell with World-Renowned Clinical Researcher Dr. Theoharides

New Frontiers in Functional Medicine

Dr. Kara Fitzgerald

105 minutes

"In my Tour de Force conversation with the brilliant Dr. Theoharis Theoharides, we covered all things mast cells, from “bench to bedside.” In case you have not yet encountered his work yet, he is one of the most highly decorated, well-published clinician researchers in the world. The focus of his life’s work has been on all things mast cells, and mast cell associated conditions. Given the meteoric rise in said conditions (and our improved understanding of the role of mast cells in most chronic diseases), as clinicians, we need to understand how to diagnose and treat.

Buckle up for this podcast, and get your pen and pad ready – the depth and breadth of Dr. T’s knowledge requires careful listening. Give a listen, then give a thumbs up for this brilliant, generous clinician!"

1660

AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management

Catherine R. Weiler MD, PhD, Lawrence B…Schwartz.MD, PhD, et al.

Journal of Allergy and Clinical Immunology

Volume 144, Issue 4, October 2019, Pages 883-896

1661

The rediscovery of hydroxychloroquine in allergic diseases in the COVID-19 era Bonzano L, Cassone G, Tarallo L, Pellacani G.

JouInvestig Allergol Clin Immun

Our reflection begins with a pioneering study from 1989, where it was shown that the pretreatment of rat mast cells with chloroquine (10-1000 µmol/L) reduced their ability to degranulate and produce prostaglandins D2, resulting in the inhibition of phospholipase A2 and histamine activity [3].

Moreover, it has also been shown in vitro that prolonged treatment with HCQ for three to five weeks on human mast cells leads to decrease the intracellular expression level of CD63 and to modify the expression pattern of CD63.

Thus, HCQ treatment does not alter intracellular levels of tryptase and chymase as detected by flow cytometry, but dramatically decreases tryptase enzymatic activity and the expression of key mast cell mediators, such as IL-8 and GM-CSF [4].

These results were also confirmed by Charous et al. They reported the antiallergic effects of HCQ in terms of selective and profound inhibition of IgE and improved airflow in subjects with moderate symptomatic asthma.

In fact, antimalarials seem to inhibit IL-4–driven IgE synthesis of human peripheral blood lymphocytes, suggesting that HCQ may decrease bronchial inflammation by reducing the IgE involved in its pathogenesis.

It has also been shown that block histamine induced bronchoconstriction and reproducibly decreased antigen-induced bronchoconstriction in animal models, suggesting potential utility in the treatment of asthma [5].

In light of these clinical observations and the potential immuno-pathological action of HCQ, as well as its tolerability, rare toxicity, inexpensive cost and immunomodulatory properties, it makes sense to investigate the possible role of HCQ for the control of severe allergic diseases in selected cases.

Prospective clinical trials are needed to further evaluate the use of HCQ in this challenging field

1662
1663

The Hormones We Have at Birth Are Linked to Disease Throughout Life

WRITTEN BY: Carmen Leitch
Sources: AAAS/Eurekalert! via Michigan State University, Proceedings of the National Academy of Sciences

New work may help explain why some autoimmune or immune-related diseases are more common in women, who are more likely to have disorders like allergies, irritable bowel syndrome, and asthma.

Researchers have connected the hormones that are present before and after birth with a lifetime risk of immune disease, and immune response. The findings, which may help open up new therapeutic options, have been reported in the Proceedings of the National Academy of Sciences.

“This research shows that it’s our perinatal hormones, not our adult sex hormones, that have a greater influence on our risk of developing mast cell-associated disorders throughout the lifespan,” said the principal investigator of the study Adam Moeser, the Matilda R. Wilson Endowed Chair and professor in the Department of Large Animal Clinical Sciences at Michigan State University. “A better understanding of how perinatal sex hormones shape lifelong mast cell activity could lead to sex-specific preventatives and therapies for mast cell-associated diseases.”

The immune system has many cell types, including mast cells, which serve multiple purposes; they can defend against invaders, help control the immune response, and play a role in wound healing. However, their activity has to be regulated. When they are overactive, they can trigger chronic inflammatory diseases and may even lead to death in some cases.

1664

Perinatal androgens organize sex differences in mast cells and attenuate anaphylaxis severity into adulthood

Emily Mackey, Kyan M. Thelen, Vedrana Bali, Mahsa Fardisi, Madalyn Trowbridge, Cynthia L. Jordan, and Adam J. Moeser

PNAS first published September 11, 2020 https://doi.org/10.1073/pnas.1915075117

Paywall $10

Mast cell (MC)-associated disorders exhibit a sex bias, with females at increased risk. While attention has been directed to adult sex hormones as a mechanism for disease risk between the sexes, epidemiological evidence clearly shows that these same sex biases also exist in prepubertal children, thus challenging this concept.

Here, we show that perinatal, but not adult gonadal, androgens play a protective role in MC-mediated anaphylaxis severity into adulthood.

We propose that perinatal androgens mediate their protective effects via programming of bone marrow MC precursors to exhibit reduced granule histamine and release.

These findings shift attention to perinatal life as a critical period for potential interventions to mitigate MC-associated disease risk across the lifespan in males and females.

https://www.pnas.org/content/early/2020/09/10/1915075117

1665

A good read.

Biology of Sex Differences in Mast Cell-Mediated Disease

Emily Mackey

A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy

Comparative Biomedical Sciences Raleigh, North Carolina 2019

Abstract

Biological sex is a risk factor in a number of immune disorders but the mechanisms are poorly understood. In many immune-related diseases such as allergy, anaphylaxis, and autoimmune diseases, females are at increased risk. However, the sex-biased factors that increase vulnerability in females or provide resiliency in males are poorly understood.

Here, we demonstrate the key to unraveling sex differences in many immune-related disorders may lie in the mast cell. Mast cells are hematopoietic-derived innate immune cells ubiquitously located in the body, and are potent orchestrators and effector cells in the immune response.

Moreover, many mast cell-associated disorders including irritable bowel syndrome, migraine, chronic pain, allergy/anaphylaxis, and autoimmune disease, exhibit a strong sex bias in which females are more susceptible.

Adult sex hormones may explain some of the underlying causes of sex-biased disease responses; however, this is challenged by the fact that sex biases in many mast cellassociated disorders are evident in prepubertal children.

In this dissertation, we demonstrate an increased severity of mast cell disease in females linked to inherent sex differences in the mast cell transcriptome, phenotype, and functional response.

Further, we demonstrate that sex differences in mast cell phenotype and immune-related disease susceptibility exist prior to the onset of puberty and are established early in life by perinatal androgens.

These findings provide novel insights for therapeutic targets for mast cell disorders with a potential for identifying sex-specific therapies in pediatric and adult disease.

Discerning how sex and perinatal hormone levels influence immune disease risk could also have significant implications in understanding how prenatal and early life stress, and environmental chemical exposures impact immune development and health of the offspring.

https://www.google.com/url?sa=t&source=web&rct=j&url=https://repository.lib.ncsu.edu/bitstream/handle/1840.20/37048/etd.pdf%3Fsequence%3D1%26isAllowed%3Dy&ved=2ahUKEwiArPqZtvrrAhVJ7qwKHQTbCJwQFjAHegQIBxAB&usg=AOvVaw1w8QE5G83SFOIYf7dxodwu

1666

Biological sex is a risk factor in a number of immune disorders but the mechanisms are poorly understood. In many immune-related diseases such as allergy, anaphylaxis, and autoimmune diseases, females are at increased risk. However, the sex-biased factors that increase vulnerability in females or provide resiliency in males are poorly understood. Here, we demonstrate the key to unraveling sex differences in many immune-related disorders may lie in the mast cell. Mast cells are hematopoietic-derived innate immune cells ubiquitously located in the body, and are potent orchestrators and effector cells in the immune response. Moreover, many mast cell-associated disorders including irritable bowel syndrome, migraine, chronic pain, allergy/anaphylaxis, and autoimmune disease, exhibit a strong sex bias in which females are more susceptible. Adult sex hormones may explain some of the underlying causes of sex-biased disease responses; however, this is challenged by the fact that sex biases in many mast cellassociated disorders are evident in prepubertal children. In this dissertation, we demonstrate an increased severity of mast cell disease in females linked to inherent sex differences in the mast cell transcriptome, phenotype, and functional response. Further, we demonstrate that sex differences in mast cell phenotype and immune-related disease susceptibility exist prior to the onset of puberty and are established early in life by perinatal androgens. These findings provide novel insights for therapeutic targets for mast cell disorders with a potential for identifying sex-specific therapies in pediatric and adult disease. Discerning how sex and perinatal hormone levels influence immune disease risk could also have significant implications in u

1667

A good read.

Biology of Sex Differences in Mast Cell-Mediated Disease

Emily Mackey

A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy

Comparative Biomedical Sciences Raleigh, North Carolina 2019

Abstract

Biological sex is a risk factor in a number of immune disorders but the mechanisms are poorly understood. In many immune-related diseases such as allergy, anaphylaxis, and autoimmune diseases, females are at increased risk. However, the sex-biased factors that increase vulnerability in females or provide resiliency in males are poorly understood.

Here, we demonstrate the key to unraveling sex differences in many immune-related disorders may lie in the mast cell. Mast cells are hematopoietic-derived innate immune cells ubiquitously located in the body, and are potent orchestrators and effector cells in the immune response.

Moreover, many mast cell-associated disorders including irritable bowel syndrome, migraine, chronic pain, allergy/anaphylaxis, and autoimmune disease, exhibit a strong sex bias in which females are more susceptible.

Adult sex hormones may explain some of the underlying causes of sex-biased disease responses; however, this is challenged by the fact that sex biases in many mast cellassociated disorders are evident in prepubertal children.

In this dissertation, we demonstrate an increased severity of mast cell disease in females linked to inherent sex differences in the mast cell transcriptome, phenotype, and functional response.

Further, we demonstrate that sex differences in mast cell phenotype and immune-related disease susceptibility exist prior to the onset of puberty and are established ea

1668

Biology of Sex Differences in Mast Cell-Mediated Disease

Emily Mackey

A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy

Comparative Biomedical Sciences
Raleigh, North Carolina 2019

1669

Mast cell degranulation activates a pain pathway underlying migraine headache

Dan Levy, Rami Burstein, […], and Andrew M. Strassman

Intracranial headaches such as that of migraine are generally accepted to be mediated by prolonged activation of meningeal nociceptors but the mechanisms responsible for such nociceptor activation are poorly understood.

In this study, we examined the hypothesis that meningeal nociceptors can be activated locally through a neuroimmune interaction with resident mast cells, granulated immune cells that densely populate the dura mater.

Using in vivo electrophysiological single unit recording of meningeal nociceptors in the rat we observed that degranulation of dural mast cells using intraperitoneal administration of the basic secretagogue agent compound 48/80 (2 mg/kg) induced a prolonged state of excitation in meningeal nociceptors.

Such activation was accompanied by increased expression of the phosphorylated form of the extracellular signal-regulated kinase (pERK), an anatomical marker for nociceptor activation.

Mast cell - induced nociceptor interaction was also associated with downstream activation of the spinal trigeminal nucleus as indicated by an increase in c-fos expression.

Our findings provide evidence linking dural mast cell degranulation to prolonged activation of the trigeminal pain pathway believed to underlie intracranial headaches such as that of migraine.

1670

Migraine Headaches: The Immunologist’s View

IMMUNOLOGY OF MIGRAINE

Theoharis C. Theoharides, Ph.D, M.D.

HOSPITAL CHRONICLES 2006, SUPPLEMENT: 79–83

Review evidence supporting the role of mast cells in migraine pathophysiology.

BACKGROUND: Mast cells are known for their role in allergic reactions, but they are also important in immunity and inflammatory diseases, especially those precipitated or worsened by stress.

Such are migraine headaches that are associated with spreading neuronal depression and neurogenic inflammation intracranially. Migraines are also comorbid with allergies and could precipitate acute coronary syndromes (ACS).

Mast cells are located perivascularly, in close association with neurons, especially in the meninges.

Mast cells can be activated by trigeminal nerve stimulation and by acute stress, leading to increased vascular permeability and neurogenic inflammation dependent on NK-1 receptors, but not necessarily on substance P (SP).

METHODS: We reviewed relevant literature and summarized our own findings.

RESULTS: Corticotropin-releasing hormone (CRH), a mediator of the stress response released from the hypothalamus, can activate CRH receptors either on the sensory nuclei of the trigeminal nerve or directly on the mast cells. They, then release proinflammatory, nociceptive and vasoactive mediators including histamine, tryptase and vascular endothelial growth factor (VEGF), thereby triggering migraine headaches.

CONCLUSIONS: These results indicate that there are several novel points of intervention for the development of therapeutic agents to help alleviate migraines. Preliminary clinical studies with brain mast cell blockers and CRH receptor antagonists suggest that they could be useful prophylactically.

1671

Mast Cells Release Migraine-Inducing PACAP

This finding may explain the observed association between allergy and migraine.

Neurology Reviews. 2018 October;26(10):45

Biologically active pituitary adenylate cyclase-activating polypeptide (PACAP) is released by mast cells: a finding that may provide an explanation for the association between allergy and migraine.

“In the investigation of the role of mast cells in migraine pathology, we found that human mast cells contain PACAP in their cytoplasmic granules.

Bioactive PACAP can be released from mast cells by inducing degranulation,” said lead author Angela J. Okragly, Senior Research Scientist at Eli Lilly and Company in Indianapolis, and colleagues.

“This finding provides a potential explanation linking mast cell activation to migraine through the release of PACAP.” Their study was published in the August issue of Cephalalgia.

Human mast cells release the migraine-inducing factor pituitary adenylate cyclase-activating polypeptide (PACAP)

Angela J Okragly et al. Cephalalgia. 2018 Aug.

https://journals.sagepub.com/doi/pdf/10.1177/0333102417740563