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Treatment of refractory mastocytic enterocolitis with budesonide


J Gastrointestin Liver Dis. 2018 Sep;27(3):327-329. doi: 10.15403/jgld.2014.1121.273.dha.

Kuruvilla ME, Mathew S, Avadhani V (Emory University, Atlanta, Georgia, USA; Mercer University School of Medicine, Macon, Georgia, USA)


Mast cells (MCs) are being increasingly implicated as a possible contributor to symptoms in diarrhea predominant irritable bowel syndrome (IBS). The term "mastocytic enterocolitis" was proposed to describe an increase in mucosal MCs in patients with chronic diarrhea due to functional gastrointestinal disease (FGID). The efficacy of anti-MC mediator therapy (antihistamines and MC stabilizers) has been well documented in this setting. Here we describe the treatment with oral budesonide of mastocytic enterocolitis refractory to standard anti-MC therapy.

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The Importance and Control of Low-Grade Inflammation Due to Damage of Cellular Barrier Systems That May Lead to Systemic Inflammation


Front Neurol. 2019; 10: 533. Published online 2019 May 29. doi: 10.3389/fneur.2019.00533

Cecilia Rönnbäck and Elisabeth Hansson (Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)

Edited by: Kempuraj Duraisamy, University of Missouri, United States

Reviewed by: Damir Janigro, Case Western Reserve University, United States; Manuel Antonio Riquelme, The University of Texas Health Science Center at San Antonio, United States

This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neurology


Systemic low-grade inflammation can be initiated in vivo after traumatic injury or in chronic diseases such as neurodegenerative, metabolic, and autoimmune diseases. Inducers of inflammation trigger production of inflammatory mediators, which alter the functionality of tissues and organs and leads to harmful induction of different barrier systems in the body, where the blood-brain barrier, the blood-retinal barrier, blood-nerve barrier, blood-lymph barrier and the blood-cerebrospinal fluid barrier play major roles. The different barriers are unique but structured in a similar way. They are equipped with sophisticated junctional complexes where different connexins, protein subunits of gap junction channels and hemichannels, constitute important partners. The cells involved in the various barriers are coupled in networks, are excitable but do not express action potentials and may be targets for inflammation leading to changes in several biochemical cellular parameters. During any type of inflammation barrier break-down is observed where any form of injury can start with low-grade inflammation and may lead to systemic inflammation.

Keywords: blood-brain barrier, blood-retinal barrier, blood-nerve barrier, blood-lymph barrier, blood-cerebrospinal fluid barrier, low-grade inflammation, systemic inflammation

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Risk factors and indicators of severe systemic insect sting reactions


Allergy. 2019 Jun 13. doi: 10.1111/all.13945. [Epub ahead of print]

Stoevesandt J, Sturm G, Bonadonna P, Oude Elberink JNG, Trautmann A


Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom allergic patients. Measurement of platelet activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: Age; mastocytosis; medication; tryptase; venom

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Irritable bowel syndrome, endometriosis and polycystic ovary syndrome: is there a link?


International Journal of Research in Medical Sciences | June 2019 | Vol 7 | Issue 6 Page 2449

Ashwath Narayan Ramji (Department of Surgery, Kempegowda Institute Medical Sciences, Bangalore, Karnataka, India)


Chronic pelvic pain is a common yet difficult problem to manage, plaguing the gynecologist as well as the gastroenterologist and general surgeon. Highlighted by increased visceral hypersensitivity, endometriosis and irritable bowel syndrome (IBS) are the most common causes or chronic unrelenting pelvic pain. Recently, the similarities between the two conditions has begged the question as to whether there is any common denominator between the two conditions and their likely co-existence and mismanagement. Further, the association of polycystic ovary syndrome (PCOS) in this cohort remains definitively uncharacterized. This report details a young female patient with the triad of POCS, IBS and endometriosis presenting with chronic pelvic pain.

Keywords: Chronic pelvic pain, Chocolate cyst, Endometriosis, Irritable bowel syndrome, Metabolic Syndrome, Pelvic inflammatory disease, Polycystic kidney disease, Visceral hypersensitivity

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Cytokine Diversity in Human Peripheral Blood Eosinophils: Profound Variability of IL-16


Michelle Ma, Caroline M. Percopo, Daniel E. Sturdevant, Albert C. Sek, Hirsh D. Komarow and Helene F. Rosenberg

J Immunol June 10, 2019, ji1900101; DOI: https://doi.org/10.4049/jimmunol.1900101. Accepted May 20, 2019.

Key Points

Eosinophils are heterogeneous with natural variations in cytokine content.

Eosinophil IL-16 content varies dramatically among normal donors (CV = 103%).

Eosinophil IL-16 content may correlate directly with donor BMI (R2 = 0.60).


Eosinophilic leukocytes develop in the bone marrow and migrate from peripheral blood to tissues, where they maintain homeostasis and promote dysfunction via release of preformed immunomodulatory mediators. In this study, we explore human eosinophil heterogeneity with a specific focus on naturally occurring variations in cytokine content. We found that human eosinophil-associated cytokines varied on a continuum from minimally (coefficient of variation [CV] ≤ 50%) to moderately variable (50% < CV ≤ 90%). Within the moderately variable group, we detected immunoreactive IL-27 (953 ± 504 pg/mg lysate), a mediator not previously associated with human eosinophils. However, our major finding was the distinct and profound variability of eosinophil-associated IL-16 (CV = 103%). Interestingly, eosinophil IL-16 content correlated directly with body mass index (R2 = 0.60, ***p < 0.0001) in one donor subset. We found no direct correlation between eosinophil IL-16 content and donor age, sex, total leukocytes, lymphocytes, or eosinophils (cells per microliter), nor was there any relationship between IL-16 content and the characterized −295T/C IL-16 promoter polymorphism. Likewise, although eosinophil IL-1β, IL-1α, and IL-6 levels correlated with one another, there was no direct association between any of these cytokines and eosinophil IL-16 content. Finally, a moderate increase in total dietary fat resulted in a 2.7-fold reduction in eosinophil IL-16 content among C57BL/6-IL5tg mice. Overall, these results suggest that relationships between energy metabolism, eosinophils, and IL-16 content are not direct or straightforward. Nonetheless, given our current understanding of the connections between asthma and obesity, these findings suggest important eosinophil-focused directions for further exploration.

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The Role of Rhodomyrtus tomentosa (Aiton) Hassk. Fruits in Downregulation of Mast Cells-Mediated Allergic Responses


BioMed Research International, Volume 2019, Article ID 3505034, 7 pages. https://doi.org/10.1155/2019/3505034

Thanh Sang Vo, Young-Sang Kim, Dai-Nghiep Ngo, and Dai-Hung Ngo

Rhodomyrtus tomentosa, a flowering plant of Myrtaceae family from southern and southeastern Asia, was known to possess a rich source of structurally diverse and various biological activities. In this study, the inhibitory effect of R. tomentosa fruit extract (RFE) on allergic responses in calcium ionophore A23187-activated RBL-2H3 mast cells was investigated. The result showed that RFE was able to inhibit mast cell degranulation via decreasing 𝛽-hexosaminidase release and intracellular Ca2+ elevation at the concentration of 400 𝜇g/ml. Moreover, the suppressive effects of RFE on the production of interleukin-1𝛽 (IL-1𝛽) and tumor necrosis factor-𝛼(TNF-𝛼)were evidenced. In addition, RFE effectively scavengedDPPH radical and suppressed the reactive oxygen species generation in a dose-dependent manner. Notably, the pretreatment of RFE caused the downregulation of tyrosine kinase Fyn phospholipid enzyme phospholipase C𝛾 (PLC𝛾), extracellular-signal-regulated kinase (ERK), and nuclear factor kappa B (NF-𝜅B) phosphorylation. These results indicated that RFE could be a promising inhibitor of allergic responses and may be developed as bioactive ingredient for prevention or treatment of allergic diseases.

Copyright © 2019 Thanh Sang Vo et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Mast Cells and Their Progenitors in Allergic Asthma


Front Immunol. 2019; 10: 821. Published online 2019 May 29. doi: 10.3389/fimmu.2019.00821

Erika Méndez-Enríquez and Jenny Hallgren (Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden)

Edited by: Clinton Mathias, Western New England University, United States

Reviewed by: Lennart K. A. Lundblad, Meakins-Christie Laboratories, Canada; Hydar Ali, University of Pennsylvania, United States

This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology


Mast cells and their mediators have been implicated in the pathogenesis of asthma and allergy for decades. Allergic asthma is a complex chronic lung disease in which several different immune cells, genetic factors and environmental exposures influence the pathology. Mast cells are key players in the asthmatic response through secretion of a multitude of mediators with pro-inflammatory and airway-constrictive effects. Well-known mast cell mediators, such as histamine and bioactive lipids are responsible for many of the physiological effects observed in the acute phase of allergic reactions. The accumulation of mast cells at particular sites of the allergic lung is likely relevant to the asthma phenotype, severity and progression. Mast cells located in different compartments in the lung and airways have different characteristics and express different mediators. According to in vivo experiments in mice, lung mast cells develop from mast cell progenitors induced by inflammatory stimuli to migrate to the airways. Human mast cell progenitors have been identified in the blood circulation. A high frequency of circulating human mast cell progenitors may reflect ongoing pathological changes in the allergic lung. In allergic asthma, mast cells become activated mainly via IgE-mediated crosslinking of the high affinity receptor for IgE (FcεRI) with allergens. However, mast cells can also be activated by numerous other stimuli e.g. toll-like receptors and MAS-related G protein-coupled receptor X2. In this review, we summarize research with implications on the role and development of mast cells and their progenitors in allergic asthma and cover selected activation pathways and mast cell mediators that have been implicated in the pathogenesis. The review places an emphasis on describing mechanisms identified using in vivo mouse models and data obtained by analysis of clinical samples.

Keywords: mast cell, mast cell progenitors, allergic asthma, mast cell development, mast cell activation

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