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https://www.readbyqxmd.com/read/28332048/histamine-release-from-mast-cells-and-basophils
#1
Francesco Borriello, Raffaella Iannone, Gianni Marone
Mast cells and basophils represent the most relevant source of histamine in the immune system. Histamine is stored in cytoplasmic granules along with other amines (e.g., serotonin), proteases, proteoglycans, cytokines/chemokines, and angiogenic factors and rapidly released upon triggering with a variety of stimuli. Moreover, mast cell and basophil histamine release is regulated by several activating and inhibitory receptors. The engagement of different receptors can trigger different modalities of histamine release and degranulation...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28293189/investigation-into-the-role-of-pi3k-and-jak3-kinase-inhibitors-in-murine-models-of-asthma
#2
Akshaya D Wagh, Manoranjan Sharma, Jogeshwar Mahapatra, Abhijeet Chatterjee, Mukul Jain, Veeranjaneyulu Addepalli
Asthma is a clinical disorder commonly characterized by chronic eosinophilic inflammation, remodeling and hyper responsiveness of the airways. However, the kinases like Phosphoinositide 3 kinase (PI3K) and Janus kinase 3 (JAK3) are involved in mast cell proliferation, activation, recruitment, migration, and prolonged survival of inflammatory cells. The present study was designed to evaluate the in-vivo comparative effects of two kinase inhibitors on airway inflammation and airway remodeling in acute and chronic models of asthma...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28262030/highly-sensitive-assays-are-mandatory-for-the-differential-diagnosis-of-patients-presenting-with-symptoms-of-mast-cell-activation-diagnostic-work-up-of-38-patients
#3
Bea Van den Poel, Anne-Marie Kochuyt, Elke Del Biondo, Barbara Dewaele, Els Lierman, Thomas Tousseyn, Gert de Hertogh, Peter Vandenberghe, Nancy Boeckx
Mastocytosis is a heterogeneous disease caused by excessive mast cell (MC) proliferation. Diagnosis of systemic mastocytosis (SM) is based on the presence of major and minor criteria defined by the World Health Organization. Symptoms of MC activation can also occur in patients without SM or without allergic or inflammatory disease. These MC activation syndromes (MCAS) can be divided into primary (monoclonal) MCAS (MMAS) vs. secondary and idiopathic MCAS. In this single center study, the diagnostic work-up of 38 patients with a clinical suspicion of SM and/or with elevated basic tryptase levels is presented...
March 6, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28261938/mast-cell-disorders-in-ehlers-danlos-syndrome
#4
REVIEW
Suranjith L Seneviratne, Anne Maitland, Lawrence Afrin
Well known for their role in allergic disorders, mast cells (MCs) play a key role in homeostatic mechanisms and surveillance, recognizing and responding to different pathogens, and tissue injury, with an array of chemical mediators. After being recruited to connective tissues, resident MCs progenitors undergo further differentiation, under the influence of signals from surrounding microenvironment. It is the differential tissue homing and local maturation factors which result in a diverse population of resident MC phenotypes...
March 6, 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/28245765/kynurenines-and-pacap-in-migraine-medicinal-chemistry-and-pathogenetic-aspects
#5
János Tajti, Délia Szok, Gábor Nagy-Grócz, Bernadett Tuka, Anna Petrovics-Balog, József Toldi, László Vécsei
BACKGROUND: Migraine is a highly disabling neurovascular primary headache disorder, with its exact pathomechanism being still unrevealed. The current leading hypotheses are based on the sensitization and activation of the trigeminovascular system. OBJECTIVE: To review the literature with focus on the effects of kynurenines (L-kynurenine and kynurenic acid) and pituitary adenylate cyclase-activating polypeptide on the regulation of the trigeminovascular system. METHOD: A literature search was conducted to identify preclinical and clinical publications (198 references) by using the keywords 'kynurenines', 'pituitary adenylate cyclase-activating polypeptide', and 'migraine' in the database of MEDLINE/PubMed up to 10 September 2016for topical review...
February 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28242819/a-rat-long-lasting-cystitis-model-induced-by-intravesical-injection-of-hydrogen-peroxide
#6
Koji Dogishi, Ken Okamoto, Tsuyoshi Majima, Shizuka Konishi-Shiotsu, Takashi Homan, Mizuki Kodera, Shohei Oyama, Tatsuya Oyama, Hisashi Shirakawa, Naoki Yoshimura, Takayuki Nakagawa, Shuji Kaneko
Novel longer lasting inflammatory bladder animal models are needed to better understand the pathophysiology of chronic cystitis. We previously developed a relatively long-lasting mouse cystitis model by intravesical injection of hydrogen peroxide (H2O2). To further evaluate its pathophysiology, in this study, we established and analyzed a rat cystitis model. Under anesthesia, 1.5% H2O2 solution was introduced transurethrally into the bladder of female rats, and kept for 30 min. The H2O2 injection significantly increased the number of micturition events up to day 14 and decreased urine volume per micturition, with the smallest volumes on day 3, compared with the vehicle-treated group...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28242292/systemic-mastocytosis-kounis-syndrome-and-coronary-intervention-case-report-and-systematic-review
#7
REVIEW
Elizabeth D Paratz, Nancy Khav, Andrew T Burns
A 72-year-old male reported a long-standing history of unexplained syncope. Stress echocardiography demonstrated inducible anterior hypokinesis, and he proceeded to percutaneous coronary intervention for an 80% stenosis of the left anterior descending artery. Thirty minutes post-procedure, he experienced a pulseless electrical activity (PEA) cardiac arrest. Urgent repeat angiography demonstrated profound coronary artery spasm consistent with Kounis syndrome. Three days later, a second PEA arrest occurred. Systemic mastocytosis was ultimately diagnosed as the cause of his recurrent syncopal episodes and cardiac arrests...
February 15, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28181948/kounis-syndrome-during-anesthesia-presentation-of-indolent-systemic-mastocytosis-a-case-report
#8
Elena de la Fuente Tornero, Arantza Vega Castro, Pedro Álvarez de Sierra Hernández, Javier Balaguer Recena, Sofía Carmen Zaragoza Casares, Francisco Miguel Serrano Baylin, Paloma Gallardo Culebradas, Beatriz Amorós Alfonso, Jose Ramón Rodríguez Fraile
Mastocytosis comprises a heterogeneous group of disorders characterized by mast cell accumulation and proliferation in distinct organs. Kounis syndrome is defined as the concurrence of acute coronary syndromes with mast cell activation in a setting of allergic or hypersensitivity reactions. This is the first reported case of an intraoperative Kounis syndrome as the onset of an indolent systemic mastocytosis probably triggered by succinylated gelatin infusion during general anesthesia. The presentation of this case is intended to contribute to the knowledge of mastocytosis and Kounis syndrome at the time of diagnostic workup during intraoperative anaphylaxis or myocardial ischemia...
February 8, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28181942/successful-management-of-a-patient-with-possible-mast-cell-activation-syndrome-undergoing-pulmonary-embolectomy-a-case-report
#9
Ellen W Richter, Kai-Ling Hsu, Vanessa Moll
We report the successful perioperative management of a patient with presumed mastocytosis undergoing pulmonary embolectomy. Postoperatively the patient went into vasodilatory shock, which was partly attributed to mast cell mediator release. H1- and H2-antagonists, steroids, and a single dose of methylene blue were given with improvement of hemodynamics. The patient was weaned off vasoactive substances and extubated by postoperative day 2. We discuss the perioperative management of patients with mastocytosis, briefly review the literature concerning anesthetic management for cardiac surgery in patients with this disorder, and discuss our patient's alternative but related diagnosis of idiopathic mast cell activation syndrome...
February 8, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28167789/dnmt3a-restrains-mast-cell-inflammatory-responses
#10
Cristina Leoni, Sara Montagner, Andrea Rinaldi, Francesco Bertoni, Sara Polletti, Chiara Balestrieri, Silvia Monticelli
DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to acute and chronic stimuli, both in vitro and in vivo...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074060/s100a8-a9-and-s100a9-reduce-acute-lung-injury
#11
Yuka Hiroshima, Kenneth Hsu, Nicodemus Tedla, Sze Wing Wong, Sharron Chow, Naomi Kawaguchi, Carolyn L Geczy
S100A8 and S100A9 are myeloid cell-derived proteins that are elevated in several types of inflammatory lung disorders. Pro- and anti-inflammatory properties are reported and these proteins are proposed to activate TLR4. S100A8 and S100A9 can function separately, likely through distinct receptors but a systematic comparison of their effects in vivo are limited. Here we assess inflammation in murine lung following S100A9 and S100A8/A9 inhalation. Unlike S100A8, S100A9 promoted mild neutrophil and lymphocyte influx, possibly mediated in part, by increased mast cell degranulation and selective upregulation of some chemokine genes, particularly CXCL-10...
January 11, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28057422/structure-activity-relationship-study-and-discovery-of-indazole-3-carboxamides-as-calcium-release-activated-calcium-channel-blockers
#12
Sha Bai, Masazumi Nagai, Steffi K Koerner, Aristidis Veves, Lijun Sun
Aberrant activation of mast cells contributes to the development of numerous diseases including cancer, autoimmune disorders, as well as diabetes and its complications. The influx of extracellular calcium via the highly calcium selective calcium-release activated calcium (CRAC) channel controls mast cell functions. Intracellular calcium homeostasis in mast cells can be maintained via the modulation of the CRAC channel, representing a critical point for therapeutic interventions. We describe the structure-activity relationship study (SAR) of indazole-3-carboxamides as potent CRAC channel blockers and their ability to stabilize mast cells...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28038453/histone-deacetylase-inhibitor-saha-mediates-mast-cell-death-and-epigenetic-silencing-of-constitutively-active-d816v-kit-in-systemic-mastocytosis
#13
Katarina Lyberg, Hani Abdulkadir Ali, Jennine Grootens, Matilda Kjellander, Malin Tirfing, Michel Arock, Hans Hägglund, Gunnar Nilsson, Johanna Ungerstedt
Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28027594/neuroimmune-factors-in-functional-gastrointestinal-disorders-a-focus-on-irritable-bowel-syndrome
#14
REVIEW
G E Boeckxstaens, M M Wouters
BACKGROUND: Abnormal abdominal pain perception is the most bothersome and difficult to treat symptom of functional gastrointestinal disorders (FGIDs). Visceral pain stimuli are perceived and transmitted by afferent neurons residing in the dorsal root ganglia that have sensory nerve endings in the gut wall and mesentery. Accumulating evidence indicates that peripheral activation and sensitization of these sensory nerve endings by bioactive mediators released by activated immune cells, in particular mast cells, can lead to aberrant neuroimmune interactions and the development and maintenance of visceral hypersensitivity...
December 27, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/27998003/vitamin-d-contributes-to-mast-cell-stabilization
#15
Zhi-Qiang Liu, Xiao-Xi Li, Shu-Qi Qiu, Yong Yu, Mao-Gang Li, Li-Tao Yang, Lin-Jing Li, Shuai Wang, Peng-Yuan Zheng, Zhi-Gang Liu, Ping-Chang Yang
BACKGROUND AND AIMS: Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells. METHODS: The stability of mast cell lines, HMC1 cells, RBL-2H3 cells, p815 cells and mouse bone marrow-derived mast cells (BMMC) was tested in the presence or absence of VitD3...
December 20, 2016: Allergy
https://www.readbyqxmd.com/read/27942432/mast-cell-clonal-disorders-classification-diagnosis-and-management
#16
REVIEW
Merel C Onnes, Luciana K Tanno, Joanne N G Oude Elberink
Mast cell clonal disorders are characterized by the clonal proliferation of pathological mast cells as a result of somatic mutations in the KIT gene, most commonly the D816V mutation. Accumulation and degranulation of these cells causes a wide variety of symptoms. Mast cell clonal disorders can be divided into mastocytosis and monoclonal mast cell activation syndrome, depending of the level of clonality. The severity of mastocytosis varies from an indolent variant with a good prognosis, to an aggressive condition with short life expectancy...
2016: Current Treatment Options in Allergy
https://www.readbyqxmd.com/read/27927825/an-update-on-mast-cell-disorders
#17
Hannah Cookson, Clive Grattan
Disorders of mast cell activation can be classified as primary (mastocytosis), secondary (reactive) or idiopathic. This article discusses how to recognise and approach the diagnosis of patients suspected to have symptoms of abnormal mast cell activation. Given the highly varied and often complex symptomatology of such patients, we advocate applying a logical step-wise approach to investigating these patients to ensure the correct diagnosis is made. Treatments of mast cell activation disorders are discussed, dividing them into those that ameliorate the effects of mast cell mediators and those that act to stabilise the mast cell...
December 2016: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/27920467/possible-therapeutic-role-of-ige-blockade-in-irritable-bowel-syndrome
#18
EDITORIAL
Eli Magen, Tinatin Chikovani
Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I IgE Fc receptors on mast cells (MCs) and basophils, inhibiting the IgE immune pathway. Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27908847/homeostasis-of-the-gut-barrier-and-potential-biomarkers
#19
Jerry M Wells, Robert J Brummer, Muriel Derrien, Thomas T MacDonald, Freddy Troost, Patrice D Cani, Vassilia Theodorou, Jan Dekker, Agnes Méheust, Willem M de Vos, Annick Mercenier, Arjen Nauta, Clara L Garcia-Rodenas
The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of sIgA and antimicrobial peptides and proteins. With exception of sIgA the expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27896225/the-urokinase-urokinase-receptor-system-in-mast-cells-effects-of-its-functional-interaction-with-fmlf-receptors
#20
Francesca Wanda Rossi, Nella Prevete, Felice Rivellese, Filomena Napolitano, Nunzia Montuori, Loredana Postiglione, Carmine Selleri, Amato de Paulis
Mast cell and basophils express the high affinity receptor for IgE (FcɛRI) and are primary effector cells of allergic disorders. The urokinase (uPA)-mediated plasminogen activation system is involved in physiological and pathological events based on cell migration and tissue remodelling, such as inflammation, wound healing, angiogenesis and metastasis. uPA is a serine protease that binds uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)-anchored receptor. uPAR focuses uPA activity at the cell surface and activates intracellular signaling through lateral interactions with integrins, receptor tyrosine kinases and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs)...
November 2016: Translational Medicine @ UniSa
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