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Leukotrienes

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https://www.readbyqxmd.com/read/28639856/adverse-events-are-rare-after-single-dose-montelukast-exposures-in-children
#1
Donald H Arnold, Nena Bowman, Theodore F Reiss, Tina V Hartert, Donna L Seger
STUDY OBJECTIVE: Montelukast sodium is a leukotriene-receptor antagonist approved as a controller medication for chronic asthma and allergic rhinitis in children and adults. We sought to characterize adverse events associated with single montelukast exposures in children ages 5-17 years and to determine whether adverse events were dose related for all-dose and for ultra-high-dose (≥50 mg) exposures. METHODS: This is a retrospective analysis of data from the National Poison Data System for exposures that included montelukast in individuals aged 5-17 years for calendar years 2000-2016...
June 22, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28639618/htlv-1-induced-leukotriene-b4-secretion-by-t-cells-promotes-t-cell-recruitment-and-virus-propagation
#2
Florent Percher, Céline Curis, Eléonore Pérès, Maria Artesi, Nicolas Rosewick, Patricia Jeannin, Antoine Gessain, Olivier Gout, Renaud Mahieux, Pierre-Emmanuel Ceccaldi, Anne Van den Broeke, Madeleine Duc Dodon, Philippe V Afonso
The human T-lymphotropic virus type 1 (HTLV-1) is efficiently transmitted through cellular contacts. While the molecular mechanisms of viral cell-to-cell propagation have been extensively studied in vitro, those facilitating the encounter between infected and target cells remain unknown. In this study, we demonstrate that HTLV-1-infected CD4 T cells secrete a potent chemoattractant, leukotriene B4 (LTB4). LTB4 secretion is dependent on Tax-induced transactivation of the pla2g4c gene, which encodes the cytosolic phospholipase A2 gamma...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28639121/montelukast-use-a-19-year-nationwide-drug-utilisation-study
#3
Daniel Pilsgaard Henriksen, Jesper Rømhild Davidsen, Christian B Laursen, Anders Christiansen, Per Damkier, Jesper Hallas, Anton Pottegård
PURPOSE: Montelukast is a leukotriene receptor antagonist used in asthma and rhinitis treatment. Despite being marketed nearly two decades ago, little is known about its utilisation pattern. METHODS: Using the Danish National Prescription Registry, we identified subjects filling a montelukast prescription between 1998 and 2017. Using descriptive statistics, we reported the development in incidence, and prevalence, as well as a measure of treatment duration, and concomitant use of asthma- or anti-allergic therapy...
June 22, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28637990/effect-of-the-leukotriene-receptor-antagonist-montelukast-on-orthodontic-tooth-movement
#4
Hossam Asaad, Rabab Al-Sabbagh, Darem Al-Tabba, Omar Kujan
Asthma is a chronic inflammatory disease, and its prevalence is relatively high among children. Optimal management of asthma often requires long-term pharmacotherapy; however, the effects of these medications on orthodontic treatment is uncertain. We evaluated the effects of the leukotriene LTD4 receptor antagonist montelukast on orthodontic tooth movement in an animal model. Eight mongrel dogs were given montelukast for periods up to 4 weeks. An orthodontic force of 150-200 g was applied to move the second and fourth premolars toward the site of the extracted third premolar...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28637652/gm-csf-and-m-csf-primed-m%C3%AF-s-present-similar-resolving-but-distinct-inflammatory-lipid-mediator-signatures
#5
Ana Lukic, Pia Larssen, Alexander Fauland, Bengt Samuelsson, Craig E Wheelock, Susanne Gabrielsson, Olof Radmark
M1 and M2 activated Mϕs have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte Mϕ colony-stimulating factor (GM-CSF) or Mϕ colony-stimulating factor (M-CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N-formylmethionyl-leucyl-phenylalanine or peptidoglycan) were quantified by liquid chromatography-mass spectrometry...
June 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28630405/sex-differences-in-prostaglandin-biosynthesis-in-neutrophils-during-acute-inflammation
#6
Simona Pace, Antonietta Rossi, Verena Krauth, Friederike Dehm, Fabiana Troisi, Rossella Bilancia, Christina Weinigel, Silke Rummler, Oliver Werz, Lidia Sautebin
The severity and course of inflammatory processes differ between women and men, but the biochemical mechanisms underlying these sex differences are elusive. Prostaglandins (PG) and leukotrienes (LT) are lipid mediators linked to inflammation. We demonstrated superior LT biosynthesis in human neutrophils and monocytes, and in mouse macrophages from females, and we confirmed these sex differences in vivo where female mice produced more LTs during zymosan-induced peritonitis versus males. Here, we report sex differences in PG production in neutrophils during acute inflammation...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627277/anti-acne-drugs-in-phase-1-and-2-clinical-trials
#7
Christos C Zouboulis, Clio Dessinioti, Fragkiski Tsatsou, Harald P M Gollnick
Despite the impressive increase of knowledge on acne etiology accumulated during the last 20 years, few efforts have been overtaken to introduce new therapeutic regiments targeting the ideal treatment of acne. The increasing emergence of microbial resistance associated with antibiotics, teratogenicity, particularly associated with systemic isotretinoin, and the need for an adverse drug profile, which can be tolerated by the patient, make the need of new pathogenesis relevant anti-acne agents an emerging issue...
June 19, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28625237/-study-on-mechanisms-and-myocardial-protective-effect-of-qishen-yiqi-dropping-pills-on-rats-with-myocardial-infarction
#8
Quan Yang, Yunshan Cao
OBJECTIVE: To approach the mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction. METHODS: Sixty clean healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and observation group (each n = 20). The rat model of acute myocardial infarction (AMI) was established by ligation of left anterior descent (LAD) branch of coronary artery. After modeling, the rats in observation group were given 0...
June 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28623130/leukotriene-signaling-via-alox5-and-cysteinyl-leukotriene-receptor-1-is-dispensable-for-in%C3%A2-vitro-growth-of-cd34-cd38-stem-and-progenitor-cells-in-chronic-myeloid-leukemia
#9
Monika Dolinska, Alexandre Piccini, Wan Man Wong, Eleni Gelali, Anne-Sofie Johansson, Johannis Klang, Pingnan Xiao, Elham Yektaei-Karin, Ulla Olsson Strömberg, Satu Mustjoki, Leif Stenke, Marja Ekblom, Hong Qian
Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein in chronic myeloid leukemia (CML) are remarkably effective inducing deep molecular remission in most patients. However, they are less effective to eradicate the leukemic stem cells (LSC), resulting in disease persistence. Therefore, there is great need to develop novel therapeutic strategies to specifically target the LSC. In an experimental mouse CML model system, the leukotriene pathway, and specifically, the expression ALOX5, encoding 5-lipoxygenase (5-LO), has been reported as a critical regulator of the LSC...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622139/immune-regulation-and-functions-of-eicosanoid-lipid-mediators
#10
Julia Esser-von Bieren
Bioactive lipids regulate most physiological processes, from digestion to blood flow and from hemostasis to labor. Lipid mediators are also involved in multiple pathologies including cancer, autoimmunity or asthma. The pathological roles of lipid mediators are based on their intricate involvement in the immune system, which comprises source and target cells of these mediators. Based on their biosynthetic origin, bioactive lipids can be grouped into different classes (e.g. sphingolipids, formed from sphingosine or eicosanoids, formed from arachidonic acid)...
June 15, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28616286/severe-and-uncontrolled-asthma-in-china-a-cross-sectional-survey-from-the-australasian-severe-asthma-network
#11
Gang Wang, Fang Wang, Peter G Gibson, Michael Guo, Wei-Jie Zhang, Peng Gao, Hong-Ping Zhang, Erin S Harvey, Hui Li, Jie Zhang
BACKGROUND: Severe asthma is largely unexplored in the Chinese population. Patients with asthma underwent systematic evaluation, by investigating the characteristics of uncontrolled asthma and of asthma treated with three different controller therapies. METHODS: This multi-centre, real-world study was conducted from March 2014 to September 2015. Adults with stable asthma underwent assessment of medication use, asthma control, quality of life, psychological symptoms, work productivity and activity impairment, bronchodilator response and sputum induction...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28616043/angioedema-suppressed-by-a-combination-of-anti-histamine-and-leukotriene-modifier
#12
Brendan N Wong, Peter Vadas
RATIONALE: Angioedema without co-existent urticaria is due to a limited number of causes, including hereditary and acquired C1 esterase inhibitor deficiency, drug-induced angioedema or idiopathic histaminergic or non-histaminergic angioedema. We describe a cohort of patients with recurrent angioedema whose clinical features and response to medications are distinct from the causes above. METHODS: Patients were accrued retrospectively from an academic allergy practice between 2007 and 2014...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28607533/cysteinyl-leukotrienes-as-potential-pharmacological-targets-for-cerebral-diseases
#13
REVIEW
Paolo Gelosa, Francesca Colazzo, Elena Tremoli, Luigi Sironi, Laura Castiglioni
Cysteinyl leukotrienes (CysLTs) are potent lipid mediators widely known for their actions in asthma and in allergic rhinitis. Accumulating data highlights their involvement in a broader range of inflammation-associated diseases such as cancer, atopic dermatitis, rheumatoid arthritis, and cardiovascular diseases. The reported elevated levels of CysLTs in acute and chronic brain lesions, the association between the genetic polymorphisms in the LTs biosynthesis pathways and the risk of cerebral pathological events, and the evidence from animal models link also CysLTs and brain diseases...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28602936/allergic-rhinitis-and-its-impact-on-asthma-aria-guidelines-2016-revision
#14
Jan L Brożek, Jean Bousquet, Ioana Agache, Arnav Agarwal, Claus Bachert, Sinthia Bosnic-Anticevich, Romina Brignardello-Petersen, G Walter Canonica, Thomas Casale, Niels H Chavannes, Jaime Correia de Sousa, Alvaro A Cruz, Carlos A Cuello-Garcia, Pascal Demoly, Mark Dykewicz, Itziar Etxeandia-Ikobaltzeta, Ivan D Florez, Wytske Fokkens, Joao Fonseca, Peter W Hellings, Ludger Klimek, Sergio Kowalski, Piotr Kuna, Kaja-Triin Laisaar, Désirée E Larenas-Linnemann, Karin C Lødrup Carlsen, Peter J Manning, Eli Meltzer, Joaquim Mullol, Antonella Muraro, Robyn O'Hehir, Ken Ohta, Petr Panzner, Nikolaos Papadopoulos, Hae-Sim Park, Gianni Passalacqua, Ruby Pawankar, David Price, John J Riva, Yetiani Roldán, Dermot Ryan, Behnam Sadeghirad, Boleslaw Samolinski, Peter Schmid-Grendelmeier, Aziz Sheikh, Alkis Togias, Antonio Valero, Arunas Valiulis, Erkka Valovirta, Matthew Ventresca, Dana Wallace, Susan Waserman, Magnus Wickman, Wojtek Wiercioch, Juan José Yepes-Nuñez, Luo Zhang, Yuan Zhang, Mihaela Zidarn, Torsten Zuberbier, Holger J Schünemann
BACKGROUND: Allergic rhinitis affects 10 to 40% of the population. It reduces quality of life, school and work performance, and is a frequent reason for office visits in general practice. Medical costs are large but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma - ARIA guidelines in 2010 prompting its update. OBJECTIVE: To provide a targeted update of the ARIA guidelines...
June 8, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28600709/cysteinyl-leukotriene-receptor-antagonists-inhibit-migration-invasion-and-expression-of-mmp-2-9-in-human-glioblastoma
#15
Pannaree Piromkraipak, Kant Sangpairoj, Wuttipong Tirakotai, Kulathida Chaithirayanon, Supeenun Unchern, Porntip Supavilai, Christopher Power, Pornpun Vivithanaporn
Glioblastoma is one of the most malignant and aggressive types of brain tumors. 5-lipoxygenase and cysteinyl leukotriene receptor 1 (CysLT1) play a role in human carcinogenesis. Leukotriene receptor antagonists (LTRAs), anti-asthmatic drugs with mild side effects, have anti-metastatic activity in epidermoid carcinoma, lung carcinoma, and colon cancers as well as neuroprotective effects. Herein, anti-migratory effects of two LTRAs, montelukast and zafirlukast, were investigated in glioblastoma cells. The level of CysLT1 in A172 cells was increased by 3...
June 9, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28600286/lipopolysaccharide-tlr4-stimulates-il-13-production-through-a-myd88-blt2-linked-cascade-in-mast-cells-potentially-contributing-to-the-allergic-response
#16
A-Jin Lee, MyungJa Ro, Kyung-Jin Cho, Jae-Hong Kim
In an experimental asthma model, the activation of TLR4 by bacterial LPS occasionally exacerbates allergic inflammation through the production of Th2 cytokines, and mast cells have been suggested to play a central role in this response. However, the detailed mechanism underlying how LPS/TLR4 stimulates the production of Th2 cytokines, especially IL-13, remains unclear in mast cells. In the current study, we observed that the expression levels of leukotriene B4 receptor-2 (BLT2) and the synthesis of its ligands were highly upregulated in LPS-stimulated bone marrow-derived mast cells and that BLT2 blockade with small interfering RNA or a pharmacological inhibitor completely abolished IL-13 production, suggesting a mediatory role of the BLT2 ligand-BLT2 axis in LPS/TLR4 signaling to IL-13 synthesis in mast cells...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28594432/involvement-of-the-ige-basophil-system-and-mild-complement-activation-in-haemophilia-b-with-anti-factor-ix-neutralizing-antibodies-and-anaphylaxis
#17
M Cugno, M E Mancuso, A Tedeschi, E Santagostino, M Lorini, V Carbonelli, F Peyvandi, P M Mannucci
INTRODUCTION: Patients with haemophilia B who develop factor IX (FIX) neutralizing antibodies (inhibitors) after FIX infusion are at high risk of hypersensitivity reactions upon FIX re-exposure, but the underlying mechanisms are incompletely understood. AIM: To investigate biomechanisms of FIX hypersensitivity. METHODS: A cellular antigen stimulation test (CAST) was employed to evaluate leukotriene C4 (LTC4) release from basophils stimulated by FIX in three treated children with haemophilia B, one of whom developed FIX inhibitor and experienced anaphylaxis following FIX re-exposure...
June 8, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28593645/ultraviolet-a-photosensitivity-profile-of-dexchlorpheniramine-maleate-and-promethazine-based-creams-anti-inflammatory-antihistaminic-and-skin-barrier-protection-properties
#18
Gustavo Facchini, Samara Eberlin, Stefano Piatto Clerici, Ana Lucia Tabarini Alves Pinheiro, Adilson Costa
BACKGROUND: Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. AIMS: In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). METHODS: We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient...
June 7, 2017: Journal of Cosmetic Dermatology
https://www.readbyqxmd.com/read/28576407/rp5063-a-novel-multimodal-serotonin-receptor-modulator-prevents-sugen-5416-hypoxia-induced-pulmonary-arterial-hypertension-in-rats
#19
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
RP5063, a multimodal dopamine (DA) and serotonin (5-HT) modulator with high affinity for DA2/3/4 and 5-HT2A/2B/7 receptors and moderate affinity for SERT, is a novel therapeutic of special interest in the treatment of pulmonary arterial hypertension (PAH). Evidence indicates that therapeutics targeting the 5-HT2A/2B receptors can influence the pathogenesis of PAH. However, the therapeutic effect of RP5063 in humans has yet to be investigated. A Sugen 5416-hypoxia (SuHx)-induced PAH model was used to evaluate twice-daily (b...
May 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28575166/lta4h-regulates-cell-cycle-and-skin-carcinogenesis
#20
Naomi Oi, Hiroyuki Yamamoto, Alyssa Langfald, Ruihua Bai, Mee-Hyun Lee, Ann M Bode, Zigang Dong
Leukotriene A4 hydrolase (LTA4H), a bifunctional zinc metallo-enzyme, is reportedly overexpressed in several human cancers. Our group has focused on LTA4H as a potential target for cancer prevention and/or therapy. In the present study, we report that LTA4H is a key regulator of cell cycle at the G0/G1 phase acting by negatively regulating p27 expression in skin cancer. We found that LTA4H is overexpressed in human skin cancer tissue. Knocking out LTA4H significantly reduced skin cancer development in the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin cancer mouse model...
May 31, 2017: Carcinogenesis
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