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Leukotriene antagonists

Karina Jahnz-Różyk, Joanna Lis, Marta Warchoł, Aleksandra Kucharczyk
BACKGROUND: Allergic asthma is the most prevalent phenotype of severe asthma where treatment with omalizumab (OMB) has been proven to be particularly beneficial. In Poland, OMB therapy is available and reimbursed within a drug programme where strict inclusion and exclusion criteria are defined. The objective of this study was to present a descriptive analysis regarding the trends in outcomes (clinical, quality of life, costs) among a cohort of patients who satisfy inclusion criteria for the initiation of OMB treatment and who successfully responded to OMB according to a set of objective criteria...
March 16, 2018: BMC Pulmonary Medicine
Nikolaos Lazarinis, Johan Bood, Cristina Gomez, Johan Kolmert, Ann-Sofie Lantz, Pär Gyllfors, Andy Davis, Craig E Wheelock, Sven-Erik Dahlén, Barbro Dahlén
BACKGROUND: Leukotriene E4 (LTE4 ) is the final active metabolite among the cysteinyl leukotrienes (CysLTs). Animal studies have identified a distinct LTE4 receptor, suggesting that current CysLT1 receptor antagonists may provide incomplete inhibition of CysLT responses. OBJECTIVE: We tested this hypothesis by assessing the influence of the CysLT1 antagonist montelukast on responses induced by inhalation of LTE4 in asthmatic subjects. METHODS: Fourteen subjects with mild intermittent asthma and two subjects with aspirin exacerbated respiratory disease (AERD) received montelukast 20 mg bid and placebo for 5-7 days in a randomized, double blind, crossover study (NCT01841164)...
March 5, 2018: Journal of Allergy and Clinical Immunology
Katharine C Pike, Melika Akhbari, Dylan Kneale, Katherine M Harris
BACKGROUND: Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere...
March 8, 2018: Cochrane Database of Systematic Reviews
Nan Chiang, Ian R Riley, Jesmond Dalli, Ana R Rodriguez, Bernd W Spur, Charles N Serhan
Resolution of acute inflammation is governed, in part, by lipid mediator class switching from proinflammatory eicosanoids to specialized proresolving mediators, including a recently identified new pathway of mediators, termed maresin conjugates in tissue regeneration (MCTR), which includes MCTR1, MCTR2, and MCTR3. Here, we addressed whether each MCTR can impact the known vascular actions of cysteinyl leukotrienes. Leukotriene D4 (LTD4 ; 1.5 nmol/mouse) initiated vascular leakage in mouse cremaster vessels, which was reduced (>75%) by MCTR1 and MCTR2 (0...
February 28, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Glaucia Souza-Almeida, Heloisa D'Avila, Patricia E Almeida, Tatiana Luna-Gomes, Sally Liechocki, Barbara Walzog, Ingrid Hepper, Hugo Caire Castro-Faria-Neto, Patricia T Bozza, Christianne Bandeira-Melo, Clarissa M Maya-Monteiro
Leptin directly activates macrophages and lymphocytes, but the role of leptin in neutrophil activation and migration is still controversial. Here, we investigate the in vivo mechanisms of neutrophil migration induced by leptin. The intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration-dependent neutrophil influx. We did not observe the enhancement of lipid bodies/droplets in neutrophils, after leptin treatment, as we had observed previously in peritoneal macrophages. The participation of leukotriene B4 (LTB4 ) in neutrophil recruitment triggered by leptin was investigated using different strategies...
2018: Frontiers in Immunology
Virginia Mirra, Silvia Montella, Francesca Santamaria
BACKGROUND: The primary goal of asthma management is to achieve disease control for reducing the risk of future exacerbations and progressive loss of lung function. Asthma not responding to treatment may result in significant morbidity. In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong or adherence to treatment may be poor. It is then crucial to distinguish these cases from the truly "severe therapy-resistant" asthmatics by a proper filtering process...
February 21, 2018: BMC Pediatrics
L Liu, J-L Wang, X-Y Xu, M Feng, Y Hou, L Chen
OBJECTIVE: Leukotriene receptor antagonists (LTRA), the anti-inflammatory agents, have been reported new therapeutic value in chronic obstructive pulmonary disease (COPD). However, the effects of LTRA on lung function decline in COPD were determined with inconsistent results and a meta-analysis is needed. MATERIALS AND METHODS: Published cohort or randomized controlled studies were retrieved from PubMed and Embase databases. RESULTS: Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated in a random effects model...
February 2018: European Review for Medical and Pharmacological Sciences
Rahmo Ibrahim Farah, Per Damkier, Anders Christiansen, Daniel Pilsgaard Henriksen
Montelukast, a leukotriene receptor antagonist, was marketed in 1998 as an oral supplementary treatment to patients with mild to moderate asthma. The aim of this study was to describe the early discontinuation pattern among montelukast users in Denmark in the period of 1 March 1998 to 31 December 2016, and to identify demographic characteristics possibly associated with early discontinuation. This nationwide drug utilization study was based on data collected from three nationwide Danish registers. All montelukast users who redeemed at least one prescription in the study period were identified...
February 13, 2018: Basic & Clinical Pharmacology & Toxicology
Antonio Di Gennaro, Ana Carolina Araújo, Albert Busch, Hong Jin, Dick Wågsäter, Emina Vorkapic, Kenneth Caidahl, Per Eriksson, Bengt Samuelsson, Lars Maegdefessel, Jesper Z Haeggström
Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl 2 -induced AAA at a dose comparable to human medical practice...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Adam Honeybrook, Matthew Ellison, Liana Puscas, Eileen Raynor
BACKGROUND: In February 2015, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNSF) published the Allergic Rhinitis Clinical Practice Guideline (AR-CPG). The objective of this study was to assess otolaryngologists' perception of the accuracy and adherence to the AR-CPG. METHODS: A survey was distributed to fellows of the American Academy of Otolaryngic Allergy and members of the American Academy of Otolaryngology-Head and Neck Surgery Foundation...
February 7, 2018: International Forum of Allergy & Rhinology
Runmin Guo, Jiamei Jiang, Zhiliang Jing, Yonghua Chen, Zhizhou Shi, Baoping Deng
Insulin resistance is an important pathological hallmark of type 2 diabetes mellitus. Glucose-stimulated insulin secretion (GSIS) plays a key role in maintaining blood glucose levels within normal range. Impaired GSIS has been associated with type 2 diabetes, however, the underlying molecular mechanisms remain largely unknown. Cysteinyl leukotriene receptor 1 (cysLT1R) is an important G protein-coupled receptor mediating the biological functions of cysteinyl leukotrienes (cys-LTs). Little is known about the effects of cysLT1R in insulin secretion and pathogenesis of T2DM...
February 2, 2018: Cellular Signalling
Mona Al-Ahmad, Tito Rodriguez-Bouza, Midhat Nurkic
BACKGROUND: A history of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity with cross-intolerance to several drugs is common in some patients with coronary artery disease. We present a series of patients with acute coronary syndrome undergoing ASA desensitization prior to a possible stent to evaluate the short- and long-term efficacy and safety. The aim was to evaluate the outcomes of an ASA desensitization protocol developed by our center based on the guidelines proposed by the EAACI drug allergy expert recommendations...
January 26, 2018: International Archives of Allergy and Immunology
Gulixian Mahemuti, Hui Zhang, Jing Li, Nueramina Tieliwaerdi, Lili Ren
Background and objective: Theophylline has been used for decades to treat both acute and chronic asthma. Despite its longevity in the practitioner's formulary, no detailed meta-analysis has been performed to determine the conditions, including concomitant medications, under which theophylline should be used for acute exacerbations of asthma. We aimed to quantify the usefulness and side effects of theophylline with or without ethylene diamine (aminophylline) in acute asthma, with particular emphasis on patient subgroups, such as children, adults, and concomitant medications...
2018: Drug Design, Development and Therapy
Junjie Mao, Xiaojun Hu, Pengfei Pang, Bin Zhou, Yaqin Zhang, Dan Li, Hong Shan
PURPOSE: To clarify the role of Cysteinyl leukotrienes receptor type 1 (CYSLTR1) and find the potential predictors of CYSLTR1 antagonists (LTRAs) responsiveness in vivo. EXPERIMENTAL DESIGN: Cysltr1 knockout (KO) mouse model was established by the CRISPR/Cas9 system. The phenotype of Cysltr1 KO mice were tested by western blotting (WB), histological examinations, and experiment of zymosan A-induced peritoneal inflammation. The differentially expressed proteins (DEPs) between the Cysltr1 KO and the wild type (WT) mice lung tissues were analyzed by the iTRAQ-based proteomic technology...
January 26, 2018: Proteomics. Clinical Applications
Melanie Jannaway, Christopher Torrens, Jane A Warner, Anthony P Sampson
BACKGROUND AND PURPOSE: Omega-6 fatty acid-derived lipid mediators such as prostanoids, thromboxane and leukotrienes have well-established roles in regulating both inflammation and smooth muscle contractility. Resolvins are derived from omega-3 fatty acids and have important roles in promoting the resolution of inflammation, but their activity on smooth muscle contractility is unknown. We investigated whether resolvin E1 (RvE1), resolvin D1 (RvD1) and resolvin D2 (RvD2) can modulate contractions of isolated segments of rat thoracic aorta (RTA) or human pulmonary artery (HPA) induced by the α1 -adrenoceptor agonist phenylephrine or the stable thromboxane A2 mimetic U46619...
January 20, 2018: British Journal of Pharmacology
Kjell Larsson, Björn Ställberg, Karin Lisspers, Gunilla Telg, Gunnar Johansson, Marcus Thuresson, Christer Janson
BACKGROUND: Severe and uncontrolled asthma is associated with increased risk of exacerbations and death. A substantial proportion of asthma patients have poor asthma control, and a concurrent COPD diagnosis often increases disease burden. The objective of the study was to describe the prevalence and managemant of severe asthma in a Swedish asthma popuöation. METHODS: In this observational cohort study, primary care medical records data (2006-2013) from 36 primary health care centers were linked to data from national mandatory Swedish health registries...
January 18, 2018: Respiratory Research
Guo Liu, Xu Zhou, Jianrong Chen, Feng Liu
Objective To evaluate whether an adjuvant therapy of leukotriene receptor antagonists (LTRAs) based on oral H1-antihistamines (H1) can increase efficacy of allergic rhinitis (AR) treatment. Data Sources The search involved databases of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, from inception up to September 23, 2017. Randomized controlled trials (RCTs) that compared efficacy of LTRAs + H1 vs H1 alone were eligible. Review Methods Pooled comparative effects were measured using weighted mean difference (WMD) and 95% confidence interval (CI)...
January 1, 2018: Otolaryngology—Head and Neck Surgery
Wei Song, Yumin Zhang, Jun Wang, Tao Ma, Linjie Hao, Kunzheng Wang
Aging is closely associated with osteoarthritis (OA). Although its underlying mechanisms remain unknown, cellular senescence in chondrocytes has become an important therapeutic target for the treatment of OA. Cysteinyl leukotriene receptors (cysLTRs) mediate the pathobiological function of cysteinyl leukotrienes (cysLTs). However, the roles of cysLTRs in the pathogenesis of OA have not been reported before. In the current study, we found that cysLTR1 but not cysLTR2 is expressed in human primary chondrocytes...
January 10, 2018: Cytokine
Min Liu, Juan Shen, Huimin Yuan, Fengling Chen, Huaidong Song, Hui Qin, Yanqin Li, Jiabo Xu, Qing Ye, Shenxian Li, Kazuko Saeki, Takehiko Yokomizo
The airway epithelium plays a crucial role in the pathogenesis of asthma. The functions of leukotriene B4 receptor 2 (BLT2) on the airway epithelial cells remains unknown. In our study, BLT2 expression in 16HBE bronchial epithelial cells were manipulated by transfection with BLT2 overexpression plasmid or BLT2 small interference RNA. 16HBE cells were then exposed to BLT2 antagonist (LY255283) or BLT2 agonist (12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid [12-HHT] or CAY10583). The results showed that BLT2 overexpression, 12-HHT stimulation or CAY10583 treatment resulted in the enhanced proliferation and migration of 16HBE cells...
January 11, 2018: Journal of Cellular Physiology
Minwen Xu, Ruiyun Hong, Xiaoli Zhang, Hailin Zou, Yi Zhang, Zhiping Hou, Liefeng Wang
Cysteinyl leukotrienes (CysLTs) play a key role in inflammatory diseases such as asthma and their receptors' antagonists are currently used as anti-asthmatic drugs. CysLTs have also been found to participate in other inflammatory reactions. Here, we reported that in rheumatoid arthritis (RA) animals model, collagen-induced arthritis, (CIA), CysLT1, a receptor for CysLTs, was up-regulated in hind paw and lymph node, while CysLTs levels in the blood were also higher than normal mice. Montelukast, a drug targeting CysLT1, has been shown to effectively reduce the CIA incidence, peak severity, and cumulative disease scores...
December 12, 2017: Oncotarget
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