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Leukotriene antagonists

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https://www.readbyqxmd.com/read/29757196/leukotriene-receptors-as-potential-therapeutic-targets
#1
Takehiko Yokomizo, Motonao Nakamura, Takao Shimizu
Leukotrienes, a class of arachidonic acid-derived bioactive molecules, are known as mediators of allergic and inflammatory reactions and considered to be important drug targets. Although an inhibitor of leukotriene biosynthesis and antagonists of the cysteinyl leukotriene receptor are clinically used for bronchial asthma and allergic rhinitis, these medications were developed before the molecular identification of leukotriene receptors. Numerous studies using cloned leukotriene receptors and genetically engineered mice have unveiled new pathophysiological roles for leukotrienes...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29726704/cysteinyl-leukotriene-receptor-antagonists-induce-apoptosis-and-inhibit-proliferation-of-human-glioblastoma-cells-by-down-regulating-b-cell-lymphoma-2-and-inducing-cell-cycle-arrest
#2
Pannaree Piromkraipak, Tipparat Parakaw, Suttinee Phuagkhaopong, Sirada Srihirun, Sukumal Chongthammakun, Kulathida Chaithirayanon, Pornpun Vivithanaporn
Glioblastoma is the most aggressive type of brain cancer with the highest proliferation, invasion and migration. Montelukast and zafirlukast, two widely used leukotriene receptor antagonists (LTRAs) for asthma treatment, inhibited invasion and migration of glioblastoma cell lines. Montelukast induces apoptosis and inhibites cell proliferation of various cancer cells. Herein, apoptotic and antiproliferative effects of montelukast and zafirlukast were investigated in two glioblastoma cell lines, A172 and U-87 MG...
May 4, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29713354/severe-eosinophilic-asthma-in-primary-care-in-canada-a-longitudinal-study-of-the-clinical-burden-and-economic-impact-based-on-linked-electronic-medical-record-data
#3
Don Husereau, Jason Goodfield, Richard Leigh, Richard Borrelli, Michel Cloutier, Alain Gendron
Background: Stratification of patients with severe asthma by blood eosinophil counts predicts responders to anti-interleukin (IL)-5 (mepolizumab and reslizumab) and anti-IL-5 receptor α (benralizumab) therapies. This study characterized patients with severe asthma who could qualify for these biologics in a primary care setting. Methods: We retrospectively selected patients from July 1, 2010, to June 30, 2014, using a linked electronic medical records (EMR) database (IMS Evidence 360 EMR Canada) for > 950,000 patients in primary care in Ontario, Canada...
2018: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/29708817/montelukast-inhibits-hypoxia-inducible-factor-1%C3%AE-translation-in-prostate-cancer-cells
#4
Caixia Tang, Hu Lei, Jinfu Zhang, Meng Liu, Jin, Hao Luo, Hanzhang Xu, Yingli Wu
Through regulating the expression of hundreds of genes, hypoxia-inducible factor -1(HIF-1) plays a critical role in hypoxic adaption of cancer cells and is considered as a target for cancer therapy. Here we show that montelukast, a clinical leukotriene receptor antagonist for the treatment of asthma, inhibits hypoxia or CoCl2 -induced HIF-1α activation and reduces its protein expression in prostate cancer cells. However, the other two leukotriene receptor antagonists, pranlukast and zafirlukast, cannot decrease HIF-1α protein, which indicates that montelukast-induced downregulation of HIF-1α is not mediated by leukotriene receptor...
April 30, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29706593/repurposing-hami3379-to-block-gpr17-and-promote-rodent-and-human-oligodendrocyte-differentiation
#5
Nicole Merten, Julia Fischer, Katharina Simon, Liguo Zhang, Ralf Schröder, Lucas Peters, Anne-Gaelle Letombe, Stephanie Hennen, Ramona Schrage, Theresa Bödefeld, Celine Vermeiren, Michel Gillard, Klaus Mohr, Qing Richard Lu, Oliver Brüstle, Jesus Gomeza, Evi Kostenis
Identification of additional uses for existing drugs is a hot topic in drug discovery and a viable alternative to de novo drug development. HAMI3379 is known as an antagonist of the cysteinyl-leukotriene CysLT2 receptor, and was initially developed to treat cardiovascular and inflammatory disorders. In our study we identified HAMI3379 as an antagonist of the orphan G protein-coupled receptor GPR17. HAMI3379 inhibits signaling of recombinant human, rat, and mouse GPR17 across various cellular backgrounds, and of endogenous GPR17 in primary rodent oligodendrocytes...
April 18, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29694289/economic-burden-associated-with-receiving-inhaled-corticosteroids-with-leukotriene-receptor-antagonists-or-long-acting-beta-agonists-as-combination-therapy-in-older-adults
#6
Shoroq M Altawalbeh, Carolyn T Thorpe, Janice C Zgibor, Sandra Kane-Gill, Yihuang Kang, Joshua M Thorpe
BACKGROUND: There is a paucity of literature on the health care expenditures associated with different pharmacologic treatments in older adults with asthma that is not well controlled on inhaled corticosteroids (ICS). OBJECTIVE: To compare asthma-related and all-cause health care expenditures associated with leukotriene receptor antagonists (LTRA) versus long-acting beta agonists (LABA) when added to ICS in older adults with asthma. METHODS: A retrospective cohort was constructed using 2009-2010 Medicare fee-for-service medical and pharmacy claims from a 10% random sample of beneficiaries continuously enrolled in Parts A, B, and D in 2009...
May 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29685001/cysteinyl-leukotrienes-c4-and-d4-downregulate-human-mast-cell-expression-of-toll-like-receptors-1-through-7
#7
V Karpov, R Ilarraza, A Catalli, M Kulka
Cysteinyl leukotrienes (CysLT) are potent inflammatory lipid molecules that mediate some of the pathophysiological responses associated with asthma such as bronchoconstriction, vasodilation and increased microvascular permeability. As a result, CysLT receptor antagonists (LRA), such as montelukast, have been used to effectively treat patients with asthma. We have recently shown that mast cells are necessary modulators of innate immune responses to bacterial infection and an important component of this innate immune response may involve the production of CysLT...
March 2018: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/29670278/blt1-in-dendritic-cells-promotes-th1-th17-differentiation-and-its-deficiency-ameliorates-tnbs-induced-colitis
#8
Jinfeng Zhou, Weiming Lai, Wanjie Yang, Juping Pan, Hu Shen, Yingying Cai, Cuixia Yang, Ningjia Ma, Yue Zhang, Ru Zhang, Xin Xie, Zhongjun Dong, Yuan Gao, Changsheng Du
Leukotriene B4 (LTB4) synthesis is enhanced in the colonic mucosa in patients with inflammatory bowel disease (IBD). BLT1, a high-affinity receptor for LTB4, exhibits no effect on the progression of dextran sodium sulfate (DSS)-induced colitis, which mostly relies on innate immunity. Here, we reported that BLT1 regulates trinitrobenzene sulfonic acid (TNBS)-induced colitis, which reflects CD4+ T-cell-dependent adaptive immune mechanisms of IBD. We found that BLT1 signaling enhanced the progression of colitis through controlling the production of proinflammatory cytokines by dendritic cells (DCs) and modulating the differentiation of Th1 and Th17...
April 18, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29625590/guideline-on-management-of-the-acute-asthma-attack-in-children-by-italian-society-of-pediatrics
#9
REVIEW
Luciana Indinnimeo, Elena Chiappini, Michele Miraglia Del Giudice
BACKGROUND: Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. METHODS: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted...
April 6, 2018: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/29604187/investigating-the-possible-mechanisms-involved-in-adenosine-preconditioning-induced-cardioprotection-in-rats
#10
Lovedeep Singh, Jasleen Kaur Virdi, L N Maslov, Nirmal Singh, Amteshwar Singh Jaggi
BACKGROUND: Adenosine is a breakdown product of adenosine triphosphate and plays an important role in pharmacological preconditioning. The cardioprotective effects of adenosine preconditioning are well established. However, the possible mechanisms need to be explored. AIM: The present study was aimed to investigate the possible mechanisms involved in adenosine preconditioning-induced cardioprotection in rats. METHODS: Rat heart was isolated and perfused on Langendorff apparatus...
March 31, 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29587693/a-case-of-allergic-bronchopulmonary-aspergillosis-successfully-treated-with-mepolizumab
#11
Takeshi Terashima, Taro Shinozaki, Eri Iwami, Takahiro Nakajima, Tatsu Matsuzaki
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease comprising a complex hypersensitivity reaction to Aspergillus fumigatus. Clinical features of ABPA are wheezing, mucoid impaction, and pulmonary infiltrates. Oral corticosteroids and anti-fungal agents are standard therapy for ABPA, but long-term use of systemic corticosteroids often causes serious side effects. CASE PRESENTATION: A 64-year-old woman was diagnosed with ABPA based on a history of bronchial asthma (from 40 years of age), elevated total IgE, the presence of serum precipitating antibodies and elevated specific IgE antibody to A...
March 27, 2018: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29587204/leukotriene-d4-induces-cellular-senescence-in-osteoblasts
#12
Jinsong Wei, Siyuan Chen, Weixiong Guo, Bailin Feng, Shukai Yang, Chengshuo Huang, Jiaqi Chu
Aging is associated with the development of osteoporosis, in which cellular senescence in osteoblasts plays a key role. Leukotriene D4 (LTD4), an important cysteinyl leukotriene (cysLT), is a powerful pro-inflammatory mediator formed from arachidonic acid. However, little information regarding the effects of LTD4 on the pathogenesis of osteoporosis has been reported before. In the present study, we defined the physiological roles of LTD4 in cellular senescence in osteoblasts. Our results indicate that LTD4 treatment decreased the expression of SIRT1 in a dose-dependent manner in MC3T3-E1 osteoblastic cells...
March 24, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29582642/leukotriene-receptor-antagonists-inhibit-mitogenic-activity-in-triple-negative-breast-cancer-cells
#13
Kran Suknuntha, Ruedeemars Yubolphan, Kanokpan Krueaprasertkul, Sirada Srihirun, Nathawut Sibmooh, Pornpun Vivithanaporn
Despite a discovery of hormonal pathways regulating breast cancer, a definitive cure for the disease requires further identification of alternative targets that provide a hormone-independent support. Apart from their role in inflammatory diseases, cysteinyl leukotriene (CysLT) receptor antagonists (LTRAs) decrease the risk of lung cancer in asthma patients and inhibit tumor progression in several malignancies. In the present study, we evaluate the effects of two chemically different, clinically relevant LTRAs (montelukast and zafirlukast) in a triple negative breast cancer cell line, MDAMB- 231...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29572192/omalizumab-for-the-treatment-of-solar-urticaria-case-series-and-systematic-review-of-the-literature
#14
Igor Snast, Noa Kremer, Moshe Lapidoth, Claes David Enk, Yuval Tal, Yossi Rosman, Ronit Confino-Cohen, Emmilia Hodak, Assi Levi
BACKGROUNDL: Solar urticaria (SU) is a rare photodermatosis causing a significant impact on patients' quality of life. Although the condition can be controlled with phototherapy and/or a combination therapy of antihistamines and leukotriene antagonist in most patients, a subset of patients require additional therapy with omalizumab; however, efficacy data is sparse. OBJECTIVE: To determine the efficacy and safety of omalizumab for treating SU. METHODS: A case series of five patients with SU refractory to antihistamine and leukotriene antagonist combination who were treated with omalizumab is described...
March 20, 2018: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29571015/enhanced-lipoxygenase-ltd4-signaling-accounts-for-the-exaggerated-hypertensive-and-nephrotoxic-effects-of-cyclosporine-plus-indomethacin-in-rats
#15
Maged W Helmy, Mai M Helmy, Mahmoud M El-Mas
The combined use of cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) causes exaggerated rises in systolic blood pressure (SBP) and nephrotoxicity. We examined whether these influences relate to the arachidonate/5-lipoxygenase (LOX) pathway. Rats were treated with CSA (20 mg kg-1  day-1 ), indomethacin (5 mg kg-1  day-1 ), or their combination for 10 days. Changes in SBP and renal biochemical/histopathological characteristics along with leukotriene levels were determined in rats treated with or without LT receptor antagonists...
March 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29548318/clinical-and-economic-impact-of-a-one-year-treatment-with-omalizumab-in-patients-with-severe-allergic-asthma-within-a-drug-programme-in-poland
#16
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
https://www.readbyqxmd.com/read/29518425/leukotriene-e-4-induces-airflow-obstruction-and-mast-cell-activation-via-the-cyslt-1-receptor
#17
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
https://www.readbyqxmd.com/read/29518252/interventions-for-autumn-exacerbations-of-asthma-in-children
#18
REVIEW
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
https://www.readbyqxmd.com/read/29490167/new-maresin-conjugates-in-tissue-regeneration-pathway-counters-leukotriene-d-4-stimulated-vascular-responses
#19
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
https://www.readbyqxmd.com/read/29467755/leptin-mediates-in-vivo-neutrophil-migration-involvement-of-tumor-necrosis-factor-alpha-and-cxcl1
#20
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
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