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Prostaglandin D2

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https://www.readbyqxmd.com/read/28406694/does-inhibition-of-aldose-reductase-contribute-to-the-anti-inflammatory-action-of-setipiprant
#1
J Ballekova, M Soltesova-Prnova, M Majekova, M Stefek
The aim of this study was to investigate aldose reductase inhibitory action of setipiprant as a potential additional mechanism contributing to its anti-inflammatory action. Aldose reductase activity was determined by spectrophotometric measuring of NADPH consumption. Setipiprant was found to inhibit aldose reductase/NADPH-mediated reduction of 4-hydroxynonenal, 4-hydroxynonenal glutathione and prostaglandin H2 substrates, all relevant to the process of inflammation. Molecular modeling simulations into the aldose reductase inhibitor binding site revealed an interaction pattern of setipiprant...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28394950/generation-and-characterization-of-an-antagonistic-monoclonal-antibody-against-an-extracellular-domain-of-mouse-dp2-crth2-gpr44-receptors-for-prostaglandin-d2
#2
Nanae Nagata, Hiroko Iwanari, Hidetoshi Kumagai, Osamu Kusano-Arai, Yuichi Ikeda, Kosuke Aritake, Takao Hamakubo, Yoshihiro Urade
Prostaglandin D2 (PGD2) is a lipid mediator involved in sleep regulation and inflammation. PGD2 interacts with 2 types of G protein-coupled receptors, DP1 and DP2/CRTH2 (chemoattractant receptor homologous molecule expressed on T helper type 2 cells)/GPR44 to show a variety of biological effects. DP1 activation leads to Gs-mediated elevation of the intracellular cAMP level, whereas activation of DP2 decreases this level via the Gi pathway; and it also induces G protein-independent, arrestin-mediated cellular responses...
2017: PloS One
https://www.readbyqxmd.com/read/28392807/efficacy-and-safety-of-setipiprant-in-seasonal-allergic-rhinitis-results-from-phase-2-and-phase-3-randomized-double-blind-placebo-and-active-referenced-studies
#3
Paul Ratner, Charles P Andrews, Frank C Hampel, Bruce Martin, Dale E Mohar, Denis Bourrelly, Parisa Danaietash, Sara Mangialaio, Jasper Dingemanse, Abdel Hmissi, Jay van Bavel
BACKGROUND: Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks. METHODS: A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28378369/a-randomized-controlled-phase-ii-clinical-trial-comparing-ono-4053-a-novel-dp1-antagonist-with-a-leukotriene-receptor-antagonist-pranlukast-in-patients-with-seasonal-allergic-rhinitis
#4
Kimihiro Okubo, Kazuhiro Hashiguchi, Tetsuo Takeda, Kanji Baba, Hideto Kitagoh, Hitoshi Miho, Hideo Tomomatsu, Shinsuke Yamaguchi, Motoi Odani, Hajime Yamamotoya
BACKGROUND: Prostaglandin D2 (PGD2 ) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea. OBJECTIVE: This study aimed to evaluate the efficacy and safety of a novel PGD2 receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR). METHODS: This study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period...
April 4, 2017: Allergy
https://www.readbyqxmd.com/read/28357126/the-anti-inflammatory-compound-palmitoylethanolamide-inhibits-prostaglandin-and-hydroxyeicosatetraenoic-acid-production-by-a-macrophage-cell-line
#5
Linda Gabrielsson, Sandra Gouveia-Figueira, Jenny Häggström, Mireille Alhouayek, Christopher J Fowler
The anti-inflammatory agent palmitoylethanolamide (PEA) reduces cyclooxygenase (COX) activity in vivo in a model of inflammatory pain. It is not known whether the compound reduces prostaglandin production in RAW264.7 cells, whether such an action is affected by compounds preventing the breakdown of endogenous PEA, whether other oxylipins are affected, or whether PEA produces direct effects upon the COX-2 enzyme. RAW264.7 cells were treated with lipopolysaccharide and interferon-γ to induce COX-2. At the level of mRNA, COX-2 was induced >1000-fold following 24 h of the treatment...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28341703/niacin-ameliorates-ulcerative-colitis-via-prostaglandin-d2-mediated-d-prostanoid-receptor-1-activation
#6
Juanjuan Li, Deping Kong, Qi Wang, Wei Wu, Yanping Tang, Tingting Bai, Liang Guo, Lumin Wei, Qianqian Zhang, Yu Yu, Yuting Qian, Shengkai Zuo, Guizhu Liu, Qian Liu, Sheng Wu, Yi Zang, Qian Zhu, Daile Jia, Yuanyang Wang, Weiyan Yao, Yong Ji, Huiyong Yin, Masataka Nakamura, Michael Lazarus, Richard M Breyer, Lifu Wang, Ying Yu
Niacin, as an antidyslipidemic drug, elicits a strong flushing response by release of prostaglandin (PG) D2 However, whether niacin is beneficial for inflammatory bowel disease (IBD) remains unclear. Here, we observed niacin administration-enhanced PGD2 production in colon tissues in dextran sulfate sodium (DSS)-challenged mice, and protected mice against DSS or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in D prostanoid receptor 1 (DP1)-dependent manner. Specific ablation of DP1 receptor in vascular endothelial cells, colonic epithelium, and myeloid cells augmented DSS/TNBS-induced colitis in mice through increasing vascular permeability, promoting apoptosis of epithelial cells, and stimulating pro-inflammatory cytokine secretion of macrophages, respectively...
March 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28280721/tissue-biomarkers-in-hepatocellular-tumors-which-when-and-how
#7
REVIEW
Luca Di Tommaso, Massimo Roncalli
Few tissue markers are currently available to pathologists in the study of hepatocellular tumors. These markers should be used carefully taking into consideration not only morphology but also, and sometimes even more important, the clinical setting where the lesion to be diagnosed had developed. Glypican-3, heat shock protein 70, and glutamine synthetase (GS) are markers currently used, as a single panel, to discriminate the nature of a <2 cm hepatocellular lesion lacking radiological features of hepatocellular carcinoma (HCC) detected in a cirrhotic patient under surveillance...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28279492/group-2-innate-lymphoid-cells-are-recruited-to-the-nasal-mucosa-in-patients-with-aspirin-exacerbated-respiratory-disease
#8
Jacqueline J Eastman, Kellen J Cavagnero, Adam S Deconde, Alex S Kim, Maya R Karta, David H Broide, Bruce L Zuraw, Andrew A White, Sandra C Christiansen, Taylor A Doherty
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2 (PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2, but it is unknown whether ILC2s are active in patients with AERD. OBJECTIVE: We sought to determine whether ILC2 numbers change in peripheral blood and the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD...
January 27, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28262205/characterization-of-mast-cell-activation-syndrome
#9
Lawrence B Afrin, Sally Self, Jeremiah Menk, John Lazarchick
BACKGROUND: Mast cell activation syndrome (MCAS), a recently recognized nonneoplastic mast cell disease driving chronic multisystem inflammation and allergy, appears prevalent and thus important. We report the first systematic characterization of a large MCAS population. METHOD: Demographics, comorbidities, symptoms, family histories, physical examination and laboratory findings were reviewed in 298 retrospective and 115 prospective patients with MCAS. Blood samples from prospective subjects were examined by flow cytometry for clonal mast cell disease and tested for cytokines potentially driving the monocytosis frequent in MCAS...
March 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28258965/assessment-of-in-vivo-mast-cell-reactivity-in-patients-with-systemic-mastocytosis
#10
T Gülen, C Möller Westerberg, K Lyberg, M Ekoff, J Kolmert, J Bood, J Öhd, A James, S-E Dahlén, G Nilsson, B Dahlén
BACKGROUND: Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype. OBJECTIVE: To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM...
March 4, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28195470/total-synthesis-confirms-the-molecular-structure-proposed-for-oxidized-levuglandin-d2
#11
Yu-Shiuan Cheng, Wenyuan Yu, Yunfeng Xu, Robert G Salomon
Levuglandins (LG)D2 and LGE2 are γ-ketoaldehyde levulinaldehyde derivatives with prostanoid side chains produced by spontaneous rearrangement of the endoperoxide intermediate PGH2 in the biosynthesis of prostaglandins. Covalent adduction of LGs with the amyloid peptide Aβ1-42 promotes formation of the type of oligomers that have been associated with neurotoxicity and are a pathologic hallmark of Alzheimer's disease. Within 1 min of their generation during the production of PGH2 by cyclooxygenation of arachidonic acid, LGs are sequestered by covalent adduction to proteins...
February 24, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28174214/excitotoxicity-induced-prostaglandin-d2-production-induces-sustained-microglial-activation-and-delayed-neuronal-death
#12
Kensuke Iwasa, Shinji Yamamoto, Sosuke Yagishita, Kei Maruyama, Keisuke Yoshikawa
Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD2, PGE2, and PGF2α are produced by cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration...
April 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28167223/anti-allergic-activity-of-2-4-6-trihydroxy-3-geranylacetophenone-thga-via-attenuation-of-ige-mediated-mast-cell-activation-and-inhibition-of-passive-systemic-anaphylaxis
#13
Ji Wei Tan, Daud Ahmad Israf, Hanis Hazeera Harith, Nur Fariesha Md Hashim, Chean Hui Ng, Khozirah Shaari, Chau Ling Tham
tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation...
March 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28167222/identification-of-sperm-mrna-biomarkers-associated-with-testis-injury-during-preclinical-testing-of-pharmaceutical-compounds
#14
Edward Dere, Daniel J Spade, Susan J Hall, Aimee Altemus, James D Smith, Jonathan A Phillips, Jeffrey S Moffit, Kerry T Blanchard, Kim Boekelheide
The human testis is sensitive to toxicant-induced injury but current methods for detecting adverse effects are limited, insensitive and unreliable. Animal studies use sensitive histopathological endpoints to assess toxicity, but require testicular tissue that is not available during human clinical trials. More sensitive and reliable molecular biomarkers of testicular injury are needed to better monitor testicular toxicity in both clinical and preclinical. Adult male Wistar Han rats were exposed for 4weeks to compounds previously associated with testicular injury, including cisplatin (0, 0...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28140476/effects-of-leukoreduction-and-storage-on-erythrocyte-phosphatidylserine-expression-and-eicosanoid-concentrations-in-units-of-canine-packed-red-blood-cells
#15
S M Muro, J H Lee, J V Stokes, M K Ross, T M Archer, R W Wills, A J Mackin, J M Thomason
BACKGROUND: Storage of canine packed red blood cells (pRBCs) can increase erythrocyte phosphatidylserine (PS) expression and eicosanoid concentrations. HYPOTHESIS/OBJECTIVES: To determine the effects of leukoreduction on erythrocyte PS expression and eicosanoid concentrations in stored units of canine pRBCs. Our hypothesis was that leukoreduction would decrease PS expression and eicosanoid concentrations. ANIMALS: Eight healthy dogs. METHODS: In a cross-over study, units of whole blood were leukoreduced (LR) or non-LR and stored (10 and 21 days) as pRBCs...
March 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28139520/effect-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2nanocapsules-on-inflammation-and-bone-regeneration-in-a-rat-bone-defect-model
#16
Qi Tang, Li-Li Chen, Fen Wei, Wei-Lian Sun, Li-Hong Lei, Pei-Hui Ding, Jing-Yi Tan, Xiao-Tao Chen, Yan-Min Wu
BACKGROUND: 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the major metabolites from prostaglandin D2 in arachidonic acid metabolic pathway, has potential anti-inflammatory properties. The objective of this study was to explore the effects of 15d-PGJ2-loaded poly(D,L-lactide-co-glycolide) nanocapsules (15d-PGJ2-NC) on inflammatory responses and bone regeneration in local bone defect. METHODS: The study was conducted on 96 Wistar rats from June 2014 to March 2016...
February 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28137629/prostaglandins-e2-and-d2-regulators-of-host-immunity-in-the-model-parasite-diphyllobothrium-dendriticum-an-immunocytochemical-and-biochemical-study
#17
Ivan A Kutyrev, Natalia M Biserova, Daniil N Olennikov, Janetta V Korneva, Olga E Mazur
The spectrum of immunomodulating molecules produced by tapeworms is not yet well understood. The aims of this study, on the tapeworm Diphyllobothrium dendriticum, were: 1) detection and quantification of prostaglandins (PGs) E2 and D2 by high performance liquid chromatography; 2) visualization of PGE2 and PGD2 in specific cells, using methods of immunocytochemistry and confocal laser scanning microscopy; and 3) investigation of the ultrastructure of the cells potentially producing PGE2 and PGD2. The PGE2 immunoreaction (IR) was found in the apical terminals of the frontal glands and sensory organs in the tegument and in small neurons belonging to the main cords and commissures...
January 27, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28115217/cysteinyl-leukotriene-e4-activates-human-group-2-innate-lymphoid-cells-and-enhances-the-effect-of-prostaglandin-d2-and-epithelial-cytokines
#18
Maryam Salimi, Linda Stöger, Wei Liu, Simei Go, Ian Pavord, Paul Klenerman, Graham Ogg, Luzheng Xue
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are a potential innate source of type 2 cytokines in the pathogenesis of allergic conditions. Epithelial cytokines (IL-33, IL-25, and thymic stromal lymphopoietin [TSLP]) and mast cell mediators (prostaglandin D2 [PGD2]) are critical activators of ILC2s. Cysteinyl leukotrienes (cysLTs), including leukotriene (LT) C4, LTD4, and LTE4, are metabolites of arachidonic acid and mediate inflammatory responses. Their role in human ILC2s is still poorly understood...
January 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28112177/adenosine-a2a-receptor-deficiency-attenuates-the-somnogenic-effect-of-prostaglandin-d2-in-mice
#19
Bin-Jia Zhang, Zhi-Li Huang, Jiang-Fan Chen, Yoshihiro Urade, Wei-Min Qu
Prostaglandin D2 (PGD2) is one of the most potent endogenous sleep promoting substances. PGD2 activates the PGD2 receptor (DPR) and increases the extracellular level of adenosine in wild-type (WT) mice but not DPR knockout (KO) mice, suggesting that PGD2-induced sleep is DPR-dependent, and adenosine may be the signaling molecule that mediates the somnogenic effect of PGD2. The aim of this study was to determine the involvement of the adenosine A2A receptor (A2AR) in PGD2-induced sleep. We infused PGD2 into the lateral ventricle of WT and A2AR KO mice between 20:00 and 2:00 for 6 h, and electroencephalograms and electromyograms were simultaneously recorded...
April 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28099503/3d-functional-corneal-stromal-tissue-equivalent-based-on-corneal-stromal-stem-cells-and-multi-layered-silk-film-architecture
#20
Chiara E Ghezzi, Benedetto Marelli, Fiorenzo G Omenetto, James L Funderburgh, David L Kaplan
The worldwide need for human cornea equivalents continues to grow. Few clinical options are limited to allogenic and synthetic material replacements. We hypothesized that tissue engineered human cornea systems based on mechanically robust, patterned, porous, thin, optically clear silk protein films, in combination with human corneal stromal stem cells (hCSSCs), would generate 3D functional corneal stroma tissue equivalents, in comparison to previously developed 2D approaches. Silk film contact guidance was used to control the alignment and distribution of hCSSCs on RGD-treated single porous silk films, which were then stacked in an orthogonally, multi-layered architecture and cultured for 9 weeks...
2017: PloS One
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