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https://www.readbyqxmd.com/read/28544596/deletion-of-the-prostaglandin-d2-receptor-dp1-exacerbates-aging-associated-and-instability-induced-osteoarthritis
#1
Yassine Ouhaddi, Sarah-Salwa Nebbaki, Lauris Habouri, Hassan Afif, Bertrand Lussier, Mohit Kapoor, Shuh Narumiya, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Mohamed Benderdour, Hassan Fahmi
OBJECTIVE: The D prostanoid receptor 1 (DP1), a receptor for prostaglandin D2 (PGD2 ), plays important roles in inflammation and cartilage metabolism. However, its role in the pathogenesis of osteoarthritis (OA) remains unknown. We undertook this study to explore the roles of DP1 in the development of OA and to evaluate the efficacy of a DP1 selective agonist in the treatment of OA. METHODS: We compared the development of aging-associated OA and destabilization of the medial meniscus (DMM)-induced OA in DP1-deficient (DP1-/-) and wild-type (WT) mice...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28533253/selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#2
Zachary R Noel, Kazuhiko Kido, Tracy E Macaulay
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosing and administration, and place in therapy of selexipag, an orally administered selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension (PAH), are reviewed. SUMMARY: The first-in-class oral prostacyclin IP receptor agonist selexipag (Uptravi, Actelion Pharmaceuticals) was approved by the Food and Drug Administration in December 2015...
May 22, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28532389/the-use-of-macitentan-in-fontan-circulation-a-case-report
#3
Polyvios Demetriades, Amir Aziz, Robin Condliffe, Sarah E Bowater, Paul F Clift
BACKGROUND: The Fontan circulation, a result of a palliative procedure in patients with single systemic ventricles, is defined by chronically elevated pulmonary vascular resistance. When traditional heart failure therapies fail, pharmacological agents that reduce pulmonary artery pressures may be used. These include endothelial-receptor antagonists, prostanoids and phosphodiesterase type 5 inhibitors. We report the first use of macitentan, an endothelin-receptor antagonist, in a patient with a Fontan circulation...
May 22, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28513869/transition-of-intravenous-treprostinil-to-oral-therapy-in-a-patient-with-functional-class-iv-chronic-thromboembolic-pulmonary-hypertension
#4
Kristina M Thurber, Breann M Williams, Ruth E Bates, Robert P Frantz
Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary emboli fail to resolve with anticoagulation. For patients with inoperable or residual CTEPH, riociguat is currently the only therapy approved by the United States Food and Drug Administration. However, some patients with CTEPH may require therapy beyond riociguat, such as intravenous prostacyclins, which can present significant administration challenges in patients with complex comorbid conditions. We describe a 42-year-old man with T12 paraplegia complicated by CTEPH (functional class IV with substantial right ventricular dysfunction) and severe pressure ulcers...
May 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28512386/oxidative-stress-biomarkers-establishment-of-reference-values-for-isoprostanes-aopp-and-npbi-in-cord-blood
#5
Mariangela Longini, Elisa Belvisi, Fabrizio Proietti, Francesco Bazzini, Giuseppe Buonocore, Serafina Perrone
Oxidative stress (OS) is a common pathogenic factor involved in the onset of several diseases in humans, from immunologic disorders to malignancy, being a serious public health problem. In perinatal period, OS has been associated with adverse outcome of pregnancy and neonatal diseases. Dangerous effects of OS are mediated by increased production of free radicals (FRs) following various mechanisms, such as hypoxia, ischemia reperfusion, hyperoxia, inflammation, mitochondrial dysfunction, Fenton chemistry, and prostaglandin metabolism...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28507431/targeted-drugs-for-pulmonary-arterial-hypertension-a-network-meta-analysis-of-32-randomized-clinical-trials
#6
Xiao-Fei Gao, Jun-Jie Zhang, Xiao-Min Jiang, Zhen Ge, Zhi-Mei Wang, Bing Li, Wen-Xing Mao, Shao-Liang Chen
BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28502103/reduced-platelet-aggregation-in-women-after-intercourse-a-possible-role-for-the-cyclooxygenase-pathway
#7
Gabriel Mayoral-Andrade, Laura Pérez-Campos-Mayoral, Abraham Majluf-Cruz, Eduardo Perez-Campos Mayoral, Carlos Perezcampos Mayoral, Ana Rocha-Núñez, Margarito Martinez, Edgar Zenteno, Leticia Hernandez-Gonzalez, María Guadalupe López Juan, Alma Dolores Pérez-Santiago, Eduardo Pérez-Campos
We hypothesise that molecules in the cyclooxygenase pathway affect platelet activity when seminal fluid (SF) is present. We considered the influence of SF on platelet aggregation in women, and believe that the prostanoids in SF signalling are significant. Thirty-one female subjects were studied, 20 of whom were sexually active. Male partners were given either aspirin or indomethacin to inhibit cyclooxygenase. The 6-keto prostaglandin F1α (6-keto PGF1α) and prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay...
May 14, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28494828/treatment-of-persistent-pulmonary-hypertension-of-the-newborn-use-of-pulmonary-vasodilators-in-term-neonates
#8
Caitlyn Luecke, Christopher McPherson
Persistent pulmonary hypertension of the newborn (PPHN) represents a challenging condition associated with significant morbidity. A successful transition from intrauterine to extrauterine life is contingent on adequate pulmonary vasodilation. Several pathophysiologies contribute to the failure of this cascade and may result in life-threatening hypoxia and acidosis in the newborn. Management includes optimal respiratory support, adequate sedation and analgesia, and support of vascular tone and cardiac function...
May 1, 2017: Neonatal Network: NN
https://www.readbyqxmd.com/read/28494686/clinical-pharmacology-efficacy-and-safety-of-selexipag-for-the-treatment-of-pulmonary-arterial-hypertension
#9
Shirin Bruderer, Noémie Hurst, Tatiana Remenova, Jasper Dingemanse
Selexipag is the first oral, non-prostanoid, selective prostacyclin receptor (IP receptor) agonist, approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients. Areas covered: This article reviews the clinical pharmacology, efficacy, and safety of selexipag in the treatment of PAH. Expert opinion: Selexipag is the first oral drug that selectively targets the prostacyclin pathway, and has evidence of long-term efficacy and safety. In the global phase 3 study GRIPHON (NCT01106014) in PAH patients, selexipag significantly reduced the risk of the primary composite outcome of morbidity/mortality (M/M)...
June 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28491485/cardiovascular-risk-of-nonsteroidal-anti-inflammatory-drugs-an-under-recognized-public-health-issue
#10
REVIEW
Zoltan Varga, Syed Rafay Ali Sabzwari, Veronika Vargova
Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs with analgesic, anti-inflammatory, and antipyretic activity. Their effect is achieved by the reduction in synthesis of prostanoids. Inhibition of prostanoids is responsible for a substantial risk of adverse effects. The risk of side effects affecting the gastrointestinal tract and kidneys has long been known. The possibilities of blood pressure elevation and the development of congestive heart failure are also widely recognized. Increased incidence of acute myocardial infarction in clinical trials with rofecoxib drew attention to the potential cardiotoxicity of selective cyclooxygenase-2 inhibitors, and similarly, concerns have been raised regarding the cardiovascular safety of non-selective NSAIDs...
April 8, 2017: Curēus
https://www.readbyqxmd.com/read/28476928/the-selexipag-active-metabolite-act-333679-displays-strong-anti-contractile-and-anti-remodeling-effects-but-low-%C3%AE-arrestin-recruitment-and-desensitization-potential
#11
John Gatfield, Katalin Menyhart, Daniel Wanner, Carmela Gnerre, Lucile Monnier, Keith Morrison, Patrick Hess, Marc Iglarz, Martine Clozel, Oliver Nayler
Prostacyclin (PGI2) receptor (IP receptor) agonists, which are indicated for the treatment of pulmonary arterial hypertension (PAH), increase cytosolic cAMP levels and thereby inhibit pulmonary vasoconstriction, pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular matrix synthesis. Selexipag (Uptravi(®)) is the first non-prostanoid IP receptor agonist, it is available orally and was recently approved for the treatment of PAH. In this study we show that the active metabolite of selexipag and the main contributor to clinical efficacy, ACT-333679 (previously known as MRE-269), behaved as full agonist in multiple PAH-relevant receptor-distal - or downstream - cellular readouts with a maximal efficacy comparable to that of the prototypic PGI2 analog iloprost: In PASMC, ACT-333679 potently induced cellular relaxation (EC50=4...
May 5, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28460684/effects-of-lpa2r-lpa3r-or-ep4r-agonists-on-luteal-or-endometrial-function-in%C3%A2-vivo-or-in%C3%A2-vitro-and-sirtuin-or-ep1r-ep2r-ep3r-or-ep4r-agonists-on-endometrial-secretion-of-pge-and-pgf2%C3%AE-in%C3%A2-vitro
#12
Magen E LaPorte, Yoshie S Weems, Alejandro Arreguin-Arevalo, Terry M Nett, Nicole Tsutahara, Tracy Sy, Jade Haberman, Michel Chon, Ronald D Randel, Charles W Weems
In previous work, an EP2 prostanoid receptor (EP2R) agonist in vivo increased mRNA expression of luteal LH receptors (LHR), unoccupied and occupied luteal; LHR, and circulating progesterone, while an EP3R or FPR agonist decreased; mRNA expression of luteal LHR, unoccupied and occupied luteal LHR, and; circulating progesterone. An EP4R and lysophosphatidic acid (LPA) LPA2R and LPA3R agonists were reported to inhibit luteal function and sirtuins have been proposed to increase prostaglandin synthesis. The objectives were to determine; whether an EP4R, LPA2R, or LPA3R agonist affect ovine luteal function in vivo or; in vitro...
June 2017: Theriogenology
https://www.readbyqxmd.com/read/28458341/the-role-of-mpges-1-in-inflammatory-brain-diseases
#13
Yuri Ikeda-Matsuo
Prostaglandin E2 (PGE2) has been thought to be an important mediator of inflammation in peripheral tissues, but recent studies clearly show the involvement of PGE2 in inflammatory brain diseases. In some animal models of brain disease, the genetic disruption and chemical inhibition of cyclooxygenase (COX)-2 resulted in the reduction of PGE2 and amelioration of symptoms, and it had been thought that PGE2 produced by COX-2 may be involved in the progression of injuries. However, COX-2 produces not only PGE2, but also some other prostanoids, and thus the protective effects of COX-2 inhibition, as well as severe side effects, may be caused by the inhibition of prostanoids other than PGE2...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28450284/eets-promote-hypoxic-pulmonary-vasoconstriction-via-constrictor-prostanoids
#14
Sharath Kandhi, Bin Zhang, Ghezal Froogh, Jun Qin, Norah Alruwali, Yicong Le, Yang-Ming Yang, Sung Hee Hwang, Bruce D Hammock, Michael S Wolin, An Huang, Dong Sun
To test the hypothesis that epoxyeicosatrienoic acids (EETs) facilitate pulmonary responses to hypoxia, male wild type (WT) and soluble epoxide hydrolase knockout (sEH-KO) mice, and WT mice chronically fed a sEH inhibitor (t-TUCB; 1mg/kg/day) were used. Right ventricular systolic pressure (RVSP) was recorded under control and hypoxic conditions. The control RVSP was comparable among all groups. However, hypoxia elicited increases in RVSP in all groups with predominance in sEH-KO and t-TUCB-treated mice. 14,15-EEZE (EET antagonist) attenuated the hypoxia-induced greater elevation of RVSP in sEH-deficient mice, suggesting an EET-mediated increment...
April 27, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28448188/effects-of-indomethacin-on-prostanoid-synthesis-and-vasomotor-responsiveness-in-endothelium-denuded-abdominal-and-thoracic-aortas-of-wistar-rats
#15
Ruth M López, Janette E López, Jorge S López, María C Castillo, Gustavo Guevara, José A Morales, Oscar A López, Jair Lozano, Enrique F Castillo
In endothelium-denuded abdominal (but not thoracic) aortas of rats, the nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed contractions evoked by α-adrenergic agonists hypothetically mediated by prostanoids. We aimed to identify these non-endothelial-derived contractile prostanoids released by α-adrenergic receptors activation. Endothelium-denuded abdominal and thoracic aortas of Wistar rats were used for biochemical and functional analyses. Western blot analysis showed that COX-1 and COX-2 protein levels were respectively equivalent in endothelium-denuded abdominal and thoracic aortas...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28445779/the-acute-cardiorespiratory-effects-of-centrally-injected-arachidonic-acid-the-mediation-of-prostaglandin-e-d-and-f2%C3%AE
#16
Leman Gizem Erkan, Burcin Altinbas, Gokcen Guvenc, Begum Aydin, Nasir Niaz, Murat Yalcin
Arachidonic acid (AA), which is released from synaptic membrane phospholipid by neuroreceptor-initiated activation of phospholipase A2, is abundant in the brain and works as a neurotransmitter and/or neuromodulator in the central nervous system. Recently we reported that centrally injected AA generated pressor and hyperventilation effects by activating thromboxane A2 (TXA2) signaling pathway. The present study was designed to investigate the mediation of other metabolites of AA such as prostaglandin (PG) D, PGE and PGF2α alongside TXA2 in the AA-evoked cardiorespiratory effects in anaesthetized rats...
April 23, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28442063/peri-ovulatory-endocrine-regulation-of-the-prostanoid-pathways-in-the-bovine-uterus-at-early-dioestrus
#17
Milena Lopes Oliveira, Fabio Luiz D'Alexandri, Guilherme Pugliesi, Veerle Van Hoeck, Fernando Silveira Mesquita, Claudia M B Membrive, João Alberto Negrão, Craig E Wheelock, Mario Binelli
We hypothesised that different endocrine profiles associated with pre-ovulatory follicle (POF) size would impact on uterine prostanoid pathways and thereby modulate the histotroph composition. Beef cows (n=15 per group) were hormonally manipulated to have small (SF-SCL group) or large (LF-LCL group) pre-ovulatory follicles (POF) and corpora lutea (CL). Seven days after induction of ovulation, animals were slaughtered and uterine tissues and flushings were collected for quantification of prostanoids. The POF and CL size and the circulating progesterone concentrations at Day 7 were greater (P<0...
March 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#18
Xu Luo, Qiquan Zhu, Jie Zhang, Qin Huang, Zongyi Xie, Yuan Cheng
Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc...
April 24, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28439968/effects-of-an-ep2-and-ep3-receptor-dual-agonist-ono-8055-on-a-radical-hysterectomy-induced-underactive-bladder-model-in-monkeys
#19
Hidekazu Matsuya, Noritoshi Sekido, Jun Kida, Hiroko Mashimo, Daisuke Wakamatsu, Hiroki Okada
OBJECTIVES: The objective was to develop an underactive bladder (UAB) model in primates and to evaluate the potential of prostanoid EP2 and EP3 receptor dual agonist ONO-8055 to become a therapeutic agent for UAB. METHODS: A surgical procedure resembling radical hysterectomy was performed on female cynomolgus monkeys. Subsequently, in vitro muscle strip studies were performed using bladder muscle strips from normal monkeys and monkeys that underwent surgery. In addition, uroflowmetric data were obtained at specified days after the surgery...
April 25, 2017: Lower Urinary Tract Symptoms
https://www.readbyqxmd.com/read/28435971/-mechanisms-underlying-rat-coronary-arterial-vasoconstriction-induced-by-blockade-of-inward-rectifier-potassium-channels-with-bacl2
#20
Fang-Wen Fan, Ze-Fang He, Meng Shi, Rong Yang, Xiao-Min Hou, Yu Liu, Ming-Sheng Zhang
In order to explore the mechanisms underlying the vasoconstriction induced by blockade of inward rectifier K(+) channels (Kir) with BaCl2, myogenic tone of isolated rat coronary artery (RCA) was recorded with wire myograph. The dependence of BaCl2- induced contraction on intracellular Ca(2+) ([Ca(2+)]i) release and extracellular Ca(2+) ([Ca(2+)]o) influx was studied by Ca(2+) deprivation and restoration. The mechanisms underlying BaCl2-induced RCA contraction were investigated with specific inhibitors. BaCl2 (0...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
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