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https://www.readbyqxmd.com/read/28737453/the-metabolism-and-drug-drug-interaction-potential-of-the-selective-prostacyclin-receptor-agonist-selexipag
#1
Carmela Gnerre, Jérôme Segrestaa, Swen Seeland, Päivi Äänismaa, Thomas Pfeifer, Stephane Delahaye, Ruben de Kanter, Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber
- The metabolism of selexipag has been studied in vivo in man and the main excreted metabolites were identified. Also, metabolites circulating in human plasma have been structurally identified and quantified. - The main metabolic pathway of selexipag in man is the formation of the active metabolite ACT-333679. Other metabolic pathways include oxidation and dealkylation reactions. All primary metabolites undergo subsequent hydrolysis of the sulphonamide moiety to their corresponding acids. ACT-333679 undergoes conjugation with glucuronic acid and aromatic hydroxylation to P10, the main metabolite detected in human faeces...
July 24, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28737104/severe-postoperative-complications-may-be-related-to-mesenteric-traction-syndrome-during-open-esophagectomy
#2
R Ambrus, L B Svendsen, N H Secher, J P Goetze, K Rünitz, M P Achiam
BACKGROUND: During abdominal surgery, traction of the mesenterium provokes mesenteric traction syndrome, including hypotension, tachycardia, and flushing, along with an increase in plasma prostacyclin (PGI2). We evaluated whether postoperative complications are related to mesenteric traction syndrome during esophagectomy. METHODS: Flushing, hemodynamic variables, and plasma 6-keto-PGF1α were recorded during the abdominal part of open ( n = 25) and robotically assisted ( n = 25) esophagectomy...
March 1, 2017: Scandinavian Journal of Surgery: SJS
https://www.readbyqxmd.com/read/28733316/inhaled-prostacyclin-as-salvage-therapy-for-ards-can-we-find-the-right-patient
#3
EDITORIAL
Amy H Attaway, Catherine Myers, Shrey Velani, Robert Schilz
No abstract text is available yet for this article.
August 2017: Respiratory Care
https://www.readbyqxmd.com/read/28732575/beraprost-sodium-a-prostacyclin-analogue-reduces-fructose-induced-hepatocellular-steatosis-in-mice-and-in-vitro-via-the-microrna-200a-and-sirt1-signaling-pathway
#4
Pengyuan Zhang, Lijuan Xu, Hongyu Guan, Liehua Liu, Juan Liu, Zhimin Huang, Xiaopei Cao, Zhihong Liao, Haipeng Xiao, Yanbing Li
PURPOSE: To determine whether beraprost sodium, a prostacyclin analogue, could reduce hepatic lipid accumulation induced by fructose in mice and cultured human hepatocytes, and to investigate the expression of microRNAs and the sirtuin 1 (SIRT1) pathway. METHODS: Male C57BL/6JNju mice were divided into three groups and fed one of the following diets: a normal diet, a high fructose diet, or a high fructose diet with beraprost sodium treatment. In addition, human-derived HepG2 cells were cultured and treated with fructose (25mmol/L) with or without beraprost sodium (10μmol/L) for 24h, and transfected with small interfering RNA (siRNA) against SIRT1, miR-200a mimic, or miR-200a inhibitor for 48h...
August 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28729387/leg-blood-flow-is-impaired-during-small-muscle-mass-exercise-in-copd-patients
#5
Ulrik Winning Iepsen, Gregers Druedal Wibe Munch, Mette Rugbjerg, Camilla Koch Ryrsø, Niels Secher, Ylva Hellsten, Peter Lange, Bente Klarlund Pedersen, Pia Thaning, Stefan P Mortensen
Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with COPD. We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex matched healthy controls were studied...
July 20, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28717253/prostacyclin-reverses-platelet-stress-fibre-formation-causing-platelet-aggregate-instability
#6
M Z Yusuf, Z Raslan, L Atkinson, A Aburima, S G Thomas, K M Naseem, S D J Calaminus
Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715904/considerations-for-optimal-management-of-patients-with-pulmonary-arterial-hypertension-a-multi-stakeholder-roundtable-discussion
#7
Sean M Studer, Martha Kingman, Luis Calo, H Eric Cannon, Jeffrey D Dunn, Thomas James, Sonya J Lewis, Robert J Gilkin, Janis A Pruett
A roundtable panel of national and regional managed care decision makers and providers met to discuss pulmonary arterial hypertension (PAH) and strategies for management. As a rare, complex disease with high economic costs and potentially devastating outcomes, PAH necessitates that managed care providers balance optimal care with efficient use of healthcare resources. PAH specialists are recognized by health plans as knowledgeable experts and integral partners in managing patients and resources. The diagnosis of PAH must be confirmed by a right heart catheterization...
May 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28711625/suppressing-mpges-1-expression-by-sinomenine-ameliorates-inflammation-and-arthritis
#8
Hua Zhou, Jian-Xin Liu, Jin-Fang Luo, Chun-Song Cheng, Elaine Lai-Han Leung, Ying Li, Xiao-Hui Su, Zhong-Qiu Liu, Ting-Bo Chen, Fu-Gang Duan, Yan Dong, Yi-Han Zuo, Chong Li, Chon Kit Lio, Ting Li, Pei Luo, Ying Xie, Xiao-Jun Yao, Pei-Xun Wang, Liang Liu
Recently, microsomal prostaglandin E synthase 1 (mPGES-1) has attracted much attention from pharmacologists as a promising strategy and an attractive target for treating various types of diseases including rheumatoid arthritis (RA), which could preserve the anti-inflammatory effect while reducing the adverse effects often occur during administration of Non-steroidal anti-inflammatory drugs (NSAIDs). Here, we report that Sinomenine (SIN) decreased prostaglandin (PG)E2 levels without affecting prostacyclin (PG)I2 and thromboxane (TX)A2 synthesis via selective inhibiting mPGES-1 expression, a possible reason of low risk of cardiovascular event compared with NSAIDs...
July 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28704616/inhibition-of-platelet-aggregation-ex-vivo-is-repressed-in-apolipoprotein-e-deficient-mice
#9
Emilie Carrier, Martin Houde, Michel Grandbois, Ghassan Bkaily, Timothy D Warner, Pedro D'Orleans-Juste
In the present study, we assessed if the endogenous platelet inhibitory mechanisms are altered in the early to moderate stages of the atherosclerotic process. Apolipoprotein E deficient mice (ApoE-/-), a mouse model of atherosclerosis, and their wild-type (WT) counterparts were used to assess agonist-stimulated synthesis of prostacyclin (PGI2), inhibition of platelet aggregation ex vivo and intra-platelet cAMP levels. Basal U46619 and ADP -induced platelet aggregation in vitro were increased in ApoE-/- mice at 18-20 weeks in comparison to 8 10 weeks of age...
July 13, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28702718/single-center-experience-using-selexipag-in-a-pediatric-population
#10
Roberto Gallotti, Diana E Drogalis-Kim, Gary Satou, Juan Alejos
Pulmonary arterial hypertension (PAH) is a rare and progressive disorder. Current treatment in the pediatric population includes phosphodiesterase 5 inhibitors (PDE-5i), endothelin receptor antagonists (ERA), and both inhaled and intravenous prostacyclin pathway agonists. As of December 22, 2015 the first oral prostacyclin pathway agonist, selexipag (Uptravi(®)), was FDA approved in the US. In this case series, we discuss our single-center experience using selexipag in a pediatric population, composed of both patients with idiopathic PAH, and patients with congenital heart disease and PAH...
July 13, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28690295/high-frequency-of-acute-adverse-cardiovascular-events-after-lung-transplantation-in-patients-with-pulmonary-arterial-hypertension-receiving-preoperative-long-term-intravenous-prostacyclin
#11
Satoshi Akagi, Takahiro Oto, Motomu Kobayashi, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Kazufumi Nakamura, Toshihiro Sarashina, Shinichiro Miyoshi, Hiroshi Ito
Adverse cardiovascular events after lung transplantation (LT) increase the mortality in patients with pulmonary arterial hypertension (PAH). Long-term intravenous prostacyclin is the usual treatment in severe patients with PAH, but it may increase the risk of hemorrhage due to its antiplatelet aggregation effect or thrombocytopenia. We investigated the impact of length of intravenous prostacyclin therapy on acute adverse cardiovascular events including hemorrhagic complication after LT. We retrospectively compared the incidence of adverse events (death, intrathoracic hematoma and bleeding, cardiac congestion or shock, cerebral infarction and pulmonary embolism) within 30 days after LT between no/short-term (median 0...
July 10, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28674339/effect-of-self-healing-encapsulation-on-the-initial-burst-release-from-plga-microspheres-containing-a-long-acting-prostacyclin-agonist-ono-1301
#12
Mai Hazekawa, Honami Kojima, Tamami Haraguchi, Miyako Yoshida, Takahiro Uchida
The purpose of this study was to perform self-healing encapsulation of ONO-1301, a long-acting prostacyclin agonist, into poly(lactide-co-glycolide) (PLGA) microspheres using the oil-in-water (o/w) emulsion solvent evaporation method in order to try to limit the initial burst release of drug. Adequate self-healing of PLGA seemed to be achieved by stirring during the evaporation of solvent at 40°C close to the glass transition temperature (Tg) of the polymer (40.1°C). The plasticizers dimethylphthalate (DEP) or tributyl O-acetylcitrate (TBAC), at concentrations of 0...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28664658/effects-of-aspirin-dose-escalation-on-platelet-function-and-urinary-thromboxane-and-prostacyclin-levels-in-normal-dogs
#13
N McLewee, T Archer, R Wills, A Mackin, J Thomason
Established "low" aspirin dosages inconsistently inhibit platelet function in dogs. Higher aspirin dosages consistently inhibit platelet function, but are associated with adverse effects. The objectives of this study were to use an escalation in dosage to determine the lowest aspirin dosage that consistently inhibited platelet function without inhibiting prostacyclin synthesis. Eight dogs were treated with five aspirin dosages: 0.5 mg/kg q24h, 1 mg/kg q24h, 2 mg/kg q24h, 4 mg/kg q24h and 10 mg/kg q12h for 7 days...
June 30, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28662006/-turmeric-not-only-spice
#14
EDITORIAL
Zygmunt Zdrojewicz, Marta Szyca, Ewa Popowicz, Tomasz Michalik, Bartłomiej Śmieszniak
The purpose of this article is to introduce the role of turmeric in medicine and summarize the current state of research on its applications. Turmeric (Curcuma longa) has had a wide range of uses in middle eastern and orietnal traditional medicine. Currently, however, its use has been truncated to a common cooking spice, despite numerous studies pointing to its healing properties and possible use in the treatment of many diseases. The main focus is on curcumin, a polyphenol which serves as the biologically active component of turmeric...
June 23, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28653193/effects-of-ripasudil-hydrochloride-hydrate-k-115-a-rho-kinase-inhibitor-on-ocular-blood-flow-and-ciliary-artery-smooth-muscle-contraction-in-rabbits
#15
Yusuke Ohta, Sanae Takaseki, Takeshi Yoshitomi
PURPOSE: Ripasudil, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, is a novel drug for glaucoma in Japan. ROCK inhibition not only reduces intraocular pressure (IOP) but also increases ocular blood flow. We investigated the effects of ripasudil on optic disc blood flow (ODBF) in rabbit eyes and in isolated rabbit ciliary arteries. METHODS: We measured IOP by tonometry and ODBF by laser speckle flowgraphy (LSFG) in male Dutch rabbits. A single drop (20 μL) of 0...
June 26, 2017: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28639216/biocomparison-study-of-adult-and-paediatric-dose-strengths-of-the-prostacyclin-receptor-agonist-selexipag
#16
Margaux Boehler, Shirin Bruderer, Ivan Ulč, Jasper Dingemanse
BACKGROUND AND OBJECTIVES: Selexipag is an oral, non-prostanoid, selective prostacyclin receptor agonist recently marketed for the treatment of pulmonary arterial hypertension (PAH) in adults. Selexipag may also be an effective treatment in children with PAH. The aim of this study was to compare the pharmacokinetics of selexipag and its active metabolite ACT-333679 following single oral administration of one tablet of 200 µg selexipag (Treatment A) vs. 4 paediatric tablets of 50 µg (Treatment B) in healthy adult male subjects...
June 21, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28632002/express-management-of-prostacyclin-side-effects-in-adult-patients-with-pulmonary-arterial-hypertension
#17
Martha Kingman, Christine Archer-Chicko, Mary Bartlett, Joy Beckmann, Robin Hohsfield, Sandra Lombardi
No abstract text is available yet for this article.
January 1, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28621447/metformin-prevents-vascular-prostanoid-release-alterations-induced-by-a-high-fat-diet-in-rats
#18
H J Lee, S M Cantú, A S Donoso, M R Choi, H A Peredo, A M Puyó
Perivascular adipose tissue dysfunction induced by high-fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator of AMP-activated protein kinase (AMPK), is currently the first-line drug treatment for type 2 diabetes (T2DM) and metabolic syndrome. Besides its glucose-lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases...
June 16, 2017: Autonomic & Autacoid Pharmacology
https://www.readbyqxmd.com/read/28609556/prevention-of-livedoid-vasculopathy-recurrence-by-prolonged-administration-of-rivaroxaban
#19
Ch Drerup, T Goerge
A 49-year-old man with known livedoid vasculopathy presented with recurrent painful (VAS 8/10) ulceration and necrosis on the foot (Figure 1). He was formerly treated with prostacyclin infusions, acetylsalicylic acid, intravenous immunoglobulins, different systemic antibiotics and a skin grafting. At admission an antithrombotic therapy with enoxaparin (Clexane(®) ) in a dose of 1 mg/ kg bodyweight (100 mg) once daily was initiated. This article is protected by copyright. All rights reserved.
June 13, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28597774/combination-therapy-in-pulmonary-arterial-hypertension-recent-accomplishments-and-future-challenges
#20
Annie-Christine Lajoie, Sebastien Bonnet, Steeve Provencher
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a progressive increase in pulmonary vascular resistance, ultimately leading to right heart failure and death. Throughout the past 20 years, numerous specific pharmacologic agents, including phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostaglandins, and more recently, soluble guanylate cyclase stimulators and selective IP prostacyclin receptor agonist, have emerged for the treatment of PAH. Early clinical trials were typically of short-term duration, comparing the effects of PAH-targeted therapies versus placebo and using exercise tolerance as the primary endpoint in most trials...
April 2017: Pulmonary Circulation
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