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Prostacyclin

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https://www.readbyqxmd.com/read/28429213/effect-of-compound-sbt-828-a-new-indole-derivative-exhibiting-antiaggregant-activity-on-the-prostacyclin-thromboxane-a2-balance
#1
A F Kucheryavenko, A A Spasov, M Tian, K F Suzdalev
We investigated the effect of a new indole derivative Sbt-828 with antiaggregant properties on prostacyclin-generating activity of the vascular wall and thromboxane A2 level in platelets of intact rats. The substance under study did not affect prostacyclin production by the vascular wall and significantly reduced thromboxane A2 level, being superior to the reference drug acetylsalicylic acid by 1.6 times, as seen from reduced malonic dialdehyde level in the thrombin-induced rat platelets.
April 20, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28420826/efficacy-and-safety-of-an-orally-administered-selective-prostacyclin-receptor-agonist-selexipag-in-japanese-patients-with-pulmonary-arterial-hypertension
#2
Nobuhiro Tanabe, Satoshi Ikeda, Nobuhiro Tahara, Keiichi Fukuda, Masaru Hatano, Hiroshi Ito, Tomotaka Nakayama, Toshihisa Anzai, Akiyoshi Hashimoto, Teruo Inoue, Kouji Kajinami, Yasuki Kihara, Hideyuki Kinoshita, Koichiro Kuwahara, Toyoaki Murohara, Osamu Okazaki, Satoshi Sakai, Toru Satoh, Yutaka Takeda, Yasuchika Takeishi, Mitsugu Taniguchi, Hiroshi Watanabe, Takeshi Yamamoto, Keiko Yamauchi-Takihara, Koichiro Yoshioka, Shigetake Sasayama
BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28414054/endothelium-dependent-vasorelaxant-effect-of-procyanidin-b2-on-human-internal-mammary-artery
#3
Aleksandra Novakovic, Marija Marinko, Goran Jankovic, Ivan Stojanovic, Predrag Milojevic, Dragoslav Nenezic, Vladimir Kanjuh, Qin Yang, Guo-Wei He
The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations...
April 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28412042/targeting-the-prostacyclin-pathway-beyond-pulmonary-arterial-hypertension
#4
REVIEW
Hélène Pluchart, Charles Khouri, Sophie Blaise, Matthieu Roustit, Jean-Luc Cracowski
Pioneering work demonstrated that an unstable substance isolated from rabbit and pig aortas could relax arterial smooth muscle and inhibit platelet aggregation. Since then, prostacyclin (prostaglandin I2, PGI2) and its analogs have raised much pharmacological interest. In this review we detail how the PGI2 signaling pathway is much more complex than was initially anticipated, involving peroxisome proliferator-activated receptors (PPARs), prostaglandin transporters (PGTs), and PGI2-thromboxane A2 (TXA2) receptor (IP TP) heterodimerization...
April 12, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28402977/molecular-mechanisms-leading-to-splanchnic-vasodilation-in-liver-cirrhosis
#5
Marco Di Pascoli, David Sacerdoti, Patrizia Pontisso, Paolo Angeli, Massimo Bolognesi
In liver cirrhosis, portal hypertension is a consequence of enhanced intrahepatic vascular resistance and portal blood flow. Significant vasodilation in the arterial splanchnic district is crucial for an increase in portal flow. In this pathological condition, increased levels of circulating endogenous vasodilators, including nitric oxide, prostacyclin, carbon monoxide, epoxyeicosatrienoic acids, glucagon, endogenous cannabinoids, and adrenomedullin, and a decreased vascular response to vasoconstrictors are the main mechanisms underlying splanchnic vasodilation...
April 13, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28399721/the-prostacyclin-pathway-in-pulmonary-arterial-hypertension-a-clinical-review
#6
R Del Pozo, I Hernandez Gonzalez, P Escribano-Subías
Prostacyclin is produced in vascular endothelial cells and acts via the IP prostacyclin receptor to cause vasodilation and inhibit smooth muscle cell proliferation and platelet aggregation. Prostacyclin production is reduced in pulmonary arterial hypertension (PAH), and drugs targeting the prostacyclin pathway are one of the pharmacotherapeutic options for PAH. Areas covered: The prostacyclin pathway and drugs that target it are discussed, including synthetic prostacyclin (epoprostenol), prostacyclin analogs (iloprost, treprostinil, beraprost) and selective prostacyclin IP receptor agonists (selexipag)...
April 12, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28386837/effect-of-delayed-onset-prostacyclin-on-markers-of-endothelial-function-and-damage-after-subarachnoid-hemorrhage
#7
Mikkel Gybel-Brask, Rune Rasmussen, Jakob Stensballe, Pär I Johansson, Sisse R Ostrowski
BACKGROUND: Subarachnoid hemorrhage (SAH) is a neurological emergency. Delayed ischemic neurological deficit is one of the main causes of poor outcome after SAH and is probably caused, at least in part, by cerebral vasospasm. The pathophysiology of this is multifaceted, but endothelial damage and activation as well as glycocalyx damage have been implicated. Prostacyclin has been shown to protect damaged and activated endothelium and to facilitate glycocalyx repair. We investigated biomarkers of endothelial activation and damage in patients with SAH randomized to 5 days prostacyclin infusion or placebo...
April 7, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28379623/on-pump-cardiac-surgery-enhances-platelet-renewal-and-impairs-aspirin-pharmacodynamics-effects-of-improved-dosing-regimens
#8
V Cavalca, B Rocca, F Veglia, G Petrucci, B Porro, V Myasoedova, R De Cristofaro, L Turnu, A Bonomi, P Songia, L Cavallotti, M Zanobini, M Camera, F Alamanni, A Parolari, C Patrono, E Tremoli
On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100mg once-daily were studied before surgery and randomized within 36 hours post-surgery to 100mg once-daily, 100mg twice-daily or 200mg once-daily for 90 days. On day 7 post-surgery, immature and mature platelets, platelet mass, thrombopoieitin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased...
April 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28374138/administration-of-inhaled-pulmonary-vasodilators-to-the-mechanically-ventilated-neonatal-patient
#9
REVIEW
Michael D Davis, Steven M Donn, Robert M Ward
Pulmonary hypertension is a life-threatening condition that affects people of all ages that can occur as an idiopathic disorder at birth or as part of a variety of cardiovascular and infectious disorders. It is commonly treated with inhaled pulmonary vasodilators such as nitric oxide and less frequently using formulations and analogs of prostacyclin. To minimize systemic effects and preserve pulmonary vasodilation, vasodilators are often administered directly into the airway. Nitric oxide is the only USA Food and Drug Administration-approved inhaled pulmonary vasodilator that can be used during mechanical ventilation...
April 3, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28373136/decreased-vasorelaxation-induced-by-iloprost-during-acute-inflammation-in-human-internal-mammary-artery
#10
Nabil Foudi, Gulsev Ozen, Yasmine Amgoud, Liliane Louedec, Christine Choqueux, Aouatef Badi, Larissa Kotelevets, Eric Chastre, Dan Longrois, Xavier Norel
Cyclooxygenase-2 (COX-2) induction in human internal mammary arteries (IMA) under inflammatory conditions has been associated with attenuated norepinephrine (NE)-induced vasoconstriction. This effect was associated with increased prostaglandin (PG) E2 and prostacyclin (PGI2) releases. The present study was designed to assess the role of these PG and their receptors (EP and IP, respectively) on the vascular reactivity during acute inflammation. Isolated IMA were cultured in the absence (Control conditions) or presence (Inflammatory conditions) of both interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS)...
March 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28370794/short-term-48-hours-intravenous-serelaxin-infusion-has-no-effect-on-myogenic-tone-or-vascular-remodeling-in-rat-mesenteric-arteries
#11
Maria Jelinic, Chen Huei Leo, Sarah A Marshall, Sevvandi N Senadheera, Laura J Parry, Marianne Tare
BACKGROUND: Short-term intravenous serelaxin (recombinant human relaxin-2) infusion enhances endothelium-dependent relaxation in mesenteric arteries. This is initially underpinned by increased nitric oxide (NO) followed by a transition to prostacyclin. The effects of short-term intravenous serelaxin treatment on pressure-induced myogenic tone and vascular remodeling in these arteries are unknown. Therefore, we investigated the effects of serelaxin infusion on pressure-induced myogenic tone and passive mechanical wall properties in mesenteric arteries...
March 31, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28368219/reduced-expression-of-adipose-triglyceride-lipase-decreases-arachidonic-acid-release-and-prostacyclin-secretion-in-human-aortic-endothelial-cells
#12
Monika Riederer, Margarete Lechleitner, Harald Köfeler, Saša Frank
BACKGROUND: Vascular endothelial cells represent an important source of arachidonic acid (AA)-derived mediators involved in the generation of anti- or proatherogenic environments. Evidence emerged (in mast cells), that in addition to phospholipases, neutral lipid hydrolases as adipose triglyceride lipase (ATGL) also participate in this process. OBJECTIVE: To examine the impact of ATGL on AA-release from cellular phospholipids (PL) and on prostacyclin secretion in human aortic endothelial cells (HAEC)...
April 3, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28361180/evaluation-of-endothelial-function-by-flow-mediated-dilation-a-comprehensive-review-in-rheumatic-disease
#13
REVIEW
Luca Moroni, Carlo Selmi, Claudio Angelini, Pier Luigi Meroni
Flow-mediated dilation (FMD) represents a non-invasive marker of endothelial function to evaluate vascular homeostasis, which reflects the effects of several mechanisms, including vessel tone regulation, cell proliferation, and inflammatory responses. Beyond classical atherosclerotic risk factors such as arterial hypertension, diabetes mellitus, smoking, obesity, and dyslipidemia, chronic inflammation contributes to the endothelial dysfunction causing plaque formation and there is growing evidence of a significantly higher cardiovascular morbidity associated with autoimmune diseases...
March 30, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28359367/nutritional-regulation-of-coupling-factor-6-a-novel-vasoactive-and-proatherogenic-peptide
#14
REVIEW
Tomohiro Osanai, Kasumi Mikami, Maiko Kitajima, Mayumi Urushizaka, Kumiko Kawasaki, Toshiko Tomisawa, Chieko Itaki, Yuka Noto, Koji Magota, Hirofumi Tomita
High sodium, high glucose, and obesity are important risk factors for age-related diseases such as cardiovascular disease (CVDs), stroke, and cancer. Coupling factor 6 (CF6) is released from vascular endothelial cells and functions as a circulating peptide that inhibits prostacyclin and nitric oxide generation by intracellular acidosis. High glucose elevates CF6 by activation of protein kinase C and p38 mitogen-activated protein kinase, whereas CF6 causes type 2 diabetes mellitus, resulting in a high glucose vicious cycle...
May 2017: Nutrition
https://www.readbyqxmd.com/read/28355094/advances-in-treatment-of-pulmonary-arterial-hypertension-patent-review
#15
Bhuvaneshwar Vaidya, Matthew Pangallo, Gregoire Ruffenach, Christine Marie Cunningham, Jeanette C Perron, Srikanth Kolluru, Mansoureh Eghbali, Vivek Gupta
Current therapeutic approaches for pulmonary arterial hypertension (PAH) commonly include use of prostacyclins, endothelin pathway antagonists or NO (nitric oxide) pathway modulators. These agents are non-specific and suffer from several important shortcomings including short half-lives, invasive routes of administration, higher dose and frequency requirements, and several dose-related systemic side effects. Hence, discovery of novel agents with improved therapeutic efficacy with respect to survival benefits and the development of non-invasive routes of administration are in critical need...
March 29, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28348727/steps-forward-in-the-treatment-of-pulmonary-arterial-hypertension-latest-developments-and-clinical-opportunities
#16
REVIEW
Jessica B Badlam, Todd M Bull
Pulmonary arterial hypertension (PAH) is a chronic disease that results in narrowing of the small pre-capillary pulmonary arteries leading to elevation of pulmonary artery pressure and pulmonary vascular resistance, subsequent right ventricular failure, and if unchecked, death. Advances in the treatment of PAH over the last two decades have markedly improved survival. These improvements reflect a combination of changes in treatments, improved patient care strategies, and varying disease phenotypes in the PAH population...
February 2017: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/28347710/prostanoids-in-the-pathophysiology-of-human-coronary-artery
#17
REVIEW
Gulsev Ozen, Xavier Norel
Coronary artery disease is one of the leading causes of death in wordwide. There is growing evidence that prostanoids are involved in the physiology and pathophysiology of the human coronary artery by controlling vascular tone, remodelling of the vascular wall or angiogenesis. In this review, the production of prostanoids and the expression of prostanoid receptors in human coronary artery in health or disease are described. In addition, the interactions between sex hormones and prostanoids, their participations in the development of coronary artery diseases have been addressed...
March 24, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28306170/impact-of-atrial-fibrillation-on-platelet-gene-expression
#18
Waldemar E Wysokinski, Alfonso Tafur, Naser Ammash, Samuel J Asirvatham, Yanhong Wu, Izabella Gosk-Bierska, Diane E Grill, Joshua P Slusser, Jozef Mruk, Robert D McBane
AIMS: Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR)...
March 17, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28287282/cerebrovascular-reactivity-in-acute-hyperoxia-in-patients-with-acute-ischaemic-stroke
#19
Ivana Hegeduš, Jakov Milić, Anita Ćosić, Krunoslav Buljan, Ines Drenjančević
AIM: This study aimed to assess the effect of acute hyperoxia on cerebral and systemic heamodynamics and the plasma concentration of prostacyclin and thromboxane in patients with stroke. METHODS: Mean blood flow velocity (MBFV), pulsatility and resistance indices of the middle cerebral artery using transcranial Doppler ultrasound before and during acute hyperoxia (4 L of 100%O2/15' over facial mask) in 92 participants - 25 patients with acute ischaemic stroke (AIS) that occurred within 72 hours and diabetes mellitus (SPDM), 26 AIS patients without DM (SP) and in 41 healthy controls (HS), were measured...
2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28277164/pharmacokinetics-of-the-selective-prostacyclin-receptor-agonist-selexipag-in-rats-dogs-and-monkeys
#20
Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber, Carmela Gnerre, Kiyoko Nonaka
1. This study examined the pharmacokinetics, distribution, metabolism and excretion of the selective prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-33679). The compounds were investigated following oral and/or intravenous administration to intact rats, dogs and monkeys, and bile-duct-cannulated rats and dogs. 2. After oral administration of [(14)C]selexipag, selexipag was well absorbed in rats and dogs with total recoveries of over 90% of the dose, mainly in the faeces...
March 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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