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Prostacyclin

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https://www.readbyqxmd.com/read/28632002/express-management-of-prostacyclin-side-effects-in-adult-patients-with-pulmonary-arterial-hypertension
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28597773/prostacyclins-have-no-direct-inotropic-effect-on-isolated-atrial-strips-from-the-normal-and-pressure-overloaded-human-right-heart
#5
Sarah Holmboe, Asger Andersen, Rebekka V Jensen, Hans Henrik Kimose, Lars B Ilkjær, Lei Shen, Lucie H Clapp, Jens Erik Nielsen-Kudsk
Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostacyclins on right heart function are still not clarified. The aim of this study was to investigate the possible direct inotropic properties of clinical available prostacyclin mimetics in the normal and the pressure-overloaded human right atrium. Trabeculae from the right atrium were collected during surgery from chronic thromboembolic pulmonary hypertension (CTEPH) patients with pressure-overloaded right hearts, undergoing pulmonary thromboendarterectomy (n = 10) and from patients with normal right hearts operated by valve replacement or coronary bypass surgery (n = 9)...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28597771/first-in-child-use-of-the-oral-selective-prostacyclin-ip-receptor-agonist-selexipag-in-pulmonary-arterial-hypertension
#6
Lianne M Geerdink, Harald Bertram, Georg Hansmann
Pulmonary arterial hypertension (PAH) is a complex disease with a poor prognosis. Selexipag is a selective prostacyclin receptor agonist with vasodilatory, anti-proliferative, anti-inflammatory, and pro-angiogenic properties. However, no clinical data on its therapeutic use in children with PAH are currently available. Here, we report the case of a 12-year-old girl who presented in World Health Organization (WHO) functional class III and right ventricular (RV) failure with recurrent syncope, dizziness, and progressive fatigue for two years...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28597769/a-systematic-review-of-transition-studies-of-pulmonary-arterial-hypertension-specific-medications
#7
Avraham Sofer, Michael J Ryan, Ryan J Tedford, Joel A Wirth, Wassim H Fares
Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between different therapeutic options, although the evidence for such transitions has not been well described. We sought to review the evidence supporting the safety and/or efficacy of transitioning between PAH-specific medications. We performed a systematic review of all published studies in the Medline database between 1 January 2000 and 30 June 2016 reporting on any transition between the currently Food and Drug Administration (FDA)-approved PAH-specific medications...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28593996/epidemiology-and-treatment-of-pulmonary-arterial-hypertension
#8
REVIEW
Edmund M T Lau, Eleni Giannoulatou, David S Celermajer, Marc Humbert
In the past 2 decades, major changes have occurred in the epidemiological and treatment landscape of pulmonary arterial hypertension (PAH). Previously regarded as a disease of the young and middle-aged, contemporary registries from the Western world have demonstrated an increase in the age of patients with PAH, many of whom are elderly with multiple comorbidities. Another important observation is the improvement in survival of patients with PAH in the modern treatment era compared with historical cohorts, before the availability of advanced therapy...
June 8, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28588054/sustained-neurological-recovery-after-stroke-in-aged-rats-treated-with-a-novel-prostacyclin-analog
#9
Changjun Yang, Kelly M DeMars, Jon C Alexander, Marcelo Febo, Eduardo Candelario-Jalil
BACKGROUND AND PURPOSE: Targeting the prostaglandin I2 prostanoid (IP) receptor to reduce stroke injury has been hindered by the lack of selective drugs. MRE-269 is the active metabolite of selexipag showing a high selectivity toward the IP receptor. Selexipag has been recently approved for clinical use in pulmonary hypertension. We hypothesized that postischemic treatment with MRE-269 provides long-lasting neuroprotection with improved neurological outcomes in a clinically relevant rat stroke model...
June 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28587821/structural-development-of-1-2-3-4-tetrahydroisoquinoline-type-positive-allosteric-modulators-of-prostacyclin-receptor-ippams-to-improve-metabolic-stability-and-investigation-of-metabolic-fate
#10
Hiroyuki Miyachi, Toshifumi Suzuki, Riyo Imamura, Tetsuo Nagano, Takayoshi Okabe
We synthesized a series of 1,2,3,4-tetrahydroisoquinoline-type positive allosteric modulators of prostacyclin receptor (IPPAMs), aiming to improve the metabolic stability of the previously identified hit compound IPPAM-3 (2). Our results indicated that the 3-position of the 2-substituted phenyl ring in this series of IPPAM-3 derivatives is a hot spot for metabolism catalyzed by human hepatic microsomes. This conclusion was confirmed by the finding that 8, in which the 3-position is blocked by a fluorine substituent, exhibited superior metabolic stability (t1/2 21min versus 7min for parent compound 2)...
May 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28583617/totally-implantable-intravenous-treprostinil-therapy-in-pulmonary-hypertension-assessment-of-the-implantation-procedure
#11
Aaron B Waxman, Hugh T McElderry, Mardi Gomberg-Maitland, Martin C Burke, Edgar L Ross, Malcolm M Bersohn, Sanjog S Pangarkar, James H Tarver, Diane L Zwicke, Jeremy P Feldman, Murali M Chakinala, Robert P Frantz, Geoffrey B Thompson, Fernando Torres, Richard L Rauck, Kathy Clagg, Louise Durst, Pei Li, Marty Morris, Kara L Southall, Leigh Peterson, Robert C Bourge
BACKGROUND: Prostacyclins improve symptoms and survival in pulmonary arterial hypertension (PAH). In response to risks associated with external delivery systems, an implantable intravenous infusion system was developed. A multicenter, prospective, single-arm, clinical trial (DelIVery for PAH) was conducted to evaluate this system for treprostinil in PAH. This analysis describes the findings related to the implant procedure. METHODS: Patients (n=64) with PAH (WHO Group 1) receiving stable intravenous treprostinil were enrolled...
June 2, 2017: Chest
https://www.readbyqxmd.com/read/28582316/new-targets-for-pulmonary-arterial-hypertension-going-beyond-the-currently-targeted-three-pathways
#12
Alice Huertas, Ly Tu, Christophe Guignabert
PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a hemodynamic state defined by a resting mean pulmonary arterial pressure at or above 25 mmHg with a normal pulmonary capillary wedge pressure, ultimately leading to right heart failure and premature death. Although considerable progress has been made in the development of drug therapies for PAH targeting abnormalities found in the three main pathobiologic pathways (nitric oxide, prostacyclin, and endothelin-1), there is no drug available to specifically stop the progressive cellular accumulation into the pulmonary artery vessel wall...
June 2, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28562527/successful-treatment-of-infliximab-in-a-patient-with-scleroderma-a-case-report
#13
Ting Li, Yaoyang Liu, Huji Xu
RATIONALE: Systemic Scleroderma (SSc) is a rare connective tissue disease clinically characterized by cutaneous sclerosis and variable systemic involvement. No drug is currently available to effectively reverse the fibrotic process in SSc. Previous reports have suggested that the tumor necrosis factor (TNF) antagonists could be useful for the treatment of fibrotic disorders. However, TNFα has long been considered as an antifibrotic cytokine. Whether TNF antagonist is effective for SSc patients needs to be tested...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28559663/consecutive-sessions-of-rescue-balloon-atrial-septostomy-for-an-idiopathic-pulmonary-arterial-hypertension-patient-with-refractory-right-heart-failure-usefulness-of-intracardiac-echocardiography-guidance
#14
Yu-Wei Chen, Hung-Chih Pan, Kuo-Yang Wang, Kae-Woei Liang
For idiopathic pulmonary artery hypertension (PAH) patients with end-stage right heart failure who received maximal medical therapy, balloon atrial septostomy (BAS) is recommended by most guidelines as a palliative therapy or a bridging treatment before lung transplantation. In this report, we described a 32-year-old woman with idiopathic PAH, who received maximal PAH-specific medical treatment, including intravenous prostacyclin, but still suffered from refractory right heart failure. The markedly enlarged right atrium (RA), high mean RA pressure of 23 mmHg, low systemic arterial oxygen saturation of 86% and concomitant pancytopenia all increased the patient's risk for BAS...
May 2017: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/28559468/severity-of-hypoxemia-and-other-factors-that-influence-the-response-to-aerosolized-prostacyclin-in-ards
#15
Richard H Kallet, Gregory Burns, Hanjing Zhuo, Kelly Ho, Justin S Phillips, Lance P Pangilinan, Vivian Yip, Antonio Gomez, Michael S Lipnick
BACKGROUND: ARDS is characterized by decreased functional residual capacity (FRC), heterogeneous lung injury, and severe hypoxemia. Tidal ventilation is preferentially distributed to ventilated alveoli. Aerosolized prostaglandin I2 exploits this pathophysiology by inducing local vasodilation, thereby increasing ventilation-perfusion matching and reducing hypoxemia. Therefore, aerosolized prostaglandin I2 efficacy may depend upon FRC. Both PaO2 /FIO2 and compliance of the respiratory system (CRS) are indirect signifiers of FRC and thus may partly determine the response to aerosolized prostaglandin I2...
May 30, 2017: Respiratory Care
https://www.readbyqxmd.com/read/28556581/population-modeling-of-selexipag-pharmacokinetics-and-clinical-response-parameters-in-patients-with-pulmonary-arterial-hypertension
#16
A Krause, M Machacek, D Lott, N Hurst, S Bruderer, J Dingemanse
Selexipag (Uptravi) is an oral selective IP prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH). The pivotal GRIPHON study was the largest clinical study ever conducted in PAH patients, providing long-term data from 1,156 patients. PAH comedication did not affect exposure to selexipag, while exposure to its active metabolite ACT-333679 was reduced by 30% when taken in combination, clinically not relevant in the context of individual dose up-titration. Using log-linear regression models linking model-predicted steady-state exposure to pharmacodynamics (PD), exposure to selexipag and ACT-333679 showed some statistically significant, albeit not clinically relevant, effects on exercise capacity, laboratory values, and the occurrence of prostacyclin-related adverse events, but not on vital signs or adverse events denoting hemorrhage...
May 27, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28547570/the-effect-of-iloprost-on-cell-proliferation-and-angiogenesis-related-gene-expression-in-human-periodontal-ligament-cells
#17
Thanomsuk Jearanaiphaisarn, Teeranuch Sanharati, Prasit Pavasant, Chalida Nakalekha Limjeerajarus
Periodontal ligament is considered a rich source of mesenchymal stem cells for pulp regeneration. This study investigated the effect of iloprost, a prostacyclin analog, on cell proliferation and the expression of angiogenesis-related genes in human periodontal ligament cells (hPDLs) in vitro. The hPDLs were treated with 10(-9)-10(-6) M iloprost for 1, 6 and 24 h. Cell proliferation was determined by an MTT assay. Vascular endothelial growth factor (VEGF), alpha-1 type I collagen (COL1), and basic fibroblast growth factor (bFGF) mRNA expression were determined by semi-quantitative and qPCR...
May 25, 2017: Odontology
https://www.readbyqxmd.com/read/28546372/inhaled-pulmonary-vasodilators-are-there-indications-within-the-pediatric-icu
#18
Bradley A Kuch, Alvin L Saville, Joan Sanchez De Toledo, Shekhar T Venkataraman
Inhaled nitric oxide (INO) is only FDA-cleared for neonates (> 34 weeks gestation) with hypoxic respiratory failure-associated pulmonary hypertension. Off-label use of INO is common in the pediatric population despite a lack of evidence regarding survival benefit, questioning whether the therapy should be considered outside the neonatal period. A lack of definitive evidence combined with increasing health-care costs has led to the use of less costly inhaled prostacyclin as an alternative to INO, presenting unique patient safety concerns...
June 2017: Respiratory Care
https://www.readbyqxmd.com/read/28545516/improving-the-regenerative-potential-of-olfactory-ensheathing-cells-by-overexpressing-prostacyclin-synthetase-and-its-application-in-spinal-cord-repair
#19
May-Jywan Tsai, Chi-Ting Huang, Yong-San Huang, Ching-Feng Weng, Song-Kun Shyue, Ming-Chao Huang, Dann-Ying Liou, Yan-Ru Lin, Chu-Hsun Cheng, Huai-Sheng Kuo, Yilo Lin, Meng-Jen Lee, Wen-Hung Huang, Wen-Cheng Huang, Henrich Cheng
BACKGROUND: Olfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28533260/relationship-between-monocyte-platelet-aggregation-and-endothelial-function-in-middle-aged-and-elderly-adults
#20
Andrew Haynes, Matthew D Linden, Elisa Robey, Louise H Naylor, Kay L Cox, Nicola T Lautenschlager, Daniel J Green
Low-grade inflammation, endothelial dysfunction, and platelet hyper-reactivity to agonists are associated with an increased risk of cardiovascular events. In vitro and animal studies infer an inverse mechanistic relationship between platelet activation and the production of endothelium-derived nitric oxide and prostacyclin. This concept is supported by evidence of an inverse relationship between endothelial function and platelet activation in high-risk cardiac patients. The aim of this study was to investigate what relationship, if any, exists between platelet and endothelial function in healthy, middle-aged, and elderly adults...
May 2017: Physiological Reports
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