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https://www.readbyqxmd.com/read/27912207/clinical-adverse-effects-of-endothelin-receptor-antagonists-insights-from-the-meta-analysis-of-4894-patients-from-24-randomized-double-blind-placebo-controlled-clinical-trials
#1
Anhua Wei, Zhichun Gu, Juan Li, Xiaoyan Liu, Xiaofan Wu, Yi Han, Jun Pu
BACKGROUND: Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis. METHODS AND RESULTS: After systematic searches of the Medline, Embase, and Cochrane Library databases and the ClinicalTrials.gov website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated...
October 26, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27906839/endothelin-contributes-to-the-blood-pressure-rise-triggered-by-hypoxia-in-severe-obstructive-sleep-apnea
#2
Christophe Janssen, Atul Pathak, Guido Grassi, Philippe van de Borne
BACKGROUND: Obstructive sleep apnea (OSA) is strongly correlated with an increased risk of systemic hypertension. However, the link between systemic hypertension and nocturnal apneas remains incompletely understood. Animal studies suggest an implication of the endothelin system. The aim of the present study is to determine if endogenous endothelin plays a role in the increase in blood pressure observed during hypoxic episodes in OSA patients, in addition to peripheral chemoreflex and neural sympathetic activation...
January 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/27905105/endothelin-1-et-1-stimulates-carboxy-terminal-smad2-phosphorylation-in-vascular-endothelial-cells-by-a-mechanism-dependent-on-et-receptors-and-de-novo-protein-synthesis
#3
Narges Sharifat, Ghorban Mohammad Zadeh, Mohammad-Ali Ghaffari, Parisa Dayati, Danielle Kamato, Peter J Little, Hossein Babaahmadi-Rezaei
OBJECTIVE: G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)-β receptor (TβRI). This signalling mechanism represents a major expansion in the cellular outcomes attributable to GPCR signalling. This study addressed the role and mechanisms involved in GPCR agonist, endothelin-1 (ET-1)-mediated transactivation of the TβRI in bovine aortic endothelial cells (BAECs)...
December 1, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27902617/efficacy-of-bosentan-in-patients-with-refractory-thromboangiitis-obliterans-buerger-disease-a-case-series-and-review-of-the-literature
#4
Javier Narváez, Carmen García-Gómez, Lorenzo Álvarez, Pilar Santo, María Aparicio, María Pascual, Mercè López de Recalde, Helena Borrell, Joan M Nolla
The cornerstone of therapy in thromboangiitis obliterans (TAO) is complete abstinence from tobacco. In addition to discontinuation of cigarette smoking, very few pharmacological and surgical options of controversial efficacy are available to date. New therapeutic options with greater efficacy are clearly needed to properly manage these patients.In this preliminary study, we assessed the effectiveness and safety of bosentan in a case series of 8 adults with TAO and severe ischemic ulceronecrotic lesions who were treated with bosentan after inadequate response to platelet inhibitors, vasodilators, and intravenous alprostadil...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27846462/from-bosentan-to-macitentan-for-pulmonary-arterial-hypertension-and-adult-congenital-heart-disease-further-improvement
#5
Ilja M Blok, Annelieke C M J van Riel, Arie P J van Dijk, Barbara J M Mulder, Berto J Bouma
No abstract text is available yet for this article.
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27846260/alternatively-activated-m2-macrophage-phenotype-is-inducible-by-endothelin-1-in-cultured-human-macrophages
#6
Stefano Soldano, Carmen Pizzorni, Sabrina Paolino, Amelia Chiara Trombetta, Paola Montagna, Renata Brizzolara, Barbara Ruaro, Alberto Sulli, Maurizio Cutolo
BACKGROUND: Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB)...
2016: PloS One
https://www.readbyqxmd.com/read/27816421/pilot-study-of-endothelin-receptor-blockade-in-heart-failure-with-diastolic-dysfunction-and-pulmonary-hypertension-baddhy-trial
#7
B Koller, R Steringer-Mascherbauer, C H Ebner, Th Weber, M Ammer, J Eichinger, I Pretsch, M Herold, J Schwaiger, H Ulmer, W Grander
BACKGROUND: In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF). MATERIALS AND METHODS: Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication...
September 28, 2016: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/27785045/buerger-s-disease-providing-integrated-care
#8
REVIEW
Peter Klein-Weigel, Theresa Sophie Volz, Leonora Zange, Jutta Richter
Buerger's disease, also known as thromboangiitis obliterans (TAO), is a segmental inflammatory disease affecting small- and medium-sized vessels, which is strongly associated with tobacco use. Although the etiology is still unknown, recent studies suggest an immunopathogenesis. Diagnosis is based on clinical and angiomorphologic criteria, including age, history of smoking, clinical presentation with distal extremity ischemia, and the absence of other risk factors for atherosclerosis, autoimmune disease, hypercoagulable states, or embolic disease...
2016: Journal of Multidisciplinary Healthcare
https://www.readbyqxmd.com/read/27777434/feasibility-of-repairing-defects-followed-by-treatment-with-pulmonary-hypertension-specific-drugs-repair-and-treat-in-patients-with-pulmonary-hypertension-associated-with-atrial-septal-defect-study-protocol-for-interventional-trial
#9
Satoshi Akagi, Kazufumi Nakamura, Teiji Akagi, Koji Nakagawa, Yoichi Takaya, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Ito
A treatment strategy for patients with pulmonary hypertension (PH) and atrial septal defect (ASD) remains unclear. This study was designed to evaluate the effects of initial repair of ASD followed by treatment with PH-specific drugs in patients with PH and ASD. Eligible patients receive transcatheter ASD closure followed by treatment with bosentan and sildenafil. Right heart catheterization is performed at baseline and at 12, 24 and 48 weeks. The primary endpoint is change in pulmonary artery pressure and pulmonary vascular resistance from baseline to follow-up...
October 2016: Acta Medica Okayama
https://www.readbyqxmd.com/read/27760762/endothelin-1-rho-kinase-interactions-impair-lung-structure-and-cause-pulmonary-hypertension-after-bleomycin-exposure-in-neonatal-rat-pups
#10
Jason Gien, Nancy Tseng, Gregory Seedorf, Katherine Kuhn, Steven H Abman
Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1-ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ETA (BQ123/BQ610) and ETB (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor)...
December 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27744392/effects-of-longterm-treatment-with-bosentan-and-iloprost-on-nailfold-absolute-capillary-number-fingertip-blood-perfusion-and-clinical-status-in-systemic-sclerosis
#11
Amelia Chiara Trombetta, Carmen Pizzorni, Barbara Ruaro, Sabrina Paolino, Alberto Sulli, Vanessa Smith, Maurizio Cutolo
OBJECTIVE: To quantify in patients with systemic sclerosis (SSc) the absolute nailfold capillary number/mm (the absolute number of capillaries, observable in the first row, in 1 mm per field) and fingertip blood perfusion (FBP) during longterm therapy with the endothelin receptor antagonist bosentan (BOSE) and the synthetic analog of prostacyclin PGI2 iloprost (ILO) by multiple diagnostic tools. Observed values were correlated with clinical outcomes. METHODS: Thirty patients with SSc already receiving intravenous ILO (80 μg/day) for 5 continuous days (every 3 mos) were recruited in the clinic...
October 1, 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27716320/bosentan-and-macitentan-prevent-the-endothelial-to-mesenchymal-transition-endomt-in-systemic-sclerosis-in-vitro-study
#12
Claudio Corallo, Maurizio Cutolo, Bashar Kahaleh, Gianluca Pecetti, Antonio Montella, Chiara Chirico, Stefano Soldano, Ranuccio Nuti, Nicola Giordano
BACKGROUND: Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype, has been reported in SSc. In the present study, we evaluated the ability of endothelin-1 (ET-1) dual receptor antagonists bosentan (BOS) and macitentan (MAC) to antagonize EndoMT in vitro...
October 6, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27703295/pulmonary-hypertension-new-trends-of-diagnostic-and-therapy
#13
Senad Pesto, Zijo Begic, Sabina Prevljak, Ehlimana Pecar, Nihad Kukavica, Edin Begic
Pulmonary hypertension is a pathophysiological state hemodynamically defined as the increase of the mean pulmonary arterial pressure above 25, or 30 mmHg at rest, measured by catheterization of the right heart. Laboratory findings usually reveals polycythemia, the ECG right ventricle hypertrophy, and x-ray characteristic of diseased branches (echocardiography and biomarkers such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP hormones are potentially helpful tools in identifying PH). Echocardiography can be found the increase of the right atrium and ventricle, right ventricular hypertrophy, abnormal contraction of the interventricular septum, left ventricular diastolic dysfunction and decreased left ventricular size, with reduced volumes of systole and end diastole...
July 27, 2016: Medical Archives
https://www.readbyqxmd.com/read/27683147/beneficial-effects-of-long-term-treatment-with-bosentan-on-the-development-of-pulmonary-arterial-hypertension-in-patients-with-systemic-sclerosis
#14
Giuseppe Murdaca, Francesca Lantieri, Francesco Puppo, Gian Paolo Bezante, Manrico Balbi
OBJECTIVE: To investigate the effects of long-term treatment with bosentan on pulmonary arterial hypertension (PAH) in patients with systemic sclerosis. METHODS: Patients with systemic sclerosis were followed between 2003 and 2014; those who developed digital ulcers were treated with standard regimens of bosentan. Patients were assessed at baseline and every 12 months using transthoracic Doppler echocardiography, 6-min walking distance test, Borg dyspnoea index and monitoring of plasma levels of 76-amino-acid N-terminal probrain natriuretic peptide...
September 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27665516/accessing-3d-microtissue-metabolism-lactate-and-oxygen-monitoring-in-hepatocyte-spheroids
#15
Andreas Weltin, Steffen Hammer, Fozia Noor, Yeda Kaminski, Jochen Kieninger, Gerald A Urban
3D hepatic microtissues, unlike 2D cell cultures, retain many of the in-vivo-like functionalities even after long-term cultivation. Such 3D cultures are increasingly applied to investigate liver damage due to drug exposure in toxicology. However, there is a need for thorough metabolic characterization of these microtissues for mechanistic understanding of effects on culture behaviour. We measured metabolic parameters from single human HepaRG hepatocyte spheroids online and continuously with electrochemical microsensors...
July 28, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27623401/corrigendum-to-future-2-results-from-an-open-label-long-term-safety-and-tolerability-extension-study-using-the-pediatric-formulation-of-bosentan-in-pulmonary-arterial-hypertension-int-j-cardiol-202-2016-52-58
#16
Rolf M F Berger, Sheila G Haworth, Damien Bonnet, Yves Dulac, Alain Fraisse, Nazzareno Galiè, D Dunbar Ivy, Xavier Jaïs, Oliver Miera, Erika B Rosenzweig, Michela Efficace, Andjela Kusic-Pajic, Maurice Beghetti
No abstract text is available yet for this article.
November 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27619758/a-comparison-of-echocardiographic-variables-of-right-ventricular-function-with-exercise-capacity-after-bosentan-treatment-in-patients-with-pulmonary-arterial-hypertension-results-from-a-multicenter-prospective-cohort-study
#17
Hyungseop Kim, Jin Bae Lee, Jae-Hyeong Park, Byung-Su Yoo, Jang-Won Son, Dong Heon Yang, Bong-Ryeol Lee
PURPOSE: Bosentan reduces pulmonary arterial pressure and improves exercise capacity in patients with pulmonary arterial hypertension (PAH). However, there are limited data regarding the extent to which the changes in echocardiographic variables reflect improvements in exercise capacity. We aimed to assess the improvement of echocardiographic variables and exercise capacity after 6 months of bosentan treatment for PAH. METHODS: We performed a prospective study from June 2012 to June 2015 in seven participating medical centers...
September 13, 2016: Journal of Clinical Ultrasound: JCU
https://www.readbyqxmd.com/read/27616782/development-and-validation-of-a-uhplc-uv-method-for-the-in-process-control-of-bosentan-monohydrate-synthesis
#18
Marta Jatczak, Katarzyna Sidoryk, Magdalena Kossykowska, Wojciech Łuniewski, Joanna Zagrodzka, Elżbieta Lipiec-Abramska
Bosentan monohydrate (4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidin-4-yl]benzene-1-sulfonamide monohydrate) is a dual endothelin receptor antagonist (ERA) applied in the treatment of pulmonary arterial hypertension. To achieve effective process control of the bosentan monohydrate synthesis, it was necessary to develop a selective and not highly time-consuming method for ultra-high performance liquid chromatography (UHPLC). The method is characterized by adequate sensitivity, reproducibility and selectivity for the determination of bosentan monohydrate and related compounds from all synthetic stages...
2016: Chromatographia
https://www.readbyqxmd.com/read/27571006/medical-therapy-in-chronic-thromboembolic-pulmonary-hypertension
#19
Joanna Pepke-Zaba, Xavier Jais, Richard Channick
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening condition resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy surgery is currently the standard of treatment, as it is potentially curative; however, not all cases are amenable to surgical intervention due to distal distribution of the organized thromboembolic material or the presence of comorbidities. Up to one-third of patients have persistent or recurrent pulmonary hypertension after pulmonary endarterectomy...
July 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27537734/bosentan-for-digital-ulcers-prevention-does-not-worsen-cardiopulmonary-exercise-test-parameters-in-ssc-patients-with-interstitial-lung-disease
#20
Antonella Romaniello, Antonietta Gigante, Marcello Di Paolo, Gaia Tallerini, Biagio Barbano, Daria Amoroso, Paolo Palange, Edoardo Rosato
No abstract text is available yet for this article.
November 15, 2016: International Journal of Cardiology
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