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Jason Gien, Nancy Tseng, Gregory J 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 intra-peritoneal bleomycin with and without selective ETA (BQ123/BQ610) and ETB (BQ788) receptor blockers, non-selective ET receptor blocker (ETRB) (bosentan) or fasudil (ROCK inhibitor)...
October 19, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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
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
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
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
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
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
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
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
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
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
Kiran More, Gayatri K Athalye-Jape, Shripada C Rao, Sanjay K Patole
BACKGROUND: Endothelin, a powerful vasoconstrictor, is one of the mediators in the causation of persistent pulmonary hypertension of the newborn (PPHN). Theoretically, endothelin receptor antagonists (ETRA) have the potential to improve the outcomes of infants with PPHN. OBJECTIVES: To assess the efficacy and safety of ETRA in the treatment of PPHN in full-term, post-term and late preterm infants.To assess the efficacy and safety of selective ETRAs (which block only the ETA receptors) and non-selective ETRAs (which block both ETA and ETB receptors) separately...
2016: Cochrane Database of Systematic Reviews
G Riemekasten, S Beissert, J H W Distler, A Kreuter, U Müller-Ladner
BACKGROUND: Digital ulcers (DU) affect up to 60 % of patients with systemic sclerosis (SSc) and have a considerable impact on quality of life and morbidity. It is unclear to what extent authorised medicines are used, and if therapy guidelines are implemented in everyday practice. METHOD: This retrospective health care study examined current standards of treatment for therapy and prevention of SSc-associated DU in an online survey with 83 physicians. Additionally, data from 161 case studies of SSc patients with DU were analysed, and the effect of DU treatment on the course of the disease determined...
August 17, 2016: Zeitschrift Für Rheumatologie
Martine Clozel
Endothelin receptor antagonists (ERAs) are used for the treatment of pulmonary arterial hypertension (PAH). Macitentan, a dual (ETA+ETB) ERA approved for the long-term treatment of PAH, was discovered through a tailored research program aimed at improving efficacy and safety over the existing ERAs. The goal of improved efficacy was based on the understanding that not only the ETA receptor but also the ETB receptor contributed to the hemodynamic and structural changes induced by endothelin-1 (ET-1) in pathological conditions and on the predefined requirements for optimal tissue penetration and binding kinetics of the antagonist...
August 17, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
S Patschan, D Tampe, C Müller, C Seitz, C Herink, G A Müller, E Zeisberg, M Zeisberg, E Henze, D Patschan
BACKGROUND: Patients with systemic sclerosis (SSc) are endagered by tissue fibrosis and by microvasculopathy, with the latter caused by endothelial cell expansion/proliferation. SSc-associated fibrosis potentially results from mesenchymal transdifferentiation of endothelial cells. Early Endothelial Progenitor Cells (eEPCs) act proangiogenic under diverse conditions. Aim of the study was to analyze eEPC regeneration and mesenchymal transdifferentiation in patients with limited and diffuse SSs (lSSc and dSSc)...
2016: BMC Musculoskeletal Disorders
A Mitchell, B Nokay, H Guberina, U Behlen-Wilm, M Nagel, M Kirschfink, T Wiech, A Kribben, A Bienholz
OBJECTIVE: Malignant hypertension as borne out by uncontrolled hypertension with accelerated target organ damage has a variable and often dire prognosis. Loss of kidney function is a hallmark of the condition and is frequently accompanied by thrombotic microangiopathy (TMA). DESIGN AND METHOD: Here we present the case of a patient with malignant hypertension, who was successfully treated using a combination of in-label and off-label medication according to the following pathophysiological concepts: 1) Innate immunity has been identified as a player in blood pressure (BP) control, 2) the complement inhibitor eculizumab has become available for treating atypical hemolytic uremic syndrome (aHUS), which shares many features of malignant hypertension, 3) endothelin (ET) antagonism, although not currently approved for these indications, has been shown to be effective for treating proteinuria and as a possible adjunct for the treatment of resistant hypertension...
September 2016: Journal of Hypertension
Michael Kuntz, Miguel M Leiva-Juarez, Suvitesh Luthra
BACKGROUND: There are currently three Food and Drug Administration approved endothelin receptor antagonists (ERAs): bosentan, ambrisentan, and macitentan. There is a growing body of evidence that demonstrates the beneficial effects of ERAs in patients with pulmonary arterial hypertension (PAH). OBJECTIVES: To compare the available evidence from randomized clinical trials for specific outcomes of different endothelin antagonists for the treatment of PAH. METHODS: A multi-database search of randomized controlled trials up to March 15, 2016 was conducted for those that would measure functional parameters of patients with PAH treated with ERA monotherapy versus placebo...
October 2016: Lung
Robin H Steinhorn, Jeffrey Fineman, Andjela Kusic-Pajic, Peter Cornelisse, Martine Gehin, Pegah Nowbakht, Christine M Pierce, Maurice Beghetti
OBJECTIVE: To evaluate the efficacy, safety, and pharmacokinetics of the endothelin receptor antagonist bosentan as adjunctive therapy for neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: This was a phase 3, multicenter, randomized, placebo-controlled exploratory trial (FUTURE-4). Eligible patients were >34 weeks gestation, <7 days old, receiving inhaled nitric oxide (iNO) treatment (≥4 hours), and had persistent respiratory failure (oxygenation index [OI] ≥12)...
October 2016: Journal of Pediatrics
Anna Krupa, Dorota Majda, Włodzimierz Mozgawa, Jakub Szlęk, Renata Jachowicz
The study provides the physicochemical characteristic of bosentan (BOS) in comparison to tadalafil (TA) and sildenafil citrate (SIL). Despite some reports dealing with thermal characteristic of SIL and TA, physicochemical properties of BOS have not been investigated so far. Recent clinical reports have indicated that the combination of bosentan and PDE-5 inhibitor can improve the effectiveness of pharmacotherapy of pulmonary arterial hypertension (PAH). However, in order to design personalized medicines for therapy of chronic rare diseases, detailed information on the thermal behaviour and solubility of each drug is indispensable...
August 5, 2016: AAPS PharmSciTech
Tahsin Görgülü, Ramazan Guler, Abdulkerim Olgun, Merve Torun, Eksal Kargi
Local skin flaps are important tools for performing plastic surgery. Skin flaps are used for closure of defects after tumor excision or in tissue losses after trauma. However, problems associated with these flaps are commonly encountered, particularly in areas of marginal necrosis. Bosentan is a vasodilator that exerts its effect through endothelin receptor blockade, and has been shown to prevent ischemic tissue damage. However, no reports have addressed the effect of bosentan on skin flaps. The aim of the study was to investigate the effects of bosentan, which may be applied clinically to promote survival of ischemic skin flaps...
August 2016: Facial Plastic Surgery: FPS
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