Search results for "Bosentan"
showing 9 items of 9 documents
Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent.
2018
Abstract Cholestasis represents a major subtype of drug-induced liver injury and novel preclinical models for its prediction are needed. Here we used primary human hepatocytes (PHH) from different donors in 2D-sandwich (2D-sw) and/or 3D-spheroid cultures to study inter-individual differences in the response towards cholestatic hepatotoxins after short-term (48–72 hours) and long-term repeated exposures (14 days). The cholestatic liabilities of drugs were determined by comparing cell viability upon exposure to the highest non-cytotoxic drug concentration in the presence and absence of a non-cytotoxic concentrated bile acid mixture. In 2D-sw culture, cyclosporine A and amiodarone presented cl…
Efecto de los antagonistas de los receptores de endotelina sobre el remodelado y reactividad de la arteria pulmonar en pacientes EPOC: estudio funcio…
2015
En la presente Tesis Doctoral se tratan los efectos del bosentan, antagonista dual de los receptores de endotelina - 1, sobre la apoptosis y la expresión de receptores de endotelina inducidas por extracto de humo de cigarrillo en células endoteliales y células de músculo liso de arteria pulmonar humana. Para ello nos centramos en la importancia clínica del la combinación de dos enfermedades de las vías aéreas íntimamente relacionadas y su tratamiento conjunto (la EPOC y la Hipertensión Arterial Pulmonar severa). La hipertensión arterial pulmonar (PAH) es una complicación común de la enfermedad crónica obstructiva pulmonar (EPOC) que cursa con vasoconstricción pulmonar, producida por hipoxia…
Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences
2010
BACKGROUND AND PURPOSEPulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ETB) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction.EXPERIMENTAL APPROACHETB receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca2+, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A2 and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phalloi…
Chronic Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction, Oxidative Stress and a Marked Increase in Vascular Endothelin-1 Express…
2011
Aims Isosorbide-5-mononitrate (ISMN) is one of the most frequently used compounds in the treatment of coronary artery disease predominantly in the USA. However, ISMN was reported to induce endothelial dysfunction, which was corrected by vitamin C pointing to a crucial role of reactive oxygen species (ROS) in causing this phenomenon. We sought to elucidate the mechanism how ISMN causes endothelial dysfunction and oxidative stress in vascular tissue. Methods and results Male Wistar rats ( n = 69 in total) were treated with ISMN (75 mg/kg/day) or placebo for 7 days. Endothelin (ET) expression was determined by immunohistochemistry in aortic sections. Isosorbide-5-mononitrate infusion caused si…
DD-008 Monitoring of the adherence to therapies for the treatment of pulmonary hypertension
2015
Background Adherence to the treatment for pulmonary arterial hypertension (PAH) is an important aspect of chronic disease management to improve the efficacy of treatment. 1 Purpose The study aimed to evaluate adherence to long-term drug treatments for PAH. Material and methods From 01/01/2010 to 04/01/2014 a retrospective analysis was done on therapeutic plans and prescriptions related to patients in treatment for at least one year by the Pneumology Unit. Items dispensed by the Clinical Pharmacist were analysed through data entered into the database F file. Mean therapeutic adherence, according to the literature, 2 was calculated using the "pharmacy-refill" method: days of dispensed treatme…
Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences
2010
BACKGROUND AND PURPOSE Pulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ETB) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction. EXPERIMENTAL APPROACH ETB receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca2+, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A2 and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phal…
Endothelin receptor expression in idiopathic pulmonary arterial hypertension: effect of bosentan and epoprostenol treatment.
2011
Endothelin receptor antagonists are used to treat idiopathic pulmonary arterial hypertension (IPAH), but human pulmonary arterial endothelin receptor expression is not well defined. We hypothesised that disease and treatment would modify normal receptor distribution in pulmonary resistance arteries of children. Using immunohistochemistry and semiquantitative analysis, we investigated endothelin receptor subtypes A and B (ET(A) and ET(B), respectively), and endothelial nitric oxide synthase (eNOS) expression in peripheral pulmonary arteries of tissue from untreated children with IPAH (n=7), following extended combined bosentan and epoprostenol therapy (n=5) and from normal subjects (n=5). Cl…
Chronic Therapy with Isosorbide-5-Mononitrate Causes Endothelial Dysfunction and Oxidative Stress – Improvement by Endothelin-Receptor Blocker (Bosen…
2012
Blood pressure variability and cardiovascular risk in 9 eastern european countries: data from the BP-Care study
2015
Methods: Total 327 patients were enrolled from 2008 to 2011 in the Korean registry program. They met the criteria of PAH and we investigated the clinical data, the medication prescribed and survival status et al. Results: Their mean age was 40.8 15.8years with female /male patient ratio of 2.7:1. The patients in WHO I/II were 32.4% and WHO III/IV were 67.6%. The peak/mean pulmonary arterial pressure was 86.3/ 56.6 mmHg. Idiopathic PAH (22%), connective tissue disease (24%) and congenital heart disease (46%) were predominant. Small number of patients with familial PAH, portal hypertension, HIV infection, pulmonary capillary hemangiomatosis (PCH) existed. The patients described bosentan were …