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Bosentan

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https://www.readbyqxmd.com/read/28078552/pediatric-development-of-bosentan-facilitated-by-modeling-and-simulation
#1
Jochen Zisowsky, Martine Géhin, Andjela Kusic-Pajic, Andreas Krause, Maurice Beghetti, Jasper Dingemanse
BACKGROUND: Bosentan is approved for use in adult patients with pulmonary arterial hypertension. The primary aim of the pharmacokinetic modeling was the provision of a systematic guidance for study design and enhanced understanding of pharmacokinetics across the entire pediatric age range. METHODS: A physiologically based pharmacokinetic model was developed for the pediatric population; starting from an adult model, the effects of body weight, age, and maturation of relevant metabolizing enzymes were incorporated to extrapolate the pharmacokinetics to children...
January 11, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28053559/systemic-lupus-erythematosus-and-pulmonary-arterial-hypertension-links-risks-and-management-strategies
#2
REVIEW
Konstantinos Tselios, Dafna D Gladman, Murray B Urowitz
Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28030574/endothelin-regulates-porphyromonas-gingivalis-induced-production-of-inflammatory-cytokines
#3
Ga-Yeon Son, Eun-Jung Bak, Ji-Hye Kim, Dong Eun Lee, Si-Mook Kang, So Yun Lee, Lin Choi, Ji Su Sun, Seul Ki Kim, Wonse Park, Baek Il Kim, Yun-Jung Yoo, Inik Chang, Dong Min Shin
Periodontitis is a very common oral inflammatory disease that results in the destruction of supporting connective and osseous tissues of the teeth. Although the exact etiology is still unclear, Gram-negative bacteria, especially Porphyromonas gingivalis in subgingival pockets are thought to be one of the major etiologic agents of periodontitis. Endothelin (ET) is a family of three 21-amino acid peptides, ET-1, -2, and -3, that activate G protein-coupled receptors, ETA and ETB. Endothelin is involved in the occurrence and progression of various inflammatory diseases...
2016: PloS One
https://www.readbyqxmd.com/read/28018840/hand-impairment-in-systemic-sclerosis-various-manifestations-and-currently-available-treatment
#4
Amber Young, Rajaie Namas, Carole Dodge, Dinesh Khanna
Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud's phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often co-exist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life...
September 2016: Current Treatment Options in Rheumatology
https://www.readbyqxmd.com/read/28008226/preparation-and-physicochemical-characterization-of-spray-dried-and-jet-milled-microparticles-containing-bosentan-hydrate-for-dry-powder-inhalation-aerosols
#5
Hyo-Jung Lee, Ji-Hyun Kang, Hong-Goo Lee, Dong-Wook Kim, Yun-Seok Rhee, Ju-Young Kim, Eun-Seok Park, Chun-Woong Park
The objectives of this study were to prepare bosentan hydrate (BST) microparticles as dry powder inhalations (DPIs) via spray drying and jet milling under various parameters, to comprehensively characterize the physicochemical properties of the BST hydrate microparticles, and to evaluate the aerosol dispersion performance and dissolution behavior as DPIs. The BST microparticles were successfully prepared for DPIs by spray drying from feeding solution concentrations of 1%, 3%, and 5% (w/v) and by jet milling at grinding pressures of 2, 3, and 4 MPa...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27994906/swift-and-complete-healing-of-digital-ulcers-after-macitentan-treatment
#6
Emilio Giner Serret
Digital ulcers are a burdensome and painful condition with sparse options of treatment. We report the case of a 78-year-old female patient with limited cutaneous systemic sclerosis that sequentially developed digital ulcers. After the appearance of digital ulcers in the soles of her feet she was successfully treated with bosentan. The report of two new digital ulcers in her hands 9 months later alongside with elevated transaminase levels led to a switch to macitentan treatment. A swift and complete healing of both digital ulcers was observed after 3 months, with the restoration of normal biochemical values...
2016: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/27986807/effects-of-4-multitargeted-receptor-tyrosine-kinase-inhibitors-on-regional-hemodynamics-in-conscious-freely-moving-rats
#7
Joanne J Carter, Laurice V Fretwell, Jeanette Woolard
VEGF inhibitors, including receptor tyrosine kinase inhibitors, are used as adjunct therapies in a number of cancer treatments. An emerging issue with these drugs is that most cause hypertension. To gain insight into the physiological mechanisms involved, we evaluated their regional hemodynamic effects in conscious rats. Male Sprague Dawley rats (350-450 g) were chronically implanted with pulsed Doppler flow probes (renal and mesenteric arteries, and the descending abdominal aorta) and catheters (jugular vein, peritoneal cavity, and distal abdominal aorta)...
December 16, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27971684/a-budget-impact-analysis-of-the-introduction-of-generic-bosentan-for-the-treatment-of-pulmonary-arterial-hypertension-in-greece
#8
K Athanasakis, F Tarantilis, C Tsakalogiannis, M Ollandezos, J Kyriopoulos
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
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
#9
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
#10
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
#11
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)...
January 2017: 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
#12
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
#13
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.
January 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27846260/alternatively-activated-m2-macrophage-phenotype-is-inducible-by-endothelin-1-in-cultured-human-macrophages
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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