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https://www.readbyqxmd.com/read/28724039/treatment-of-digital-ulcers-in-systemic-sclerosis-case-series-study-of-thirteen-patients-and-discussion-on-outcome
#1
Yahia Abuowda, Raquel Sousa Almeida, Ana Alves Oliveira, Petra Pego, Cristina Santos, João Matos-Costa
Introduction: In systemic sclerosis (SSc), digital ulcers (DU) are debilitating and recurrent. They are markers of prognosis and are associated with disability and mortality. Treatment strategies have been developed to block the proposed mechanisms of this complication. Objective: Clinical description of a population of SSc patients with DU, treatment, complications and outcome. Method: Analysis of 48 SSc patients meeting 2013 ACR-EULAR criteria, followed between 1999-2015; 13 patients had DU...
May 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28707522/the-effect-of-endothelin-receptor-antagonists-in-the-endotoxin-induced-uveitis-rabbit-model
#2
Emine Esra Karaca, Feyzahan Uzun, Ergin Dileköz, Gökçe Sevim Öztürk Fincan, Sevim Ercan, Oğuz Kul, Emin Ümit Bağrıaçık, Meral Or
PURPOSE: To investigate the effect of Bosentan (non-selective endothelin receptor antagonist) and BQ123 (ETA receptor antagonist) on intraocular inflammation in an endotoxin-induced uveitis (EIU) rabbit model METHODS: Uveitis was induced by intravitreal injection of lipopolysaccharide (LPS). The animals were divided into 7 groups and there were 6 rabbits in each group (saline, saline and ethanol, Bosentan, BQ123, Lipopolysaccharide(LPS), Bosentan and LPS, BQ123 and LPS injected groups)...
July 14, 2017: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/28660556/the-effect-of-endothelin-receptor-antagonists-in-patients-with-eisenmenger-syndrome-a-systematic-review
#3
REVIEW
Abdelrahman Elshafay, Duy Hieu Truong, Mohamed M AboElnas, Hossam Idrees, Hatem G Metwali, Nguyen Lam Vuong, Omar Ahmed Saad, Kenji Hirayama, Nguyen Tien Huy
INTRODUCTION: The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically review the safety and effects of ERAs in improving the quality of life and basic cardiac functions of these patients. METHODS: Twelve databases were searched, including PubMed, Web of Science, Scopus, Virtual Health Library, World Health Organization (WHO) Global Health Library, Google Scholar, POPLINE, Systems for Information of Grey Literature in Europe, New York Academy of Medicine, ClinicalTrials...
June 28, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28655665/effect-of-amphiphilic-graft-co-polymer-carrier-on-physical-stability-of-bosentan-nanocomposite-assessment-of-solubility-dissolution-and-bioavailability
#4
Prakash N Kendre, Pravin D Chaudhari
Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). But the solubility and bioavailability of this drug are poor, which has restricted the design and development of dosage forms for efficient and successful therapy. The present study was carried out to develop nanocomposites using an amphiphilic graft co-polymer (Soluplus®) as a carrier to enhance the solubility and bioavailability of bosentan. The graft co-polymer-based nanocomposite formulation was prepared using the single-emulsion technique...
June 24, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28640077/improvement-of-peripheral-artery-disease-with-sildenafil-and-bosentan-combined-therapy-in-a-patient-with-limited-cutaneous-systemic-sclerosis-a-case-report
#5
Loukman Omarjee, Cedric Fontaine, Guillaume Mahe, Vincent Jaquinandi
RATIONALE: Sildenafil, a phosphodiesterase-5-inhibitor and Bosentan, an endothelin-1-receptor antagonist combined therapy could have beneficial effect in systemic sclerosis (SSc) patients with peripheral artery disease. PATIENT CONCERNS: We report a case of a 48-year-old Black woman, who developed severe left limb claudication and walking limitation following a left femoropopliteal bypass occlusion in 2014. She was a heavy smoker and had a history of right middle cerebral artery ischemic stroke and bilateral Raynaud phenomenon...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28628863/simultaneous-quantification-of-endothelin-receptor-antagonists-and-phosphodiesterase-5-inhibitors-currently-used-in-pulmonary-arterial-hypertension
#6
Yeliz Enderle, Lukas Witt, Heinrike Wilkens, Ekkehard Grünig, Walter E Haefeli, Jürgen Burhenne
Combination treatment with endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitors (PDE5I) improved efficacy of pulmonary arterial hypertension (PAH) therapy. However, drug-drug interactions, variable exposure, non-adherence can influence plasma levels. For these reasons, drug quantification may be advantageous particularly in patients with poor treatment responses. We developed, validated, and applied an assay for the simultaneous quantification of ambrisentan, bosentan, macitentan, sildenafil, and tadalafil as well as their main (and partly active) metabolites in human plasma...
September 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28618763/comparison-of-endothelin-and-nitric-oxide-synthase-blockers-on-hemorheological-parameters-in-endotoxemic-rats
#7
Neslihan H Dikmenoğlu Falkmarken, Okan Arihan, Alper B Iskit
BACKGROUND/AIM: Septic shock is an important health problem that vastly alters cardiovascular and hemodynamic status. Increased production of nitric oxide (NO) and endothelin is a counterpart of this endotoxemic state. This study was conducted to test the hypothesis that nonselective NO synthesis blocker (L-NAME), inducible NO synthesis blocker (L-canavanine), or endothelin receptor antagonist (bosentan) will reverse the effects of sepsis on hemorheological parameters. MATERIALS AND METHODS: Forty-eight male Sprague-Dawley rats were used in 8 groups: saline (control), endotoxin, bosentan, L-NAME, L-canavanine, endotoxin + bosentan, endotoxin + L-NAME, and endotoxin + L-canavanine...
June 12, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28616089/severe-pulmonary-arterial-hypertension-associated-with-congenital-cardiac-shunts-evolution-under-specific-treatment
#8
R I Negoi, I Ghiorghiu, F Filipoiu, M Hostiuc, I Negoi, C Ginghina
Objective: The aim of this study was to compare the effects of Sildenafil, Bosentan and combined therapy in patients with congenital cardiac shunts associated pulmonary artery hypertension (CCS-PAH). Design: Prospective observational study (February 2011 - January 2014) with a historical control group (January 2009 - January 2011). Setting: "CC Iliescu" Institute for Emergency Cardiovascular Diseases of Bucharest, a tertiary university-affiliated center. Patients: All cases with CCS-PAH. Interventions: Specific vasodilatory therapy: Sildenafil, Bosentan or combined therapy...
April 2017: Journal of Medicine and Life
https://www.readbyqxmd.com/read/28597771/first-in-child-use-of-the-oral-selective-prostacyclin-ip-receptor-agonist-selexipag-in-pulmonary-arterial-hypertension
#9
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
#10
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/28597546/endothelin-1-receptor-blockade-as-new-possible-therapeutic-approach-in-multiple-myeloma
#11
Anna Russignan, Cecilia Spina, Nicola Tamassia, Adriana Cassaro, Antonella Rigo, Anna Bagnato, Laura Rosanò, Angela Bonalumi, Michele Gottardi, Lucia Zanatta, Alice Giacomazzi, Maria Teresa Scupoli, Martina Tinelli, Ugo Salvadori, Federico Mosna, Alberto Zamò, Marco A Cassatella, Fabrizio Vinante, Cristina Tecchio
New effective treatments are needed to improve outcomes for multiple myeloma (MM) patients. Receptors with restricted expression on plasma cells (PCs) represent attractive new therapeutic targets. The endothelin-1 (EDN1) axis, consisting of EDN1 acting through EDN-receptor A (EDNRA) and B (EDNRB), was previously shown to be overexpressed in several tumours, including MM. However, there is incomplete understanding of how EDN1 axis regulates MM growth and response to therapy. Besides EDNRA, the majority of MM cell lines and primary malignant PCs express high levels of EDNRB and release EDN1...
June 9, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28558396/-german-guideline-for-idiopathic-pulmonary-fibrosis-update-on-pharmacological-therapies-2017
#12
Jürgen Behr, Andreas Günther, Francesco Bonella, Klaus Geißler, Dirk Koschel, Michael Kreuter, Antje Prasse, Nicolas Schönfeld, Helmut Sitter, Joachim Müller-Quernheim, Ulrich Costabel
Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a median survival of 2 - 4 years after diagnosis. Since the publication of the German IPF guideline in 2013 new treatment trials have been published, necessitating an update of the pharmacological therapy of IPF. Different from the previous guideline, the GRADE system was discarded and replaced by the Oxford evidence classification system which allows a more differentiated judgement. The following pharmacological therapies were rated not suitable for the treatment of IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone, azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan...
July 2017: Pneumologie
https://www.readbyqxmd.com/read/28500979/ultra-sensitive-and-selective-quantification-of-endothelin-1-in-human-plasma-using-ultra-performance-liquid-chromatography-coupled-to-tandem-mass-spectrometry
#13
Yosuke Suzuki, Lukas Witt, Walter Mier, Gerd Mikus, Christoph Markert, Walter E Haefeli, Jürgen Burhenne
Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor peptide and the plasma concentrations are commonly quantified by immunoassays such as enzyme-linked immuno-sorbent assays (ELISA) with the disadvantage of possible cross-reactivity with closely related endothelin derivatives. The aim of this study was to develop and validate an ultra-sensitive and selective assay for the quantification of ET-1 in human plasma, using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) after solid phase extraction...
April 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28495568/quantitative-analyses-of-the-influence-of-parameters-governing-rate-determining-process-of-hepatic-elimination-of-drugs-on-the-magnitudes-of-drug-drug-interactions-via-hepatic-oatps-and-cyp3a-using-physiologically-based-pharmacokinetic-models
#14
Takashi Yoshikado, Maeda Kazuya, Hiroyuki Kusuhara, Ken-Ichi Furihata, Yuichi Sugiyama
Physiologically-based pharmacokinetic (PBPK) models were constructed for hepatic organic anion transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) substrates (bosentan, repaglinide, clarithromycin, and simeprevir), a CYP3A probe substrate (midazolam), and selective inhibitors for OATPs (rifampicin) and CYP3A (itraconazole), though the role of OATPs in the hepatic uptake of clarithromycin is unclear. The pharmacokinetic data were obtained from our previous clinical drug-drug interaction (DDI) study...
May 8, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28494463/plasma-drug-concentrations-in-patients-with-pulmonary-arterial-hypertension-on-combination-treatment
#15
Ekkehard Grünig, Johanna Ohnesorge, Nicola Benjamin, Jürgen Burhenne, Yeliz Enderle, Benjamin Egenlauf, Christine Fischer, Satenik Harutyunova, Andrea Huppertz, Hans Klose, Walter E Haefeli
BACKGROUND: Combination therapy with the phosphodiesterase type 5 inhibitors (PDE-5i) sildenafil or tadalafil and the endothelin receptor antagonists (ERA) bosentan, ambrisentan, or macitentan may cause mutual pharmacokinetic interactions in patients with pulmonary arterial hypertension (PAH). OBJECTIVE: The objective of this study was to analyze plasma drug concentrations in PAH patients receiving different combination treatments. METHODS: PAH patients receiving a stable combination treatment with ERA and PDE-5i with targeted dosage for at least 1 month were routinely assessed, including clinical parameters and plasma drug concentrations...
2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28486684/superior-vasodilation-of-human-pulmonary-vessels-by-vardenafil-compared-with-tadalafil-and-sildenafil-additive-effects-of-bosentan%C3%A2
#16
Michael Ried, Reiner Neu, Karla Lehle, Christian Großer, Tamas Szöke, Gunter Lang, Hans-Stefan Hofmann, Markus Hoenicka
OBJECTIVES: Pulmonary arterial hypertension is characterized by pulmonary vascular proliferation and remodelling, leading to a progressive increase in pulmonary arterial resistance. Vasodilator properties of 3 different phosphodiesterase (PDE)-5 inhibitors alone and in combination with an endothelin (ET) receptor antagonist were compared in an ex vivo model. METHODS: Segments of human pulmonary arteries (PAs) and pulmonary veins (PVs) were harvested from lobectomy specimens...
May 9, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28484975/a-clinical-cassette-dosing-study-for-evaluating-the-contribution-of-hepatic-oatps-and-cyp3a-to-drug-drug-interactions
#17
Takashi Yoshikado, Kazuya Maeda, Sawako Furihata, Hanano Terashima, Takeshi Nakayama, Keiko Ishigame, Kazunobu Tsunemoto, Hiroyuki Kusuhara, Ken-Ichi Furihata, Yuichi Sugiyama
PURPOSE: To demonstrate the relative importance of organic anion-transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) in the hepatic elimination of substrate drugs. METHODS: A cocktail of subtherapeutic doses of bosentan, repaglinide, clarithromycin, darunavir, simeprevir, and midazolam (CYP3A probe) was administered orally to eight healthy volunteers. Rifampicin (OATP inhibitor; 600 mg, p.o.) and itraconazole (CYP3A inhibitor; 200 mg, i.v.) were coadministered with the cocktail in the second and third phases, respectively...
August 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28468519/atrasentan-for-the-treatment-of-diabetic-nephropathy
#18
REVIEW
Jesus Egido, Jorge Rojas-Rivera, Sebastian Mas, Marta Ruiz-Ortega, Ana Belen Sanz, Emilio Gonzalez Parra, Carmen Gomez-Guerrero
Endothelin-1 (ET-1) is the most potent vasoconstrictor, and is involved in the renal regulation of salt and water homeostasis. When produced in excess in the kidney, ET-1 promotes proteinuria and tubulointerstitial injury. There is great interest in the clinical use of endothelin receptor antagonists (ERAs) in chronic kidney disease (CKD), mainly in diabetic nephropathy (DN). Areas covered: Physiopathological actions of ET-1 on the kidney. Both dual ETAR/ETBR (bosentan) or ETAR specific endothelin antagonists (avosentan and atrasentan, among others), which have progressed to early clinical development, with particular emphasis on atrasentan...
June 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28449795/long-term-effect-of-endothelin-receptor-antagonism-with-bosentan-on-the-morbidity-and-mortality-of-patients-with-severe-chronic-heart-failure-primary-results-of-the-enable-trials
#19
Milton Packer, John J V McMurray, Henry Krum, Wolfgang Kiowski, Barry M Massie, Avi Caspi, Craig M Pratt, Mark C Petrie, David DeMets, Isaac Kobrin, Sebastien Roux, Karl Swedberg
OBJECTIVES: The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. BACKGROUND: Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. METHODS: In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction <35% to receive placebo or bosentan (target dose 125 mg twice daily) for a median of 1...
May 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28435843/mmp-7-is-a-predictive-biomarker-of-disease-progression-in-patients-with-idiopathic-pulmonary-fibrosis
#20
Yasmina Bauer, Eric S White, Simon de Bernard, Peter Cornelisse, Isabelle Leconte, Adele Morganti, Sebastien Roux, Oliver Nayler
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease...
January 2017: ERJ Open Research
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