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https://www.readbyqxmd.com/read/29760739/antiarrhythmic-effects-of-carvedilol-and-flecainide-in-cardiomyocytes-derived-from-catecholaminergic-polymorphic-ventricular-tachycardia-patients
#1
R P Pölönen, K Penttinen, H Swan, K Aalto-Setälä
Mutations in the cardiac ryanodine receptor (RYR2) are the leading cause for catecholaminergic polymorphic ventricular tachycardia (CPVT). In this study, we evaluated antiarrhythmic efficacy of carvedilol and flecainide in CPVT patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carrying different mutations in RYR2. iPSC-CMs were generated from skin biopsies of CPVT patients carrying exon 3 deletion and L4115 or V4653F mutation in RYR2 and of a healthy individual. Ca2+ kinetics and drug effects were studied with Fluo-4 AM indicator...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29754646/effect-of-carvedilol-vs-metoprolol-succinate-on-mortality-in-heart-failure-with-reduced-ejection-fraction
#2
Tarek Ajam, Samer Ajam, Srikant Devaraj, Kahee Mohammed, Stephen Sawada, Masoor Kamalesh
BACKGROUND: Beta blocker therapy is indicated in all patients with heart failure with reduced ejection fraction (HFrEF) as per current guidelines. The relative benefit of carvedilol to metoprolol succinate remains unknown. This study aimed to compare survival benefit of carvedilol to metoprolol succinate. METHODS: The VA's databases were queried to identify 114,745 patients diagnosed with HFrEF from 2007 to 2015 who were prescribed carvedilol and metoprolol succinate...
May 2018: American Heart Journal
https://www.readbyqxmd.com/read/29752864/%C3%AE-blockers-interfere-with-cell-homing-receptors-and-regulatory-proteins-in-a-model-of-spontaneously-hypertensive-rats
#3
Bruna Eibel, Melissa Kristochek, Thiago R Peres, Lucinara D Dias, Daniela R Dartora, Karina R Casali, Renato A K Kalil, Alexandre M Lehnen, Maria Claudia Irigoyen, Melissa M Markoski
AIM: To examine the interference of β-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7 and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme linked immunosorbent assay (ELISA)...
May 12, 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29747861/effects-of-carvedilol-versus-metoprolol-on-platelet-aggregation-in-patients-with-acute-coronary-syndrome-the-plate-block-study
#4
Federica Ilardi, Giuseppe Gargiulo, Gabriele Giacomo Schiattarella, Giuseppe Giugliano, Roberta Paolillo, Giovanni Menafra, Elena De Angelis, Laura Scudiero, Anna Franzone, Eugenio Stabile, Cinzia Perrino, Plinio Cirillo, Carmine Morisco, Raffaele Izzo, Valentina Trimarco, Giovanni Esposito
Platelet aggregation plays a pivotal role in acute coronary syndrome (ACS). In this setting, β-blockers (BBs) are used to counteract the effects of catecholamines on heart. Circulating catecholamines can also potentiate platelet reactivity, mainly through α2 - and β2 -adrenoceptors on human platelets' surface, thus BB may affect platelet aggregation; however, the effects of different BBs on platelet aggregation in contemporary-treated patients with ACS have been poorly investigated. One hundred patients with ACS on dual antiplatelet therapy with aspirin and ticagrelor were randomized to receive treatment with carvedilol, a nonselective BB (n = 50), or metoprolol, a selective β1 -blocker (n = 50), at maximum tolerated dose...
April 3, 2018: American Journal of Cardiology
https://www.readbyqxmd.com/read/29735493/recurrent-blistering-distal-dactylitis-due-to-staphylococcus-aureus-in-an-immunocompetent-elderly-woman
#5
Colin A Hinkamp, Nikhil H Shah, Neal Holland, Ashleigh Wright
An 86-year-old woman presented with marked blistering of her left index fingertip and ulceration of the left middle fingertip, with a 2-year history of recurrent blistering and ulceration of her fingers bilaterally. She denied any preceding finger trauma, although she reported frequent gardening. She denied systemic symptoms. Her medical history was significant for a 2-year history of atrial fibrillation on carvedilol, amiodarone and apixaban, and she was a lifetime non-smoker. On admission, she had elevated inflammatory markers but unremarkable autoantibodies...
May 7, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29710286/carvedilol-for-treatment-of-red-vulva-syndrome
#6
Carla Hajj, Nakhle Ayoub
No abstract text is available yet for this article.
April 25, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29703600/vascular-toxicities-with-vegf-inhibitor-therapies-focus-on-hypertension-and-arterial-thrombotic-events
#7
REVIEW
Rhian M Touyz, Sandra M S Herrmann, Joerg Herrmann
The vascular endothelial growth factor (VEGF) signaling pathway (VSP) fulfills a cardinal role in endothelial cells and its inhibition has profound cardiovascular impact. This is true not only for the normal vasculature but also for the tumor vasculature when VSP inhibitors are used as anti-angiogenic therapies. Generalized endothelial dysfunction predisposes to vasoconstriction, atherosclerosis, platelet activation, and thrombosis (arterial more than venous). All of these have been reported with VSP inhibitors and collectively give rise to vascular toxicities, the most concerning of which are arterial thromboembolic events (ATE)...
March 21, 2018: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/29692206/pilot-investigation-of-the-effect-of-carvedilol-on-stress-precipitated-smoking-lapse-behavior
#8
Terril L Verplaetse, Andrea H Weinberger, Rebecca L Ashare, Brian P Pittman, Julia M Shi, Jeanette M Tetrault, Meaghan Lavery, Sherry A McKee
INTRODUCTION: Separate α1- and β-adrenergic antagonists have shown efficacy in reducing nicotine-motivated behaviors in rodents and humans, supporting a role for the noradrenergic system in mediating the reinforcing properties of drugs of abuse. However, the effect of the combined α1- and β-adrenergic antagonist, carvedilol, on stress-related smoking is unknown. METHODS: Using a well-established human laboratory model of stress-precipitated smoking-lapse behavior, we examined whether carvedilol (0 or 50 mg/day; between subject, n=17 per group), administered to steady-state, would attenuate the ability to resist smoking following stress imagery (vs...
April 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29684191/importance-of-beta-blocker-dose-in-prevention-of-ventricular-tachyarrhythmias-heart-failure-hospitalizations-and-death-in-primary-prevention-implantable-cardioverter-defibrillator-recipients-a-danish-nationwide-cohort-study
#9
A C Ruwald, G H Gislason, M Vinther, J B Johansen, J C Nielsen, B T Philbert, C Torp-Pedersen, S Riahi, C Jøns
Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Methods and results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers...
April 19, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29678315/effects-of-carvedilol-therapy-in-patients-with-heart-failure-with-preserved-ejection-fraction-results-from-the-croatian-heart-failure-cro-hf-registry
#10
Markovic Domagoj, Jurcevic Zidar Branka, Macanovic Jelena, Milicic Davor, Glavas Duska
BACKGROUND AND OBJECTIVE: According to recent guidelines, the best approach for treatment of heart failure patients with preserved ejection function is still not defined. The aim of this study was to investigate how carvedilol therapy influences the survival rate, ejection fraction and NYHA class in these patients. PATIENTS AND METHODS: We conducted study on heart failure patients with preserved systolic function from the Croatian heart failure registry who were hospitalized in the period between 2005 and 2010...
April 17, 2018: Medicina Clínica
https://www.readbyqxmd.com/read/29675426/a-novel-method-for-drug-screen-to-regulate-g-protein-coupled-receptors-in-the-metabolic-network-of-alzheimer-s-disease
#11
Yang Li, Wei Zheng, Wuyun Qiqige, Shujuan Cao, Jishou Ruan, Yanping Zhang
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder and the pathogenesis of AD is poorly understood. G protein-coupled receptors (GPCRs) are involved in numerous key AD pathways and play a key role in the pathology of AD. To fully understand the pathogenesis of AD and design novel drug therapeutics, analyzing the connection between AD and GPCRs is of great importance. In this paper, we firstly build and analyze the AD-related pathway by consulting the KEGG pathway of AD and a mass of literature and collect 25 AD-related GPCRs for drug discovery...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29649569/the-use-of-molecular-descriptors-in-the-development-of-co-amorphous-formulations
#12
Helena Meng-Lund, Georgia Kasten, Katrine Tarp Jensen, Antti Poso, Tatu Pantsar, Thomas Rades, Jukka Rantanen, Holger Grohganz
Co-amorphous systems consisting of a drug and an amino acid have been investigated extensively for the enhancement of drug solubility and amorphous stability. The purpose of this study is to investigate which molecular descriptors are important for predicting the likelihood of a successful co-amorphisation between amino acid and drug. The predictions are thought to be used in an early screening phase to identify potential drug-amino acid combinations for further studies. A large variety of molecular descriptors was calculated for six drugs (carvedilol, mebendazole, carbamazepine, furosemide, indomethacin and simvastatin) and the twenty naturally occurring amino acids...
April 9, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29644737/editorial-optimal-dose-of-carvedilol-in-portal-hypertension%C3%A2-nearly-there
#13
EDITORIAL
D Tripathi, A J Stanley
No abstract text is available yet for this article.
May 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29644735/editorial-optimal-dose-of-carvedilol-in-portal-hypertension%C3%A2-nearly-there-authors-reply
#14
EDITORIAL
T Reiberger, A Ferlitsch
No abstract text is available yet for this article.
May 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29627294/%C3%AE-arrestin-biased-agonism-of-%C3%AE-adrenergic-receptor-regulates-dicer-mediated-microrna-maturation-to-promote-cardioprotective-signaling
#15
Jian-Peng Teoh, Ahmed S Bayoumi, Tatsuya Aonuma, Yanyan Xu, John A Johnson, Huabo Su, Neal L Weintraub, Yaoliang Tang, Il-Man Kim
RATIONALE: MicroRNAs (miRs) are small, non-coding RNAs that function to post-transcriptionally regulate target genes. First transcribed as primary miR transcripts (pri-miRs), they are enzymatically processed by Drosha into premature miRs (pre-miRs) and further cleaved by Dicer into mature miRs. Initially discovered to desensitize β-adrenergic receptor (βAR) signaling, β-arrestins are now well-appreciated to modulate multiple pathways independent of G protein signaling, a concept known as biased signaling...
April 6, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29626349/phosphoproteome-profiling-provides-insight-into-the-mechanism-of-action-for-carvedilol-mediated-cancer-prevention
#16
Kristan H Cleveland, Steven Yeung, Kevin M Huang, Sherry Liang, Bradley T Andresen, Ying Huang
Recent studies suggest that the β-blocker drug carvedilol prevents skin carcinogenesis but the mechanism is unknown. Carvedilol is one of a few β-blockers identified as biased agonist based on an ability to promote β-arrestin-mediated processes such as ERK phosphorylation. To understand the role of phosphoproteomic signaling in carvedilol's anticancer activity, the mouse epidermal JB6 P+ cells treated with EGF, carvedilol or their combination were analyzed using the Phospho Explorer Antibody Array containing 1318 site-specific and phospho-specific antibodies of over 30 signaling pathways...
April 6, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29618986/the-antioxidant-therapy-new-insights-in-the-treatment-of-hypertension
#17
REVIEW
Daniela Sorriento, Nicola De Luca, Bruno Trimarco, Guido Iaccarino
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a key role in the regulation of the physiological and pathological signaling within the vasculature. In physiological conditions, a delicate balance between oxidants and antioxidants protects cells from the detrimental effects of ROS/RNS. Indeed, the imbalance between ROS/RNS production and antioxidant defense mechanisms leads to oxidative and nitrosative stress within the cell. These processes promote the vascular damage observed in chronic conditions, such as hypertension...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29607517/amorphous-solid-dispersions-of-carvedilol-along-with-ph-modifiers-improved-pharmacokinetic-properties-under-hypochlorhydoria
#18
Shimul Halder, Aiko Tabata, Yoshiki Seto, Hideyuki Sato, Satomi Onoue
Carvedilol (CAR) belongs to biopharmaceutics classification system class-II drugs, with poor aqueous solubility and pH-dependent solubility. The present study aimed to develop a novel amorphous solid dispersion (ASD) of CAR with acidic counter ions for pH modifications in microenvironment to improve the pharmacokinetic properties under hypochlorhydric conditions. CAR-ASD was prepared by freeze-drying in combination with counter ions and hydroxypropyl cellulose, and their physicochemical properties including dissolution behavior, storage stability, and photostability were characterized...
April 2, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29605455/integration-of-in-vitro-biorelevant-dissolution-and-in-silico-pbpk-model-of-carvedilol-to-predict-bioequivalence-of-oral-drug-products
#19
Manuel Ibarra, Cristian Valiante, Patricia Sopeña, Alejandra Schiavo, Marianela Lorier, Marta Vázquez, Pietro Fagiolino
Bioequivalence implementation in developing countries where a high proportion of similar drug products are being marketed has found several obstacles, impeding regulatory agencies to move forward with this policy. Biopharmaceutical quality of these products, several of which are massively prescribed, remains unknown. In this context, an in vitro-in silico-in vivo approach is proposed as a mean to screen product performance and target specific formulations for bioequivalence assessment. By coupling in vitro biorelevant dissolution testing in USP-4 Apparatus (flow-through cell) with physiologically-based pharmacokinetic (PBPK) modeling in PK-Sim® software (Bayer, Germany), the performance of seven similar products of carvedilol tablets containing 25 mg available in the Uruguayan market were compared with the brand-name drug Dilatrend®...
March 29, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29574705/a-comprehensive-approach-to-identifying-repurposed-drugs-to-treat-scn8a-epilepsy
#20
Talia A Atkin, Chani M Maher, Aaron C Gerlach, Bryant C Gay, Brett M Antonio, Sonia C Santos, Karen M Padilla, JulieAnn Rader, Douglas S Krafte, Matthew A Fox, Gregory R Stewart, Slavé Petrovski, Orrin Devinsky, Matthew Might, Steven Petrou, David B Goldstein
OBJECTIVE: Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. METHODS: We developed cellular models expressing wild-type or an R1872Q mutation in the Nav 1.6 sodium channel encoded by SCN8A...
April 2018: Epilepsia
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