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https://www.readbyqxmd.com/read/28189026/mass-spectrometry-based-in%C3%A2-vitro-assay-investigations-on-the-transformation-of-pharmaceutical-compounds-by-oxidative-enzymes
#1
Lara F Stadlmair, Thomas Letzel, Jörg E Drewes, Johanna Graßmann
The ubiquitous presence of trace organic chemicals in wastewater and surface water leads to a growing demand for novel removal technologies. The use of isolated enzymes has been shown to possess the capability for a targeted application but requires a clearer mechanistic understanding. In this study, the potential of peroxidase from horseradish (HRP) and laccase from Pleurotus ostreatus (LccPO) to transform selected trace organic chemicals was studied using mass spectrometry (MS)-based in vitro enzyme assays...
February 2, 2017: Chemosphere
https://www.readbyqxmd.com/read/28134617/modeling-susceptibility-to-drug-induced-long-qt-with-a-panel-of-subject-specific-induced-pluripotent-stem-cells
#2
Francesca Stillitano, Jens Hansen, Chi-Wing Kong, Ioannis Karakikes, Christian Funck-Brentano, Lin Geng, Stuart Scott, Stephan Reynier, Ma Wu, Yannick Valogne, Carole Desseaux, Joe-Elie Salem, Dorota Jeziorowska, Noël Zahr, Ronald Li, Ravi Iyengar, Roger J Hajjar, Jean-Sébastien Hulot
A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol...
January 30, 2017: ELife
https://www.readbyqxmd.com/read/28102360/modification-of-distinct-ion-channels-differentially-modulates-ca-2-dynamics-in-primary-cultured-rat-ventricular-cardiomyocytes
#3
Xichun Li, Liping Shen, Fang Zhao, Xiaohan Zou, Yuwei He, Fan Zhang, Chunlei Zhang, Boyang Yu, Zhengyu Cao
Primary cultured cardiomyocytes show spontaneous Ca(2+) oscillations (SCOs) which not only govern contractile events, but undergo derangements that promote arrhythmogenesis through Ca(2+) -dependent mechanism. We systematically examined influence on SCOs of an array of ion channel modifiers by recording intracellular Ca(2+) dynamics in rat ventricular cardiomyocytes using Ca(2+) specific fluorescence dye, Fluo-8/AM. Voltage-gated sodium channels (VGSCs) activation elongates SCO duration and reduces SCO frequency while inhibition of VGSCs decreases SCO frequency without affecting amplitude and duration...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097003/application-of-a-systems-pharmacology-model-for-translational-prediction-of-herg-mediated-qtc-prolongation
#4
Verena Gotta, Zhiyi Yu, Frank Cools, Karel van Ammel, David J Gallacher, Sandra A G Visser, Frederick Sannajust, Pierre Morissette, Meindert Danhof, Piet H van der Graaf
Drug-induced QTc interval prolongation (Δ QTc) is a main surrogate for proarrhythmic risk assessment. A higher in vivo than in vitro potency for hERG-mediated QTc prolongation has been suggested. Also, in vivo between-species and patient populations' sensitivity to drug-induced QTc prolongation seems to differ. Here, a systems pharmacology model integrating preclinical in vitro (hERG binding) and in vivo (conscious dog Δ QTc) data of three hERG blockers (dofetilide, sotalol, moxifloxacin) was applied (1) to compare the operational efficacy of the three drugs in vivo and (2) to quantify dog-human differences in sensitivity to drug-induced QTc prolongation (for dofetilide only)...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28070113/pharmacological-characterization-of-microminipig-as-a-model-to-assess-the-drug-induced-cardiovascular-responses-for-non-clinical-toxicity-and-or-safety-pharmacology-studies
#5
Hirofumi Yokoyama, Yuji Nakamura, Hiroyuki Saito, Yukitoshi Nagayama, Kiyotaka Hoshiai, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Yasuki Akie, Atsushi Sugiyama
We tried to establish the halothane-anesthetized microminipigs as an alternative animal model for non-clinical toxicity and/or safety pharmacology studies. In order to characterize the halothane-anesthetized microminipigs, we firstly clarified the effects of halothane anesthesia on their cardiovascular system (n = 5). Then, we examined the cardiovascular effects of dl-sotalol in doses of 0.1, 0.3 and 1 mg/kg, i.v. on the halothane-anesthetized microminipigs (n = 6). Induction of the halothane anesthesia by itself prolonged the QT interval as well as QTcF, suggesting that the halothane anesthesia can reduce the cardiac repolarization reserve in microminipigs like in dogs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27990843/impact-of-qt-interval-prolongation-following-antiarrhythmic-drug-therapy-on-left-ventricular-function
#6
Konstantinos Chouchoulis, John Chiladakis, Nikolaos Koutsogiannis, Periklis Davlouros, Maria Kaza, Dimitrios Alexopoulos
AIM: We assessed whether antiarrhythmic drug-induced QT interval prolongation affects left ventricular function. METHODS: Study population included 54 patients with symptomatic recent onset atrial fibrillation spontaneously cardioverted to sinus rhythm. Electrocardiographic and echocardiographic studies were done before initiating and after achieving drug's steady state. RESULTS: Significantly prolonged corrected QT interval (QTc) was noticed following only sotalol and amiodarone...
January 2017: Future Cardiology
https://www.readbyqxmd.com/read/27939893/use-of-flecainide-in-combination-antiarrhythmic-therapy-in-patients-with-arrhythmogenic-right-ventricular-cardiomyopathy
#7
Simon Ermakov, Edward P Gerstenfeld, Yana Svetlichnaya, Melvin M Scheinman
BACKGROUND: Antiarrhythmic therapy is commonly used for suppression of arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) in conjunction with implantable cardioverter-defibrillators and catheter ablation. The efficacy of combination flecainide and sotalol/metoprolol therapy for patients refractory to single agents and/or catheter ablation has not been well established. OBJECTIVE: The purpose of this study was to describe our experience with the addition of flecainide in combination with sotalol/metoprolol for treatment of arrhythmias in patients with ARVC...
December 9, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27931611/arrhythmogenic-right-ventricular-cardiomyopathy-clinical-course-and-predictors-of-arrhythmic-risk
#8
Andrea Mazzanti, Kevin Ng, Alessandro Faragli, Riccardo Maragna, Elena Chiodaroli, Nicoletta Orphanou, Nicola Monteforte, Mirella Memmi, Patrick Gambelli, Valeria Novelli, Raffaella Bloise, Oronzo Catalano, Guido Moro, Valentina Tibollo, Massimo Morini, Riccardo Bellazzi, Carlo Napolitano, Vincenzo Bagnardi, Silvia G Priori
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its progression over time and predictors of arrhythmias are still being defined. OBJECTIVES: This study sought to describe the clinical course of ARVC and occurrence of life-threatening arrhythmic events (LAE) and cardiovascular mortality; identify risk factors associated with increased LAE risk; and define the response to therapy. METHODS: We determined the clinical course of 301 consecutive patients with ARVC using the Kaplan-Meier method adjusted to avoid the bias of delayed entry...
December 13, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27925253/fast-and-sensitive-analysis-of-beta-blockers-by-ultra-highperformance-liquid-chromatography-coupled-with-ultrahigh-resolution-tof-mass-spectrometry
#9
Jana Tomková, Peter Ondra, Eva Kocianová, Jan Václavík
This paper presents a method for the determination of acebutolol, betaxolol, bisoprolol, metoprolol, nebivolol and sotalol in human serum by liquid-liquid extraction (LLE) and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry (UHPLC-UHR-TOF MS). After liquid-liquid extraction, beta blockers were separated on a reverse phase analytical column Acclaim RS 120 (100 × 2.1 mm, 2.2 µm). The total run time was 6 min for each sample. Linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effects, specificity, precision, accuracy, recovery and sample stability were evaluated...
December 7, 2016: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/27909477/sotalol-versus-amiodarone-in-treatment-of-atrial-fibrillation
#10
John Somberg Md, Janos Molnar Md
The availability of intravenous (IV) Sotalol has equalized the treatment options since both amiodarone and sotalol are available in both IV and oral formulations. A review of the efficacy of sotalol as compared to amiodarone both for conversion of atrial fibrillation (AF) and maintenance of normal sinus rhythm (NSR) following cardiac surgery was undertaken. Standard methods of meta-analysis were employed. Full text publications of clinical trials written in English that compared the efficacy of sotalol to amiodarone were included in the analysis...
February 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27903390/-current-status-of-antiarrhythmic-drug-use-and-safety-assessment-in-chinese-patients-with-atrial-fibrillation
#11
R He, X Du, S W Liu, L J Sun, Y Li, H Zeng, Y Y Li, C Sun, Y Zhang, C S Ma, W Gao
Objective: To investigate the current status of antiarrhythmic drugs (AADs) use in Chinese patients with atrial fibrillation(AF) and assess the safety of AADs in this patient cohort. Methods: From January 2011 to December 2013, a total of 4 008 AF patients treated with AADs was enrolled in this study and patients were followed up for 24 months. Detailed information of prescribed drug, the causes of drug discontinuation and side effects were recorded. Results: Amiodarone was prescribed to 64.3%(2 579 cases) and propafenone to 31...
November 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/27882422/predictors-of-pharmacological-therapy-of-ectopic-atrial-tachycardia-in-children
#12
Haiyan Ge, Xiaomei Li, Haiju Liu, He Jiang
Ectopic atrial tachycardia (EAT) is a relatively common type of supraventricular tachycardia in the pediatric population, and it can be resistant to antiarrhythmic drugs and lead to tachycardia-induced cardiomyopathy (TIC) if not properly managed. The purpose of this study was to determine the predictors of the response to pharmacological therapy in children with EAT. From January 2009 to April 2014, 115 children were admitted to our hospital with a diagnosis of EAT and placed on antiarrhythmic drugs. We examined the clinical history, response to therapy, and follow-up of the children...
November 24, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27857521/global-chemical-reactivity-parameters-for-several-chiral-beta-blockers-from-the-density-functional-theory-viewpoint
#13
Mona Maria Talmaciu, Ede Bodoki, Radu Oprean
BACKGROUND AND AIM: Beta-adrenergic antagonists have been established as first line treatment in the medical management of hypertension, acute coronary syndrome and other cardiovascular diseases, as well as for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices, glaucoma, and have recently become the main form of treatment of infantile hemangiomas. The aim of the present study is to calculate for 14 beta-blockers several quantum chemical descriptors in order to interpret various molecular properties such as electronic structure, conformation, reactivity, in the interest of determining how such descriptors could have an impact on our understanding of the experimental observations and describing various aspects of chemical binding of beta-blockers in terms of these descriptors...
2016: Clujul Medical (1957)
https://www.readbyqxmd.com/read/27785856/minimal-t-wave-representation-and-its-use-in-the-assessment-of-drug-arrhythmogenicity
#14
Saeed Shakibfar, Claus Graff, Jørgen K Kanters, Jimmi Nielsen, Samuel Schmidt, Johannes J Struijk
BACKGROUND: Recently, numerous models and techniques have been developed for analyzing and extracting features from the T wave which could be used as biomarkers for drug-induced abnormalities. The majority of these techniques and algorithms use features that determine readily apparent characteristics of the T wave, such as duration, area, amplitude, and slopes. METHODS: In the present work the T wave was down-sampled to a minimal rate, such that a good reconstruction was still possible...
October 27, 2016: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/27765191/pitx2-modulates-atrial-membrane-potential-and-the-antiarrhythmic-effects%C3%A2-of%C3%A2-sodium-channel-blockers
#15
Fahima Syeda, Andrew P Holmes, Ting Y Yu, Samantha Tull, Stefan Michael Kuhlmann, Davor Pavlovic, Daniel Betney, Genna Riley, Jan P Kucera, Florian Jousset, Joris R de Groot, Stephan Rohr, Nigel A Brown, Larissa Fabritz, Paulus Kirchhof
BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs...
October 25, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27759583/does-sotalol-still-have-a-role-in-the-management-of-arrhythmias
#16
Sahan P Semasinghe Bandaralage, Selvanayagam Nirthanan, Selvanayagam Niranjan
Despite proven effectiveness in treating tachyarrhythmias, sotalol is proarrhythmic and can cause torsades de pointes. Given the emergence of studies that show no benefit from rhythm control strategies in managing atrial fibrillation, as well as the introduction of nonpharmacological approaches to treating arrhythmias, we felt it necessary to ascertain if there was any role for sotalol given its side effects. Review of the literature regarding sotalol use in the prevention and treatment of supraventricular and ventricular tachyarrhythmias seems to show that more effective and safer agents and nonpharmacological alternatives are currently available...
October 3, 2016: American Journal of Therapeutics
https://www.readbyqxmd.com/read/27756610/promising-approach-for-the-preclinical-assessment-of-cardiac-risks-using-left-ventricular-pressure-volume-loop-analyses-in-anesthetized-monkeys
#17
Tomomichi Ishizaka, Yu Yoshimatsu, Yu Maeda, Wataru Takasaki, Katsuyoshi Chiba, Kazuhiko Mori
INTRODUCTION: Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy. In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dependent inotropic, hemodynamic and electrocardiographic changes in isoflurane-anesthetized monkeys. METHODS: The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a β-blocker), or dl-sotalol (a β+IKr blocker) intravenously over 10min at two dose levels including clinically relevant doses (n=5/drug)...
October 15, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27755533/digoxin-and-prostate-cancer-survival-in-the-finnish-randomized-study-of-screening-for-prostate-cancer
#18
Kalle J Kaapu, Teemu J Murtola, Kirsi Talala, Kimmo Taari, Teuvo Lj Tammela, Anssi Auvinen
BACKGROUND: Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study. METHODS: Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Study of Screening for Prostate Cancer diagnosed during 1996-2009 (485 digoxin users)...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27751700/best-clinical-practice-emergency-medicine-management-of-stable-monomorphic-ventricular-tachycardia
#19
Brit Long, Alex Koyfman
BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation are the causes of approximately 300,000 deaths per year in the United States. VT is classified based on hemodynamic status and appearance. Stable, monomorphic VT treatment is controversial. OBJECTIVE: Our aim was to provide emergency physicians with an evidence-based review of the medical management of stable, monomorphic VT. DISCUSSION: Stable, monomorphic VT is part of a larger class of ventricular dysrhythmias defined by a rate of at least 120 beats/min with QRS > 120 ms without regularly occurring P:QRS association...
October 14, 2016: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27733494/long-term-outcome-after-catheter-ablation-of-ventricular-tachycardia-in-patients-with-nonischemic-dilated-cardiomyopathy
#20
Daniele Muser, Pasquale Santangeli, Simon A Castro, Rajeev K Pathak, Jackson J Liang, Tatsuya Hayashi, Silvia Magnani, Fermin C Garcia, Mathew D Hutchinson, Gregory G Supple, David S Frankel, Michael P Riley, David Lin, Robert D Schaller, Sanjay Dixit, Erica S Zado, David J Callans, Francis E Marchlinski
BACKGROUND: Catheter ablation (CA) of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy can be challenging because of the complexity of underlying substrates. We sought to determine the long-term outcomes of endocardial and adjuvant epicardial CA in nonischemic dilated cardiomyopathy. METHODS AND RESULTS: We examined 282 consecutive patients (aged 59±15 years, 80% males) with nonischemic dilated cardiomyopathy who underwent CA. Ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal electrograms for unmappable VT...
October 2016: Circulation. Arrhythmia and Electrophysiology
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