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https://www.readbyqxmd.com/read/29027845/the-potent-mechanism-based-inactivation-of-cyp2d6-and-cyp3a4-with-fusidic-acid-in-in-vivo-bioaccumulation
#1
Xiu-Xian Lin, Guang-Hui Lian, Ying Xu, Qing Zhao, Jian Xiao, Shi-Fang Peng, Mei-Fang Xiao, Dong-Sheng Ouyang, Zhi-Rong Tan, Yi-Cheng Wang, Jing-Bo Peng, Wei Zhang, Yao Chen
1. The accumulation of fusidic acid (FA) after multiple doses of FA has been reported on in previous studies but the related mechanisms have not been clarified fully. In the present study, we explain the mechanisms related to the mechanism-based inactivation of CYP2D6 and CYP3A4. 2. The irreversible inhibitory effects of FA on CYP2D6 and CYP3A4 were examined via a series of experiments, including: a) time-, concentration- and NADPH-dependent inactivation, b) substrate protection in enzyme inactivation and c) partition ratio with recombinant human CYP enzymes...
October 13, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29023958/stroke-induced-chronic-systolic-dysfunction-driven-by-sympathetic-overactivity
#2
Michael Bieber, Rudolf A Werner, Edit Tanai, Ulrich Hofmann, Takahiro Higuchi, Kai Schuh, Peter U Heuschmann, Stefan Frantz, Oliver Ritter, Peter Kraft, Christoph Kleinschnitz
OBJECTIVE: Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. While it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function...
October 10, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29018635/a-new-wavelet-based-ecg-delineator-for-the-evaluation-of-the-ventricular-innervation
#3
Matteo Cesari, Jesper Mehlsen, Anne-Birgitte Mehlsen, Helge Bjarup Dissing Sorensen
T-wave amplitude (TWA) has been proposed as a marker of the innervation of the myocardium. Until now, TWA has been calculated manually or with poor algorithms, thus making its use not efficient in a clinical environment. We introduce a new wavelet-based algorithm for the delineation QRS complexes and T-waves, and the automatic calculation of TWA. When validated in the MIT/BIH Arrhythmia database, the QRS detector achieved sensitivity and positive predictive value of 99.84% and 99.87%, respectively. The algorithm was validated also on the QT database and it achieved sensitivity of 99...
2017: IEEE Journal of Translational Engineering in Health and Medicine
https://www.readbyqxmd.com/read/28988245/basic-in-vitro-characterization-of-the-vasodilatory-potential-of-2-aminoethyl-nitrate-fixed-dose-combinations-with-cilostazol-metoprolol-and-valsartan
#4
Matthias Oelze, Philipp Welschof, Maike Knorr, Lan P Tran, Elisabeth Ullmann, Paul Stamm, Swenja Kröller-Schön, Thomas Jansen, Maximilian Kopp, Eberhard Schulz, Tommaso Gori, Karl Burgin, Armin Scherhag, Dirk Sartor, Thomas Münzel, Andreas Daiber
BACKGROUND/AIMS: 2-aminoethyl nitrate (CLC-1011) is a member of the class of organic nitrates that cause vasodilation by the generation of nitric oxide (•NO). These drugs are mainly used for the treatment of angina pectoris and ischemic heart disease. The aim of this study was to characterize the vasodilatory potency of this organic nitrate alone and in combination with clinically established cardiovascular drugs. METHODS: Vasodilation by CLC-1011 was tested by isometric tension studies, either alone or combined with cilostazol, valsartan, and metoprolol...
October 7, 2017: Pharmacology
https://www.readbyqxmd.com/read/28975092/self-limited-membranous-nephropathy-after-intravitreal-bevacizumab-therapy-for-age-related-macular-degeneration
#5
Gebran Khneizer, Ahmad Al-Taee, Bahar Bastani
BACKGROUND: Monoclonal antibodies targeting vascular endothelial growth factor (VEGF), such as bevacizumab, are administered intravitreally for the treatment of wet or exudative age-related macular degeneration (ARMD). Systemic use of bevacizumab has been linked to a wide range of renal adverse effects including proteinuria and hypertension. CASE PRESENTATION: We present the case of a 77-year-old Caucasian male with a past medical history of hypertension, vitamin D deficiency and paroxysmal atrial fibrillation who presented to primary care clinic with a 2-week history of bilateral lower extremity edema, 2 months after completing four monthly intravitreal injections of bevacizumab for ARMD...
July 2017: Journal of Nephropathology
https://www.readbyqxmd.com/read/28965022/does-wastewater-treatment-plant-upgrading-with-activated-carbon-result-in-an-improvement-of-fish-health
#6
Sabrina Wilhelm, Anja Henneberg, Heinz-R Köhler, Magali Rault, Doreen Richter, Marco Scheurer, Séverine Suchail, Rita Triebskorn
In the present study, the efficiency of a wastewater treatment plant (WWTP) upgraded with a powdered activated carbon unit for the reduction of micropollutants and the related advantages for fish health have been analyzed by means of different biomarkers, i.e. histopathological investigations, analyses of glycogen content and stress proteins, as well as by chemical analyses in different matrices. Comparative analyses were conducted prior and subsequent to the installation of the additional purification unit...
September 21, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28956773/metoprolol-reduces-hemodynamic-and-metabolic-overload-in-asymptomatic-aortic-valve-stenosis-patients-a-randomized-trial
#7
RANDOMIZED CONTROLLED TRIAL
Nils Henrik Hansson, Jens Sörensen, Hendrik Johannes Harms, Won Yong Kim, Roni Nielsen, Lars Poulsen Tolbod, Jørgen Frøkiær, Kirsten Bouchelouche, Karen Kaae Dodt, Inger Sihm, Steen Hvitfeldt Poulsen, Henrik Wiggers
BACKGROUND: Currently, no pharmacological treatment can modify the natural history of aortic valve stenosis (AS). This underlines the critical need to explore novel treatment strategies, which could postpone or prevent the need for aortic valve replacement in patients with asymptomatic AS. The objectives of this study were to investigate whether metoprolol reduce the hemodynamic and metabolic burden imposed by AS. METHODS AND RESULTS: In a double-blinded design, 40 patients with moderate-severe asymptomatic AS (aortic valve area, 0...
October 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28940643/blood-pressure-response-to-metoprolol-and-chlorthalidone-in-european-and-african-americans-with-hypertension
#8
Mai Mehanna, Yan Gong, Caitrin W McDonough, Amber L Beitelshees, John G Gums, Arlene B Chapman, Gary L Schwartz, Julie A Johnson, Stephen T Turner, Rhonda M Cooper-DeHoff
Despite the availability of many antihypertensive drug classes, half of patients with hypertension have uncontrolled blood pressure (BP). The authors sought to assess the effect of age on BP response in European American and African American patients with hypertension. Clinic BP from the PEAR2 (Pharmacogenomics Evaluation of Antihypertensive Responses 2) study was used to estimate BP responses from baseline following sequential treatment with metoprolol 100 mg twice daily and chlorthalidone 25 mg daily for 8 to 9 weeks each, with a minimum 4-week washout between treatments...
September 21, 2017: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/28940051/erratum-to-evaluation-of-the-safety-and-efficacy-of-metoprolol-infusion-for-children-and-adolescents-with-hypertensive-crises-a-retrospective-case-series
#9
Rola Saqan, Hanan Thiabat
No abstract text is available yet for this article.
November 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28932497/evaluation-of-amiodarone-versus-metoprolol-in-treating-atrial-fibrillation-after-coronary-artery-bypass-grafting
#10
Alireza Kamali, Amir Sanatkar, Mehrzad Sharifi, Esmaeil Moshir
INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia affecting patients in open heart ICU after coronary artery bypass grafting (CABG). Most cardiac surgery textbooks recommend beta blockers as the drug of choice for treating such a condition while many experienced physicians and a number of anesthesiology references offer amiodarone as the drug of choice. Therefore, because of insufficient evidence and the aforementioned controversy, we decided to conduct a study evaluating these two antiarrhythmic medicines...
June 2017: Interventional Medicine & Applied Science
https://www.readbyqxmd.com/read/28930747/quantification-of-bisoprolol-and-metoprolol-in-simultaneous-human-serum-and-cerebrospinal-fluid-samples
#11
Ali Sigaroudi, Martina Kinzig, Oliver Wahl, Christoph Stelzer, Michael Schroeter, Uwe Fuhr, Ulrike Holzgrabe, Fritz Sörgel
BACKGROUND: Bisoprolol and metoprolol are moderately lipophilic, beta(1)-selective betablockers reported to cause adverse effects in the central nervous system (CNS), such as sleep disturbance, suggesting that both drugs may reach relevant concentrations in the brain. CNS beta(2)-receptor blockade has been suspected to be related to such effects. The higher molecular size of bisoprolol (325 Dalton) and the higher beta(1)-selectivity compared to metoprolol (267 Dalton) would suggest a lower rate of CNS effects...
September 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28929443/short-term-fasting-alters-pharmacokinetics-of-cytochrome-p450-probe-drugs-does-protein-binding-play-a-role
#12
Laureen A Lammers, Roos Achterbergh, Johannes A Romijn, Ron A A Mathôt
BACKGROUND AND OBJECTIVES: Short-term fasting differentially alters cytochrome P450 (CYP) mediated drug metabolism. This has been established by using CYP-enzyme selective probe drugs. However, the observed effects of fasting on the pharmacokinetics of these probe drugs may also include the effects of altered plasma protein binding of these drugs. Therefore, we studied the effect of short-term fasting on protein binding of five commonly used probe drugs [caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and S-warfarin (CYP2C9)]...
September 19, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28924743/a-physiologically-based-pharmacokinetic-model-for-pregnant-women-to-predict-the-pharmacokinetics-of-drugs-metabolized-via-several-enzymatic-pathways
#13
André Dallmann, Ibrahim Ince, Katrin Coboeken, Thomas Eissing, Georg Hempel
BACKGROUND: Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women. The objective of this study was to extend and verify a previously developed physiologically based pharmacokinetic model for pregnant women for the prediction of pharmacokinetics of drugs metabolized via several cytochrome P450 enzymes. METHODS: Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted...
September 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28920690/regional-intestinal-permeability-in-rats-a-comparison-of-methods
#14
Carl Roos, David Dahlgren, Erik Sjögren, Christer Tannergren, Bertil Abrahamsson, Hans Lennernäs
Currently, the screening of new drug candidates for intestinal permeation is typically based on in vitro models which give no information regarding regional differences along the gut. When evaluation of intestinal permeability by region is undertaken, two preclinical rat models are commonly used, the Ussing chamber method and single-pass intestinal perfusion (SPIP). To investigate the robustness of in vivo predictions of human intestinal permeability, a set of four model compounds was systematically investigated in both these models, using tissue specimens and segments from the jejunum, ileum, and colon of rats from the same genetic strain...
October 5, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28917751/structural-characterization-of-electrochemically-and-in-vivo-generated-potential-metabolites-of-selected-cardiovascular-drugs-by-ec-uhplc-esi-ms-using-an-experimental-design-approach
#15
Małgorzata Szultka-Młyńska, Sylwia Bajkacz, Irena Baranowska, Bogusław Buszewski
In the last few years, a number of studies were conducted which aimed at understanding the mechanisms of cardiovascular drug, metabolism, and there is still the need to determine the metabolites of cardiac drugs for the purpose of metabolism control. In this study, we employ a direct combination of electrochemical oxidation and mass spectrometric (EC-MS) identification for monitoring the oxidation pathway of ten cardiovascular drugs (metoprolol, propranolol, propafenone, mexiletine, oxprenolol, pirbuterol, pindolol, cicloprolol, acebutolol and atenolol)...
January 1, 2018: Talanta
https://www.readbyqxmd.com/read/28911302/what-is-the-real-efficacy-of-beta-blockers-for-the-treatment-of-essential-hypertension
#16
Christian Höcht, Facundo M Bertera, Julieta S Del Mauro, Yanina Santander Plantamura, Carlos A Taira, Ariel H Polizio
OBJECTIVE: This review covers the pharmacokinetics and pharmacodynamic of β-blockers, the rationale for their use, some recent controversies in its use for managing hypertension, as well as, the beneficial properties of the third-generation β-blockers beyond hypertension. BACKGROUND: The efficacy and safety of -blockers in the treatment of hypertension and other cardiovascular diseases have been established during more than 50 years of clinical experience. Recent updates of clinical guidelines have downgraded the use of -blockers for the treatment of uncomplicated hypertension to second and third line therapy...
June 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28894360/the-evaluation-of-%C3%AE-adrenoceptor-blocking-agents-in-patients-with-copd-and-congestive-heart-failure-a-nationwide-study
#17
Kuang-Ming Liao, Tien-Yu Lin, Yaw-Bin Huang, Chen-Chun Kuo, Chung-Yu Chen
OBJECTIVE: β-Blockers are safe and improve survival in patients with both congestive heart failure (CHF) and COPD. However, the superiority of different types of β-blockers is still unclear among patients with CHF and COPD. The association between β-blockers and CHF exacerbation as well as COPD exacerbation remains unclear. The objective of this study was to compare the outcome of different β-blockers in patients with concurrent CHF and COPD. PATIENTS AND METHODS: We used the National Health Insurance Research Database in Taiwan to conduct a retrospective cohort study...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28882337/meta-analysis-comparing-metoprolol-and-carvedilol-on-mortality-benefits-in-patients-with-acute-myocardial-infarction
#18
Jingen Li, Zhuo Chen, Xiang Gao, He Zhang, Wenjing Xiong, Jianqing Ju, Hao Xu
Although carvedilol, a nonselective beta-blocker with alpha-adrenergic blocking and multiple ancillary activities, has been demonstrated to be superior to metoprolol in chronic heart failure, it remains unclear whether the superiority of carvedilol still exists in myocardial infarction (MI). Therefore, we performed a network meta-analysis of randomized controlled trials (RCTs) to compare the 2 drugs in patients with MI. All RCTs that compared either 2 of the following interventions, carvedilol, metoprolol, and placebo, for the treatment of MI were included...
November 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28874950/appropriateness-of-bolus-antihypertensive-therapy-for-elevated-blood-pressure-in-the-emergency-department
#19
Joseph B Miller, Andrew Arter, Suprat S Wilson, Alexander T Janke, Aaron Brody, Brian P Reed, Phillip D Levy
INTRODUCTION: While moderate to severely elevated blood pressure (BP) is present in nearly half of all emergency department (ED) patients, the incidence of true hypertensive emergencies in ED patients is low. Administration of bolus intravenous (IV) antihypertensive treatment to lower BP in patients without a true hypertensive emergency is a wasteful practice that is discouraged by hypertension experts; however, anecdotal evidence suggests this occurs with relatively high frequency. Accordingly, we sought to assess the frequency of inappropriate IV antihypertensive treatment in ED patients with elevated BP absent a hypertensive emergency...
August 2017: Western Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28869814/multi-residue-determination-of-47-organic-compounds-in-water-soil-sediment-and-fish-turia-river-as-case-study
#20
Eric Carmona, Vicente Andreu, Yolanda Picó
A sensitive and reliable method based on solid-liquid extraction (SLE) using McIlvaine-Na2EDTA buffer (pH=4.5)-methanol and solid-phase extraction (SPE) clean up prior to ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) was applied to determine 47 organic contaminants in fish, soil and sediments. The SPE procedure to clean-up the extracts was also used as extraction method to determine these compounds in water. Recoveries ranged from 38 to 104% for all matrices with RSDs<30%...
August 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
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