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https://www.readbyqxmd.com/read/28822959/na2s-a-fast-releasing-h2s-donor-given-as-suppository-lowers-blood-pressure-in-rats
#1
Lenka Tomasova, Adrian Drapala, Halina Jurkowska, Maria Wróbel, Marcin Ufnal
BACKGROUND: Hydrogen sulfide (H2S) is involved in blood pressure control. The available slow-releasing H2S-donors are poorly soluble in water and their ability to release H2S in biologically relevant amounts under physiological conditions is questionable. Therefore, new slow-releasing donors or new experimental approaches to fast-releasing H2S donors are needed. METHODS: Hemodynamics and ECG were recorded in male, anesthetized Wistar Kyoto rats (WKY) and in Spontaneously hypertensive rats (SHR) at baseline and after: 1) intravenous (iv) infusion of vehicle or Na2S; 2) administration of vehicle suppositories or Na2S suppositories...
April 19, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28820736/long-qt-syndrome-diagnosed-in-two-sisters-with-propionic-acidemia-a-case-report
#2
Ensar Duras, Ahmet İrdem, Ozan Özkaya
Propionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). This disorder mostly progresses with episodes of metabolic acidosis. Cardiomyopathy is among the cardiac complications known to occur during metabolic decompensation episodes. However, several recent papers emphasized the association of PA and long QT syndrome (LQTS) which may lead to extremely serious and fatal consequences. In this report, we describe two sisters with PA who have prolonged QT duration that were incidentally detected in an outpatient setting...
August 18, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28812984/modelling-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-3-in-the-human-ventricles
#3
Cunjin Luo, Kuanquan Wang, Henggui Zhang
Short QT syndrome (SQTS) is an inherited cardiac channelopathy, but at present little information is available on its pharmacological treatment. SQT3 variant (linked to the inward rectifier potassium current IK1) of SQTS, results from a gain-of-function mutation (Kir2.1 D172N) in the KCNJ2-encoded channels, which is associated with ventricular fibrillation (VF). Using biophysically-detailed human ventricular computer models, this study investigated the potential effects of quinidine, disopyramide, and E-4031 on SQT3...
August 16, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28808933/cardiovascular-disease-in-clozapine-treated-patients-evidence-mechanisms-and-management
#4
REVIEW
Kathlyn J Ronaldson
Myocarditis occurs in about 3% of those initiated on clozapine but monitoring reduces the risk of serious outcome. Cardiomyopathy may develop after myocarditis, or from prolonged tachycardia. Monitoring using echocardiography is not deemed cost effective. Tachycardia, orthostatic hypotension and reduced heart rate variability are a group of clozapine-related adverse effects associated with autonomic dysfunction and may have serious consequences in the long term. Elevated heart rate and poor heart rate variability can be treated with a β-blocker or a non-dihydropyridine calcium channel blocker, while orthostatic hypotension can be alleviated by increased fluid intake and abdominal binding, but may require pharmacological intervention...
August 14, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28804970/arrhythmogenic-gene-remodelling-in-elderly-patients-with-type-2-diabetes-with-aortic-stenosis-and-normal-left-ventricular-ejection-fraction
#5
R Ashrafi, P Modi, A Y Oo, D M Pullan, K Jian, H Zhang, J Yanni Gerges, G Hart, M R Boyett, G K Davis, J P H Wilding
Type 2 diabetes is associated with higher rate of ventricular arrhythmias and this is hypothesised to be independent of coronary artery disease or hypertension. To investigate further we compared changes in left ventricular myocardial gene expression in Type 2 diabetes to patients in a control group with left ventricular hypertrophy. 9 control patients and 7 patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal averaged ECGs and echocardiograms prior to surgery...
August 14, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28803378/qt-interval-prolongation-in-hospitalized-patients-on-cardiology-wards-a-prospective-observational-study
#6
Qasim Khan, Mohammad Ismail, Iqbal Haider, Inam Ul Haq, Sidra Noor
PURPOSE: Prolonged QT interval may lead to a lethal form of arrhythmia, torsades de pointes (TdP), which is associated with cardiovascular mortality. Therefore, we aimed to identify prevalence of QT interval prolongation, compare clinical characteristics of patients with normal and prolonged QT interval, and identify predictors of QT interval prolongation. METHODS: A prospective observational study was conducted in cardiology wards of two teaching hospitals in Pakistan...
August 12, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28801207/crediblemeds-org-what-does-it-offer
#7
REVIEW
Raymond L Woosley, Kristin Black, C William Heise, Klaus Romero
Since the 1990s, when numerous non-cardiac drugs were first recognized to have the potential to prolong the QT interval and cause torsades de pointes (TdP), clinicians, drug regulators, drug developers, and clinical investigators have become aware of the complexities of assessing evidence and determining TdP causality for the many drugs being marketed or under development. To facilitate better understanding, the Arizona Center for Education and Research on Therapeutics, known as AZCERT, has developed the CredibleMeds...
August 1, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28800275/polyphenol-rich-fraction-of-parquetina-nigrescens-mitigates-dichlorvos-induced-cardiorenal-dysfunction-through-reduction-in-cardiac-nitrotyrosine-and-renal-p38-expressions-in-wistar-rats
#8
Ademola A Oyagbemi, Temidayo O Omobowale, Grace O Ochigbo, Ebunoluwa R Asenuga, Olufunke Eunice Ola-Davies, Temitayo O Ajibade, Adebowale B Saba, Adeolu A Adedapo
Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined...
August 11, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28799823/lack-of-qt-prolongation-for-2-o-methoxyethyl-modified-antisense-oligonucleotides-based-on-retrospective-exposure-response-analysis-of-ten-phase-1-dose-escalation-placebo-controlled-studies-in-healthy-subjects
#9
Rosie Z Yu, Rudy Gunawan, Richard S Geary, Steven G Hughes, Scott P Henry, Yanfeng Wang
The potential of QT prolongation of ten 2'-O-methoxyethyl-modified (2'-MOE) antisense oligonucleotides (ASOs) was evaluated retrospectively via exposure/response (ER) analysis using data from Phase 1 clinical studies in healthy subjects. All Phase 1 studies were double-blind, placebo-controlled, single and multiple ascending dose studies designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the ASOs in healthy subjects. The active doses in these studies ranged from 50 to 450 mg administered by subcutaneous (SC) injection in single and multiple ascending dose cohorts...
August 11, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28798290/bradycardia-and-hypothermia-complicating-azithromycin-treatment
#10
Kerri Benn, Sam Salman, Madhu Page-Sharp, Timothy M E Davis, Jim P Buttery
BACKGROUND Azithromycin is a macrolide antibiotic widely used to treat respiratory, urogenital, and other infections. Gastrointestinal upset, headache, and dizziness are common adverse effects, and prolongation of the rate-corrected electrocardiographic QT interval and malignant arrhythmias have been reported. There are rare reports of bradycardia and hypothermia but not in the same patient. CASE REPORT A 4-year-old boy given intravenous azithromycin as part of treatment for febrile neutropenia complicating leukemia chemotherapy developed hypothermia (rectal temperature 35...
August 11, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28797793/bpc-157-counteracts-qtc-prolongation-induced-by-haloperidol-fluphenazine-clozapine-olanzapine-quetiapine-sulpiride-and-metoclopramide-in-rats
#11
Dean Strinic, Zeljka Belosic Halle, Kresimir Luetic, Ana Nedic, Igor Petrovic, Mario Sucic, Gordana Zivanovic Posilovic, Dijana Balenovic, Sanja Strbe, Mario Udovicic, Domagoj Drmic, Mirjana Stupnisek, Martina Lovric Bencic, Sven Seiwerth, Predrag Sikiric
AIM: Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. MAIN METHODS: To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0...
August 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/28794082/loss-of-function-kcne2-variants-true-monogenic-culprits-of-long-qt-syndrome-or-proarrhythmic-variants-requiring-secondary-provocation
#12
Jason D Roberts, Andrew D Krahn, Michael J Ackerman, Ram K Rohatgi, Arthur J Moss, Babak Nazer, Rafik Tadros, Brenda Gerull, Shubhayan Sanatani, Yanushi D Wijeyeratne, Alban-Elouen Baruteau, Alison R Muir, Benjamin Pang, Julia Cadrin-Tourigny, Mario Talajic, Lena Rivard, David J Tester, Taylor Liu, Isaac R Whitman, Julianne Wojciak, Susan Conacher, Lorne J Gula, Peter Leong-Sit, Jaimie Manlucu, Martin S Green, Robert Hamilton, Jeff S Healey, Coeli M Lopes, Elijah R Behr, Arthur A Wilde, Michael H Gollob, Melvin M Scheinman
BACKGROUND: Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the KCNE2-encoded voltage-gated channel β-subunit, is limited. We sought to further characterize its clinical phenotype. METHODS AND RESULTS: Individuals with reported pathogenic KCNE2 mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry. Previously reported LQT6 cases were identified through a search of the MEDLINE database...
August 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28793999/association-of-qt-prolonging-medication-use-in-ckd-with-electrocardiographic-manifestations
#13
Soren Snitker, Rebecca M Doerfler, Elsayed Z Soliman, Rajat Deo, Wendy L St Peter, Susan Kramlik, Michael J Fischer, Sankar Navaneethan, Patrice Delafontaine, Bernard G Jaar, Akinlolu Ojo, Gail K Makos, Anne Slaven, Matthew R Weir, Min Zhan, Jeffrey C Fink
BACKGROUND AND OBJECTIVES: Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogram QT-prolonging medications in predialysis CKD and their association with QT duration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 3252 Chronic Renal Insufficiency Cohort participants with at least one study electrocardiogram between 2003 and 2011 were included. QT-prolonging medications used in 100 or more visits (n=16,451 visits) along with diuretics and proton pump inhibitors, given their potential for electrolyte disturbances, were examined for QT interval prolongation...
August 9, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28791627/influence-of-intravenous-administration-of-the-antipsychotic-drug-benperidol-on-the-qt-interval
#14
Alexander Schmidt, Peter Fischer, Beate Wally, Joachim Scharfetter
A group effect is generally assumed regarding the prolongation of the QT interval through butyrophenone antipsychotics like haloperidol. Consequently intravenous administration of benperidol is seen critically notwithstanding sparse evidence; thus benperidol and haloperidol were compared regarding their cardiac risk of prolonging the QT interval when administered intravenously for acute sedation of psychotic patients. The QT interval was measured by a 12-lead ECG. For the correction of QT values Bazett's formula was used...
August 8, 2017: Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation
https://www.readbyqxmd.com/read/28783871/cardiac-safety-of-ozanimod-a-novel-sphingosine-1-phosphate-receptor-modulator-results-of-a-thorough-qt-qtc-study
#15
Jonathan Q Tran, Jeffrey P Hartung, Allan D Olson, Boaz Mendzelevski, Gregg A Timony, Marcus F Boehm, Robert J Peach, Sheila Gujrathi, Paul A Frohna
Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17...
August 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28782696/heritability-in-a-scn5a-mutation-founder-population-with-increased-female-susceptibility-to-non-nocturnal-ventricular-tachyarrhythmia-and-sudden-cardiac-death
#16
Rachel M A Ter Bekke, Aaron Isaacs, Andrei Barysenka, Marije B Hoos, Jan D H Jongbloed, Jan C A Hoorntje, Alfons S M Patelski, Apollonia T J M Helderman-van den Enden, Arthur van den Wijngaard, Monika Stoll, Paul G A Volders
BACKGROUND: Heritable cardiac sodium-channel dysfunction is associated with various arrhythmia syndromes, some predisposing to ventricular fibrillation. Phenotypic diversity among carriers of identical-by-descent mutations is often remarkable, suggesting influences of genetic modifiers. OBJECTIVE: We identified a unique SCN5A-mutation founder population with mixed clinical phenotypes and sudden cardiac death, and investigated the heritability of electromechanical traits besides the SCN5A-mutation effect...
August 3, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28776165/prolongation-of-the-qtc-interval-in-hiv-infected-individuals-compared-to-the-general-population
#17
Nico Reinsch, Marina Arendt, Marie Henrike Geisel, Christina Schulze, Volker Holzendorf, Anna Warnke, Till Neumann, Norbert H Brockmeyer, Dirk Schadendorf, Lewin Eisele, Raimund Erbel, Susanne Moebus, Karl-Heinz Jöckel, Stefan Esser
OBJECTIVES: Prolonged QT interval is associated with arrhythmias and sudden death. An increased prevalence of QT interval prolongation in human immunodeficiency virus-infected (HIV) subjects was previously described. The impact of different medications and HIV infection itself on the QT interval is rarely investigated in large HIV+ cohorts. METHODS: We compared QT interval measurement in 496 HIV(+) patients of the HIV-HEART study (HIVH) and 992 sex- and age-matched controls of the population-based German Heinz Nixdorf Recall study (HNR)...
August 3, 2017: Infection
https://www.readbyqxmd.com/read/28774576/synthesis-and-biological-investigation-of-tetrahydropyridopyrimidinone-derivatives-as-potential-multireceptor-atypical-antipsychotics
#18
Hainimu Xiamuxi, Zhen Wang, Jianfeng Li, Yu Wang, Chunhui Wu, Feipu Yang, Xiangrui Jiang, Yongjian Liu, Qingjie Zhao, Weiming Chen, Jian Zhang, Yuanchao Xie, Tianwen Hu, Mingshuo Xu, Shuang Guo, Haji Akber Aisa, Yang He, Jingshan Shen
In the present study, a series of tetrahydropyridopyrimidinone derivatives, possessing potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (10d) held the best pharmacological profile. It not only exhibited potent and balanced activities for D2, 5-HT1A, and 5-HT2A receptors, but was also endowed with low activities for α1A, 5-HT2C, H1 receptors and hERG channels, suggesting a low propensity for inducing orthostatic hypotension, weight gain and QT prolongation...
July 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28770276/a-comparative-study-of-qt-prolongation-with-serotonin-reuptake-inhibitors
#19
Ana Ojero-Senard, Justine Benevent, Emmanuelle Bondon-Guitton, Geneviève Durrieu, Leila Chebane, Melanie Araujo, Francois Montastruc, Jean-Louis Montastruc
BACKGROUND: QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). METHODS: Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected...
August 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28768059/-epicatechin-rescues-the-as2-o3-induced-herg-k-channel-deficiency-possibly-through-upregulating-transcription-factor-sp1-expression
#20
Zengxiang Dong, Yuanqi Shi, Lifang Feng, Zhaoqian Shen, Li Fang, Sijia Zheng, Xin Hai, Baoxin Li
(-)-Epicatechin (EPI) has beneficial effects on the cardiovascular disease. The human ether-a-go-go-related gene (HERG) potassium channel is crucial for repolarization of cardiac action potential. Dysfunction of the HERG channel can cause long QT syndrome type 2 (LQT2). Arsenic trioxide (As2 O3 ) has shown efficacy in the treatment of acute promyelocytic leukemia. However, As2 O3 can induce the deficiency of HERG channel and cause LQT2. In this study, we examined whether EPI could rescue the As2 O3 -induced HERG channel deficiency...
August 2, 2017: Journal of Biochemical and Molecular Toxicology
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