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https://www.readbyqxmd.com/read/29139267/-preparation-of-nanosuspension-of-quercetin-with-a-miniaturized-milling-method
#1
Xiao Liu, Juan Liu, Jian-Yun Pang, Bao-de Shen, Cheng-Ying Shen, Wang-Quan Lian, Xiao-Fang Li, Hai-Long Yuan
The nanosuspension of quercetin (QT-NS) was prepared by a miniaturized milling method, and the process was optimized by Box-Behnken response surface method. Then the accumulative release rate of QT-NS in vitro was determined. The results showed that the optimal process parameters were as follows: ZrO2 4.5 mL, milling speed 690 r•min⁻¹ and milling time 1.5 h; the particle size of QT-NS was (169±5) nm, polydispersity index of 0.204±0.006 and stability index of 0.827±0.014, respectively. There was a little deviation between the theoretically predicted value and the measured value, indicating that this model had a good prediction effect...
August 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29139041/drug-safety-analysis-in-a-real-life-cohort-of-parkinson-s-disease-patients-with-polypharmacy
#2
Saskia Müller-Rebstein, Claudia Trenkwalder, Jens Ebentheuer, Wolfgang H Oertel, Carsten Culmsee, Günter U Höglinger
BACKGROUND: Polypharmacy is common in geriatric Parkinson's disease (PD) patients in advanced disease stages with multiple comorbidities, bearing multiple risks for drug safety in theory. OBJECTIVE: The aim of this study was to empirically identify the most frequent and relevant contraindications and drug interactions actually occurring and compromising drug safety in PD in real life. METHODS: We conducted a prospective observational study in a multimorbid cohort of PD patients with polypharmacy admitted to a specialized hospital...
November 14, 2017: CNS Drugs
https://www.readbyqxmd.com/read/29133340/effects-of-hawthorn-crataegus-pentagyna-leaf-extract-on-electrophysiologic-properties-of-cardiomyocytes-derived-from-human-cardiac-arrhythmia-specific-induced-pluripotent-stem-cells
#3
Sara Pahlavan, Marziyeh Shalchi Tousi, Mahdi Ayyari, Abolfazl Alirezalu, Hassan Ansari, Tomo Saric, Hossein Baharvand
Cardiac arrhythmias are major life-threatening conditions. The landmark discovery of induced pluripotent stem cells has provided a promising in vitro system for modeling hereditary cardiac arrhythmias as well as drug development and toxicity testing. Nowadays, nutraceuticals are frequently used as supplements for cardiovascular therapy. Here we studied the cardiac effects of hawthorn (Crataegus pentagyna) leaf extract using cardiomyocytes (CMs) differentiated from healthy human embryonic stem cells, long QT syndrome type 2 (LQTS2), and catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) patient-specific induced pluripotent stem cells...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127493/late-sodium-current-associated-cardiac-electrophysiological-and-mechanical-dysfunction
#4
REVIEW
Shandong Yu, Gang Li, Christopher L-H Huang, Ming Lei, Lin Wu
Late sodium current (INaL) is a small sustained inward current observed during the cardiac action potential plateau phase following decay of the early peak INa. The endogenous INaL is relatively small in normal hearts but exerts functionally significant effects on cardiomyocyte repolarization with potentially pro-arrhythmic effects in hearts with reduced repolarization reserve. Enhanced INa,L occurs in long QT syndrome 3 (LQTS 3) patients, and under a number of pathological and pharmacological cardiovascular conditions, including bradycardia, myocardial ischemia, reperfusion injury, and heart failure...
November 10, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29126124/predicting-drug-safety-and-communicating-risk-benefits-of-a-bayesian-approach
#5
Stanley E Lazic, Nicholas Edmunds, Christopher E Pollard
Drug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk...
November 6, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29116540/long-term-safety-of-long-acting-octreotide-in-patients-with-diabetic-retinopathy-results-of-pooled-data-from-2-randomized-double-blind-placebo-controlled-phase-3-studies
#6
Rosario Pivonello, Giovanna Muscogiuri, Geoffrey Holder, Michaela Paul, Severine Sarp, Anastasia Lesogor, Pierre Jordaan, Johannes Eisinger, Annamaria Colao
PURPOSE: Octreotide (OCT) has been successfully used for treatment of acromegaly and neuroendocrine tumors for more than 30 years. However, long-term safety of OCT has not been documented in placebo-controlled setting. This present analysis pooled safety data from two similarly-designed, randomized, and placebo-controlled studies to evaluate long-term safety of long-acting OCT (20, 30 mg); targeted post-hoc analyzes focused on cardiac, hepatic, and renal safety. METHODS: Two studies (NCT00131144, NCT001308450) were conducted in patients with diabetic retinopathy (OCT20 = 191, OCT30 = 348, placebo = 347)...
November 7, 2017: Endocrine
https://www.readbyqxmd.com/read/29110351/posaconazole-liquid-vs-tablet-formulation-in-lung-transplant-recipients
#7
D Telzer, A Weber, F Ihle, S Matthes, F Ceelen, G Zimmermann, N Kneidinger, R Schramm, H Winter, M Zoller, M Vogeser, J Behr, C Neurohr
BACKGROUND: Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). OBJECTIVES: The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity, and pharmacokinetics of POS-Liq vs. POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently...
November 6, 2017: Mycoses
https://www.readbyqxmd.com/read/29107482/prevalence-and-outcome-of-high-risk-qt-prolongation-recorded-in-the-emergency-department-from-an-institution-wide-qt-alert-system
#8
Heather N Anderson, J Martijn Bos, Kristina H Haugaa, Bruce W Morlan, Robert F Tarrell, Pedro J Caraballo, Michael J Ackerman
BACKGROUND: QT prolongation is an independent risk factor for sudden death, stroke, and all-cause mortality. However, additional studies have shown that in certain settings, QT prolongation may be transient and a result of external factors. OBJECTIVE: In this study, we evaluated the clinical characteristics and outcomes of patients seen in the emergency department (ED) with QT prolongation. METHODS: Between November 2010 and June 2011, 7522 patients had an electrocardiogram (ECG) obtained during their evaluation in the ED...
October 26, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29104543/simultaneous-quantification-of-spatially-discordant-alternans-in-voltage-and-intracellular-calcium-in-langendorff-perfused-rabbit-hearts-and-inconsistencies-with-models-of-cardiac-action-potentials-and-ca-transients
#9
Ilija Uzelac, Yanyan C Ji, Daniel Hornung, Johannes Schröder-Scheteling, Stefan Luther, Richard A Gray, Elizabeth M Cherry, Flavio H Fenton
Rationale: Discordant alternans, a phenomenon in which the action potential duration (APDs) and/or intracellular calcium transient durations (CaDs) in different spatial regions of cardiac tissue are out of phase, present a dynamical instability for complex spatial dispersion that can be associated with long-QT syndrome (LQTS) and the initiation of reentrant arrhythmias. Because the use of numerical simulations to investigate arrhythmic effects, such as acquired LQTS by drugs is beginning to be studied by the FDA, it is crucial to validate mathematical models that may be used during this process...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29103053/domperidone-for-hypotension-in-parkinson-s-disease-a-systematic-review
#10
Stephen Bacchi, Ivana Chim, Philippe Kramer, Ronald B Postuma
BACKGROUND: Domperidone is a proposed treatment of orthostatic hypotension (OH) in Parkinson's disease (PD). However, domperidone use in PD is tempered by concerns regarding QT prolongation and ventricular tachyarrhythmia and sudden cardiac death (VT/SCD). OBJECTIVE: The aim is to identify peer-reviewed studies in which either (1) the effect of domperidone on blood pressure in patients with PD, or (2) the adverse effects associated with domperidone use in PD patients has been reported...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/29095381/ventricular-tachycardia-induced-by-propafenone-intoxication-in-a-pediatric-patient
#11
Margherita Rosa, Serena Pappacoda, Carolina DʼAnna, Onorina Di Mita, Eduardo Ponticiello, Pierluigi Marzuillo, Vincenzo Tipo
Unintentional poisonings are a global health problem frequently resulting in hospital admissions. Propafenone is a class 1C antiarrhythmic drug used in the second-line management of supraventricular and ventricular arrhythmias and, when unintentionally ingested, can lead to severe and life-threatening poisoning. We describe a case of a 3-year-old male patient unintentionally ingesting 300 mg (20 mg/kg) of propafenone and presenting with ventricular tachycardia with QT prolongation. Two boli of intravenous hypertonic sodium bicarbonate (total amount of 3 mEq/kg), followed by 3-hours continuous infusion of 1 mEq kg h sodium bicarbonate, were able to restore the clinical conditions of the patient...
October 31, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/29089623/enzalutamide-inhibits-testosterone-induced-growth-of-human-prostate-cancer-xenografts-in-zebrafish-and-can-induce-bradycardia
#12
Nicole Melong, Shelby Steele, Morgan MacDonald, Alice Holly, Colin C Collins, Amina Zoubeidi, Jason N Berman, Graham Dellaire
The zebrafish has become a popular human tumour xenograft model, particularly for solid tumours including prostate cancer (PCa). To date PCa xenotransplantation studies in zebrafish have not been performed in the presence of testosterone, even when employing androgen-dependent cell models, such as the LNCaP cell line. Thus, with the goal of more faithfully modelling the hormonal milieu in which PCa develops in humans, we sought to determine the effects of exogenous testosterone on the growth of LNCaP, or androgen-independent C4-2 cells xenografted into zebrafish embryos...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29066038/assessing-responsiveness-of-health-systems-to-drug-safety-warnings
#13
Lauren B Gerlach, Hyungjin Myra Kim, Matheos Yosef, Anne E Sales, Claire Stano, Helen C Kales, Kara Zivin
OBJECTIVE: In 2011-2012 the U.S. Food and Drug Administration (FDA) issued safety announcements cautioning providers against prescribing high doses of citalopram given concerns for QT prolongation. The authors evaluated Veterans Affairs (VA) national trends in citalopram use and dose compared with alternative antidepressants after the FDA warnings. METHODS: Time series analyses estimated the effect of the FDA warnings on citalopram and other antidepressant across three periods: before the first FDA warning in August 2011, after the 2011 FDA warning until the second warning in March 2012, and after the 2012 FDA warning...
September 28, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/29061081/pharmacogenetics-of-trazodone-in-healthy-volunteers-association-with-pharmacokinetics-pharmacodynamics-and-safety
#14
Miriam Saiz-Rodríguez, Carmen Belmonte, Nieves Derqui-Fernández, Teresa Cabaleiro, Manuel Román, Dolores Ochoa, María Talegón, María C Ovejero-Benito, Francisco Abad-Santos
AIM: The aim was to evaluate the effect of polymorphisms in metabolizing enzymes and transporters on the pharmacokinetics, pharmacodynamics and adverse effects of trazodone in healthy volunteers. MATERIALS & METHODS: 36 healthy volunteers receiving a single 100-mg oral dose of trazodone were genotyped for 11 variants in CYP3A4, CYP3A5, CYP2D6 and ABCB1 by real-time PCR. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry method...
October 24, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29059199/effectiveness-of-beta-blockers-depending-on-the-genotype-of-congenital-long-qt-syndrome-a-meta-analysis
#15
Jinhee Ahn, Hyun Jung Kim, Jong-Il Choi, Kwang No Lee, Jaemin Shim, Hyeong Sik Ahn, Young-Hoon Kim
BACKGROUND: Beta-blockers are first-line therapy in patients with congenital long-QT syndrome (LQTS). OBJECTIVE: This study sought to determine the differences in effectiveness of beta-blockers on risk reduction according to LQTS genotype. METHODS: We searched MEDLINE, EMBASE, and CENTRAL databases to investigate the use of beta-blockers (atenolol, nadolol, propranolol, and metoprolol) in patients with LQTS. Hazard ratio (HR) and relative risk (RR) were extracted or calculated from studies reporting cardiac events (syncope, aborted cardiac arrest (ACA), or sudden cardiac death (SCD))...
2017: PloS One
https://www.readbyqxmd.com/read/29058821/a-thorough-qt-study-to-evaluate-the-effects-of-supratherapeutic-doses-of-ledipasvir-on-the-qtc-interval-in-healthy-subjects
#16
Polina German, Anita Mathias, Diana M Brainard, Qinghua Song, John Ling, Brian P Kearney
This study evaluated the effect of supratherapeutic exposure of the anti-HCV drug ledipasvir on the QTc interval in healthy subjects. Sixty healthy volunteers were randomized to receive twice-daily blinded ledipasvir (120 mg) or placebo, administered for 10 days each, or single doses of open-label moxifloxacin (400 mg). Serial plasma samples for ledipasvir concentration analysis were collected after each treatment. Triplicate time-matched electrocardiograms were collected at baseline and after each treatment...
October 23, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29058180/studying-kcnq1-mutation-and-drug-response-in-type-1-long-qt-syndrome-using-patient-specific-induced-pluripotent-stem-cell-derived-cardiomyocytes
#17
Heming Wei, Jianjun Wu, Zhenfeng Liu
Patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) are becoming a valuable model for studying inherited cardiac arrhythmias. Type 1 long-QT syndrome is associated with the genetic variants of KCNQ1 gene that encodes Kv7.1, the α-subunit of the voltage-gated potassium channel QKT subfamily member 1 that channels the slow component of the outwardly rectifying K(+) channel current in cardiac myocytes. Patient- or disease-specific hiPSC-CM model could facilitate the characterization of the genotype-phenotype relationships and testing of individualized drug responses...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29057715/structural-and-functional-alterations-of-the-heart-in-parkinson-s-disease
#18
Jesús Piqueras-Flores, Ana López-García, Álvaro Moreno-Reig, Alicia González-Martínez, Amalia Hernández-González, Julia Vaamonde-Gamo, Alfonso Jurado-Román
Parkinson's disease (PD) patients have most frequently heart failure. The cause of this increased prevalence is not known. We designed a study to assess the cardiac function and cardiac structure in patients with PD compared to a control group. METHODS: Cross-sectional study with 50 PD patients and 50 healthy matched controls. We performed electro and echocardiograms to all patients and controls. The measurements were blind. In addition, we performed a neurological assessment. RESULTS: PD patients had higher left ventricular mass index (114...
October 23, 2017: Neurological Research
https://www.readbyqxmd.com/read/29042382/drugs-and-life-threatening-ventricular-arrhythmia-risk-results-from-the-dare-study-cohort
#19
Abigail L Coughtrie, Elijah R Behr, Deborah Layton, Vanessa Marshall, A John Camm, Saad A W Shakir
OBJECTIVES: To establish a unique sample of proarrhythmia cases, determine the characteristics of cases and estimate the contribution of individual drugs to the incidence of proarrhythmia within these cases. SETTING: Suspected proarrhythmia cases were referred by cardiologists across England between 2003 and 2011. Information on demography, symptoms, prior medical and drug histories and data from hospital notes were collected. PARTICIPANTS: Two expert cardiologists reviewed data for 293 referred cases: 130 were included...
October 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29037240/kh176-under-development-for-rare-mitochondrial-disease-a-first-in-man-randomized-controlled-clinical-trial-in-healthy-male-volunteers
#20
Saskia Koene, Edwin Spaans, Luc Van Bortel, Griet Van Lancker, Brant Delafontaine, Fabio Badilini, Julien Beyrath, Jan Smeitink
BACKGROUND: Mitochondrial disorders are a clinically, biochemically and genetically heterogeneous group of multi-system diseases, with an unmet medical need for treatment. KH176 is an orally bio-available small molecule under development for the treatment of mitochondrial(-related) diseases. The compound is a member of a new class of drugs, acting as a potent intracellular redox-modulating agent essential for the control of oxidative and redox pathologies. The aim of this randomized, placebo controlled, double-blinded phase 1 study was to test safety, tolerability and pharmacokinetics of single and multiple doses of KH176 in healthy male volunteers...
October 16, 2017: Orphanet Journal of Rare Diseases
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