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Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam,(More)
Using time-related phenotypic data, methods of composite interval mapping and multiple-trait composite interval mapping based on least squares were applied to map quantitative trait loci (QTL) underlying the development of tiller number in rice. A recombinant inbred population and a corresponding saturated molecular marker linkage map were constructed for(More)
Cellular and ionic causes of variability in the electrophysiological activity of hearts from individuals of the same species are unknown. However, improved understanding of this variability is key to enable prediction of the response of specific hearts to disease and therapies. Limitations of current mathematical modeling and experimental techniques hamper(More)
BACKGROUND AND PURPOSE The regulatory guidelines (ICHS7B) recommending inhibition of the delayed rectifier K(+) current (I(Kr)), carried by human ether-a-go-go-related gene (hERG) channels in cardiac cells (the hERG test), as a 'first line' test for identifying compounds inducing QT prolongation, have limitations, some of which are outlined here. (More)
INTRODUCTION In the present study, we investigated whether a new biomarker - index of cardiac electrophysiological balance (iCEB=QT/QRS) - could predict drug-induced cardiac arrhythmias (CAs), including ventricular tachycardia/ventricular fibrillation (VT/VF) and Torsades de Pointes (TdPs). METHODS The rabbit left ventricular arterially-perfused-wedge was(More)
BACKGROUND Recently a new risk marker for drug-induced arrhythmias called index of cardio-electrophysiological balance (iCEB), measured as QT interval divided by QRS duration, was evaluated in an animal model. It was hypothesized that iCEB is equivalent to the cardiac wavelength λ (λ = effective refractory period (ERP) x conduction velocity) and that an(More)
The prolongation of the ventricular repolarization and proarrhythmic effects (Torsade de Pointes: TdP) of five reference antibiotics were compared in four in-vitro models. 1. Using the patch clamp technique on the human ether-a-gogo-related gene (HERG) current, the rank order for blockade of the HERG-current (IC(50)) was: sparfloxacin (44(More)
Unexpected induction of arrhythmias in the heart is still one of the major risks of new drugs despite recent improvements in cardiac safety assays. Here we address this in a novel emerging assay system. Eleven reference compounds were administrated to spontaneously beating clusters of cardiomyocytes from human pluripotent stem cells (hPSC-CM) and the(More)
INTRODUCTION Although isolated Purkinje fibers (PFs) often are used to evaluate the electrophysiologic effects of new drugs in terms of prolongation of action potential duration (APD) and induction of early afterdepolarizations (EADs), species differences in this respect remain elusive. We evaluated potential species-specific differences in drug-induced(More)
In addition to in silico and in vitro measurements, cardiac electrophysiology in experimental animals plays a decisive role in the selection of a potential 'cardio-safe' new chemical entity (NCE). The present synopsis critically reviews such in vivo techniques in experimental animals. In anaesthetized guinea-pigs, surface ECG recordings readily identify the(More)