The purpose of this study was ( 1) to evaluate the sensitivity of a new, fully implantable telemetry device, and ( 2) to highlight the importance of the device to simultaneously measure cardiac output and left ventricular pressure in order to adequately evaluate the full potential for a drug to impact global cardiovascular function. Methods: 4 dogs were instrumented with Konigsberg Instruments, Inc. (KI) TU7/T27H series fully implantable telemetry device and recovered

for > 8 weeks. Sotalol ( 8 mg/kg), milrinone ( 0.2 mg/kg), hydralazine ( 0.2 mg/kg) and control were administered 1 week apart. Data were collected for 1 h pre- and 24 h post-treatment and time-averaged to fully characterize the a priori pharmacodynamic effects of interest for each drug. This included PR and QTci (sotalol); HR, AOP and LVP ( milrinone); HR, AOP, CO and systemic vascular resistance (SVR) ( ABT-263 clinical trial hydralazine). NSC 66389 Results: Expected changes in CV parameters were observed following all drugs with the following detection sensitivities: PR and QTci of 4 ms and 3 ms, respectively ( sotalol); AOP and

LVP dP/dt+(max) of 5 mm Hg and 232mm Hg/s, respectively ( milrinone); HR, CO and SVR of 11 bpm, 0.302 l/min and 5mmHg*min/l, respectively ( hydralazine). Discussion: KI TU7/T27H implant detects drug-induced CV changes with statistical significance using a standard, four-subject design. The ability of the TU7/T27H to also measure CO and LVP allowed for full characterization of the CV impact of hydralazine and milrinone, which could have been misinterpreted/missed altogether if these drugs were novel and the endpoints evaluated were prospectively limited to the minimum suggested in ICH S7A. (C) 2014 Elsevier

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“Three bisbenzylisoquinoline alkaloids were isolated for the first time from Stephania rotunda tuber. Their structures were elucidated by spectroscopic methods and their antiplasmodial activity was investigated in vitro on CAL-101 cost chloroquine resistant Plasmodium falciparum strain W2. These alkaloids were identified as 2-norcepharanthine (1), cepharanoline (2) and fangchinoline (3). In vitro, they displayed significant antiplasmodial activity with inhibitory concentration 50 values of 0.3, 0.2 and 0.3 mu M.”
“Introduction: Voltage- and state-dependent blocks are important mechanisms by which drugs affect voltage-gated ionic channels. However, spontaneous (i.e. drug-free) time-dependent changes in the activation and inactivation of hERG and Na+ channels have been reported when using conventional whole-cell patch-clamp in HEK-293 cells. Methods: hERG channels were heterologously expressed in HEK-293 cells and in Xenopus laevis oocytes.