Methods: RIP calibration data were generated in conscious, ketamine-sedated, or propofol-anesthetized NHP to determine the most appropriate method. Calibration accuracy was assessed using a CO2 rebreathe maneuver. Regardless of the technique, the RIP system reliably demonstrated accurate assessment

of the CO2 rebreathe response when expressed as a percent change with respect to control. Four male NHP were given single oral doses of vehicle, 1.25 and 5 mg/kg test article followed by 20 mg/kg repeatedly for 7 days. Telemetry-derived cardiovascular parameters (PR, QRS, QT, heart rate corrected QT (QTcR) intervals, blood pressure [BP], and heart eFT-508 rate [HR]) and RIP-derived respiratory parameters (respiration rate [RR], tidal

volume [TV], and minute volume [MV]) were determined for 24 h pretest, 2 h predose and 24 h postdose. Results: A single dose of the test article at 5 or 20 mg/kg was associated with slight increases in HR, BP, RR, and MV at 2 to 7 h postdose, followed by decreases in HR, RR, TV, and MV at 5-23 h postdose. Decreases inHR, RR, TV, and MV were observed following 7 days of dosing at 20 mg/kg. Slight QTcR prolongation at 1 to 11 h postdose was observed following a single dose of 20 mg/kg. Conclusion: These data show that the integrated assessment of cardiovascular and respiratory parameters in NHP is achievable continuously for at least 24 h postdose. The use of RIP as a method to assess the effects of a novel compound on the respiratory system complements, but VS-6063 chemical structure does not interfere with, the

cardiovascular assessment of new drugs. (C) 2012 Elsevier Inc. All rights reserved.”
“OBJECTIVE: Dengue is a worldwide public health problem with approximately 50 million cases reported annually. The World Health Organization proposed a revised classification system in 2008 to more effectively identify the patients who are at increased risk of complications from dengue. Few studies have validated this new classification system in clinical practice. We conducted a cross-sectional study of patients hospitalized for dengue Protein Tyrosine Kinase inhibitor in Dourados, Mato Grosso do Sul, Brazil, to evaluate the capacity of the two classification systems for detecting severe cases of dengue.

MATERIALS AND METHODS: We conducted a cross-sectional study of survey data from the medical records of patients admitted to the University Hospital of the Federal University of Grande Dourados under clinical suspicion of dengue during an epidemic from September 2009 to April 2010.

RESULTS: The distribution of patients according to the traditional classification system was as follows: dengue fever, 150/181 (82.9%); dengue hemorrhagic fever, 27/181 (14.9%); and dengue hemorrhagic shock, 4/181 (2.2%).