This study was designed to elucidate the possible mechanisms underlying these two electrophysiological profiles. Methods: Effects of representative torsadogenic agents and non torsadogenic drugs on IK(r), IK(s), IK(1), I(Na) and I(CaL) were studied in transfected HEK 293 cells using the path-clamp method as

well as in conscious beagle dogs and cynomolgus monkeys by telemetry. Results: Patch-clamp studies confirmed that torsadogenic molecules could be discriminated into at least two subgroups. The first subgroup can be defined as apparently pure blockers. The second subgroup can be defined as I(Kr) blockers with ancillary properties on sodium and/or calcium channels which counterbalance the I(Kr) MAPK inhibitor prolongation component. This discrimination is transposable to the telemetered cynomolgus monkey model in terms of QT prolongation but not to the telemetered beagle dog model. This latter inter-species difference could be related to the sympathetic/parasympathetic balance and could involve

reserve repolarisation dependent mechanisms. Discussion: The confirmation that torsadogenic drugs might have at least two different electrophysiological profiles should be taken CUDC-907 price into consideration in preclinical safety pharmacology studies because it increases the value of the cynomolgus monkey model in two particular situations: firstly when an NCE causes sympathetic activation and secondly, when an NCE exhibits a pure blocker pattern independently of its potency to block HERG channels. (C) 2011 Elsevier Inc. All rights reserved.”
“Posterior spinal ligament pathology is becoming increasingly recognized as a significant cause of low back pain. Despite the growing clinical importance of interspinous ligament degeneration in low back pain click here patients, formal reliability studies for the magnetic resonance imaging (MRI) evaluation of interspinous ligaments have not been performed. We proposed an MRI classification system for interspinous ligament degeneration and conducted a comprehensive reliability and reproducibility assessment. Fifty patients who had low back pain with or without leg discomfort (26 males and

24 females) with a mean age of 48.8 years (range 23-85 years) were studied. The classification for lumbar interspinous ligament degeneration was developed on the basis of the literature using mid-sagittal T1- and T2-weighted images. Three spine surgeons independently graded a total of 200 interspinous ligament levels. Intraobserver and interobserver reliability were assessed by kappa statistics. The frequency of disagreement was also identified. The intraobserver agreement was excellent in all readers (kappa range 0.840-0.901). The interobserver agreement was lower as expected, and was substantial to excellent (kappa range 0.726-0.818). Overall complete agreement was obtained in 87.8% of all interspinous ligament levels. A difference of 1, 2, and 3 grades occurred in 8.1, 3.0, and 1.1% of readings, respectively.