(C) 2009 Society of Chemical Industry”
“Introduction: Drug-induced glucose dysregulation and insulin resistance have been associated with weight gain and potential induction and/or exacerbation of diabetes mellitus in the clinic suggesting they may be safety biomarkers when developing antipsychotics. Glucose and insulin have also been suggested as potential efficacy biomarkers for some oncology compounds. The objective of check details this study was to qualify a medium throughput rat in vivo acute Intravenous Glucose Tolerance Test (IVGTT)
for predicting compounds that will induce altered blood glucose and/or insulin levels. Methods: Acute and sub-chronic studies were performed to qualify an acute IVGTT model. Double cannulated male rats (Han-Wistar and Sprague-Dawley) were administered vehicle, olanzapine, aripiprazole or other compounds at t = -44 min for acute studies and at time = -44 min on the last day of dosing for sub-chronic studies, treated with dextrose (time = 0 min; i.v.) and blood collected using an automated Culex (R) system for glucose and insulin analysis (time = -45, -1, 2, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180 min). Results: Olanzapine significantly increased glucose
and insulin area under TPX-0005 Protein Tyrosine Kinase inhibitor the curve (AUC) values while aripiprazole AUC values were similar to control, in both acute and sub-chronic studies. All atypical antipsychotics evaluated were consistent with literature references of clinical weight gain. As efficacy biomarkers, insulin AUC but not glucose AUC values were increased with a compound known to have insulin growth factor-1 (IGF-1) activity, compared to control treatment. Discussion: These studies qualified the medium throughput acute IVGTT model to more quickly screen compounds for 1) safety – the potential to elicit LY2603618 glucose dysregulation and/or insulin resistance and 2) efficacy – as a surrogate for compounds affecting the glucose and/or insulin regulatory pathways. These data demonstrate that the same in vivo rat model and assays can be used to predict both clinical safety and efficacy of compounds. (C) 2013 Elsevier Inc. All rights
“Radical cystectomy is associated with the highest morbidity and mortality of all commonly performed urological cancer treatment procedures. Postoperative infection remains a major problem. We herein report the results of an open prospective study involving radical cystectomies, undertaken to evaluate the efficacy of 0.5/2 g tazobactam-piperacillin (TAZ-PIPC) in the prevention of postoperative infectious complications. Antimicrobial prophylaxis was performed using 0.5/2 g TAZ-PIPC (2.5 g i.v.) every 3 h during surgery and then twice a day for 3 days postoperatively. The patients were monitored to detect any postoperative infections. During surgery, irrigation fluid from the total abdominal cavity was taken for bacterial culture just before closing the abdomen.