Lactate dehydrogenase leakage was measured as an indicator of OGD-induced injury in PC12 cells

nses in humans. 1 Efficacy Testing in Rodent Models of T1D Given the broad evolutionary conservation of MedChemExpress PF-562271 immune mechanisms between rodents and humans, a well-understood and properly applied rodent model is useful in providing tools for studying possible pathogenic mechanisms and therapeutic interventions. Many studies have demonstrated efficacy in the prevention and/or reversal of spontaneous T1D in rodent models. Noting the many differences between rodents and humans, it is also not surprising that some of these mechanisms operating in rodents may ultimately fail in human clinical trials for T1D prevention or reversal. It is also expected that some mechanisms important for human disease will be missed if the particular rodent models, e.g., the NOD mouse, is exclusively relied upon, or conversely, that enthusiasm for interventions with real therapeutic potential in humans may be dampened by poor results in a rodent study. Neither of these caveats justifies abandoning rodent models, but they must be acknowledged. In addition to the limitations imposed by the differences in biology of rodents and humans, methodological factors also play a part in determining the usefulness of 10336542 animal models. As reported by Landis and colleagues, a systematic review and meta-analysis of published animal studies revealed that inadequate reporting correlated with failures of rodent models to predict clinical success. For example, deficient methodological reporting correlated with overstated findings, while studies that reported randomization and blinding of animal experiments tended to show smaller effect sizes of tested agents. This suggests that methodological flaws in animal model studies could be common, and suggests that the animal models literature should be cautiously approached. The aim of each animal study and its methods must be carefully considered when interpreting the power of the results for predicting clinical trial success. This is an important problem because animal studies often provide part of the preclinical data used to justify clinical trials, and if they are inadequate, they might add to unnecessary risks for subjects, and waste research resources. Of course, a thorough review of available and relevant animal data is a responsibility shared by translational researchers and regulatory agencies. We attempted to address the issue of consistency in study design, reporting, and interpretation of results by funding an independent testing laboratory using internally standardized and validated methods for preclinical testing of potential therapies in the spontaneous NOD mouse and BB rat models. We established the testing program with the intent to publish all results, whether positive or negative, hoping to reduce publication bias in favor of “positive” findings, and to make study results freely available to 20590636 the research community. Scientists developing agents may not have access to the most appropriate animal models for efficacy testing in T1D. To fill this gap, NIDDK established a contract with Biomedical Research Models, Inc., to provide preclinical testing of agents for efficacy in reversing or preventing T1D in rodents. NIDDK issued a Request for Information that provided a pathway for scientists to propose agents for testing. Proposed agents were reviewed for program applicability and translational potential by an independent review committee. In this initial stage of the testing program, we emphasized testing of agents for which there was