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We determined the role of p38 mitogen-activated protein kinase (MAPK), 72-kDa heat shock protein (HSP72), and antioxidant enzymes in whole body heat stress (HS)-induced cardioprotection in mouse hearts. Adult male mice were treated with either HS or anesthesia only. At 0.5, 48, 72, or 120 h later, the hearts were subjected to 20 min of global ischemia and 30 min of reperfusion in Langendorff mode. A significant protection against ischemia-reperfusion injury was observed 48 h after HS as demonstrated by: 1) reduction in infarct size; 2) decrease in leakage of lactate dehydrogenase; and 3) enhanced postischemic ventricular contractile function. No such protection was observed at other post-HS time points. HS caused an ~25% increase in phosphorylated c-Jun [NH.sub.2]-terminal kinase (JNK) but not p38 MAPK in the heart during the first 2-h post-HS time period. Cardioprotection was abolished by the MAPK inhibitor SB-203580, which also partially suppressed the HS-induced JNK phosphorylation. The protective effect was associated with a two- to threefold increase in HSP72 protein accumulation, but not antioxidant enzyme activities (catalase and Cu/Zn and Mn SOD) in the myocardium. Although HSP72 levels remained high 72 h after HS, the cardioprotection had already disappeared. We conclude that HS induces a transient delayed cardioprotection at 48 h after thermal stress in mice which appears to be mediated via a MAPK-signaling pathway. ischemia; reperfusion; signal transduction; antioxidants; myocardial preconditioning

Purpose To determine aspects of the design of pediatric registries that contribute to the success of registries conducted as a postmarketing study following approval of drugs or biological products by the US Food and Drug Administration. Methods Pediatric registries for drugs and biological products were identified by searching the US Food and Drug Administration Postmarketing Requirements and Commitments database. Based on the recruitment of patients, the meeting of predetermined deadlines, and the submission of data, we classified studies as successful, unsuccessful, or unevaluable. Design aspects of successful and unsuccessful registries were examined for commonalities. Results Thirty-eight studies were identified, and ten registries met the criteria for successful. Four (40%) successful registries utilized a registry established prior to product approval, and six (60%) were disease-based. Among unsuccessful registries, none were disease-based or utilized a pre-existing registry. Conclusions Characteristics identified as more common to successful registries included utilizing a disease-based registry and a registry established prior to product approval. Future studies might examine a larger sample of registries to see if these aspects consistently result in successful studies. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]