TRAUMA: REGULATORS AND MODULATORS OF THE CATABOLIC STATE

该提案将侧重于事件链中的各个步骤，这些事件 描述炎症、代谢和免疫学反应 创伤性损伤。各种假设将得到检验：这些研究 可能提供潜在逆转分解代谢组织破坏性的洞察力 与意外伤害相关的过程，从而减少发病率和 死亡率。其中一个项目将研究细胞和分子机制。 与骨骼肌中的胰岛素抵抗有关。第二个项目 将评估损伤、饥饿和脓毒症后的肌肉能量学 使用核磁共振波谱。潜在的治疗方法 还将研究扭转这些反应的措施。的调解人 将检测内毒素的作用，并观察其抑制作用 糖皮质激素对这些反应的影响将被确定。新一代人 内毒素注射后的特定细胞因子将通过以下方式确定 循环细胞中信使核糖核酸的特征。 其他已知的增强免疫功能的方法，如 生长激素和白介素2(IL-2)与布洛芬联合应用 在对照试验中用于创伤患者。免疫学 函数以及其他终结点(如 败血症发作的频率。这个中心的最后一个研究领域是 确定组织氧化在创伤性脓毒症和器官损伤中的作用 失败了。将测试各种模式，包括管理 肠外或主题抗氧化剂对表面的损伤，以确定组织是否 可以防止伤害和/或扭转这种破坏组织的过程。 所有这些研究都将在单独的实验室进行， 获得中央核心设施，以加强这项工作的有效性 联合课题组。

This proposal will focus on the various steps in the chain of events which characterize the inflammatory, metabolic and immunologic responses to traumatic injury. A variety of hypotheses will be tested: these studies may provide insight to potentially reverse the catabolic tissue-destructive process associated with accidental injury and thereby reduce morbidity and mortality. One project will examine the cellular and molecular mechanisms associated with insulin resistance in skeletal muscle. A second project will evaluate muscle energetics following injury, starvation and sepsis using nuclear magnetic resonance spectroscopy. Potential therapeutic measures to reverse these responses will also be studied. The mediators of the effects of endotoxin will be examined and the suppressive role of glucocorticoids on these responses will be determined. The generation of specific cytokines following endotoxin administration will be determined by characterizing the messenger RNA in circulating cells. Other modalities which are known to enhance immunologic function such as growth hormone and interleukin-2 (IL-2) combined with ibuprofen will be administered in trauma patients in controlled trials. Immunological function will be monitored, along with other endpoints such as the frequency of septic episodes. The final area of study in this Center is to determine the role of tissue oxidation in posttraumatic sepsis and organ failure. A variety of modalities will be tested, including administering parenteral or topic antioxidants to surface injury, to determine if tissue injury can be prevented and/or this tissue-destructive process reversed. All of these studies will be carried out in individual laboratories with access to a central core of facilities to enhance the effectiveness of this combined research group.