TRAUMA: REGULATORS AND MODULATORS OF THE CATABOLIC STATE

本提案将侧重于一系列事件中的各个步骤， 表征炎症、代谢和免疫反应， 外伤 各种假设将被测试：这些研究 可以提供潜在的逆转分解代谢组织破坏性的见解， 与意外伤害相关的过程，从而降低发病率， mortality. 其中一个项目将研究细胞和分子机制 与骨骼肌的胰岛素抵抗有关。 第二个项目 将评估受伤、饥饿和败血症后的肌肉能量学 使用核磁共振光谱。 潜在治疗 还将研究扭转这些反应的措施。 调解人 将检测内毒素的作用， 将确定糖皮质激素对这些反应的影响。 的产生 内毒素给药后的特异性细胞因子将通过 表征循环细胞中的信使RNA。 其他已知可增强免疫功能的方式，如 生长激素和白细胞介素-2（IL-2）与布洛芬联合使用将 在对照试验中对创伤患者进行治疗。 免疫 函数沿着其他端点（如 败血症发作的频率。 该中心的最后一个研究领域是 确定组织氧化在创伤后脓毒症和器官损伤中的作用 失败 将测试各种模式，包括管理 胃肠外或局部抗氧化剂对表面损伤的影响，以确定组织 可以防止损伤和/或逆转这种组织破坏过程。 所有这些研究将在各个实验室进行， 获得一个中心核心设施，以提高这一效率， 联合研究小组。

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.