HOST DEFENSE MECHANISM--CONTROL OF SURGICAL INFECTION

宿主防御机制——手术感染的控制

• 批准号: 3125330
• 负责人: J. WESLEY ALEXANDER
• 金额: $ 47.73万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-05-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3125330
• 关键词: Candida albicans; Escherichia coli; Pseudomonas aeruginosa; Staphylococcus aureus; allopurinol; autoradiography; bactericidal immunity; binding proteins; bioenergetics; burns; carbon; cortisone; diet therapy; dietary fiber; dietary lipid; disease /disorder model; endotoxins; gastrointestinal epithelium; glucagon; glutamine; guinea pigs; host organism interaction; immunoelectron microscopy; immunofluorescence technique; immunoregulation; immunosuppression; laboratory mouse; macrophage; model design /development; nutrition related tag; omega 3 fatty acid; prostaglandin analogs; prostaglandins; radionuclides; radiotracer; retinoids; tissue /cell culture; tocopherols; tritium; tube feeding; Candida albicans; Escherichia coli; Pseudomonas aeruginosa; Staphylococcus aureus; allopurinol; autoradiography; bactericidal immunity; binding proteins; bioenergetics; burns; carbon; cortisone; diet therapy; dietary fiber; dietary lipid; disease /disorder model; endotoxins; gastrointestinal epithelium; glucagon; glutamine; guinea pigs; host organism interaction; immunoelectron microscopy; immunofluorescence technique; immunoregulation; immunosuppression; laboratory mouse; macrophage; model design /development; nutrition related tag; omega 3 fatty acid; prostaglandin analogs; prostaglandins; radionuclides; radiotracer; retinoids; tissue /cell culture; tocopherols; tritium; tube feeding

Infections in surgical patients continue to be a major source of morbidity and mortality, especially in patients admitted to intensive care units. Studies have been designed to improve resistance to infection by means of nutritional therapy and improvement of gut barrier functions. Routine and immunofluorescent light microscopy, transmission and immuno-electron microscopy, and isotope techniques will be used to determine how and where microbes and endotoxin traverse the epithelial barrier of the intestine, and follow their disposition within various cells and tissues. Quantitation of translocation will employ probes of 14C endotoxin, 3H- labeled and unlabeled E. coli and 3H labeled and unlabeled C. albicans in mice and guinea pigs. Rates and amounts of translocation will be correlated with mortality in burn and burn infected animals, extent of activation in various macrophages, stimulation of catabolic hormone release, stimulation of resting energy expenditure, the ability to clear S. aureus from inoculated sites, and stimulation of resting energy expenditure, the ability to clear S. aureus from inoculated sites, and selected immunologic responses. The following variables will be evaluated for their ability to reduce translocation of endotoxin after burn injury: intestinal hormones, growth hormones, endotoxin binders, prostaglandin analogues, allopurinol and various types of dietary lipids, various soluble fibers, tocopherol, vitamin A, glutamine, and proteins in different physical states. Potential synergism between modulatory agents and dietary components will be studies as well as the effects of reducing translocation by these means on outcome. Selected fatty acids of the omega 3, 6, 9 families will be studied in vitro and in vivo for their influence on macrophage functions. The investigators have previously shown that survival in animals with protracted peritonitis is improved with diets which are hypocaloric, low in protein, high in both omega 3 and 6 fatty acids, and high in vitamins C and E. Further studies will define the optimal amounts of vitamin A, selenium, and soluble fibers for this partially formulated diet. The investigators have also shown that hypocaloric diets, enriched in protein and omega 6 fatty acids and vitamin E will improve survival of normal animals given an infectious challenge. Further investigations will determine the roles of vitamins A, C, and E, and selenium in resistance to infection in normal and malnourished animals given a septic challenge. The biological effects of these diets on bacterial virulence, toxin production, and immune function will be studied in additional experiments.

手术患者的感染仍然是发病率的主要来源 和死亡率，特别是在接受重症监护病房的患者中。 研究旨在通过 营养疗法和肠道障碍功能的改善。 常规和 免疫荧光光学显微镜，传播和免疫电子 显微镜和同位素技术将用于确定如何和何处 微生物和内毒素穿越肠的上皮屏障， 并跟随它们在各种细胞和组织中的处置。 易位定量将采用14C内毒素的探针，3H- 标记和未标记的大肠杆菌和3H标记和未标记的白色念珠菌在 小鼠和豚鼠。 易位的费率和数量将是 与烧伤和烧伤感染动物的死亡率相关 在各种巨噬细胞中的激活，刺激分解代谢激素 释放，刺激静止能量消耗，清除S的能力。 来自接种位点的金黄色葡萄球菌，并刺激静息能 支出，从接种地点清除金黄色葡萄球菌的能力以及 选定的免疫反应。 将评估以下变量 因为它们能够减少烧伤后内毒素易位的能力： 肠激素，生长激素，内毒素粘合剂，前列腺素 类似物，别嘌醇和各种饮食脂质，各种可溶性 不同的纤维，生育酚，维生素A，谷氨酰胺和蛋白质 物理状态。 调节剂与饮食中的潜在协同作用 组件将是研究以及减少易位的影响 通过这些方式。 Omega 3，6，9的选定脂肪酸 家庭将在体外和体内研究他们的影响 巨噬细胞功能。 调查人员以前已经表明 饮食可改善患有肠胃炎的动物的生存 低温，蛋白质低，在欧米茄3和6脂肪中都高 酸，以及较高的维生素C和E。进一步的研究将定义 为此，最佳的维生素A，硒和可溶性纤维 部分配制的饮食。 调查人员还表明 低温饮食，富含蛋白质和欧米茄6脂肪酸和维生素 考虑到感染性挑战，E将提高正常动物的生存。 进一步的研究将确定维生素A，C和E的作用 和硒在正常和营养不良的动物中抵抗感染 鉴于化粪池挑战。 这些饮食对 将研究细菌毒力，毒素产生和免疫功能 在其他实验中。