INVESTIGATIONS OF NEW THERAPIES IN SEPTIC SHOCK

感染性休克新疗法的研究

• 批准号: 3874266
• 负责人: C NATANSON
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874266
• 关键词: MHC class II antigen; antireceptor antibody; blood filtration; colony stimulating factor; disease /disorder model; dogs; endotoxins; ibuprofen; immunotherapy; lipids; monoclonal antibody; nonhuman therapy evaluation; plasmapheresis; platelet activating factor; protein C; shock; tumor necrosis factor alpha

Septic shock and related sequelae of infection (eg., multiple organ system failure) are the most common cause of death in intensive care units. Deaths due to sepsis can occur in previously healthy individuals, in all age groups, and in a variety of common clinical settings. Some common predisposing conditions are premature neonates, previously healthy children with acquired infections (e.g., meningitis, pneumonia, upper respiratory infections), teenagers and young adults with trauma or cancer, and elderly patients with pneumonia or gall bladder disease. Half of all children and adults who acquire septic shock die from the syndrome. Thus, septic shock, which affects young children and the elderly alike (even those without predisposing illness), is a common and important clinical problem with substantial mortality and produces great financial burden on society. Surprisingly, little is known about the pathophysiology of this disease infection (organism virulence factors and toxins) and factors related to the host response (endogenous molecules that affect and modulate the inflammatory response). Thus, successful treatment of the septic shock syndrome which reduces morbidity and mortality will result from curing the infection and interrupting the effects of these organism and host mediators. Using purpose-bred beagles, the canine model of septic shock has successfully provided information on the pathophysiology and treatment of the human disease. This model, of acute and chronic infection simulates the course and cardiovascular changes seen routinely in children and adults with septic shock. Prior experiments using the model have established the role of specific bacterial (gram positive and gram negative), bacterial toxins (endotoxin), and host mediators (TNF) to produce septic shock. Thus, the canine model has been highly successful in simulating the human disease and guiding therapy for humans. There are several therapies under investigation that might be effective in human septic shock. As these therapies are potentially human disease. The canine model, which simulates the cardiovascular changes seen in children and adult humans with septic shock, is ideally suited for preclinical trials of these new therapies. The canine model allows properly controlled trials to evaluated therapeutic mechanisms and adverse effects of therapies, that is not always possible in human studies. We are evaluating or have planned to evaluate the following therapies of septic shock in the canine model: Lipid X Z; Plasmapheresis; Ibuprofen; Monoclonal Antibodies to Endotoxin; Antibody to Tumor Necrosis Factor; Pentoxyphylline; Granulocyte Stimulating Factor; Antibodies to Platelet Activation Factor; Antibodies to Protein C; Antibodies to Receptors on White Blood Cells; Continuous A-V Hemofitration.

感染性休克和相关的感染后遗症（例如，多器官系统 失败）是重症监护病房中最常见的死亡原因。死亡 由于脓毒症可发生在先前健康的个体中， 组，并在各种常见的临床设置。一些常见 易感条件是早产儿，以前健康的儿童 对于获得性感染（例如，脑膜炎、肺炎、上呼吸道 感染），青少年和年轻人创伤或癌症，以及老年人 肺炎或胆囊疾病患者。一半的儿童和 感染性休克的成年人死于该综合征。因此，感染性休克， 这会影响幼儿和老年人（即使是那些没有 诱发疾病），是一种常见的和重要的临床问题， 死亡率很高，给社会造成很大的经济负担。 令人惊讶的是，很少有人知道这种疾病的病理生理学 感染（生物体毒力因子和毒素）和相关因子 宿主反应（影响和调节宿主免疫应答的内源性分子）， 炎症反应）。因此，脓毒性休克的成功治疗 降低发病率和死亡率的综合征将由治愈 感染和中断这些生物体和宿主的影响 调解员使用专门饲养的比格犬，感染性休克的犬模型 成功提供了有关病理生理学和治疗的信息 人类疾病。这个急性和慢性感染的模型模拟了 儿童和成人常见的病程和心血管变化 感染性休克使用该模型的先前实验已经建立了 特定细菌（革兰氏阳性和革兰氏阴性）、细菌 毒素（内毒素）和宿主介质（TNF）产生败血性休克。因此，在本发明中， 狗模型在模拟人类疾病方面非常成功 并指导人类的治疗有几种治疗方法， 可能对人类感染性休克有效的研究。因为这些 治疗是潜在的人类疾病。犬类模型， 儿童和成人脓毒症患者的心血管变化 休克，非常适合这些新疗法的临床前试验。的 犬模型允许适当的对照试验，以评估治疗 机制和治疗的不良反应，这并不总是可能的， 人类研究我们正在评估或计划评估以下内容 犬感染性休克模型的治疗：脂质X Z;血浆置换; 抗内毒素单克隆抗体 因子;喷托茶碱;粒细胞刺激因子;抗 血小板活化因子;抗蛋白C抗体;抗 白色血细胞上的受体;连续A-V血液滤过。