Post-Irradiation Intervention to Mitigate and Treat Non Hematological Radiation

减轻和治疗非血液放射的放射后干预

• 批准号: 7275265
• 负责人: JOHN E MOULDER
• 金额: $ 358.36万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-31 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275265
• 关键词: Post; Irradiation; Intervention; Mitigate; Treat

The overall goal of the Center is to develop pharmacologic approaches for the mitigation and treatment of the non-hematological radiation injuries that will occur in victims of radiological terrorism or radiation accidents who receive doses in excess of 5 Gy, and for whom hematological toxicity is prevented or avoided. For uniform total body irradiation, injury to bone marrow is likely to be the primary life-threatening injury. But for partial-body exposure or for internally-deposited radioisotopes (where radiation doses may be high but some bone marrow may be spared), or if the bone marrow damage can be treated with cytokines or stem cell transplants, other types of acute (e.g., Gl, skin, lung) and late (e.g. renal, lung, CNS) injuries are expected to occur. It is these non-hematological injuries which are the focus of the proposed Center; although treatment and mitigation of injuries to these tissues will be of little importance to victims of radiological terrorism or radiation accidents unless there are advancements in the mitigation and treatment of hematological injuries. The Center will be a Consortium made up of 5 projects and 5 cores drawn from 4 institutions: the Medical College of Wisconsin, the Henry Ford Health Systems, the University of Toronto, and Eukarion, Inc. The organ systems to be studied are the Gl tract (Project 1), the kidney (Project 2), the lung (Projects 3 and 4) and the CNS (Project 5), as these are some of the major organ systems that will be at risk if doses exceed 5 Gy and if fatal hematological injury is prevented or avoided. The rodent radiation-induced renal injury model system used in Project 2 and the canine model for Gl injury (Project 1) are already well-developed; but further model development is required for large-animal renal models (Project 2), and for rodent models of Gl injury (Project 1), lung injury (Projects 3 and 4) and CNS injury (Project 5). The major pharmaceutical approaches that will be assessed are suppression of the renin-angiotensin system (Projects 1, 2, 3, 5), and suppression of acute and chronic oxidative stress (Projects 1, 2, 4, 5). The Projects will be supported by an Irradiation Core and a SOD/Catalase Mimetic Core; and the Center will also contain a Pilot Grant Program and a Teaching and Education Program).

该中心的总体目标是开发药理学方法，以减轻和治疗非血液学辐射损伤，这种损伤将发生在接受超过5GY剂量的辐射恐怖主义或辐射事故的受害者身上，并对其血液毒性进行预防或避免。对于均匀的全身照射，骨髓损伤很可能是主要的危及生命的损伤。但对于部分身体暴露或内部储存的放射性同位素(辐射剂量可能很高，但一些骨髓可以幸免)，或者如果骨髓损伤可以用细胞因子或干细胞移植治疗，预计还会发生其他类型的急性(如Gl、皮肤、肺)和晚期(如肾、肺、中枢神经系统)损伤。这些非血液损伤是拟建中心的重点；尽管除非在血液损伤的缓解和治疗方面取得进展，否则对这些组织的损伤的治疗和减轻对放射性恐怖主义或辐射事故的受害者来说并不重要。该中心将是一个由来自4个机构的5个项目和5个核心组成的联合体：威斯康星医学院、亨利·福特健康系统、多伦多大学和尤卡里恩公司。要研究的器官系统是胃肠道(项目1)、肾脏(项目2)、肺(项目3和4)和中枢神经系统(项目5)，因为这些是一些主要器官系统，如果剂量超过5GY，并且如果预防或避免致命的血液损伤，这些器官系统将面临风险。项目2中使用的辐射致鼠肾损伤模型系统和犬肾损伤模型(项目1)已经比较成熟，但大动物肾脏模型(项目2)、大鼠肾脏损伤模型(项目1)、肺损伤(项目3和4)和中枢神经系统损伤模型(项目5)还需要进一步的模型开发。将评估的主要药物方法是抑制肾素-血管紧张素系统(项目1、2、3、5)和抑制急性和慢性氧化应激(项目1、2、4、5)。这些项目将得到一个辐射核心和一个超氧化物歧化酶/过氧化氢酶模拟核心的支持；该中心还将包括一个试点赠款计划和一个教学和教育计划。