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: 7483660
• 负责人: JOHN E MOULDER
• 金额: $ 359.44万
• 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/7483660
• 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制定药理学方法，以减轻和治疗放射恐怖主义或辐射事故受害者所受剂量超过5 Gy的非血液学辐射损伤，并预防或避免血液学毒性。对于均匀全身照射，骨髓损伤可能是主要的危及生命的损伤。但是，对于部分身体照射或体内沉积的放射性同位素（辐射剂量可能很高，但一些骨髓可能不会受到影响），或者如果骨髓损伤可以用细胞因子或干细胞移植来治疗，则预计会发生其他类型的急性（例如Gl、皮肤、肺）和晚期（例如肾脏、肺、中枢神经系统）损伤。这些非血液学损伤是该中心的重点；尽管对这些组织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不太重要，除非在减轻和治疗血液学损伤方面取得进展。该中心将是一个由来自4个机构的5个项目和5个核心组成的联盟：威斯康星医学院、亨利福特卫生系统、多伦多大学和Eukarion公司。要研究的器官系统是Gl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），因为如果剂量超过5gy，并且如果预防或避免致命的血液学损伤，这些是一些将处于危险中的主要器官系统。项目2中使用的啮齿动物辐射肾损伤模型系统和项目1中使用的犬肾损伤模型已经较为完善；但大型动物肾脏模型（项目2）、啮齿动物Gl损伤模型（项目1）、肺损伤模型（项目3和4）和中枢神经系统损伤模型（项目5）有待进一步的模型开发。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），以及抑制急性和慢性氧化应激（项目1,2,4,5）。这些项目将得到辐照核心和SOD/过氧化氢酶模拟核心的支持；该中心还将包含一个试点拨款计划和一个教学和教育计划)。