GASTROINTESTIONAL MOTOR EFFECTS OF IONIZING RADIATION

电离辐射对胃肠运动的影响

• 批准号: 3464284
• 负责人: MARY F. OTTERSON
• 金额: $ 7.7万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-10 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3464284
• 关键词: allopurinol; biliary tract surgery; degenerative motor system disease; disease /disorder model; dogs; electrophysiology; free radicals; gastrointestinal function; indomethacin; inhibitor /antagonist; ionizing radiation; neoplasm /cancer radiation therapy; neuromuscular disorder chemotherapy; radiation dosage; radiation recovery; reflux esophagitis; sensorimotor system

Radiation therapy is a major modality in the treatment of cancer. However, as the application and efficacy of this increased, so has the concern for normal tissue toxicity. For the treatment of abdominal and pelvic tumors, intestinal tolerance is often a major limiting factor. Recent studies from our lab (1, 17) and other laboratories (9, 10, 16, 18) have demonstrated that dramatic changes occur in the small intestinal motor activity following fractionated or single sub-lethal doses of ionizing radiation. Many of these changes may have a direct symptomatic relevance to patients receiving radiation therapy. the primary objectives of this research proposal, therefore, are 1) to expand our previous work on the effects of fractionated doses of irradiation on the small intestine to the colon, 2) to delineate the myogenic neural and chemical mechanisms that may be responsible for the changes in small intestinal motor activity after radiation, and 3) to extend the animal studies to the human model. In the canine model, the contractile and myoelectric recording will be made by using strain gauge transducer and bipolar electrodes, respectively. These devices will be implanted in the animal using sterile surgical techniques. The role of bile in the production of abnormal contractile patterns during radiation schedule will be studied by diverting the bile through exteriorized silastic catheters implanted in conscious state after a 10 day recovery period. The recordings from the human colon and small intestine will be made by manometric methods. The analysis of data will be done visually and by computer methods developed in our laboratory. Our ultimate aim is to delineate the mechanisms that produce abnormal motor patterns during radiation therapy in humans. The understanding for these mechanisms would help in proposing appropriate pharmacologic agents that may block these effects and improve human tolerance to radiation exposure.

放射疗法是治疗癌症的主要方式。 然而，在这方面， 随着其应用和功效的增加， 正常组织毒性。 对于腹部和盆腔肿瘤的治疗， 肠耐受性通常是主要的限制因素。 最近的研究来自 我们的实验室（1，17）和其他实验室（9，10，16，18）已经证明 小肠运动活动发生了巨大的变化 在分次或单次亚致死剂量的电离辐射之后。 这些变化中的许多可能与患者的症状直接相关 接受放射治疗 本研究的主要目的 因此，建议是：1）扩展我们之前关于影响的工作 对小肠至结肠的分次剂量照射，2） 描绘肌源性神经和化学机制， 负责小肠运动活动的变化后， 辐射，和3）将动物研究扩展到人类模型。 在犬模型中，将记录收缩和肌电 分别使用应变传感器和双极电极。 这些器械将通过无菌手术植入动物体内 技术. 胆汁在产生异常收缩中的作用 将通过转移胆汁来研究放射计划期间的模式 通过在清醒状态下植入的外置硅橡胶导管， 10天的恢复期。 人类结肠和小肠的记录 将通过测压方法制备肠。 数据分析将 通过视觉和我们实验室开发的计算机方法完成。 我们的最终目标是描绘产生异常运动的机制 在人类放射治疗过程中的模式。 对这些的理解 机制将有助于提出适当的药理学试剂， 可以阻断这些效应，提高人体对辐射的耐受性。