FETAL MATURATION IN A MODEL SYSTEM

模型系统中的胎儿成熟

• 批准号: 2430746
• 负责人: Michael Glenn Ross
• 金额: $ 12.54万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-20 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430746
• 关键词: baboons; bronchopulmonary dysplasia; combination chemotherapy; cooperative study; corticosteroids; disease /disorder model; embryo /fetus chemotherapy; growth /development; hormone receptor; hormone therapy; lipid metabolism; nonhuman therapy evaluation; premature infant animal; protein metabolism; pulmonary surfactants; respiratory function; thyroxine; ultrasound

This is a proposal to evaluate new clinically relevant strategies to improve postnatal outcome of the preterm. The goal is to test the efficacy and safety of potential maturational agents given 24 hr. before preterm delivery of baboons at 125 days gestational age, a point in gestation that will just permit survival with the combined use of surfactant therapy and intensive care. The treatment interval of 24 hr. and the gestational age at delivery are selected based on information being collected using a preterm sheep model funded separately and are selected to focus the studies on the questions most relevant to treatment of humans at risk of preterm labor. The fetal baboons will initially be treated with a single dose of intramuscular betamethasone using fetal ultrasound to direct the injections. The initial experiment will permit the selection of a corticosteroid dose using physiologic measures of efficacy over 24 hr. after delivery followed by measurements of corticosteroid effects in a variety of tissues. T(4) then will be evaluated when used in conjunction with corticosteroids. We then will perform 10 day postnatal studies of animals treated with the corticosteroid alone, corticosteroid plus T4 and a control group. These studies will be followed in later years by evaluations of other effector molecules as well as by changes in the timing of delivery after fetal treatment. Following fetal treatment and preterm delivery, each newborn will be extensively studied in terms of performance as a newborn by evaluating lung function, cardiovascular performance, neuroendocrine adaptation and kidney function. Tissues then will be collected for focused studies of effects of the fetal treatments. Lung tissue will be used to evaluate selected aspects of surfactant lipid and protein metabolism. Kidney tissue will be used to evaluate receptor systems and Na+K+ATPase activity. Plasma samples will be processed for hormone levels, for provocative tests of the thyroid axis and the adrenal axis, and tissues will be collected for measurements of receptor systems. The experimental goal is to combine physiologic with biochemical and molecular indicators of maturation for a number of organ systems to characterize how the fetus will perform as a newborn and what changes occur as a result of the fetal therapy.

这是一项评估新的临床相关策略的提案 改善早产儿的产后结局。 目标是测试 24 小时给予潜在成熟剂的功效和安全性。前 孕龄 125 天的狒狒早产，这是 妊娠期仅能通过联合使用来生存 表面活性剂疗法和重症监护。 治疗间隔为24小时。 并根据信息选择分娩胎龄 使用单独资助的早产羊模型收集并 选择将研究重点放在与治疗最相关的问题上 面临早产风险的人类。 胎儿狒狒最初会 使用胎儿进行单剂量肌肉注射倍他米松治疗 超声引导注射。 初步实验将允许 使用生理测量来选择皮质类固醇剂量 24小时以上的疗效。交付后进行测量 皮质类固醇对多种组织的作用。 T(4) 则为 与皮质类固醇联合使用时进行评估。 然后我们将 对接受过治疗的动物进行 10 天的产后研究 单独皮质类固醇、皮质类固醇加 T4 组和对照组。 这些 研究将在随后的几年中对其他效应器进行评估 分子以及胎儿出生后分娩时间的变化 治疗。 在胎儿治疗和早产后，每个新生儿 将在新生儿的表现方面进行广泛的研究 评估肺功能、心血管功能、神经内分泌 适应和肾功能。 然后将收集组织用于 集中研究胎儿治疗的效果。 肺组织将 用于评估表面活性剂脂质和蛋白质的选定方面 代谢。 肾脏组织将用于评估受体系统和 Na+K+ATP酶活性。 血浆样本将进行激素处理 水平，用于甲状腺轴和肾上腺轴的激发测试， 将收集组织用于受体系统的测量。 这 实验目标是将生理学与生化和分子学结合起来 一些器官系统的成熟指标来描述如何 胎儿的表现与新生儿一样，并且会发生什么变化 胎儿疗法。