FETAL MATURATION IN A MODEL SYSTEM

这是一项评估新的临床相关策略的建议， 改善早产儿的产后结局。 目标是测试 前24小时给予的潜在成熟剂的有效性和安全性 狒狒在胎龄125天时早产， 妊娠期，将允许生存与结合使用 表面活性剂治疗和重症监护。 治疗间隔为24小时。 和分娩时的胎龄是基于信息选择的 使用单独资助的早产绵羊模型收集， 选择的目的是将研究重点放在与治疗最相关的问题上 有早产风险的人。 胎儿狒狒最初会 用单剂量的肌内注射倍他米松治疗， 超声波引导注射 最初的实验将允许 皮质类固醇剂量的选择使用生理测量， 分娩后24小时内的疗效，随后测量 皮质类固醇在各种组织中的作用。 T（4）则为 与皮质类固醇联合使用时进行评价。 然后我们将 对用以下药物处理的动物进行10天产后研究 单独皮质类固醇、皮质类固醇加T4和对照组。 这些 研究将在以后的几年中进行其他效应物的评价。 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 将被广泛研究的表现作为一个新生儿， 评估肺功能、心血管性能、神经内分泌 适应和肾功能。 然后收集组织， 对胎儿治疗效果的集中研究。 肺部组织将 用于评价表面活性剂脂质和蛋白质的选定方面 新陈代谢. 肾组织将用于评估受体系统， Na+K+ ATP酶活性。 将对血浆样本进行激素处理 水平，用于甲状腺轴和肾上腺轴的激发试验， 并收集组织用于受体系统的测量。 的 实验目标是将生理学、生物化学和分子生物学联合收割机结合起来 一些器官系统的成熟指标，以表征如何 胎儿将表现为新生儿和什么变化发生的结果， 胎儿治疗

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.