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。我们的目标是测试 潜在成熟剂给药24小时的有效性和安全性。在此之前 在怀孕125天的时候早产，一个时间点 在联合使用的情况下可以存活的妊娠 表面活性物质治疗和重症监护。治疗间隔24小时。 以及分娩时的孕周是基于信息选择的 使用单独资助的早产绵羊模型收集，并 选择将研究重点放在与治疗最相关的问题上 有早产风险的人类。最初，这些胎儿狒狒将会是 单次肌肉注射倍他米松治疗胎儿 超声波引导注射。最初的实验将允许 应用生理测量选择皮质类固醇的剂量 药效超过24小时。在交付之后，测量 皮质类固醇在各种组织中的作用。那么T(4)将是 当与皮质类固醇联合使用时进行评估。然后我们就会 进行动物出生后10天的研究，用 单用糖皮质激素、糖皮质激素加T4及对照组。这些 研究将在以后几年进行，并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。在胎儿治疗和早产之后，每个新生儿 将被广泛地研究作为新生儿的表现 评估肺功能、心血管功能、神经内分泌 适应与肾功能。然后将收集组织用于 对胎儿治疗效果的重点研究。肺组织将会被 用于评价表面活性物质的脂类和蛋白质的某些方面 新陈代谢。肾脏组织将被用来评估受体系统和 Na+K+ATPase活性。将对血浆样本进行激素检测 对于甲状腺轴和肾上腺轴的刺激性测试， 组织将被收集用于受体系统的测量。这个 实验目标是将生理、生化和分子相结合。 一些器官系统成熟的指标，以表征如何 胎儿会像新生儿一样表现，以及由于 胎儿疗法。

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.