COMPARTMENTAL ANALYSIS OF PROTEOMIC BIOMARKERS DURING INTRA-UTERINE INFECTIONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究和职业发展资助的目的是利用非人灵长类动物微小解脲支原体宫内感染的实验模型来表征在子宫感染上升的特定阶段(从绒毛蜕膜到羊膜内模型)母体和胎儿体内生物标记物(即IGFBP-1蛋白降解片段、钙颗粒蛋白A和B以及膜联蛋白II)之间的时间和机制相互作用。我们的假设是，特定的生物标志物特征(空间和时间特征)将作为宫内感染进展阶段的替代物。本研究的一个重要方面是确定胎儿对羊膜内感染的生理适应(即内分泌状态、呼吸参数以及局部和胎盘循环的血流动力学变化)，并评估综合治疗方法改善胎儿心肺稳态的效果。这项工作的独特之处在于，在宫内感染的非人类灵长类动物模型(实验性绒毛-蜕膜阶段和羊膜内阶段)中，结合使用了诊断和干预策略。我们期望这些研究的结果将促进临床管理，并促进因宫内感染而面临早产风险的妇女的早期诊断。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objectives of this research and career development grant are to utilize a nonhuman primate experimental model of intra-uterine infection with Ureaplasma parvum to characterize the temporal and mechanistic interactions among biomarker expression profiles (i.e., IGFBP-1 proteolytic fragments, calgranulins A and B and annexin II), in maternal and fetal compartments at defined stages of ascending uterine infection (from choriodecidual to intra-amniotic models). It is our hypothesis that specific biomarker profiles (spatial and temporal characteristics), will serve as surrogates for the stage of progression of ascending intra-uterine infection. An important aspect of this study is to determine the fetal physiologic adaptations to intra-amniotic infection (i.e., endocrine status, respiratory parameters and hemodynamic changes in regional and placental circulations), and to assess the efficacy of a combined therapeutic approach for improving fetal cardio-respiratory homeostasis. The work proposed is unique in its combined use of diagnostic and interventional strategies in a nonhuman primate model of intra-uterine infection (experimental choriodecidual and intra-amniotic stages). It is our expectation that the results of these studies will advance clinical management and facilitate the early diagnosis of women that are at risk for preterm delivery as a consequence of intra-uterine infection.