COMPARTMENTAL ANALYSIS OF PROTEOMIC BIOMARKERS DURING INTRA-UTERINE INFECTIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项研究和职业发展资助的目的是利用子宫内感染微小脲原体的非人灵长类动物实验模型来表征生物标志物表达谱之间的时间和机制相互作用（即，IGFBP-1蛋白水解片段，钙颗粒蛋白A和B以及膜联蛋白II），在上行性子宫感染的确定阶段（从绒毛膜蜕膜到羊膜内模型）的母体和胎儿隔室中。我们的假设是，特定的生物标志物谱（空间和时间特征）将作为上行性子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、呼吸参数和局部和胎盘循环中的血液动力学变化），并评估用于改善胎儿心肺稳态的组合治疗方法的功效。所提出的工作是独特的，其诊断和干预策略的结合使用在非人灵长类动物模型的子宫内感染（实验绒毛膜蜕膜和羊膜内阶段）。我们期望这些研究的结果将促进临床管理，并促进早期诊断因宫内感染而有早产风险的妇女。

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.