Compartmental analysis of proteomic biomarkers during intra-uterine infections

子宫内感染期间蛋白质组生物标志物的区室分析

基本信息

批准号：
7871391
负责人：
Peta Louise Grigsby
金额：
$ 24.65万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-13 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7871391
关键词：
ANXA2 gene Amniotic Fluid Anti-Inflammatory Agents Anti-inflammatory Antibiotic Therapy Antibiotics Arteries Azithromycin Bacterial Vaginosis Biological Markers Blood Blood Circulation Blood flow Calgranulin B Cardiac Cardiac Output Cardiovascular system Cervical Cesarean section Characteristics Clinical Color Complement Control Animal Data Decidua Depressed mood Descending aorta Dexamethasone Diagnosis Dinoprostone Disease Progression Doppler Ultrasonography Ductus Arteriosus Effectiveness Endocrine Experimental Models Fetal Monitoring Fetal Tissues Functional disorder Gelatinase B Genital system Gestational Age Health Heating IL8 gene Image In Vitro Individual Indomethacin Infection Inferior vena cava structure Inflammation Mediators Inflammatory Response Insulin-Like Growth-Factor Binding Protein 1 Interleukin-6 Invaded Length Leukocytes Link Matrix Metalloproteinases Measurement Membrane Modeling Molecular Profiling Monitor Monkeys Mycoplasma Myocardial Neonatal Palpation Performance Physiological Adaptation Plasma Premature Birth Premature Labor Production Proteomics Pulmonary valve structure Research Proposals Role Series Simulate Source Staging Structure of ductus venosus Structure of umbilical artery Therapeutic Therapeutic Intervention Tissues Ultrasonography Ultrasonography, Doppler, Pulsed Ureaplasma Ureaplasma urealyticum biovar 1 amnion amniotic cavity aortic valve comparative cytokine fetal fetal blood genital infection hemodynamics in vivo indexing intraamniotic infection killings microbial novel novel strategies premature prevent progesterone 11-hemisuccinate-(2-iodohistamine)prognostic indicator respiratory response uterine contractility vaginal fluid

项目摘要

The objectives of this research proposal are to characterize the mechanistic and temporal relationships among biomarker expression profiles (e.g., IGFBP-1 proteolytic fragments, calgranulin B and annexin II) in maternal and fetal compartments during defined stages of ascending infection with genital mycoplasmas (from choriodecidual to intra-amniotic models). It is our hypothesis that spatial and temporal characteristics of specific proteomic biomarkers in cervical vaginal fluid (CVF), amniotic fluid, maternal and fetal blood, will act as surrogates for the stage of progression of intra-uterine infection; similarly, changes in biomarker expression profiles during maternal therapeutic interventions (antibiotic and anti-inflammatory agents), will serve as prognostic indicators. Fetal physiological adaptations (i.e., cardiovascular hemodynamics, respiratory parameters,endocrine status) will be assessed in early and advanced stages of infection, and in response to maternal antibiotic therapy. Complemetary in vitro studies will assess the ability of U. parvum to invade and transcytose through intact chorioamniotic membranes and gain entry into the amniotic cavity. The production rates of specific biomarkers and the secretory profiles of IL-1B, TNF-a, IL-6 and IL-8 by component tissue layers will illuminate the tissue source of specific biomarker profiles observed in the amniotic fluid and cervical vaginal fluid (CVF) during intra-uterine infection. Moreover, these studies will provide important information on the contribution of the amnion or choriodecidua to the inflammatory response following U. parvum exposure. A number of specific endpoints will be ascertained that will aid in our understanding of causal links among choriodecidual colonization with U. parvum and the biologic and clinical manifestations of early and late stages of ascending uterine infection. Uterine contractility, serial assesment of cervical length (by ultrasound and palpation), amniotic fluid levels of PGE2, PGF2a, cytokines, leukocytes and MMPs will be correlated with biomarker expression profiles in the CVF, amniotic fluid and maternal and fetal blood. Quantitative cultures and PCR for ureaplasmas will be performed on amniotic fluid, blood and fetal tissues.

这项研究建议的目标是表征生物标志物表达谱之间的机械和时间关系（例如，在具有生殖器菌群（Choroiodecidual choriodecidual choriodecidual contection contection cantection）阶段，在母体和胎儿隔室中，在母体和胎儿隔室中，在孕产妇和胎儿隔室中的机械和时间关系到宽阔的模型）。我们的假设是，特异性蛋白质组学生物标志物在宫颈阴道液（CVF），羊水，母体和胎儿血液中的空间和时间特征将充当前肠内感染阶段的替代。同样，在母体治疗干预措施（抗生素和抗炎剂）期间，生物标志物表达谱的变化将用作预后指标。胎儿生理适应（即心血管血流动力学，呼吸参数，内分泌状态）将在感染的早期和晚期阶段进行评估，并应对母体抗生素治疗。补体的体外研究将评估U. Parvum通过完整的绒毛膜膜侵袭和跨膜的能力，并进入羊水腔。由组件组织层通过特定生物标志物和IL-1B，TNF-A，IL-6和IL-8的分泌曲线的生产率将阐明在羊水和宫颈阴道流体（CVF）中观察到的特定生物标志物特征的组织来源）在河内感染期间。此外，这些研究将提供有关羊膜或绒毛膜脉络膜对炎症反应的贡献的重要信息。将确定许多具体的终点，这将有助于我们理解脉络膜上的定植与U. Parvum的因果关系，以及上升子宫感染的早期和晚期阶段的生物学和临床表现。子宫收缩性，颈长度的连续分析（通过超声和触诊），PGE2，PGF2A的羊水水平，PGF2A，细胞因子，白细胞和MMP与CVF，羊膜液和羊膜和胎儿和胎儿和胎儿血液中的生物标志物表达谱相关。将在羊水，血液和胎儿组织上进行定量培养物和PCR。