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：
7799992
负责人：
Peta Louise Grigsby
金额：
$ 24.9万
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/7799992
关键词：
ANXA2 gene Address Amniotic Fluid Animals Anti-Inflammatory Agents Anti-inflammatory Antibiotic Therapy Antibiotics Arteries Award Bacteria Bacterial Vaginosis Biological Assay Biological Markers Blood Brain Injuries Calgranulin B Cardiovascular system Catheters Cells Cervical Cesarean section Characteristics Chorion Clinical Control Groups Data Detection Diagnosis Diagnostic Dinoprostone Disease Progression Dose Early Diagnosis Electrodes Endocrine Experimental Models Femoral vein Fetal Lung Fetal Membranes Fetal Tissues Fetus Functional disorder Genital system Gestational Age Growth Hour IL8 gene Immunoassay Implant In Situ Hybridization In Vitro Individual Infection Inflammation Inflammatory Inflammatory Response Infusion procedures Insulin-Like Growth-Factor Binding Protein 1 Interleukin-6 Invaded Laboratories Length Leukocytes Link Macaca mulatta Matrix Metalloproteinases Measurement Membrane Mentors Methodology Methods Microbe Modeling Molecular Profiling Monitor Monkeys Mycoplasma Neonatal Operative Surgical Procedures Palpation Pan Genus Phase Physiological Adaptation Plasma Postoperative Care Pregnancy Premature Birth Premature Labor Procedures Process Production Property Proteins Proteomics Protocols documentation Research Design Research Proposals Resolution Saline Sampling Schedule Simulate Source Staging Sterility Stimulus System Techniques Therapeutic Therapeutic Intervention Tissues Ultrasonography Umbilical Cord Blood Ureaplasma Ureaplasma urealyticum biovar 1 Western Blotting amnion amniotic cavity cytokine fetal fetal blood genital infection hemodynamics implantation intraamniotic infection microorganism myometrium nonhuman primate novel novel strategies premature prevent 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.

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).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。由组件组织层通过组成组织层IL-1B，TNF-A，IL-6和IL-8的特定生物标志物的生产率以及在炎症内感染期间观察到的特定生物标志物特征的组织来源。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。子宫收缩力，宫颈长度的序列分析（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，羊膜液和羊膜液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。