Preterm Labor and Fetal Sequelae: Role of Ureaplasmas

早产和胎儿后遗症：解脲支原体的作用

基本信息

批准号：
7230460
负责人：
MILES J. NOVY
金额：
$ 35.5万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-01-01 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7230460
关键词：
Address Adrenal Glands Adverse effects Alveolus Amniotic Fluid Anti-Inflammatory Agents Anti-inflammatory Antibiotic Therapy Antibiotics Apoptosis Awareness Azithromycin Biological Biological Assay Birth Brain Bronchopulmonary Dysplasia Central Nervous System Infections Cerebrum Cessation of life Clinical Clinical Management Clinical Research Combined Antibiotics Count Defect Development Dexamethasone Dinoprostone Dysbarism Encephalitis End Point Endocrine Enterocolitis Environment Epithelial Cells Evolution Experimental Models Fetal Lung Fetal Tissues Fetus Gastrointestinal tract structure Gelatinase B Genital system Goals Grant Growth Histologic Human Immune Immunomodulators Indomethacin Infection Infection of amniotic sac and membranes Inflammation Inflammatory Injury Intervention Intravenous Labor Onset Lead Lesion Leukocytes Link Localized Lung Lung diseases Macaca mulatta Macrolide Antibiotics Matrix Metalloproteinases Measurement Mechanical ventilation Meninges Messenger RNA Methods Microbial Colony Count Modeling Molecular Mycoplasma Mycoplasma hominis Necrosis Neonatal Neuraxis Newborn Infant Numbers Oligodendroglia Organism Pan Genus Pathogenesis Patient currently pregnant Patients Physiological Placenta Play Pneumonia Polymerase Chain Reaction Premature Birth Premature Infant Premature Labor Prematurity of fetus Primates Process Progress Reports Prostaglandins Pulmonary Hypertension Research Research Personnel Respiratory Failure Respiratory System Risk Role Safety Sepsis Series Severities Site Stem cells Structure Study Section Study models Techniques Therapeutic Intervention Time Tissues Translating Up-Regulation Ureaplasma Ureaplasma Infections Ureaplasma urealyticum Ureaplasma urealyticum biovar 1 Uterine Contraction Woman Work animal data base brain cell cell type clinically relevant cytokine fetal fetal blood fetal infection in utero inhibitor/antagonist intraventricular hemorrhage lung injury microbial microorganism morphometry myelination nonhuman primate prenatal prevent progenitor programs reproductive research study response uterine contractility white matter

项目摘要

DESCRIPTION (provided by applicant): The objectives of this Research Plan are to assess the efficacy of antibiotic and anti-inflammatory therapy on preterm labor and relevant sequelae of prematurity (i.e., fetal lung injury) in mobile, chronically catheterized pregnant rhesus monkeys infected intraamniotically with Ureaplasma parvum (formerly U. urealyticum serovar 1). It is our hypothesis that prenatal treatment of intrauterine ureaplasmal infection with an intravenous macrolide antibiotic combined with an anti-inflammatory agent and an immunomodulator will inhibit preterm labor, delay premature delivery, and ameliorate or prevent fetal/neonatal lung disease Physiological studies together with cellular and molecular studies of intrauterine and fetal tissues will address the following questions: (1) Does therapy with azithromycin combined with a prostaglandin synthesis inhibitor (indomethacin) and with dexamethasone inhibit intraamniotic microbial growth and downregulate the cytokine/prostaglandin cascade? (2) Do these interventions prevent preterm labor and fetal lung disease without adverse fetal side-effects? The effect of no treatment, antibiotic therapy, and combined antibiotic/anti-inflammatory therapy on preterm labor and fetal sequelae will be compared. A number of endpoints will be ascertained to establish links among ureaplasma infections, preterm labor, fetal lung injury and the response to therapy including potential fetal side-effects (e.g., intraventricular hemorrhage, enterocolitis). Continuous recordings of uterine contractility will be correlated with amniotic fluid levels of prostaglandins, cytokines, leukocytes, MMPs and maternal, fetal and amniotic fluid levels of azithromycin. Quantitative cultures and PCR for ureaplasmas will be performed on amniotic fluid, blood and fetal tissues. Tissue cytokine mRNA will be quantitated by real-time PCR. Fetal lung damage will be assessed by histopathologic and immunohistochemical methods and by lung morphometry. The gastrointestinal tract, meninges and brain will be examined for inflammation. Death of oligodendrocyte progenitors and other cell types in cerebral white matter will be evaluated by immunohistochemical methods and assays for apoptosis. The work proposed is unique in its use of combined interventional strategies in a well established nonhuman primate model of intrauterine infection. The results should illuminate the causal role of ureaplasma in prematurity and lead to advances in clinical management.

描述（由申请人提供）：本研究计划的目的是评估抗生素和抗炎治疗对羊膜内感染的可移动、长期插入导管的怀孕恒河猴的早产和相关早产后遗症（即胎儿肺损伤）的疗效微小解脲支原体（以前称为解脲支原体血清型 1）。我们的假设是，用静脉注射大环内酯类抗生素联合抗炎剂和免疫调节剂对宫内解脲脲原体感染进行产前治疗将抑制早产，延迟早产，并改善或预防胎儿/新生儿肺部疾病。宫内和胎儿组织的分子研究将解决以下问题：（1）阿奇霉素与前列腺素合成抑制剂（吲哚美辛）联合治疗是否有效？地塞米松抑制羊膜内微生物生长并下调细胞因子/前列腺素级联？ (2) 这些干预措施是否可以预防早产和胎儿肺部疾病而不会对胎儿产生不良副作用？将比较不治疗、抗生素治疗和抗生素/抗炎联合治疗对早产和胎儿后遗症的影响。将确定许多终点，以建立解脲支原体感染、早产、胎儿肺损伤和治疗反应（包括潜在的胎儿副作用（例如脑室内出血、小肠结肠炎））之间的联系。子宫收缩力的连续记录将与羊水中前列腺素、细胞因子、白细胞、MMP 的水平以及母体、胎儿和羊水中阿奇霉素的水平相关。将对羊水、血液和胎儿组织进行解脲脲原体定量培养和 PCR。组织细胞因子 mRNA 将通过实时 PCR 进行定量。将通过组织病理学和免疫组织化学方法以及肺形态测量来评估胎儿肺损伤。将检查胃肠道、脑膜和大脑是否有炎症。将通过免疫组织化学方法和细胞凋亡测定来评估脑白质中少突胶质细胞祖细胞和其他细胞类型的死亡。这项工作的独特之处在于，它在一个完善的非人类灵长类动物宫内感染模型中使用了联合干预策略。研究结果应阐明解脲支原体在早产中的因果作用，并促进临床管理的进步。