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：
7423873
负责人：
Juha Pekka Rasanen
金额：
$ 35.82万
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/7423873
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.

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).我们的假设是，用静脉内大花环抗生素与抗炎剂和免疫调节剂相结合的宫内尿中感染和免疫调节剂相结合，会抑制早产，过早递送，并延迟过早递送或与胎儿/新生肺疾病的生理学研究：跟随胎儿疾病的生理研究：（1）阿奇霉素的治疗与前列腺素合成抑制剂（吲哚美辛）和地塞米松结合抑制了燃料内微生物的生长并下调细胞因子/前列腺素级联脉络膜吗？（2）这些干预措施是否可以预防不良胎儿副作用的早产和胎儿肺疾病？没有治疗，抗生素治疗以及抗生素/抗炎疗法对早产和胎儿后遗症的影响。将确定许多终点，以在尿素倍率感染，早产，胎儿肺损伤和对治疗的反应之间建立联系，包括潜在的胎儿副作用（例如，脑室内出血，小肠结肠炎）。子宫收缩力的连续记录将与羊水，细胞因子，白细胞，MMP以及孕妇，胎儿和羊水的羊水水平相关。将在羊水，血液和胎儿组织上进行定量培养物和PCR。组织细胞因子mRNA将通过实时PCR进行定量。胎儿肺损伤将通过组织病理学和免疫组织化学方法以及肺形态计量法评估。将检查胃肠道，脑膜和大脑的炎症。少突胶质细胞祖细胞和其他细胞类型在脑白质中的死亡将通过免疫组织化学方法和细胞凋亡的测定进行评估。提出的工作在使用宫内感染的非人类灵长类动物模型中使用了联合介入策略是独一无二的。结果应阐明尿素成倍率在早产中的因果作用，并导致临床管理的进步。