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:
- 金额:$ 35.82万
- 依托单位:
- 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:
- 关键词:AddressAdrenal GlandsAdverse effectsAlveolusAmniotic FluidAnti-Inflammatory AgentsAnti-inflammatoryAntibiotic TherapyAntibioticsApoptosisAwarenessAzithromycinBiologicalBiological AssayBirthBrainBronchopulmonary DysplasiaCentral Nervous System InfectionsCerebrumCessation of lifeClinicalClinical ManagementClinical ResearchCombined AntibioticsCountDefectDevelopmentDexamethasoneDinoprostoneDysbarismEncephalitisEnd PointEndocrineEnterocolitisEnvironmentEpithelial CellsEvolutionExperimental ModelsFetal LungFetal TissuesFetusGastrointestinal tract structureGelatinase BGenital systemGoalsGrantGrowthHistologicHumanImmuneImmunomodulatorsIndomethacinInfectionInfection of amniotic sac and membranesInflammationInflammatoryInjuryInterventionIntravenousLabor OnsetLeadLesionLeukocytesLinkLocalizedLungLung diseasesMacaca mulattaMacrolide AntibioticsMatrix MetalloproteinasesMeasurementMechanical ventilationMeningesMessenger RNAMethodsMicrobial Colony CountModelingMolecularMycoplasmaMycoplasma hominisNecrosisNeonatalNeuraxisNewborn InfantNumbersOligodendrogliaOrganismPan GenusPathogenesisPatient currently pregnantPatientsPhysiologicalPlacentaPlayPneumoniaPolymerase Chain ReactionPremature BirthPremature InfantPremature LaborPrematurity of fetusPrimatesProcessProgress ReportsProstaglandinsPulmonary HypertensionResearchResearch PersonnelRespiratory FailureRespiratory SystemRiskRoleSafetySepsisSeriesSeveritiesSiteStem cellsStructureStudy SectionStudy modelsTechniquesTherapeutic InterventionTimeTissuesTranslatingUp-RegulationUreaplasmaUreaplasma InfectionsUreaplasma urealyticumUreaplasma urealyticum biovar 1Uterine ContractionWomanWorkanimal databasebrain cellcell typeclinically relevantcytokinefetalfetal bloodfetal infectionin uteroinhibitor/antagonistintraventricular hemorrhagelung injurymicrobialmicroorganismmorphometrymyelinationnonhuman primateprenatalpreventprogenitorprogramsreproductiveresearch studyresponseuterine contractilitywhite 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(由申请方提供):本研究计划的目的是评估抗生素和抗炎治疗对早产和早产相关后遗症(即,胎儿肺损伤)在移动的,长期插管的妊娠恒河猴感染支原体(以前U.解脲支原体血清型1)。我们的假设是,产前治疗宫内脲原体感染,静脉注射大环内酯类抗生素联合抗炎剂和免疫调节剂,将抑制早产,延迟早产,改善或预防胎儿/新生儿肺部疾病。生理学研究以及宫内和胎儿组织的细胞和分子研究将解决以下问题:(1)阿奇霉素联合前列腺素合成抑制剂(吲哚美辛)和地塞米松治疗是否能抑制羊膜内微生物生长并下调细胞因子/前列腺素级联反应?(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?将比较未治疗、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,以建立支原体感染、早产、胎儿肺损伤和对治疗的反应(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中的阿齐兰定、细胞因子、白细胞、MMPs水平以及母体、胎儿和羊水中的阿奇霉素水平相关。将对羊水、血液和胎儿组织进行支原体定量培养和PCR。将通过实时PCR定量组织细胞因子mRNA。将通过组织病理学和免疫组织化学方法以及肺形态学评估胎仔肺损伤。将检查胃肠道、脑膜和大脑的炎症。将通过免疫组织化学方法和细胞凋亡测定来评价脑白色物质中少突胶质细胞祖细胞和其他细胞类型的死亡。所提出的工作是独特的,在一个完善的非人灵长类动物宫内感染模型中使用联合干预策略。该结果应阐明脲原体在早产中的因果作用,并导致临床管理的进步。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Juha Pekka Rasanen其他文献
Juha Pekka Rasanen的其他文献
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{{ truncateString('Juha Pekka Rasanen', 18)}}的其他基金
PRETERM LABOR AND FETAL SEQUELAE: ROLE OF MYCOPLASMAS
早产和胎儿后遗症:支原体的作用
- 批准号:
7958410 - 财政年份:2009
- 资助金额:
$ 35.82万 - 项目类别:
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