Periodontitis and Preterm Birth:Nonhuman Primate Model

描述（由申请方提供）：当前人类流行病学报告 表明早产/低出生体重 (PTB/LBW）新生儿和母亲牙周病患病率。六十 婴儿死亡率百分比（非先天性/解剖缺陷所致） 与PTB/LBW有关。本项目的目的是调查 PTB/LBW和牙周炎之间的联系的潜在机制，在一个 体内模型系统。狒狒，Papio anubis，有超过95%的基因， 与人类的同源性将用于研究目的检验假设，即：（1） 牙周炎的发病率和严重程度导致发病率增加 PTB/LBW新生儿;（2）牙周炎的进展特征在于 致病性龈下微生物种类增加和 与PTB/LBW发病率增加相关的菌斑致病性 新生儿;和（3）牙周炎的进展的特点是局部 和全身炎症生物标志物，这与增加 PTB/LBW新生儿的发病率。400只雌性狒狒， 生物医学研究基金会（SFBR），NIH地区灵长类动物中心，将 随机分为两组。在基线样品收集（血液， 龈沟液（GCF），龈下菌斑，临床评估） 狒狒，将放置结扎线（一个上颌/一个下颌象限; 6 实验组（n=200）。两组将在 介绍给男性。将确认妊娠并确定胎龄 在大约3个月时使用超声波。口腔样本将于 在该时间点，随后在对侧放置结扎线 实验组上下颌象限延长， 暴露变量（即牙周炎）。动物采样时间为 妊娠和结扎完成后约30天 删除.在实验组和对照组中， 体重将在出生后14天内获得。将采集IGCF血样 测定急性期反应物和内毒素活性。塞拉也将是 分析口腔微生物的IgG抗体。临床和 将评估结果之间的实验室参数（PTB/LBW vs.正常 新生儿）和组间（实验组与对照组）。结果从这个 调查将描述这种联系的机制，并有助于 制定治疗和临床干预战略。

DESCRIPTION (provided by applicant): Current human epidemiologic reports indicate a positive association between preterm birth/low birth weight (PTB/LBW) neonates and periodontal disease prevalence in the mother. Sixty percent of infant mortality (not attributable to congenital/anatomical defects) is linked with PTB/LBW. It is the objective of this project to investigate potential mechanisms of the association between PTB/LBW and periodontitis in an in vivo model system. The baboon, Papio anubis, which has a >95 percent genetic homology to humans will be used to investigate Aims testing hypotheses that: (1) the incidence and severity of periodontitis results in an increased incidence of PTB/LBW neonates; (2) the progression of periodontitis is characterized by an increase in pathogenic subgingival microbial species and systemic expression of plaque pathogenicity, which correlate with an increased incidence of PTB/LBW neonates; and (3) the progression of periodontitis is characterized by local and systemic inflammatory biomarkers, which correlate with an increased incidence of PTB/LBW neonates. 400 female baboons, housed at the Southwest Foundation for Biomedical Research (SFBR), a NIH Regional Primate Center, will be randomized into two groups. Following baseline sample collection (blood, crevicular fluid (GCF), subgingival plaque, clinical assessment) from all baboons, ligature will be placed (one maxillary/one mandibular quadrant; 6 molar teeth) in the experimental group (n=200). Both groups will then be introduced to males. Pregnancy will be confirmed and gestational age determined using ultrasound at approximately 3 months. Oral samples will be collected at this time point, followed by placement of ligatures on the contralateral maxillary and mandibular quadrants of the experimental group to extend the exposure variable (i.e. periodontitis). Animals will be sampled at approximately 30 days following the completion of the pregnancy and ligatures removed. In both experimental and control groups, dates of birth and post-natal weights will be obtained within 14 days of birth. Blood IGCF samples will be assayed for acute phase reactants and endotoxin activity. Sera will also be analyzed for IgG antibody to oral microorganisms. Differences in clinical and laboratory parameters will be assessed between outcome (PTB/LBW vs. normal neonates) and between groups (experimental vs. control). Results from this investigation will describe mechanisms of this linkage and contribute to the development of therapeutic and clinical intervention strategies.