Periodontitis and Preterm Birth:Nonhuman Primate Model

描述(由申请人提供)：当前的人类流行病学报告 表明早产和低出生体重之间存在正相关 (PTB/LBW)新生儿和母亲的牙周病患病率。六十 婴儿死亡率百分比(不是由于先天/解剖缺陷) 与PTB/LBW相关联。这个项目的目标是调查 慢性牙周炎患者PTB/LBW与牙周炎关系的可能机制 体内模型系统。鹦鹉帕皮奥·阿努比斯，它有95%的基因 与人类的同源性将被用来研究测试假设的目的：(1) 牙周炎的发病率和严重性导致发病率增加。 (2)牙周炎的进展特征是牙周炎 致病的龈下微生物种类和系统性表达增加 斑块致病性，与肺结核/LBW发病率增加相关 新生儿；以及(3)牙周炎的进展以局部为特征 和全身性炎症生物标志物，它们与增加的 新生儿肺结核/低出生体重儿发病率。400只雌性狒狒，栖息在西南部 NIH地区灵长类中心生物医学研究基金会(SFBR)将 被随机分成两组。在基线样本采集之后(血液， 沟液(GCF)、龈下菌斑、临床评估) 狒狒，将放置结扎器(一个上颌/一个下颌象限；6 磨牙)，试验组200颗。然后两个小组都将被 被介绍给雄性。将确认怀孕并确定孕龄 在大约3个月时使用超声波。口腔样本将在以下地点采集 这个时间点，然后在对侧放置结扎物 实验组上颌骨象限延长 暴露变量(即牙周炎)。动物的样本将在 妊娠和结扎完成后约30天 已删除。在试验组和对照组中，出生日期和出生后 体重将在出生后14天内获得。血液IGCF样本将是 检测急性期反应物和内毒素活性。Sera也将被 口腔微生物免疫球蛋白抗体检测。临床和临床上的差异 实验室参数将在结果(PTB/LBW与正常之间)进行评估 新生儿)和组间(试验组与对照组)。由此产生的结果 调查将描述这种联系的机制，并有助于 治疗和临床干预策略的发展。

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.