Biologic Basis of Refractory Periodontal Disease

描述：这项研究的长期目标是能够适当地 诊断并成功治疗所有牙周病患者。 目前，约有15%的牙周炎患者常规治疗失败。 并被认为是“难对付的”。此应用程序检查以下假设： 难治性牙周病与非难治性牙周病不同， 寻求前瞻性地识别这些患者的方法。这些目标是 有4个具体目标。目的我将检验这样一个假设，即受试者 难治性疾病可以与可治疗的疾病区分开来 基于微生物图谱的牙周炎和牙周健康。牙龈下 斑块样本将从28个地点采集，每个地点至少有80名受试者 两个病变组和40名健康受试者。将对样品进行分析 使用棋盘DNA分别计算约120个分类群的水平 杂交分析。疱疹病毒也将受到监测。它的意义 这一目标是，它将识别这些物种(包括可栽培和 目前不能种植的)，可用来区分耐火材料 和可治疗的牙周炎，以及健康。目标2将检验这一假设 难治性疾病的受试者可以与可治疗的受试者区分开来。 牙周炎和基于宿主因素的牙周健康，如血清 40种特定牙周细菌的抗体水平和细胞因子的产生 刺激后外周血单核细胞。这一目标的意义 是识别区分疾病的关键宿主标志物 团体和健康。AIM 3将开发一种人类口腔微生物芯片 在人类体内发现的600种可培养和不可培养的口腔物种的检测 口腔。来自AIM 1的微生物样本将使用 这个微阵列提供了基本完整的微生物覆盖。这 微阵列将促进口腔生态学、感染性的其他研究工作 疾病和临床研究。该微阵列具有明显的诊断价值。 目标4将使用结合的临床、微生物和宿主数据来区分 顽固性牙周炎来自可治疗的牙周炎或健康，并 辨别难治性综合征。这个项目的完成将填补主要的空白 对口腔总菌群在难治性和慢性牙周炎中的作用的认识存在差距 可治疗的牙周炎以及细胞因子、趋化因子和它们的作用 感受器。消除顽固性疾病将对 提供牙周治疗的总成本。

DESCRIPTION: The long-term goal of this research is to be able to appropriately diagnose and successfully treat all patients with periodontal disease. Currently, about 15 percent of periodontitis patients fail conventional therapy and are deemed "refractory." This application examines the hypothesis that refractory disease is distinct from non-refractory periodontal disease, and seeks means for prospectively identifying these patients. These objectives are addressed in 4 Specific Aims. Aim I will test the hypothesis that subjects with refractory disease can be distinguished from subjects with treatable periodontitis and periodontal health based upon microbial profiles. Subgingival plaque samples will be taken from 28 sites from at least 80 subjects in each of the 2 diseased groups and 40 healthy subjects. The samples will be analyzed individually for levels of approximately 120 taxa using checkerboard DNA hybridization assays. Herpes viruses will also be monitored. The SIGNIFICANCE of this Aim is that it will identify those species (both cultivable and presently uncultivable) that are useful for distinguishing between refractory and treatable periodontitis, and health. Aim 2 will test the hypothesis that subjects with refractory disease can be distinguished from those with treatable periodontitis, and periodontal health based upon host factors, such as serum antibody levels to 40 specific periodontal bacteria and cytokine production by peripheral blood monocytes following stimulation. The SIGNIFICANCE of this Aim is the identification of key host markers that differentiate between disease groups and health. Aim 3 will develop a Human Oral Microbe Microarray for the detection of 600 cultivable and uncultivable oral species found in the human oral cavity. The microbial samples from Aim 1 will be reanalyzed using the essentially complete microbial coverage provided by this microarray. This microarray will facilitate other research efforts in oral ecology, infectious diseases, and clinical studies. The microarray has obvious diagnostic value. Aim 4 will use the combined clinical, microbial and host data to differentiate refractory periodontitis from treatable periodontitis or health, and to identify refractory syndromes. Completion of this project will fill in major gaps in knowledge of the role of the total oral flora in refractory and treatable periodontitis, and of the role of cytokines, chemokines and their receptors. Eliminating refractory disease would have an enormous impact on the total cost of delivering periodontal therapy.