ORAL INFECTION AND SEPTIC CHALLENGE

口腔感染和化脓性挑战

• 批准号: 6156414
• 负责人: RAY C WILLIAMS
• 金额: --
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6156414
• 关键词: acute phase protein; antiinfective agents; bacterial disease; blood chemistry; clinical research; dental caries; enzyme linked immunosorbent assay; fibrinogen; human subject; human therapy evaluation; inflammation; interleukin 6; oral bacteria; oral health; oxidative stress; periodontitis; tooth extraction

Ongoing research in animal models and human populations continues to implicate oral infections like periodontitis in the etiology of systemic conditions such as atherosclerosis and pre-term low birth weight. Indeed, the chronic and septic challenge posed by oral pathogens appears to perpetuate both the local and systemic release of inflammatory mediators leading to manifestations of disease at both levels. The proposed human cohort study aims 1) to determine the extent of systemic inflammatory responses in patients with advanced, end-stage oral injections; and 2) to evaluate changes in these responses following complete elimination and/or treatment of the oral infection. 195 patients meeting inclusion criteria will be recruited from the pool of patients seeking conventional, comprehensive care at UNC School of Dentistry Clinics. At baseline, patients will be categorized on one of four oral disease cohorts: 1) terminal dentition (i.e. most teeth requiring extraction) due to periodontitis (TD-P); 2) terminal dentition due to caries (TD-C); 3) terminal dentition due to periodontitis and caries (i.e., mixed) (TD-M); an 4) moderate to advanced adult periodontitis (AP) but with a salvageable dentition. Baseline data regarding patient demographics, medical and dental histories, oral health impact profile (OHIP) and oral health status (dental, periodontal and gingival crevicular fluid evaluations) will be collected. Thereafter, terminal dentition patients will be treated with prescribed extraction and prosthetic treatments. AP patients will be treated with conventional non-surgical therapy. At baseline (pretreatment) and at 2, 6, 26, and 52 weeks post-treatment, whole blood will be collected for all patients. Serum samples will be analyzed using ELISA techniques for the following groups of mediators: acute phase response reactants (IL-6, haptoglobin, LPS-binding protein and C-reactive protein), oxidative stress markers (8-epi-PGF2a) and homeocystein. In addition, serum fibrinogen levels and while blood counts will be reported as markers of hemostasis and hematology. Inter-group differences in mediator responses secondary to the interventions will be analyzed using repeated measures ANCOVA. If the data indicate a pronounced reduction in systemic inflammatory mediators following oral infection elimination (especially TD-P), protocols evaluating oral disease preventive interventions and systemic, clinical outcomes may be justified.

在动物模型和人群中进行的研究继续暗示口腔感染如牙周炎在全身性疾病如动脉粥样硬化和早产低出生体重的病因学中。事实上，口腔病原体造成的慢性和脓毒性挑战似乎使炎症介质的局部和全身释放永久化，导致两个水平的疾病表现。拟定的人类队列研究旨在1）确定晚期终末期口服注射患者的全身炎症反应程度; 2）评价完全消除和/或治疗口腔感染后这些反应的变化。 195名符合入选标准的患者将从寻求传统的，综合护理的患者库中招募。在基线时，患者将被分类为四个口腔疾病群组中的一个：1）由于牙周炎（TD-P）导致的终末牙列（即，大多数牙齿需要拔除）; 2）由于龋齿（TD-C）导致的终末牙列; 3）由于牙周炎和龋齿（即，混合型）（TD-M）; 4）中度至晚期成人牙周炎（AP），但有可挽救的牙列。将收集有关患者人口统计学、病史和牙科史、口腔健康影响概况（OHIP）和口腔健康状况（牙科、牙周和龈沟液评价）的基线数据。此后，终末牙列患者将接受规定的拔牙和修复治疗。AP患者将接受常规非手术治疗。在基线（治疗前）和治疗后2、6、26和52周，将采集所有患者的全血。将使用ELISA技术分析血清样本中的以下介质组：急性期反应反应物（IL-6、触珠蛋白、LPS结合蛋白和C反应蛋白）、氧化应激标志物（8-epi-PGF 2a）和同型半胱氨酸。此外，将血清纤维蛋白原水平和白细胞计数报告为止血和血液学标志物。将使用重复测量ANCOVA分析干预措施继发的中介反应的组间差异。如果数据表明口腔感染消除后全身炎症介质显著减少（特别是TD-P），则评估口腔疾病预防干预措施和全身临床结局的方案可能是合理的。