ORAL INFECTION AND SEPTIC CHALLENGE

口腔感染和化脓性挑战

• 批准号: 6300934
• 负责人: RAY C WILLIAMS
• 金额: $ 11.68万
• 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/6300934
• 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.

对动物模型和人群正在进行的研究继续表明，牙周炎等口腔感染与动脉粥样硬化和早产低出生体重等全身性疾病的病因有关。事实上，口腔病原体造成的慢性和脓毒症挑战似乎使炎症介质的局部和全身释放永久化，导致两个层面的疾病表现。拟议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) 评估完全消除和/或治疗口腔感染后这些反应的变化。 将从北卡罗来纳大学牙科诊所寻求常规综合护理的患者中招募 195 名符合纳入标准的患者。在基线时，患者将被分为四个口腔疾病队列之一：1）由于牙周炎（TD-P）导致的末牙列（即大多数需要拔牙的牙齿）； 2）由于龋齿导致的末牙列（TD-C）； 3) 由于牙周炎和龋齿导致的终牙列（即混合型）（TD-M）； 4) 中度至晚期成人牙周炎 (AP)，但牙列可挽救。将收集有关患者人口统计、医疗和牙科病史、口腔健康影响概况 (OHIP) 和口腔健康状况（牙科、牙周和龈沟液评估）的基线数据。此后，终牙列患者将接受规定的拔牙和修复治疗。 AP患者将接受传统的非手术治疗。在基线（治疗前）以及治疗后 2、6、26 和 52 周，将为所有患者收集全血。将使用 ELISA 技术分析以下介质组的血清样本：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）、氧化应激标记物 (8-epi-PGF2a) 和同型半胱氨酸。此外，血清纤维蛋白原水平和血细胞计数将作为止血和血液学的标志物进行报告。将使用重复测量ANCOVA 来分析继发于干预措施的中介反应的组间差异。如果数据表明口腔感染消除（尤其是 TD-P）后全身炎症介质显着减少，则评估口腔疾病预防干预措施和全身临床结果的方案可能是合理的。