ORAL INFECTION AND SEPTIC CHALLENGE

口腔感染和化脓性挑战

• 批准号: 6340843
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340843
• 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.

在动物模型和人类群体中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儿低出生体重等全身疾病的病因有关。事实上，口腔病原体造成的慢性和脓毒症挑战似乎使局部和全身炎症介质的释放永久化，从而导致两种水平的疾病表现。这项拟议的人类队列研究旨在1)确定晚期口腔注射患者全身炎症反应的程度；2)评估在口腔感染完全消除和/或治疗后这些反应的变化。符合纳入标准的195名患者将从北卡罗来纳大学牙科学校诊所寻求常规、全面护理的患者池中招募。在基线水平上，患者将被归类为四种口腔疾病队列中的一种：1)因牙周炎(TD-P)而导致的末牙期(即大多数牙齿需要拔除)；2)因龋齿(TD-C)而导致的末牙期(TD-C)；3)因牙周炎和龋齿(即混合性牙周炎)而导致的末牙期(TD-M)；4)中度至重度成人牙周炎(AP)，但具有可挽救的牙列。将收集有关患者人口统计、病史和牙科病史、口腔健康影响概况(OHIP)和口腔健康状况(牙科、牙周和牙龈沟液评估)的基线数据。此后，牙列晚期患者将接受指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)、治疗后2周、6周、26周和52周，对所有患者采集全血。血清样本将使用ELISA技术分析以下几组介体：急性时相反应反应物(IL-6、结合珠蛋白、内毒素结合蛋白和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被报告为止血和血液学的标志。将使用重复测量ANCOVA分析干预后继发的调解人反应的组间差异。如果数据显示口腔感染消除后全身炎症介质显著减少(尤其是TD-P)，评估口腔疾病预防干预措施和系统性临床结果的方案可能是合理的。