SEVERE PERIODONTITIS AS A RHEOLOGIC MODIFIER

作为流变调节剂治疗严重牙周炎

• 批准号: 6024648
• 负责人: STEVEN P ENGEBRETSON
• 金额: $ 9.77万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6024648
• 关键词: acute phase protein; bacteria infection mechanism; biomarker; blood chemistry; clinical research; cytokine; dental disorder diagnosis; endotoxins; enzyme linked immunosorbent assay; fibrinogen; gram negative bacteria; hemostasis; human subject; human therapy evaluation; inflammation; interleukin 6; lipopolysaccharides; longitudinal human study; molecular pathology; periodontitis; plasminogen activator inhibitors; serum; statistics /biometry; thrombosis; tumor necrosis factor alpha

Cytokines play a key role in the host response to microbial infection. These mediators are induced following contact with Gram (-) bacteria, and have a wide range of effects including influencing hemostatic factors, which are risk indicators for thrombotic events. Experimental evidence has conclusively established that a low-dose endotoxin bolus in healthy human volunteers alters rheologic parameters via a cytokine cascade resulting in a transient procoagulant state. Further, recent case-control studies have shown severe periodontal disease to be a strong independent risk factor for myocardial infarct and stroke. While causation has not been established, the initiating step is likely the transient bacteremia that result when the highly vascular, chronically inflamed periodontium is mechanically irritated by chewing, toothbrushing, and dental procedures. We hypothesize that chronic Gram(-) infection of the periodontium represents a potential source of circulating endotoxin which may adversely effect the coagulation system via a transient bacteremia-induced cytokine cascade, resulting in a net procoagulant state. The goal of this study is to explore the association of severe periodontitis and hemostatic variables. We suggest that patients with severe chronic adult periodontitis are at risk for altered rheologic and hemostatic variables as has been shown in experimental endotoxemia studies. Specifically, we will monitor the sera of 20 adults with severe periodontitis during common dental manipulations and periodontal treatment to determine the temporal appearance of endotoxin, inflammatory cytokines, and coagulation products, and to test whether conservative therapy can reduce serum levels of acute phase proteins. This study will help to define the pathophysiology of the thrombotic disorder-periodontitis relationship, and identify future thrombotic disorder prevention strategies. This study will be the first to experimentally demonstrate whether periodontal disease is a systemic modifier of clinically relevant hemostatic variables, and is designed to establish a molecular mechanism to explain this relationship. A positive finding in this regard should have broad ramifications for both dentistry and medicine. Dr. Engebretson will receive training in research methodology and molecular biology in order to explore the mechanisms of periodontal medicine through the conduct of human clinical studies as a career goal.

细胞因子在宿主对微生物感染的反应中起关键作用。 这些介质在与革兰氏（-）菌接触后被诱导，并具有广泛的影响，包括影响止血因素，这是血栓形成事件的风险指标。 实验证据已最终确定，健康人类志愿者中的低剂量内毒素推注通过细胞因子级联改变流变学参数，导致短暂的促凝血状态。 此外，最近的病例对照研究表明，严重的牙周病是心肌梗死和中风的一个强有力的独立危险因素。 虽然因果关系尚未确定，但最初的步骤很可能是当高度血管化、慢性炎症的牙周组织受到咀嚼、刷牙和牙科手术的机械刺激时导致的短暂菌血症。 我们假设牙周组织的慢性革兰氏阴性菌感染是循环内毒素的一个潜在来源，可能通过瞬时菌血症诱导的细胞因子级联反应对凝血系统产生不利影响，导致净促凝状态。 本研究的目的是探讨严重牙周炎和止血变量之间的关系。 我们认为，严重的慢性成人牙周炎患者有改变流变学和止血变量的风险，已经在实验性内毒素血症研究中显示。 具体来说，我们将监测20名成人严重牙周炎的血清中常见的牙科操作和牙周治疗，以确定内毒素，炎症细胞因子和凝血产物的时间外观，并测试是否保守治疗可以降低血清中的急性时相蛋白水平。 本研究将有助于明确血栓性疾病与牙周炎之间的病理生理学关系，并确定未来血栓性疾病的预防策略。 这项研究将是第一个实验证明牙周病是否是临床相关止血变量的全身修饰剂，并旨在建立一个分子机制来解释这种关系。 在这方面的积极发现应该对牙科和医学产生广泛的影响。 Engebretson博士将接受研究方法和分子生物学方面的培训，以通过开展人类临床研究来探索牙周医学的机制。