SEVERE PERIODONTITIS AS A RHEOLOGIC MODIFIER

细胞因子在宿主对微生物感染的反应中起着关键作用。这些介质是在接触革兰氏(-)细菌后诱导的，具有广泛的影响，包括影响止血因素，这是血栓事件的风险指标。实验证据确凿地证明，健康志愿者服用低剂量内毒素丸后，通过细胞因子级联反应改变血液流变学参数，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烈的独立危险因素。虽然病因尚未确定，但最初的步骤很可能是当高度血管的、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一过性菌血症。我们假设牙周组织的慢性革兰氏(-)感染是循环内毒素的潜在来源，循环内毒素可能通过短暂的菌血症诱导的细胞因子级联作用对凝血系统产生不利影响，从而导致净促凝状态。本研究的目的是探讨重度牙周炎与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存在血液流变学和止血变量改变的风险，正如实验性内毒素血症研究所显示的那样。具体地说，我们将监测20名患有严重牙周炎的成年人在常规牙科操作和牙周治疗期间的血清，以确定内毒素、炎性细胞因子和凝血产物的暂时出现，并测试保守治疗是否可以降低血清急性时相蛋白水平。这项研究将有助于明确血栓性疾病-牙周炎的病理生理学关系，并确定未来血栓性疾病的预防策略。这项研究将首次从实验上证明牙周病是否是临床相关止血变量的系统性修饰物，并旨在建立一个解释这种关系的分子机制。在这方面的积极发现应该会对牙科和医学产生广泛的影响。Engebretson博士将接受研究方法论和分子生物学方面的培训，以通过进行人类临床研究来探索牙周医学的机制，作为职业目标。

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.