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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23DE000449-01
Application #
6024648
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Lipton, James A
Project Start
2000-02-01
Project End
2004-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
1
Fiscal Year
2000
Total Cost
$97,658
Indirect Cost
Name
Columbia University (N.Y.)
Department
Dentistry
Type
Schools of Dentistry
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Engebretson, Steven P; Hey-Hadavi, Judith (2011) Sub-antimicrobial doxycycline for periodontitis reduces hemoglobin A1c in subjects with type 2 diabetes: a pilot study. Pharmacol Res 64:624-9
Chen, Chia-Yi; Hasselgren, Gunnar; Serman, Neill et al. (2007) Prevalence and quality of endodontic treatment in the Northern Manhattan elderly. J Endod 33:230-4
Engebretson, S; Chertog, R; Nichols, A et al. (2007) Plasma levels of tumour necrosis factor-alpha in patients with chronic periodontitis and type 2 diabetes. J Clin Periodontol 34:18-24
Engebretson, Steven P; Vossughi, Faranak; Hey-Hadavi, Judith et al. (2006) The influence of diabetes on gingival crevicular fluid beta-glucuronidase and interleukin-8. J Clin Periodontol 33:784-90
Engebretson, Steven P; Lamster, Ira B; Elkind, Mitchell S V et al. (2005) Radiographic measures of chronic periodontitis and carotid artery plaque. Stroke 36:561-6
Engebretson, Steven P; Hey-Hadavi, Judith; Ehrhardt, Fernando J et al. (2004) Gingival crevicular fluid levels of interleukin-1beta and glycemic control in patients with chronic periodontitis and type 2 diabetes. J Periodontol 75:1203-8
Zhang, Fan; Engebretson, Steven P; Morton, Rakhi S et al. (2003) The overexpression of cyclo-oxygenase-2 in chronic periodontitis. J Am Dent Assoc 134:861-7