BACKGROUND: In the US 47.2% of adults have periodontitis. Alcohol affects the host response, impairs immune function, has toxic effects on the liver and affects with protein metabolism, and therefore may increase the risk of periodontitis. Alcohol may also interfere with homocysteine (Hcy) metabolism and result in hyperhomocysteinemia (HHcy), a risk factor for inflammatory diseases such as cardiovascular disease and possibly periodontal disease. Understanding the exact relationship between alcohol consumption, HHcy and periodontitis is incomplete. OBJECTIVES: To add to our understanding of the alcohol-periodontitis, periodontitis-Hcy and alcohol-Hcy associations longitudinally by addressing methodological issues that confound past research. Methods: The study used existing data from 562 male participants in the VA Dental Longitudinal Study (DLS) who answered food frequency questionnaires (FFQ), underwent periodontal examinations and had plasma . Hcy measurements (N=469). Periodontitis was defined using the CDC case definition (Eke et al., 2009) and categorized into none/mild/moderate or severe disease. HHcy was defined as Hcy ≥10.2 umol/L based on Spence et al., 2001. Alcohol intake was categorized as none, ≤ 1 drink/day, >1 but <2 drinks/day, or ≥ 2 drinks/day. RESULTS: In longitudinal analyses, the risk of developing severe periodontitis among alcohol consumers was 10-17% higher over a period of 19-years compared to non-drinkers after controlling for age, smoking, diabetes, education, and number of teeth present. These estimates were higher still among men with lower than average vitamin B6 or B12 intakes. However, these results were not statistically significant The analyses suggested that men with mild, moderate or severe periodontitis had greater hazards of developing HHcy compared to disease-free participants after adjusting for covariates, but these results were not statistically significant. Consuming more than 2 drinks of alcohol per day significantly increased the risk of developing HHcy by 76% (p= 0.037). SUMMARY: Our findings suggest that alcohol consumption may increase the hazards of developing severe periodontal disease especially if vitamin B complex intakes are low. These results also suggest that periodontal disease and alcohol consumption each increases the hazards of hyperhomocysteinemia. We believe this is the first prospective cohort study to examine associations among periodontitis, homocysteine and alcohol consumption.

The importance of oral health on systemic health is a highly researched area of study in recent years. There has been a shift in dental visits from acute emergencies to ongoing preventative care due to the knowledge connecting oral and systemic health. One of the commonly researched connections is the link between periodontal disease and heart disease. Periodontal disease is defined as inflammation of the gum tissue, resulting in periodontal pockets that can lead to infection, bone loss and even loss of the tooth. Cardiovascular disease, or heart disease, is a term that encompasses many different conditions of the heart, including heart failure, myocardial infarction, atherosclerosis and angina. There is constant research to better understand the relationship between the two diseases, as well as any causality that may exist. Recent studies have been able to link the diseases, but no causal link has been found. The role of the bacteria involved in both diseases has recently been considered to see if these organisms are related to a potential causal link. Two particular bacteria that are known to be involved with periodontal disease are Porphyromona gingivalis and Treponema denticola. These bacteria are present when a patient develops periodontal disease, but they are not usually present in a healthy individual. Additionally, the bacteria that make up the contents of plaque found in the heart have been studied to see if there are any similarities with oral microbes. It has been found that oral bacteria can be present in arterial plaque samples. This research may allow a better understanding of how and why heart disease occurs and potentially serve as a way to treat heart disease accompanied by periodontal disease, if a causal relationship is elucidated. Heart disease is usually a devastating disease, sometimes resulting in the death of the patient. If more patients attend the dentist as a preventative measure, the risk of periodontal disease and associated pathologies may be reduced. Additionally, those that have already developed periodontal disease can work with a dental professional to reverse the disease. It is known that the bacteria in the mouth can enter the bloodstream upon infection, so patients with suspected periodontitis should be treated to avoid the bacteria from entering the blood and affecting other organs such as the heart. An examination of the bacteria commonly found in the oral cavity at times of periodontal disease may lead to a better understanding of how and why these bacteria invade the bloodstream. It would be beneficial to compare the microbiota of both the plaque in the mouth and the plaque in a vessel supplying the heart in a patient suffers from heart disease. This understanding may lead to therapeutic interventions that aid in the prevention of bacteria traveling in the bloodstream. For many Americans, oral health care was believed to end at home by brushing and flossing. However, it is important to see a dental professional to avoid any possible complications that may not be apparent to the untrained eye. A simple dental cleaning may be important to detect the start of periodontal disease, and treatment can be initiated to end the potential spread of bacteria. It is important to maintain positive oral health in order to maintain overall systemic health, including the avoidance of heart disease.

Current understanding of periodontal disease derives from studies mostly conducted in developed countries. However, the disease process among those studied populations may be confounded by the professional dental care. There have been few attempts to investigate factors related to the disease among populations of developing countries where the natural history of the disease is minimally confounded by care. This imbalance is evident in risk assessment research on the associations between periodontal disease and smoking-one of the most significant risk factors for the disease. Also, most studies on smoking used convenience or purposive samples, which may bias the findings. Therefore, there is a need for research conducted among a representative sample of a developing country. The present study aimed to describe the prevalence, extent and severity of chronic adult periodontitis among representative Vietnamese middle-aged adults. Also, it aimed to investigate smoking, which is highly prevalent in Vietnam, as a risk indicator for periodontal disease in a population with minimal access to dental care. The study was designed as a cross-sectional population-based study with a multistage, stratified random sample with probability of selection proportional to population size. The US National Institute of Dental Research (NIDR) protocol was used to assess loss of periodontal attachment among 575 dentate subjects in two randomly selected provinces. Assessment was made at mesial and buccal sites of every present tooth, excluding third molars. A parallel social survey collected socio-demographic information and smoking history, which were assessed for possible association with the disease status. Periodontal disease was highly prevalent among the sample. The patterns of the disease were similar to those reported from other populations. Virtually all subjects expressed some levels of disease, whereas only a few subjects or sites had severe disease. Bivariate analyses revealed significant associations between smoking and lower socio-economic status with more severe expression of the disease. Smoking was consistently associated with poorer periodontal status irrespective of outcome measure investigated. Multivariate models showed that smoking was the most predictive factor for the disease. The Odds Ratio of having severe periodontitis (that is, having 2+sites with loss of attachment more than or equal to 5 mm and 1+sites with pocket depth more than or equal to 4 mm) was 7.93 for heavy smokers compared to non-smokers. A dose-response effect of the association between smoking and the outcomes of the disease was also evident. The study provided a picture of the periodontal status of the representative sample from Vietnamese middle-aged adult population where the disease was less confounded by dental care. Furthermore, the study contributes consistency, strength and dose-response effect to the association of smoking as a risk indicator for periodontal destruction. The study should be used to assist the public health agencies in planning appropriate policies for Vietnam to address smoking and periodontal disease. / Thesis (M.Sc.)--Dental School, 2001.

Objectives: Periodontal disease is a chronic inflammation resulting in periodontal attachment loss. Keratinocyte Growth Factor-1 (KGF-1) is upregulated in chronic inflammation and specifically stimulates epithelial cell proliferation by signaling through the epithelial-specific Keratinocyte Growth Factor Receptor (KGFR). First, we examined KGF-1 and KGFR expression and localization in human periodontal tissues. Second, we extended these studies by developing an in vitro mechanical wound model to mimic trauma to the periodontal pocket epithelium and examined ligand independent KGFR activation and cell migration. Methods: In our study of human gingival tissues, we used immunohistochemistry and laser capture microdissection with RT-PCR to analyze KGF-1 and KGFR expression and localization. To study ligand independent KGFR phosphorylation, KGFR internalization along the wound edge was imaged using immunohistochemical staining and KGFR phosphorylation confirmed using immunoprecipitation with western blotting. Wounding induced oxidative stress was detected using DCFH-DA (2',7'-dichlorofluorescin diacetate) and modulated by pretreatment with an antioxidant. Changes in migration were examined in the presence or absence of pathway specific inhibitors. Results: KGF-1 protein localized to areas of junctional and basal oral epithelial cells was significantly increased in periodontal pocket epithelium (p<0.01) and oral epithelium (p<0.05) of disease-associated tissues. KGFR localized to the junctional and the parabasal cells of oral epithelium, and was increased in disease-associated pocket epithelium (p<0.05). Laser capture microdissection with RT-PCR confirmedKGF-1 and KGFR were specifically expressed by connective tissue and epithelium, respectively. In our cell culture model, mechanical wounding induced ligand independent KGFR activation. ROS (Reactive Oxygen Species) generation along the wound edge was associated with KGFR activation and scavenging of ROS reduced KGFR phosphorylation. The c-Src family inhibitor, PP1, significantly inhibited KGFR phosphorylation. Functionally cell migration was reduced by PP1 (82.7%), SU5402(70%) and PD98059 (57%). Conclusions: KGF-1 and KGFR proteins are expressed in health but significantly induced in human diseased periodontal tissues. Microwounding associated generation of ROS mediates KGFR phosphorylation via c-Src kinase signaling and induced wound edge cell migration. Therefore, regulation of epithelial cell behavior associated with the onset and progression of periodontal disease may possibly be mediated by two related but distinct mechanisms. (1) Ligand-dependent activation of KGFR due to upregulation of KGF-1. (2) Ligand-independent activation of KGFR due to chronic microwounding.

abstract / Dentistry / Doctoral / Doctor of Philosophy

Objectives: Periodontal disease is a chronic inflammation resulting in periodontal attachment loss. Keratinocyte Growth Factor-1 (KGF-1) is upregulated in chronic inflammation and specifically stimulates epithelial cell proliferation by signaling through the epithelial-specific Keratinocyte Growth Factor Receptor (KGFR). First, we examined KGF-1 and KGFR expression and localization in human periodontal tissues. Second, we extended these studies by developing an in vitro mechanical wound model to mimic trauma to the periodontal pocket epithelium and examined ligand independent KGFR activation and cell migration. Methods: In our study of human gingival tissues, we used immunohistochemistry and laser capture microdissection with RT-PCR to analyze KGF-1 and KGFR expression and localization. To study ligand independent KGFR phosphorylation, KGFR internalization along the wound edge was imaged using immunohistochemical staining and KGFR phosphorylation confirmed using immunoprecipitation with western blotting. Wounding induced oxidative stress was detected using DCFH-DA (2',7'-dichlorofluorescin diacetate) and modulated by pretreatment with an antioxidant. Changes in migration were examined in the presence or absence of pathway specific inhibitors. Results: KGF-1 protein localized to areas of junctional and basal oral epithelial cells was significantly increased in periodontal pocket epithelium (p<0.01) and oral epithelium (p<0.05) of disease-associated tissues. KGFR localized to the junctional and the parabasal cells of oral epithelium, and was increased in disease-associated pocket epithelium (p<0.05). Laser capture microdissection with RT-PCR confirmedKGF-1 and KGFR were specifically expressed by connective tissue and epithelium, respectively. In our cell culture model, mechanical wounding induced ligand independent KGFR activation. ROS (Reactive Oxygen Species) generation along the wound edge was associated with KGFR activation and scavenging of ROS reduced KGFR phosphorylation. The c-Src family inhibitor, PP1, significantly inhibited KGFR phosphorylation. Functionally cell migration was reduced by PP1 (82.7%), SU5402(70%) and PD98059 (57%). Conclusions: KGF-1 and KGFR proteins are expressed in health but significantly induced in human diseased periodontal tissues. Microwounding associated generation of ROS mediates KGFR phosphorylation via c-Src kinase signaling and induced wound edge cell migration. Therefore, regulation of epithelial cell behavior associated with the onset and progression of periodontal disease may possibly be mediated by two related but distinct mechanisms. (1) Ligand-dependent activation of KGFR due to upregulation of KGF-1. (2) Ligand-independent activation of KGFR due to chronic microwounding.

Current understanding of periodontal disease derives from studies mostly conducted in developed countries. However, the disease process among those studied populations may be confounded by the professional dental care. There have been few attempts to investigate factors related to the disease among populations of developing countries where the natural history of the disease is minimally confounded by care. This imbalance is evident in risk assessment research on the associations between periodontal disease and smoking-one of the most significant risk factors for the disease. Also, most studies on smoking used convenience or purposive samples, which may bias the findings. Therefore, there is a need for research conducted among a representative sample of a developing country. The present study aimed to describe the prevalence, extent and severity of chronic adult periodontitis among representative Vietnamese middle-aged adults. Also, it aimed to investigate smoking, which is highly prevalent in Vietnam, as a risk indicator for periodontal disease in a population with minimal access to dental care. The study was designed as a cross-sectional population-based study with a multistage, stratified random sample with probability of selection proportional to population size. The US National Institute of Dental Research (NIDR) protocol was used to assess loss of periodontal attachment among 575 dentate subjects in two randomly selected provinces. Assessment was made at mesial and buccal sites of every present tooth, excluding third molars. A parallel social survey collected socio-demographic information and smoking history, which were assessed for possible association with the disease status. Periodontal disease was highly prevalent among the sample. The patterns of the disease were similar to those reported from other populations. Virtually all subjects expressed some levels of disease, whereas only a few subjects or sites had severe disease. Bivariate analyses revealed significant associations between smoking and lower socio-economic status with more severe expression of the disease. Smoking was consistently associated with poorer periodontal status irrespective of outcome measure investigated. Multivariate models showed that smoking was the most predictive factor for the disease. The Odds Ratio of having severe periodontitis (that is, having 2+sites with loss of attachment more than or equal to 5 mm and 1+sites with pocket depth more than or equal to 4 mm) was 7.93 for heavy smokers compared to non-smokers. A dose-response effect of the association between smoking and the outcomes of the disease was also evident. The study provided a picture of the periodontal status of the representative sample from Vietnamese middle-aged adult population where the disease was less confounded by dental care. Furthermore, the study contributes consistency, strength and dose-response effect to the association of smoking as a risk indicator for periodontal destruction. The study should be used to assist the public health agencies in planning appropriate policies for Vietnam to address smoking and periodontal disease. / Thesis (M.Sc.)--Dental School, 2001.

Thesis (Ph. D.)--University of Sydney, 2003. / Includes list of published articles: leaf vi. Includes bibliographical references. Also available in print form.

Thesis (doctoral)--Universität Tübingen, 1933.

Thesis (M.S.)--University of Louisville, 1998. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.