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published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

Periodontitis is a chronic inflammatory disease caused by pathogenic bacteria residing in a complex biofilm within a susceptible host. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate. Our study aimed to evaluate the efficacy of amixicile, when compared to metronidazole, in inhibiting the growth of bacteria present in a microbiome harvested from patients with chronic periodontitis. Plaque samples were harvested from patients with severe chronic periodontitis and cultured under anaerobic conditions. The microbiomes were grown in the presence of amixicile and metronidazole and the growth was compared to that of bacteria grown in the absence of the antimicrobials. Following 24 hour growth the bacterial DNA was analyzed using quantitative PCR (qPCR) using primers specific for 12 bacterial species: P. gingivalis (Pg), P. intermedia (Pi), F.nucleatum (Fn), S.gordonii (Sg), S. anginosus (Sa), V. atypical (Va), L. acidophilus (La), A.actinomycetemcomitans (Aa), T.denticola (Td), S.mutans (Sm), and S.sanguis (Ss). Both drug treatment groups yielded a statistical significant reduction for several anaerobic bacteria: Pi (P

Background: Current research has demonstrated that aspirin and fish oil (EFA) increase plasma levels of specialized pro-resolution molecules (SPMs). This study investigates their effects on SPM precursor pools in platelet rich fibrin (PRF). Methods: Twenty healthy volunteers were randomly assigned to take aspirin; EFA or aspirin and EFA. Four hours later, SPM precursor levels were quantified using combined Liquid Chromatography tandem mass spectrometry. The differences between the groups: Aspirin (yes or no), EFA (yes or no), were analyzed by ANCOVA, testing for group differences after covarying out the baseline value. Results: There were 4 significant interactions, 1 with an aspirin effect, 2 with an EFA effect, and 64 with no difference between the groups. The significant interaction effect was found for the following lipidome: LPE(20:4), LPI(16:1), LPI(18:1), and LPI(20:3). Aspirin decreased the LPG(16:4) levels, and EFA decreased the LPE(22:5) and PG(16:0/18:0) lipidomes. Conclusions: Some SPM precursor pools in PRF were increased following supplementation.

Evidence linking periodontitis and cardiovascular disease points to systemic inflammation as the primary etiology. The investigation into this association has focused on periodontitis as a low grade chronic infection, and subsequently, systemic inflammation and the cascade of numerous markers and mediators integrally involved in the human inflammatory response. The aim of this study was to measure the differences in circulating levels of C-reactive protein and human soluble CD40 ligand as markers and mediators of systemic inflammation in the serum of patients with moderate to severe periodontitis before, during, and after non-surgical periodontal therapy.Twenty-one patients were treated with full mouth scaling and root planing performed on two separate appointments spaced approximately 2 weeks apart. The third visit, an evaluation of non-surgical therapy, occurred 8 weeks after completion of scaling and root planing. Blood samples were procured from each patient at the first and second appointment prior to scaling and root planing and again at a third visit. CRP and sCD40 ligand levels were measured using ELISA. CRP levels remained relatively constant throughout the study maintaining a mean level of 2.44 mg/L at visit 1, 2.53 mg/L at visit 2, and 2.63 mg/L at visit 3. These differences were not statistically significant. sCD40 ligand mean levels were reported to be 847.7 pg/mL, 637.3 pg/mL, and 859.5 pg/mL, respectively for visits 1, 2, and 3. These values were not statistically significant. Within the limitations of this study, no evidence was found to directly relate non-surgical periodontal therapy with the lowering of systemic markers CRP and human soluble CD40 ligand.

Cellular adhesion molecules (CAMs) and selectins are cell-surface proteins involved in the binding of cells to the vascular endothelium. Elevated levels of sCAMs and soluble E-selectin (sE-selectin) have been reported in patients with periodontitis. The aim of this study was to determine if periodontal scaling and root planing would influence the serum concentration of sICAM-1, sVCAM-1, and sE-selectin. Twenty-one subjects with chronic periodontitis received scaling and root planing in conjunction with blood serum sample analysis using enzyme-linked immunosorbent assay (ELISA), to determine if periodontal instrumentation results in changes in serum concentrations of sICAM-1, sVCAM-1, and sE-selectin. No change was observed in serum concentration of sICAM-1 or sVCAM-1. However, in a subset of 17 patients a statistically significant change in serum sE-selectin was observed (P < 0.05). This suggests that there is a decrease in endothelial activation following periodontal treatment.

Objective: To examine whether self-assessment of videotaped surgeries helps improve periodontal residents’ ergonomics. Methods: Residents (n=8) provided self-assessments of their own ergonomics while performing periodontal surgery using a questionnaire with open and closed items. Results were analyzed using quantitative and qualitative means. Results: Comparison of responses resulted in a change between Pre-video Surgery 1 and PSV1 (p<0.05) and between the three occasions for flat foot and horizontal shoulder positions (p<0.05). Resident goals were most numerous for improving positions of shoulder, back and neck and most notable responses for failure to achieve goals were the need for surgical access and being too focused the procedure. Conclusions: Videotape review is a valid means of self-assessment. Intervention solely in the form of a questionnaire and videotape review was insufficient in its ability to change the residents’ ergonomics. Barriers to implementation of proper ergonomics were identified.

Background: There is mounting evidence to indicate that periodontitis may be a risk factor for cardiovascular disease (CVD). Periodontitis may be linked to CVD as either an etiologic mechanism or a predisposing factor that can hasten disease progression. Proinflammatory cytokines, elevated fibrinogen, and platelet aggregation are all potential mechanisms. The purpose of this study is to compare and review the serological differences in subjects with severe periodontitis, some of which involve established risk factors for atherosclerosis, particularly heightened C-reactive protein levels. Methods: A total of 184 subjects, comprising of two periodontal subgroups, non-periodontal (NP = 91) and generalized aggressive periodontitis (SP = 93), had serum evaluated for C-reactive protein (CRP) levels using a high sensitive ELISA test. The CRP levels were compared against clinical and demographical data to include race, age, gender, number of teeth, probing depth, attachment level, bleeding index, plaque index, and gingival index. Results: After adjusting for potential confounding variables, probing depth (p Conclusion: Pocket depth is significantly related to elevated levels of CRP, which is why it is imperative to treat periodontal pockets. This study may provide a possible link between CRP and periodontal disease, but a causal relationship cannot be inferred.

The patient population consisted of a maximum of 18,570 subjects who completed the NHANES III questionnaire and examination from 1988 - 1994. The physical examination included such things as body mass index and serum samples, social and medical history. The periodontal examination recorded probing depth, attachment loss and gingival bleeding. Serum samples were analyzed for CRP levels, cholesterol levels etc. Demographic, cardiovascular and oral health variables were compared in subjects with a history of heart attack. Result showed that history of heart attack is associated with increased odds ratio for elevated CRP, diabetes, hypertension, cholesterol, male gender, non-white race and smoking. Of the periodontal indicators of disease, only gingival bleeding had an increased odds ratio for association with heart attack history. The unadjusted odds ratio was 1.25 with 95% CI[0.84-1.87]. The adjusted odds ratio increase to 1.93 with 95% CI [1.02-3.71]. These findings are consistent with previous research indicating that elevated CRP is associated with increased risk of heart attack. The interesting finding of this study is that only gingival bleeding, not probing depth or attachment loss, had an increased odds ratio for an associated with self-reported history of heart attack.

Aim: The aim of this study is to determine the frequency of single nucleotide polymorphisms (SNPs) in various pattern recognition receptor (PRR) genes, including Toll like receptors (TLR) -2, -4, -9, and CD14 in chronic (CP), localized (LAP) and generalized aggressive (GAP) periodontitis and periodontally healthy (NP) patients in an African American population. Methods: A total of 205 subjects were involved in the study. The LAP group consists of 25 subjects, the GAP group 50 subjects, the CP group 73 subjects and the NP group 57subjects. Genotyping was performed in TLR2 (G2408A), TLR4 (A896G),TLR9 (T1486C) and CD14 (C260T) genes by TaqMan® allelic discrimination using Assay-by-DesignSM SNP Genotyping Assays (Applied Biosystems). Accuracy of genotyping was confirmed by known DNA samples of each genotype and by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses on selected samples. Fisher’s exact test and chi-square analyses were performed to compare genotype and allele frequencies. Within disease groups, we investigated whether SNPs were related to disease severity by step-wise logistic regression adjusted for age, gender, and smoking status. Results: There was a significant difference in the distribution of specific TLR9 (T1486C) genotypes between diseased-groups versus reference group. Expression of TT genotype was more prevelant in periodontally-diseased individuals compared to periodontally-healthy subjects (p<0.0001) whereas individuals expressing C allele of the TLR9 SNP (CC&CT) were more frequently found in healthy group after adjusting for age, gender, and smoking status (p<0.0001) There was no statistically significant difference in the distribution of genotypes between groups for any other TLRs or CD 14 polymorphism. Conclusion: Based on findings of this study, homozygocity for the T allele of TLR 9 polymorphism was related to the periodontal disease susceptibility in African Americans. Additionally, presence of C allele at TLR-9 appeared to confer resistance to periodontal destruction. Our results showed that specific SNPs in TLR-2, -4 and CD 14 genes are not related to periodontitis in African Americans. However, low copy number of certain alleles warrants further investigations with increased sample size to explore the role of SNPs in periodontal disease. This study was supported by the Alexander Fellowship.