Dolphus R. Dawson

Salivary Biomarkers of Periodontal Disease in Response to Treatment

BACKGROUND Salivary biomarkers of periodontitis were assessed longitudinally to determine response to therapy. METHODS A 6-month case-controlled study of adults with chronic periodontitis was performed, with 33 participants receiving oral hygiene instructions (OHI) alone and 35 with scaling and root planing (SRP) combined with OHI. Saliva samples collected at week 0, 16 and 28 were analysed for interleukin (IL)-1β, IL-8, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase-8 (MMP-8), osteoprotegerin (OPG), and tumour necrosis factor-α (TNF)-α. Clinical measures of periodontal disease were recorded at each visit. RESULTS All parameters of periodontal health improved significantly in both groups by week 16 (p<0.0001) with the SRP group demonstrating greater benefit at week 16 and 28. Baseline OPG and TNF-α levels changed significantly at both follow-up visits (p<0.03), regardless of treatment group. IL-1β and MMP-8 levels decreased significantly from baseline (p<0.04) in the SRP group only. OPG, MMP-8, and MIP-1α were significantly reduced in responders compared with non-responders (p=0.04, 0.01, 0.05, respectively). In receiver-operating characteristic analyses, MMP-8 produced the highest area under the curve (0.7; p=0.01). CONCLUSION Salivary levels of IL-1β, MMP-8, OPG, and MIP-1α reflected disease severity and response to therapy suggesting their potential utility for monitoring periodontal disease status.

Rheumatoid Arthritis and Salivary Biomarkers of Periodontal Disease

AIM To test the hypothesis that rheumatoid arthritis (RA) influenced levels of salivary biomarkers of periodontal disease. METHODS Medical assessments, periodontal examinations and pain ratings were obtained from 35 RA, 35 chronic periodontitis and 35 age- and gender-matched healthy controls in a cross-sectional, case-controlled study. Unstimulated whole saliva samples were analysed for interleukin-1β (IL-1β), matrix metalloproteinase-8 (MMP-8) and tumour necrosis factor-α (TNF-α) concentrations. RESULTS The arthritis and healthy groups had significantly less oral disease than the periodontitis group (P<0.0001), with the arthritis group having significantly more sites bleeding on probing (BOP) than matched controls (P=0.012). Salivary levels of MMP-8 and IL-1β were significantly elevated in the periodontal disease group (P<0.002), and IL-1β was the only biomarker with significantly higher levels in the arthritis group compared with controls (P=0.002). Arthritis patients receiving anti-TNF-α antibody therapy had significantly lower IL-1β and TNF-α levels compared with arthritis patients not on anti-TNF-α therapy (P=0.016, 0.024) and healthy controls (P<0.001, P=0.011), respectively. CONCLUSION RA patients have higher levels of periodontal inflammation than healthy controls, i.e., an increased BOP. Systemic inflammation appears to influence levels of select salivary biomarkers of periodontal disease, and anti-TNF-α antibody-based disease-modifying therapy significantly lowers salivary IL-1β and TNF-α levels in RA.

Effects of caloric restriction on inflammatory periodontal disease

OBJECTIVE Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model. METHODS The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age. RESULTS Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and ss-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota. CONCLUSION Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females.

Differential gender effects of a reduced-calorie diet on systemic inflammatory and immune parameters in nonhuman primates

BACKGROUND AND OBJECTIVE Dietary manipulation, including caloric restriction, has been shown to impact host response capabilities significantly, particularly in association with aging. This investigation compared systemic inflammatory and immune-response molecules in rhesus monkeys (Macaca mulatta). MATERIAL AND METHODS Monkeys on continuous long-term calorie-restricted diets and a matched group of animals on a control ad libitum diet, were examined for systemic response profiles including the effects of both gender and aging. RESULTS The results demonstrated that haptoglobin and alpha1-antiglycoprotein levels were elevated in the serum of male monkeys. Serum IgG responses to Campylobacter rectus, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were significantly elevated in female monkeys. While only the antibody to Fusobacterium nucleatum was significantly affected by the calorie-restricted diet in female monkeys, antibody levels to Prevotella intermedia, C. rectus and Treponema denticola demonstrated a similar trend. CONCLUSION In this investigation, only certain serum antibody levels were influenced by the age of male animals, which was seemingly related to increasing clinical disease in this gender. More generally, analytes were modulated by gender and/or diet in this oral model system of mucosal microbial challenge.

Real-time polymerase chain reaction to determine the prevalence and copy number of epstein-barr virus and cytomegalovirus DNA in subgingival plaque at individual healthy and periodontal disease sites.

BACKGROUND Detection of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in plaque from patients with periodontal disease provides support for the theory that these viruses play a role in the pathogenesis of periodontitis. This study sought to further define this relationship by determining the prevalence of these viruses at individual disease and healthy sites of patients with periodontal disease and to determine whether the presence and amount of viral DNA correlate with disease severity. METHODS Subgingival plaque from three healthy and three disease sites of 65 patients who had chronic periodontitis were evaluated for the presence and amount of EBV, CMV, and Fusobacterium nucleatum DNA using real-time polymerase chain reaction. Patient serum was evaluated for antibodies against EBV and CMV using enzyme-linked immunosorbent assays. RESULTS EBV DNA was detected in 18.5% of subgingival plaque samples (72/390) and in at least one of the six plaque samples in 44.6% (29/65) of the patients. CMV DNA was detected in one plaque sample (0.3%). EBV was significantly more prevalent in disease sites (28.2%; 55/195) than in healthy sites (8.7%; 17/195; P = 0.002). However, neither EBV prevalence nor its amount correlated with increased probing depth >5 mm or attachment loss >2 mm, whereas the amount of F. nucleatum DNA did. Sites positive for EBV had a median copy number of eight. Antibodies against EBV and CMV were detected in 85.7% and 78.6% of persons evaluated, respectively. CONCLUSION EBV was infrequent and CMV was rarely present in individual subgingival sites affected by chronic periodontitis.

Systemic endotoxin levels in chronic indolent periodontal infections.

BACKGROUND AND OBJECTIVE Periodontal disease has been linked with an increased risk of various systemic diseases. A plausible biologic explanation for this link includes the opportunity for oral pathogens to translocate to the circulation as a result of breakdown in integrity of the oral epithelium. This study refined a methodology used to detect endotoxin activity in the serum of subjects with indolent periodontal infections. MATERIAL AND METHODS The QCL Kinetic Chromogenic Assay (Cambrex) is a kinetic measure of endotoxin activity. Sera from 211 pregnant women with periodontitis enrolled in the Obstetrics and Periodontal Therapy Trial were used to develop the assay further and to evaluate the detection of endotoxin activity that might accompany a low-level bacteremia in chronic periodontitis. RESULTS We optimized the system to increase the sensitivity and reproducibility of the assay. The refined system was able to detect endotoxin activity in serum at > 0.0125 EU/mL. At baseline (13-16 wk of gestation), 35.5% of the women were positive for endotoxin activity (1.62 +/- 2.21; range: 0.38-15 EU/mL). CONCLUSION This report describes a sensitive measure of endotoxin activity in serum. The procedure allowed us to document levels of this microbial virulence factor in serum of individuals with indolent infections such as periodontal disease.

Dietary modulation of the inflammatory cascade

Dietary supplementation has traditionally consisted of adding vitamins and/or minerals to correct or prevent a nutritional deficiency. When supplementing the diet with other inflammatory mediators, such as essential fatty acids, there is an adjunctive benefit to the standard therapies used in the control of chronic inflammatory diseases such as Crohns disease or rheumatoid arthritis. This review focuses on the strategies utilized for therapeutic modulation of the inflammatory cascade through dietary supplementation with specific biomolecules. Examples of how these biomolecules affect local and systemic immune responses to chronic inflammation are examined. In particular, an overview of the literature identifying the potential to modify the host response to chronic periodontitis is provided.

Detection of human cytomegalovirus in dental plaque from individual periodontal sites by real-time polymerase chain reaction.

OBJECTIVE The aim was to evaluate three primer-probe sets and real-time polymerase chain reaction (PCR) for the detection of human cytomegalovirus (HCMV) in dental plaque from individual periodontal sites. STUDY DESIGN Fifty subgingival plaque specimens from 13 healthy subjects (on average at least 2 healthy and 2 periodontal disease sites per subject) and 50 saliva specimens from 24 subjects, including 16 controls, were assessed using 3 primer-probe sets (polymerase [POL], glycoprotein B [gB], and US14) and real-time PCR. Kappa statistics were performed to measure agreement between the primer-probe sets. RESULTS There was excellent agreement between the gB and POL primers in the detection of HCMV (kappa statistic = 0.85 [95% confidence interval 0.71-0.99]), yielding a prevalence of 4% (2 out of 50) at individual periodontal disease sites and a similar rate of 8.8% (3 out of 34) in saliva. CONCLUSION Human cytomegalovirus was infrequently detected in dental plaque. Of 3 primer-probe sets evaluated, those targeting the POL and gB genes were more accurate in the detection of HCMV than that targeting US14.

Cross-talk between clinical and host-response parameters of periodontitis in smokers.

BACKGROUND AND OBJECTIVE Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host-response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens and oral commensal bacteria; and (iv) other variables of interest, in a population of smokers with (n = 171) and without (n = 117) periodontitis. MATERIAL AND METHODS Bayesian network structured learning (BNSL) techniques were used to investigate potential associations and cross-talk between the four broad sets of variables. RESULTS BNSL revealed two broad communities with markedly different topology between the populations of smokers, with and without periodontitis. Confidence of the edges in the resulting network also showed marked variations within and between the periodontitis and nonperiodontitis groups. CONCLUSION The results presented validated known associations and discovered new ones with minimal precedence that may warrant further investigation and novel hypothesis generation. Cross-talk between the clinical variables and antibody profiles of bacteria were especially pronounced in the case of periodontitis and were mediated by the antibody response profile to Porphyromonas gingivalis.

Key systemic and environmental risk factors for implant failure.

Dental implants are an important treatment option for patients interested in replacing lost or missing teeth. Although a robust body of literature has reviewed risk factors for tooth loss, the evidence for risk factors associated with dental implants is less well defined. This article focuses on key systemic risk factors relating to dental implant failure, as well as on perimucositis and peri-implantitis.