Shaneen Leishman

Cardiovascular disease and the role of oral bacteria.

Abstract In terms of the pathogenesis of cardiovascular disease (CVD) the focus has traditionally been on dyslipidemia. Over the decades our understanding of the pathogenesis of CVD has increased, and infections, including those caused by oral bacteria, are more likely involved in CVD progression than previously thought. While many studies have now shown an association between periodontal disease and CVD, the mechanisms underpinning this relationship remain unclear. This review gives a brief overview of the host-bacterial interactions in periodontal disease and virulence factors of oral bacteria before discussing the proposed mechanisms by which oral bacterial may facilitate the progression of CVD.

Infection or inflammation: the link between periodontal and cardiovascular diseases

Evolution of tumor cell phenotypes promotes heterogeneity and therapy resistance. Here we found that induction of CD73, the enzyme that generates immunosuppressive adenosine, is linked to melanoma phenotype switching. Activating MAPK mutations and growth factors drove CD73 expression, which marked both nascent and full activation of a mesenchymal-like melanoma cell state program. Proinflammatory cytokines like TNFα cooperated with MAPK signaling through the c-Jun/AP-1 transcription factor complex to activate CD73 transcription by binding to an intronic enhancer. In a mouse model of T-cell immunotherapy, CD73 was induced in relapse melanomas, which acquired a mesenchymal-like phenotype. We also detected CD73 upregulation in melanoma patients progressing under adoptive T-cell transfer or immune checkpoint blockade, arguing for an adaptive resistance mechanism. Our work substantiates CD73 as a target to combine with current immunotherapies, but its dynamic regulation suggests limited value of CD73 pretreatment expression as a biomarker to stratify melanoma patients. Cancer Res; 77(17); 4697-709. ©2017 AACR.

High Antibody Levels to P. gingivalis in Cardiovascular Disease

Recent evidence suggests that strain variation in the serum IgG response to Porphyromonas gingivalis occurs in periodontal disease and cardiovascular disease (CVD). This study aimed to test the hypothesis that different P. gingivalis strains would elicit different levels of IgG, depending on a patient’s cardiovascular (CV) and periodontal health. For CVD patients, serum antibody levels increased significantly with increasing numbers of deep pockets for all strains of P. gingivalis, except W50 (p < 0.001). We used a two-way analysis of variance to examine differences in antibody responses across several CV and periodontal groups simultaneously. There was a significant interaction effect (p < 0.05) between periodontal status and CV status for antibody levels to ATCC33277, UQD605, and Su63. This study shows variation in strain type with respect to serum IgG response in several CV and periodontal categories, providing further support for the role of the immune response to P. gingivalis in the relationship between periodontal disease and CVD.

Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual.

Influence of a triclosan toothpaste on periodontopathic bacteria and periodontitis progression in cardiovascular patients: a randomized controlled trial.

BACKGROUND AND OBJECTIVE Triclosan/copolymer toothpaste is effective in controlling plaque and gingivitis and in slowing the progression of periodontitis. This study describes its influence on microbiological and clinical outcomes, over a 5-year period, in patients with established cardiovascular disease (CVD). MATERIAL AND METHODS Four-hundred and thirty-eight patients were recruited from the Cardiovascular Unit at The Prince Charles Hospital, Brisbane, Australia, and randomized to triclosan or placebo groups. Six sites per tooth were examined annually for probing pocket depth and loss of attachment. These outcomes were analysed, using generalized linear modelling, in 381 patients who had measurements from consecutive examinations. Concurrent load of the periodontal pathogens Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Tannerella forsythia and Porphyromonas gingivalis was determined, using quantitative real-time PCR, in 437 patients with baseline plaque samples. Group comparisons were expressed as geometric means. The chi-square test was used to test for differences between the two groups of patients with regard to the proportion of patients with different numbers of bacterial species. RESULTS There was no difference in general health or periodontal status between the groups at baseline. There was a significant reduction in the number of interproximal sites showing loss of attachment between examinations, by 21% on average (p < 0.01), in the triclosan group compared with the placebo group. The prevalence of patients with F. nucleatum and A. actinomycetemcomitans was high and remained relatively constant throughout the 5 years of the study. In contrast, the prevalence of T. forsythia and P. gingivalis showed more variability; however, there was no significant difference between the groups, at any time point, in the prevalence of any organism. A significant difference in the geometric means for P. gingivalis (p = 0.01) was seen at years 1 and 4, and for F. nucleatum (p = 0.01) and in the total bacterial load (p = 0.03) at year 2; however, these differences were not statistically significant following a Bonferroni correction for multiple comparisons. There was no difference between the groups in the geometric means for each organism at year 5. CONCLUSION Within the limitations of the study, these data suggest that the use of triclosan/copolymer toothpaste significantly slowed the progression of periodontitis in patients with CVD but that it had little influence on key subgingival periodontopathic bacteria in these patients over the 5 years of the study.

Improved periodontal health and cardiovascular risk.

BACKGROUND Previous studies have demonstrated variable effects on systemic inflammatory and immune responses following improved periodontal health. This study examined changes in serum levels of the inflammatory mediators IL-1β, IL-6, TNF-α and sICAM-1, and antibodies to Porphyromonas gingivalis, human heat shock protein (hHSP) 60 and P. gingivalis GroEL following improvement in periodontal health in high cardiovascular (CV) risk and low CV-risk patients. METHODS Patients retrospectively selected from a longitudinal study, had undergone yearly periodontal examinations and peripheral blood collections. They had demonstrated a quantifiable improvement in periodontal health (>60% reduction in number of sites with probing depth ≥ 4 mm from the baseline visit) and could be classified as either high CV-risk (≥ 6 classical risk factors, n = 13) or low CV-risk (≤ 1 classical risk factor, n = 14). Serum levels of the cytokines and antibodies were measured using ELISA. RESULTS For sICAM-1 and anti-P. gingivalis GroEL and anti-hHSP60 antibodies, most patients recorded decreased levels. Reductions in serum sICAM-1 levels were more notable in low CV-risk patients (p = 0.006); and reductions in levels of anti-P. gingivalis GroEL and anti-hHSP60 antibodies (p = 0.001 and 0.009 respectively) were more notable in high CV-risk patients. CONCLUSIONS This study found that subsequent to improved periodontal health, the anti-HSP (HSP60 and GroEL) antibody response was reduced, particularly for high CV-risk patients. sICAM-1 levels were also lowered, more so for low CV-risk patients.

Association of erosion with timing of detection and selected risk factors in primary dentition: a longitudinal study

OBJECTIVE The aims of this study were to determine the prevalence of erosion in a birth cohort at 24, 36, and 48 months and to investigate risk factors for erosion. METHODS One hundred and fifty-four children from a birth cohort were followed at 24, 36, and 48 months of age. RESULTS Of the 154 children examined, 0% (0/154), 7% (11/154), and 28% (40/154) had erosion detected for the first time at 24, 36, and 48 months, respectively (P < 0.001). A cumulative total of 51 (33%) children and 256 (8%) teeth had erosion by the age of 48 months. There were no significant associations between erosive lesions first detected at 36 months and oral hygiene behaviour, medical conditions, or dietary habits reported at the 24- or 36-month examinations (all P > 0.05). In contrast, erosive lesion first detected at 48 months was positively associated with the use of a feeding bottle reported at the 36-month examination (P = 0.026). CONCLUSIONS The prevalence of dental erosion in young children increased with age, with clinically detectable lesions forming between 24 and 36 months of age. Erosive lesions first detected at 48 months were positively associated with the use of a feeding bottle reported at 36 months.

Inhibitory effects of antiseptic mouthrinses on Streptococcus mutans, Streptococcus sanguinis and Lactobacillus acidophilus.

BACKGROUND Oral antiseptics are valuable in controlling oral infections caused by cariogenic bacteria. The aim of this study was to investigate the effects of mouthrinses and pure antiseptic compounds on Streptococcus mutans and non-mutans bacteria (Streptococcus sanguinis and Lactobacillus acidophilus). METHODS The agar diffusion assay was employed to determine bacterial growth inhibition. RESULTS Commercial mouthrinses containing chlorhexidine gluconate (0.2%), cetylpyridinium chloride (0.05%) and sodium fluoride (0.05%) produced statistically similar growth inhibition of S. mutans, S. sanguinis and L. acidophilus (with zones of inhibition ranging from 7.56 ± 0.52 mm to 7.39 ± 0.53 mm, 17.44 ± 0.94 mm to 18.31 ± 0.62 mm and 8.61 ± 1.43 to 8.67 ± 1.43 mm respectively, p > 0.05). The chlorhexidine mouthwash produced the greatest mean growth inhibition of S. sanguinis and S. mutans compared to all other mouthrinses tested (p < 0.01). The minimum concentrations at which inhibition against S. mutans could be detected were chlorhexidine gluconate at 0.005% (wt/vol), cetylpyridinium chloride 0.01% (wt/ vol), povidone iodine 10% (wt/vol) and sodium hypochlorite 0.5% (vol/vol). CONCLUSIONS Chlorhexidine (0.01%), cetylpyridinium chloride (0.01%), povidone iodine (10%) and sodium hypochlorite (0.5%) are effective at inhibiting the growth of S. mutans, S. sanguinis and L. acidophilus.

Analysis of Front-of-Pack labelling systems on packaged non-alcoholic beverages for Australian consumer guidance

Aim Numerous Front-of-Pack nutrition labelling systems have been proposed in recent years to assist consumers in making healthier food choices, including reducing sugar intake. Packaged beverages represent one product category that has undergone significant diversification and has emerging new subcategories. The present study examined the implications of applying three different currently used or proposed Front-of Pack nutrition labels to a range of pre-packaged beverage products to descriptively assess their potential utility. Methods The Traffic Light System, % Daily Intake label and the Health Star Rating system were applied in accordance with established criteria and standards on 31 non-alcoholic pre-packaged beverages representing eight subcategories. Results There were often considerable differences between labelling system ratings for the same products. The Traffic Light System had similar labelling when comparing soft drinks and fruit juice and sodium content was marked as low for all tested products. Percentage Daily Intake reflected similar results for regular soft drinks and fruit juices; however, in terms of energy, liquid breakfast ranked highest followed by energy drinks, fruit juice and soft drinks. The Health Star Rating showed the fruit juice category to be healthier than other beverages, including water. Diet products scored 0.5–1 stars more than regular products. Conclusions The Health Star Rating system was concluded to be more suitable to label beverages based on better utility, applicability and ease of identifying healthier beverage choices; however, this system would benefit from further refinement. Labelling simplicity, health representativeness, marketplace utility and consumer comprehensiveness are important considerations for future labelling development.

A Longitudinal Observational Study of Developmental Defects of Enamel from Birth to 6 Years of Age

Developmental defects of the enamel (DDE) commonly occur in the primary dentition. Although several cross-sectional studies have shown the association of DDE with caries, there is a paucity of longitudinal studies demonstrating that teeth with DDE are at greater risk of caries than are normal teeth. Therefore, the aim of the present study was to longitudinally track a total of 14,220 primary teeth in 725 children from a large birth cohort study, who were interviewed by telephone or home visits at 6-mo intervals. There were 74 children with at least 1 tooth with DDE. We compared teeth with and without DDE by calculating hazard ratios for caries using a Cox proportional hazards model and by plotting caries-free probabilities by child’s age for DDE categories in a Kaplan-Meier plot. Our results show that teeth with DDE had a much higher risk for caries and developed caries earlier than did teeth without DDE. The hazard ratios (95% confidence intervals) for caries were 6.0 (2.4 to 14.6; P < 0.001) for pits, 5.5 (3.8 to 7.8; P < 0.001) for missing enamel, and 4.5 (1.8 to 11.3; P < 0.002) for hypoplasia occurring with yellow-brown opacities. Kaplan-Meier survival plots of caries-free probabilities by age, depending on DDE type, suggest that all types of enamel hypoplasia are associated with a statistically significant increased risk for caries. The study provides longitudinal evidence that DDE are a strong determinant for caries in the primary dentition (ACTRN No. 012606000356561). Knowledge Transfer Statement: The study provides longitudinal evidence that developmental defects of enamel of the primary dentition are strongly associated with increased risk of early childhood caries.