Single nucleotide variants in the IL33 and IL1RL1 (ST2) genes are associated with periodontitis and with Aggregatibacter actinomycetemcomitans in the dental plaque biofilm: A putative role in understanding the host immune response in periodontitis.

The Interleukin (IL)-33 is important in several inflammatory diseases and its cellular receptor is the Interleukin 1 receptor-like 1 (IL1RL1), also called suppression of tumorigenicity 2 ligand (ST2L). This study investigated associations between single nucleotide variants (SNVs) in the IL33 gene and in the IL1RL1 (ST2) gene with periodontitis. Additionally, aimed to determine the role of Aggregatibacter actinomycetemcomitans (Aa) relative amount in the subgingival biofilm in these associations. A cross-sectional study was carried out with 506 individuals that answered a structured questionnaire used to collect their health status, socioeconomic-demographic, and behavioral characteristics. Periodontal examination was performed to determine the presence and severity of periodontitis, and subgingival biofilm samples were collected to quantify the relative amount of Aa by real time polymerase chain reaction. Human genomic DNA was extracted from whole blood cells and SNV genotyping was performed. Logistic regression estimated the association measurements, odds ratio (OR), and 95% confidence interval (95%CI), between the IL33 and ST2 genes with periodontitis, and subgroup analyses assessed the relative amount of Aa in these associations. 23% of individuals had periodontitis. Adjusted measurements showed a statistically significant inverse association between two SNVs of the ST2; rs148548829 (C allele) and rs10206753 (G allele). These two alleles together with a third SNV, the rs11693204 (A allele), were inversely associated with moderate periodontitis. One SNV of the IL33 gene also showed a statistically significant inverse association with moderate periodontitis. Nine SNVs of the ST2 gene were inversely associated with the relative amount of Aa. In the high Aa subgroup, there was a direct association between 11 SNVs of the ST2 gene and moderate periodontitis and two SNVs of the ST2 gene and severe periodontitis, and eight SNVs of the ST2 gene and periodontitis. These exploratory findings of genetic variants in IL-33/ST2 axis support the concept that the different tissue responses among individuals with periodontitis may be modulated by the host's genetics, influencing the physiopathology of the disease.

Stage II and stage III periodontitis clinical burdens of HIV-1 undergoing antiretroviral therapy.

OBJECTIVES: The aim of this retrospective cross-sectional study was to estimate the association of HIV-1 infection under highly active antiretroviral treatment (HAART) on the clinical parameters of periodontitis. MATERIALS AND METHODS: A total of 205 patients were divided in two groups: 74 HIV + and 131 HIV - . Periodontal probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and visible supragingival biofilm (VSB) were recorded. The association of HIV-1 infection with the presence of at least 3 sites with PPD ≥ 5 mm and/or CAL ≥ 4 mm in non-adjacent teeth was estimated using binary logistic regression models. RESULTS: The variables HIV-1 infection (OR = 5.53, p < 0.0001, 95% CI: 2.45-13.64), age [range 35-50 years old (OR = 5.73, p < 0.0001, 95% CI: 2.49-13.20); > 50 years old (OR = 6.29, p = 0.002, 95% CI: 1.94-20.42)], and VSB (OR = 23.68, p < 0.0001, 95% CI: 8.07-69.53) showed a significant direct association with BOP outcome. CONCLUSIONS: HIV-1 infection under HAART did not have association with the presence of at least 3 sites with PPD ≥ 5 mm and/or CAL ≥ 4 mm. However, HIV patients on HAART had direct association of HIV-1 infection with BOP and an inverse association with PPD. CLINICAL RELEVANCE: These results support that monitoring gingival bleeding associated with oral prophylaxis would be beneficial in the prevention and management of periodontitis in HIV-1 patients on HAART.

Reduction of hsCRP levels following an Oral Health Education Program combined with routine dental treatment.

OBJECTIVES: The present study aimed to determine the effect of a personalised oral health education program, in combination with routine dental treatment, on serum biomarkers of systemic disease compared to dental treatment alone in a population from a low-socioeconomic community with poor oral health. METHODS: This secondary analysis of a randomised clinical trial involved 295 participants (mean age, 45.4 ± 11 years) assigned to two groups. One group received dental treatment combined with the Oral Health Education Program (OHEPDT), while the second group (DT) received dental care without the Education Program. Serum levels of high-sensitivity C-reactive protein (hsCRP), lipid profile (total cholesterol, triglycerides, and high- and low-density lipoprotein cholesterol), and HbA1c levels were analysed at baseline and after 12 months. Changes in diet, smoking and alcohol consumption were also determined. RESULTS: No intergroup differences were observed for the lipid profile and HbA1c levels. A reduction in the hsCRP levels at the 12-month follow-up was observed in the OHEPDT group, which was significantly different from the DT group (p = 0.01). Multivariate modelling indicated that baseline hsCRP levels (p = 0.000), baseline body mass index (p = 0.000), and higher consumption of vegetables (p = 0.021) predicted a reduction in hsCRP levels. CONCLUSIONS: This study demonstrated that personalised oral health education combined with routine dental treatment was associated with a significant reduction in hsCRP levels subsequent to dietary behavioural changes. These findings suggest that personalised oral health education in combined with routine dental treatment may have beneficial effects on general health. CLINICAL SIGNIFICANCE: The strategy for developing an oral health program that involves education of the modifiable common risk factors for general health has beneficial effects and should be one of the priority components of these programs to improve oral and general health, particularly for at-risk communities.

The Effect of a Personalized Oral Health Education Program on Periodontal Health in an At-Risk Population: A Randomized Controlled Trial.

While periodontal disease is associated with many risk factors, socioeconomically disadvantaged communities experience the highest disease burden. The aim of this study was to evaluate the effectiveness of a personalized oral health education program, in combination with routine dental treatment, in participants from a low socioeconomic community. We used a randomized, controlled, examiner-blinded clinical trial. A total of 579 participants (aged 18-60 years) were randomly grouped: the intervention group (n = 292) received a personalized oral health education program in combination with routine dental care and the control group (n = 287) received routine dental care. All participants were assessed for improvement in oral health care behaviors, dental plaque, and periodontal status at baseline, 12 months, and 24 months. We found a significant drop (p < 0.001) in the plaque indices, Periodontal Probing Depths (PPD) and Bleeding on Probing (BOP) between baseline and the 12-month follow-up for both groups. For BOP, the number of sites positive was significantly different between baseline and the 24-month follow-up (p = 0.037). No differences were found between the two groups for any evaluated clinical outcome. The personalized oral health education program used in the current study did not appear to add significant improvement to clinical outcomes of periodontal health compared with routine restorative dental care per se.

Is there association between stress and periodontitis?

OBJECTIVE: This study estimated the association between stress and periodontitis. MATERIALS AND METHODS: A cross-sectional study was conducted with a sample of 621 individuals. Information about individuals was obtained through a questionnaire. Stress was evaluated using the Perceived Stress Scale. The diagnosis of periodontitis was based on a complete periodontal examination including clinical attachment level, probing depth, and bleeding on probing. Prevalence ratios (PR), crude and adjusted, and their respective 95% confidence intervals (95%CI) were estimated by Poisson regression analysis. RESULTS: In the final sample, 48.47% (301) of the individuals were classified as having stress, of which, 23.92% (72) had the diagnosis of periodontitis. Association measurements between stress and probing depth ≥ 4 mm (PRadjusted = 1.28, 95%CI [1.04 to 1.58]), stress and clinical attachment level ≥ 5 mm (PRadjusted = 1.15, 95%CI [1.01 to 1.31]), and stress and periodontitis (PRadjusted = 1.36, 95%CI [1.01 to 1.83]) showed that the frequency of these outcomes among those exposed to stress was 15-36% higher than those without the condition of stress, after adjustment for age, sex, schooling level, current smoking habit, pulmonary disease, and body mass index. CONCLUSIONS: The findings showed positive association between exposure to stress and the presence of periodontitis, reaffirming the need to prevent and control stress. CLINICAL RELEVANCE: Although there are limitations in this study, the results showed that an association exists between stress and periodontitis, signaling the necessity of a multidisciplinary attention when considering the psychological status in the management of oral and general health conditions of the individual.

Oral bacteriome of HIV-1-infected children from Rio de Janeiro, Brazil: Next-generation DNA sequencing analysis.

BACKGROUND AND AIM: This study compared the oral bacteriome between HIV-1-infected and non-HIV-1-infected Brazilian children/teenagers. METHODS: Whole saliva, biofilm from the dorsal surface of the tongue and biofilm from supragingival and subgingival sites were collected from 27 HIV-1-infected and 30 non-HIV-1-infected individuals. Bacterial genomic DNA was extracted and 16S rRNA genes were sequenced using next-generation sequencing technology (Ion Torrent). RESULTS: In the supragingival biofilm, the phylum Firmicutes and genus Streptococcus sp. were more frequent in HIV-1-infected (95% and 78%, respectively) than in non-HIV-1-infected individuals (40% and 24%, respectively). In the subgingival biofilm of HIV-infected participants, the relative abundance of the Veillonella sp. and Prevotella sp. genera were higher than in non-HIV-1-infected participants. On the tongue, the genera with greater relative abundance in HIV-1-infected individuals were Neisseria sp. (21%). In saliva, the difference of the genus Prevotella sp. between non-HIV-1-infected and HIV-1-infected individuals was 15% and 7%, respectively. The Chao index revealed an increase in the richness of both sub- and supragingival biofilms in the HIV-1-infected samples compared with non-HIV-1-infected samples. CONCLUSION: HIV-1-infected children/teenagers have a higher frequency of the phyla Firmicutes and genus Streptococcus, and their oral microbiome shows more complexity than that of non-HIV-1-infected children/teenagers.

The impact of caries in combination with periodontitis on oral health-related quality of life in Bahia, Brazil.

BACKGROUND: Both dental caries and periodontal disease, as isolated conditions, can generate limitations and disabilities with negative repercussions on the individual's quality of life, but the combination of both oral diseases has not been investigated yet. This study aimed to evaluate the association between the combined exposure to dental caries and periodontitis and the impact on oral health-related quality of life. METHODS: A cross-sectional study was conducted among 306 individuals seen in the public health services in Feira de Santana, Bahia, Brazil. The individuals were divided into three groups: individuals without caries and periodontitis (n = 60), those with caries or periodontitis separately (n = 155), and those with both caries and periodontitis (n = 91). Information regarding sociodemographic, health conditions, behavioral aspects, and health-care characteristics were obtained through structured questionnaires. Oral clinical examination was performed to evaluate dental caries (decayed, missing, and filled teeth DMFT) and periodontal status including bleeding on probing, visible plaque index, probing depth, and clinical attachment level. The impact of oral health on quality of life was measured using the Brazilian version of the Oral Health Impact Profile (OHIP-14). RESULTS: In terms of the OHIP-14, the mean ±SD and median of the severity scores were 11.07 ±9.45 and 9, respectively, and mean ±SD of the extension score: 1.78 ±2.27. The adjusted association measurement showed that in individuals exposed simultaneously to caries and periodontitis, the occurrence of the impact on quality of life was 63% greater than among those without these diseases. CONCLUSIONS: The results suggest that the combined occurrence of dental caries and periodontitis is associated with a significant impact on oral health-related quality of life when compared with absence of these oral diseases.

Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history-based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic-periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.

Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history-based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic-periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.

Factors associated with dental caries, periodontitis and intra-oral lesions in individuals with HIV / AIDS.

This study aimed to investigate the factors associated with oral diseases in individuals with HIV/AIDS. A cross sectional study was carried out which included 312 individuals registered in the Specialized Care Services for HIV/AIDS in three municipalities of the State of Bahia: Feira de Santana, Santo Antonio de Jesus and Juazeiro, Brazil. Socioeconomic-demographic characteristics related to life style and to dental caries, periodontitis and intra-oral mucosal lesions were investigated in patients with HIV/AIDS infection. Prevalence Ratio with 95% Confidence Interval and significance level of 5% were employed for the statistical analysis. The majority of the individuals evaluated were male with a mean age (± standard deviation) of 41.5 ± 11.3 years, and a mean time of HIV infection diagnosis (± standard deviation) of 5.2 ± 4.4 years. The presence of dental caries was observed in 78.7% of the sample, periodontitis in 25.4% and 36.2% showed intra-oral lesions. Oral health status showed a statistically significant association with the following variables: gender, age, schooling level, current occupation, family income, past and current smoking, antiretroviral use time, latest viral burden dosage, latest CD4-positive T lymphocyte count, use of complete/partial dental prosthesis, need for dental prosthesis, and use of dental floss. With the exception of those factors directly related to HIV/AIDS i.e., antiretroviral use time, latest viral burden dosage and latest CD4-positive T lymphocyte count, the factors associated with oral diseases in this population were the same as those associated with oral diseases in the non-HIV/AIDS population.

Natural history of periodontitis: Disease progression and tooth loss over 40 years.

OBJECTIVES: To assess long-term attachment and periodontitis-related tooth loss (PTL) in untreated periodontal disease over 40 years. MATERIAL AND METHODS: Data originated from the natural history of periodontitis study in Sri Lankan tea labourers first examined in 1970. In 2010, 75 subjects (15.6%) of the original cohort were re-examined. RESULTS: PTL over 40 years varied between 0 and 28 teeth (mean 13.1). Four subjects presented with no PTL, while 12 were edentulous. Logistic regression revealed attachment loss as a statistically significant covariate for PTL (p < .004). Markov chain analysis showed that smoking and calculus were associated with disease initiation and that calculus, plaque, and gingivitis were associated with loss of attachment and progression to advanced disease. Mean attachment loss <1.81 mm at the age of 30 yielded highest sensitivity and specificity (0.71) to allocate subjects into a cohort with a dentition of at least 20 teeth at 60 years of age. CONCLUSIONS: These results highlight the importance of treating early periodontitis along with smoking cessation, in those under 30 years of age. They further show that calculus removal, plaque control, and the control of gingivitis are essential in preventing disease progression, further loss of attachment and ultimately tooth loss.

Multiple cells express interleukin 17 in oral squamous cell carcinoma.

BACKGROUND: Interleukin (IL)-17 is a pro-inflammatory cytokine with pro- and antitumour effects. The aim of this study was to investigate the presence and potential sources of IL-17 in oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was used to label and compare IL-17+ cells in the tissue sections of OSCC and inflammatory controls (IC), n = 14 for both. In OSCC, the comparison was made between the number of IL-17+ cells in the tumoral islands (TI), tumour-stroma interface (TS) and more distant stroma (DS). Cells expressing IL-17 were identified using double-labelling immunofluorescence and examined using laser scanning microscopy. The production of IL-17 from tumour cells was determined in the culture supernatants of OSCC cell lines, SCC4, SCC15 and SCC25, using sandwich ELISA. RESULTS: Significantly more IL-17+ cells were observed in OSCC compared with IC (Mann-Whitney, P < 0.0001). In OSCC, the numbers of IL-17+ cells were not significantly different in three compartments, TI, TS and DS (one-way ANOVA, P > 0.05). However, the TI had significantly fewer IL-17+ cells than the combined stroma (both TS and DS together, Mann-Whitney, P < 0.01). Laser scanning microscopy revealed helper T cells, cytotoxic T cells, macrophages and mast cells co-expressed IL-17. ELISA experiments did not detect IL-17 in the supernatants of OSCC cell lines. CONCLUSIONS: Although the tumour cells themselves did not express IL-17, a range of cell types did, suggesting multiple cellular sources for IL-17 in OSCC. The spatial distribution of IL-17+ cells suggests specific interactions with cells within the tumour microenvironment, implying that IL-17+ cells are likely to play a role in the pathogenesis of OSCC.

Unfolded protein response-related gene regulation in inflamed periodontal tissues with and without Russell bodies.

OBJECTIVE: To examine the expression of unfolded protein response (UPR) genes, a set of genes that are activated to assist in protein trafficking and cellular homeostasis when endoplasmic reticulum (ER) stress occurs, in inflamed and uninflamed periodontal tissues, with or without Russell bodies (RB). RB are a histologically apparent extension of the ER that represents an accumulation of abnormal proteins that cannot be secreted or degraded and may serve as a marker of ER stress. DESIGN: Periodontal tissue specimens were collected and categorised histologically based on the presence of inflammation and the quantity of RB. The differential regulation of 84 UPR-related genes was examined by qRT(2)-PCR. RESULTS: UPR genes related to the inositol-requiring ER-to-nucleus signal kinase (IRE)-1 pathway, molecular chaperones and ER quality control were up-regulated in RB(+) tissues compared with RB(-) tissues, irrespective of inflammation. Inflamed periodontal tissues showed a marked down-regulation of heat shock protein (HSP)-70 family members. CONCLUSION: The presence of RB in inflamed periodontal tissues correlated with the expression of a unique set of ER stress-related genes and therefore may serve as a marker of UPR response in periodontal inflammation. Inflamed periodontal tissues showed a marked down-regulation of UPR genes, in particular HSP70. This may be contributory to disease progression in periodontal disease.

Risk factors that may modify the innate and adaptive immune responses in periodontal diseases.

Plaque-induced periodontal diseases occur in response to the accumulation of dental plaque. Disease manifestation and progression is determined by the nature of the immune response to the bacterial complexes in plaque. In general, predisposing factors for these periodontal diseases can be defined as those factors which retain or hinder the removal of plaque and, depending upon the nature of the immune response to this plaque, the disease will either remain stable and not progress or it may progress and result in chronic periodontitis. In contrast, modifying factors can be defined as those factors that alter the nature or course of the inflammatory lesion. These factors do not cause the disease but rather modify the chronic inflammatory response, which, in turn, is determined by the nature of the innate and adaptive immune responses and the local cytokine and inflammatory mediator networks. Chronic inflammation is characterized by vascular, cellular and repair responses within the tissues. This paper will focus on how common modifying factors, such as smoking, stress, hormonal changes, diabetes, metabolic syndrome and HIV/AIDS, influence each of these responses, together with treatment implications. As treatment planning in periodontics requires an understanding of the etiology and pathogenesis of the disease, it is important for all modifying factors to be taken into account. For some of these, such as smoking, stress and diabetic control, supportive health behavior advice within the dental setting should be an integral component for overall patient management.

Analysis of P. gingivalis, T. forsythia and S. aureus levels in edentulous mouths prior to and 6 months after placement of one-piece zirconia and titanium implants.

BACKGROUND: It has been suggested that completely edentulous patients harbour fewer periodontopathic bacteria compared with dentate patients, due to the removal of the subgingival periodontal environment. However, reappearance of certain microbes has been reported after the placement of implants in these patients. AIM: The aim of this study was to determine whether the periodontopathic bacteria Porphyromonas gingivalis and Tannerella forsythia, as well as the non-periodontopathic bacterium, Staphylococcus aureus, emerged in edentulous patients 6 months after placement of one-piece zirconia and titanium implants. MATERIALS AND METHODS: Twenty-six patients were included in the study (titanium = 13, zirconia = 13). Microbial samples were collected from the tongue prior to implant placement and 6 months after implant placement from both the tongue and from around the implants. A qRT-PCR assay using SYBR green/ROX chemistry was used for the detection and quantification of rgp, nuc and karilysin single-copy gene of P. gingivalis, T. forsythia and S. aureus, respectively. Positive controls used in the study were pure bacterial gDNA purified from cultures of P. gingivalis and S. aureus, a cloned sequence of the karilysin gene for T. forsythia, a plaque sample positive for P. gingivalis and T. forsythia, and nasal gDNA for S. aureus. RESULTS: The results show that prior to implant placement, all three bacterial species were below the lower limit of quantification in all edentulous patients. The samples collected from the tongue and around the implants remained below the lower limit of quantification for each of the three species. However, all positive controls used in the study were detectable in the samples. qPCR standard curves showed correlation coefficients >0.97 and efficiencies >94.5% (slope range -3.19 to -3.46) for each of the SYBR green PCR assays. CONCLUSION: The results of this study indicate that the tested organisms did not emerge 6 months after implant placement irrespective of the nature of the implant biomaterial. A further follow-up of at least 2 years post-implantation of these patients is suggested to determine whether there are any changes in the oral microbiota and whether such changes are associated with the development of peri-implant disease.

Downregulation of toll-like receptor-mediated signalling pathways in oral lichen planus.

OBJECTIVE: The objective of this study was to investigate the expression of Toll-like receptors (TLR) and TLR-associated signalling pathway genes in oral lichen planus (OLP). METHODS: Initially, immunohistochemistry was used to determine TLR expression in 12 formalin-fixed archival OLP tissues with 12 non-specifically inflamed oral tissues as controls. RNA was isolated from further fresh samples of OLP and non-specifically inflamed oral tissue controls (n = 6 for both groups) and used in qRT(2)-PCR focused arrays to determine the expression of TLRs and associated signalling pathway genes. Genes with a statistical significance of ±two-fold regulation (FR) and a P-value < 0.05 were considered as significantly regulated. RESULTS: Significantly more TLR4(+) cells were present in the inflammatory infiltrate in OLP compared with the control tissues (P < 0.05). There was no statistically significant difference in the numbers of TLR2(+) and TLR8(+) cells between the groups. TLR3 was significantly downregulated in OLP (P < 0.01). TLR8 was upregulated in OLP, but the difference between the groups was not statistically significant. The TLR-mediated signalling-associated protein genes MyD88 and TIRAP were significantly downregulated (P < 0.01 and P < 0.05), as were IRAK1 (P < 0.05), MAPK8 (P < 0.01), MAP3K1 (P < 0.05), MAP4K4 (P < 0.05), REL (P < 0.01) and RELA (P < 0.01). Stress proteins HMGB1 and the heat shock protein D1 were significantly downregulated in OLP (P < 0.01). CONCLUSION: These findings suggest a downregulation of TLR-mediated signalling pathways in OLP lesions.

The Influence of Triclosan on Biomarkers of Cardiovascular Risk in Patients in the Cardiovascular and Periodontal Study (CAPS): A Randomized Controlled Trial.

BACKGROUND: Triclosan toothpaste is effective in controlling plaque and gingivitis and slowing progression of periodontitis; however, its influence on inflammatory biomarkers of cardiovascular disease (CVD), as well as on kidney and liver function, is unknown. METHODS: Patients recruited from the Cardiovascular Unit at Prince Charles Hospital, Brisbane, Australia, were randomized to triclosan (n = 193) or placebo (n = 190) groups and assessed for total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, triglycerides, C-reactive protein, erythrocyte sedimentation rate (ESR), hemoglobin, total white cell count (WCC), estimated glomerular filtration rate (eGFR), and liver function enzymes, annually for 5 years. A standard mixed model for each marker included group, sex, age, hypertension, diabetes, periodontal status, statin and anti-inflammatory drug use, and smoking as covariates. Changes in eGFR, WCC, and ESR were further analyzed using transition modeling. RESULTS: Triclosan toothpaste led to a greater decrease in TC (P = 0.03), LDL cholesterol (P = 0.04), and HDL cholesterol (P = 0.05) than placebo toothpaste. ESR increased at a slower rate in the triclosan group (P ≈ 0.06) and was less likely to increase and more likely to improve in males on statins but not anti-inflammatory drugs in the triclosan group versus the placebo group. Markov modeling of the binary response for eGFR (greater than or less than/equal to the baseline median value) showed that patients with diabetes in the placebo group were significantly (P ≈ 0.05) more likely to deteriorate than either patients with diabetes in the triclosan group or patients without diabetes in each group. CONCLUSIONS: These data suggest that triclosan toothpaste may influence some inflammatory biomarkers of CVD, but not kidney or liver function. However, it is unclear if this influence is clinically significant.

The influence of a triclosan toothpaste on adverse events in patients with cardiovascular disease over 5-years.

Adverse effects of long-term usage of triclosan-containing toothpaste in humans are currently unknown. We assessed the effect of long-term use of 0.3% triclosan-toothpaste on serious adverse events (SAEs) in patients with cardiovascular disease (CVD). 438 patients with a history of stable CVD were entered into the 5-year longitudinal Cardiovascular and Periodontal Study at Prince Charles Hospital, Brisbane, Australia and randomised into test (triclosan) or placebo groups. There were no significant differences in demographics or clinical features between the groups. Patients were examined at baseline, and annually for 5-years. SAEs were classified according to the System Organ Classes defined by MedDRA (Medical Dictionary for Regulatory Activities). Results were analysed using chi square and Kaplan Meier analysis. Overall, 232 patients (123 in the triclosan group; 109 in the placebo group) experienced 569 SAEs (288 in the triclosan group and 281 in the placebo group). There was no significant difference between the groups in numbers of patients experiencing SAEs (p=0.35) or specific cardiovascular SAEs (p=0.82), nor in time to the first SAE or first cardiovascular SAE, irrespective of gender, age or BMI after adjusting for multiple comparisons (p>0.05). The adjusted odds of experiencing an SAE were estimated to increase by 2.7% for each year of age (p=0.02) and the adjusted odds of experiencing a cardiovascular SAE were estimated to increase by 5.1% for each unit increase in BMI (p=0.02). Most cardiovascular events were related to unstable angina or myocardial infarcts, 21 were associated with arrhythmia and 41 were vascular events such as aortic aneurysm and cerebrovascular accident. Within the limitations of the present study the data suggest that the use of triclosan-toothpaste may not be associated with any increase in SAEs in this CVD population. The long-term impact of triclosan on hormone-related disease, such as cancer, in humans remains to be determined.