Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.

Effects of a toothpaste containing 0.3% triclosan on periodontal parameters of subjects enrolled in a regular maintenance program: A secondary analysis of a 2-year randomized clinical trial.

BACKGROUND: The triclosan-containing dentifrices are effective in controlling biofilm formation and maintaining gingival health; however, there is limited information on their effects during the periodontal maintenance phase. Therefore, the aim of this study was to evaluate the clinical effects of a toothpaste containing 0.3% triclosan on the periodontal parameters of subjects that have been treated for peri-implantitis and were enrolled in a regular maintenance program. METHODS: Subjects presenting at least one implant with peri-implantitis and received surgical anti-infective therapy were selected. Sixty days post-surgery (baseline), subjects were randomized into two groups: (1) toothpaste containing 0.3% triclosan + 2.0% PVM/MA copolymer + 1450 ppm fluoride (test) or (2) toothpaste containing 1450 ppm fluoride (control), and were instructed to brush with the assigned toothpaste twice/day for 2 years. They received clinical monitoring at baseline, 3, 6, 12, 18, and 24 months, and professional maintenance every 3 months. RESULTS: Eighty-eight subjects with natural teeth were enrolled in the study (Test, n = 39; Control, n = 49). The test group showed a greater reduction in the percentage of sites exhibiting bleeding on probing (primary outcome) and lower levels of plaque in comparison with the control group after 24 months (P < 0.05). The mean percentage of sites with probing depth ≥5 mm was reduced over the course of the study only in the test group (P < 0.05). CONCLUSION: A toothpaste containing 0.3% triclosan was more effective than a regular fluoride toothpaste in improving the periodontal clinical condition around natural teeth of periodontally healthy subjects enrolled in a regular maintenance program for 2 years.

Effects of a toothpaste containing 0.3% triclosan in the maintenance phase of peri-implantitis treatment: 2-Year randomized clinical trial.

OBJECTIVE: To evaluate the effects of a toothpaste containing 0.3% triclosan in volunteers that have been treated for peri-implantitis and were enrolled in a maintenance program. MATERIAL AND METHODS: Subjects presenting at least one implant with peri-implantitis were selected. They received anti-infective surgical therapy, and sixty days post-surgery (baseline) were randomized into two groups, brushing twice/day for 2 years (a) with a toothpaste containing 0.3% triclosan+2.0% PVM/MA copolymer (GantrezTM )+1,450 ppm fluoride (test) or (b) with a toothpaste containing 1,450 ppm fluoride (control). They received clinical and microbiological monitoring at baseline, 3, 6, 12, 18, and 24 months, and professional maintenance every 3 months. RESULTS: A total of 102 subjects were enrolled (test: 48; control: 54). The control group showed loss of clinical attachment (CA) around treated implants over the course of the study (p < 0.05), while the test group was stable for this parameter. The difference between groups (0.55 mm) for CA change between baseline and 24 months (primary outcome variable) was statistically significant (p < 0.05). Red complex pathogens were only reduced in the test group at 24 months. The implants with no history of peri-implantitis in the test group had a significant reduction in the percentage of sites with bleeding on probing and in mean probing depth, throughout the study (p < 0.05). This improvement was not observed in the control group. CONCLUSION: A toothpaste containing 0.3% triclosan was more effective than a toothpaste without triclosan in maintaining a healthy peri-implant environment around treated implants and implants with no history of peri-implantitis during a 2-year maintenance program (ClinicalTrials.govNCT03191721).

Control of dentin/root sensitivity during non-surgical and surgical periodontal treatment.

AIM: To determine the efficacy of a desensitizing regimen compared to a control in preventing the occurrence and/or alleviating dentin/root sensitivity (DRS) following non-surgical (NSPT) and surgical periodontal treatment (SPT). METHODS: Seventy-four chronic-periodontitis patients (CPP) were randomized into a test group (n = 38) using an in-office prophylaxis paste and a toothpaste at home both containing 8% arginine and calcium carbonate (Pro-Argin(™) Technology) or into a control group (n = 36) receiving a fluoride-free prophylaxis paste and a fluoride toothpaste. The examiner applied the assigned paste onto selected teeth for 3 s following NSPT and for 60 s before flap closure. Patients brushed with the assigned toothpaste twice daily throughout the study. DRS to air stimulus was assessed by the Schiff scale (0-3) and the Visual Analog Scale (VAS: 0-100 mm) six times over 17 weeks. RESULTS: In the test group, VAS scores significantly decreased at 8, 11 and 17 weeks from baseline (p ≤ 0.003) and Schiff scores at 8 and 11 weeks from baseline (p ≤ 0.014). The control group exhibited significant increases in VAS and Schiff during the study period (p ≤ 0.006). Marked inter-group differences were noted at all time points (p < 0.001). CONCLUSIONS: The combined use of desensitizing products (8% arginine and calcium carbonate) in-office and at-home prevented DRS development and maintained this effect for 17 weeks following NSPT and SPT.

Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease.

Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non-diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and α-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non-diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine), increased amino acid levels suggesting protein degradation, and increased ω-3 (docosapentaenoate) and ω-6 fatty acid (linoleate and arachidonate) signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic signatures associated with periodontal disease in diabetics. The metabolites identified in this study that discriminated the periodontal groups may be useful for developing diagnostics and therapeutics tailored to the diabetic population.

Efficacy of two different toothbrush heads on a sonic power toothbrush compared to a manual toothbrush on established gingivitis and plaque.

OBJECTIVE: To evaluate the efficacy of a power toothbrush with distinct multi-directional cleaning action using two different heads (Colgate ProClinical C200 toothbrush with either a triple clean head or a sensitive head) as compared to a manual flat-trim toothbrush (Oral B Indicator toothbrush) on supragingival plaque and established gingivitis. METHODS: This examiner-blind, randomized, controlled, three-treatment, parallel-group clinical research study assessed plaque removal via the comparison of pre- to post-brushing after a single use and again after four weeks of use, using the Rustogi Modified Navy Plaque Index. This study also assessed gingivitis at four weeks using the Löe-Silness Gingival Index. Qualifying adult male and female subjects from the central New Jersey, USA area reported to the study site after refraining from any oral hygiene procedures for 24 hours, and from eating, drinking, and smoking for four hours. Following an examination for plaque and gingivitis, they were randomized into three balanced groups. Subjects were instructed to brush their teeth for two minutes under supervision with their assigned toothbrush and a commercially available toothpaste (Colgate Cavity Protection toothpaste), after which they were again evaluated for plaque. Subjects were dismissed from the study site with the toothpaste and their assigned toothbrush to use at home twice daily for the next four weeks. They reported to the study site after four weeks of product use, at which time they were evaluated for plaque and gingivitis. RESULTS: One hundred twenty (120) enrolled subjects complied with the protocol and completed the clinical study. The results of the study indicated that all three test products provided statistically significant reductions in pre-brushing to post-brushing plaque scores for whole mouth and interproximal sites after a single use. For gingival margin plaque sites, only the Colgate ProClinical C200 toothbrush, with either the triple clean head or the sensitive head, provided statistically significant reductions in pre- to post-brushing plaque scores. After four weeks of product use, all three test products provided statistically significant reductions in baseline to four-week whole mouth and interproximal site plaque scores, but only the Colgate ProClinical C200 toothbrush, with either the triple clean head or the sensitive head, provided a statistically significant reduction in plaque scores at gingival margin sites. All three test products provided statistically significant reductions in gingival and gingivitis severity index scores after four weeks of product use. Relative to the manual toothbrush group, after a single tooth brushing the Colgate ProClinical C200 toothbrush, with either the triple clean head or sensitive head, provided statistically significantly greater reductions in whole mouth plaque index scores (51.9% and 59.3%, respectively), in gingival margin plaque index scores (700% and 650%, respectively), and interproximal plaque index scores (64.2% and 60.4%, respectively). Relative to the manual toothbrush group, after four weeks of use the Colgate ProClinical C200 toothbrush, with either the triple clean head or sensitive head, provided statistically significantly greater reductions in whole mouth plaque index scores (78.6%, and 82.1%, respectively), in gingival margin plaque index scores (3700% and 3400%, respectively), and interproximal plaque index scores (50.8% and 52.5%, respectively). Relative to the manual toothbrush group, after four weeks of use the Colgate ProClinical C200 toothbrush, with either the triple clean head or sensitive head, provided statistically significantly greater reductions in gingival index scores of 900% and 833%, respectively, and in gingivitis severity index scores of 466.7% and 600%, respectively. All statistically significant reductions were at the p ≤ 0.05 level. There were no statistically significant differences between the scores of the Colgate ProClinical C200 toothbrush with triple clean head and the scores of the Colgate ProClinical C200 toothbrush with sensitive head at any comparison time point. CONCLUSION: The Colgate ProClinicaI C200 toothbrush, with either a triple clean head or a sensitive head, provides statistically significant and clinically relevant levels of efficacy in the removal of supragingival dental plaque in the whole mouth, at the gingival margin, and interproximally after a single tooth brushing and after four weeks of use, as well as a statistically significantly greater level of efficacy in the reduction of gingivitis and gingival bleeding when compared to a manual flat-trim toothbrush.

Comparative efficacy of a specially engineered sonic powered toothbrush with unique sensing and control technologies to two commercially available power toothbrushes on established plaque and gingivitis.

OBJECTIVE: To evaluate the efficacy on plaque and established gingivitis of a new specially engineered sonic powered toothbrush with unique sensing and control technologies as compared to two commercially available power toothbrushes. METHODS: This examiner-blind, three-treatment, parallel clinical study assessed plaque reduction via the comparison of pre- to postbrushing after a single use, and following four weeks' use measured by the Rustogi Modification of the Modified Navy Plaque Index. This study also assessed gingivitis using the Löe and Silness Gingival Index after four weeks' use. Qualifying adult male and female subjects from the northern New Jersey area reported to the study site after refraining from all oral hygiene procedures for 24 hours, and from eating, drinking, or smoking for four hours. Following an examination for gingivitis and plaque (pre-brushing), they were randomized into three balanced groups, each group using one of the three study toothbrushes in the order specified by a predetermined randomization plan. Subjects were instructed to brush their teeth for two minutes under supervision with their assigned toothbrush according to the manufacturers' instructions and a commercially available toothpaste (Colgate Cavity Protection), after which they were once again evaluated for plaque (post-brushing). Subjects were then dismissed from the study site with the toothpaste and their assigned toothbrush to use at home twice daily for the next four weeks. They again reported to the study site at which time they were evaluated for plaque and gingivitis. RESULTS: One-hundred eighty-four subjects complied with the protocol and completed the clinical study. Relative to the two commercially available toothbrushes, the new specially engineered sonic powered toothbrush with unique sensing and control technologies provided statistically significantly (p < 0.05) greater reductions in whole mouth plaque index scores (21.9 and 25.8%, respectively), gingival margin plaque index scores (14.5% and 18.9%, respectively), interproximal plaque index scores (160.0% and 136.4%, respectively), facial plaque index scores (17.9% for both), lingual plaque index scores (29.2% for both), and interproximal lingual plaque index scores (200.0% and 350.0%, respectively) after a single tooth brushing. Relative to the two commercially available toothbrushes, the new sonic powered toothbrush also provided statistically significantly (p < 0.05) greater reductions in whole mouth plaque index scores (47.4% and 40.0%, respectively), gingival margin plaque index scores (46.2% and 40.7%, respectively), interproximal plaque index scores (650% and 1400%, respectively), facial plaque index scores (47.6% and 40.9%, respectively), lingual plaque index scores (47.1% and 31.6%, respectively), and interproximal lingual plaque index scores (350.0% and 500.0%, respectively) after four weeks. There was no statistically significant (p > 0.05) difference between the two commercially available toothbrushes for any plaque index score comparison. Relative to one of the commercially available toothbrushes, the new sonic powered toothbrush provided statistically significant reductions (p < 0.05) in gingival index scores (25.0%) and gingivitis severity scores (33.3%) after four weeks of product use. There were no statistically significant (p > 0.05) differences in gingivitis or gingivitis severity index scores between the new sonic powered toothbrush and the other commercially available toothbrush. CONCLUSION: A new specially engineered sonic powered toothbrush with unique sensing and control technologies provides significantly greater levels of efficacy on the removal of dental plaque after a single tooth brushing and after four weeks' use when compared to two commercially available power toothbrushes. The new sonic powered toothbrush also provides significantly greater levels of efficacy on the reduction of gingivitis and gingival bleeding when compared to one of the commercially available power toothbrushes.

A comparative investigation to evaluate the clinical efficacy of an alcohol-free CPC-containing mouthwash as compared to a control mouthwash in controlling dental plaque and gingivitis: a six-month clinical study on adults in San Jose, Costa Rica.

OBJECTIVE: This study was designed to evaluate the clinical efficacy of an antiplaque alcohol-free mouthwash containing 0.075% cetylpyridinium chloride (CPC) and 0.05% sodium fluoride (NaF), as compared to a control mouthwash containing only 0.05% NaF, in controlling established dental plaque and gingivitis after three and six months of product use. METHODS: This was a single-center, parallel-group, two-cell, double-blind, randomized clinical study. Prospective adult male and female subjects from San Jose, Costa Rica reported to the clinical facility having refrained from all oral hygiene procedures for 12 hours, and from eating, drinking, or smoking for four hours prior to their visit. Qualifying subjects who presented with Gingival Index scores (Löe and Silness Index) of at least 1.0 and Plaque Index scores (Turesky Modified Quigley-Hein Index) of at least 1.5 were allowed to participate in this study. Subjects were randomly assigned to one of two treatment groups according to their baseline gingival and plaque scores. In the first treatment group (Test), subjects used an alcohol-free mouthwash containing 0.075% CPC and 0.05% NaF, whereas in the second treatment group (Control), subjects used a mouthwash containing only 0.05% NaF. Gingivitis and plaque assessments, and examinations of oral hard and soft tissues were conducted after three months and six months of product use. RESULTS: One-hundred and ten (110) subjects complied with the protocol and completed the six-month study. After six months of product use, the Test Mouthwash group exhibited statistically significant reductions from baseline with respect to Gingival (33.5%), Gingival Interproximal (34.5%), Gingival Severity (63.2%), Plaque (33.6%), Plaque Interproximal (30.0%), and Plaque Severity (73.6%) Index scores. After six months of product use, the Control Mouthwash group exhibited statistically significant increases from baseline with respect to Gingival (6.9%), Plaque Interproximal (7.2%), and Plaque Severity (32.7%) Index scores. Furthermore, after six months of product use, the Control Mouthwash group exhibited reductions from baseline with respect to Plaque (6.1%), Gingival Interproximal (3.6%), and Gingival Severity (1.1%) Index scores which were not statistically significant. After three months of product use, the Test Mouthwash group exhibited statistically significant reductions in Gingival (25.0%), Gingival Interproximal (22.3%), Gingival Severity (38.9%), Plaque (26.1%), Plaque Interproximal (22.4%), and Plaque Severity (75.0%) Index scores as compared to the Control Mouthwash group. After six months of product use, the Test Mouthwash group exhibited statistically significant reductions in Gingival (38.1%), Gingival Interproximal (37.1%), Gingival Severity (63.6%), Plaque (36.5%), Plaque Interproximal (33.2%), and Plaque Severity (78.5%) Index scores as compared to the Control Mouthwash group. CONCLUSION: The results of this double-blind clinical study support that 1) an alcohol-free mouthwash containing a combination of 0.075% CPC and 0.05% NaF produces statistically significant reductions in dental plaque and gingivitis after three and six months compared to baseline, and 2) the alcohol-free CPC mouthwash provides a statistically significantly greater level of efficacy in controlling established dental plaque and gingivitis after three and six months of product use as compared to the Control Mouthwash containing only NaF.

Triclosan inhibition of acute and chronic inflammatory gene pathways.

AIM: We sought to determine whether triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether), an extensively used anti-plaque agent with broad-spectrum anti-microbial activity, with reported anti-inflammatory effects via inhibition of prostaglandin E2 and interleukin 1 (IL-1)beta, could also more broadly suppress multiple inflammatory gene pathways responsible for the pathogenesis of gingivitis and periodontitis. MATERIALS AND METHODS: As an exploratory study, the effects of triclosan on the inflammatory gene expression profile were assessed ex vivo using peripheral whole blood samples from eight periodontally healthy donors. Ten-millilitres whole blood aliquots were incubated 2 h with 0.3 microg/ml Escherichia coli lipopolysaccharide (LPS) with or without 0.5 microg/ml triclosan. Affymetrix microarray gene expression profiles from isolated leucocytes and pathway-specific quantitative polymerase chain reaction arrays were used to investigate changes in expression of target cytokines and cell signalling molecules. RESULTS: Ex vivo human whole blood assays indicated that triclosan significantly down-regulated the LPS-stimulated expression of Toll-like receptor signalling molecules and other multiple inflammatory molecules including IL-1 and IL-6 and the dampening of signals that activate the T-helper type 1 acquired immune response via suppression of CD70 with concomitant up-regulation of growth factors related to bone morphogenetic protein (BMP)2 and BMP6 synthesis. CONCLUSIONS: Anti-inflammatory effects were found in this exploratory survey, including suppression of microbial-pathogen recognition pathway molecules and the suppression of acute and chronic mediators of inflammation.