In situ clinical effects of new dentifrices containing 1.5% arginine and fluoride on enamel de- and remineralization and plaque metabolism.

OBJECTIVE: The primary objective of the three studies reported in this paper was to evaluate the effects of new dentifrices containing 1.5% arginine, an insoluble calcium compound, and fluoride for their ability to promote remineralization of demineralized enamel, and to prevent mineral loss from sound enamel specimens. A secondary objective was to determine the effects on plaque metabolism with respect to the conversion of arginine to ammonia and sucrose to lactic acid. METHODS: In Study 1, an intraoral remineralization/demineralization clinical model was used to assess the ability to promote remineralization of enamel of two dentifrices containing 1.5% arginine and 1450 ppm fluoride, as sodium monofluorophosphate (MFP), relative to a positive control with dicalcium phosphate dihydrate (Dical) and 1450 ppm fluoride, and a negative control with Dical and 250 ppm fluoride. One of the arginine-containing dentifrices contained Dical, and the other contained calcium carbonate as the source of insoluble calcium. Microradiography and image analysis were used to measure mineral changes. The study used a double-blind crossover design with a two-week treatment period. Each treatment period was preceded by a one-week washout period. Each product was used twice a day for two weeks. In the two other studies, the ability of dentifrices containing 1.5% arginine and fluoride to prevent demineralization of sound enamel blocks was assessed using an intraoral demineralization/remineralization clinical model and a double-blind crossover design with a five-day treatment period. A one-week minimum washout period preceded each treatment phase. Microhardness was used to assess mineral changes. Cariogenic challenges were administered by dipping each intraoral retainer into a 10% sucrose solution four times per day. Each product was used twice per day during the treatment period. Plaque was harvested from the specimens to measure the ability of the plaque to convert arginine to ammonia (Studies 2 and 3) and sucrose to lactic acid (Study 3) at the end of each treatment period. In Study 2, a dentifrice containing 1.5% arginine, Dical, and 1450 ppm fluoride as MFP was compared to a matched positive control containing 1450 ppm fluoride and to a matched negative control containing 250 ppm fluoride. In Study 3, a dentifrice containing 1.5% arginine, calcium carbonate, and 1000 ppm fluoride as MFP was compared to a matched positive control containing 1000 ppm fluoride and to a matched negative control containing 0 ppm fluoride. RESULTS: In Study 1, the percent mineral changes were +18.64, +16.77, +4.08, and -24.95 for the 1.5% arginine/Dical/1450 ppm fluoride, the 1.5% arginine/calcium carbonate/1450 ppm fluoride, the positive control, and negative control dentifrices, respectively. Study validation was successfully achieved by showing that the positive control was statistically significantly better that the negative control in promoting remineralization (p = 0.0001). The two arginine-containing test products were statistically significantly better than the positive control (p < 0.05). No significant difference was observed in efficacy between the two arginine-containing products, indicating that efficacy in promoting remineralization was independent of the choice of Dical or calcium carbonate as the source of insoluble calcium. In Study 2, the percent demineralization values were -8.50, +1.67, and +12.64 for the 1.5% arginine/Dical/1450 ppm fluoride, the positive control, and negative control dentifrices, respectively. Study validation was successfully achieved by showing that the positive control was statistically significantly better at preventing demineralization than the negative control (p < 0.0001). The arginine-containing dentifrice was shown to be statistically significantly better at preventing enamel demineralization than the positive control (p < 0.0001). Plaque metabolism measures for plaque exposed to the three treatments gave the following values for ammonia production after an arginine-sucrose challenge, expressed in nanomoles per milligram plaque: 162.7; 105.4; and 115.9 for the 1.5% arginine/Dical/1450 ppm fluoride, positive control, and negative control dentifrices, respectively. No statistically significant differences were observed between the three treatments, but the arginine-based dentifrice showed directionally higher ammonia production than both the positive and negative controls In Study 3, the percent demineralization values were +1.16, +4.96, and +15.34, for the 1.5% arginine/calcium carbonate/1 000 ppm fluoride, the positive control, and negative control dentifrices, respectively. Study validation was successfully achieved by showing that the positive control was statistically significantly better at preventing demineralization than the negative control (p < 0.0001). The arginine-containing dentifrice was shown to be statistically significantly better at preventing enamel demineralization than the positive control (p < 0.05). Plaque metabolism measures for plaque exposed to the three treatments gave the following values for ammonia production after an arginine-sucrose challenge, expressed in nanomoles per milligram plaque: 99.6; 56.2; and 42.2 for the 1.5% arginine/calcium carbonate/1000 ppm fluoride, the positive control, and negative control dentifrices, respectively. Plaque treated with the arginine- containing dentifrice produced significantly more ammonia than the positive and negative control dentifrices (p < 0.05). No significant difference in ammonia production was observed between the two controls. Lactic acid production after a sucrose challenge gave the following values, expressed as nanomoles per milligram plaque: 4.06; 5.12; and 4.64 for the 1.5% arginine/calcium carbonate/1000 ppm fluoride, the positive control, and negative control dentifrices, respectively. No significant difference was observed between the three treatments, but the arginine-based treatment showed directionally lower lactic acid production. RESULTS: The results of these three studies show that dentifrices containing 1.5% arginine, an insoluble calcium compound, and fluoride have a significantly improved ability to promote remineralization and prevent demineralization of enamel relative to dentifrices containing the same level of fluoride alone. Two different sources of insoluble calcium were evaluated, Dical and calcium carbonate. Dentifrices with Dical and with calcium carbonate, each in combination with 1.5% arginine and fluoride, provided superior efficacy as compared to matched dentifrices with fluoride alone, and the two products demonstrated comparable efficacy in promoting remineralization. The results of these studies demonstrate that the addition of 1.5% arginine to Dical-and calcium carbonate-based fluoride dentifrices provides superior efficacy in preventing demineralization and promoting remineralization, and, further, indicate that he arginine-containing dentifrices enhance the ability of plaque to metabolize arginine to ammonia.

In vivo effects of a new dentifrice containing 1.5% arginine and 1450 ppm fluoride on plaque metabolism.

OBJECTIVE: This paper presents the results of a clinical study assessing the in vivo effects on plaque metabolism of a new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride compared to a commercially available dentifrice containing 1450 ppm fluoride alone. METHODS: A four-week, parallel, randomized, double-blind clinical study using 54 subjects was conducted at the New York University College of Dentistry Bluestone Center for Clinical Research. Two study groups used the following products for two weeks: 1) a dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride as sodium monofluorophosphate (MFP; test); and 2) a commercial silica dentifrice with 1450 ppm fluoride as sodium fluoride (NaF; control). In the following two-week period, all subjects used the control product. The effects of product use on plaque metabolism in vivo were assessed by conducting ex vivo analyses at baseline, after two weeks of assigned product use, and after two weeks of control product use. These plaque analyses comprised pH measurements before and after an in vivo sucrose rinse, and measurements of ammonia production and lactate production. RESULTS: The study showed that subjects using the test dentifrice, containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, had significantly higher plaque pH values before the sucrose challenge than those using the commercially available control dentifrice (p < or = 0.01). Plaque samples from subjects using the arginine-containing dentifrice also produced significantly higher levels of ammonia (p < or = 0.01). Subjects using the arginine-containing dentifrice also had a directionally higher plaque pH after the sucrose challenge, and their plaque samples produced a directionally lower level of lactate during the two-week treatment period compared to subjects using the control dentifrice. Following two weeks of subsequent use of the control product, there were no significant differences in plaque metabolism measures between groups. CONCLUSION: A new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride has been shown in this study to modulate plaque metabolism, increasing ammonia production and decreasing lactate production, thereby increasing plaque pH to help restore a pH-neutral environment.

Clinical efficacy of a specifically targeted antimicrobial peptide mouth rinse: targeted elimination of Streptococcus mutans and prevention of demineralization.

BACKGROUND/AIMS: Streptococcus mutans, the major etiological agent of dental caries, has a measurable impact on domestic and global health care costs. Though persistent in the oral cavity despite conventional oral hygiene, S. mutans can be excluded from intact oral biofilms through competitive exclusion by other microorganisms. This suggests that therapies capable of selectively eliminating S. mutans while limiting the damage to the normal oral flora might be effective long-term interventions to fight cariogenesis. To meet this challenge, we designed C16G2, a novel synthetic specifically targeted antimicrobial peptide with specificity for S. mutans. C16G2 consists of a S. mutans-selective 'targeting region' comprised of a fragment from S. mutans competence stimulation peptide (CSP) conjoined to a 'killing region' consisting of a broad-spectrum antimicrobial peptide (G2). In vitro studies have indicated that C16G2 has robust efficacy and selectivity for S. mutans, and not other oral bacteria, and affects targeted bacteria within seconds of contact. METHODS: In the present study, we evaluated C16G2 for clinical utility in vitro, followed by a pilot efficacy study to examine the impact of a 0.04% (w/v) C16G2 rinse in an intra-oral remineralization/demineralization model. RESULTS AND CONCLUSIONS: C16G2 rinse usage was associated with reductions in plaque and salivary S. mutans, lactic acid production, and enamel demineralization. The impact on total plaque bacteria was minimal. These results suggest that C16G2 is effective against S. mutans in vivo and should be evaluated further in the clinic.

Effects of low dose chlorhexidine mouthrinses on oral bacteria and salivary microflora including those producing hydrogen sulfide.

BACKGROUND/AIMS: Clinical studies have demonstrated the considerable effects of chlorhexidine on dental plaque and oral microbiota as well as improvements in indices of oral health. This investigation examined the efficacy of lower concentrations of chlorhexidine. METHODS: Mouthrinses with 0.03%, 0.06%, 0.12% chlorhexidine and a control rinse without chlorhexidine were examined. Alamar blue, an oxidation-reduction dye with fluorescent end-points proportional to bacterial viability, was used to determine bacterial viability. Further clinical studies examined the effects of these rinses on salivary bacteria and on bacteria producing hydrogen sulfide (H(2)S) and implicated in halitosis. RESULTS: In laboratory tests, a significant dose-dependent effect was observed with Actinomyces viscosus as a model system using the Alamar blue procedure (P < 0.05). Clinical studies examined the effects 1.5 h and 3 h post-treatment on salivary bacteria and bacteria producing H(2)S. The first study compared the control rinse with the 0.03% and 0.06% chlorhexidine rinses; a second study compared the effects of the control rinse and the 0.06% and 0.12% chlorhexidine mouthrinses. In both studies, chlorhexidine rinses demonstrated significant dose-dependent effects post-treatment on salivary bacteria vs. the control rinse (P < 0.05). Significant decreases in H(2)S-producing bacteria were noted with these chlorhexidine rinses vs. the control rinse (P < 0.05). CONCLUSION: The results highlight the dose-dependent relationships noted in laboratory and clinical tests which have potential implications for the use of lower doses of chlorhexidine to inhibit oral bacteria, including those implicated in halitosis.

Evaluation of Urgotol plus K-Four compression for venous leg ulcers.

In this non-comparative clinical evaluation, 36 subjects with venous leg ulcers, 85% of which were indolent or deteriorating, were treated with Urgotul lipidocolloid wound dressing and the K-Four multilayer compression bandaging system for 12 weeks or to healing--whichever occurred first. Results show that Urgotul was an ideal dressing in combination with K-Four, being easy to apply (98.7%) and remove (98.1%), and largely pain-free (95.6%) and non-adherent (99.7%). In a patient group of "hard-to-heal" ulcers, 50% of the ulcers healed within the treatment period. Ulcers not healed after 12 weeks achieved almost 50% area reduction on average. The treatment combination proved safe, with only one of seven adverse events reported being probably related to the products used. This study supports the use of a combination of Urgotul dressing and K-Four compression to provide a "matched" treatment for venous leg ulcers.

The effects of a chlorhexidine mouthrinse on culturable microorganisms of the tongue and saliva.

A randomized and cross-over design clinical study with normal adult volunteers examined the effects of a 0.12% chlorhexidine (CHX) mouthrinse and a control rinse on a range of microflora including those implicated in halitosis on the tongue and saliva. Saliva and tongue scrapings were collected from 13 subjects prior to treatments with additional samples collected at 3 h post-treatment cultured on media to enumerate anaerobic, Gram-positive and Gram-negative bacteria, odorigenic bacteria producing hydrogen sulphide (H2S) and oral bacteria with proteolytic activity. In comparison to the control, rinsing with CHX demonstrated statistically significant reductions that ranged from 81-90% for tongue microflora with a 89-95% decrease noted on salivary flora (p<0.05). The effects of CHX on anaerobic, Gram-positive and Gram-negative bacteria are in accord with those noted on odorigenic bacteria producing H2S or proteolytic activity. These results help to explain previous clinical results on the malodor efficacy of CHX and highlight microbiological approaches for bacteria implicated in malodor.

A rapid procedure to ascertain the antimicrobial efficacy of oral care formulations.

A rapid method examining the antimicrobial efficacy of oral care formulations with alamar blue, an oxidation-reduction dye with fluorescent end-points, is described. Significant correlations between increasing viable plate counts of the oral bacteria Actinomyces viscosus, Streptococcus sanguis, Streptococcus mutans and Actinobacillus actinomycetemcomitans and increased alamar fluorescence were noted. Metabolically active bacteria reduced alamar with the reduced dye found in the cell-free filtrate. Insignificant alamar reductions were noted in the absence of bacteria or by spent culture supernatants. The efficacy of mouthrinses with clinically proven antiplaque agents such as chlorhexidine or cetylpyridinium chloride were determined by alamar blue. In a model system with A. viscosus, triclosan dentifrices demonstrate a dose-dependent effect on bacteria. Human salivary bacteria demonstrate increasing alamar fluorescence with increasing plate counts. A clinical study examined the effects of rinsing with chlorhexidine or cetylpyridinium chloride mouthrinses in comparison with a placebo mouthrinse and water on salivary bacteria. Rinsing with chlorhexidine resulted in the least number of bacteria by alamar and plate count methods. In summary, the current study demonstrates the utility of alamar blue to examine the antimicrobial effects of oral care formulations in laboratory and clinical studies.