Two-Year Caries Clinical Study of the Efficacy of Novel Dentifrices Containing 1.5% Arginine, an Insoluble Calcium Compound and 1,450 ppm Fluoride

ArticleinCaries Research 47(6):582-590 · August 2013with 118 Reads
DOI: 10.1159/000353183 · Source: PubMed
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Abstract
A 2-year double-blind randomized three-treatment controlled parallel-group clinical study compared the anti-caries efficacy of two dentifrices containing 1.5% arginine, an insoluble calcium compound (di-calcium phosphate or calcium carbonate) and 1,450 ppm fluoride (F), as sodium monofluorophosphate, to a control dentifrice containing 1,450 ppm F, as sodium fluoride, in a silica base. The 6,000 participants were from Bangkok, Thailand and aged 6-12 years initially. They were instructed to brush twice daily, in the morning and evening, with their randomly assigned dentifrice. Three trained and calibrated dentists examined the children at baseline and after 1 and 2 years using the National Institute of Dental Research Diagnostic Procedures and Criteria. The number of decayed, missing and filled teeth (DMFT) and surfaces (DMFS) for the three study groups were very similar at baseline, with no statistically significant differences among groups. After 1 year, there were no statistically significant differences in caries increments among the three groups. After 2 years, the two groups using the dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm F had statistically significantly (p < 0.02) lower DMFT increments (21.0 and 17.7% reductions, respectively) and DMFS increments (16.5 and 16.5%) compared to the control dentifrice. The differences between the two groups using the new dentifrices were not statistically significant. The results of this pivotal clinical study support the conclusion that dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm F provide significantly greater protection against caries lesion cavitation, in a low to moderate caries risk population, than dentifrices containing 1,450 ppm F alone.

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  • Article
    Objective: To assess the anti-caries effect of arginine-containing formulations in vivo on caries lesions compared with fluorides or placebo. Methods: Randomized or quasi-randomized human clinical trials wherein arginine was delivered by any method were considered. The MEDLINE, Web of Science, EMBASE, Cochrane Library, and CBM databases were searched to identify relevant articles published up to December 2014. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using data collection forms. Each included study was assessed using the Cochrane risk of bias assessment tool. Results: Of the 470 studies screened, 31 full articles were scrutinized and assessed for eligibility. Ten studies (n = 15,546 participants) were selected for final inclusion. The meta-analysis results (n = 7 studies) demonstrated a synergistic effect of arginine when used in conjunction with fluoride on early coronal and root caries compared with placebo or fluoride alone. No specific side effects related to arginine usage were identified. Conclusions: When used in combination with a calcium compound and fluoride, arginine potentially provides a superior anti-caries effect compared with matched formulations of fluoride alone. However, the level of evidence was downgraded because of risks of bias and potential publication bias. In the future, more high quality, non-industry-supported clinical studies in this research area are required before any definitive recommendations can be made.
  • Article
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  • Article
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  • Article
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    A double blind, randomized, unsupervised, parallel-group clinical trial was conducted on over 5,500 children in Sichuan Province, China. This clinical trial compared the anti-caries efficacy of two test dentifrices to that of a control dentifrice. The test dentifrices contained 1.5% arginine, 1450 ppm fluoride as sodium monofluorophosphate (MFP), and an insoluble calcium compound (either dicalcium phosphate or calcium carbonate). The positive control dentifrice contained 1450 ppm fluoride as sodium fluoride (NaF), in a silica base. The children were randomly assigned one of the toothpastes, and children residing in the same household were assigned the same dentifrice to use at home, twice a day. Three calibrated dentists examined the children at baseline, as well as after one and two years of product use. After one year of product use, there were no statistically significant differences among the three groups with respect to decayed, missing, and filled teeth (DMFT) or to decayed, missing, and filled surfaces (DMFS). After two years of product use, subjects in the two test groups using the dentifrices containing 1.5% arginine, 1450 ppm fluoride as MFP, and an insoluble calcium compound had a statistically significant reduction in DMFT increments of 20.5% and in DMFS increments of 19.6% when compared to subjects in the group using the positive control dentifrice. After two years, there were no statistically significant differences with respect to DMFT or DMFS between the two groups using the dentifrices containing 1.5% arginine, 1450 ppm fluoride as MFP, and an insoluble calcium compound. The use of the two test dentifrices demonstrated significant reductions in decayed, missing, and filled teeth and surfaces, however there was no statistically significant different between the two test dentifrices clinically after two years of using the toothpastes. The results of this two-year clinical investigation support the conclusion that dentifrices containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride as MFP provide superior protection against caries lesion cavitation compared to a positive control dentifrice containing only 1450 ppm fluoride as NaF.
  • Article
    The ability of certain oral biofilm bacteria to moderate pH through arginine metabolism by the arginine deiminase system (ADS) is a deterrent to the development of dental caries. Here, we characterize a novel Streptococcus, designated A12, isolated from supragingival dental plaque of a caries-free individual. A12 not only expressed the ADS pathway at high levels under a variety of conditions, but also effectively inhibited growth and two intercellular signaling pathways of the dental caries pathogen Streptococcus mutans. A12 produced copious amounts of H2O2 via the pyruvate oxidase enzyme; sufficient to arrest the growth of S. mutans. A12 also produced a protease similar to Challisin (Sgc) of Streptococcus gordonii that was able to block the CSP-ComDE signaling system, which is essential for bacteriocin production by S. mutans. Wild-type A12, but not an sgc mutant derivative could protect the sensitive indicator strain Streptococcus sanguinis SK150 from killing by the bacteriocins of S. mutans. A12, but not S. gordonii, could also block the XIP (comX-inducing peptide) signaling pathway, which is the proximal regulator of genetic competence in S. mutans; but Sgc was not required for this activity. The complete genome sequence of A12 was determined and phylogenomic analyses compared A12 to streptococcal reference genomes. A12 was most similar to Streptococcus australis and Streptococcus parasanguinis, but sufficiently different that it may represent a new species. A12-like organisms may play crucial roles in promotion of stable, health-associated oral biofilm communities by moderating plaque pH and interfering with the growth and virulence of caries pathogens.
  • Article
    A selected group of oral bacteria commonly associated with dental health is capable of producing alkali via the arginine deiminase system (ADS), which has a profound impact on the pH of human oral biofilms. An increased risk for dental caries has been associated with reduced ADS activity of the bacteria in oral biofilms. Arginolytic bacterial strains from dental plaque samples of caries-free and caries-active adults were isolated and characterized to investigate the basis for differences in plaque ADS activity between individuals. Fifty-six ADS-positive bacterial strains were identified by 16S rRNA gene sequencing, and their ADS activity levels were compared under standard growth conditions. The spectrum of bacterial ADS activity ranged from 45.2 to 688.0 units (mg protein)(-1). Although Streptococcus sanguinis was the most prevalent species, other Streptococcus sp. were also represented. Biochemical assays carried out using 27 ADS-positive strains under conditions known to induce or repress ADS gene expression showed substantial variation in arginolytic activity in response to pH, oxygen and the availability of carbohydrate or arginine. This study reveals that the basis for the wide spectrum of arginolytic expression observed among clinical strains is, at least in part, attributable to differences in the regulation of the ADS within and between species. The results provide insights into the microbiological basis for intersubject differences in ADS activity in oral biofilms and enhance our understanding of dental caries as an ecologically driven disease in which arginine metabolism moderates plaque pH and promotes dental health. © 2015 S. Karger AG, Basel.
  • Article
    Full-text available
    This is the first spanish guideline for the prevention and non-invasive treatment of dental caries with strategies developed to diagnose caries, monitor caries risk and promote evidence-based recommendations and clinical non-invasive treatments
  • Article
    Full-text available
    Purpose: To evaluate the clinical effect on plaque metabolism of a dentifrice containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm fluoride compared to a commercially available dentifrice containing 1,450 ppm fluoride in a silica base. Methods: A 12-week, parallel, randomized, double-blind study using 48 subjects was conducted at the Colgate-Palmolive Technology Center (Piscataway, NJ, USA). One group used a test dentifrice containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm fluoride as sodium monofluorophosphate (MFP), and the other group used a commercial silica dentifrice with 1,450 ppm fluoride as sodium fluoride (NaF) as a control. Plaque metabolism analyses were conducted at baseline and after 2, 4, 6, 8, and 12 weeks of assigned product use. The plaque analyses included pH measurements before and after a sucrose rinse, ammonia production and lactic acid production. Results: Subjects using the test dentifrice had significantly higher plaque pH values before (P< or = 0.01) and after (P< or = 0.045) a sucrose challenge than those using the commercially available control dentifrice. Subjects using the test dentifrice also produced higher levels of ammonia and lower levels of lactic acid compared to subjects using the control dentifrice.
  • Article
    Full-text available
    Objective To compare the efficacy of a new dentifrice containing 1.5% arginine and 1450 ppm fluoride to a positive control dentifrice containing 1450 ppm fluoride alone in arresting and reversing primary root caries lesions in adults. Study design A total of 3779 subjects from Piracicaba, Säo Paulo, Brazil were screened; 284 had at least one leathery primary root caries lesion and were eligible for the study. The new dentifrice contained 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate; the matched positive control dentifrice contained 1450 ppm fluoride. One lesion for each subject was selected for inclusion in the study and was examined at baseline, 3 and 6 months. Results A total of 253 subjects completed the study with 129 of 144 subjects included in the final statistical analysis for the test dentifrice and 124 of 140 for the positive control. The mean age of subjects was 45.7 (±9.19) years and 56.5% were female. After 6 months product use, 70.5% of root caries lesions improved for subjects using the arginine-containing dentifrice compared to 58.1% for subjects using the positive control. The difference in the number of root caries lesions becoming hard in the two groups was statistically significant (p = 0.038). Conclusion A new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate, provided statistically significantly superior efficacy in arresting and reversing active root caries lesions in adults compared to a matched positive control dentifrice containing fluoride alone.
  • Article
    The role of the BDJ is to inform its readers of ideas, opinions, developments and key issues in dentistry - clinical, practical and scientific - stimulating interest, debate and discussion amongst dentists of all disciplines.
  • Article
    Arginine (Arg) is derived from dietary intake, body protein breakdown, and endogenous Arg production, and is also present in saliva. Arg has been introduced as an additive in toothpaste and other fluoride‐containing dental care products and is now being promoted as more efficacious than conventional fluoride‐only toothpaste for the prevention of dental caries. Arg inclusion in dentifrice could potentially inhibit oral biofilm formation and destabilize dental plaque. Arg is expected to inhibit oral biofilm formation and destabilize complex aggregates in dental plaque and its inclusion in mouth rinse could facilitate oral biofilm removal. The destabilization of the oral biofilm by Arg may facilitate the removal of dental plaque during routine oral care. Since removing this solid biological plaque from tooth surfaces by water rinsing or brushing can be difficult, Arg metabolism in oral biofilms leading to an increase in pH decreases the risk for caries development. Moreover, clinical data have shown that Arg‐containing toothpaste increased benefits leading to the prevention of dental caries. However, there are concerns regarding the use of Arg dentifrice in caries progression or regression and some studies contradict the claims of Arg benefits in caries progression or regression.
  • Chapter
    Dental caries is a typical polymicrobial infectious disease affecting tooth hard tissue. The theory of caries etiology has been developing from the early stage “chemicoparasitic theory” to the currently well-recognized “ecological plaque hypothesis,” which proposes the oral biofilm as a dynamic interactive component of the human body. The disturbance of host-microbe homeostasis is considered as the central factor initiating dental caries. The development of high-throughput metagenomic sequencing has advanced our understanding of the structure and function of oral microbiome, and novel approaches focused on restoring oral microbial equilibrium will eventually lead to better management of the dental caries.
  • Article
    Dental caries remains a major public health problem, especially for certain high-risk population groups. The goal of this study was to assess the evidence regarding strategies meant to be used as alternatives or booster/supplements to fluoride for caries prevention and management. Articles were selected for inclusion if they had a prospective longitudinal design, with a fluoride control arm, and were conducted in human subjects. Of the included studies, 7/18 studies on calcium-based strategies favored the test product (the majority of studies included exposure of fluoride in all groups). All the arginine studies (8/8) included a combination of arginine and a calcium base, and concluded that this has the potential to significantly boost the performance of fluoride. The remaining included studies focused on the addition of microbial-related strategies to a fluoride-containing vehicle (2 xylitol studies and 1 study using a probiotic milk), and all favored the combination as a booster to fluoride. Thus, the current study did not identify evidence for any strategy to effectively be used as a substitute or alternative to fluoride, but identified some consistent evidence derived from the use of prebiotic strategies (primarily from use of arginine combined with calcium) to support their potential use to boost the mechanism of action of fluoride. Thus, fluoride-based strategies remain the standard for caries prevention and management, with some evidence that boosting the effects of fluoride by the use of prebiotic strategies is a promising possibility.
  • Article
    Importance: Dental caries is one of the most prevalent and costly infectious diseases worldwide caused by a biofilm formed on tooth surfaces. Novel strategies that compromise the ability of virulent species to assemble and maintain pathogenic biofilms could be effective alternative to conventional antimicrobials that indiscriminately kill other oral species, including commensal bacteria. 1.5% L-arginine has been shown to be clinically effective in modulating cariogenic biofilms via alkali production by arginolytic bacteria. Using a mixed-species ecological model, we show new mechanisms by which L-arginine disrupts the process of biofilm matrix assembly and the dynamic microbial interactions that are associated with cariogenic biofilm development, without impacting the bacterial viability. These results may aid in the development of enhanced methods to control biofilms using L-arginine.
  • Article
    Dental plaque metabolizes both carbohydrates and amino acids. The former can be degraded to acids mainly, while the latter can be degraded to various metabolites, including ammonia, acids and amines, and associated with acid-neutralization, oral malodor and tissue inflammation. However, amino acid metabolism in dental plaque is still unclear. This study aimed to elucidate what kinds of amino acids are available as metabolic substrates and how the amino acids are metabolized in supragingival plaque, by a metabolome analysis. Amino acids and the related metabolites in supragingival plaque were extracted and quantified comprehensively by CE-TOFMS. Plaque samples were also incubated with amino acids, and the amounts of ammonia and amino acid-related metabolites were measured. The concentration of glutamate was the highest in supragingival plaque, while the ammonia-production was the highest from glutamine. The obtained metabolome profile revealed that amino acids are degraded through various metabolic pathways, including deamination, decarboxylation and transamination and that these metabolic systems may link each other, as well as with carbohydrate metabolic pathways in dental plaque ecosystem. Moreover, glutamine and glutamate might be the main source of ammonia production, as well as arginine, and contribute to pH-homeostasis and counteraction to acid-induced demineralization in supragingival plaque.
  • Chapter
    The demineralisation and remineralisation cycle needs to be controlled in order to prevent the decomposition of dental tissues. The use of fluoridated products, especially the consumption of fluoridated water and use of fluoridated toothpaste, provides significant reduction in caries risk in a cost-effective manner. Fluoride has also been used as a caries-preventive agent in varnishes and gels; for decades anti-fluoride propaganda questioned the public and the dental sector about its safety. Therefore, it is important to discuss the pros and cons of fluoride therapy using scientific evidence. More recently, a number of products containing calcium and phosphate have been released onto the market – these products use a variety of technologies and have varying levels of evidenced-based justification. The mechanisms of action of fluoride- and calcium-based technologies will be discussed in detail.
  • Article
    Full-text available
    La caries dental es una de las enfermedades más prevalen-tes del ser humano y puede tener importantes repercusio-nes a nivel bucodental, social e interpersonal, por lo que su prevención es un factor crucial en el control de esta patolo-gía. Las principales medidas preventivas en el desarrollo de la caries dental son el control de los azúcares de la dieta (especialmente la sacarosa), la correcta remoción mecánica de la placa mediante el cepillado dental y los dispositivos in-terproximales, la aplicación de fluoruros y los selladores de fisuras. Sin embargo, se están desarrollando nuevos agen-tes químicos, como es el caso de la tecnología con argini-na, que pretende no sólo actuar sobre la resistencia de las estructuras dentarias frente a la acción de los ácidos, sino también modificar las condiciones físico-químicas de la pla-ca y así fomentar los procesos de remineralización. Es por ello que el objetivo de este artículo es revisar los distintos niveles de evidencia de un dentífrico a base de arginina (Pro-Argin TM) en el tratamiento y prevención de la caries dental.-Metabolismo del biofilm. Esta tecnología puede fomentar la producción de compuestos alcalinos (NH4+), aumentando el pH de la placa, favoreciendo las condiciones que incremen-tarían la remineralización y disminuirían la desmineralización.-Remineralización/desmineralización del esmalte. Los dentífricos con arginina al 1,5% obtuvieron un beneficio adi-cional con respecto a los dentífricos con monofluorofosfa-to de sodio en cuanto a la remineralización de las lesiones iniciales y la prevención de la desmineralización del esmal-te sano.-Detención/corrección de la lesión por caries. Los den-tífricos con arginina fueron capaces de reducir en mayor ex-tensión las lesiones iniciales de caries, tanto a nivel del es-malte como de la superficie radicular en comparación a un dentífrico similar sin arginina o a un control negativo.-Prevención de caries a largo plazo. El nuevo dentífrico fue capaz de disminuir el incremento de los índices CAOD y CAOS entre el 16,5% y el 21%, en comparación a un dentí-frico sin arginina con la misma concentración de monofluo-rofosfato de sodio. abstract Dental caries is one of the most prevalent diseases on humans and can cause important consequences at the oral, social or interpersonal level. This is the reason why its prevention is a crucial factor to control this pathology. The main preventive strategies in the development of dental caries are to control sugar from the diet, the proper mechanical removal of dental plaque with dental brushes and interproximal devices , the application of fluorides and the fissure sealants. Nevertheless, new chemical agents are being developed, as it is the case of arginine technology, which pretends not only to increase the resistance of dental structures to acids, but also to modify the physic-chemical properties of dental plaque , increasing the process of re-mineralization. Therefore, the objective of this article is to review the different levels of evidence of a toothpaste containing arginine (Pro-ArginTM) in the treatment and prevention of dental caries.-Biofilm metabolism. This technology can promote the production of alkaline compounds (NH4+) and increase the plaque pH, favouring the conditions that would enhance remineralization and prevent des-mineralization. - Enamel re-mineralization/des-mineralization. Toothpastes containing arginine at 1,5% obtained an additional benefit compare to fluoride toothpastes in terms of re-mineralization of initial lesions and the prevention of des-mineralization of healthy enamel. - Caries lesion arrestment/correction. Toothpastes containing arginine were able to reduce in a grater extension the initial caries lesion, both at enamel and at the root surface in comparison to the same toothpaste without arginine or to a negative control without fluoride and arginine. - Long-term caries prevention. The new toothpaste decreased the increments in the DMFT and DMFS indexes between 16,5 and 21% in comparison to a toothpaste with the same fluoride concentration but without arginine. Key words: toothpaste, fluoride, arginine, caries, calcium.
  • Article
    Streptococcus mutans is a common constituent of oral biofilms and a primary etiologic agent of human dental caries. The bacteria associated with dental caries have potent abilities to produce organic acids from dietary carbohydrates and to grow and metabolize in acidic conditions. By contrast, many commensal bacteria produce ammonia through the arginine deiminase system (ADS), which moderates the pH of oral biofilms. Arginine metabolism by the ADS is a significant deterrent to the initiation and progression of dental caries. In this study, we observed how exogenously provided l-arginine affects the growth, the virulence properties, and the tolerance of environmental stresses of S. mutans. Supplementation with 1.5% arginine (final concentration) had an inhibitory effect on the growth of S. mutans in complex and chemically defined media, particularly when cells were exposed to acid or oxidative stress. The genes encoding virulence factors required for attachment/accumulation (gtfB and spaP), bacteriocins (nlmA, nlmB, nlmD, and cipB), and the sigma factor required for competence development (comX) were downregulated during growth with 1.5% arginine. Deep sequencing of RNA (RNA-Seq) comparing the transcriptomes of S. mutans growing in chemically defined media with and without 1.5% arginine revealed differential expression of genes encoding ATP-binding cassette transporters, metal transporters, and constituents required for survival, metabolism, and biofilm formation. Therefore, the mechanisms of action by which arginine inhibits dental caries include direct adverse effects on multiple virulence-related properties of the most common human dental caries pathogen. IMPORTANCE Metabolism of the amino acid arginine by the arginine deiminase system (ADS) of certain oral bacteria raises the pH of dental plaque and provides a selective advantage to health-associated bacteria, thereby protecting the host from dental caries (cavities). Here, we examine the effects of arginine on the cavity-causing bacterium Streptococcus mutans. We find that arginine negatively impacts the growth, the pathogenic potential, and the tolerance of environmental stresses in a way that is likely to compromise the ability of S. mutans to cause disease. Using genetic and genomic techniques, multiple mechanisms by which arginine exerts its influence on virulence-related properties of S. mutans are discovered. This report demonstrates that a primary mechanism of action by which arginine inhibits the initiation and progression of dental caries may be by reducing the pathogenic potential of S. mutans.
  • Article
    Full-text available
    Dental caries is closely associated with the microbial dybiosis between acidogenic/aciduric pathogens and alkali-generating commensal bacteria colonized in the oral cavity. Our recent studies have shown that arginine may represent a promising anti-caries agent by modulating microbial composition in an in vitro consortium. However, the effect of arginine on the oral microbiota has yet to be comprehensively delineated in either clinical cohort or in vitro biofilm models that better represent the microbial diversity of oral cavity. Here, by employing a clinical cohort and a saliva-derived biofilm model, we demonstrated that arginine treatment could favorably modulate the oral microbiota of caries-active individuals. Specifically, treatment with arginine-containing dentifrice normalized the oral microbiota of caries-active individuals similar to that of caries-free controls in terms of microbial structure, abundance of typical species, enzymatic activities of glycolysis and alkali-generation related enzymes and their corresponding transcripts. Moreover, we found that combinatory use of arginine with fluoride could better enrich alkali-generating Streptococcus sanguinis and suppress acidogenic/aciduric Streptococcus mutans, and thus significantly retard the demineralizing capability of saliva-derived oral biofilm. Hence, we propose that fluoride and arginine have a potential synergistic effect in maintaining an eco-friendly oral microbial equilibrium in favor of better caries management.
  • Article
    Full-text available
    Arginine is an important pH-elevating agent in the oral cavity. It has been incorporated in oral hygiene formulations to mitigate sensitivity and to prevent caries. In this investigation, the effects of sustained arginine dosing of dental plaque microcosms on bacteriological composition and pH were evaluated under controlled conditions. Plaque microcosms were established in constant-depth film fermentors (CDFFs) using salivary inocula and fed continuously with artificial saliva. To simulate resting and cariogenic states, the CDFFs were supplemented with sterile water or 5% sucrose, respectively. Plaques were then dosed twice daily with a dentifrice with 1.5% arginine arginine added (DA) or without arginine (DN). This regimen continued for over 3 weeks, after which fermentors were maintained without dosing. Microcosms were analyzed by differential viable counting, with a pH microelectrode, and by eubacterial DNA profiling. Sucrose dosing was associated with significantly (P < 0.001) decreased pH, significantly (P < 0.05) increased counts of total aerobes, Gram-negative anaerobes, aciduric species, acidogenic species, arginine utilizing species, bifidobacteria, lactobacilli and streptococci, and significant (P < 0.05) changes in DNA profiles. Plaques dosed with DA had a significantly (P < 0.001) higher pH than those dosed with DN, with or without sucrose supplementation. Dosing with DA but not DN significantly (P < 0.05) decreased counts of all functional bacterial groups apart from the total anaerobes in cariogenic plaques, and in resting plaques, dosing with DA significantly (P < 0.05) decreased counts of streptococci, lactobacilli, bifidobacteria, and acidogenic bacteria. In summary, sustained exposure of oral microcosms to arginine in formulation significantly increased plaque pH and significantly reduced the viability of cariogenic bacterial species.
  • Article
    Objectives: The objective of this study was to evaluate the association between salivary and plaque arginine levels/ADS activities with dental caries. Materials and methods: A systematic search was performed as per PRISMA statement using PubMed, Scopus, Cochrane Library, and Web of Science. Published studies that investigated adults and children (P) with caries-active status (E) and caries-free status (C), whereby arginine levels/ADS activity (O) was measured in saliva/plaque to analyze exposure-outcome association compared to the control group were deemed eligible for inclusion. Quality assessment was performed using combined Newcastle-Ottawa Scale and Modified RTI Item Bank scale. Meta-analysis was performed for effect size, precision estimation, and subgroup effects analysis. Results: Of 233 records identified, seven (κ = 1.00) were included for qualitative synthesis (systematic review) and four for quantitative synthesis (meta-analysis). No specific bias could be identified in five studies assessed as per the Modified RTI Item Bank scale. Two studies received lower scores on the Newcastle Ottawa scale. Plaque ADS activity in adults (effect size = 0.93, p = 0.008), salivary ADS activity in adults and children (effect size = 0.85, p < 0.001), and salivary ADS activity in adults (effect size = 0.87, p < 0.001) identified a statistically significant effect size. Subgroup analysis demonstrated non-significant variance (Q value = 0.042, p = 0.838) between saliva and plaque ADS activities of adults. Conclusions: The results of this review suggest the salivary and plaque ADS activities appear to be promising caries risk indicators for adults, while results remain inconclusive in children. Clinical relevance: Measuring ADS activities (saliva or plaque) can be a potential caries risk indicator in adults. The protocol was registered on PROSPERO database: CRD42017060701.
  • Article
    Carious lesions develop in tooth surfaces where there is an imbalance of the processes of acid and alkali production by supragingival biofilms. Since low pH is the main driving factor in the development of carious lesions, most efforts to identify an effective anticaries therapy have focused on targeting the acid-producing bacteria and their mechanisms of acid production. An expanding area of oral microbiology has now been devoted to explore microbial metabolic activities that help to neutralize biofilm pH and thus inhibit the caries process. Arginine metabolism via the arginine deiminase pathway (ADS) produces alkali in the form of ammonia that counteracts the effects of biofilm acidification from bacterial glycolysis. ADS also functions as an adaptive strategy used by certain bacteria to thrive in oral biofilms. Substantial evidence accumulated from laboratory and clinical observations supports the hypotheses that measurements of arginine metabolism via ADS may serve as an important caries risk assessment criterion and that providing arginine regularly to supragingival biofilms can be an effective therapy for caries intervention. This article reviews the potential of arginine-based therapies such as the use of arginine as prebiotic, ADS⁺ strains as probiotics, and oral care formulations containing arginine for prevention and management of dental caries.
  • Article
    Full-text available
    We focus on scalable public health interventions that prevent and delay the development of caries and enhance resistance to dental caries lesions. These interventions should occur throughout the life cycle, and need to be age appropriate. Mitigating disease transmission and enhancing resistance are achieved through use of various fluorides, sugar substitutes, mechanical barriers such as pit-and-fissure sealants, and antimicrobials. A key aspect is counseling and other behavioral interventions that are designed to promote use of disease transmission-inhibiting and tooth resistance-enhancing agents. Advocacy for public water fluoridation and sugar taxes is an appropriate dental public health activity.
  • Article
    There is limited evidence that arginine-containing fluoridated dentifrices (AFD) have a better anticaries effect than regular fluoridated dentifrices (FD), especially in subjects at a higher risk for caries development. This study aimed to assess the effect of AFD on enamel demineralization and on the microbial and biochemical compositions of biofilm formed under different frequencies of sucrose exposure. It consisted of an in situ split-mouth design, where 12 adult volunteers who used FD for at least 2 months prior to the beginning of this study wore acrylic palatal appliances containing 4 bovine enamel specimens (1 pair at each side of the appliance) during 2 phases of 14 days each. FD slurry (3×/day) and 20% sucrose solution (4× and 8×/day) were dripped on the specimens during the first experimental phase. The same volunteers then used AFD during a 2-month washout period, followed by a second experimental phase where the AFD slurry and sucrose solution were applied onto a new subset of specimens. The percentage of enamel surface hardness loss (%SHL), the lesion depth (LD), the integrated mineral loss (IML), microbial counts on biofilms, the biomass, and inorganic and insoluble extracellular polysaccharide (IEPS) biofilm concentrations were determined. Higher %SHL, biomass, and IEPS and lower fluoride values were found at sucrose 8×/day exposure. Lower IEPS were found in the presence of AFD compared to FD. Similar %SHL, LD, and IML values were found between FD and AFD, irrespectively of the cariogenic challenge. The results suggest that AFD have an anticaries effect similar to that of regular FD.
  • Article
    Full-text available
    Health-associated oral Streptococcus species are promising probiotic candidates to protect against dental caries. Ammonia production through the arginine deiminase system (ADS), which can increase the pH of oral biofilms, and direct antagonism of caries-associated bacterial species are desirable properties for oral probiotic strains. ADS and antagonistic activities can vary dramatically among individuals, but the genetic basis for these differences is unknown. We sequenced whole genomes of a diverse set of clinical oral Streptococcus isolates and examined the genetic basis of variability in ADS and antagonistic activities. A total of 113 isolates were included and represented 10 species: Streptococcus australis, A12-like, S. cristatus, S. gordonii, S. intermedius, S. mitis, S. oralis including S. oralis subsp. dentisani, S. parasanguinis, S. salivarius, and S. sanguinis. Mean ADS activity and antagonism on Streptococcus mutans UA159 were measured for each isolate, and each isolate was whole genome shotgun sequenced on an Illumina MiSeq. Phylogenies were built of genes known to be involved in ADS activity and antagonism. Several approaches to correlate the pan-genome with phenotypes were performed. Phylogenies of genes previously identified in ADS activity and antagonism grouped isolates by species, but not by phenotype. A genome-wide association study (GWAS) identified additional genes potentially involved in ADS activity or antagonism across all the isolates we sequenced as well as within several species. Phenotypic heterogeneity in oral streptococci is not necessarily reflected by genotype and is not species specific. Probiotic strains must be carefully selected based on characterization of each strain and not based on inclusion within a certain species. IMPORTANCE Representative type strains are commonly used to characterize bacterial species, yet species are phenotypically and genotypically heterogeneous. Conclusions about strain physiology and activity based on a single strain therefore may be inappropriate and misleading. When selecting strains for probiotic use, the assumption that all strains within a species share the same desired probiotic characteristics may result in selection of a strain that lacks the desired traits, and therefore makes a minimally effective or ineffective probiotic. Health-associated oral streptococci are promising candidates for anticaries probiotics, but strains need to be carefully selected based on observed phenotypes. We characterized the genotypes and anticaries phenotypes of strains from 10 species of oral streptococci and demonstrate poor correlation between genotype and phenotype across all species.
  • Article
    Introduction: Ammonia production via the arginine deiminase system (ADS) of oral bacteria can function to reduce the cariogenicity of oral biofilms by neutralizing glycolytic acids that cause tooth demineralization. Objectives: This cohort study investigated the relationship between ADS activity and bacterial profile changes of supragingival biofilms with caries experience among children over time. Methods: A total of 79 children aged 2 to 7 y at baseline were assessed every 6 mo for a period of 18 mo. Children were grouped as caries free (CF), caries active with enamel lesions (CAE), or caries active with dentin lesions (CA). Supragingival plaque samples were collected from caries-free surfaces (PF) and from enamel (PE) and dentin (PD) lesions. Plaque ADS activity was measured by monitoring citrulline production from arginine and compared with ribosomal 16S rRNA-derived taxonomic profiles for the same samples. Results: At baseline, 37% of the children were CF, 34% CAE, and 29% CA. At 18 mo, 26% were CF, 41% CAE, 23% CA, and 10% were caries experienced (new restorations but no caries activity). Throughout the study period, ADS activity was significantly higher in the CF group than the CA group (P < 0.0001), and ADS activity in the PF samples was significantly higher than in the PE and PD samples (P < 0.0001). Distance-based redundancy analysis showed that the bacterial communities could be differentiated when plaque samples are grouped into levels of high and low ADS activity. Conclusions: There is a positive correlation between caries activity and low arginolytic capacity of the supragingival oral biofilms of children and tooth surfaces over time. Measurements of arginine metabolism via ADS may be useful to differentiate the caries risk of individuals and tooth surfaces. Knowledge transfer statement: Findings from this study support the development of new strategies for caries risk assessment and prevention based on modulation of the virulence of the oral microbiome through arginine metabolism in supragingival biofilms.
  • Article
    Full-text available
    Objective To compare the efficacy of a new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride to a matched, positive control dentifrice containing 1450 ppm fluoride in arresting and reversing early coronal caries lesions in children using Quantitative Light-induced Fluorescence (QLF). Study design 331 children from Chiang Mai, Thailand, aged 7–14 years, with one or more visible early enamel caries lesions on the upper anterior teeth, completed the study. The new dentifrice contained 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate; the matched positive control contained 1450 ppm fluoride only. Subjects brushed twice daily at home and additionally once on school days under teacher's supervision. Digital images of the upper six anterior teeth were captured at the baseline, 3- and 6-month examinations using a custom apparatus for reproducible acquisition of Quantitative Light-induced Fluorescence data. Results At the 3-month examination, the ΔQ (representing lesion volume) for the test group decreased from a mean of 28.62 at baseline to 20.53 mm2% and for the positive control group to 23.38 mm2%. The difference between groups was not statistically significant (p = 0.055). At the 6-month examination, the ΔQ decreased for the test group to 15.85 mm2% and for the positive control group to 20.35 mm2%. The difference between groups was statistically significant (p < 0.001). Conclusion A new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate, provided statistically significant superior efficacy in arresting and reversing active coronal caries lesions in children than brushing with a matched positive control dentifrice containing fluoride alone.
  • Article
    Alkali generation by oral bacteria plays a key role in plaque pH homeostasis and may be a major impediment to the development of dental caries. To determine if the capacity of oral samples to produce ammonia from arginine or urea was related to caries experience, the arginine deiminase system (ADS) and urease activity in saliva and dental plaque samples were measured in 45 adult subjects. The subjects were divided into three groups according to caries status; 13 caries-free (CF) individuals (decayed, missing, and filled teeth = 0); 21 caries-active (CA) individuals (decayed teeth >or= 4); and 11 caries-experienced (CE) individuals (decayed teeth = 0; missing and filled teeth > 0). Real-time polymerase chain reaction was used to quantify the proportion of certain acid- or alkali-producing organisms in the samples. The amount of ammonia generated from the test substrates by plaque samples was generally higher than that produced by salivary samples in all groups. Significantly higher levels of salivary ADS activity and plaque urease activity were observed in CF subjects compared to CA subjects (P = 0.0004 and P = 0.014, respectively). The proportions of Streptococcus mutans from saliva and dental plaque of CA subjects were significantly higher than those from the CF group (P = 0.0153 and P = 0.0009, respectively). In the CA group, there was an inverse relationship between urease activity and the levels of S. mutans (P < 0.0001). This study supports the theory that increased caries risk is associated with reduced alkali-generating capacity of the bacteria colonizing the oral cavity; providing compelling evidence to further our understanding of oral alkali-generation in health and disease.
  • Article
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    Objective To compare the efficacy of a new dentifrice containing 1.5% arginine and 1450 ppm fluoride to a positive control dentifrice containing 1450 ppm fluoride alone in arresting and reversing primary root caries lesions in adults. Study design A total of 3779 subjects from Piracicaba, Säo Paulo, Brazil were screened; 284 had at least one leathery primary root caries lesion and were eligible for the study. The new dentifrice contained 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate; the matched positive control dentifrice contained 1450 ppm fluoride. One lesion for each subject was selected for inclusion in the study and was examined at baseline, 3 and 6 months. Results A total of 253 subjects completed the study with 129 of 144 subjects included in the final statistical analysis for the test dentifrice and 124 of 140 for the positive control. The mean age of subjects was 45.7 (±9.19) years and 56.5% were female. After 6 months product use, 70.5% of root caries lesions improved for subjects using the arginine-containing dentifrice compared to 58.1% for subjects using the positive control. The difference in the number of root caries lesions becoming hard in the two groups was statistically significant (p = 0.038). Conclusion A new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate, provided statistically significantly superior efficacy in arresting and reversing active root caries lesions in adults compared to a matched positive control dentifrice containing fluoride alone.
  • Article
    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. 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. 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. 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.
  • Article
    Full-text available
    The purpose of this six-month study was to assess the ability of a new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate, to arrest and reverse primary root caries lesions in adults. Three test groups used dentifrices which contained either: 1) 1.5% arginine and 1450 ppm fluoride as sodium monofluorophosphate in a calcium base (experimental); 2) 1450 ppm fluoride as sodium fluoride in a silica base (positive control); or 3) no fluoride in a calcium base (negative control). The study participants were residents of the city of Chengdu, Sichuan Province, China. In order to take part, subjects had to have at least one non-cavitated primary root caries lesion. A total of 412 subjects completed the study. They were aged from 50 to 70 years (mean age 64 +/- 4.1 years) and 53.6% were female. Efficacy for arresting and reversal of primary root caries was assessed by clinical hardness measures and through the use of the Electrical Caries Monitor. After three months of product use, clinical hardness measures showed that 27.7%, 24.6%, and 13.1% of lesions had improved in the experimental, positive, and negative control groups, respectively, and 0.7%, 4.5%, and 16.8% had become worse, respectively. The differences in the distribution of lesion change between the negative control group and both the experimental (p < 0.001) and positive control (p = 0.001) were statistically significant. The Electrical Caries Monitor was also used as an objective measure of lesion severity. The end values increased from baseline to the three-month examinations, but none of the differences between the groups attained statistical significance. After six months, clinical hardness measures showed that only one lesion (0.7%) was worse than at the baseline examination-in the experimental group compared to 9.0% and 18.2% in the positive and negative control groups, respectively. In addition, 61.7%, 56.0%, and 27.0%, respectively, showed improvement for the three groups. The differences in the distribution of lesion change scores between the negative control group and both the experimental (p < 0.001) and positive control (p < 0.001) were statistically significant, as was the difference between the experimental group and the positive control (p = 0.006). The Electrical Caries Monitor end values for the experimental, positive, and negative control groups at the six-month examination were 7.9, 1.9 mega omega(s), and 387 kilo omegas(s), respectively. The differences between the negative control group and both the experimental (p < 0.001) and positive control (p < 0.001) were statistically significant. The difference between the experimental and positive control groups was also statistically significant (p = 0.03). It is concluded that the new toothpaste containing 1.5% arginine and 1450 ppm fluoride, as sodium monofluorophosphate in a calcium base, provided greater anticaries benefits than a conventional toothpaste containing 1450 ppm fluoride. Both fluoride toothpastes demonstrated greater benefits than non-fluoride toothpaste.
  • Article
    Full-text available
    The purpose of this study was to assess the ability of a new dentifrice containing arginine, an insoluble calcium compound, and fluoride to arrest or reverse naturally occurring buccal caries lesions measured using Quantitative Light-induced Fluorescence (QLF). Three study groups used dentifrices which contained 1) 1.5% arginine and 1450 ppm fluoride as sodium monofluorophosphate (experimental), 2) 1450 ppm fluoride as sodium monofluorophosphate (positive control), and 3) no fluoride (negative control). All three dentifrices were formulated in the same calcium base. The study participants were from three schools in the city of Chengdu, Sichuan Province, China. A total of 446 of 450 recruited subjects completed the study. Of these, 147 were in the experimental, 148 in the positive control, and 151 in the negative control groups. The initial age of the children was 10-12 years (mean 11.4 +/- 0.54); 47.5% were female. Using QLF, assessments of buccal caries lesions were made at baseline and after three and six months of product use. For AQ, representing lesion volume, the baseline mean value for the three groups was 27.30, and at the three-month examination the mean values were 16.76, 19.25, and 25.89 for the experimental, positive, and negative control dentifrices, respectively. This represents improvements from baseline of 38.6%, 29.5%, and 5.2%. At six months, the deltaQ values for the three groups were 13.46, 18.47, and 24.18, representing improvements from baseline of 50.7%, 32.3%, and 11.4%. For all QLF metrics, deltaF (loss of fluorescence), area, and deltaQ, the differences between the negative control and both the experimental and positive control groups were statistically significant (p < or = 0.01). The differences between the experimental and positive control groups attained statistical significance for deltaQ (p < or = 0.003) at the six-month examination. It is concluded that both of the fluoride-containing toothpastes are significantly better at arresting and reversing buccal caries lesions than the non-fluoride toothpaste. Furthermore, it is concluded that the new dentifrice containing arginine, an insoluble calcium compound, and fluoride provides significantly greater anticaries benefit than a dentifrice containing fluoride alone.
  • Article
    This paper provides an overview of modern concepts of dental caries, including its etiology, prevalence, and risk factors. The multifactorial nature of the disease is reviewed, and the concept of reducing caries initiation and progression by reducing pathological factors and restoring caries balance is discussed. In addition, the role and efficacy of fluoride in reducing and preventing caries is highlighted, demonstrating its successes and limitations. A novel technology, based upon arginine and an insoluble calcium compound, has been identified which targets dental plaque to prevent initiation and progression of the caries process by reducing pathological factors. As the mechanisms of action of arginine and fluoride are highly complementary, a next-generation dentifrice has been developed, which combines arginine, an insoluble calcium compound, and fluoride, and has been clinically proven to provide superior caries prevention.
  • Article
    Traditionally, caries clinical trials of oral care products have focused on the prevention of caries in children and adolescents at the "cavitation" level. Because of a general reduction in caries incidence and the use of positive control comparators, studies have grown both in size and duration to improve statistical power. Currently, they tend to be of 2 to 3 years' duration, with up to 2,000 high-risk individuals per group. During the past decade, there has been a shift in emphasis from a restorative approach to the treatment of dental caries to a therapeutic approach focused on the remineralization of early caries lesions. However, caries clinical trials of oral care products have not often reflected this paradigm change. This manuscript reviews alternative caries clinical trial methods for oral care products. It is concluded that methods focused on the detection and monitoring of enamel caries and root caries, by visual approaches such as ICDAS and instrumental methods such as QLF, Diagnodent, and Electrical Caries Monitors, provide viable alternatives to traditional methods. In particular, such approaches more accurately reflect the modes of action of many therapeutic agents and formulations and may reduce the cost and duration of product innovation.
  • Article
    Full-text available
    This study investigated the relationship of arginine deiminase (ADS) and urease activities with dental caries through a case-control study. ADS and urease activities were measured in dental smooth-surface supragingival plaque and whole saliva samples from 93 subjects, who were in three different groups: caries-free (n = 31), caries-active (n = 30), and caries-experienced (n = 32). ADS activity was measured by quantification of the ammonia generated from the incubation of plaque and saliva samples in a mixture containing 50 mM arginine-HCl and 50 mM Tris-maleate buffer, pH 6.0. ADS-specific activity was defined as nanomoles of ammonia generated per minute per milligram of protein. Urease activity was determined by quantification of ammonia produced from 50 mM urea. For bacterial identification and enumeration real-time qPCR analysis was used. Groups were compared using Kruskal-Wallis tests. Spearman correlations were used to analyze plaque metabolic activity and bacterial relationships. The results revealed significantly higher ammonia production from arginine in saliva (1.06 vs. 0.18; p < 0.0001) and plaque samples (1.74 vs. 0.58; p < 0.0001) from caries-free subjects compared to caries-active subjects. Urease levels were about 3-fold higher in the plaque of caries-free subjects (p < 0.0001). Although higher urease activity in saliva of caries-experienced and caries-free subjects was evident, no significant difference was found between the groups.
  • Article
    Many children experience painful tooth decay which can lead to the tooth/teeth being extracted. Even if teeth are not extracted the tooth decay may be distressing, be expensive to treat and may involve children and their carers having time off school and work. Another Cochrane review showed that fluoride toothpastes do reduce dental decay, by about 24% on average, when compared with a non-fluoride toothpaste. This review compares toothpastes with different amounts of fluoride. This review includes 79 trials on 73,000 children. As expected the use of toothpaste containing more fluoride is generally associated with less decay. Toothpastes containing at least 1000 parts per million (ppm) fluoride are effective at preventing tooth decay in children, which supports the current international standard level recommended. Although none of the trials included in the review looked at fluorosis or mottling of the children's teeth, fluorosis may be an unwanted result of using fluoride toothpaste in young children and a Cochrane review on this topic has also been published. The possible risk of fluorosis should be discussed with your dentist who may recommend using a toothpaste containing less than 1000 ppm fluoride.
  • Article
    Full-text available
    Objective To compare the efficacy of a new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride to a matched, positive control dentifrice containing 1450 ppm fluoride in arresting and reversing early coronal caries lesions in children using Quantitative Light-induced Fluorescence (QLF). Study design 331 children from Chiang Mai, Thailand, aged 7–14 years, with one or more visible early enamel caries lesions on the upper anterior teeth, completed the study. The new dentifrice contained 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate; the matched positive control contained 1450 ppm fluoride only. Subjects brushed twice daily at home and additionally once on school days under teacher's supervision. Digital images of the upper six anterior teeth were captured at the baseline, 3- and 6-month examinations using a custom apparatus for reproducible acquisition of Quantitative Light-induced Fluorescence data. Results At the 3-month examination, the ΔQ (representing lesion volume) for the test group decreased from a mean of 28.62 at baseline to 20.53 mm2% and for the positive control group to 23.38 mm2%. The difference between groups was not statistically significant (p = 0.055). At the 6-month examination, the ΔQ decreased for the test group to 15.85 mm2% and for the positive control group to 20.35 mm2%. The difference between groups was statistically significant (p < 0.001). Conclusion A new dentifrice containing 1.5% arginine, an insoluble calcium compound, and 1450 ppm fluoride, as sodium monofluorophosphate, provided statistically significant superior efficacy in arresting and reversing active coronal caries lesions in children than brushing with a matched positive control dentifrice containing fluoride alone.
  • Article
    While there is broad consensus in the research community that fluoride dentifrices provide important anticaries benefits, debate still remains as to the most efficient form of fluoride used in toothpastes. Recently, the authors of this paper collaborated as part of a scientific advisory group whose objective was to comprehensively review all clinical information available comparing the anticaries efficacy of the two agents most widely used in fluoridated toothpastes, sodium fluoride (NaF) and sodium monofluorophosphate (SMFP). This review included a detailed analysis of each published study pertinent to the question, a comprehensive meta-analysis of all available clinical findings, and an epidemiological assessment of how anticaries benefits of dentifrices may be anticipated to propagate with time. Overall, the use of meta-analysis of head-to-head clinical comparisons between the two fluoride-active systems was found to be the most valid means for comparing the relative efficacy of NaF and SMFP dentifrices. Results of this analysis demonstrated that NaF was significantly more effective than SMFP in preventing caries (p
  • Article
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    Comparative attributes are terms or phrases commonly employed in the vernacular of the biomedical literature to convey the results of comparative studies. Examples are such terms as "equivalent" or "superior." Recently, there has developed an increasing tendency in certain areas of application toward the institution of guidelines which provide both a uniform set of criteria for defining such attributes and a set of requirements which must be satisfied in order to demonstrate that such attributes may hold in a particular situation. The present paper provides a general discussion of comparative attributes, from which the application of the underlying concepts to any particular context might better be understood. Second, it provides an explicit and comprehensive discussion regarding the American Dental Associations's guidelines concerning the attributions of "superiority," "equivalence," and "at least as good as," as they are applied to the comparison of the clinical anticaries efficacy of fluoride dentifrices.
  • Article
    The aim of this paper was to describe what experts of today believe are the main reasons explaining the caries decline seen in many westernized countries over the past 3 decades. We have collected the views of a number of international experts, trying to answer the specific question "What are the main reasons why 20-25-year-old persons have less caries nowadays, compared to 30 years ago?". A questionnaire was mailed to 55 experts with a number of thinkable explanations to be scored according to a predetermined scale. The 25 items were divided into main groups under the heading of diet, fluorides, plaque, saliva, dentist/dental materials and other factors. The experts were asked to think of a specific country or area, and also to specify whether the chosen area had water fluoridation or not. The main finding of our study, based on a 95% response rate, was that there is a very large variation in how the experts graded the impact of various possible factors. For the use of fluoride toothpaste, there was a clear agreement of a definite positive effect.
  • Article
    To provide a head-to-head comparison of the anticaries efficacy associated with two commercially-available and American Dental Association-accepted dentifrices: Crest Cavity Fighting Toothpaste with Fluoristat, containing 0.243% sodium fluoride in a silica base, and Colgate Great Regular Flavor Fluoride Toothpaste, containing 0.76% sodium monofluorophosphate in a dicalcium phosphate dihydrate base. The study was conducted in harmony with the published 1988 American Dental Association guidelines for studies geared toward this purpose. The study employed a double-blind, parallel-groups, multi-center two-treatment design, and involved third, fourth, and fifth grade schoolchildren from Newark, New Jersey, and from the Cidra and Lares areas of Puerto Rico. Qualifying subjects were stratified according to age and sex, and were randomly assigned to the two treatment groups, with multiple subjects in the same household all assigned to the dentifrice randomly allocated to the first among them. Caries examinations were conducted in accordance with U.S. Food and Drug Administration guidelines for the clinical evaluation of drugs to prevent dental caries. After treatment assignment, study participants were instructed to brush their teeth at home with their assigned dentifrice at least twice daily. Brushing instructions were reinforced by the presentation of educational films and lectures at school, by semi-annual mailings to parents, and through the periodic distribution of small novelty gifts along with the dentifrice deliveries, in order to enhance the interest and enthusiasm of study participants. Post-baseline examinations were performed after 1 and after 2 yrs of product use. Two thousand four hundred seventy-nine (2,479) subjects completed this 2-yr study. For these subjects, the mean (S.D.) DFS scores at baseline were 2.77 (3.35) for the Crest group, and 2.66 (3.18) for the Colgate group. For caries increment after 1 yr, the respective means were 1.68 (2.53) and 1.70 (2.57). After 2 yrs, the mean caries increments were 3.56 (4.11) for the Crest group, and 3.56 (4.05) for the Colgate group. The analysis of the 2-yr caries increment scores support the conclusion that the anticaries efficacy associated with Colgate Great Regular Flavor Fluoride Toothpaste is equivalent to that associated with Crest Cavity Fighting Toothpaste with Fluoristat, in accordance with the procedures and standards provided by the published guidelines of the American Dental Association. Further, consistent with those same standards, the results of this study serve to lend additional support to the conclusion that dentifrices formulated with sodium monofluorophosphate provide an equivalent level of anticaries efficacy as to those formulated with sodium fluoride.
  • Article
    Children who brush their teeth at least once a day with a toothpaste that contains fluoride will have less tooth decay. Tooth decay (dental caries) is painful, expensive to treat and can sometimes lead to serious damage to teeth. Fluoride is a mineral that prevents tooth decay. The review of trials found that children aged 5 to 16 years who used a fluoridated toothpaste had fewer decayed, missing and filled permanent teeth after three years (regardless of whether their drinking water was fluoridated). Twice a day use increases the benefit. No conclusion could be reached about the risk that using fluoride toothpastes could mottle teeth (fluorosis), an effect of chronic ingestion of excessive amounts of fluoride when children are young.
  • Article
    Full-text available
    This study assessed the effect of an arginine bicarbonate/calcium carbonate (CaviStat)-containing dentifrice on caries development, mainly in 11- to 12-year-old Venezuelan children over a two-year period. Children (726) with a DMFT between 3 and 6 were examined at baseline, six months, and one and two years using a mirror, probe, and DMFS scoring. Subjects who completed the study consisted of two groups; 304 test and 297 control. The test group received a CaviStat-containing dentifrice, and the controls used a commercially available 1100 ppm fluoride toothpaste. All subjects were instructed to brush three times a day for 1 minute followed by swishing for 30 seconds. After six months, the mean DMFS scores increased only slightly from baseline in both groups, 6.93 +/- 0.22 in the control and 6.59 +/- 0.22 in the test subjects. After one year, the mean DMFS score in the control group rose to 8.00 +/- 0.24 and leveled off at 7.92 +/- 0.30 at two years. In contrast, the mean DMFS score in the test group decreased to 5.50 +/- 0.24 after one year before rising to 6.99 +/- 0.28 at two years. DMFS difference between the two groups was highly significant (p < 0.001), but mainly due to the large difference seen at one year. Dissection of the data showed that the erupted first molars dominated the overall DMFS changes. At the beginning of this study, first molar scores started at high values and showed a pattern thereafter like that seen for the total data. In contrast, premolars/molars, which erupt 4-6 years later (and at the start of the study had a mean DMFS score slightly above zero), showed a clear rise in the DMFS score in the control group during the first year of the study, which continued to rise until the end of the investigation. In contrast, the CaviStat group showed no change in the premolar/second molar DMFS score from baseline during the first year (giving the impression of 100% inhibition at one year), but showed a delayed rise thereafter that paralleled that seen in the controls between one and two years (58.3% inhibition at two years). Reversal of the development of early dental caries lesions in the CaviStat subjects and limitations of the diagnosis of very early caries lesions with standard dental explorers was suggested for the interesting first molar, first year data. Inhibition of caries initiation and caries progression in the CaviStat group was also observed and easier to see in the premolar/second molar, second year data where the DMFS scores were very low at baseline and reversals are not a significant issue. The results were subjected to statistical analysis including analysis of covariance. Largely because of the first year and first molar data, the difference between control and experimental groups was highly significant (p < 0.001). Similar comparison with the later-erupting premolar/molar teeth showed the CaviStat effect was also significant but at a lower level (p < 0.05). The differences could not be due to examiner error since the Kappa for 10% of the subjects randomly selected and re-examined was 0.898 overall and 0.914 for the first molar data. The data also suggested CaviStat inhibition of caries progression because of a slower rate of rise of missing+filled teeth in the CaviStat vs. the control group (p < 0.05). A CaviStat-containing toothpaste was more effective both clinically and statistically in inhibiting caries initiation and progression than the fluoride toothpaste control, and manifested its effects differently in the already-erupted first molars than in the later-erupting premolars and second molars.