Explorations of the chemical constitution and aqueous solution status of caries-arresting silver(I)-diammine fluoride and silver(I)-fluoride products using high-resolution 19F NMR analysis. Spectroscopic and SEM investigations of their interactions with human saliva: evidence for the in vivo salivary-catalysed autoconstruction of Ag/AgCl-based nanoparticles (IV-SCAN)-part I.

Introduction: Silver(I)-diammine fluoride (SDF) and silver(I)-fluoride (SF) complexes have been successfully employed for the arrest of dental caries for many years. However, to date there are very few studies available reporting on the molecular structural compositional and solution status of these agents [typically applied as highly-concentrated 38% (w/v) solutions]. Here, we explored the solution status and chemical constitution of commercially-available SDF and SF products, and secondly investigated the multicomponent interplay of these products with biomolecules present in intact human whole-mouth salivary supernatants (WMSSs) in vitro. Methods: High-resolution 19F NMR analysis was employed to explore SDF and SF product solutions, and to determine WMSS fluoride (F-) concentrations, whereas ammonia (NH3) release form SDF was tracked by 1H NMR spectroscopy. SEM and thin-film FTIR-ATR analyses were employed to explore the atomic and molecular compositions of sequentially-generated AgCl deposits and chromophoric Ag/AgCl nanoparticles (CSNPs); the time-dependent generation of the latter was followed spectrophotometrically. Results: 19F NMR spectra of aqueous SF solutions contained a very broad F- signal (Δv1/2 70 Hz), demonstrating that much of its solvated F- content was rapidly exchanging with Ag(I) on the NMR timescale, but those of SDF had a much sharper resonance, similar to that of "free" F- (4 Hz). Moreover, further NMR results revealed that a popular SDF product contained high molar excesses of both F- and NH3. Treatment of WMSSs with SDF and SF generated an off-white precipitate, which slowly developed into CSNPs at 23°C; SEM demonstrated high contents of both silver and chloride in this material (ca.1:1 atomic content ratio). FTIR-ATR analysis found that the CSNPs formed contained a range of salivary biomolecules, which appear to encapsulate the Ag/AgCl core (significant thiocyanate contents were also found). In conclusion, NMR results acquired demonstrated that SF, but not SDF, product solutions feature rapidly-exchanging F - between its "free" and Ag(I)-bound forms, and that SDF contains large excesses of both F- and its NH3 ligands. Characterised AgCl deposits and CSNPs were sequentially produced from the interactions of these complexes with WMSS biomolecules. Discussion: In view of their well-known microbicidal and cariostatic properties, the observed autobioconstruction of CSNPs involving salivary catalysis is of much therapeutic significance.

Updates and Original Case Studies Focused on the NMR-Linked Metabolomics Analysis of Human Oral Fluids Part II: Applications to the Diagnosis and Prognostic Monitoring of Oral and Systemic Cancers.

Human saliva offers many advantages over other biofluids regarding its use and value as a bioanalytical medium for the identification and prognostic monitoring of human diseases, mainly because its collection is largely non-invasive, is relatively cheap, and does not require any major clinical supervision, nor supervisory input. Indeed, participants donating this biofluid for such purposes, including the identification, validation and quantification of surrogate biomarkers, may easily self-collect such samples in their homes following the provision of full collection details to them by researchers. In this report, the authors have focused on the applications of metabolomics technologies to the diagnosis and progressive severity monitoring of human cancer conditions, firstly oral cancers (e.g., oral cavity squamous cell carcinoma), and secondly extra-oral (systemic) cancers such as lung, breast and prostate cancers. For each publication reviewed, the authors provide a detailed evaluation and critical appraisal of the experimental design, sample size, ease of sample collection (usually but not exclusively as whole mouth saliva (WMS)), their transport, length of storage and preparation for analysis. Moreover, recommended protocols for the optimisation of NMR pulse sequences for analysis, along with the application of methods and techniques for verifying and resonance assignments and validating the quantification of biomolecules responsible, are critically considered. In view of the authors' specialisms and research interests, the majority of these investigations were conducted using NMR-based metabolomics techniques. The extension of these studies to determinations of metabolic pathways which have been pathologically disturbed in these diseases is also assessed here and reviewed. Where available, data for the monitoring of patients' responses to chemotherapeutic treatments, and in one case, radiotherapy, are also evaluated herein. Additionally, a novel case study featured evaluates the molecular nature, levels and diagnostic potential of 1H NMR-detectable salivary 'acute-phase' glycoprotein carbohydrate side chains, and/or their monomeric saccharide derivatives, as biomarkers for cancer and inflammatory conditions.

Potential Advantages of Peroxoborates and Their Ester Adducts Over Hydrogen Peroxide as Therapeutic Agents in Oral Healthcare Products: Chemical/Biochemical Reactivity Considerations In Vitro, Ex Vivo And In Vivo.

Peroxides present in oral healthcare products generally exert favourable protective activities against the development and progression of tooth decay, plaque, gingivitis, and halitosis, etc. However, despite the high level of research focus on hydrogen and carbamide peroxides as therapeutically active (and tooth-whitening) agents, to date the use of alternative chemical forms of peroxides such as peroxoborates for these purposes has received only scant attention. Intriguingly, peroxoborate and its esters with polyols, such as glycerol, have a very diverse chemistry/biochemistry in aqueous solution, for which there is an increasing amount of evidence that it remains distinctive from that of hydrogen peroxide; such properties include self-associative and hydrolytic equilibria, and their abilities to participate in electrophile- or nucleophile-scavenging, metal ion-complexing, redox and free radical reactions, for example. Therefore, the purpose of this detailed commentary is to evaluate both differences and similarities between the molecular/biomolecular reactivities of peroxoborate species and hydrogen peroxide in vitro, ex-vivo and in vivo. It encompasses brief sectional accounts regarding the molecular heterogeneity of peroxoborates, the release of bioactive agents therefrom, and their oxidative attack on oral cavity biomolecules (the nucleophilic or electrophilic character of these oxidations are discussed). Further areas explored are the abilities of borates and peroxoborates to enhance the solubility of iron ions in aqueous solution, their involvements in free radical biochemistry (particularly the complexation of oxygen radical-promoting transition metal ions by, and antioxidant properties of, peroxoborate-polyol ester adducts), and the specific inhibition of protease enzymes. Further aspects focus on the tooth-whitening, oral malodor neutralizing, and potential mutagenic and genotoxic properties of peroxoborates, along with possible mechanisms for these processes. The abilities of peroxoborates, and peroxides in general, to modulate the activities of inflammatory mediators and vitamins, antioxidant or otherwise, are also explored.

Summary of: Side effects of external tooth bleaching: a multi-centre practice-based prospective study.

OBJECTIVE: The study was performed to assess the risk of at-home and in-office bleaching procedures, and to recognise potential predictors for side effects. DESIGN: Multi-centre, questionnaire-based prospective study with follow-ups at around 14 days and around one year post-treatment. SETTING: General practices and university clinics during the years 2007-2009 in Scandinavia. SUBJECTS: Patients with tooth bleaching as part of the treatment plan.Results The prevalence of experienced tooth sensitivity at first follow-up was independent of bleaching procedure (at-home = 50.3% [n = 143]; in-office = 39.3% [n = 28]; p >0.05; 95% CI [OR]: 0.198-1.102) whereas prevalence of gingival irritation was higher after in-office treatment (at-home = 14.0%; in-office = 35.7%; p <0.05) (mean age: 37.3 years; 73.7% women; n = 171). At the second follow-up, two and three patients reported side effects attributed to the bleaching treatment in the at-home and in-office groups, respectively. Predictors for side effects were tooth sensitivity, surface loss and gingivitis when observed at inclusion. Treatment-related predictors were bleaching concentration and contact between tray and gingiva. CONCLUSIONS: Bleaching treatment, irrespective of method, caused a high prevalence of side effects. Patients associated with the predictors at inclusion mentioned above should be notified of the risk for side effects and treated only if bleaching is indicated based on a proper diagnosis.

Wyman Chan: 'technically, I have been doing my job illegally for the past 20 years'. Interview by Ruth Doherty.

Wyman Chan talks to the BDJ about his mission to deliver pain-free whitening treatments and his views on the recent tooth-whitening legislation.