Melbourne Dental School - Research Publications

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    Anticariogenic efficacy of a saliva biomimetic in head-and-neck cancer patients undergoing radiotherapy
    Sim, CPC ; Walker, GD ; Manton, DJ ; Soong, YL ; Wee, JTS ; Adams, GG ; Reynolds, EC (WILEY, 2019-03)
    BACKGROUND: The aim of this study was to investigate the effect of treatment with the saliva biomimetic, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and SnF2 /NaF compared with SnF2 /NaF alone on coronal surface caries progression in head-and-neck cancer patients undergoing radiotherapy. METHODS: Twenty-four participants were randomized into two groups. Both groups used 0.4% SnF2 gel and a 0.32% NaF toothpaste; the test group also applied a crème containing 10% CPP-ACP three times daily while the control group used an identical crème without CPP-ACP (placebo). Resting saliva flow rate and saliva fluoride concentrations were determined. Caries status was assessed using ICDASII at baseline and 12-weeks postradiotherapy. Data were statistically analysed using a linear mixed effects model. RESULTS: Both groups showed significantly reduced resting saliva flow rate (P < 0.001) postradiotherapy. There were no significant differences in flow rates and fluoride concentration between groups. The CPP-ACP group exhibited a significant (P < 0.05) 51% reduction in coronal surface caries progression compared with the placebo group. CONCLUSION: Resting salivary flow rate was significantly reduced in head-and-neck cancer patients following radiotherapy and use of CPP-ACP with SnF2 /NaF significantly lowered caries progression compared with SnF2 /NaF alone.
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    Xerostomia, salivary characteristics and gland volumes following intensity-modulated radiotherapy for nasopharyngeal carcinoma: a two-year follow up
    Sim, CPC ; Soong, YL ; Pang, EPP ; Lim, C ; Walker, GD ; Manton, DJ ; Reynolds, EC ; Wee, JTS (WILEY, 2018-06)
    BACKGROUND: To evaluate changes in xerostomia status, salivary characteristics and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma patients. METHODS: Xerostomia scores, salivary flow rates, pH and buffering capacity were measured at pre-radiotherapy, mid-radiotherapy, 2 weeks, 3 months and 2 years post-radiotherapy. Salivary gland volumes and their correlation with radiation dose were also assessed. RESULTS: Mean radiation dose to oral cavity, parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively. Parotid and SMG volumes decreased 33% at 3 months post-radiotherapy; volumes at 2 years post-radiotherapy were 84% and 51% of pre-radiotherapy levels, respectively. Correlations were observed between parotid gland volume per cent reduction and its radiation dose and between resting salivary flow rate reduction and post-radiotherapy/pre-radiotherapy SMG volume ratio. Salivary flow rates and resting saliva pH remained significantly low at 2 years post-radiotherapy (both flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia scores remained significantly higher compared with pre-radiotherapy levels. CONCLUSIONS: Submandibular gland volumetric shrinkage persisted 2 years after radiotherapy. Xerostomia scores remained significantly higher, and salivary flow rates and resting saliva pH remained significantly lower, suggesting that study participants were still at risk for hyposalivation-related oral diseases.
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    Temporal development of the oral microbiome and prediction of early childhood caries
    Dashper, SG ; Mitchell, HL ; Le Cao, K-A ; Carpenter, L ; Gussy, MG ; Calache, H ; Gladman, SL ; Bulach, DM ; Hoffmann, B ; Catmull, D ; Pruilh, S ; Johnson, S ; Gibbs, L ; Amezdroz, E ; Bhatnagar, U ; Seemann, T ; Mnatzaganian, G ; Manton, DJ ; Reynolds, EC (NATURE PORTFOLIO, 2019-12-24)
    Human microbiomes are predicted to assemble in a reproducible and ordered manner yet there is limited knowledge on the development of the complex bacterial communities that constitute the oral microbiome. The oral microbiome plays major roles in many oral diseases including early childhood caries (ECC), which afflicts up to 70% of children in some countries. Saliva contains oral bacteria that are indicative of the whole oral microbiome and may have the ability to reflect the dysbiosis in supragingival plaque communities that initiates the clinical manifestations of ECC. The aim of this study was to determine the assembly of the oral microbiome during the first four years of life and compare it with the clinical development of ECC. The oral microbiomes of 134 children enrolled in a birth cohort study were determined at six ages between two months and four years-of-age and their mother's oral microbiome was determined at a single time point. We identified and quantified 356 operational taxonomic units (OTUs) of bacteria in saliva by sequencing the V4 region of the bacterial 16S RNA genes. Bacterial alpha diversity increased from a mean of 31 OTUs in the saliva of infants at 1.9 months-of-age to 84 OTUs at 39 months-of-age. The oral microbiome showed a distinct shift in composition as the children matured. The microbiome data were compared with the clinical development of ECC in the cohort at 39, 48, and 60 months-of-age as determined by ICDAS-II assessment. Streptococcus mutans was the most discriminatory oral bacterial species between health and current disease, with an increased abundance in disease. Overall our study demonstrates an ordered temporal development of the oral microbiome, describes a limited core oral microbiome and indicates that saliva testing of infants may help predict ECC risk.
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    Biocompatibility and Osteogenic/Calcification Potential of Casein Phosphopeptide-amorphous Calcium Phosphate Fluoride
    Dawood, AE ; Manton, DJ ; Parashos, P ; Wong, RH ; Singleton, W ; Holden, JA ; O'Brien-Simpson, NM ; Reynolds, EC (ELSEVIER SCIENCE INC, 2018-03)
    INTRODUCTION: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and CPP-ACP with fluoride (CPP-ACFP) have been shown to provide bioavailable ions to promote mineralization. Hence, the aim of this study was to evaluate the materials' biocompatibility and osteogenic/calcification potential for endodontic applications. METHODS: Human and mouse osteoblast-like and fibroblast-like cell lines were incubated with 0.05%-3.0% w/v CPP-ACP and CPP-ACFP, and toxicity, proliferation, alkaline phosphatase, interleukin (IL)-1α, and IL-6 production, collagen type I, osteocalcin, and osteopontin production, and mineralization/calcification were determined. RESULTS: CPP-ACP and CPP-ACFP were non-toxic and had no significant effect on proliferation or production of the inflammatory cytokine IL-1α. Alkaline phosphatase activity of the osteoblast-like cells was significantly increased (P < .05) by CPP-ACP and CPP-ACFP, as was the production of the osteotropic cytokine IL-6, the formation of calcium mineral deposits, and the secretion of mineralization-related proteins (collagen type I and osteocalcin). CONCLUSIONS: CPP-ACP and CPP-ACFP are biocompatible and have the potential to induce osteoblastic differentiation and mineralization. Potential applications include apexification, perforation repair, vital pulp therapy, and regenerative endodontic procedures.
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    Characterisation of developmentally hypomineralised human enamel
    Crombie, FA ; Manton, DJ ; Palamara, JEA ; Zalizniak, I ; Cochrane, NJ ; Reynolds, EC (ELSEVIER SCI LTD, 2013-07)
    OBJECTIVES: To investigate and clarify physical and chemical properties of enamel affected by molar incisor hypomineralisation (MIH). METHODS: A series of in vitro studies were performed on extracted molars affected by MIH and sound teeth for controls. Tooth sections underwent Vickers microhardness testing before lapping and subsequent transverse microradiographic analysis and examination under polarised light microscopy. Carbonate content was determined by CO2 release from acid digestion. Unprepared and fractured surfaces were examined under scanning electron microscopy. RESULTS: MIH-affected molars demonstrated a severe degree of hypomineralisation with an average mineral content of only 58.8%vol% mineral. Vickers microhardness was significantly reduced in MIH compared with controls (1.8±1.1 v 4.4±1.0 GPa, p<0.05) and polarised light microscopy revealed the bulk of MIH lesions had a porosity of ≤5% but also substantial areas of ≥10% and smaller areas exceeding 25% porosity. A surface layer was frequently observed on both intact and broken-down lesions and cervical regions of MIH teeth were typically spared. Carbonate content of MIH enamel was higher than control samples (6.6±2.1 v 4.4±1.1 wt%, p<0.05). Scanning electron microscopy showed that both the enamel rod and surface ultrastructure were defective. Clinical characteristics did not consistently correlate with all properties. CONCLUSIONS: The properties of MIH-affected enamel significantly differ from those of normal enamel and were highly variable, however some common characteristics were observed. Implications for aetiology and clinical management are discussed.