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    ABSTRACT: Functional recovery from injuries to the brain or spinal cord represents a major clinical challenge. The transplantation of stem cells, traditionally isolated from embryonic tissue, may help to reduce damage following such events and promote regeneration and repair through both direct cell replacement and neurotrophic mechanisms. However, the therapeutic potential of using embryonic stem/progenitor cells is significantly restricted by the availability of embryonic tissues and associated ethical issues. Populations of stem cells reside within the dental pulp, representing an alternative source of cells that can be isolated with minimal invasiveness, and thus should illicit fewer moral objections, as a replacement for embryonic/fetal-derived stem cells. Here we discuss the similarities between dental pulp stem cells (DPSCs) and the endogenous stem cells of the central nervous system (CNS) and their ability to differentiate into neuronal cell types. We also consider in vitro and in vivo studies demonstrating the ability of DPSCs to help protect against and repair neuronal damage, suggesting that dental pulp may provide a viable alternative source of stem cells for replacement therapy following CNS damage. © 2013 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 08/2013;
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    ABSTRACT: The in vitro effect of a novel, oligosaccharide nanomedicine OligoG against oral pathogen-related biofilms, both alone and in the presence of the conventional anti-bacterial agent triclosan, was evaluated. The effect of OligoG±triclosan was assessed against established Streptococcus mutans and Porphyromonas gingivalis biofilms by bacterial counts and image analysis using LIVE/DEAD(®) staining and atomic force microscopy (AFM). The effect of triclosan and OligoG surface pre-treatments on bacterial attachment to titanium and polymethylmethacrylate was also studied. OligoG potentiated the antimicrobial effect of triclosan, particularly when used in combination at 0.3% against S. mutans grown in artificial saliva. OligoG was less effective against established P. gingivalis biofilms. However, attachment of P. gingivalis, to titanium in particular, was significantly reduced after surface pre-treatment with OligoG and triclosan at 0.01% when compared to controls. Light microscopy and AFM showed that OligoG was biocidal to P. gingivalis, but not S. mutans. OligoG and triclosan when used in combination produced an enhanced antimicrobial effect against two important oral pathogens and reduced bacterial attachment to dental materials such as titanium, even at reduced triclosan concentrations. Whilst the use of triclosan against oral bacteria has been widely documented, its synergistic use with OligoG described here, has not previously been reported. The use of lower concentrations of triclosan, if used in combination therapy with OligoG, could have environmental benefits. The potentiation of antimicrobial agents by naturally-occurring oligomers such as OligoG may represent a novel, safe adjunct to conventional oral hygiene and periodontal therapy. The ability of OligoG to inhibit the growth and impair bacterial adherence highlights its potential in the management of peri-implantitis.
    Journal of dentistry 07/2013;
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    ABSTRACT: The influence of a novel, safe antibiofilm therapy on the mechanical properties of Pseudomonas aeruginosa and Acinetobacter baumannii biofilms in vitro was characterized. A multiscale approach employing atomic force microscopy (AFM) and rheometry was used to quantify the mechanical disruption of the biofilms by a therapeutic polymer based on a low-molecular weight alginate oligosaccharide (OligoG). AFM demonstrated structural alterations in the biofilms exposed to OligoG, with significantly lower Young's moduli than the untreated biofilms, (149 MPa vs 242 MPa; p < 0.05), a decreased resistance to hydrodynamic shear and an increased surface irregularity (Ra) in the untreated controls (35.2 nm ± 7.6 vs 12.1 nm ± 5.4; p < 0.05). Rheology demonstrated that increasing clinically relevant concentrations of OligoG (<10%) were associated with an increasing phase angle (δ) over a wide range of frequencies (0.1-10 Hz). These results highlight the utility of these techniques for the study of three-dimensional biofilms and for quantifying novel disruption therapies in vitro.
    Biofouling 04/2013; 29(4):413-21.
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    ABSTRACT: Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. The organism is however, commonly encountered as a commensal in healthy individuals where it is a component of the normal microflora. The key determinant in the type of relationship that Candida has with its host is how it interacts with the epithelial surface it colonises. A delicate balance clearly exists between the potentially damaging effects of Candida virulence factors and the nature of the immune response elicited by the host. Frequently, it is changes in host factors that lead to Candida seemingly changing from a commensal to pathogenic existence. However, given the often reported heterogeneity in morphological and biochemical factors that exist between Candida species and indeed strains of C. albicans, it may also be the fact that colonising strains differ in the way they exploit resources to allow persistence at mucosal surfaces and as a consequence this too may affect the way Candida interacts with epithelial cells. The aim of this review is to provide an overview of some of the possible interactions that may occur between C. albicans and host epithelial surfaces that may in turn dictate whether Candida removal, its commensal persistence or infection follows.
    Journal of Oral Microbiology 01/2013; 5.
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    ABSTRACT: Human infections involving yeast of the genus Candida often occur in the presence of bacteria, and, as such, it is important to understand how these bacteria influence innate host immunity towards Candida. Dectin-1 is a cell receptor of macrophages for Candida albicans recognition. The aim of this study was to examine dectin-1 expression by monocytes after stimulation with bacterial lipopolysaccharide (LPS), followed by heat-killed C. albicans (HKC). Freshly isolated human peripheral blood monocytes (PBMCs) and human monocytes cell line (THP-1) cells expressed low levels of dectin-1. Stimulation with LPS and GM-CSF/IL-4 was found to increase dectin-1 expression in both CD14(+) human PBMC and THP-1 cells. Enhanced dectin-1 expression resulted in increased phagocytosis of Candida. When THP-1 cells were challenged only with HKC, detectable levels of IL-23 were not evident. However, challenge by LPS followed by varying concentrations of HKC resulted in increased IL-23 expression by THP-1 cells in HKC dose-dependent manner. Increased expression of IL-17 by PBMC also occurred after stimulation with Candida and LPS. In conclusion, bacterial LPS induces an enhanced immune response to Candida by immune cells, and this occurs through increasing dectin-1 expression.
    Clinical and Developmental Immunology 01/2013; 2013:320168.
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    ABSTRACT: Members of the Streptococcus anginosus group (SAGs) are significant pathogens. However, their pathogenic mechanisms are incompletely understood. This study investigates the adherence of SAGs to the matrix proteoglycans decorin and biglycan of soft gingival and alveolar bone. Recombinant chondroitin 4-sulphate(C4S)-conjugated decorin and biglycan were synthesised using mammalian expression systems. C4S-conjugated decorin/biglycan and dermatan sulphate (DS) decorin/biglycan were isolated from ovine alveolar bone and gingival connective tissue, respectively. Using surface plasmon resonance, adherence of the SAGs S. anginosus, Streptococcus constellatus and Streptococcus intermedius to immobilised proteoglycan was assessed as a function of real-time biofilm formation. All isolates adhered to gingival proteoglycan, 59% percent of isolates adhered to alveolar proteoglycans, 70% to recombinant decorin and 76% to recombinant biglycan. Higher adherence was generally noted for S. constellatus and S. intermedius isolates. No differences in adherence were noted between commensal and pathogenic strains to decorin or biglycan. DS demonstrated greater adherence compared to C4S. Removal of the glycosaminoglycan chains with chondroitinase ABC resulted in no or minimal adherence for all isolates. These results suggest that SAGs bind to the extracellular matrix proteoglycans decorin and biglycan, with interaction mediated by the conjugated glycosaminoglycan chain.
    Research in Microbiology 07/2012; 163(6-7):436-47.
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    ABSTRACT: The uncontrolled, often inappropriate use of antibiotics has resulted in the increasing prevalence of antibiotic-resistant pathogens, with major cost implications for both United States and European health care systems. We describe the utilization of a low-molecular-weight oligosaccharide nanomedicine (OligoG), based on the biopolymer alginate, which is able to perturb multidrug-resistant (MDR) bacteria by modulating biofilm formation and persistence and reducing resistance to antibiotic treatment, as evident using conventional and robotic MIC screening and microscopic analyses of biofilm structure. OligoG increased (up to 512-fold) the efficacy of conventional antibiotics against important MDR pathogens, including Pseudomonas, Acinetobacter, and Burkholderia spp., appearing to be effective with several classes of antibiotic (i.e., macrolides, β-lactams, and tetracyclines). Using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), increasing concentrations (2%, 6%, and 10%) of alginate oligomer were shown to have a direct effect on the quality of the biofilms produced and on the health of the cells within that biofilm. Biofilm growth was visibly weakened in the presence of 10% OligoG, as seen by decreased biomass and increased intercellular spaces, with the bacterial cells themselves becoming distorted and uneven due to apparently damaged cell membranes. This report demonstrates the feasibility of reducing the tolerance of wound biofilms to antibiotics with the use of specific alginate preparations.
    Antimicrobial Agents and Chemotherapy 07/2012; 56(10):5134-41.
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    ABSTRACT: To examine the influence of extracellular matrix (ECM) proteins in enhancing bacterial adhesion and biofilm formation on titanium surfaces. The adherence of 21 bacterial isolates to prepolished 1 cm(2) titanium samples was screened using fluorescence microscopy. Three isolates that exhibited "low" (Porphyromonas gingivalis R17870), "moderate" (Porphyromonas gingivalis 5335), and "extensive" (Prevotella denticola R9102) adherence to titanium were then examined for titanium adherence in the presence of the ECM proteins vitronectin, fibronectin, laminin, collagen type I, and collagen type IV. Several ECM proteins had a considerable effect on increasing adherence of the bacteria to titanium compared to a control (no protein treatment). The most significant difference was seen with vitronectin for P. gingivalis 5335 (p < 0.001 at 4 h, 24-h incubation times) and P. gingivalis R17870 (p < 0.05 at 4 h, 24 h incubation times). For P. denticola R9102, vitronectin was not found to enhance adherence at 4 h, (p > 0.05), whilst collagen type I and fibronectin did result in significantly enhanced adherence (p < 0.05, 24 h). ECM matrix proteins promote adherence of potential periodontal pathogenic bacteria to titanium surfaces. Management of diseases such as peri-implantitis should focus on limitation of this bacterial adherence to reduce/eliminate biofilms.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 05/2012; 100(5):1319-27.
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    ABSTRACT: This study investigated the effects of combined titanium nano-/micron-scale roughness, induced by hydrogen peroxide pre-treatments, on bone marrow stromal cell responses and Porphyromonas gingivalis adherence in vitro. Untreated surfaces exhibited nano-scale features, while hydrogen peroxide treatments promoted increased nano-/micron-scale roughness. Bone marrow stromal cell attachment and proliferation were maintained with 6 h and 24 h treatments, but significantly decreased on 1-week and 4-week-treated surfaces. Bone marrow stromal cells on 6 h-4 week-treated titanium demonstrated enhanced osteogenic differentiation versus untreated surfaces. P. gingivalis adherence was significantly increased on 24 h-4 week surfaces. Results suggest that 6 h but less than 24 h treatments maintain or promote bone marrow stromal cell responses while minimizing microbial adherence, potentially enhancing titanium surface bio-activation for osseointegration.
    Journal of Biomaterials Applications 03/2012;
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    ABSTRACT: Removable partial dentures (RPDs) remain a mainstay of prosthodontic care for partially dentate patients. Appropriately designed, they can restore masticatory efficiency, improve aesthetics and speech, and help secure overall oral health. However, challenges remain in providing such treatments, including maintaining adequate plaque control, achieving adequate retention, and facilitating patient tolerance. The aim of this paper is to review the successful provision of RPDs. CLINICAL RELEVANCE: Removable partial dentures are a successful form of treatment for replacing missing teeth, and can be successfully provided with appropriate design and fabrication concepts in mind.
    Dental update 03/2012; 39(2):118-20, 122-6.
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