• HDACi: cellular effects, opportunities for restorative dentistry.

      Duncan, H F; Smith, A J; Fleming, G J P; Cooper, P R; Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland. (2011-12)
      Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be 'tipped' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between 'normal' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.
    • The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs.

      Lyons, Frank G; Al-Munajjed, Amir A; Kieran, Stephen M; Toner, Mary E; Murphy, Ciara M; Duffy, Garry P; O'Brien, Fergal J; Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland. (2010-12)
      One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.
    • Histone Acetylation as a Regenerative Target in the Dentine-Pulp Complex.

      Yamauchi, Yukako; Cooper, Paul Roy; Shimizu, Emi; Kobayashi, Yoshifumi; Smith, Anthony J; Duncan, Henry Fergus (2020-02-06)
      If dental caries (or tooth decay) progresses without intervention, the infection will advance through the dentine leading to severe pulpal inflammation (irreversible pulpitis) and pulp death. The current management of irreversible pulpits is generally root-canal-treatment (RCT), a destructive, expensive, and often unnecessary procedure, as removal of the injurious stimulus alone creates an environment in which pulp regeneration may be possible. Current dental-restorative-materials stimulate repair non-specifically and have practical limitations; as a result, opportunities exist for the development of novel therapeutic strategies to regenerate the damaged dentine-pulp complex. Recently, epigenetic modification of DNA-associated histone 'tails' has been demonstrated to regulate the self-renewal and differentiation potential of dental-stem-cell (DSC) populations central to regenerative endodontic treatments. As a result, the activities of histone deacetylases (HDAC) are being recognised as important regulators of mineralisation in both tooth development and dental-pulp-repair processes, with HDAC-inhibition (HDACi) promoting pulp cell mineralisation in vitro and in vivo. Low concentration HDACi-application can promote de-differentiation of DSC populations and conversely, increase differentiation and accelerate mineralisation in DSC populations. Therapeutically, various HDACi solutions can release bioactive dentine-matrix-components (DMCs) from the tooth's extracellular matrix; solubilised DMCs are rich in growth factors and can stimulate regenerative processes such as angiogenesis, neurogenesis, and mineralisation. The aim of this mini-review is to discuss the role of histone-acetylation in the regulation of DSC populations, while highlighting the importance of HDAC in tooth development and dental pulp regenerative-mineralisation processes, before considering the potential therapeutic application of HDACi in targeted biomaterials to the damaged pulp to stimulate regeneration.
    • Histone deacetylase inhibitors induced differentiation and accelerated mineralization of pulp-derived cells.

      Duncan, Henry F; Smith, Anthony J; Fleming, Garry J P; Cooper, Paul R; Division of Restorative Dentistry and Periodontology, Dublin Dental University Hospital, Trinity College Dublin, Dublin, Ireland. Hal.Duncan@dental.tcd.ie (2012-03)
      Histone deacetylase inhibitors (HDACis) alter the homeostatic balance between 2 groups of cellular enzymes, histone deacetylases (HDACs) and histone acetyltransferases (HATs), increasing transcription and influencing cell behavior. This study investigated the potential of 2 HDACis, valproic acid (VPA) and trichostatin A (TSA), to promote reparative processes in pulp cells as assayed by viability, cell cycle, and mineralization analyses.
    • History of the oral systemic relationship.

      Claffey, N; Polyzois, I; Williams, R (Professional Audience Communications, 2010)
    • HIV transmission in the dental setting and the HIV-infected oral health care professional: workshop 1C.

      Flint, S R; Croser, D; Reznik, D; Glick, M; Naidoo, S; Coogan, M; Dublin Dental School and Hospital and Trinity College, Dublin, Ireland. Stephen.flint@dental.tcd.ie (2011-04)
      This workshop addressed two important issues: first, the global evidence of HIV transmission from health care provider to patient and from patient to health care provider in the general health care environment and the dental practice setting; second, in the era of highly active antiretroviral therapy, whether oral health care professionals living with HIV pose a risk of transmission to their patients and whether standard infection control is adequate to protect both the patient and the oral health care professional in dental practice. The workshop culminated in a general discussion and the formulation of a consensus statement from the participating delegates, representing more than 30 countries, on the criteria under which an HIV-infected oral health care professional might practice dentistry without putting patients at risk. This consensus statement, the Beijing Declaration, was agreed nem con.
    • How do implant surface characteristics influence peri-implant disease?

      Renvert, Stefan; Polyzois, Ioannis; Claffey, Noel; Department of Health Sciences, Kristianstad University, Kristianstad, Sweden. stefan.renvert@hkr.se (2011-03)
      To review the literature on how implant surface characteristics influence peri-implant disease.
    • Identification and characterization of the multidrug resistance gene cfr in a Panton-Valentine leukocidin-positive sequence type 8 methicillin-resistant Staphylococcus aureus IVa (USA300) isolate.

      Shore, Anna C; Brennan, Orla M; Ehricht, Ralf; Monecke, Stefan; Schwarz, Stefan; Slickers, Peter; Coleman, David C; Microbiology Research Unit, Division of Oral Biosciences, School of Dental Science and Dublin Dental Hospital, University of Dublin, Trinity College Dublin, Dublin 2, Ireland. (2010-12)
      The staphylococcal cfr gene mediates resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A, a phenotype that has been termed PhLOPS(A). The cfr gene has mainly been associated with coagulase-negative staphylococcal isolates from animals, and only a few cfr-positive methicillin-resistant Staphylococcus aureus (MRSA) isolates have been described so far. This study reports the first description of a cfr-positive MRSA isolate (M05/0060) belonging to the pandemic Panton-Valentine leukocidin (PVL)-positive sequence type 8 MRSA IVa/USA300 (ST8-MRSA-IVa/USA300) clone. The cfr gene was detected in M05/0060 using a DNA microarray which was used to screen PVL-positive MRSA isolates for the presence of virulence genes, typing markers, and antimicrobial resistance genes. Antimicrobial susceptibility testing revealed that M05/0060 exhibited the cfr-associated resistance phenotype. Molecular analysis identified the presence of cfr and a second phenicol resistance gene, fexA, on a novel 45-kb conjugative plasmid, which was designated pSCFS7. Within pSCFS7, a DNA segment consisting of cfr, a truncated copy of insertion sequence IS21-558, and a region with homology to the DNA invertase gene bin3 of transposon Tn552 from Bacillus mycoides was integrated into the transposase gene tnpB of the fexA-carrying transposon Tn558. The emergence of a multidrug-resistant cfr-positive variant of ST8-MRSA-IVa/USA300 is alarming and requires ongoing surveillance. Moreover, the identification of a novel conjugative plasmid carrying the cfr gene indicates the ability of cfr to spread to other MRSA strains.
    • Improving the standard of the standard for glass ionomers: an alternative to the compressive fracture strength test for consideration?

      Dowling, Adam H; Fleming, Garry J P; McGinley, Emma L; Addison, Owen; Materials Science Unit, Division of Oral Biosciences, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland. (2012-03)
      Three strength tests (compressive, three point flexure and biaxial) were performed on three glass ionomer (GI) restoratives to assess the most appropriate methodology in terms of validity and reliability. The influence of mixing induced variability on the data sets generated were eliminated by using encapsulated GIs.
    • Incisor reduction: a provisional aesthetic technique for traumatised teeth.

      Darby, L J; O'Connell, A C; Cork University Dental School and Hospital, Wilton, Cork, Ireland. (2010-12-11)
      Patients in the mixed dentition who have suffered severe extrusion or avulsion injuries often present with difficult treatment decisions, especially when the initial emergency care has been compromised. Here we describe a well-tolerated, aesthetically acceptable and conservative method for treating such patients until a definitive treatment plan is possible.
    • Influence of doxorubicin on fluconazole susceptibility and efflux pump gene expression of Candida dubliniensis.

      Schulz, Bettina; Knobloch, Mathias; Moran, Gary P; Weber, Kai; Ruhnke, Markus; Charité-Universitätsmedizin Berlin, Charit Campus Mitte, Medical Department, Division of Oncology and Haematology, Berlin, Germany. bettina_schulz@arcor.de (Medical mycology : official publication of the International Society for Human and Animal Mycology, 2012-05)
      The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C. dubliniensis was investigated. Isolates were exposed to DOX and FLU in a chequerboard assay and resistance gene expressions were analysed after DOX exposure. The susceptibility of the yeast to FLU was decreased in the presence of DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect. Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found to have an impact on resistance mechanisms in C. dubliniensis isolates.
    • Influence of halogen irradiance on short- and long-term wear resistance of resin-based composite materials.

      Bhamra, Gurcharn S; Fleming, Garry J P; Materials Science Unit, Division of Oral Biosciences, Dublin Dental School & Hospital, Trinity College Dublin, Dublin 2, Ireland. (2009-02)
      The Oregon Health Science University (OHSU) four-chamber oral wear simulator was used to examine the impact of halogen irradiance on the short- and long-term wear behavior of four-methacrylate resin-based composites (RBCs). The hypothesis proposed was that exacerbated wear would occur following the long-term wear of RBCs irradiated under non-optimized irradiance conditions.
    • Influence of LED irradiance on flexural properties and Vickers hardness of resin-based composite materials.

      Bhamra, G S; Fleming, G J P; Darvell, B W; Materials Science Unit, Division of Oral Biosciences, Dublin Dental School & Hospital, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland. (2010-02)
      To investigate the effect of irradiance through choice of LED light-curing unit (LCU) and fiber-optic tip on the mechanical properties of methacrylate resin-based composites (RBCs).
    • The influence of monomeric resin and filler characteristics on the performance of experimental resin-based composites (RBCs) derived from a commercial formulation.

      Hahnel, Sebastian; Dowling, Adam H; El-Safty, Samy; Fleming, Garry J P; Regensburg University Medical Center, Department of Prosthetic Dentistry, Regensburg, Germany. Sebastian.Hahnel@klinik.uni-regensburg.de (Dental materials : official publication of the Academy of Dental Materials, 2012-04)
      To explore experimental RBCs derived from a successful commercially available RBC (Grandio) to investigate resin monomer blend and filler parameters (volume fraction, density and diameter) on RBC performance.
    • The influence of poly(acrylic) acid number average molecular weight and concentration in solution on the compressive fracture strength and modulus of a glass-ionomer restorative.

      Dowling, Adam H; Fleming, Garry J P; Materials Science Unit, Division of Oral Biosciences, Dublin Dental School & Hospital, Trinity College Dublin, Dublin, Ireland. adam.dowling@dental.tcd.ie (2011-06)
      The aim was to investigate the influence of number average molecular weight and concentration of the poly(acrylic) acid (PAA) liquid constituent of a GI restorative on the compressive fracture strength (σ) and modulus (E).
    • The influence of resin flexural modulus on the magnitude of ceramic strengthening.

      Fleming, Garry J P; Hooi, Paul; Addison, Owen; Materials Science Unit, Division of Oral Biosciences, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland. garry.fleming@dental.tcd.ie (2012-07)
      The aim was to determine the magnitude of ceramic resin-strengthening with resin-based materials with varying flexural moduli using a regression technique to assess the theoretical strengthening at a 'zero' resin-coating thickness. The hypothesis tested was that experimentally, increasing resin flexural modulus results in increased resin-strengthening observed at a theoretical 'zero' resin-coating thickness.
    • Influence of S. mutans on base-metal dental casting alloy toxicity.

      McGinley, EL; Dowling, AH; Moran, GP; Fleming, GJ (British dental journal, 2013-03-22)
      'cause for concern...especially following prosthodontic or orthodontic treatment with base-metal dental casting alloys.'
    • Interaction of L-lysine and soluble elastin with the semicarbazide-sensitive amine oxidase in the context of its vascular-adhesion and tissue maturation functions.

      Olivieri, Aldo; O'Sullivan, Jeff; Fortuny, Luis Raimon Alvarez; Vives, Itziar Larrauri; Tipton, Keith F; School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. oliviera@tcd.ie (2010-04)
      The copper-containing quinoenzyme semicarbazide-sensitive amine oxidase (EC; SSAO) is a multifunctional protein. In some tissues, such as the endothelium, it also acts as vascular-adhesion protein 1 (VAP-1), which is involved in inflammatory responses and in the chemotaxis of leukocytes. Earlier work had suggested that lysine might function as a recognition molecule for SSAO/VAP-1. The present work reports the kinetics of the interaction of L-lysine and some of its derivatives with SSAO. Binding was shown to be saturable, time-dependent but reversible and to cause uncompetitive inhibition with respect to the amine substrate. It was also specific, since D-lysine, L-lysine ethyl ester and epsilon-acetyl-L-lysine, for example, did not bind to the enzyme. The lysine-rich protein soluble elastin bound to the enzyme relatively tightly, which may have relevance to the reported roles of SSAO in maintaining the extracellular matrix (ECM) and in the maturation of elastin. Our data show that lysyl residues are not oxidized by SSAO, but they bind tightly to the enzyme in the presence of hydrogen peroxide. This suggests that binding in vivo of SSAO to lysyl residues in physiological targets might be regulated in the presence of H(2)O(2), formed during the oxidation of a physiological SSAO substrate, yet to be identified.
    • An introduction to single implant abutments.

      Warreth, Abdulhadi; Fesharaki, Hamed; McConville, Ryan; McReynolds, David; Dublin Dental University Hospital, Dublin, Ireland. (Dental update, 2013-01)
      This article is an introduction to single implant abutments and aims to provide basic information about abutments which are essential for all dental personnel who are involved in dental implantology. Clinical Relevance: This article provides a basic knowledge of implants and implant abutments which are of paramount importance, as replacement of missing teeth with oral implants has become a well-established clinical procedure.
    • An introduction to the medically important Candida species

      Moran, G; Coleman, D; Sullivan, D (ASM Press, 2012)