Thesis (doctoral)--Ludwig-Maximilians-Universität zu München. / At head of title: Aus der Abteilung für Zahn- und Kiefereinsatz ... des Zahnärztlichen Universitäts-Instituts in München. Includes bibliographical references (p. 29).

Thesis (doctoral)--Universität Leipzig, 1924. / Vita. Includes bibliographical references (p. 27).

Thesis (M.D.S.)--University of Hong Kong, 2005.

Thesis (PhD Dentistry)--University of Pretoria, 2006. / Includes bibliographical references.

Thesis (PhD(Dentistry))--University of Pretoria, 2006. / Includes bibliographical references.

Thesis (M.S.)--Ohio State University, 1975. / Includes bibliographical references.

<p> Recent studies indicate that cone beam computed tomography (CBCT) provides better information on interproximal bone loss of the implant patients. However, in order to detect the bone loss, the patient needs to get CBCT scanned more than once at the same time interval. It is important to find the same position that the patient was in on the first scan, every time. Doing this, we are able to measure bone loss accurately. A sensitivity analysis done with Plenmeca Promax 3D CBCT, to investigate the measurement sensitivity during the image acquisition, showed that getting the same position is not possible with the current CBCT process tasks. Based on this sensitivity analysis, a new proposed head immobilizer was designed, and a face tracking software using tracking algorithms was developed. The results showed that using the proposed head immobilizer and the face tracking software as a system reduced the patient positioning variations on X (horizontal) axis by 44.54%, on Y (vertical) axis by 65.42%, and on Z (depth) axis by 59.12%. The study shows that it is possible to reduce the patient positioning error during the CBCT scan, and this study will allow more successful results in the future.</p><p>

Periodontal ligament inflammation or periodontitis is a common disease characterised by gradual destruction of connective tissue fibres that attach a tooth to the alveolar bone within which it sits. Diabetes and inflammation enhances periodontal bone loss through enhanced resorption and diminished bone formation. Periodontal ligament fibroblast attachment to collagen-I and function was impaired by methylglyoxal (MG) modification in vitro. The glyoxalase system is an anti-glycation defence in all cells that metabolises MG and thereby suppresses MG-mediated protein damage. Overexpression of Glo1 decreased the intracellular levels of MG The aim of this investigation was to improve the understanding of protein damage in PDL in diabetes, focusing on protein damage by MG in human periodontal ligament fibroblasts (hPDLFs) in hyperglycaemia and to evaluate the effects of high and low glucose concentrations on MG metabolism in hPDLFs with or without Glo1 inducers. The effect of high glucose concentration on the formation and metabolism of MG was studied in hPDLFs in vitro. The ability of two small molecule Glo1 inducers, individually and in synergistic combination, to counter dicarbonyl stress in hPDLFs in vitro was studied. Interactions between hPDLFs to the extracellular matrix protein, collagen-I, were investigated and impairments in hPDLFs adhesion to MG-modified collagen-I coated plates were assessed. Protein susceptible to MG modification and inactivation in the cytosol of hPDLFs were identified by high resolution mass spectrometry proteomics. The effect of clinical periodontitis on plasma protein glycation, oxidation and nitration was also investigated in a pilot clinical investigation. When hPDLFs were incubated with high glucose concentration in vitro there was a 45% decrease in Glo1 activity and 42% increase in D-lactate flux – surrogate indication of MG flux of formation, which contributed to increased cellular concentration of MG and increase in MG-H1 residue content of cell protein, compared to low glucose control. This indicated dicarbonyl stress was induced in hPDLFs by high glucose concentration in vitro, a model for hyperglycaemia in vivo. Decrease of Glo1 activity and increase in cellular MG concentration and MG-H1 residue content of cell protein was corrected with the addition of Glo1 inducers. The binding of hPDLFs to collagen-I was decreased by 30% in high glucose concentration and was corrected by addition of Glo1 inducers. Proteomics analysis of cytosolic extracts of hPDLFs indicated that high glucose incubations produced changes in MG-modified proteins and also up-regulated and down-regulated unmodified proteins in hPDLFs. The pilot investigation of clinical periodontitis suggested a systemic effect of this local inflammation which was associated with changes in plasma protein glycation, oxidation and nitration. This study reveals that dicarbonyl stress is a potential contributory pathogenic mechanism in hPDLFs in periodontitis and countering it may provide new treatment options to prevent and treat decline in periodontal health, particularly in diabetes. Small molecule inducers of Glo1 expression may in future contribute to improving periodontal health, particularly in diabetes.

Critically ill patients often require mechanical ventilation (MV) to facilitate treatment for respiratory failure or airway protection when consciousness is impaired. Whilst the endotracheal tube (ETT) is an essential interface between the patient and ventilator, it may promote VAP by impeding host defence mechanisms and by translocating microorganisms from dental plaque to the lower airways. Ventilator-associated pneumonia (VAP), which may be challenging to diagnose, is the most frequent hospital-acquired infection in critical care. It has been reported that when patients receive MV the composition of dental plaque changes to include respiratory pathogens such as Meticillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The primary aim of this research was to confirm that dental plaque communities altered during MV and to identify the potential causes of these changes. A combination of culture-based microbiology, community profiling molecular techniques and proteomic analysis of saliva was performed to analyse the microbiological content of the oral cavity, and to also quantify changes in dental plaque composition and saliva. For the first time, this study comprehensively analysed the dental plaque of mechanically ventilated patients and documented considerable species richness and diversity. Numerous potential respiratory pathogens were detected including Staphylococcus aureus, P. aeruginosa and Streptococcus pneumoniae in approximately one-third of mechanically ventilated patients. In addition, salivary flow rate was decreased and both the salivary pH and concentration of pro-inflammatory cytokines were significantly elevated during intubation. Dental plaque is a reservoir for VAP, and preventing or reducing respiratory colonisation may play a role in the management of ventilated patients. Interventions to prevent colonisation could include the modulation of salivary parameters such as pH and volume and further work may lead to the identification of specific proteins that are significant. Reducing the incidence of VAP will not only reduce mortality in the ICU, but will also have a great impact on hospital economics by reducing inpatient stay.

The novel epoxy-tiglianes, EBC-46 and ‘lesser activity’ EBC-211, are sourced from seeds of the Fountain’s Blushwood Tree (Fontainea picrosperma), indigenous to Queensland Tropical Rainforest. Australian biotechnology company, QBiotics Ltd.,has demonstrated that EBC-46 stimulates exceptional dermal wound healing responses in vivo, following cancer treatment and tumour destruction in domesticated animals. Consequently, QBiotics is developing EBC-46 as a veterinary anti-cancer pharmaceutical and performing human clinical trials. However, little is known on how EBC-46 induces its exceptional healing effects, manifested as accelerated wound re-epithelialisation, closure and reduced scarring. This study aimed to elucidate how EBC-46 and EBC-211 mediates these exceptional wound healing effects in vitro, through analysis of HaCaT keratinocyte and dermal fibroblast/myofibroblast genotypic and phenotypic responses, following epoxytigliane treatment (0.001-100μg/ml). A number of key wound healing responses were assessed, including proliferation, cell cycle progression, scratch wound repopulation; and transforming growth factor-β1 (TGF-β1)-driven, fibroblastmyofibroblast differentiation. Studies demonstrated that both EBC-46 and EBC-211 induced fibroblast and HaCaT cytotoxicity at 100μg/ml. EBC-46 and EBC-211 (0.001-10μg/ml) significantly retarded fibroblast proliferation and delayed S/G2 cell cycle transition, but exerted no significant effects on fibroblast migratory responses. Although EBC-46 had no effects on α-smooth muscle actin (α-SMA) expression, stress fibre organization and myofibroblast formation (0.001-0.01μg/ml and 1-10μg/ml), EBC-46 significantly inhibited α-SMA expression and stress fibre formation at 0.1μg/ml, with cells retaining normal fibroblast morphologies. EBC-211 induced similar effects at 10μg/ml Both EBC-46 and EBC-211 (0.001-10μg/ml) stimulated significant HaCaT proliferation, G1/S and S/G2 cell cycle transitions; and accelerated scratch wound repopulation, even with mitomycin C. Microarray analysis and protein level validation, identified numerous differentially expressed genes in epoxy-tiglianetreated, HaCaTs. Up-regulated genes included certain keratins and others associated with promoting cell cycle progression, proliferation and migration. Down-regulated genes included other keratins and genes associated with inhibiting cell cycle progression and proliferation, including certain cytokines and chemokines. This study has provided evidence to explain the enhanced re-epithelialisation and reduced scarring responses observed in epoxy-tigliane-treated skin. Furthermore, it highlights the potential of epoxy-tiglianes as novel therapeutics for impaired dermal wound healing and excessive scarring situations.