Thesis (M.D.S.)--University of Hong Kong, 1995. / Includes bibliographical references (leaf 89-107). Also available in print.

Thesis (doctoral)--Rijksuniversiteit te Gent, 1988. / Summary in Dutch and English. Includes bibliographies.

Thesis (doctoral)--University of Göteborg, 1984. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Veillonella spp. are found in high numbers in the mouth in dental plaque and on the mucosa. Veillonellae utilize lactic acid for their metabolic needs. A symbiotic relationship between Veillonellae and other oral bacteria, including a nutritional relationship with some streptococci, has been demonstrated both in vitro and in vivo. Thus, Veillonellae may protect the host from dental caries. Adherence is the initial step in bacterial colonization of oral surfaces. Recent evidence suggests that certain oral bacteria express molecules (adhesins) on their cell surface, which recognize receptors on other oral bacteria and/or in salivary pellicle. It has been previously demonstrated that Veillonella spp. bind avidly to Streptococcus. spp. found in subgingival plaque. The present study investigated the ability of V. atypica PK1910 to bind to saliva-coated hydroxyapatite (SHA), a model for adherence to the salivary pellicle. The results show that there was statistically significant enhanced binding of Veillonella atypica PK1910 to saliva-coated hydroxyapatite beads. (p< 0.05) Three classes of coaggregation-defective mutants of V. atypica PK1910 were tested for their ability to bind to SHA. Interestingly, they did not demonstrate any enhanced binding to saliva-coated hydroxyapatite beads. Heating of PK1910 did not effect binding to SHA. In contrast, protease treatment of the veillonella cell surface inactivated binding. Therefore, it appears that V. atypica PK1910, in addition to binding to oral Streptoccoccus spp. in dental plaque, may also colonize the tooth surface by binding directly to the salivary pellicle. It appears that a distinct heat stable protein may mediate this binding to SHA.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21418号 / 医博第4408号 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 髙橋 良輔, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background The mouth can be colonized by many bacterial species that are associated with both health and disease. Bacteria analyses are an important part of diagnosing and treating dental diseases, but there is no consensus regarding which sampling method to use for these analyses. Aim The aim of this study was to find out whether there are differences in bacterial composition in one, two and three days old dental plaque and if there are regional differences between anterior, posterior, right and left surfaces in the mouth over time. Method Plaque sample collection was performed at specific tooth sites on six healthy young adults. Sampling was made three times after dental plaque had been accumulated for one, two and three days respectively. During the accumulation periods the participants had to abstain from all forms of oral hygiene. Bacteria DNA extraction was performed followed by 16S sequencing. All gene sequences were matched against the Human Oral microbiome database. The results were analyzed in SPSS and SIMCA.  Result When comparing the bacteria composition between day one, two and three a statistically significant difference was found. The analyzes also showed a difference in composition between the posterior and anterior regions of the mouth over time, but no significant difference between the right and the left side of the mouth over time.  Conclusion  The result suggests that the sampling method should be chosen carefully and determined by the specific aim of the dental plaque analysis.

Introduction. Atherosclerotic plaque rupture may occur without warning leading to severe clinical events such as heart attack and stroke. The mechanisms causing plaque rupture are not well understood. It is hypothesized that mechanical forces may play an important role in the plaque rupture process and that image-based computational mechanical analysis may provide useful information for more accurate plaque vulnerability assessment. The objectives of this dissertation are: a) develop in vivo magnetic resonance imaging (MRI)-based 3D computational models with fluid-structure Interactions (FSI) for human atherosclerotic carotid plaques; b) perform mechanical analysis using 3D FSI models to identify critical stress/strain conditions which may be used for possible plaque rupture predictions. Data, Model, and Methods. Histological, ex vivo/ in vivo MRI data of human carotid plaques were provided by the University of Washington Medical School and Washington University Medical School. Blood flow was assumed to be laminar, Newtonian, viscous and incompressible. The Navier-Stokes equations with arbitrary Lagrangian-Eulerian (ALE) formulation were used as the governing equations for the flow model. The vessel and plaque components were assumed to be hyperelastic, isotropic, nearly-incompressible and homogeneous. The nonlinear Mooney-Rivlin model was used to describe the nonlinear properties of the materials with parameter values chosen to match available experimental data. The fully-coupled FSI models were solved by a commercial finite element software ADINA to obtain full 3D flow and stress/strain distributions for analysis. Validation of the computational models and Adina software were provided by comparing computational solutions with analytic solutions and experimental data. Several novel methods were introduced to address some fundamental issues for construction of in vivo MRI-based 3D FSI models: a) an automated MRI segmentation technique using a Bayes theorem with normal probability distribution was implemented to obtain plaque geometry with enclosed components; b) a pre-shrink process was introduced to shrink the in vivo MRI geometry to obtain the no-load shape of the plaque; c) a Volume Component-Fitting Method was introduced to generate a 3D computational mesh for the plaque model with deformable complex geometry, FSI and inclusions; d) a method using MRI data obtained under in vitro pressurized conditions was introduced to determine vessel material properties. Results. The effects of material properties on flow and wall stress/strain behaviors were evaluated. The results indicate that a 100% stiffness increase may decrease maximal values of maximum principal stress (Stress-P1) and maximum principal strain (Strain-P1) by about 20% and 40%, respectively; flow Maximum-Shear-Stress (FMSS) and flow velocity did not show noticeable changes. By comparing ex vivo and in vivo data of 10 plaque samples, the average axial (25%) and inner circumferential (7.9%) shrinkages of the plaques between loaded and unloaded state were obtained. Effects of the shrink-stretch process on plaque stress/strain distributions were demonstrated based on six adjusted 3D FSI models with different shrinkages. Stress-P1 and Strain-P1 increased 349.8% and 249% respectively with 33% axial stretch. The effects of a lipid-rich necrotic core and fibrous cap thickness on structure/flow behaviors were investigated. The mean values of wall Stress-P1 and Strain-P1 from lipid nodes from a ruptured plaque were significantly higher than those from a non-ruptured plaque (112.3 kPa, 0.235 & 80.1 kPa, 0.185), which was 40.2% and 26.8% higher, respectively (p<0.001). High stress/strain concentrations were found at the thin fibrous cap regions. These results indicate that high stress concentrations and thin fibrous cap thickness might be critical indicators for plaque vulnerability. Conclusion. In vivo image-based 3D FSI models and mechanical image analysis may have the potential to provide quantitative risk indicators for plaque vulnerability assessment.

INTRODUCTION: The“vulnerable plaque" is defined as the“precursor lesion" that ultimately ends in acute coronary thrombi (clots) that create a heart attack. Macrophages and inflammatory cells, found preferentially in vulnerable plaque, sustain their activity in the plaque through anaerobic metabolism and lactate production. The ultimate goal is to assess anaerobic metabolism in-vivo by measuring tissue pH and lactate concentration in atherosclerotic plaques using optical spectroscopy. The proposed in-vitro optical probe design, experimental method, and spectroscopic data analysis methodology are established in this research. METHODS: A fiber optic probe was designed and built based on both Monte Carlo simulations and bench testing with the goal to collect light from a small volume of tissue. A simulation of the depth penetration of the proposed probe was performed on normal and atherosclerotic aortic tissue, and the final probe was bench tested using normal aorta. A method was developed to preserve plaque metabolic status of tissue harvested from patients. Human atherosclerotic tissue obtained immediately after carotid endarterectomy was placed in Minimum Essential Medium (MEM) with non-essential amino acids supplement, bubbled with 75%O2/20%N2/5%CO2 at 37°C. Tissue pH, pCO2, pO2 and temperature with (n=7) and without (n=2) the media preparation over time were reviewed to assess plaque viability and maintenance of physiological conditions. Additional plaques placed in media were used for development of chemometric methods to measure pH and lactate. Areas of each plaque were randomly chosen for analysis. Reflectance spectra were collected with a dispersive spectrometer (400-1100 nm) and a Fourier-transform near-infrared spectrometer (1100-2400 nm) using the fiber optic probe. Reference measurements for tissue pH and lactate were made with glass microelectrodes and micro-enzymatic assay, respectively. Partial least-squares (PLS) data analysis was used to develop multivariate calibration models on an initial set of 5-6 plaques relating the optical spectra to the reference tissue pH (n=20) or the lactate concentration (n=21) to assess data quality. The coefficient of multiple determination (R2), the standard error of cross-validation (SECV), and the number of factors were used to assess the model performance. Additional points were collected from ~14 plaques and added to preliminary data. Pre-processing techniques were then used to see if preliminary data results could be improved by reducing different sources of variability with the introduction of more points. RESULTS: Monte Carlo simulations and depth penetration tests with the final probe design showed light is collected from ~1 mm3 volume of tissue using a 50 micron source-receiver separation. Tissue pH, pCO2, pO2 and temperature values demonstrated that the plaques were viable and stable in the media preparation for a maximum of 4 hours. Data from the first six plaques collected for lactate analysis showed that for seventeen points, a six-factor model produced adequate results (R2=0.83 SECV=1.4 micromoles lactate/gram tissue). Data from the first five plaques collected for tissue pH analysis, showed for seventeen different points, a three-factor model produced adequate results (R2=0.75 SECV=0.09 pH units). When additional points were added to either data set, model results were degraded. CONCLUSIONS: The in-vitro optical probe design and experimental procedures was established and the feasibility of the optical method demonstrated with preliminary data. However, with the addition of more data points, different sources of tissue and spectral variability were observed to affect calibration. The gross pathology type and mismatched optical volume to reference measurement volume limited the tissue pH determination. The reference measurement precision, the spatial resolution of the reference lactate measurement, and unmodeled tissue variability (water and proteins) limited the lactate determination. Large variability in all optical measurements was observed. Additional in-vitro data collection would be required such that the variability due to the tissue is reduced and any spectrometer variability adequately compensated to be able to use the optical calibration in-vivo.

Xylitol, classified as a natural sugar substitute, has for about 35 years been known as an agent that may act against caries. The mechanism of action; how it inhibits mutans streptococci (MS) and the clinical dose-response relationship are not however fully investigated. The general aim of the investigations was to evaluate the effect of xylitol on oral ecology in children and adolescents. A series of experimental and controlled clinical trials were performed in which samples of saliva and plaque was collected and analysed with respect to xylitol content, pH, microbial composition and lactic acid production. In paper I, significantly reduced proportions of xylitol-sensitive MS in saliva were demonstrated after 18 weeks of regular use of two dose regimens of xylitol-containing tablets (1.7g and 3.4g xylitol/day) but the acidogenicity in dental plaque was not affected. In paper II, the effect on interdental plaque-pH of two different single dose intakes (2.0g and 6.0g) of xylitol was evaluated. The higher xylitol dose counteracted the pH-drop significantly (p&lt;0.05) when the chewing was followed by a sucrose rinse while the lower dose did not differ from the control. In paper III, the xylitol concentrations in saliva after use of different common xylitol-containing products (0.1g-1.3g) were investigated. Statistically significant elevations of salivary xylitol levels were demonstrated for all products during the first 8-16 min when compared with baseline (p&lt;0.05) but the individual variation was considerable. In samples of supragingival dental plaque, a high dose rinse (6.0g) increased the xylitol concentrations for a longer period (&gt;30 min) than a low dose rinse (2.0g). In paper IV, it was demonstrated that 6.0g of xylitol in chewing gums, every day in 4 weeks, gave significantly less visible plaque and a significantly reduced sucrose-induced lactic acid formation (p&lt;0.05) in saliva. Furthermore, the proportion of MS decreased significantly (p&lt;0.05) compared to baseline. In paper V, the salivary uptake of [14C]-xylitol was compared with a specific assay determining xylitol-sensitive MS and a fair positive correlation (p&lt;0.05) between the two assays was found. In a controlled trial, the proportions of MS and the salivary xylitol uptake decreased significantly (p&lt;0.05) in the xylitol gum test group after 4 weeks compared to baseline which was in contrast to the control gum group. No serious adverse effects were reported in any of the investigations. The main conclusions from this thesis were: a) various xylitol-containing products increased the xylitol levels in saliva and plaque, b) 6.0g of xylitol could counteract the interdental pH-drop after sugar consumption and reduce lactic acid formation in saliva c) a daily dose of 6.0g xylitol reduced the amount of visible plaque and altered the salivary microbial composition, d) a transient shift of MS strains in saliva was demonstrated during periods of regular intake of xylitol products but no long-term impact was found after its termination. The relatively high amount of xylitol needed for a beneficial effect on the oral ecology calls for a further development of effective and safe routes for administration.