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published_or_final_version / abstract / Pathology / Master / Master of Philosophy

Includes bibliography / 135 leaves, 7 leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, 1986

published_or_final_version / Zoology / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Surgery / Master / Master of Philosophy

The purpose of this study was to examine the pharmacokinetics of d-xylose in man as a function of age with particular emphasis on its absorption characteristics. This study required the development of a specific and sensitive method for the quantitation of xylose from plasma and urine. Following a clean-up procedure, plasma or urine samples are concentrated and undergo two sequential derivatization steps and then are quantitated by capillary column gas liquid chromatography (GLC). D-Xylose is frequently quantitated by a tedious colorimetric assay involving the use of thiourea, a proven animal carcinogen. We have evaluated a more expedient colorimetric assay employing less toxic reagents. Based upon these comparisons the "phloroglucinol" method has been recommended as a replacement for the currently used clinical method for quantitating d-xylose. The human studies revealed age related changes in some but not all d-xylose disposition parameters. Systemic, renal, and nonrenal clearances all declined with advancing age. The terminal elimination half life increased with age. Age had very little influence on the various volumes of distribution. In general, parameters relating to oral absorption showed no age-related dependence. In contrast to what is generally believed, the bioavailability of d-xylose did not decline with age. Lastly, this dissertation addresses the problem of how infusion data may best be fit. Concentration-time data may be fit by a nonlinear regression algorithm in two ways; (1) concentration-time data may be collected and fit both during infusion and after infusion is terminated, (2) concentration-time data may be collected only after the infusion is terminated and be fit as a bolus. Concentration-time data were computer simulated with random error and we found that fitting the entire curve gave the most accurate estimates of disposition parameters.

The ability of essential oils (EO) to manipulate the intestinal microbiota may potentiate their application in food as nutraceutical and as prophylactic agents for colonic disease. Little is known about the influence of EO on gut bacteria, the mechanism of their antibacterial action and genotoxicity to the host. Here, the antibacterial activities of EO in pure and in a mixed faecal culture were investigated. These antibacterial activities were further studied to compare the selective nature of EO and their effects on membrane integrity. The growth of gut pathogens and commensals was inhibited in a dose-dependent manner in pure culture, with most of the pathogens, Escherichia coli O157:H7, Clostridium difficile, C. perfringens and Salmonella typhimurium are sensitive to nerolidol, thymol, eugenol and geraniol at a half maximal inhibitory concentration (IC50) of 50-500 ppm. These concentrations of EO and mainly nerolidol were also inhibitory to some gut commensals, in particular affecting Faecalibacterium prausnitzii adversely in pure culture. In contrast, in the mixed culture system beneficial groups of bacteria, including F. prausnitzii, as determined by qPCR of 16S rRNA genes were not affected. Thymol and geraniol at 500 ppm suppressed the growth of total bacteria, resulting in minimal fermentation. A lower dose of 100 ppm of EO compounds was effective in suppressing the pathogen, C. difficile with no concern for commensal bacteria or their fermentation products, acetate, propionate and butyrate. This study also discovered that the proteome of commensal, Faecalibacterium prausnitzii and pathogenic gut bacteria, Escherichia coli, in response to EO compounds are affected differently. Thymol and eugenol down-regulated virulence factors in E. coli. The tested EO compounds were not genotoxic in the comet assay at non-toxic doses. Differential effects of EO compounds on gut pathogens and commensals and their non-toxicity but geno-protective properties could be applicable in improving gut health in man.

Orientador: Izabelle Auxiliadora Molina de Almeida Teixeira / Coorientador: Carla Joice Härter / Banca: Rafael Fernandes Leite / Banca: Kleber Tomas de Resende / Resumo: Este trabalho foi realizado utilizando informações de 7 estudos, em que foram ajustadas curvas de crescimento ao desenvolvimento dos órgãos do sistema visceral de fêmeas, machos castrados e machos inteiros da raça Saanen de 0,5 a 19,5 meses de idade. Inicialmente, foram avaliados oito modelos: Regressão linear simples; Quadrático; Monomolecular; Brody; Von Bertalanffy; Logística; Gompertz; e Richards. Os dados dos órgãos viscerais (fígado, pâncreas, baço, rúmen-retículo, omaso, abomaso, intestino delgado e intestino grosso) e tecido adiposo mesentérico (TAM), foram ajustados nos modelos usando o procedimento NLMIXED do SAS. O melhor modelo ajustado foi escolhido com base no Critério de Informações Akaike corrigido para pequenas amostras (AICc) e nos coeficientes de correlação de concordância (CCC). Após a escolha do modelo que melhor ajustou a curva de crescimento dos órgãos viscerais avaliados, modelamos a variância buscando um melhor ajuste. Os parâmetros dos modelos para cada sexo foram comparados utilizando o comando CONTRAST (p < 0,10). Em geral, o modelo que melhor descreveu o crescimento de órgãos do sistema visceral foi o logístico (menor AICc e maior CCC). Quando os órgãos foram expressos em gramas, o sexo não influenciou os parâmetros das equações para predição do crescimento dos órgãos avaliados (p > 0,10), exceto o MAT (p < 0,02); em que as fêmeas apresentaram menor taxa de deposição comparada aos machos inteiros e castrados (0,318 ± 0,034 vs 0,659 ± 0,062), e um ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This work was performed gathering information of 7 studies, in which growth curves were fitted to the visceral organs of female, intact male, and castrated male Saanen goats from 0.5 to 19.5 months old. Initially, eight models were assessed: Monomolecular; Simple linear regression; Quadratic; Monomolecular; Brody; Von Bertalanffy; Logistics; Gompertz; and Richards. Data of the visceral organs (liver, pancreas, spleen, rumen-reticulum, omasum, abomasum, small intestine, and large intestine) and mesenteric adipose tissue (MAT) were fitted in the models using NLMIXED procedure of SAS. The best fitted model was choosing based on the Akaike Corrected Information Criterion for small samples (AICc) and values and the concordance correlation coefficient (CCC). After choosing the model that best fitted the growth curve of the evaluated visceral organs, we modelled the variance seeking a better fit. Parameters of the models for each sex were compared using the CONTRAST statement (p < 0.10). Overall, the model that best described visceral organ growth was the logistic (i.e., lower AICc and higher CCC). When organs were expressed in grams, the sex did not influence the parameters of equations to predict the growth of the evaluated organs (p > 0.10), except for TAM (p < 0.02); females presented a lower deposition rate compared to intact males and castrated males (0.318 ± 0.034 vs 0.659 ± 0.062), and a inflection point higher than intact males and castrated males (7.65 vs 3.69 months). However, this difference between the sexes is not found when TAM is expressed in % to empty body weight (EBW). Irrespective of sex, at the beginning of growth, liver stood for 2.75 ± 0.113 % of EBW, grew (g) at a maximum rate of 0.531 ± 0.062, and its inflection point of the curve occurred at 1.7 months. The gastrointestinal t... (Complete abstract click electronic access below) / Mestre

Thesis (M.Pharm. (Pharmaceutics) -- University of Limpopo, 2018 / Griseofulvin is an antibiotic fungistatic drug used in the treatment of dermatophyte and ringworm infections. About 50% of a dose of griseofulvin passes the gastro- intestinal tract unabsorbed and is excreted in faeces. Since griseofulvin is highly soluble in acidic pH, a gastro-retentive floating matrix system was developed to control dissolution rate and thereby enhance solubility in an effort to develop an improved and convenient dosage form. Preformulation studies included selection of excipients and evaluation of their compatibility with griseofulvin. Using the chosen excipients, floating tablets of griseofulvin were formulated. Floating tablets containing 100 mg of griseofulvin were prepared by wet granulation technique with varying ratios of Methocel™, Accurel MP and Polyvinylpyrrolidone as determined by Design Expert software. Pre and post-compression studies, buoyancy capability and dissolution studies were carried out to assess the influence of the tablet components. Results obtained revealed that a density of less than 0.00091 g/cm3 was necessary for tablet floatation. Tablets that float immediately upon contact with dissolution medium and continue floating for over 12 hours were achieved with at least 28% Accurel MP by mass of the tablet. Dissolution studies revealed that an increase in tablet hardness reduced the rate of griseofulvin release only up to 120 minutes. From 120 minutes onwards, tablet hardness had no significant influence on griseofulvin release from tablets. Methocel™ had the most significant influence on griseofulvin release. The amount of Methocel™ included in the formulation was indirectly proportional to the rate of griseofulvin release. Using Design Expert software, optimized formulation was achieved with 1% Polyvinylpyrrolidone, 30% Methocel™, 60% Accurel MP and hardness ranging between 8 – 9 N. Pre and post-compression parameters of the optimized tablets were found to be within pharmacopoeial limits and thus compressed tablets were of acceptable quality. Tablets produced floated immediately upon contact with the medium and remained floating for at least 12 hours. Griseofulvin was released from the optimized tablets in a near zero order fashion, with a total of 80.8% griseofulvin released at the end of the 12 hour dissolution test period. Results of accelerated stability studies indicated potential stability of the manufactured tablets months.

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