Bibliography: p. 207-236. / 236 p. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the systemic and cerebral pharmacokinetics and pharmacodynamics of propofol following rapid administration, using regional pharmacokinetic techniques in a sheep preparation. New methods for measurement of cerebral blood flow, cerebral metabolic rate and depth of anaesthesia are developed and validated. The final studies show that distribution of propofol to the brain is dependent on cardiac output. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anaesthesia and Intensive Care, 1997?

Bibliography: leaves 282-354 / 354 leaves : ill ; 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, Dept. of Physiology, 1986

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[Truncated abstract] In obstetric practice, pregnant women at risk of pre-term delivery between 24 and 34 weeks of gestation are administered synthetic glucocorticoids (betamethasone or dexamethasone) to induce fetal organ maturation. During this gestational period, the fetal kidney is undergoing a phase of rapid organogenesis with an increase in renal growth and active nephrogenesis occurring. The studies comprising this thesis examine the effects of prenatal betamethasone exposure on the fetal and adult ovine kidney. The central hypothesis of these studies was that exposure of the fetal kidney to betamethasone in late gestation would change renal structure and induce long-term alterations in the expression of glucocorticoid-sensitive genes and proteins. In the fetal studies, pregnant Merino ewes bearing single fetuses received single or repeated-weekly intra-muscular (i.m.) injections of betamethasone (0.5 mg/kg body weight) or saline commencing on day 104 of gestation (term is 150 days). Kidneys were collected from fetuses at 109, 116, 121 and 146 days of gestation (d). Using gold standard unbiased stereological techniques, the physical disector/fractionator method, total glomerular (nephron) number and glomerular volume were determined in 146 d fetal kidneys exposed to repeated maternal saline or betamethasone administration. In the adult study, kidneys were collected from 3.5-year-old sheep that had been exposed to ... In this thesis I have demonstrated that renal growth restriction as a result of betamethasone exposure is associated with a reduction in fetal nephron endowment. Although betamethasone does not appear to consistently alter nephron number or glomerular size, it may indirectly affect total nephron endowment through effects on renal growth. I have also provided evidence which suggests that lategestation betamethasone exposure in sheep does not program permanent alterations in the renal expression of genes or proteins involved in glucocorticoid hormone action or components of the renin-angiotensin system. Therefore, exposure of the fetal kidney to betamethasone during nephrogenesis may alter renal structure if kidney growth is perturbed; however, there are no persistent alterations in the expression of glucocorticoid-sensitive genes. These findings are consistent with the preservation of normal basal blood pressure in the adult sheep I studied and with the limited results from human studies of late-gestation maternal glucocorticoid administration.

No description available.

Resumo: A frequência de hipovitaminose D é alta na população. A deficiência de vitamina D tem sido considerada problema de saúde pública no Brasil e no mundo. Além disso, a deficiência dessa vitamina está associada com o aumento do risco de várias doenças crônicas. Assim, está ocorrendo uso indiscriminado de vitamina D sem conhecer ao certo seus efeitos adversos. Estudos mostraram que essa vitamina é importante para o desenvolvimento e funcionamento adequado do coração. A deficiência de vitamina D provoca remodelação cardíaca enquanto que a suplementação de vitamina D, em modelos de agressão, atenua a remodelação. Porém pouco se sabe sobre sua influência no coração normal. O objetivo foi verificar se a suplementação com diferentes doses de vitamina D3 na dieta promove remodelação cardíaca com alterações na estrutura, na função, no metabolismo energético e nos moduladores inflamatórios do coração normal de ratos Wistar. Para isso foram utilizados 86 ratos machos, alocados em quatro grupos: Controle (C, n=21) recebeu dieta padrão; 3D (n=22), 5D (n=22) e 10D (n=21) receberam 3.000, 5.000 e 10.000 UI de colicalciferol/kg de dieta respectivamente. Após dois meses foi realizada a pressão arterial caudal e o estudo ecocardiográfico. Os animais foram eutanasiados, o soro e o ventrículo esquerdo foram utilizados para análises bioquímicas. Para análise estatística foi realizado ANOVA de 1 via e pós teste de Tukey ou Kruskal Wallis e pós teste de Dunn. Para avaliar a resposta dose dependente foi utilizado o teste de tendência (correlação de Spearman). As concentrações séricos de cálcio e fósforo foram maiores no grupo 5D e 10D em relação ao C. A pressão caudal foi maior nos grupos 3D e 10D em relação ao C e apresentou aumento dose dependente. A concentração sérica de 25 (OH) D3 foi maior no grupo 5D em relação aos outros grupos e foi maior... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Frequency of hypovitaminosis D in population is high and vitamin D deficiency has been considered a public health problem. Moreover, Vitamin D deficiency is associated with increased risk of many chronic diseases. Thus, it is widespread use of vitamin D without knowing its adverse effects. Studies have shown that this vitamin is important for cardiac development and functioning. Vitamin D deficiency results in cardiac remodeling and vitamin D supplementation in cardiac aggression models attenuates cardiac remodeling. However, influence of vitamin D supplementation in normal rats is not completed known. The aim of this study was to evaluate whether supplementation with vitamin D3 results in cardiac remodeling with changes in structure, function, energy metabolism and inflammatory mediators in the heart of normal rats. We used 86 male rats allocated into four groups: control (C, n = 11) received standard diet; 3D (n = 12), 5D (n = 13) and 10D (n = 11) received 3000, 5000 and 10,000 IU of cholecalciferol / kg diet. After two months the animals were submitted to functional study, morphometric, and biochemical. For the statistical analysis was used the ANOVA test of variance complemented by Tukey, the test Kruskal Wallis complemented by Dunn. To evaluate the dose response was used the Spearman correlation. Serum calcium and phosphorus were higher in the 5D and 10D in relation to the group C. The blood pressure was higher in the groups 3D and 10D in relation to the group C. The increase in blood pressure was dose dependent. Serum 25 (OH) D3 was higher in the group 5D in relation to the other groups and it was higher in the group 10D in relation to the group C. There were no differences in echocardiographic variables of morphology and function. The activity of the enzyme β hydroxyacyl coenzyme A dehydrogenase was smaller in the groups 5D and 10D in relation to other groups... (Complete abstract click electronic access below) / Orientador: Sérgio Alberto Rupp de Paiva / Coorientador: Leonardo A. M. Zornoff / Banca: Marcelo Macedo Rogero / Banca: Paula Schmidt Azevedo Gaiola / Mestre

HIV/AIDS is a global pandemic that poses a great threat especially in Sub-Saharan Africa where the highest population of those infected with the virus is found. It has far reaching medical, socio-economic and scientific implications. The HIV-1 protease enzyme is a prime therapeutic target that has been exploited in an effort to reduce morbidity and mortality. However problems arise from drug toxicity and drug-resistant mutations of the protease which is a motivation for research for new, safer and effective therapies. Evidence exists to show that there are significant genomic differences in Subtype B and C that have a negative effect on the intrinsic binding of inhibitors. It is imperative to look at all perspectives from epidemiological, molecular to the pharmacological ones so as to achieve rational design of therapeutic agents. This study involved the use of in silico structural analysis of the effects of mutations in the active site. The data was provided by the National Institute of Communicable Diseases consisting of HIV-1 Subtype C protease sequences of 29 infants exhibiting drug-resistance to ritonavir and lopinavir. The major active site mutations causing drug resistance identified in this study were M46I, I54V and V82A using the Stanford HIV database tool. Homology modeling without extra restraints produced models with improved quality in comparison to those with restraints. MetaMQAPII results differed when models were visualized as dimers giving erroneous modeled regions in comparison to monomers. A broader study with a larger dataset of HIV-1 subtype C protease sequences is required to increase statistical confidence and in order to identify the pattern of drug resistant mutations. Homology modeling without extra restraints is preferred for calculating homology models for the HIV-1 subtype C. Further investigations needs to be done to ascertain the accuracy of validation results for dimers from MetaMQAPII as it is designed for evaluation of monomers.

New drugs, particularly antibiotics, are urgently required to combat the increasing problem of antibiotic resistant human pathogens. Due to the scarcity of products available today, the pharmaceutical industry is now under pressure to reassess compounds derived from plants, soil and marine organisms. Pharmaceutical companies are showing renewed interest in marine biotechnology as the oceans represent a rich source of both biological and chemical diversity of novel molecular structures with anti-cancer, anti-inflammatory and antibiotic properties. Formerly unexplored locations, such as deep ocean sediments, show great potential as a source of genetically novel microorganisms producing structurally unique secondary metabolites. In this research, a metabolite producing marine Pseudoalteromonas strain, known as AP5, was initially used to develop methods for the detection, optimisation of production and extraction of bioactive metabolites from other potentially novel marine isolates. Two hundred and seventy six (276) marine isolates from water and sediment samples from the Antarctic Ocean and Marion Island were isolated. Ten visually different isolates were screened for bioactivity against Gram-positive and -negative bacteria, fungi and yeast. Three out of the 10 isolates, WL61 , WL 114 and WL 136, appeared to be novel Streptomyces spp. showing activity against different test organisms. Many of these marine microorganisms are difficult to culture in the laboratory, particularly when they are cultivated continuously in shake flasks as they can stop producing bioactive compounds. The cultivation of marine isolates in bioreactors may be a more beneficial process for the optimisation of metabolite production compared to conventional liquid fermentation techniques whereby the solid-liquid-air interface of membrane bioreactors can imitate the natural environment of microbes. The membrane bioreactor system is a stable growth environment with low shear that supports steady-state biofilm growth consisting of a high cell density due to a high mass transfer of nutrients and oxygen to the cells. This approach was employed and isolates WL61, WL114 and WL136 were immobilised onto ceramic membranes using Quorus single fibre bioreactors (SFR). The SFRs were used to establish the most suitable growth medium for continuous secondary metabolite production. The best growth conditions were applied to the Quorus multifibre bioreactor (MFR) for scale up of biologically active metabolites, highlighting the potential of bioreactor technology for use in bioprospecting for isolating and screening novel and known organisms for new and interesting natural products. Furthermore, the Quorus MFR was shown to be suitable for the production of high yields of antimicrobial metabolites and is an efficient new fermentation production system. Purification by HPLC fractionation was used to characterise four major compounds from isolate WL 114 extracts. NMR structure elucidation identified one of the two primary compounds as Bisphenol A. The complete chemical structure for the second potent bioactive compound could not be determined due to the low concentration and volume of material. / KMBT_363 / Adobe Acrobat 9.54 Paper Capture Plug-in

Made available in DSpace on 2014-06-11T19:25:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T18:53:45Z : No. of bitstreams: 1 santos_pp_me_botfm.pdf: 349987 bytes, checksum: 913fc9a75063c45bd784ef00c6dc221f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A frequência de hipovitaminose D é alta na população. A deficiência de vitamina D tem sido considerada problema de saúde pública no Brasil e no mundo. Além disso, a deficiência dessa vitamina está associada com o aumento do risco de várias doenças crônicas. Assim, está ocorrendo uso indiscriminado de vitamina D sem conhecer ao certo seus efeitos adversos. Estudos mostraram que essa vitamina é importante para o desenvolvimento e funcionamento adequado do coração. A deficiência de vitamina D provoca remodelação cardíaca enquanto que a suplementação de vitamina D, em modelos de agressão, atenua a remodelação. Porém pouco se sabe sobre sua influência no coração normal. O objetivo foi verificar se a suplementação com diferentes doses de vitamina D3 na dieta promove remodelação cardíaca com alterações na estrutura, na função, no metabolismo energético e nos moduladores inflamatórios do coração normal de ratos Wistar. Para isso foram utilizados 86 ratos machos, alocados em quatro grupos: Controle (C, n=21) recebeu dieta padrão; 3D (n=22), 5D (n=22) e 10D (n=21) receberam 3.000, 5.000 e 10.000 UI de colicalciferol/kg de dieta respectivamente. Após dois meses foi realizada a pressão arterial caudal e o estudo ecocardiográfico. Os animais foram eutanasiados, o soro e o ventrículo esquerdo foram utilizados para análises bioquímicas. Para análise estatística foi realizado ANOVA de 1 via e pós teste de Tukey ou Kruskal Wallis e pós teste de Dunn. Para avaliar a resposta dose dependente foi utilizado o teste de tendência (correlação de Spearman). As concentrações séricos de cálcio e fósforo foram maiores no grupo 5D e 10D em relação ao C. A pressão caudal foi maior nos grupos 3D e 10D em relação ao C e apresentou aumento dose dependente. A concentração sérica de 25 (OH) D3 foi maior no grupo 5D em relação aos outros grupos e foi maior... / Frequency of hypovitaminosis D in population is high and vitamin D deficiency has been considered a public health problem. Moreover, Vitamin D deficiency is associated with increased risk of many chronic diseases. Thus, it is widespread use of vitamin D without knowing its adverse effects. Studies have shown that this vitamin is important for cardiac development and functioning. Vitamin D deficiency results in cardiac remodeling and vitamin D supplementation in cardiac aggression models attenuates cardiac remodeling. However, influence of vitamin D supplementation in normal rats is not completed known. The aim of this study was to evaluate whether supplementation with vitamin D3 results in cardiac remodeling with changes in structure, function, energy metabolism and inflammatory mediators in the heart of normal rats. We used 86 male rats allocated into four groups: control (C, n = 11) received standard diet; 3D (n = 12), 5D (n = 13) and 10D (n = 11) received 3000, 5000 and 10,000 IU of cholecalciferol / kg diet. After two months the animals were submitted to functional study, morphometric, and biochemical. For the statistical analysis was used the ANOVA test of variance complemented by Tukey, the test Kruskal Wallis complemented by Dunn. To evaluate the dose response was used the Spearman correlation. Serum calcium and phosphorus were higher in the 5D and 10D in relation to the group C. The blood pressure was higher in the groups 3D and 10D in relation to the group C. The increase in blood pressure was dose dependent. Serum 25 (OH) D3 was higher in the group 5D in relation to the other groups and it was higher in the group 10D in relation to the group C. There were no differences in echocardiographic variables of morphology and function. The activity of the enzyme β hydroxyacyl coenzyme A dehydrogenase was smaller in the groups 5D and 10D in relation to other groups... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:30:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-05-26Bitstream added on 2014-06-13T18:40:28Z : No. of bitstreams: 1 goncalvesjunior_i_dr_botfm.pdf: 14978707 bytes, checksum: bc384bf4e8557c0376c390efbcb98d16 (MD5) / Universidade Estadual Paulista (UNESP) / O uso de diferentes inibidores selectivos da COX-2 em vários estudos mostraram resultados conflitantes, relacionados principalmente a uma elevada taxa de deiscências nas suturas intestinal.Basedo na hipótese de que o uso de um antibiótico de largo espectro pode reduzir a carga bacteriana no sítio de lesão e, inversamente, reduzir a migração celular de PMNLs, o objetivo deste estudo foi determinar os efeitos do Paracoxibe, uma droga inibidora da COX- 2,disponível comercialmente, associada ou não ao Imipenem na cicatrização de anastomoses no ileo ecólon de ratos. Trezentos e sessenta e oito ratos brancos Wistar foram submetidos a laparotomia, a transecção do cólon esquerdo e do íleo terminalreanastomose randomizados para receber paracoxibe (0,66 mg / Kg), imipenem (30mg/Kg) ou solução salina (controles) por via intramuscular por 4 dias. Os ratos foram distribuídos em quatro grupos de 92 ratos: Grupo 1 (controle), grupo 2 (Paracoxib), grupo 3 (Imipenem) e grupo 4 (paracoxib / imipenem) Os animais em cada grupo foram sacrificados após 4,7,14 e 21 dias, sendo as anastomoses avaliadas por meio de medidas de força de ruptura e pelo exame histológico do processo de cicatrização. Doze animais do grupo paracoxibe (13%) e oito do grupo paracoxibe / Imipenem (8,7%) foram a óbito no 5° e 7° dia de pós operatóriopor deiscências da anastomose ileal. A força de ruptura nos ratos tratados com paracoxibe foi significativamente menor do que no grupo controle no 7°, 14° e 21° dias de pósoperatório das anastomoses do íleo (87,6 g, 184,3 g e 212,5 g<127,8 g, 243,6 g e 251G , P = 0,026) e no 4°,7°,14° e 21° dias de pós operatório as anastomoses de cólon (139,3 g, 170,4 g, 202,9 g e 299,9 g<203,3 g, 254,3 g, 364,2 g e 401g, p = 0,026). Não houve diferenças significativas entre os grupos paracoxibe, imipenem e paracoxib / imipenem. A tendência de aumento da força de... / The use of different selective COX-2 inhibitors in several studies showed conflicting results, related mostly from a high rate of dehiscence’s on intestinal sutures. Based on the hypothesis that the use of a broad spectrum antibiotic can decrease the bacterial load at the injured site and conversely reduce PMNLs cell migration, the aim of this study was to determine the effects of a new commercially available COX-2 inhibitor Paracoxib, associated or not to Imipenem on the healing of ileal and colonic anastomosis in rats. Three hundred and sixty eight white Wistar rats underwent laparotomy, ileal and left colon transection and reanastomosis and randomized to receive paracoxib (0,66 mg/Kg ), imipenem ( 30mg/Kg) or saline solution ( controls ) by intramuscular injections for 4 days. The rats were distributed in four groups of 92 rats: group1 (control); group 2 ( Paracoxib); group 3 ( Imipenem ) and group 4 (paracoxib/imipenem). Animals in each group were killed after 4,7,14 and 21 days, and the anastomosis evaluated by means of breaking strength measures and by histological examination of the healing process. Twelve animals in paracoxibe group (13% ) and eight on paracoxib/Imipenem group ( 8,7% ) died on on days 5 and 7 related to ileal anastomotic dehiscences. Breaking strength in rats treated with paracoxib was significantly lower than in the control group in post-operative day 7, 14 and 21 in ileal anastomoses ( 87,6g, 184,3g and 212,5g < 127,8g, 243,6g and 251g, p=0.026 ) and on days 4,7,14 and 21 in colonic anastomoses ( 139,3g, 170,4g, 202,9g and 299,9g < 203,3g, 254,3g, 364,2g and 401g, p=0.026 ). There were no significant diferences between imipenem, paracoxib and paracoxib/imipenem treated animals. A tendency of increased breaking strength were observed in paracoxib/imipenem group when compared to imipenem and paracoxib groups. The breaking strength increased progressivelly ... (Complete abstract click electronic access below)