Source: Dissertation Abstracts International, Volume: 69-10, Section: B, page: 6010. Advisers: Herbert L. Dupont; Pablo C. Okhuysen. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references.

Thesis (Ph. D.)--Victoria University (Melbourne, Vic.), 2008. / Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Also available online.

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

Orientador: Katia Sivieri / Coorientador: Magali Monteiro da Silva / Banca: Elaine Cristina Pereira de Martinis / Banca: Thais Borges Cesar / Resumo: A microbiota intestinal apresenta impacto direto na saúde do hospedeiro sendo fortemente influenciada pela dieta. O consumo de suco de laranja vem sendo associado à redução do risco de desenvolvimento de doenças crônicas, principalmente devido à presença de compostos bioativos. Os compostos bioativos presentes no suco de laranja, especialmente os polifenóis, também podem estar relacionados com a composição e o metabolismo da microbiota intestinal. O objetivo desse trabalho foi avaliar a influência do suco de laranja fresco e pasteurizado sobre a microbiota intestinal usando o Simulador do Ecossistema Microbiano Humano (SEMH®). O SEMH® foi utilizado para investigar a fermentação do suco de laranja ao longo do cólon e para avaliar as alterações na composição e no metabolismo microbiano. A atividade antioxidante dos sucos e das amostras dos compartimentos do SEMH® também foi avaliada. Foi observado no tratamento com suco de laranja fresco aumento (p≤0,05) das populações de Lactobacillus spp., Enterococcus spp., Bifidobacterium spp. e Clostridium spp. e diminuição (p≤0,05) de enterobactérias, enquanto no tratamento com suco de laranja pasteurizado houve aumento (p≤0,05) da população de Lactobacillus spp. e diminuição (p≤0,05) de enterobactérias. A análise de PCR-DGGE mostrou redução dos valores de riqueza da população de bactérias totais para ambos os sucos. Em relação ao metabolismo microbiano, foi observado aumento (p≤0,05) da produção de ácidos graxos de cadeia curta (AGCC) e diminuição (p≤0,05) do conteúdo de íons amônio no tratamento com os sucos de laranja fresco e pasteurizado. A atividade antioxidante das amostras dos compartimentos do SEMH® no tratamento com os sucos de laranja foi elevada, com ligeira redução em comparação àquela do suco fresco e do suco pasteurizado.... / Abstract: The gut microbiota has a direct impact on host's health being strongly influenced by diet. Orange juice consumption has been associated with a reduced risk of chronic diseases, largely because of the presence of bioactive compounds. The bioactive compounds present in orange juice, particularly polyphenols, may also be associated with the composition and metabolism of gut microbiota. The aim of this work was to evaluate the influence of fresh orange juice and pasteurized orange juice on gut microbiota using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). SHIME® was used to investigate orange juice fermentation throughout the colon and to assess changes in microbial composition and microbial metabolism. Antioxidant activity of the SHIME® vessels and juice was also evaluated. An increase (p≤0.05) in Lactobacillus spp., Enterococcus spp., Bifidobacterium spp. and Clostridium spp. population was observed in fresh orange juice treatment, as well as a reduction (p≤0.05) in enterobacteria. Regarding pasteurized orange juice treatment, an increase (p≤0.05) in Lactobacillus spp. population and a decrease (p≤0.05) in enterobacteria was observed. The PCR-DGGE analysis showed a reduction in total bacteria population richness values on both juices. According to microbial metabolism, an increasing (p≤0.05) of short-chain fatty acids (SCFA) production and decreasing (p≤0.05) of ammonium was observed for two juices treatments evaluated. The antioxidant activity of the samples from the SHIME® vessels in the orange juice treatments was high, with a slight reduction compared to that of fresh juice and pasteurized juice. Both fresh and pasteurized orange juice influenced on gut microbiota according to Principal Component Analysis (PCA), which enabled to differentiate the orange juice treatments from control and washout periods. Both juices ... / Mestre

Purpose: Hypoxia in colorectal cancer (CRC) and gastroesophageal cancer (GEC) decreases tumour responsiveness to radio and chemotherapy leading to cancer progression and poor prognosis. This is the first study to utilise [18F]FAZA hypoxia radiotracer in patients with CRC and GEC. Methods: Six patients (mean age 68±8 years, 2 males and 4 females) with CRC and 4 patients diagnosed with GEC (mean age 65 years, 3 males and 1 female) were included in the study. [18F]FAZA was synthesised at the John Mallard Scottish PET Centre. After injection with 370 MBq of [18F]FAZA, PET/CT images with 60 min dynamic scan were acquired. In addition, 15 min static scans 2 hr post injection were performed. 3D PET images were reconstructed iteratively using an ordered subset expectation maximization (OSEM) method and fused to the corresponding low-dose CT images. [18F]FAZA uptake parameters including maximum standard uptake value (SUVmax), tumour-to-muscle ratio (T/M), tumour-to-bowel ratio (T/B) and volume of interest (VOI) were measured. Results: 4 out 6 patients with CRC (66%) showed clear uptake of [18F]FAZA in the primary tumour. The mean tumour SUVmax was 2.2±0.91 (range 1.12 - 3.71). The tumour SUVmax was significantly higher compared with muscle and bowel (t(5) =3.11, P=0.03), (t(5) =3.08, P=0.03), respectively. However, tumour SUVmean didn't differ significantly compared with muscle and bowel (t(5) =2.41 , P=0.06), (t(5) =2.46 , P=0.06) respectively. The mean tumour to muscle ratio (T/M) ratio was 1.89±0.64 (range 1.10 - 2.87), while the mean tumour to normal bowel (T/B) was 1.92±0.64 (range 1.08 - 2.74). However, [18F]FAZA did not accumulate in any of the tumours found in patients with GEC. Conclusions: [18F]FAZA PET/CT imaging is suitable and feasible for detecting CRC hypoxic tumour regions with image quality that can be used in clinical practice.

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This thesis presents studies relating to the role of the gastrointestinal tract in postprandial blood pressure regulation. The areas that have been addressed include : ( i ) the methodological approaches to the evaluation of gastric emptying, blood pressure, splanchnic blood flow, intraluminal manometry and gut hormones and ( ii ) the pathophysiological mechanisms underlying postprandial hypotension, with a particular focus on ' gastric ' and ' small intestinal ' mechanisms and their potential therapeutic relevance. All of the studies have been either published or manuscripts have been prepared for publication. While scintigraphy represents the ' gold standard ' for the measurement of gastric emptying, recent studies suggest that three - dimensional ( 3D ) ultrasonography may also allow a precise measure of gastric emptying. Concurrent scintigraphic and ultrasonographic measurements of gastric emptying of liquids were performed in healthy young volunteers. There was a good correlation and agreement between scintigraphic measurements of gastric emptying and 3D ultrasonography after ingestion of both low - and high - nutrient drinks, indicating that 3D ultrasonography, provides a valid measure of gastric emptying of liquid meals in normal subjects. Postprandial hypotension, defined as a fall in systolic blood pressure of ≥ 20mmHg,occurring within two hours of a meal is now recognised as an important clinical problem, particularly in the elderly and in patients with type 2 diabetes. The mechanisms mediating postprandial hypotension are poorly understood. The effects of variations in concentration of intraduodenal glucose on the magnitude of the fall in blood pressure were evaluated in healthy elderly subjects. Blood pressure fell, and heart rate and blood glucose increased over time during infusions, however, there was no difference in blood pressure, heart rate or blood glucose concentrations between the study days. These observations suggest that glucose induced postprandial hypotension is a load rather, than concentration, dependent phenomenon. The effect of meal composition has been reported to influence the hypotensive response to a meal and information relating to the effects of triglyceride and protein on blood pressure is inconsistent. The comparative effects of isocaloric and isovolaemic intraduodenal infusions of glucose, triglyceride and protein on the magnitude of the postprandial fall in blood pressure and rise in heart rate and superior mesenteric artery blood flow were evaluated in healthy elderly subjects. There were comparable falls in systolic blood pressure and rises in heart rate, however, the maximum fall in systolic blood pressure occurred later after triglyceride and protein and the stimulation of superior mesenteric artery blood flow was less after protein. These observations suggest that the relatively slower systolic blood pressure response after triglyceride and protein may potentially reflect the time taken for digestion of triglyceride to free fatty acids and protein to amino acids. Acarbose is an antidiabetic drug that slows both gastric emptying and small intestinal glucose absorption. The effects of acarbose, on blood pressure, heart rate, gastric emptying of, and the glycaemic, insulin, glucagon - like peptide - 1 ( GLP - 1 ) and glucosedependent insulinotropic - polypeptide ( GIP ) responses to, an oral sucrose load were evaluated in healthy elderly subjects. Acarbose attenuated the fall in blood pressure and increase in heart rate induced by oral sucrose. Acarbose slowed gastric emptying and was associated with increased retention in the distal stomach. Stimulation of GLP - 1 may contribute to the slowing of gastric emptying and suppression of postprandial glycaemia by acarbose. These findings suggest that acarbose may represent a therapeutic option for the treatment of patients with postprandial hypotension. Recent studies indicate that gastric distension attenuates the postprandial fall in blood pressure. The effects of gastric distension on blood pressure and heart rate during intraduodenal infusion of glucose at a constant load and concentration were evaluated in healthy elderly subjects. Intragastric administration of water markedly attenuated the falls in systolic and diastolic blood pressure induced by intraduodenal glucose. Heart rate increased, with and without gastric distension, in response to intraduodenal glucose infusion but not after intraduodenal saline infusion. This study suggests that gastric distension may potentially be used as a simple adjunctive treatment in the management of postprandial hypotension. Studies employing nitric oxide synthase blockers have established, in animals, that nitric oxide mechanisms are important in the regulation of splanchnic blood flow and, hence, may effect postprandial blood pressure. The role of the nitric oxide synthase inhibitor, NG - nitro - L - arginine - methyl - ester ( L - NAME ), on gastric emptying, postprandial blood pressure, plasma insulin concentration and incretin hormone ( ie GIP and GLP - 1 ) release, following an oral glucose load, were evaluated in healthy elderly subjects. L - NAME attenuated the postprandial fall in blood pressure and increase in heart rate but had no effect on gastric emptying of glucose. L - NAME attenuated the glucose - induced rise in plasma insulin but had no effect on the incretin ( GIP and GLP - 1 ) hormone response to oral glucose. The study indicates that the magnitude of the fall in blood pressure and increase in heart rate and stimulation of insulin secretion induced by oral glucose in healthy elderly subjects are mediated by nitric oxide mechanisms by an effect unrelated to changes in gastric emptying, or the secretion of GIP and GLP - 1. Studies utilising 5 - hydroxytryptamine ( 5 - HT ) infusions in animals have demonstrated regional variations in intestinal blood flow suggesting a role for 5 - HT in postprandial haemodynamic responses. The effects of the 5 - hydroxytryptamine 3 ( 5 - HT3 ) antagonist, granisetron, on the blood pressure, heart rate, antropyloroduodenal motility and glycaemic responses to intraduodenal glucose infusion were assessed in healthy elderly subjects. Granisetron had no effect on blood pressure, heart rate or antral and pyloric motor responses but modulated the duodenal motor response, to intraduodenal glucose. This study indicates that while the cardiovascular response to intraduodenal glucose does not appear to be influenced by the stimulation of 5 - HT3 receptors, this receptor may be involved in the modulation of the duodenal motor activity. / Thesis (Ph.D.)--School of Medicine, 2006.