A cirrose é uma doença cosmopolita que causa milhares de mortes a cada ano e encontra-se em estado de atenção pelos sistemas de saúde governamentais. Em auxílio à sua compreensão, utiliza-se o modelo de indução de cirrose pela tioacetamida (TAA) em ratas. Porém este modelo tem carência de informações sobre a presença de células inflamatórias no fígado, as quais desempenham ação destrutiva e estimulam o desenvolvimento da cirrose. Propusemos nesta pesquisa a detecção de macrófagos e células dendríticas neste modelo nas primeiras sete semanas com o uso de tioacetamida na dose de 200mg/kg em aplicações intraperitoneais, correlacionando-as com a apoptose de hepatócitos, a presença de células MCP-1 positivas e o desenvolvimento da fibrose em fígado de ratas. Com isto, esperou-se encontrar o aumento contínuo de macrófagos teciduais e exsudativos, juntamente com o aumento de células dendríticas, atraídas pela secreção de MCP-1 pelas células estreladas hepáticas. Esperou-se também a detecção de hepatócitos em apoptose e consequente deposição de fibras colágenas pelas células estreladas hepáticas. A ação tóxica da tioacetamida foi observada pela necrose de sacabocado e reação tecidual com proliferação de ductos biliares. A tioacetamida foi eficiente em desencadear a presença de macrófagos e hepatócitos em apoptose nas primeiras semanas, contudo foi ineficaz em manter o aumento destes eventos de forma constante até o final da sétima semana. Além disso, o aumento do tecido colágeno não foi significante, indicando indiretamente a presença de macrófagos e a lesão de hepatócitos não foi suficientemente intensa para desencadear a ação máxima das células estreladas hepáticas durante as sete semanas de tratamento. A utilização de 200 mg/kg de tioacetamida induziu a presença de células inflamatórias, todavia a lesão do parênquima hepático foi atenuada com o tempo. Portanto, a fim de se manter a constante lesão e inflamação do fígado, possivelmente será necessário aumentar a dose de TAA / Cirrhosis is a cosmopolitan disease that causes thousands of deaths each year and is in a state of attention by governmental health systems. In aid for its comprehension, we use the model of cirrhosis induced by thioacetamide (TAA) in rats. But this model has a lack of information about the presence of inflammatory cells in the liver, which play destructive action and stimulate the development of cirrhosis. We have proposed in this research to detect macrophages and dendritic cells in this model using 200mg/kg of thioacetamide via intraperitoneal for seven weeks and correlate them with apoptosis in hepatocytes, the presence of MCP-1 positive cells and the development of fibrosis in the liver of female rats. It was hoped to find steady increase in tissue and exudative macrophages and of dendritic cells attracted by the release of MCP-1 by hepatic stellate cells, to detect apoptosis in hepatocytes and consequent increase collagen deposition by hepatic stellate cells. The toxic action of thioacetamide was observed by piecemeal necrosis and tissue reaction with bile duct proliferation. The thioacetamide was effective in triggering the presence of macrophages and hepatocyte apoptosis in the first weeks, but ineffective in maintaining steadily increase of these events until the end of the seventh week. Furthermore, the increase of collagen tissue was not significant; indicating indirectly that the presence of macrophages and hepatocyte injury was not enough intense to trigger the maximum action of hepatic stellate cells during the seven weeks of treatment. The use of 200 mg / kg of thioacetamide induced the presence of inflammatory cells; however the injury of the hepatic parenchyma was attenuated with time.Therefore, in order to keep the constant liver injury and inflammation possibly will be necessary to increase the dose of TAA

A cirrose é uma doença cosmopolita que causa milhares de mortes a cada ano e encontra-se em estado de atenção pelos sistemas de saúde governamentais. Em auxílio à sua compreensão, utiliza-se o modelo de indução de cirrose pela tioacetamida (TAA) em ratas. Porém este modelo tem carência de informações sobre a presença de células inflamatórias no fígado, as quais desempenham ação destrutiva e estimulam o desenvolvimento da cirrose. Propusemos nesta pesquisa a detecção de macrófagos e células dendríticas neste modelo nas primeiras sete semanas com o uso de tioacetamida na dose de 200mg/kg em aplicações intraperitoneais, correlacionando-as com a apoptose de hepatócitos, a presença de células MCP-1 positivas e o desenvolvimento da fibrose em fígado de ratas. Com isto, esperou-se encontrar o aumento contínuo de macrófagos teciduais e exsudativos, juntamente com o aumento de células dendríticas, atraídas pela secreção de MCP-1 pelas células estreladas hepáticas. Esperou-se também a detecção de hepatócitos em apoptose e consequente deposição de fibras colágenas pelas células estreladas hepáticas. A ação tóxica da tioacetamida foi observada pela necrose de sacabocado e reação tecidual com proliferação de ductos biliares. A tioacetamida foi eficiente em desencadear a presença de macrófagos e hepatócitos em apoptose nas primeiras semanas, contudo foi ineficaz em manter o aumento destes eventos de forma constante até o final da sétima semana. Além disso, o aumento do tecido colágeno não foi significante, indicando indiretamente a presença de macrófagos e a lesão de hepatócitos não foi suficientemente intensa para desencadear a ação máxima das células estreladas hepáticas durante as sete semanas de tratamento. A utilização de 200 mg/kg de tioacetamida induziu a presença de células inflamatórias, todavia a lesão do parênquima hepático foi atenuada com o tempo. Portanto, a fim de se manter a constante lesão e inflamação do fígado, possivelmente será necessário aumentar a dose de TAA / Cirrhosis is a cosmopolitan disease that causes thousands of deaths each year and is in a state of attention by governmental health systems. In aid for its comprehension, we use the model of cirrhosis induced by thioacetamide (TAA) in rats. But this model has a lack of information about the presence of inflammatory cells in the liver, which play destructive action and stimulate the development of cirrhosis. We have proposed in this research to detect macrophages and dendritic cells in this model using 200mg/kg of thioacetamide via intraperitoneal for seven weeks and correlate them with apoptosis in hepatocytes, the presence of MCP-1 positive cells and the development of fibrosis in the liver of female rats. It was hoped to find steady increase in tissue and exudative macrophages and of dendritic cells attracted by the release of MCP-1 by hepatic stellate cells, to detect apoptosis in hepatocytes and consequent increase collagen deposition by hepatic stellate cells. The toxic action of thioacetamide was observed by piecemeal necrosis and tissue reaction with bile duct proliferation. The thioacetamide was effective in triggering the presence of macrophages and hepatocyte apoptosis in the first weeks, but ineffective in maintaining steadily increase of these events until the end of the seventh week. Furthermore, the increase of collagen tissue was not significant; indicating indirectly that the presence of macrophages and hepatocyte injury was not enough intense to trigger the maximum action of hepatic stellate cells during the seven weeks of treatment. The use of 200 mg / kg of thioacetamide induced the presence of inflammatory cells; however the injury of the hepatic parenchyma was attenuated with time.Therefore, in order to keep the constant liver injury and inflammation possibly will be necessary to increase the dose of TAA

Kam, Kin Ting. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 169-192). / Abstracts in English and Chinese. / Chapter 1. --- Abstract --- p.ii / English --- p.ii / Chinese --- p.v / Chapter 2. --- Acknowledgments --- p.vii / Chapter 3. --- Abbreviations and N-glycan representation --- p.viii / Chapter 4. --- Introduction --- p.1 / Chapter 5. --- Review of Literatures --- p.2 / Chapter 5.1. --- Introduction to Liver Fibrosis --- p.2 / Chapter 5.1.1. --- Pathogenesis of Liver Fibrosis --- p.2 / Chapter 5.1.2. --- Changes of liver architecture - basis of liver fibrosis diagnosis --- p.4 / Chapter 5.2. --- Current Diagnosis of Liver Fibrosis - from Biopsy Examination to Serum Test --- p.5 / Chapter 5.3. --- Glycomics and its Potential as Biomarkers --- p.9 / Chapter 5.3.1. --- Overview of Biochemical and Functional Characteristics of Glycan --- p.13 / Chapter 5.3.2. --- N-linked and O-linked Glycosylations - A Valuable Source of Biomarkers --- p.15 / Chapter 5.3.3. --- Glycomics 一 An Uprising Approach for Biomarker Discovery --- p.17 / Chapter 5.3.4. --- Human Proteome Organisation Human Disease Glycomics/Proteome Initiative --- p.19 / Chapter 5.3.5. --- Recent Applications of Glycomics to Biomarker Discovery --- p.20 / Chapter 5.4. --- Current Technologies for Glycomic Study --- p.22 / Chapter 5.4.1. --- MALDI-TOF MS --- p.22 / Chapter 5.4.2. --- Lectin Microarray --- p.25 / Chapter 5.4.3. --- Liquid Chromatography --- p.27 / Chapter 5.4.4. --- Capillary Electrophoresis --- p.29 / Chapter 5.4.5. --- Quantitative Profiling of Tissue Glycome --- p.31 / Chapter 6 --- Project Rationales and Objectives --- p.36 / Chapter 7 --- Section 1: Methodology Development of Quantitative N- glycomic Profiling --- p.37 / Chapter 1. --- Introduction --- p.37 / Chapter 2. --- Method and Materials --- p.39 / Chapter 3. --- Results --- p.46 / Chapter 4. --- Discussion --- p.65 / Chapter 5. --- Conclusion --- p.71 / Chapter 8. --- Section 2: Serum N-glycomic Profile as Biomarker for Liver Fibrosis 一 Pilot Study --- p.73 / Chapter 1. --- Introduction --- p.73 / Chapter 2. --- Method and Materials --- p.75 / Chapter 3. --- Results --- p.79 / Chapter 4. --- Discussion --- p.86 / Chapter 5. --- Conclusion --- p.94 / Chapter 9. --- Section 3: Serum N-glycomic Profile as Biomarker for Liver Fibrosis -Verification Study --- p.96 / Chapter 1. --- Introduction --- p.96 / Chapter 2. --- Method and Materials --- p.98 / Chapter 3. --- Results --- p.104 / Chapter 4. --- Discussion --- p.137 / Chapter 5. --- Conclusion --- p.152 / Chapter 10. --- General Discussion --- p.153 / Chapter 11. --- Conclusion --- p.167 / Chapter 12. --- Original Data --- p.168 / Chapter 13. --- References --- p.169 / Chapter 14. --- Publications --- p.196