Fundação de Amparo a Pesquisa do Estado de Minas Gerais / A radioterapia é uma das principais abordagens terapêuticas utilizadas no tratamento do câncer e é indicada, principalmente, em casos onde as lesões são inoperáveis. No entanto, uma de suas limitações advém dos próprios efeitos biológicos da radiação, além de outros fatores tais como a radiorresistência inerente a alguns tipos tumorais, tais como os cerebrais. Então, a aplicação concomitante de agentes antineoplásicos com radioterapia vem sendo praticada na clínica de modo a maximizar o efeito benéfico do último e ao mesmo tempo minimizar os efeitos colaterais da exposição à radiação ionizante. Dentro deste contexto geral é importante a pesquisa de novos compostos que possam ser selecionados como protótipos para o desenvolvimento de agentes que possuam os menores efeitos adversos possíveis. As tiossemicarbazonas são uma classe de compostos sintéticos que apresenta um amplo perfil farmacológico e já demonstraram atividade antitumoral. Também já foi relatado que a complexação destes compostos com cátions metálicos pode ser capaz de torná-los mais eficazes. O objetivo do presente trabalho foi avaliar o potencial radiossensibilizador de uma tiossemicarbazona derivada de N(4)-metil-toluil-2-acetilpiridina e seu complexo com cobre sobre linhagens celulares de glioblastoma multiforme, o qual de todos os tumores cerebrais é o que apresenta a maior agressividade e o maior índice de morbidade. Foi avaliada a sensibilidade de linhagens celulares de glioblastoma com diferentes status de p53 RT2 e U87 (p53 selvagem) e T98 (p53 mutante) à radiação gama de uma fonte de 60Co. Os resultados de citotoxicidade indicaram que as linhagens em questão apresentam uma radiossensibilidade similar, p53-independente. Os efeitos citotóxicos da tiossemicarbazona Lac e seu complexo CuLac foram avaliados e os resultados indicaram que ambas possuem excelente efeito citotóxico na ordem de 10-8 M em todas as linhagens avaliadas, portanto menores que drogas como a hidroxiuréia, cisplatina e etoposídeo (IC50 entre 10-4 e 10-6 M em média). O tratamento com as tiossemicarbazonas seguido de 6 Gy de radiação gama se mostrou mais eficiente que o tratamento com radiação isolada em todas as linhagens. A complexação com cobre não alterou de modo significativo o efeito antitumoral da tiossemicarbazona livre sobre as linhagens testadas. Análises de fotomicrografias ópticas indicaram que todos os tratamentos ocasionaram alterações morfológicas, tais como arredondamento celular, redução do volume citoplasmático e surgimento de vesículas na membrana citoplasmática. O conjunto de dados indicam que a tiossemicarbazona Lac e seu complexo de cobre possuem potente efeito antitumoral e também induzem radiossensibilização nas linhagens testadas. / Radiation therapy is one of the main therapeutical approaches used for the treatment of cancer and is indicated, mostly, in cases which the lesions are inoperable. However, one of its limitations comes from its own biological effects, besides other factors such as the radioresistance inherent to some types of tumors like the cerebral ones. Therefore, the concurrent aplication of antineoplasic agentes with the radiation therapy has been used in the clinical pratice with the objective of maximize the benefical effects of the latter and at the same time minimize the side effects of the exposure to ionizing radiation. In this general context is important the research for new compounds that can be selected as prototypes for the development of agents that possess the least adverse effects as possible. The thiosemicarbazones are a class of synthetic compounds that present a broad pharmacological profile and have demonstrated antitumoral activity. Also has been reported that the coordination of these compounds to metallic cations may be capable of make them more effective. The objective of the present work was to evaluate the radiosensitizing potential of a thisemicarbazone derived from N(4)-methyl-tolyl-2-acetylpyridine and its copper complex against glioblastoma multiforme cell lines, which of all brain tumors types, are the most agressive and have the highest morbidity. The sensitivity of glioblastoma cell lines with different p53 status RT2 and U87 (p53 wild type) and T98 (p53 mutant) to gamma radiation from a 60Co source was assessed. Citotoxicity results indicated that the cell lines in study presented a similar radiosensitivity, p53-independent. The citotoxic effects of the thiosemicarbazone Lac and its complex CuLac were assayed and the results indicated that both possess na excelent effect at the order of 10-8 M in all cell lines evaluated, therefore smaller than drugs such as hydroxyurea, cisplatin and etoposide (IC50 between 10-4 and 10-6 M). The treatment with the thiosemicarbazones followed by a 6 Gy gamma radiation dose showed to be more effective than the radiation alone in all cell lines. Coordination to Cooper had not changed significantly the antitumoral effect of the free thiosemicarbazone agains the cell lines tested. Morphological analysis of optical photomicrographies indicated that all treatment caused alterations, such as cell rounding, diminishing of the cytoplasmic volume and rising of vesicles at the cytoplasmic membrane. Together these data indicate that the thiosemicarbazone Lac and its metallic complex possess potent antitimoral effect amd also induce radiosensitivity in the tested cell lines.

Sun Qiang. / "December 1999." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 119-139). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

shum Wai Chi. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 259-279). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Leung Pak Heng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 163-189). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

by Yuen Mei Ling, Miranda. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 73-83.

by Choi, Heung Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 79-95). / Acknowledgement --- p.iv / Abstract --- p.vi / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- Cocaine --- p.1 / Chapter 1.1.1 --- History --- p.1 / Chapter 1.1.2 --- Epidemiology --- p.2 / Chapter 1.1.3 --- Pharmacology --- p.3 / Chapter 1.2 --- Maternal Cocaine Abuse --- p.5 / Chapter 1.2.1 --- Human Studies --- p.5 / Chapter 1.2.1.1 --- Prevalence --- p.5 / Chapter 1.2.1.2 --- Effects of Cocaine on the Developing Fetus --- p.7 / Chapter 1.2.1.2.1 --- Fetal Mortality --- p.8 / Chapter 1.2.1.2.2 --- Placental Abruption --- p.9 / Chapter 1.2.1.2.3 --- Premature Birth --- p.9 / Chapter 1.2.1.2.4 --- Neonatal Effects --- p.10 / Chapter 1.2.1.3 --- Congenital Abnormalities --- p.11 / Chapter 1.2.1.3.1 --- Cardiovascular Abnormality --- p.11 / Chapter 1.2.1.3.2 --- Genitourinary Tract Malformation --- p.12 / Chapter 1.2.1.3.3 --- Gastrointestinal Abnormality --- p.12 / Chapter 1.2.1.3.4 --- Respiratory Disorders --- p.13 / Chapter 1.2.1.3.5 --- Visual and Hearing Disorders --- p.14 / Chapter 1.2.1.3.6 --- CNS and Behavioural Abnormalities --- p.15 / Chapter 1.2.2 --- Animal Studies --- p.17 / Chapter 1.2.2.1 --- "Routes of Administration, Dosage and Tissue Distribution " --- p.18 / Chapter 1.2.2.2 --- Maternal and Offspring Effects --- p.21 / Chapter 1.2.2.2.1 --- Fetal and Maternal Mortality --- p.22 / Chapter 1.2.2.2.2 --- Gestational Length --- p.22 / Chapter 1.2.2.2.3 --- Maternal Weight Gain and Fetal Weight --- p.23 / Chapter 1.2.2.2.4 --- Little Size --- p.24 / Chapter 1.2.2.3 --- Congenital Abnormalities --- p.24 / Chapter 1.2.2.4 --- Behavioral Changes --- p.26 / Chapter 1.2.2.5 --- Neurochemical Changes --- p.28 / Chapter 1.2.2.5.1 --- Glucose Metabolism --- p.28 / Chapter 1.2.2.5.2 --- Dopamine Transporter --- p.29 / Chapter 1.2.2.5.3 --- Dopamine D1 Receptor --- p.29 / Chapter 1.2.2.5.4 --- Dopamine D2 Receptor --- p.30 / Chapter 1.2.2.5.5 --- Tyrosine Hydroxylase --- p.30 / Chapter 1.2.2.5.6 --- Other Changes --- p.31 / Chapter 1.3 --- The Aim of the Study --- p.31 / Chapter CHAPTER II --- MATERIALS AND METHODS / Chapter 2.1 --- Administration of Cocaine --- p.34 / Chapter 2.2 --- Biochemical Studies --- p.35 / Chapter 2.2.1 --- Receptor Binding Assays --- p.36 / Chapter 2.2.1.1 --- Dopamine Transporter --- p.37 / Chapter 2.2.1.1.1 --- Specific Binding Assay and Scatchard Analysis --- p.37 / Chapter 2.2.1.2 --- Dopamine D1 Receptor --- p.38 / Chapter 2.2.1.2.1 --- Association Curve --- p.38 / Chapter 2.2.1.2.2 --- Competition Assay --- p.39 / Chapter 2.2.1.2.3 --- Specific Binding Assay and Scatchard Analysis --- p.39 / Chapter 2.2.1.3 --- Dopamine D2 Receptor --- p.39 / Chapter 2.2.1.3.1 --- Association Curve --- p.40 / Chapter 2.2.1.3.2 --- Competition Assay --- p.40 / Chapter 2.2.1.3.3 --- Specific Binding Assay and Scatchard Analysis --- p.40 / Chapter 2.2.1.4 --- Assay for Residual Cocaine in Maternal Brain --- p.41 / Chapter 2.3 --- Statistics --- p.42 / Chapter 2.4 --- Morphological Studies --- p.42 / Chapter 2.4.1 --- Tyrosine Hydroxylase (TH) Immunocytochemical Staining --- p.42 / Chapter 2.5 --- Molecular Genetic Studies --- p.44 / Chapter 2.5.1 --- Material for DNA Insert --- p.44 / Chapter 2.5.1.1 --- "Dopamine Transporter, D2 receptor and β-actin cDNA Probe " --- p.44 / Chapter 2.5.2 --- Preparation for DNA Insert --- p.45 / Chapter 2.5.2.1 --- Competent Cells and Transformation of Plasmid --- p.45 / Chapter 2.5.2.2 --- Growth Transformed Bacteria and Isolation of DNA --- p.46 / Chapter 2.5.2.3 --- Purification of cDNA by Geneclean® II Kit --- p.47 / Chapter 2.5.3 --- Isolation of Total mRNA From Tissue --- p.47 / Chapter 2.5.4 --- Northern Blot Analysis --- p.48 / Chapter 2.5.4.1 --- Analysis of Northern Blots --- p.50 / Chapter 2.5.5 --- In Situ Hybridization --- p.50 / Chapter 2.5.5.1 --- Tissue Preparation --- p.50 / Chapter 2.5.5.2 --- Preparation of Dopamine Transporter Ribroprobe …… --- p.50 / Chapter 2.5.5.3 --- In Situ Hybridization Histochemistry --- p.51 / Chapter CHAPTER III --- RESULTS / Chapter 3.1 --- "Litter Size, Birth Weight and Maternal Weight Gain " --- p.53 / Chapter 3.2 --- Biochemical Studies --- p.53 / Chapter 3.2.1 --- Specific Binding --- p.53 / Chapter 3.2.2 --- Dopamine Transporter - Scatchard Analysis --- p.54 / Chapter 3.2.3 --- Dopamine Receptor --- p.55 / Chapter 3.2.3.1 --- Association Curve --- p.56 / Chapter 3.2.3.2 --- Competitive Curve --- p.57 / Chapter 3.2.3.3 --- Scatchard Analysis --- p.57 / Chapter 3.2.4 --- Dopamine D2 Receptor --- p.59 / Chapter 3.2.4.1 --- Association Curve --- p.59 / Chapter 3.2.4.2 --- Competitive Curve --- p.59 / Chapter 3.2.4.3 --- Scatchard Analysis --- p.59 / Chapter 3.2.5 --- Residual Cocaine Assay in Maternal Brain --- p.61 / Chapter 3.2.5.1 --- Specific Binding --- p.61 / Chapter 3.2.5.1.1 --- Dopamine Transporter --- p.61 / Chapter 3.3.5.1.2 --- Dopamine D1 Receptor --- p.62 / Chapter 3.3.5.1.3 --- Dopamine D2 Receptor --- p.62 / Chapter 3.3 --- Morphological Studies --- p.62 / Chapter 3.3.1 --- Tyrosine Hydroxylase (TH) Immunocytochemical Staining --- p.62 / Chapter 3.4 --- Molecular Genetic Studies --- p.63 / Chapter 3.4.1 --- Northern Blot Analysis --- p.63 / Chapter 3.4.1.1 --- Dopamine Transporter --- p.63 / Chapter 3.4.1.2 --- Dopamine D2 Receptor --- p.64 / Chapter 3.4.2 --- In Situ Hybridization --- p.64 / Chapter CHAPTER IV --- DISCUSSION AND CONCLUSION / Chapter 4.1 --- Discussion --- p.65 / Chapter 4.2 --- Conclusion --- p.77 / References --- p.79 / Publications --- p.95

Wai Kei Chan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 155-164). / Abstracts in English and Chinese. / Chapter Chapter 1 --- Introduction / Chapter 1.1. --- Sulfonylureas --- p.1 / Chapter 1.2. --- Biological action of sulfonylurea drugs --- p.2 / Chapter 1.2.1 --- Effects on pancreatic β cells --- p.5 / Chapter 1.2.2. --- Effects on cardiac myocytes --- p.7 / Chapter 1.2.3. --- Effects on smooth muscle cells --- p.11 / Chapter 1.2.4. --- Effects on endothelial cells --- p.14 / Chapter 1.3. --- Side effects and toxicity --- p.15 / Chapter 1.4. --- Objectives of the present study --- p.17 / Chapter Chapter 2 --- Methods and Marterials / Chapter 2.1. --- Tissue and Cell Preparation --- p.20 / Chapter 2.1.1. --- Preparation of the isolated rat aorta and mesenteric artery --- p.20 / Chapter 2.1.2. --- Removal of the functional endothelium --- p.20 / Chapter 2.1.3. --- Cell culture --- p.21 / Chapter 2.1.3.1. --- Materials --- p.21 / Chapter 2.1.3.2. --- Aortic smooth muscle cells in primary culture --- p.21 / Chapter 2.1.3.3. --- Aortic endothelial cells in primary culture --- p.23 / Chapter 2.1.3.4. --- Cultured rat aortic smooth muscle cell line (A7r5) --- p.23 / Chapter 2.1.3.5. --- Cultured human umbilical vein endothelial cell line (ECV-304) --- p.24 / Chapter 2.1.3.6. --- Cell subculture --- p.24 / Chapter 2.1.3.7. --- Immunostaining of endothelial cells in primary culture --- p.24 / Chapter 2.2. --- Organ Bath Set-up --- p.25 / Chapter 2.3. --- Force Measurement --- p.28 / Chapter 2.3.1. --- Vascular action of glibenclamide --- p.28 / Chapter 2.3.1.1. --- Antagonistic effect of glibenclamide on relaxation induced by K+ channel openers --- p.28 / Chapter 2.3.1.2. --- Relaxant response of glibenclamide --- p.29 / Chapter 2.3.1.3. --- Role of endothelium-derived vasoactive factors in glibenclamide induced relaxation --- p.29 / Chapter 2.3.1.4. --- Effect of endothelial prostanoids in glibenclamide-induced relaxation --- p.30 / Chapter 2.3.1.5. --- Effects of putative K+ channel blockers on glibenclamide-induced relaxation --- p.30 / Chapter 2.3.1.6. --- Effect of glibenclamide on high K+- and CaCl2-induced contraction --- p.31 / Chapter 2.3.1.7. --- Effect of glibenclamide on prostaglandin F2α-induced contraction --- p.32 / Chapter 2.3.1.8. --- Effect of glibenclamide on protein kinase C-mediated contraction --- p.32 / Chapter 2.3.2. --- Vascular action of glipizide --- p.33 / Chapter 2.3.3. --- Vascular action of tolbutamide --- p.33 / Chapter 2.3.3.1. --- Contractile response of tolbutamide --- p.33 / Chapter 2.3.3.2. --- Effects of inhibitors of endothelium-derived factors --- p.33 / Chapter 2.3.3.3. --- Effects of inhibitors of Ca2+ influx --- p.34 / Chapter 2.3.3.4. --- Effect of protein kinase C inhibitor --- p.34 / Chapter 2.3.3.5. --- Effects of neural factors --- p.34 / Chapter 2.4. --- Cyclic GMP measurement --- p.35 / Chapter 2.4.1. --- Material --- p.35 / Chapter 2.4.2. --- Methods --- p.35 / Chapter 2.4.2.1. --- Tissue preparation --- p.35 / Chapter 2.4.2.2. --- Plasma and tissue according to protocols provided by Amersham --- p.35 / Chapter 2.4.2.3. --- Cyclic GMP content measurement --- p.36 / Chapter 2.4.2.4. --- Protein content measurement --- p.39 / Chapter 2.4.2.5. --- Cyclic GMP measurement protocol --- p.40 / Chapter 2.5. --- Ca2+ measurement --- p.40 / Chapter 2.5.1. --- Materials --- p.40 / Chapter 2.5.1.1. --- PTI RatioMaster Fluorescence System --- p.40 / Chapter 2.5.1.2. --- Confocal Imaging System --- p.42 / Chapter 2.5.2. --- Method --- p.42 / Chapter 2.5.3. --- Protocols for Ca2+ measurement --- p.45 / Chapter 2.5.3.1. --- Effect of glibenclamide in endothelial cells --- p.45 / Chapter 2.5.3.2. --- Effect of glibenclamide in vascular smooth muscle cells --- p.45 / Chapter 2.5.3.3. --- Effect of tolbutamide in vascular smooth muscle cells --- p.46 / Chapter 2.6. --- Cell proliferation --- p.45 / Chapter 2.6.1. --- Materials --- p.45 / Chapter 2.6.2. --- Method --- p.46 / Chapter 2.6.3. --- Protocols for cell proliferation --- p.47 / Chapter 2.6.3.1. --- Effect of glibenclamide on endothelial cell proliferation --- p.47 / Chapter 2.6.3.2. --- Effect of glibenclamide on aortic smooth muscle cell proliferation --- p.47 / Chapter 2.7. --- Chemicals and solutions --- p.48 / Chapter 2.8. --- Statistical analysis --- p.50 / Chapter Chapter 3 --- Results / Chapter 3.1. --- Glibenclamide --- p.51 / Chapter 3.1.1. --- Effect of glibenclamide on the K+ channel activity --- p.51 / Chapter 3.1.2. --- Relaxant response of glibenclamide --- p.55 / Chapter 3.1.3. --- Effects of inhibitors of nitric oxide activity on glibenclamide- induced relaxation --- p.57 / Chapter 3.1.4. --- Role of endothelial relaxing prostanoids in glibenclamide-induced relaxation --- p.69 / Chapter 3.1.5. --- Effect of putative K+ channel blockers on glibenclamide-induced relaxation --- p.73 / Chapter 3.1.6. --- Effect of glibenclamide on high K+-induced arterial contraction --- p.75 / Chapter 3.1.7. --- Effect of glibenclamide on protein kinase C-mediated contraction --- p.83 / Chapter 3.1.8. --- Effect of glibenclamide on prostaglandin F2α-induced contraction --- p.83 / Chapter 3.2 --- Glipizide --- p.85 / Chapter 3.2.1. --- Relaxant response of glipizide --- p.85 / Chapter 3.3. --- Tolbutamide --- p.91 / Chapter 3.3.1. --- Contractile response to tolbutamide --- p.91 / Chapter 3.3.2. --- Effects of endothelium-derived factors --- p.94 / Chapter 3.3.3. --- Effects of inhibitors of Ca2+ influx on tolbutamide-induced contraction --- p.98 / Chapter 3.3.4. --- "Effects of forskolin, sodium nitroprusside, staurosporine on tolbutamide-induced contraction" --- p.102 / Chapter 3.3.5. --- Effect of neural factors --- p.106 / Chapter 3.4. --- Effect of glibenclamide on cGMP levels --- p.112 / Chapter 3.5. --- Effect of glibenclamide on intracellular[Ca2+ ] in cultured endothelial cells --- p.112 / Chapter 3.6. --- Effect of glibenclamide on intracellular [Ca2+] in cultured aortic smooth muscle cells --- p.115 / Chapter 3.7. --- Effect of tolbutamide on intracellular [Ca2+] in cultured aortic smooth muscle cells --- p.121 / Chapter 3.8. --- Effect of glibenclamide on proliferation of cultured endothelial cells --- p.121 / Chapter 3.9. --- Effect of glibenclamide on proliferation of cultured aortic smooth muscle cells --- p.123 / Chapter Chapter 4 --- Discussion / Chapter 4.1. --- Effect of glibenclamide --- p.133 / Chapter 4.2. --- Effect of glipizide --- p.143 / Chapter 4.3. --- Effect of tolbutamide --- p.144 / Chapter 4.4. --- Conclusion --- p.152 / References --- p.155 / Publications --- p.163

Sha Ou. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 167-189). / Abstracts in English and Chinese. / abstract --- p.i / 中文摘要 --- p.iv / acknowledgements --- p.vii / Chapter chapter 1. --- introduction --- p.1 / Chapter 1.1 --- Overview --- p.1 / Chapter 1.2 --- Ribosome-inactivating proteins (RIPs) --- p.1 / Chapter 1.2.1 --- Classification --- p.2 / Chapter 1.2.2 --- Structure --- p.3 / Chapter 1.2.3 --- Enzymatic activities --- p.3 / Chapter 1.3 --- Type II RIPs --- p.5 / Chapter 1.3.1 --- Ricin --- p.5 / Chapter 1.3.2 --- Ricinus communis agglutinin (RCA) --- p.6 / Chapter 1.3.3 --- Intracellular mechanism --- p.7 / Chapter 1.3.4 --- Application of RIPs in neuroscience research: suicide axonal transport --- p.10 / Chapter 1.4 --- Type I RIPs --- p.12 / Chapter 1.4.1 --- Trichosanthin (TCS) --- p.12 / Chapter 1.4.2 --- Ricin A chain (RTA) --- p.15 / Chapter 1.4.3 --- Medical applications: immunolesioning and immunotherapy --- p.16 / Chapter 1.5 --- The types of Cell death --- p.17 / Chapter 1.5.1 --- Necrosis --- p.18 / Chapter 1.5.2 --- Apoptosis --- p.18 / Chapter 1.6 --- Inflammations --- p.21 / Chapter 1.6.1 --- Acute inflammation --- p.21 / Chapter 1.6.2 --- Chronic inflammation --- p.22 / Chapter 1.6.3 --- Retinitis --- p.22 / Chapter 1.7 --- Eye model for neurotoxicity studies in CNS --- p.23 / Chapter 1.8 --- Objective of present study --- p.24 / Chapter CHAPTER 2. --- MATERIALS AND METHODS --- p.25 / Chapter 2.1 --- Plan of this chapter --- p.25 / Chapter 2.2 --- Toxins and methods used --- p.25 / Chapter 2.3 --- Animals --- p.26 / Chapter 2.4 --- Preparation of toxin solutions --- p.27 / Chapter 2.4.1 --- RIP solutions --- p.27 / Chapter 2.4.2 --- Labeling type I RIPs with fluorescence --- p.27 / Chapter 2.4.3 --- Control solutions --- p.29 / Chapter 2.5 --- Administrations of solutions --- p.30 / Chapter 2.5.1 --- Basic procedures of vitreous chamber injection --- p.30 / Chapter 2.5.2. --- Injection of trichosanthin (TCS) --- p.31 / Chapter 2.5.3 --- Injection of ricin A chain (RTA) --- p.31 / Chapter 2.5.4 --- Injection of ricinus communis agglutinin (RCA) --- p.32 / Chapter 2.5.5 --- Administration of FITC-TCS --- p.33 / Chapter 2.5.6 --- Administration of FITC-RTA --- p.33 / Chapter 2.6 --- Retinal tissue processing --- p.33 / Chapter 2.6.1 --- Paraffin method --- p.34 / Chapter 2.6.2 --- Cryostatic method --- p.35 / Chapter 2.6.3 --- Electron microscopic method --- p.35 / Chapter 2.7 --- General effects of RIPs on rat retinas --- p.36 / Chapter 2.7.1 --- Hematoxylin-and-eosin staining --- p.36 / Chapter 2.7.2 --- Retinal thickness --- p.37 / Chapter 2.7.3 --- Pathological changes --- p.38 / Chapter 2.7.4 --- Dosage study on TCS --- p.39 / Chapter 2.7.5 --- Statistics --- p.40 / Chapter 2.8 --- Mechanisms of cell death --- p.40 / Chapter 2.8.1 --- Terminal dUTP nick-end labeling (TUNEL) --- p.40 / Chapter 2.8.2 --- Immunohistochemistry for caspase-3 --- p.42 / Chapter 2.8.3 --- Double staining of cleaved caspase-3 and TUNEL --- p.42 / Chapter 2.8.4 --- Electronic microscope observation --- p.43 / Chapter 2.9 --- Entry of type I RIPs into cells --- p.43 / Chapter 2.9.1 --- Propidium iodide staining --- p.43 / Chapter 2.9.2 --- Immunohistochemical localization of Muller cells --- p.44 / Chapter 2.9.3 --- Double staining of Muller cells and TUNEL --- p.44 / Chapter 2.9.4 --- Confocal microscope --- p.44 / Chapter 2.10 --- Reactions of glial cells --- p.45 / Chapter CHAPTER 3. --- RESULTS --- p.47 / Chapter 3.1 --- Preparation of fluorescein-type I RIP conjugates --- p.47 / Chapter 3.1.1 --- Conjugate of FITC-TCS --- p.47 / Chapter 3.1.2 --- Conjugate of FITC-RTA --- p.47 / Chapter 3.2 --- Effects of TCS on retina --- p.47 / Chapter 3.2.1 --- Retina cell count - a dose-dependence study --- p.48 / Chapter 3.2.2 --- Retinal thickness measurement - a time-course study --- p.49 / Chapter 3.2.3 --- Pathological changes --- p.50 / Chapter 3.3 --- Effects of RTA on retina --- p.51 / Chapter 3.3.1 --- Retinal thickness measurement - a time-course study --- p.51 / Chapter 3.3.2 --- Pathological changes --- p.53 / Chapter 3.4 --- Effects of RCA on retina --- p.54 / Chapter 3.4.1 --- Retinal thickness measurement --- p.54 / Chapter 3.4.2 --- Pathological changes --- p.55 / Chapter 3.5 --- Summary of results: general effects of RIPs --- p.56 / Chapter 3.6 --- Cell death - TUNEL method --- p.56 / Chapter 3.6.1 --- TCS experiment --- p.57 / Chapter 3.6.2 --- RTA experiment --- p.58 / Chapter 3.6.3 --- RCA experiment --- p.58 / Chapter 3.7 --- Cell death 一 cleaved caspase-3 immunohistochemistry --- p.58 / Chapter 3.7.1 --- TCS experiment --- p.59 / Chapter 3.7.2 --- RTA experiment --- p.59 / Chapter 3.8 --- EM observation --- p.59 / Chapter 3.8.1 --- TCS experiment --- p.59 / Chapter 3.8.2 --- RTA experiment --- p.60 / Chapter 3.9 --- Summary of results: mode of cell death --- p.60 / Chapter 3.10 --- Localisation of type I RIPs --- p.61 / Chapter 3.10.1 --- FITC-TCS --- p.62 / Chapter 3.10.2 --- FITC-TCS and Muller cell double staining --- p.63 / Chapter 3.10.3 --- Muller cell and TUNEL double staining --- p.64 / Chapter 3.10.4 --- FITC-RTA --- p.64 / Chapter 3.10.5 --- Summary of results: route of intoxication --- p.65 / Chapter 3.11 --- Glial cell reactions after RIP treatment --- p.65 / Chapter 3.11.1 --- TCS experiment --- p.65 / Chapter 3.11.2 --- RTA experiment --- p.66 / Chapter 3.11.3 --- RCA experiment --- p.67 / Chapter 3.11.4 --- Summary of results: glial reactions --- p.67 / Chapter CHAPTER 4. --- DISCUSSION --- p.69 / Chapter 4.1 --- General effects of RIPs on rat retinas --- p.69 / Chapter 4.1.1 --- Effects of trichosanthin (TCS) --- p.69 / Chapter 4.1.2 --- Effects of ricin A chain (RTA) --- p.71 / Chapter 4.1.3 --- Effects of ricinus communis agglutinin (RCA) --- p.73 / Chapter 4.2 --- The mechanisms of cell death --- p.74 / Chapter 4.2.1 --- Cell death caused by TCS --- p.75 / Chapter 4.2.2 --- Caspase-3 and the retina of RCS rat --- p.77 / Chapter 4.2.3 --- Cell death caused by RTA --- p.78 / Chapter 4.2.4 --- Cell death caused by RCA --- p.80 / Chapter 4.2.5 --- Mechanism of RTA - induced necrosis --- p.81 / Chapter 4.3 --- The mechanisms of type I RIPs entering cells --- p.82 / Chapter 4.3.1 --- Transport of TCS in retinal cells --- p.82 / Chapter 4.3.2 --- The uptake of Pure FITC by rat retina --- p.85 / Chapter 4.4 --- Reactions of glial cells --- p.85 / Chapter 4.4.1 --- Glial cell reactions in TCS experiment --- p.86 / Chapter 4.4.2 --- Glial cell reactions in RTA and RCA experiments --- p.87 / Chapter 4.5 --- Possible applications of RIPs on retinal studies --- p.88 / Chapter 4.5.1 --- Potential applications of TCS --- p.88 / Chapter 4.5.2 --- Possible uses of RTA and RCA --- p.90 / Chapter CHAPTER 5. --- CONCLUSIONS --- p.91 / "FIGURES, TABLES, GRAPHS, AND LEGENDS" --- p.93 / APPENDICES --- p.154 / Appendix A Source of materials --- p.154 / Appendix B Dosages for vitreous chamber injection --- p.156 / Appendix C Protocol of conjugate fluorescein to proteins --- p.157 / Appendix D Electronic Microscope methods --- p.160 / Appendix E Histological methods --- p.162 / Appendix F Protocols of TUNEL --- p.163 / Appendix G Protocols of Immunohistochemistry staining --- p.165 / REFERENCES --- p.167

by Chan Hung Chuen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 143-151). / Abstract also in Chinese. / Acknowledgments --- p.i / Abstract --- p.ii / Abstract (Chinese version) --- p.v / Abbreviations --- p.viii / Content --- p.ix / Chapter CHAPTER ONE --- INTRODUCTION / Chapter 1. --- Free radical and free radical-mediated antitumor drugs --- p.1 / Chapter 2. --- Mitomycin C (MC) / Chapter 2.1 --- Drug actions of MC --- p.2 / Chapter 2.2 --- Adverse side effects of MC --- p.5 / Chapter 3. --- Doxorubicin (DOX) / Chapter 3.1 --- Drug actions of DOX --- p.7 / Chapter 3.2 --- Adverse side effects of DOX --- p.8 / Chapter 4. --- Antioxidants --- p.14 / Chapter 5. --- Effects of exogenous ATP on the antitumor activity of Doxorubicin and Mitomycin C / Chapter 5.1 --- Glutathione (GSH) and related enzymes --- p.17 / Chapter 5.2 --- Glutathione (GSH) and Anticancer Quinones --- p.19 / Chapter 5.3 --- Glutathione and the cardiac toxicity of the anticancer drugs --- p.20 / Chapter 5.4 --- Glutathione depletion in tumor cells by exogenous ATP --- p.21 / Chapter 6. --- Aim of research --- p.24 / Chapter CHAPTER TWO --- THE EFFECT OF ANTIOXIDANTS ON DOXORUBICIN- OR MITOMYCIN C-INDUCED CYTOTOXICITY ON HUMAN TUMOR AND NORMAL CELL LINES / Chapter 2.1 --- Introduction --- p.26 / Chapter 2.2 --- Materials and Methods --- p.28 / Chapter 2.3 --- Results --- p.36 / Chapter 2.4 --- Discussion --- p.60 / Chapter CHAPTER THREE --- STUDY OF CARDIOPROTECTIVE EFFECTS OF ANTIOXIDANTS AGAINST DOXORUBICIN- OR MITOMYCIN C-INDUCED TOXICITY BY LANGENDORFF PERFUEED ISOLATED RAT HEART MODEL / Chapter 3.1 --- Introduction --- p.64 / Chapter 3.2 --- Materials and Methods --- p.67 / Chapter 3.3 --- Results --- p.75 / Chapter 3.4 --- Discussion --- p.76 / Chapter CHAPTER FOUR --- THE EFFECT OF ANTIOXIDANTS DURING CHEMOTHERAPY OF DOXORUBICIN OR MITOMYCIN C IN TUMOR-BEARING MICE / Chapter 4.1 --- Introduction --- p.78 / Chapter 4.2 --- Materials and Methods --- p.80 / Chapter 4.3 --- Results --- p.83 / Chapter 4.4 --- Discussion --- p.93 / Chapter CHAPTER FIVE --- HISTOLOGICAL STUDY AND LIPID PEROXIDATION STUDY OF PROTECTIVE EFFECT OF ANTIOXIDANTS IN TUMOR-BEARING MICE TREATED WITH DOXORUBICIN OR MITOMYCIN C / Chapter 5.1 --- Introduction --- p.95 / Chapter 5.2 --- Materials and Methods --- p.98 / Chapter 5.3 --- Results --- p.103 / Chapter 5.4 --- Discussion --- p.117 / Chapter CHAPTER SIX --- EFFECT OF EXOGENOUS ATP ON THE ANTITUMOR ACTIVITY OF DOXORUBICIN AND MITOMYCIN C ON CULTURED HUMAN HEPATOMA CELLS / Chapter 6.1 --- Introduction --- p.122 / Chapter 6.2 --- Materials and Methods --- p.124 / Chapter 6.3 --- Results --- p.126 / Chapter 6.4 --- Discussion --- p.136 / Chapter CHAPTER SEVEN --- CONCLUSION / Chapter 7.1 --- Conclusion --- p.139 / Chapter 7.2 --- Future perspective --- p.141 / Bibliography --- p.142

Web mediated communications revolutionized traditional social interactions. It is designed tofacilitate information exchange between individuals and to enable people to connect with friends,family, classmates etc. virtually. By the formation of virtual communities, “web mediatedcommunication” is defined as a wider concept known as “social media”. Social media enhancesthe volume of communications and interpersonal interactions based on the power of web 2.0technology. People join to the virtual communities of online social networks to procureinformation from everywhere, share ideas, experiences, photos, videos and memorable momentswhile extending friendships beyond the geographical and cultural borders. The emergence and fastgrowth of social media among people added value to the web activities and convinced web mastersto integrate web services such as e-mail, chat, discussion rooms, forums and third partyapplications to the social media web sites. Many of social media web sites are hosting millions ofmembers, equipping their web sites with communication tools, sharing options, dynamic contentcreation and collaborative authoring facilities which never experienced before. Facebook, Twitterand GooglePlus are examples of most known social media web sites which gained popularityamong people so fast.Social media helps people to make new friends, find lost friends and old classmates whileproviding an opportunity to build new friendships. This new communication technology empowerspeople to collaborate in authoring of the web content and causes the information sharing synergy.Such positive aspects are enough for people to ignore the consequences of joining social media.Despite the rise of friendships in number, the physical encounters are substituted by virtual oneswhich causes weak friendship ties. In addition, social media platforms promise the security andprivacy of users, but issues such as identity theft and worm attacks threaten users' privacy andsecurity. Social media is in its infancy, adopted among people for less than a decade whereas a lackof research in this field is evident. The author of this thesis aimed at filling this gap byinvestigating the positive and negative effects of using social media through collecting the users'experiences and professionals' viewpoints. Theoretical study primarily illuminated the mainpositive and negative aspects while the findings of empirical research verified by theoretical studyidentified other practical effects and aspects of social media. / Program: Magisterutbildning i informatik