Made available in DSpace on 2016-08-10T10:55:21Z (GMT). No. of bitstreams: 1 ANNELISE CARRILHO CORREA DE CASTRO.pdf: 753705 bytes, checksum: 5d1101ab7100c09cec08b3f615f42a08 (MD5) Previous issue date: 2007-11-21 / Nifedipine is a diidropirine widely used for the control of arterial hypertension, wich because of its vessel dilating, in particular for the blockade by the entry of calcium. However, the chronic use of this calcium channel blocker is associated with the gingival overgrowth, resulting in the esthetic, phonetic and mastication problems. Data from the literature aren t unanimous in suggesting that cells density alterations of gingival tissues might be caused by nifedipine. The aim of this study was to analyze the variations in mast cells densities and associated with collagen and vasculature degrees of the gingival tissues by effect of nifedipine. In order to do so, fourteen samples of gingival tissue of patients undergoing chronic treatment with nifedipine were obtained. For comparative purposes, fifteen samples of gingival tissues of healthy patients who did not use drugs associated with gingival overgrowth were used. The samples were analysed in the department of oral pathology, Federal University of Goiás. The histochemical analysis of the collagen degree was made using picrosirius staining. To evaluate mast cells and blood vessels density, the samples were processed by standard immunoperoxidase immunohistochemical technique using mast cell tryptase and CD31 antibodies. The results showed that the number of tryptase-positive mast cells in nifedipine group was significantly higher than the number of tryptasepositive mast cells in the control group (Mann-Whitney test, P=0,02). However, there wasn t relationship between mast cells density and the degree of angiogenesis (Pearson test, P=0,3). The number of tryptase-positive mast cells was not correlated with collagen degree (Spearman test, P=0,6). Also there wasn t relationship between mast cells density and dose or duration of the nifedipine therapy (Pearson test, P=0,2 and P=0,7). Microscopic alterations observed in the connective tissue of nifedipine users suggest that this drug might be associated to alterations observed in tryptase-positive mast cells density. / A nifedipina é uma diidropiridina amplamente utilizada no tratamento antihipertensivo devido à sua ação vasodilatadora, especialmente, por bloquear o influxo de cálcio. Entretanto, o uso crônico deste bloqueador dos canais de cálcio está associado ao aumento da mucosa gengival, gerando problemas estéticos, fonéticos e mastigatórios. Os dados da literatura não são unânimes em sugerir que a nifedipina possa resultar na alteração da densidade celular do tecido gengival. O presente trabalho teve como objetivo avaliar a densidade de mastócitos e sua relação com os processos de colagenização e vascularização no tecido gengival sob efeito da nifedipina. Para este fim, foram utilizadas 14 amostras de tecido gengival de pacientes usuários de nifedipina. Para fins comparativos, foram utilizadas 15 amostras de tecido gengival de indivíduos saudáveis. As amostras foram avaliadas no departamento de Patologia Bucal da Universidade Federal de Goiás. A análise histoquímica do grau de colagenização foi realizada por meio da coloração de picrosirius. Para a avaliação da densidade de mastócitos, foi realizado um estudo quantitativo destas células a partir da técnica imunoistoquímica com marcação pelo anticorpo anti-triptase. A mensuração da densidade de vasos sangüíneos foi avaliada através de técnica imunoistoquímica com marcação pelo anticorpo anti-CD 31. Os resultados revelaram que os pacientes usuários de nifedipina apresentavam um aumento estatisticamente significante do número de MCs-triptase+, quando comparados ao grupo controle (Mann-Whitney, P=0,02). No entanto, não houve correlação entre a densidade de vasos e a densidade de mastócitos (Teste de Pearson, P=0,3), assim como não houve correlação entre o grau de colagenização e a densidade de mastócitos (Teste de Spearman, P=0,6). Também não foi observada correlação entre a densidade de MCs e a dose e/ou duração da terapia com nifedipina (Teste de Pearson, P=0,2 e P=0,7, respectivamente). As alterações microscópicas observadas no tecido conjuntivo de pacientes usuários de nifedipina sugerem que esta medicação está relacionada às alterações na densidade dos MCs-triptase+.

Sam Sze Wing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 156-184). / Abstracts in English and Chinese. / Publications based on work in this thesis --- p.ii / Abstract --- p.iii / Acknowledgements --- p.vii / Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Corticosteroids --- p.2 / Chapter 1.1.1 --- Chemical Structure of Steroids --- p.3 / Chapter 1.1.2 --- Biosynthesis of Endogenous Corticosteroids --- p.3 / Chapter 1.1.2.1 --- Regulation of Cortisol synthesis and negative feedback system --- p.4 / Chapter 1.1.3 --- Biological Significance of Corticosteroids --- p.5 / Chapter 1.1.3.1 --- Involvement of corticosteroids as anti-inflammatory drugs --- p.6 / Chapter 1.1.3.2 --- Eicosanoid biosynthesis --- p.7 / Chapter 1.1.3.3 --- Lipoxygenase pathway --- p.9 / Chapter 1.1.3.4 --- Side-effects of prolonged use of corticosteroids --- p.9 / Chapter 1.2 --- Organisation of the Emetic Reflex --- p.11 / Chapter 1.2.1 --- Motor Pathway of Emetic Reflex --- p.12 / Chapter 1.2.1.1 --- Retching and vomiting --- p.12 / Chapter 1.2.1.2 --- Nausea --- p.13 / Chapter 1.2.2 --- Components of the Emetic Reflex --- p.14 / Chapter 1.2.2.1 --- The vomiting centre (VC) --- p.15 / Chapter 1.2.2.2 --- Area postrema (AP) / Chemoreceptor trigger zone (CTZ) --- p.15 / Chapter 1.2.2.3 --- The nucleus tractus solitarius (NTS) --- p.17 / Chapter 1.2.2.4 --- Gastrointestinal tract and vagus nerves --- p.17 / Chapter 1.2.2.5 --- Neurotransmitter receptors --- p.18 / Chapter 1.3 --- Chemotherapy-Induced Emesis --- p.19 / Chapter 1.3.1 --- Cancer as a cause of mortality in Man --- p.20 / Chapter 1.3.2 --- Chemotherapeutic Agents --- p.20 / Chapter 1.3.2.1 --- Different classes --- p.20 / Chapter 1.3.2.2 --- Emetogenic potential --- p.21 / Chapter 1.3.3 --- Cisplatin-Induced Emesis --- p.23 / Chapter 1.3.3.1 --- Unfavourable effects associated with chemotherapy-induced nausea and emesis --- p.24 / Chapter 1.3.3.2 --- Anticipatory nausea and vomiting --- p.24 / Chapter 1.3.3.3 --- Profile of cisplatin-induced emesis --- p.25 / Chapter 1.3.4 --- Animal Models of Cisplatin-Induced Acute and Delayed Emesis --- p.26 / Chapter 1.3.5 --- Mechanisms and Pathways Involves in Chemotherapy-Induced Emesis --- p.28 / Chapter 1.3.6 --- Anti-Emetic Drugs for the Treatment of Chemotherapy-Induced Emesis --- p.31 / Chapter 1.3.6.1 --- 5-HT3 receptor antagonists --- p.31 / Chapter 1.3.6.2 --- Dopamine receptor antagonists --- p.33 / Chapter 1.3.6.3 --- Benzodiazepines --- p.35 / Chapter 1.3.6.4 --- Cannabinoids --- p.35 / Chapter 1.3.6.5 --- Antihistamines and anticholinergics --- p.35 / Chapter 1.3.6.6 --- NK1 receptor antagonists --- p.37 / Chapter 1.3.6.7 --- Corticosteroids --- p.38 / Chapter 1.3.6.8 --- Multi-agent anti-emetic regimens --- p.39 / Chapter 1.4 --- Motion-Induced Emesis --- p.41 / Chapter 1.4.1 --- Incidence --- p.42 / Chapter 1.4.2 --- Mechanisms and Pathways Involved in Motion Sickness --- p.43 / Chapter 1.4.2.1 --- Importance of the vestibular apparatus --- p.44 / Chapter 1.4.2.2 --- Importance of the area postrema --- p.45 / Chapter 1.4.2.3 --- The nucleus tractus solitarius --- p.46 / Chapter 1.4.2.4 --- Hormone and neurotransmitters --- p.46 / Chapter 1.4.3 --- Animal models in Motion-Induced Emesis --- p.47 / Chapter 1.4.4 --- Anti-Emetic Drugs for the Treatment of Motion Sickness --- p.48 / Chapter 1.4.4.1 --- Anticholinergics --- p.49 / Chapter 1.4.4.2 --- Antihistamines --- p.49 / Chapter 1.4.4.3 --- Non-selective muscarinic and histamine receptor antagonists --- p.51 / Chapter 1.4.4.4 --- Sympathomimetics --- p.51 / Chapter 1.4.4.5 --- NK1i receptor antagonists --- p.51 / Chapter 1.4.4.6 --- 5-HT1A agonists --- p.52 / Chapter 1.4.4.7 --- 5-HT2 receptor agonist --- p.52 / Chapter 1.4.4.8 --- Arginine vasopressin (AVP) antagonists --- p.53 / Chapter 1.4.4.9 --- Opioid receptor agonists --- p.53 / Chapter 1.4.4.10 --- Dexamethasone and hormone levels --- p.54 / Chapter 1.4.4.11 --- Other anti-emetic drugs --- p.55 / Chapter 1.5 --- Aims of the Studies --- p.56 / Chapter 2 --- Methods --- p.59 / Chapter 2.1 --- Cisplatin-Induced Emesis Studies --- p.60 / Chapter 2.1.1 --- Animals --- p.60 / Chapter 2.1.2 --- Induction and Measurement of Emesis --- p.60 / Chapter 2.1.3 --- The Effects of Corticosteroids on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.63 / Chapter 2.1.4 --- "The Effects of Dexamethasone (1 mg/kg, i.p.) Administered as an Intervention Treatment on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.63 / Chapter 2.1.5 --- The Effects of Cortrosyn Depot (Tetracosactrin) on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.63 / Chapter 2.1.6 --- The Effects of Metyrapone on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.64 / Chapter 2.1.7 --- The Effects of Indomethacin on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.64 / Chapter 2.1.8 --- "The Effects of DFU and L-745,337 Administered as an Intervention Treatments on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.64 / Chapter 2.1.9 --- "The Effects of MK-886 (L-663,536) on Cisplatin-Induced Acute and Delayed Retching and Vomiting" --- p.65 / Chapter 2.1.10 --- The Effects of a Combination of Indomethacin and MK-886 on Cisplatin- Induced Acute and Delayed Retching and Vomiting --- p.65 / Chapter 2.1.11 --- Statistical Analysis --- p.66 / Chapter 2.2 --- Motion-Induced Emesis Studies --- p.67 / Chapter 2.2.1 --- Animals --- p.67 / Chapter 2.2.2 --- Measurement of Emesis --- p.67 / Chapter 2.2.3 --- Induction of Emesis in Motion-Naive Suncus murinus: Effects of Glucocorticoids --- p.68 / Chapter 2.2.4 --- Induction of Emesis in Motion-Sensitive Suncus murinus: Effects of Dexamethasone --- p.70 / Chapter 2.2.5 --- Preparation of Serum --- p.72 / Chapter 2.2.6 --- Measurement of Serum Cortisol by Enzyme-Linked Immunoassay (ELISA) --- p.72 / Chapter 2.2.6.1 --- Immunoassay kit --- p.72 / Chapter 2.2.6.2 --- Assay procedures --- p.73 / Chapter 2.2.7 --- Measurement of Serum Adrenocorticotrophin (ACTH) by Radioimmunoassay (RIA) --- p.75 / Chapter 2.2.7.1 --- Immunoassay kit --- p.75 / Chapter 2.2.7.2 --- Assay procedures --- p.76 / Chapter 2.2.8 --- Statistical Analysis --- p.79 / Chapter 3 --- Results --- p.81 / Chapter 3.1 --- Cisplatin-Induced Emesis --- p.82 / Chapter 3.1.1 --- General Profile of Emesis Induced by Cisplatin --- p.82 / Chapter 3.1.2 --- Antagonism of Cisplatin-Induced Emesis by Corticosteroids --- p.82 / Chapter 3.1.3 --- "The Effect of Dexamethasone (1 mg/kg, i.p.) Administered as an Intervention Treatment on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.84 / Chapter 3.1.4 --- The Effect of Cortrosyn Depot (Tetracosactrin) on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.85 / Chapter 3.1.5 --- The Effect of Metyrapone on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.85 / Chapter 3.1.6 --- "The Effect of Indomethacin, DFU and L-745,337 on Cisplatin-Induced Acute and Delayed Retching and Vomiting" --- p.86 / Chapter 3.1.7 --- The Effect of MK-886 on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.88 / Chapter 3.1.8 --- The Effect of Combination of Indomethacin and MK-886 on Cisplatin- Induced Acute and Delayed Retching and Vomiting --- p.89 / Chapter 3.2 --- Motion-Induced Emesis --- p.91 / Chapter 3.2.1 --- General Effect of Motion on Serum Cortisol and ACTH Levelsin Motion Naive Suncus murinus --- p.91 / Chapter 3.2.2 --- The Effect of Glucocorticoids on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion-Naive Male Suncus murinus --- p.92 / Chapter 3.2.2.1 --- Effect of dexamethasone --- p.92 / Chapter 3.2.2.2 --- Effect of betamethasone --- p.93 / Chapter 3.2.2.3 --- Effect of methylprednisolone --- p.93 / Chapter 3.2.3 --- The Effect of Glucocorticoids on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion Naive Female Suncus murinus --- p.94 / Chapter 3.2.3.1 --- Effect of dexamethasone --- p.94 / Chapter 3.2.3.2 --- Effect of betamethasone --- p.95 / Chapter 3.2.3.3 --- Effect of methylprednisolone --- p.95 / Chapter 3.2.4 --- The Effect of Dexamethasone on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion-Sensitive Suncus murinus --- p.96 / Chapter 3.2.4.1 --- Effect of dexamethasone on male motion-sensitive animals --- p.97 / Chapter 3.2.4.2 --- Effect of dexamethasone on female motion-sensitive animals --- p.97 / Chapter 4 --- Discussion --- p.131 / Chapter 4.1 --- "Cisplatin (5 mg/kg, i.p.)-Induced Emesis in Control Animals" --- p.132 / Chapter 4.2 --- Anti-Emetic Action of Corticosteroids in the Ferret --- p.133 / Chapter 4.3 --- Metyrapone Study --- p.138 / Chapter 4.4 --- Cortrosyn Depot Study --- p.139 / Chapter 4.5 --- Role of Cycloxygenase --- p.141 / Chapter 4.6 --- Role of 5-Lipoxygenase --- p.143 / Chapter 4.7 --- Duel Inhibition of Cycloxygenase and 5-Lipoxygenase --- p.144 / Chapter 4.8 --- Anti-Emetic Potential of Glucocorticoids in Suncus murinus --- p.145 / Chapter 4.9 --- General Summary --- p.149 / Appendix I --- p.152 / Appendix II --- p.154 / References --- p.156

Tingan Chen. / "March 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 100-142). / 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.

Yuen Mong Ting. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 155-169). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract (English) --- p.ii / Abstract (Chinese) --- p.v / Contents --- p.vi / Chapter Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Developmental biology of the prostate --- p.1 / Chapter 1.1.1 --- Development of the prostate gland in humans and rodents --- p.1 / Chapter 1.1.2 --- Mesenchymal-epithelial interaction --- p.2 / Chapter 1.2 --- Overview of the endocrinology of prostate --- p.3 / Chapter 1.3 --- Estrogen in male and prostate gland --- p.4 / Chapter 1.3.1 --- Stimulating effect of estrogen on prostate gland --- p.4 / Chapter 1.3.2 --- Inhibitory effect of estrogen on prostate gland --- p.5 / Chapter 1.4 --- Study of the role of estrogen receptors in prostate gland with the use of estrogen receptor knockout mice --- p.6 / Chapter 1.4.1 --- The two isoforms of estrogen receptors (ER): ERα and ERβ --- p.6 / Chapter 1.4.2 --- The use of estrogen receptor knockout mice for the study of ER --- p.7 / Chapter 1.5 --- Estrogen as a carcinogen --- p.8 / Chapter 1.5.1 --- Formation of DNA adducts --- p.8 / Chapter 1.5.2 --- Formation of oxidants --- p.9 / Chapter 1.5.3 --- Estrogen as a microtubule-disrupting agent --- p.10 / Chapter 1.6 --- Estrogen carcinogenicity in animal models --- p.11 / Chapter 1.6.1 --- Syrian golden hamster model --- p.11 / Chapter 1.6.2 --- Rat model --- p.12 / Chapter 1.7 --- Animal models of prostate cancer by hormonal induction --- p.12 / Chapter 1.7.1 --- Canine model --- p.13 / Chapter 1.7.2 --- Noble rat model --- p.13 / Chapter 1.7.3 --- Sprague-Dawley rat model --- p.15 / Chapter 1.7.4 --- Wistar and F344 rat model --- p.15 / Chapter 1.8 --- Perinatal estrogen exposure and prostate development --- p.16 / Chapter 1.8.1 --- Prenatal estrogen exposure --- p.15 / Chapter 1.8.2 --- Neonatal estrogen exposure --- p.17 / Chapter 1.9 --- Therapeutic use of synthetic estrogen --- p.18 / Chapter 1.9.1 --- Use of diethylstilbestrol in treating prostate cancer --- p.18 / Chapter 1.9.2 --- Use of diethylstilbestrol during pregnancy --- p.19 / Chapter 1.10 --- Estrogen contamination in food --- p.20 / Chapter 1.10.1 --- Estrogen in milk and dairy products --- p.20 / Chapter 1.10.2 --- Estrogen in meat --- p.21 / Figure 1.1 --- p.23 / Chapter Chapter 2. --- Materials and methods --- p.25 / Chapter 2.1 --- In vitro study of estrogen carcninogenicity in normal prostatic cell line --- p.25 / Chapter 2.1.1 --- NRP-152 cell line --- p.25 / Chapter 2.1.2 --- In vitro estrogen treatment on NRP-152 cells --- p.25 / Chapter 2.1.3 --- Colony formation by soft agar assay --- p.27 / Chapter 2.1.4 --- Determination of growth parameters of estrogen-treated and untreated NRP-152 cells --- p.29 / Chapter 2.1.5 --- Gene expression profiling in estrogen-transformed and untreated parental NRP-152 cells by cDNA microarray --- p.30 / Chapter 2.1.6 --- Immunohistochemistry of cultured cells --- p.34 / Chapter 2.1.7 --- Immunofluorescence on cultured cells --- p.36 / Chapter 2.1.8 --- Electron microscopy of the estrogen-transformed and untreated parental NRP-152 cells --- p.37 / Chapter 2.1.9 --- Tumorigenicity in nude mice --- p.38 / Chapter 2.1.10 --- Protein expressions and Western blottings in estrogen-transformed and untreated parental NRP-152 cells --- p.39 / Chapter 2.2 --- In vivo study of estrorgen carcinogenicity in rat protstate gland --- p.41 / Chapter 2.2.1 --- Origin and supply of Noble rats --- p.41 / Chapter 2.2.2 --- Perinatal estrogen imprinting on male Noble rats with diethylstilbestrol --- p.42 / Chapter 2.2.3 --- Long-term hormonal treatment with sex steroids on male Noble rats at adulthood --- p.43 / Chapter 2.2.4 --- Morphological study of Noble rat prostates --- p.44 / Chapter 2.2.5 --- Protein expressions by immunohistochemistry in estrogen-primed and hormone-treated Noble rat prostates --- p.45 / Tables 2.1 -2.2 --- p.48 / Chapter Chapter 3. --- Results --- p.50 / Chapter 3.1 --- In vitro study --- p.50 / Chapter 3.1.1 --- Dose selection for estrogen treatment of NRP-152 cells from cell proliferation assay --- p.50 / Chapter 3.1.2 --- Colony formation in soft agar --- p.50 / Chapter 3.1.3 --- Morphology of NRP-152 cells and the estrogen-transformed clones --- p.51 / Chapter 3.1.4 --- Study of growth parameters --- p.52 / Chapter 3.1.5 --- CDNA array analysis of differentia] gene pattern --- p.53 / Chapter 3.1.6 --- Immunohistochemistry of untreated parental and estrogen- transformed NRP-152 cells --- p.55 / Chapter 3.1.7 --- Electron microscopy --- p.58 / Chapter 3.1.8 --- Tumorigenicity of NRP-152 cells and the estrogen-transformed clones --- p.59 / Chapter 3.1.9 --- Western blottings --- p.59 / Chapter 3.2 --- In vivo study --- p.52 / Chapter 3.2.1 --- Survival of male Nobel rats during perinatal and long-term hormone treatment --- p.62 / Chapter 3.2.2 --- Histological studies of Noble rat prostates --- p.63 / Chapter 3.2.3 --- Immunohistochemistry of the hormone-treated and control Noble rat prostates --- p.65 / Figure 3.1.1 -3.1.44 --- p.73 / Figure 3.2.1 - 3.2.50 --- p.97 / Table 3.1 -3.4 --- p.117 / Chapter Chapter 4. --- Discussions --- p.121 / Chapter 4.1 --- The study on the transformation of cells and soft agar assay --- p.121 / Chapter 4.2 --- Growth patterns of the estrogen-transformed clones --- p.123 / Chapter 4.3 --- Altered differential gene expression --- p.124 / Chapter 4.3.1 --- TUBA --- p.124 / Chapter 4.3.2 --- PTEN --- p.125 / Chapter 4.3.3 --- RAP 1A --- p.126 / Chapter 4.3.4 --- BRCA2 --- p.126 / Chapter 4.4 --- Ultrastructural study in the estrogen-transformed and untreated parental NRP-152 cells --- p.127 / Chapter 4.5 --- Neoplastic lesions induced in prostates of estrogen-imprinted and long-term combined hormone treated Noble rats --- p.129 / Chapter 4.6 --- Altered protein expressions in estrogen-transformed NRP-152 cells and estrogen-imprinted and hormone-treated Noble rat prostates --- p.132 / Chapter 4.6.1 --- Alteration in steroid hormone receptors --- p.132 / Chapter 4.6.2 --- Alternation in cytoskeleton (tubulin-α) --- p.138 / Chapter 4.6.3 --- Alternation in PTEN --- p.141 / Chapter 4.6.4 --- Alternation in Rap1 --- p.143 / Chapter 4.6.5 --- Alternation in BRCA2 --- p.145 / Chapter 4.6.6 --- "Altered in scavenger enzyme (Superoxide dismutase, SOD-1)" --- p.147 / Chapter Chapter 5. --- Summary --- p.150 / Reference --- p.155

Cheung Shu Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 124-137). / Abstracts in English and Chinese. / Abstract (English) --- p.i / Abstract (Chinese) --- p.iii / Acknowledgements --- p.iv / Contents --- p.v / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Epidemiology of Breast Cancer --- p.1 / Chapter 1.1.1 --- Epidemiology of Breast Cancer in Females --- p.1 / Chapter 1.1.2 --- Incidence and Morality of Female Breast Cancer in Hong Kong --- p.2 / Chapter 1.1.3 --- Epidemiology of Breast Cancer in Males --- p.3 / Chapter 1.2 --- Risk Factors for Female Breast Cancer --- p.4 / Chapter 1.2.1 --- Genetic Risk Factors --- p.4 / Chapter 1.2.2 --- Hormonal Risk Factors --- p.6 / Chapter 1.2.2.1 --- Endogenous Hormonal Risk Factors --- p.7 / Chapter 1.2.2.2 --- Exogenous Hormonal Risk Factors --- p.8 / Chapter 1.2.3 --- Other Environmental Risk Factors --- p.9 / Chapter 1.3 --- Oncogenetic Basis of Female Breast Cancer --- p.10 / Chapter 1.4 --- Hormonal Basis of Female Breast Cancer --- p.12 / Chapter 1.4.1 --- Mechanisms of Hormone Action --- p.12 / Chapter 1.4.1.1 --- Estrogen and Progesterone --- p.12 / Chapter 1.4.1.2 --- Prolactin --- p.14 / Chapter 1.4.2 --- Hormonal Regulation of Normal Breast Development --- p.15 / Chapter 1.4.3 --- Hormonal Regulation of Breast Carcinogensis and Its Subsequent Progression --- p.17 / Chapter 1.4.3.1 --- Androgen --- p.17 / Chapter 1.4.3.2 --- Estrogen --- p.18 / Chapter 1.4.3.3 --- Progesterone --- p.20 / Chapter 1.4.3.4 --- Prolactin --- p.22 / Chapter 1.5 --- Animal Models for Breast Cancer --- p.23 / Chapter 1.5.1 --- Mouse Models --- p.24 / Chapter 1.5.2 --- Rat Models --- p.25 / Chapter 1.5.2.1 --- Carcinogen Induced Rat Models --- p.26 / Chapter 1.5.2.2 --- Hormone Induced Rat Models --- p.28 / Chapter 1.5.2.3 --- Spontaneously Developed Rat Models --- p.31 / Chapter 1.6 --- Aims of Study --- p.34 / Tables and Figures --- p.35 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- Origin and Supply of Noble Rats --- p.37 / Chapter 2.2 --- Supply of Materials --- p.37 / Chapter 2.3 --- Induction of Mammary Tumors by Singe Dose of Chemical Carcinogens in Female Rats --- p.38 / Chapter 2.3.1 --- Induction by 7，12-Dimethylbenz[a]anthracene in Female Noble Rats --- p.38 / Chapter 2.3.2 --- Induction by N-Methyl-N-Nitrosourea in Female Sprague- Dawley Rats --- p.38 / Chapter 2.4 --- Induction of Mammary Tumors by Long-Term Treatments with Steroid Hormone --- p.39 / Chapter 2.4.1 --- Preparation of Steroid Hormone-filled Silastic® Tubings --- p.39 / Chapter 2.4.2 --- Surgical Implantation of Silastic® Tubings --- p.40 / Chapter 2.4.3 --- Protocols of Hormonal Treatments --- p.40 / Chapter 2.5 --- Collection of Spontaneously Developed Mammary Tumors in Noble Rats --- p.41 / Chapter 2.6 --- Transplantation of Spontaneously Developed Mammary Tumors into Noble Rats --- p.41 / Chapter 2.7 --- Bilateral Ovariectomy of Female Noble Rats bearing Spontaneously Developed Mammary Tumors --- p.42 / Chapter 2.8 --- Measurement of Mammary Tumor Growth --- p.43 / Chapter 2.9 --- Whole Mount Preparation of the Hormone-Treated Mammary Glands in Noble Rats --- p.44 / Chapter 2.10 --- Histological Examination of Mammary Gland and Tumors in Noble Rats --- p.45 / Chapter 2.11 --- Detection of Protein Expression of Hormone Receptors in Normal Mammary Glands and Mammary Tumors of Noble Rats --- p.45 / Chapter 2.11.1 --- Antibodies --- p.45 / Chapter 2.11.2 --- Immunohistochemistry --- p.47 / Chapter 2.11.3 --- "Protein extraction, SDS-PAGE and western blotting analysis" --- p.48 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Gross Appearance of Mammary Tumors --- p.51 / Chapter 3.2 --- Incidence Rate of Mammary Tumors --- p.53 / Chapter 3.2.1 --- Spontaneously Developed Mammary Tumors in Noble Rats --- p.53 / Chapter 3.2.2 --- Hormone Induced Mammary Tumors in Female Noble Rats --- p.53 / Chapter 3.2.3 --- DMBA Induced Mammary Tumors in Female Noble Rats --- p.54 / Chapter 3.2.4 --- NMU Induced Mammary Tumors in Female SD Rats --- p.54 / Chapter 3.3 --- Histology of Normal and Lactating Mammary Glands in Female Noble Rats --- p.54 / Chapter 3.4 --- Histopathology of Mammary Tumors --- p.55 / Chapter 3.4.1 --- Histopathology of Spontaneously Developed Mammary Tumors in Noble Rats --- p.55 / Chapter 3.4.2 --- Histopathology of Hormone Induced Mammary Tumors in Female Noble Rats --- p.59 / Chapter 3.4.3 --- Histopathology of DMBA Induced Mammary Tumors in Female Noble Rats --- p.60 / Chapter 3.4.4 --- Histopathology of NMU Induced Mammary Tumors in Female SD Rat --- p.60 / Chapter 3.5 --- Whole Mount Preparation of Mammary Glands under Hormonal Treatments --- p.61 / Chapter 3.6 --- Effects of Bilateral Ovariectomy on the Growth of Spontaneously Developed Mammary Tumors --- p.61 / Chapter 3.7 --- Transplanability of the Spontaneously Developed Mammary Tumors in Noble Rats --- p.62 / Chapter 3.8 --- Examination of the Malignancy of Mammary Tumors by Immunohistochemical analysis of Epithelial Keratin Expression --- p.62 / Chapter 3.9 --- Immunohistochemical Analysis of Expression and Localization of Hormone Receptor Protein in Normal and Neoplastic Mammary Tissues of Female Noble Rats --- p.63 / Chapter 3.9.1 --- Expression and Localization of Hormone Receptors in Control Tissue --- p.63 / Chapter 3.9.2 --- Expression and Localization of Estrogen Receptor α --- p.64 / Chapter 3.9.3 --- Expression and Localization of Estrogen Receptor β --- p.65 / Chapter 3.9.4 --- Expression and Localization of Progesterone Receptor --- p.65 / Chapter 3.9.5 --- Expression and Localization of Androgen Receptor --- p.66 / Chapter 3.9.6 --- Expression and Localization of Prolactin Receptor --- p.66 / Chapter 3.10 --- Western Blot Analysis of Expression of Hormone Receptor Proteins in Normal and Neoplastic Mammary Tissues of Female Noble Rats - --- p.67 / Chapter 3.10.1 --- Expression of Estrogen Receptor α --- p.67 / Chapter 3.10.2 --- Expression of Estrogen Receptorβ --- p.68 / Chapter 3.10.3 --- Expression of Progesterone Receptor --- p.68 / Chapter 3.10.4 --- Expression of Androgen Receptor --- p.69 / Chapter 3.10.5 --- Expression of Prolactin Receptor --- p.69 / Figures and Tables --- p.71 / Chapter Chapter 4 --- Discussions / Chapter 4.1 --- Comparison of the Incidence Rate of Spontaneously developed Mammary Tumors in Noble Rats with the Previously Reported Incidence Rate --- p.102 / Chapter 4.2 --- Comparison of the Incidence rate of Spontaneously Developed Mammary Tumors in Noble Rats with the Incidence Rate in Other Rat Strains --- p.103 / Chapter 4.3 --- Crucial Factors Influencing the Incidence Rate of Spontaneously Developed Mammary Tumors in Noble Rats --- p.104 / Chapter 4.4 --- Comparison of the T+E2 Induced Mammary Tumors with the T+DES Induced Mammary Tumors in Female Noble Rats --- p.105 / Chapter 4.5 --- Comparison of the Incidence Rate & Latency Period of the Hormone Induced Mammary Tumors in Noble Rats with the Previously Reported Data --- p.106 / Chapter 4.6 --- Comparison of the Phenotypic Behaviors in Spontaneously Developed Mammary Tumors with the Hormone Induced Mammary Tumors in Female Noble Rats --- p.107 / Chapter 4.7 --- Comparison of the Behaviors of Carcinogen Induced Mammary Tumors with Spontaneously Developed & Hormone Induced Mammary Tumors in Female Noble Rats --- p.109 / Chapter 4.8 --- "Comparison of Expression Patterns of Hormone Receptor Proteins in Spontaneously Developed, Hormone Induced & Carcinogen Induced Mammary Tumors in Female Noble Rats" --- p.111 / Chapter 4.9 --- "Expressions of ERα & ERβ Proteins in Spontaneously Developed, Hormone Induced and Carcinogen Induced Mammary Tumors in Female Noble Rats" --- p.112 / Chapter 4.10 --- "Expressions of PR Proteins in Spontaneously Developed, Hormone Induced and Carcinogen Induced Mammary Tumors in Female Noble Rats" --- p.115 / Chapter 4.11 --- "Expressions of AR Proteins in Spontaneously Developed, Hormone Induced and Carcinogen Induced Mammary Tumors in Female Noble Rats" --- p.116 / Chapter 4.12 --- "Expressions of PRLR Proteins in Spontaneously Developed, Hormone Induced and Carcinogen Induced Mammary Tumors in Female Noble Rats" --- p.120 / Chapter Chapter 5 --- Conclusions --- p.123 / References --- p.124

O presente trabalho descreve o preparo, a caracterização e o uso de eletrodo modificado com polímero de azul de metileno (PMB) imobilizado sobre a superfície de eletrodo de carbono vítreo (GCE-PMB) na análise do herbicida glifosato. O método utilizado para a preparação dos filmes do PMB foi a eletropolimerização. Os filmes preparados por este método apresentam características diferenciadas tais como robustez, estabilidade e propriedade redox satisfatória. As condições experimentais otimizadas foram a velocidade de varredura (50 mV s-1), o intervalo de potencial (-0,4 a +1,2 V), o número de ciclos (30) e o pH da solução do eletrólito suporte (pH 8). A solução de eletrólito suporte foi preparada a partir das soluções de tampão fosfato (0,05 mol L-1) e NaNO3 (0,1 mol L-1), pH 8. A mesma foi utilizada no preparo da solução de azul de metileno (MB) (0,25 x 10-3 mol L-1), no pré-tratamento do eletrodo de carbono vítreo (GC) por voltametria cíclica (CV) e no preparo de soluções para os estudos iniciais com o GCE-PMB. O pré-tratamento da superfície do eletrodo de GC foi realizado aplicando + 0,9 V por 240 s seguido de várias varreduras cíclicas de -0,4 a +1,0 V com velocidade de varredura de 50 mV s-1 até obter um perfil estável do voltamograma do eletrodo. Após o preparo do GCE-PMB, a atividade eletrocatalítica do eletrodo foi investigada para o Ácido Ascórbico (AA) e a L-Cisteína (L-Cys) por CV de -0,4 a +0,6. Foi observado aumento da corrente de pico e diminuição do sobrepotencial em relação ao eletrodo de GC. Nos estudos na presença do glifosato, o GCE-PMB apresentou resposta eletroquímica direta, por voltametria cíclica, para o glifosato (1,0 x 10-3 mol L-1) em solução de KCl 0,1 mol L-1 (pH 5,3) de -0,4 a +0,6 V e velocidade de varredura 50 mV s-1. A resposta voltamétrica apresentou picos anódico e catódico em 0,2 e 0, respectivamente. Para os estudos realizados por meio da técnica de voltametria de onda quadrada (SWV), os parâmetros freqüência, amplitude e incremento de varredura foram otimizados. A partir desses estudos foi possível obter informações relevantes sobre a interação do GCE-PMB com o glifosato. Os resultados mostraram que é possível observar a eletroatividade do herbicida glifosato sobre uma superfície eletródica sem a presença de metais como agentes complexantes. / This work describes the preparation, characterization and the use of the modified electrode with methylene blue polymer (PMB) immobilized onto the surface of glassy carbon electrode (GCE-PMB) in the analysis of the herbicide glyphosate. Concerning the methodology aspects, the method used for the preparation of the films PMB was the electropolymerization. The films prepared by this method present a differentiated characteristic such as robustness, stability and good redox properties. The optimized experimental conditions are the scan rate (50 mV s-1), the potential range (-0.4 to +1.2 V), the number of cycles (30) and the pH of the supporting electrolyte (pH 8). The supporting electrolyte solution was prepared from phosphate buffer solutions (0.05 mol L-1) and NaNO3 (0.1 mol L-1), pH 8. The same solution was used to prepare the solution of methylene blue (MB) (0.25 x 10-3 mol L-1), the pretreatment of the GC electrode by cyclic voltammetry (CV). It was also utilized in preparing solutions for the initial studies with GCE-PMB. The pre-treatment of the electrode surface of GC was performed, considering 0.9 V during 240 s, followed by several cyclic scans from -0.4 to 1.0 V (with scan rate of 50 mV s-1) until a stable profile of the voltammogram. After preparing the GCE-PMB, electrocatalytic activity it was investigated for Ascorbic Acid (AA) and L-Cysteine (L-Cys) by CV from -0.4 to +0.6 V. It was observed increase in peak current and decrease the overpotential comparing to glassy carbon electrodes. The GCE-PMB presented direct electrochemical response, for glyphosate (1 x 10-3 mol L-1) in KCl 0.1 mol L-1 (pH 5.3) from -0.4 to +0.6 V and scan rate 50 mV s-1. The voltammetric response showed anodic and cathodic peaks in 0.2 and 0, respectively. Using the square wave voltammetry (SWV), the parameters frequency, amplitude and scan increment were optimized. It was possible to find relevant information about the interaction between GCE-PMB and glyphosate. These results showed that is possible observe the electroactivity of glyphosate on a modified electrodic surface in absence of metals or complexing agents.

After the 1999 Kocaeli Earthquake, the use of chemically bonded post-installed anchors has seen a great growth for retrofits in Turkey. Currently, chemically bonded post-installed anchors are designed from related tables provided by adhesive manufacturers and a set of equations based on laboratory pullout tests on normal or high strength concretes. Unfortunately, concrete compressive strengths of existing buildings, which need retrofit for earthquake resistance, ranges within 5 to 16 MPa. The determination of tensile strength of chemically bonded anchors in low-strength concretes is an obvious prerequisite for the design and reliability of retrofit projects. Since chemically bonded anchors result in the failure of concrete, adhesive-concrete interface or anchored material, the ultimate resistance of anchor can be predicted through the sum of the contributions of concrete strength, properties of anchored material (which is steel for this work), and anchorage depth. In this work, all three factors and the predictions of current tables and equations related to anchorages are examined throughout site tests.

The specific interactions of macromolecules along with the activity of enzymes are central to all aspects of biology. It is well recognized that when the relative concentration or activity of macromolecules is perturbed, it can lead to human diseases. Thus, the development of simple methods for the detection of macromolecules and the activity of enzymes in complex environments is important for understanding biology. Moreover, the development of methods for measuring interactions allows for the testing of inhibitors that can be used as tools or drugs for improving human health. Towards this goal, a promising new method has been developed, which is the focus of this thesis, called split-protein reassembly or protein fragment complementation. In this method, a protein reporter, such as the green fluorescent protein or firefly luciferase, is dissected into two fragments, which are attached to designed adaptor proteins. The designed split-protein systems only produce a measurable signal, either fluorescence or luminescence, when a specific macromolecular interaction or activity is present. In this thesis, I have extended previous research on the direct detection of DNA using split-protein sensors utilizing a red fluorescent protein, dsRED from Discosoma that allows for multiplexed DNA detection. I have designed a new split-luciferase based sensor for detection of poly (ADP-ribose) or PAR, which plays a key role in the response to DNA damage and have applied it for monitoring the activity of poly (ADP-ribose) glycohydrolase that controls PAR levels in the cell. Furthermore, I have significantly expanded upon a three-hybrid split-luciferase system for identifying protein kinase inhibitors. I have designed and tested two orthogonal peptide based chemical inducers of dimerization based on BAD and p53mt conjugates. I have studied these chemically induced dimerization systems in detail in order to begin to provide a theoretical basis for the observed experimental results. Finally, in a less related area, I have developed methods for producing water soluble semiconductor nanoparticles called Quantum Dots (QDs), with potential application in biological imaging. I have developed methods for functionalizing the QDs with orthogonal peptides, which can be potentially used for the assembly of high affinity non-covalent QD targeted proteins.

The urban sprawl creates a gap between producers and consumers and the a sustainable circuitof nutrients and energy is difficult to maintain. Many times the waste that is created in urbanareas is not reused and the circuit is lost. In this project, wastewater treatment is looked atwith the view point that resource recovery is possible through energy production and reuse ofnutrients. In order to optimally run each process step at a wastewater treatment plant forimproved resource recovery, more knowledge is needed in order to not disregard the finaleffluent quality. The goal of this project was to develop a model in MATLAB/Simulink for achemically enhanced primary clarifier at a wastewater treatment plant. The potential ofproducing more biogas and reducing the aeration energy needed in the biological treatmentstep was looked at by focusing on describing the settling velocity of suspended solids.Experimental analysis on settling properties for solids was performed on sampled wastewaterentering the primary settler after changing the addition of chemicals prior in the process line.The wastewater samples were homogenized and then rapidly vacuum pumped up in a column.The solids in the column could thereafter settle and was retained in a cup at the bottom. Themass of total suspended solids (TSS) was classified in five different settling velocity classes,each class assigned a characteristic settling velocity. The experimental procedure followed theViCA's protocol (French acronym for Settling Velocity for Wastewater). A settler, much likethe secondary settler in the Benchmark Simulation Model No. 2 (BSM2), a 10 layer nonreactivetank was modeled. The mass balance in each layer of the settler was decided by thevertical solid flux in the tank and built on the characteristic settling velocity gained from theexperiments. Re-circulation of excess sludge from the subsequent steps at the plant showed toeffect the settling properties of the sludge in the primary settler. The components of TSSshowed to have the largest effect on the distribution of settling velocity. The variation in doseof both coagulant and cationic polymer prior the primary settling tank showed to effect theparticle settling distribution somewhat. A first simulation with an applicable dynamic influentscenario was run. Despite any proper calibration the model gave fairly good predictions ofmeasured TSS in the effluent and sludge outtake water. / När urbana områden växer uppstår svårigheter i att bibehålla ett hållbart kretslopp av energioch näringsämnen. Avståndet mellan producent och konsument ökar och många gångeråteranvänds inte det avfall som städerna producerar och det hållbara kretsloppet bryts. Dettaprojekt har fokuserat på resursåteranvändningen i avloppsvattenhanteringen genommöjligheterna som finns i energiproduktion i form av biogas samt återanvändning avnäringsämnen genom slamåterförsel. Mer kunskap behövs inom varje processteg för attoptimalt använda avloppsreningsverk för förbättrad resurs-återvinning så att inte utgåendevattenkvalitet blir lidande. Målet med projektet var att utveckla en modell iMATLAB/Simulink för primärsedimentering med kemisk fällning. Experimentelltanalyserades sedimentationsegenskaperna hos primärslam genom provtagning avavloppsvatten inkommande till försedimenteringen efter tillsatser av fällnings-kemikalier.Proverna homogeniserades och vakuumpumpades sedan snabbt upp i en kolonn. Detpartikulära materialet i kolonnen kunde därefter sedimentera och fångades upp i en kopp ibotten. Den sedimenterade massan av totalt suspenderat material (TSS) klassificerades i femolika sedimenteringshastighetsklasser och varje klass tilldelades en karakteristisksedimentationshastighet Det experimentella förfarandet följde ViCA’s protokoll (franskförkortning för sedimentationshastigheter för avloppsvatten). En modell av ensedimentationstank, ungefär som för sekundär-sedimenteringen i Benchmark SimulationModel No. 2 (BSM2), utvecklades som en 10 lager icke reaktiv tank. Massbalansen i varjelager bestämdes av det vertikala flödet av partiklar och beräknades med de experimentelltframtagna karakteristiska sedimentationshastigheterna. Återcirkulering av överskottsslam frånde efterföljande reningsstegen visade sig ha stor påverkan på slammetssedimentationsegenskaper i försedimenteringen. Typen av TSS-komponenter hade den störstainverkan på fördelningen av sedimentationshastigheter. Variationen i dos av bådefällningskemikalie och katjonspolymer före primär-sedimenteringstanken hade en visspåverkan på fördelningen. En första simulering med ett sannolikt dynamisk inflödesscenariokördes. Utan någon riktig kalibrering av modellen gav den ändå en relativt realistisk prognospå TSS i utgående vatten och i slamuttaget. / I samarbete med forskningsgruppen ModelEAU, Quebec, Kanada

In this thesis, chemically reacting flows are studied mainly for detonation problems under 1D, cylindrical and spherical symmetry conditions. The mathematical formulation of chemically reacting, inviscid, unsteady flows with species conservation equations and finite-rate chemistry is described. The Euler equations with finite-rate chemistry are discretized by Finite-Volume method and solved implicitly by using a time-spliting method. Inviscid fluxes are computed using Roe Flux Difference Splitting Model. The numerical solution is implemented in parallel using domain decomposition and PVM library routines for inter-process communication. The solution algorithm is validated first against the numerical and experimental data for a shock tube problem with and without chemical reactions and for a cylindrical and spherical propagation of a shock wave. 1D, cylindrically and spherically symmetric detonations of H2:O2:Ar mixture are studied next.