Kan Ka-wing. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. [161]-[184]). / 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.

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

Lau Hoi Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 134-157). / Abstracts in English and Chinese. / PUBLICATIONS BASED ON WORK IN THIS THESIS --- p.I / ABSTRACT --- p.II / ACKNOWLEDGEMENTS --- p.VI / TABLE OF CONTENTS --- p.VIII / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Emesis --- p.3 / Chapter 1.2.1 --- Introduction --- p.3 / Chapter 1.2.2 --- Retching & Vomiting --- p.3 / Chapter 1.2.3 --- Nausea --- p.4 / Chapter 1.2.4 --- Motor Components of Emetic Reflex --- p.5 / Chapter 1.2.4.1 --- Pre-ejection Phase --- p.5 / Chapter 1.2.4.2 --- Ejection Phase --- p.5 / Chapter 1.2.4.3 --- Post-ejection Phase --- p.6 / Chapter 1.2.5 --- Components of Emetic Reflex --- p.6 / Chapter 1.2.5.1 --- Area Postrema (AP) --- p.6 / Chapter 1.2.5.2 --- Nucleus Tractus Solitarius (NTS) --- p.7 / Chapter 1.2.5.3 --- Vomiting Centre --- p.8 / Chapter 1.2.5.4 --- Vestibular System --- p.10 / Chapter 1.2.5.5 --- Abdominal Visceral Afferents --- p.10 / Chapter 1.2.5.6 --- Forebrain --- p.11 / Chapter 1.2.6 --- Neurotransmitters & Receptors --- p.12 / Chapter 1.2.7 --- Anti-emetics --- p.13 / Chapter 1.3 --- Models of Nausea --- p.16 / Chapter 1.3.1 --- Introduction --- p.16 / Chapter 1.3.2 --- Conditioned Taste Aversion --- p.18 / Chapter 1.3.3 --- Pica Behaviour --- p.20 / Chapter 1.3.4 --- Studies of the Involvement of Vasopressin --- p.21 / Chapter 1.3.5 --- Tachygastria --- p.24 / Chapter 1.3.6 --- Locomotor Activity --- p.26 / Chapter 1.4 --- Markers of Neuronal Activity --- p.27 / Chapter 1.4.1 --- General Comments --- p.27 / Chapter 1.4.2 --- c-fos Expression as a Marker of Neuronal Activity --- p.28 / Chapter 1.4.2.1 --- What is c-fos? --- p.28 / Chapter 1.4.2.2 --- Regulation of c-fos Expression --- p.30 / Chapter 1.4.2.2.1 --- Calcium Response Element --- p.31 / Chapter 1.4.2.2.2 --- Serum Response Element --- p.32 / Chapter 1.4.2.3 --- Types of Receptors Involved in c-fos Expression --- p.32 / Chapter 1.4.2.4 --- Feasibility of Using c-fos Expression as Marker of Cellular Activity --- p.36 / Chapter 1.4.2.5 --- Identification of Emetic Pathway by c-fos Immunohistochemistry --- p.36 / Chapter 1.5 --- Aims & Objectives --- p.37 / Chapter CHAPTER 2 --- METHODS --- p.42 / Chapter 2.1 --- Animals --- p.42 / Chapter 2.1.1 --- Ferrets --- p.42 / Chapter 2.1.2 --- Suncus murinus --- p.42 / Chapter 2.2 --- Measurement of Animal Behaviour --- p.43 / Chapter 2.2.1 --- Experiment Design --- p.43 / Chapter 2.2.2 --- Recording of Animal Behaviour --- p.43 / Chapter 2.2.3 --- Calibration of Equipment Used to Record Spontaneous Locomotor Activity --- p.44 / Chapter 2.2.4 --- Behaviour Recorded by the Observer --- p.45 / Chapter 2.3 --- Administration of Drugs --- p.46 / Chapter 2.3.1 --- Ferrets --- p.46 / Chapter 2.3.1.1 --- General Comments --- p.46 / Chapter 2.3.1.2 --- Drug Antagonism Studies --- p.47 / Chapter 2.3.2 --- Suncus murinus --- p.47 / Chapter 2.3.2.1 --- General Comments --- p.47 / Chapter 2.3.2.2 --- Dose-Response Studies --- p.48 / Chapter 2.3.2.3 --- Drug Antagonism Studies --- p.48 / Chapter 2.4 --- c-fos Expression Studies in Ferret Brainstems --- p.50 / Chapter 2.4.1 --- Animals and Anaesthesia --- p.50 / Chapter 2.4.2 --- Perfusion and fixation --- p.50 / Chapter 2.4.3 --- Dehydration of brains --- p.51 / Chapter 2.4.4 --- Embedding of tissue --- p.52 / Chapter 2.4.5 --- Sectioning --- p.52 / Chapter 2.4.6 --- Staining --- p.52 / Chapter 2.4.7 --- Antibodies used --- p.55 / Chapter 2.4.8 --- Positive Control Slides --- p.55 / Chapter 2.5 --- Experimental Design and Statistics --- p.56 / Chapter 2.5.1 --- Randomization of Treatments --- p.56 / Chapter 2.5.2 --- Statistics --- p.57 / Chapter 2.5.2.1 --- Ferrets --- p.57 / Chapter 2.5.2.2 --- Suncus murinus --- p.59 / Chapter 2.6 --- Drugs and Chemicals Used --- p.60 / Chapter 2.6.1 --- Drugs Used --- p.60 / Chapter 2.6.2 --- Chemicals Used --- p.62 / Chapter CHAPTER 3 --- RESULTS --- p.63 / Chapter 3.1 --- Ferret --- p.63 / Chapter 3.1.1 --- "The Effect of Ondansetron and CP-99,994 on Emesis and Locomotor Activity Changes Induced by Cisplatin in the Ferret" --- p.63 / Chapter 3.1.2 --- The Effect of Domperidone on Emesis and Locomotor Activity Changes Induced by Apomorphine in the Ferret --- p.69 / Chapter 3.1.3 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Apomorphine in the Ferret" --- p.74 / Chapter 3.1.4 --- c-fos Expression Studies in Ferret Brainstems --- p.79 / Chapter 3.1.4.1 --- Cisplatin-treated Ferrets --- p.79 / Chapter 3.1.4.2 --- Positive Control Slides --- p.84 / Chapter 3.2 --- Suncus murinus --- p.88 / Chapter 3.2.1 --- The Emetic Potential of Nicotine and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.88 / Chapter 3.2.2 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Nicotine in Suncus murinus" --- p.92 / Chapter 3.2.3 --- The Emetic Potential of Copper Sulphate and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.95 / Chapter 3.2.4 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Copper Sulphate in Suncus murinus" --- p.98 / Chapter 3.2.5 --- The Emetic Potential of Cisplatin and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.101 / Chapter 3.2.6 --- The Effect of Ondansetron on Emesis and Locomotor Activity Changes Induced by Cisplatin in Suncus murinus --- p.104 / Chapter 3.2.7 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Cisplatin in Suncus murinus" --- p.107 / Chapter 3.2.8 --- "The Effects of Ondansetron and CP-99,994 on Locomotor Activity in Suncus murinus" --- p.110 / Chapter CHAPTER 4 --- DISCUSSION --- p.113 / Chapter CHAPTER 5 --- GENERAL SUMMARY --- p.130 / REFERENCES --- p.134

Made available in DSpace on 2015-07-22T20:50:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-07-30. Added 1 bitstream(s) on 2015-08-11T03:25:42Z : No. of bitstreams: 1 Publico-10756.pdf: 198016 bytes, checksum: b1b248dd88de1aeab5859b81fa05e4c2 (MD5) / INTRODUÇÃO: Os antagonistas 5HT-3 e corticosteróides são drogas importantes no controle da emese induzida por quimioterapia Apresentam controle de 50-80% da emese aguda porém controlam menos de 50% da emese tardia induzida por quimioterapia. Em estudo prévio realizado em nossa instituição, observou-se que o controle da emese tardia poderia ser melhorado com a omissão do segundo dia dos antagonistas 5HT-3. Reportamos aqui os resultados de um estudo fase III confirmando os achados prévios PACIENTES E MÉTODOS: Estudo fase III randomizado e duplo-cego foi realizado na FMABC Santo André/Brasil. Pacientes submetidos a esquemas quimioterápicos alta e moderadamente emetogênicos pela 1ª vez receberam Ondasetron 16mg e Dexametasona 20 mg IV antes da quimioterapia no Dia 1. Foram então randomizados em dois grupos. Grupo A recebeu metoclopramida VO 10mg 8/8hs, Granisetron VO 0,5mg/dia,e dexametasona VO 8mg /dia por 2 dias, a partir do dia 2 (dias 2 e 3). Metoclopramida VO 10 mg 8/8 hs foi continuada no dia 4. Grupo B recebeu placebo no dia 2 e o mesmo esquema de drogas dia 3 e dia 4. Pacientes foram entrevistados no dia 1 e dia 6. RESULTADOS: 73 pacientes foram incluídos no estudo. Os grupos foram bem balanceados em relação as suas características clinicas com exceção ao melhor controle da emese aguda no grupo A (p=0,04). Proteção completa de náuse a e vômito tardios (do dia 2 ao 5 ), foi semelhante em ambos os grupos (30% vs. 32%; p=0.5). Em análise multivariada, tanto a proteção completa da emese aguda (p=0.001) quanto grupo de estudo (p=0.06) estavam independentemente relacionados à proteção completa da náusea e vômito tardios. Selecionando apenas os pacientes que obtiveram controle completo da emese na fase aguda, pacientes do grupo B obtiveram maior proteção da emese tardia (85% vs 50% ,p=0,02). CONCLUSÃO: A omissão da medicação antiemética no dia 2 representa uma estratégia para redução do custo da profilaxia da emese tardia induzida pela quimioterapia. / BACKGROUND: Nausea and vomiting are important symptoms observed in cancer patients. In a previous study we showed that delayed chemotherapyinduced nausea and vomiting (CINV) control could be potentially improved by skipping the administration of a 5HT3-antagonist on day 2. We report here a trial confirming our previous findings. PATIENTS/METHODS: A phase-IIIrandomized- placebo-controlled trial was conducted in which patients received (IV) ondansetron 16mg, dexamethasone 20mg and ranitidine 50mg before highly/moderately emetogenic chemotherapy (day 1).Starting on day 2, all patients received metoclopramide 10mg PO q8 hours (days 2,3 and 4, Dexamethasone 8mg QD (days 2 and 3) and Ranitidine 150mg q12 hours (days 2 and 3). Patients were randomized to receive either Granisetron 0.5mg PO (days 2 and 3) (Group A) or Placebo instead for Granisetron on day 2 and Granisetron 0.5mg on day 3 and 4 (Group B) RESULTS: 73 patients were enrolled. Groups were similar regarding clinical characteristics, despite better control during the acute phase of CINV in group A (p=0.04). Complete delayed protection from nausea/vomiting (DCPNV) from day 2 to 5 was similar in both groups. (30% vs. 32%; p=0.5). Analyzing DCPNV by logistic regression multivariate analyses, acute complete protection from nausea/vomiting (ACPNV) (p=0.001) and study group (p=0.06) were independently associated with DCPNV. Selecting patients who achieved ACPNV, we observed that group B had a superior DCPNV (85% vs 50%, p=0.02). CONCLUSION: DCPNV can be improved just by skipping day 2 of 5HT3- antagonists. Future studies should compare this inexpensive strategy with NK1- antagonists or second generation 5HT3-antagonists. Key words: delayed chemotherapy-induced nausea and vomiting, tachyphylaxis, cost- saving regimen, antiemetics, Granisetron/administration and dosage. / TEDE / BV UNIFESP: Teses e dissertações