Investigation into the mechanism of action of corticosteroids to antagonise cisplatin- and motion-induced emesis.

• Other Authors: Sam, Sze Wing.
• Format: Others
• Language: English; Chinese
• Published: 2000
• Subjects: Adrenal Cortex Hormones > therapeutic use; Vomiting > drug therapy; Vomiting > chemically induced; Cisplatin > adverse effects
• Online Access: http://library.cuhk.edu.hk/record=b5890434; http://repository.lib.cuhk.edu.hk/en/item/cuhk-323007

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