Rowlands Dewi Kenneth. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 113-121). / Abstract --- p.i / Acknowledgements --- p.iii / Publications --- p.iv / Abbreviations --- p.v / Contents --- p.vii / Chapter Chapter 1 --- Prostaglandins --- p.1 / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.2 --- Prostanoid biosynthesis and metabolism --- p.1 / Chapter 1.3 --- Prostaglandin receptors --- p.3 / Chapter 1.3.1 --- DP-receptors --- p.3 / Chapter 1.3.2 --- EP1-receptors --- p.4 / Chapter 1.3.3 --- EP2-receptors --- p.4 / Chapter 1.3.4 --- EP3-receptors --- p.5 / Chapter 1.3.5 --- EP4-receptors --- p.6 / Chapter 1.3.6 --- FP-receptors --- p.7 / Chapter 1.3.7 --- IP-receptors --- p.8 / Chapter 1.3.8 --- TP-receptors --- p.11 / Chapter 1.4 --- Agonists and antagonists --- p.11 / Chapter Chapter 2 --- Role of prostacyclin in pain modulation --- p.14 / Chapter 2.1 --- Pain --- p.14 / Chapter 2.2 --- Prostaglandins and pain --- p.15 / Chapter 2.3 --- Prostacyclin and pain --- p.16 / Chapter 2.3.1 --- [3H]-Iloprost binding sites --- p.16 / Chapter 2.3.2 --- IP-receptor mRNA --- p.17 / Chapter 2.3.3 --- IP-receptor knockout mice --- p.17 / Chapter 2.3.4 --- Direct nociceptive action of prostacyclin --- p.18 / Chapter 2.4 --- Treatment of prostanoid-induced pain --- p.19 / Chapter Chapter 3 --- Dorsal root ganglion cells --- p.21 / Chapter 3.1 --- In vitro model of pain --- p.21 / Chapter 3.2 --- Characteristics of cultured DRG cells --- p.22 / Chapter 3.2.1 --- Size and distribution --- p.22 / Chapter 3.2.2 --- Biochemical and physiological characteristics --- p.22 / Chapter 3.2.2.1 --- Gapsaicin-sensitive neurones --- p.23 / Chapter 3.2.2.2 --- Neuropeptide content --- p.23 / Chapter 3.2.2.3 --- Elevation of [Ca2+］i --- p.24 / Chapter 3.3 --- Effect of nerve growth factor --- p.24 / Chapter Chapter 4 --- Materials and solutions --- p.26 / Chapter 4.1 --- Materials --- p.26 / Chapter 4.2 --- Solutions --- p.30 / Chapter 4.2.1 --- Culture medium --- p.30 / Chapter 4.2.2 --- Buffers --- p.31 / Chapter 4.2.3 --- Solutions --- p.32 / Chapter Chapter 5 --- Development of dorsal root ganglion cell preparation --- p.33 / Chapter 5.1 --- Introduction --- p.33 / Chapter 5.2 --- Methods --- p.34 / Chapter 5.2.1 --- Dissection of dorsal root ganglia --- p.34 / Chapter 5.2.2 --- Preparation of a single-cell suspension --- p.34 / Chapter 5.2.2.1 --- Effect of trimming dorsal root ganglia --- p.34 / Chapter 5.2.2.2 --- Enzymatic dissociation --- p.35 / Chapter 5.2.2.3 --- Mechanical dissociation --- p.36 / Chapter 5.2.3 --- Neuronal cell enrichment --- p.36 / Chapter 5.2.3.1 --- Differential adhesion --- p.36 / Chapter 5.2.3.2 --- BSA gradient --- p.37 / Chapter 5.2.3.3 --- Combination of BSA gradient and differential adhesion --- p.37 / Chapter 5.2.4 --- Cell counting --- p.37 / Chapter 5.2.5 --- Culture conditions --- p.38 / Chapter 5.2.6 --- Size distribution of DRG cells --- p.39 / Chapter 5.2.7 --- Immunocytochemistry --- p.39 / Chapter 5.3 --- Results and discussion --- p.40 / Chapter 5.3.1 --- Preparation of single-cell suspension --- p.40 / Chapter 5.3.2 --- Neuronal cell enrichment --- p.42 / Chapter 5.3.3 --- Size distribution of DRG cells --- p.32 / Chapter 5.3.4 --- Effects of mitotic inhibitors and NGF --- p.45 / Chapter 5.3.5 --- Immunocytochemistry --- p.48 / Chapter 5.4 --- Conclusions --- p.48 / Chapter Chapter 6 --- Methods --- p.53 / Chapter 6.1 --- Dorsal root ganglion cell preparation --- p.53 / Chapter 6.1.1 --- Preparation of tissue culture plates and coverslips --- p.54 / Chapter 6.1.2 --- Preparation of Pasteur pipettes --- p.54 / Chapter 6.2 --- Measurement of adenylate cyclase activity --- p.55 / Chapter 6.2.1 --- Introduction --- p.55 / Chapter 6.2.2 --- Preparation of columns --- p.55 / Chapter 6.2.3 --- Measurement of [3H]-cyclic AMP production --- p.56 / Chapter 6.2.4 --- Data analysis --- p.57 / Chapter 6.3 --- Measurement of phospholipase C activity --- p.58 / Chapter 6.3.1 --- Introduction --- p.58 / Chapter 6.3.2 --- Preparation of columns --- p.58 / Chapter 6.3.3 --- Measurement of [3H]-inositol phosphate production --- p.59 / Chapter 6.3.4 --- Data analysis --- p.60 / Chapter 6.4 --- Measurement of [Ca2+]i --- p.60 / Chapter 6.4.1 --- Introduction --- p.60 / Chapter 6.4.2 --- Preparations of cells --- p.61 / Chapter 6.4.3 --- Measurement of Fura-2 fluorescence --- p.62 / Chapter 6.5 --- Measurement of neuropeptides --- p.62 / Chapter 6.5.1 --- Introduction --- p.62 / Chapter 6.5.2 --- Preparation of cells --- p.63 / Chapter 6.5.3 --- CGRP assay --- p.64 / Chapter 6.5.4 --- Substance P assay --- p.64 / Chapter 6.5.5 --- Purification of samples using Sep-Pak cartridges --- p.65 / Chapter Chapter 7 --- Characterisation of prostacyclin receptors on adult rat dorsal root ganglion cells --- p.66 / Chapter 7.1 --- Stimulation of adenylate cyclase --- p.66 / Chapter 7.1.1 --- Introduction --- p.66 / Chapter 7.1.2 --- Agonist concentration-response curves --- p.67 / Chapter 7.1.3 --- Cross-desensitisation experiments --- p.72 / Chapter 7.1.4 --- Evidence for EP3-receptors --- p.77 / Chapter 7.1.5 --- G-protein coupling of the IP-receptor --- p.77 / Chapter 7.1.6 --- Discussion --- p.78 / Chapter 7.1.7 --- Conclusions --- p.82 / Chapter 7.2 --- Stimulation of phospholipase C --- p.82 / Chapter 7.2.1 --- Introduction --- p.82 / Chapter 7.2.2 --- Agonist concentration-response curves --- p.83 / Chapter 7.2.3 --- G-protein coupling --- p.83 / Chapter 7.2.4 --- Discussion and Conclusions --- p.84 / Chapter 7.3 --- Stimulation of changes in [Ca2+]i --- p.87 / Chapter 7.3.1 --- Introduction --- p.87 / Chapter 7.3.2 --- Preliminary results --- p.87 / Chapter 7.3.3 --- Discussion and conclusions --- p.89 / Chapter Chapter 8 --- Neuropeptide release by adult rat dorsal root ganglion cells --- p.90 / Chapter 8.1 --- Introduction --- p.90 / Chapter 8.2 --- Methods and Results --- p.91 / Chapter 8.3 --- Discussion --- p.91 / Chapter 8.4 --- Conclusions --- p.92 / Chapter Chapter 9 --- Regulation of prostacyclin receptors on adult rat DRG cells --- p.93 / Chapter 9.1 --- Introduction --- p.93 / Chapter 9.2 --- Contribution of non-neuronal cells --- p.93 / Chapter 9.3 --- Effect of DRG cell density --- p.94 / Chapter 9.4 --- Effect of indomethacin --- p.99 / Chapter 9.5 --- Contribution of endogenously-produced non-prostanoid ligands --- p.100 / Chapter 9.6 --- Effect of PKC activation --- p.102 / Chapter 9.7 --- Discussion --- p.104 / Chapter 9.8 --- Conclusions --- p.106 / Chapter Chapter 10 --- General Discussion and Conclusions --- p.107 / Chapter 10.1 --- Development of DRG cell preparation --- p.107 / Chapter 10.2 --- Effect of prostanoid mimetics on intracellular messengers --- p.108 / Chapter 10.3 --- Regulation of prostacyclin receptors --- p.109 / Chapter 10.4 --- Role of prostacyclin in pain modulation --- p.111 / References --- p.113

Kwan Hon Pong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 115-156). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iii / Abbreviations --- p.v / Acknowledgment --- p.vii / Chapter 1. --- Introduction / Chapter 1.1 --- Diabetes mellitus - general introduction --- p.1 / Chapter 1.1.1 --- Animal models of diabetes --- p.5 / Chapter 1.1.2 --- Streptozotocin-induced diabetes (SID) --- p.6 / Chapter 1.1.2.1 --- Mechanism of the diabetogenic effect of STZ --- p.7 / Chapter 1.1.2.2 --- Administration of STZ --- p.9 / Chapter 1.2 --- Impairment of cognitive function in diabetes mellitus --- p.9 / Chapter 1.3 --- Common mechanisms suggested in diabetic neuropathy --- p.15 / Chapter 1.3.1 --- Polyol pathway activation --- p.15 / Chapter 1.3.2 --- Redox potential alterations --- p.16 / Chapter 1.3.3 --- Nonenzymatic glycation --- p.17 / Chapter 1.3.4 --- PKC alteration --- p.18 / Chapter 1.4 --- Do the common mechanisms of neuropathy induced the cognitive impairment in diabetes --- p.18 / Chapter 1.5 --- Structure and function of the hippocampus --- p.20 / Chapter 1.6 --- The definition and mechanism of learning and memory --- p.21 / Chapter 1.7 --- The mechanisms underlying the early and late phases of LTP in hippocampus --- p.23 / Chapter 1.7.1 --- Perforant and schaffer collaterals pathways --- p.23 / Chapter 1.7.2 --- Mossy fibre pathway --- p.24 / Chapter 1.7.3 --- Late phase of LTP in hippocampus --- p.25 / Chapter 1.8 --- GABAergic interaction in hippocampal plasticity --- p.25 / Chapter 1.9 --- The objective of the project --- p.27 / Chapter 1.10 --- Hypothesis --- p.27 / Chapter 1.10.1 --- The initial role of glutamate receptors --- p.28 / Chapter 1.10.2 --- Involvement of putative retrograde messengers --- p.30 / Chapter 1.10.3 --- The role of GABA receptors --- p.37 / Chapter 1.10.4 --- The role of the CREB --- p.40 / Chapter 2. --- Materials and methods / Chapter 2.1 --- Animals --- p.43 / Chapter 2.1.1 --- Induction of diabetes mellitus --- p.43 / Chapter 2.1.2 --- Insulin therapy --- p.45 / Chapter 2.1.3 --- Sample collection --- p.46 / Chapter 2.2 --- Isolation of total RNA --- p.47 / Chapter 2.3 --- Quantitation of total RNA --- p.51 / Chapter 2.4 --- Reverse transcription --- p.53 / Chapter 2.5 --- PCR --- p.54 / Chapter 2.5.1 --- Preparation of PCR --- p.54 / Chapter 2.5.2 --- Purification of PCR product --- p.60 / Chapter 2.5.3 --- Confirmation of PCR products by DNA sequencing --- p.61 / Chapter 2.5.4 --- PCR analysis --- p.62 / Chapter 2.5.4.1 --- Quantitation of cDNA --- p.62 / Chapter 2.5.4.2 --- Radioactive PCR --- p.65 / Chapter 2.5.4.3 --- cDNA gel electrophoresis --- p.66 / Chapter 3. --- Results / Chapter 3.1 --- Ionotropic glutamate receptor subtypes --- p.72 / Chapter 3.1.1 --- Non-NMDA receptors --- p.72 / Chapter 3.1.1.1 --- AMPA receptors --- p.72 / Chapter 3.1.1.2 --- Kainate receptors --- p.72 / Chapter 3.1.2 --- NMDA receptors --- p.76 / Chapter 3.2 --- Metabotropic glutamate receptor subtypes --- p.79 / Chapter 3.2.1 --- Group I subtype --- p.79 / Chapter 3.2.2 --- Group II subtypes --- p.79 / Chapter 3.3 --- Synthases of retrograde messengers --- p.79 / Chapter 3.4 --- Calcium-related receptors --- p.82 / Chapter 3.5 --- "GABA receptor subtypes (Aαl-4,BRla)" --- p.85 / Chapter 3.6 --- Glutamic acid decarboxylase (GAD) --- p.88 / Chapter 3.7 --- Enzyme genes related to CREB dephosphorylation --- p.88 / Chapter 3.8 --- Effect of insulin therapy on ionotropic glutamate receptor subtypes --- p.91 / Chapter 3.9 --- Effect of insulin therapy on metabotropic glutamate receptor subtypes --- p.91 / Chapter 3.10 --- Effect of insulin therapy on synthases of retrograde messenger --- p.91 / Chapter 3.11 --- Effect of insulin therapy on GAB A receptor subtype --- p.91 / Chapter 4. --- Discussion / Chapter 4.1 --- SID on Glutamate receptor subtypes --- p.96 / Chapter 4.2 --- SID on Calcium-related receptors --- p.105 / Chapter 4.3 --- SID on Synthases of retrograde messengers --- p.106 / Chapter 4.4 --- SID on GABA receptor subtypes --- p.109 / Chapter 4.5 --- SID on enzyme genes related to dephosphorylation of CREB --- p.111 / Chapter 4.6 --- Effect on insulin therapy on gene expression in hippocampus --- p.113 / Chapter 5. --- References --- p.115

No description available.

Ph.d.

Cells experiencing a low oxygen tension show relative resistance to the lethal effects of radiation. It is believed that the effectiveness of the treatment of certain human tumors is hindered by the existence of such radioresistant cells within the tumor. The purpose of this work was to study the drug Ro-07-0582 both for its toxic effects and its ability to preferentially sensitize hypoxic cells to the lethal effects of radiation (radiosensitize). These properties were examined in vitro in two Chinese hamster cell lines, CHO and CH2B2, and also in the mouse tumour cell line EMT6. Ro-07-0582 is shown to have a chemotherapeutic potential in that it demonstrates a very selective toxicity for hypoxic cells after a few hours exposure. It is much less toxic to aerobic cells. These toxic properties were studied extensively, both in hypoxic and aerobic cell suspensions. The measured endpoint was the ability of a cell to multiply and form a colony of 50 or more cells within an allotted incubation time. Hypoxic toxicity was greater at 37°C than at 22°C and was affected by small changes (~30ppm) in 0₂ concentration in the cell suspension. The toxic effects were similar in the three cell lines. The radiosensitizing capability of Ro-07-0582 was determined by measuring the Dose Modifying Factors (DMF's) for various drug concentrations with each cell line. DMF's were calculated by comparison of survival curves for cell suspensions irradiated under hypoxia in the presence of drug with the survival curve for cell suspensions irradiated under hypoxia in the absence of drug. The DMF for the irradiation of aerobic cells in the absence of drug is called the Oxygen Enhancement Ratio (OER) and was approximately 3.0 in all three cell lines. Ro-07-0582 was found to selectively radiosensitize hypoxic cells in suspension with high efficiency. For each cell line, sensitization was observed with drug concentrations as low as 0.1mM, while concentrations of 10mM or greater yielded DMF's within the measured range of OER values. The presence of 1mM Ro-07-0582 during irradiation of hypoxic cells yields a DMF of 1.8. Introduction of the drug before or after irradiation, instead of during irradiation, had little if any effect. Radiosensitization measurements were also carried out at high cell concentrations (cell pellets), where many sensitizers are ineffective. Results showed that the 0582 radiosensitization attained in cell pellets is quite comparable with that attained in dilute suspension. The attributes of Ro-07-0582 as a potential radiosensi-tizer were considered. The sensitization achieved by Ro-07-0582 is very good, and surpasses that of metronidazole, a chemical under study for clinical use. For drug doses necessary to achieve high levels of sensitization the toxicity of Ro-07-0582 to aerobic cells is quite acceptable. The toxicity to hypoxic cells, however, is much increased over the toxicity to aerobic cells, and this may prove to be a useful adjunct to the drug's sensitizing properties in destroying hypoxic tumour cells. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / The bisphosphonate etidronate, a drug commonly used to treat osteolytic bone disorders, produces a long lasting inhibition of bone resorption. Since continual bone remodeling appears crucial for the long-term success of endosseous implants, the effects of this drug on the bone surrounding implants were investigated. The specific objective was to quantify the static and dynamic histomorphometric properties of bone surrounding implants placed in 12 beagle dogs treated with this drug. The dogs were divided into three groups (4 dogs/group) based on the bisphosphonate treatment dose: 0, 0.5 and 5.0 mg/kg/day. Since remodeling is different at distinct sites around implants, we analyzed bone at different distances (<1, 1-2 and 2-3 mm from the implant) and in different regions (periosteal and endosteal calluses and intracortical bone). Factorial ANOVA with repeated measures was used to compare site and regional differences in the dose groups. Results show that etidronate treatment produced a decrease in remodeling activity in the treated groups. The high dose group had impaired bone formation and a complete inhibition of remodeling. Low dose produced the same trend, but was not statistically different from controls. The significant differences (p < 0.05) were shown by the high dose group compared to controls for Mineralizing Surface (MS/BS), Activation Frequency (AcF), Mineral Apposition Rate (MAR), Bone Formation Rate (BFR), Formation Period (FP), Mineralization Lag Time (MLT), Adjusted Apposition Rate (AjAr) and Bone Volume (BV/TV), while Osteoid Volume (OV/TV) and Osteoid Thickness (OTh) were higher (p < 0.05) in the high dose group. Since it has been suggested that a remodeling rate of 500 percent per year is achieved in the first millimeter around an implant in successful osseointegration, the area within the first millimeter, as expected, was more affected by all the parameters than further away. These results agree with earlier studies in which areas of high remodeling were shown to be more affected by bisphosphonate therapy than areas of low remodeling. The area closest to the implant showed significantly greater BV/TV, Void Volume (VV/TV), Osetoid Volume over Bone volume (OV/BV), Osteoid Surface (OS/BS), MS/BS, BFR, FP, AcF and MLT while OV/TV was significantly increased in the area most distant from the implant. It was found that etidronate interfered with normal bone mineralization, since there was a decrease in MLT and an accumulation of osteoid. If remodeling is high around implants so as to repair or prevent microdamage, then etidronate could impair this from happening, thereby resulting in eventual implant failure. Though these high doses are not ordinarily used for the clinical treatment of osteoporosis, a low dose might still be harmful if given long-term. These data confirm our hypothesis that etidronate affects bone resorption and mineralization around an implant, when given at the high dose. Two hypotheses were rejected, since in this study, the effect of etidronate was not dose-dependent. This study was supported by NIH 2PO1AG05793, Merck and CO., and Procter and Gamble Pharmaceuticals.

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, for the degree of Doctor of Philosophy in Medicine. / Despite having been initially described more than fifty years ago, sclerotherapy of oesophageal varices has only relatively recently became regarded as one of the primary modalities both to control bleeding oesophageal varices and to prevent recurrent bleeding. Sclerotherapy, however, ts associated with numerous complications and its exact mechanism of action, particularly that pertaining to its effect on haemostasis, has to date been poorly documented. One of the problems of comparing the various trials has been the diversity of both the technique and the type and concentration of the sclerosants used. (Abbreviation abstract) / Andrew Chakane 2018

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.