No description available.

The synthesis of substituted non-symmetric tropones has proven to be a considerable synthetic challenge. Particularly, a 3,4,6-tnsubstituted tropone which is required for the total synthesis of CP-225,917 is currently being undertaken by our group. / Two approaches towards the synthesis of substituted tropones are presented. Both utilize linear diene precursors which are closed to 7-membered cycloheptene rings via ring closing metathesis. In the first method, linear precursors are synthesized by addition of nucleophilic substituents to carbonyl groups to form alcohol groups. After forming the cycloheptene ring, the alcohol groups are eliminated to form the tropone. The second method uses an oxidation protocol to form a,(3-unsaturation on either side of a cycloheptenone precursor. An attempt towards the synthesis of the desired tropone required for the CP-225,917 synthesis is also presented. / The methods described here use simple inexpensive starting materials and provide access to tropone substitution not readily available through other means.

Lo Ho Yin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 142-149). / 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.

Wang Xin Ning. / "May 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 201-236). / 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.

Lee Chi-man. / "July 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / 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.

Chen Yu. / Thesis submitted in: November 2001. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 98-112). / Abstracts in English and Chinese. / Acknowledgements --- p.I / List of publications --- p.II / Abstract --- p.III / Abstract (Chinese) --- p.IV / Abbreviations --- p.V / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Tea --- p.1 / Chapter 1.2 --- Green tea --- p.3 / Chapter a) --- Chemical composition of green tea --- p.3 / Chapter b) --- Pharmacological activities of green tea polyphenols --- p.6 / Chapter c) --- Pharmacokinetics of green tea polyphenols --- p.10 / Chapter 1.3 --- Objective --- p.14 / Chapter Chapter 2 --- Validation of analysis method for tea catechins --- p.15 / Chapter 2.1 --- Materials and methods --- p.16 / Chapter a) --- Preparation of a catechin-mixture from tea --- p.16 / Chapter b) --- Preparation of stock solutions --- p.18 / Chapter c) --- Preparation of biofluid samples --- p.18 / Chapter d) --- HPLC analysis of tea catechins --- p.19 / Chapter 2.2 --- Results --- p.21 / Chapter a) --- Catechin-mixture (tea extracts) --- p.21 / Chapter b) --- "Extraction from plasma, urine and feces" --- p.21 / Chapter c) --- HPLC analysis of biofluid samples --- p.23 / Chapter 2.4 --- Discussion --- p.26 / Chapter Chapter 3 --- Pharmacokinetics of tea catechins following administration of different doses of the catechin-mixture --- p.32 / Chapter 3.1 --- Materials and methods --- p.33 / Chapter a) --- Surgery and animal maintenance --- p.33 / Chapter b) --- Dosing and sample collection --- p.33 / Chapter c) --- Pharmacokinetics analysis of tea catechins --- p.35 / Chapter 3.2 --- Results --- p.36 / Chapter 3.3 --- Discussion --- p.50 / Chapter Chapter 4 --- Pharmacokinetics of tea catechins following administration of different doses of individual catechins --- p.52 / Chapter 4.1 --- Materials and methods --- p.53 / Chapter a) --- Chemicals and reagents --- p.53 / Chapter b) --- Pharmacokinetic study of tea catechins and the HPLC analysis --- p.53 / Chapter c) --- Pharmacokinetic analysis of tea catechins --- p.54 / Chapter 4.2 --- Results --- p.55 / Chapter 4.3 --- Discussion --- p.67 / Chapter Chapter 5 --- Plasma protein binding of tea catechins --- p.69 / Chapter 5.1 --- Introduction --- p.69 / Chapter 5.2 --- Materials and methods --- p.72 / Chapter a) --- Ultrafiltration --- p.72 / Chapter b) --- Preparation of stock solution --- p.73 / Chapter c) --- Determination of nonspecific binding of the catechins --- p.73 / Chapter d) --- Determination of ultrafiltration conditions --- p.74 / Chapter e) --- In vitro plasma protein binding assay --- p.74 / Chapter f) --- Statistical analysis --- p.75 / Chapter 5.3 --- Results --- p.76 / Chapter a) --- Nonspecific binding in ultrafiltration --- p.76 / Chapter b) --- Protein binding of the catechins --- p.76 / Chapter c) --- Statistical analysis --- p.76 / Chapter 5.4 --- Discussion --- p.80 / Chapter Chapter 6 --- Partition of tea catechins in red blood cell --- p.82 / Chapter 6.1 --- Materials and methods --- p.83 / Chapter a) --- Prepare of stock solution --- p.83 / Chapter b) --- In-vitro erythrocyte partition --- p.83 / Chapter c) --- Data Analysis --- p.83 / Chapter 6.2 --- Results --- p.85 / Chapter a) --- Selection of experiment conditions --- p.85 / Chapter b) --- Partition of catechins to RBC --- p.85 / Chapter 6.3 --- Discussion --- p.87 / Chapter Chapter 7 --- Comparison of pharmacokinetics of tea catechins in mixture form versus pure compound --- p.89 / Chapter Chapter 8 --- Conclusion --- p.95 / References --- p.98

Lau Kin Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 97-103). / Abstracts in English and Chinese. / Contents --- p.1 / Chapter Chapter 1 --- Introduction --- p.5 / Chapter 1.1 --- Calcium Signaling in Endothelial Cells --- p.5 / Chapter 1.1.1 --- Calcium and its functions --- p.5 / Chapter 1.1.2 --- "Second Messengers: Inositol-1,4,5-Triphosphate and Diacylglycerol" --- p.6 / Chapter 1.1.3 --- Propagation of Ca2+ Signals --- p.8 / Chapter 1.1.4 --- Ca2+-ATPases --- p.9 / Chapter 1.1.5 --- Regulation of Sarcoplasmic Reticulum --- p.10 / Chapter 1.1.6 --- Agonist-induced Ca2+ Entry --- p.11 / Chapter 1.2 --- Mechanism of Store-Operated Ca2+ Entry --- p.14 / Chapter 1.2.1 --- Signaling Mechanisms of SOC --- p.14 / Chapter 1.2.1.1 --- A Diffusible Messenger --- p.14 / Chapter 1.2.1.2 --- Conformational Coupling --- p.15 / Chapter 1.2.1.3 --- Vesicle Secretion --- p.16 / Chapter 1.3 --- Regulation of Ca2+ Entry by cGMP --- p.20 / Chapter 1.4 --- Molecular Structres of Store-operated Channels --- p.22 / Chapter 1.4.1 --- Drosophila Transient Receptor Potential (trp) Gene --- p.22 / Chapter 1.4.2 --- Trpl Gene --- p.23 / Chapter Chapter 2 --- Methods and Materials --- p.27 / Chapter 2.1 --- Materials --- p.27 / Chapter 2.1.1 --- Phosphate-buffered saline --- p.27 / Chapter 2.1.2 --- Culture Media and Materials --- p.27 / Chapter 2.2 --- Preparations and Culture of Cells --- p.28 / Chapter 2.2.1 --- Culture of Rat Aortic Endothelial Cells --- p.28 / Chapter 2.2.2 --- Culture of Human Bladder Epithelial Cell Line --- p.29 / Chapter 2.2.3 --- Culture of Human Embryonic Kidney Epithelial Cell Line --- p.29 / Chapter 2.3 --- Cell. Subculture and Marvest --- p.29 / Chapter 2.4 --- Intracellular Free Calcium Ions ([Ca2+]i) measurment --- p.30 / Chapter 2.4.1 --- Chemicals --- p.30 / Chapter 2.4.2 --- Bathing solutions --- p.31 / Chapter 2.4.3 --- Preparations of Cells for [Ca2+]i Measurement --- p.31 / Chapter 2.4.3.1 --- Plating cells on Glass Cover Slips for [Ca2+]i Measurement with PTI RatioMaster Fluorescence System --- p.31 / Chapter 2.4.3.2 --- Plating cells on Glass Cover Slips for [Ca2+]i Measurement with Confocal Imaging System and Confocal Laser Scanning Microscopy --- p.32 / Chapter 2.4.4 --- PTI RatioMaster Fluorescence System --- p.35 / Chapter 2.4.4.1 --- Experimental Setup --- p.35 / Chapter 2.4.4.2 --- Fura-2/AM Dye loading --- p.35 / Chapter 2.4.4.3 --- Background Fluorescence and [Ca ]i Measurement --- p.37 / Chapter 2.4.5 --- Confocal Imaging System --- p.37 / Chapter 2.4.5.1 --- Experimental Setup --- p.37 / Chapter 2.4.5.2 --- Fluo-3/AM Dye Loading --- p.39 / Chapter 2.4.5.3 --- [Ca2+]i Measurement --- p.39 / Chapter 2.4.6 --- Confocal Laser Scanning Microscopy --- p.40 / Chapter 2.4.6.1 --- Principles --- p.40 / Chapter 2.5 --- Cloning and expression of Trpl in HEK293 cell line --- p.43 / Chapter 2.5.1 --- Cloning of Htrpl Gene into pcDNA3 Vector --- p.43 / Chapter 2.5.1.1 --- Enzyme Digestion --- p.43 / Chapter 2.5.1.2 --- Gel electrophoresis and Isolation of Htrpl by GeneCIean II Kit --- p.44 / Chapter 2.5.1.3 --- Ligation of Trpl and pcDNA3 Vector --- p.44 / Chapter 2.5.1.4 --- Transformation --- p.47 / Chapter 2.5.1.5 --- Purification of cloned Trpl-pcDNA3 by QIAprep Spin Miniprep Kit --- p.47 / Chapter 2.5.2 --- Transfection of HEK293 Cells with Htrpl and pEGFP-Nl Vector --- p.48 / Chapter 2.5.2.1 --- Cell Preparation for Transfection --- p.48 / Chapter 2.5.2.2 --- Transfection --- p.48 / Chapter 2.5.3 --- Fluorescence Labeling of Expressed Htrpl Channel in HEK293 Cells --- p.49 / Chapter 2.5.3.1 --- Immunostaining with Anti-TRPCl Antibody --- p.49 / Chapter 2.5.3.2 --- Labeling with FITC2° Antibody --- p.50 / Chapter Chapter 3 --- Results --- p.51 / Chapter 3.1 --- Propagation of Ca2+ Signaling --- p.51 / Chapter 3.2. --- Effect of cGMP on SERCA --- p.55 / Chapter 3.2.1 --- ATP stimulated Ca2+ release from internal stores --- p.55 / Chapter 3.2.2 --- Effect of cGMP on the falling phase of [Ca2+]i --- p.55 / Chapter 3.2.3 --- Effect of CPA on the falling phase of [Ca2+]i --- p.58 / Chapter 3.2.4 --- Effect of KT5823 on cGMP --- p.63 / Chapter 3.3. --- Effect of cGMP on bradykinin-activated capacitative Ca2+ entry --- p.65 / Chapter 3.3.1 --- Bradykinin induced capacitative Ca2+ entry --- p.65 / Chapter 3.3.2 --- Effect of cGMP on Ca2+ entry activated by bradykinin --- p.67 / Chapter 3.3.3 --- Effect of KT5823 on the inhibitory effect of cGMP on Ca2+ entry activated by bradykinin --- p.67 / Chapter 3.3.4. --- Effect of cGMP and KT5823 on capacitative Ca2+ entry activated by a combination of different agonists. --- p.71 / Chapter 3.4 --- Cloning and expression of htrpl in HEK 293 cell line --- p.75 / Chapter 3.4.1 --- Optimizing transfection conditions using pEGFP-Nl --- p.78 / Chapter 3.4.2 --- Transient transfection of htrpl channel in HEK293 cells --- p.81 / Chapter 3.4.3 --- Channel properties of expressed htrpl channel --- p.84 / Chapter Chapter 4 --- Discussion --- p.88 / Chapter 4.1 --- Ptopagation of Ca2+ Signaling --- p.88 / Chapter 4.2 --- Effect of cGMP on[Ca2+]i of Vascular Endothelial Cells --- p.89 / Chapter 4.2.1 --- Effect of cGMP on SERCA --- p.89 / Chapter 4.2.2 --- Effect of cGMP on Regulation of Agonist-Activated Capacitative Ca2+ Entry --- p.92 / Chapter 4.2.3 --- Physiological Property of Expressed Htrpl in HEK293 cells --- p.95 / References --- p.97

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.

A series of novel alpha-aminoxy peptides have been recently developed, and showed a therapeutic potential for the treatment of CI- channel dysfunctional diseases. The present study aimed to investigate the pharmacokinetics of five structural related tx-aminoxy peptides (P1 to P5), and effect of structural modifications on their pharmacokinetic properties. / P1 showed significantly low intestinal permeability due to P-gp-mediated efflux. Structural modifications resulted in alterations of transport mechanisms from P-gp-mediation (P1, P2) to multidrug resistance-associated protein (MRP)-mediation (P3), MRP plus breast cancer resistance protein (BCRP)-mediation (P4) active transport, or even passive paracellular diffusion (P5) without any efflux transporters involved. Comparing with P1, the absorbable permeability in Caco-2 monolayer increased to about 7-fold (P3), 4-fold (P4) and 11-fold (P5), respectively, and the absorption through intestine in SPIP model significantly increased to about 36-fold (P2), 42-fold (P3), 55-fold (P4) and 102-fold (P5), respectively. P1 was unstable in the GI tract with 41% degradation in SGF within 1 h and 47% degradation in SIF within 3 h. The other four peptides were much more stable than P1 with degradation less than 6% under the same incubated conditions. For the hepatic metabolism, about 31% of P1 was metabolized by rat liver S9 within 30 min, while the metabolic stability was significantly improved to 3.3-fold (P3), 2.9-fold (P4) and 7.5-fold (P5), respectively with no metabolism for P2. Their metabolism was mainly via oxidation catalyzed by CYP enzymes to form hydroxylated metabolites. After i.v. administration (5 mg/kg), both P1 and P5 was eliminated rapidly. P1 mainly distributed to liver and lung, while P5 to kidney and intestine. P1 was cleared mainly through metabolism via oxidation followed by sulphation (∼80% of the dose), while P5 was mainly eliminated as an intact form (∼53% of the dose). Oral bioavailability of P1 was low (0.36%) due to instability in the GI tract and poor intestinal absorption mediated by P-gp efflux transport. Oral bioavailability of P5 was improved to about 3-fold comparing with P1 but still low mainly because of poor intestinal absorption through passive diffusion and some unknown factor(s). / The present studies demonstrated that our rationale for the structural modifications of the designed cc-aminoxy peptides is an effective way to improve their intestinal absorption, gastrointestinal and metabolic stability, and appropriate pharmacokinetic properties. Our findings also provide scientific evidence to support further development of better alpha-aminoxy peptide cadidates with high oral bioavailability and appropriate pharmacokinetic properties. / Three absorption models, including Caco-2 cell monolayer, Ussing chamber and in situ rat single-pass intestinal perfusion (SPIP) model, were used. The stability in gastrointestinal (GI) tract was determined using simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The hepatic metabolism was investigated in rat liver subcellular fractions and human liver microsome. P1 and P5 were selected for pharmacokinetic study in rats. / Ma, Bin. / Adviser: Ge Lin. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 199-215). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Heung May-sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references. / Abstracts in English and Chinese. / Title Page --- p.i / Acknowledgement --- p.ii / Table of Contents --- p.iii / List of Abbreviations --- p.vi / List of Figures --- p.viii / List of Tables --- p.xii / Abstract --- p.xiv / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Epstein-Barr Virus --- p.1-1 / Chapter 1.1.1 --- Virus structure --- p.1-1 / Chapter 1.1.2 --- Genome structure --- p.1-1 / Chapter 1.1.3 --- Nomenclature for EBV open reading frames --- p.1-2 / Chapter 1.1.4 --- Biology of EBV --- p.1-2 / Chapter 1.1.5 --- EBV latency --- p.1-7 / Chapter 1.1.6 --- EBV latent gene promoters --- p.1-8 / Chapter 1.2 --- EBV Infection and Its Persisence --- p.1-9 / Chapter 1.3 --- DNA Methylation --- p.1-17 / Chapter 1.3.1 --- Aberrant CpG island methylation in cancer --- p.1-18 / Chapter 1.3.2 --- DNA methylation and EBV --- p.1-19 / Chapter 1.4 --- Demethylating Agents --- p.1-21 / Chapter 1.5 --- Aims of the Study --- p.1-23 / Chapter Chapter 2 --- EBV Latency Patterns / Chapter 2.1 --- Introduction --- p.2-1 / Chapter 2.2 --- Materials and Methods --- p.2-1 / Chapter 2.2.1 --- Cell line culture --- p.2-1 / Chapter 2.2.2 --- NPC biopsies culture --- p.2-2 / Chapter 2.2.3 --- RNA extraction --- p.2-3 / Chapter 2.2.4 --- RNA quantification --- p.2-4 / Chapter 2.2.5 --- Deoxyribonuclease I treatment for NPC biopsies --- p.2-5 / Chapter 2.2.6 --- Reverse transcriptase-polymerase chain reaction --- p.2-5 / Chapter 2.2.7 --- Gel Electrophoresis --- p.2-10 / Chapter 2.3 --- Results --- p.2-11 / Chapter 2.3.1 --- Burkitt' s lymphoma and lymphoblastoid cell lines --- p.2-11 / Chapter 2.3.2 --- Nasopharyngeal carcinoma biopsies --- p.2-11 / Chapter 2.4 --- Discussion --- p.2-19 / Chapter Chapter 3 --- Treatment with Demethylating Agents on Rael / Chapter 3.1 --- Introduction --- p.3-1 / Chapter 3.2 --- Materials and Methods --- p.3-2 / Chapter 3.2.1 --- Rael cell line culture --- p.3-2 / Chapter 3.2.2 --- Drug treatment --- p.3-2 / Chapter 3.2.3 --- Viability staining --- p.3-2 / Chapter 3.2.4 --- Statistical analysis --- p.3-3 / Chapter 3.2.5 --- RNA extraction and quantification --- p.3-3 / Chapter 3.2.6 --- RT-PCR and gel electrophoresis --- p.3-3 / Chapter 3.2.7 --- DIG oligonucleotide 3'-end labeling --- p.3-3 / Chapter 3.2.8 --- Southern blot --- p.3-10 / Chapter 3.3 --- Results --- p.3-13 / Chapter 3.3.1 --- 5-azacytidine --- p.3-13 / Chapter 3.3.2 --- 5-aza-2-deoxycytidine --- p.3-26 / Chapter 3.4 --- Discussion --- p.3-39 / Chapter Chapter 4 --- Treatment with Demethylating Agents on NPC Biopsies / Chapter 4.1 --- Introduction --- p.4-1 / Chapter 4.2 --- Materials and Methods --- p.4-2 / Chapter 4.2.1 --- NPC biopsy culture --- p.4-2 / Chapter 4.2.2 --- Drug treatment --- p.4-2 / Chapter 4.2.3 --- RNA extraction and quantification --- p.4-2 / Chapter 4.2.4 --- DNase I treatment for NPC biopsies --- p.4-2 / Chapter 4.2.5 --- RT-PCR and gel electrophoresis --- p.4-2 / Chapter 4.3 --- Results --- p.4-3 / Chapter 4.4 --- Discussion --- p.4-3 / Chapter Chapter 5 --- Conclusion --- p.5-1 / Reference --- p.R-1 / Appendix --- p.A-l