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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
541

Evaluation of xanthine oxidase inhibitory and antioxidant activities of compounds from natural sources.

January 2005 (has links)
Lam Rosanna Yen Yen. / Thesis submitted in: September 2004. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 142-154). / Abstracts in English and Chinese. / Abstract --- p.i / Chinese Abstract --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Abbreviations --- p.xii / List of Figures --- p.xv / List of Tables --- p.xix / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Reactive oxygen species --- p.1 / Chapter 1.1.1 --- Intracellular sources of ROS --- p.1 / Chapter 1.1.2 --- Extracellular sources of ROS --- p.2 / Chapter 1.1.3 --- Superoxide anion radicals --- p.2 / Chapter 1.1.4 --- Hydrogen peroxide --- p.3 / Chapter 1.1.5 --- Hydroxyl radicals --- p.3 / Chapter 1.1.6 --- Singlet oxygen --- p.4 / Chapter 1.1.7 --- Peroxyl radicals and peroxides --- p.4 / Chapter 1.1.8 --- Damage of cellular structures by ROS --- p.5 / Chapter 1.2 --- Antioxidative defence in the body --- p.6 / Chapter 1.2.1 --- Antioxidant proteins --- p.6 / Chapter 1.2.2 --- Antioxidant enzymes --- p.6 / Chapter 1.2.3 --- Antioxidant compounds --- p.7 / Chapter 1.2.3.1 --- Vitamin E --- p.8 / Chapter 1.2.3.2 --- Vitamin C --- p.9 / Chapter 1.2.3.3 --- Glutathione --- p.9 / Chapter 1.2.3.4 --- Urate --- p.9 / Chapter 1.2.3.4.1 --- Purine metabolism --- p.10 / Chapter 1.2.3.4.2 --- Xanthine oxidase --- p.12 / Chapter 1.2.4 --- Oxidative stress and antioxidant defence mechanisms in RBC --- p.12 / Chapter 1.2.5 --- Oxidative stress and antioxidant defence mechanisms in LDL --- p.16 / Chapter 1.3 --- Human diseases originated from pro-oxidant conditions --- p.16 / Chapter 1.3.1 --- Atherosclerosis --- p.17 / Chapter 1.3.2 --- Ischemia /reperfusion injury --- p.17 / Chapter 1.3.3 --- Glucose-6-phosphate dehydrogenase deficiency --- p.18 / Chapter 1.3.4 --- DNA mutation --- p.18 / Chapter 1.3.5 --- Other pro-oxidant state related diseases --- p.19 / Chapter 1.4 --- Hyperuricemia and gout: diseases originated from an extreme antioxidant condition --- p.19 / Chapter 1.4.1 --- Inhibition of XOD as a treatment method for hyperuricemia --- p.20 / Chapter 1.4.2 --- Relationship between ROS injury and hyperuricemia --- p.22 / Chapter 1.5 --- Antioxidants in human nutrition --- p.23 / Chapter 1.6 --- Chinese medicinal therapeutics --- p.23 / Chapter 1.6.1 --- Rhubarb --- p.25 / Chapter 1.6.2 --- Aloe --- p.26 / Chapter 1.6.3 --- Ginger --- p.27 / Chapter 1.6.4 --- Objectives of the project --- p.30 / Chapter 1.6.5 --- Strategies applied to achieve the objectives of the present project --- p.30 / Chapter Chapter 2 --- Materials and methods --- p.31 / Chapter 2.1 --- XOD inhibition assay --- p.31 / Chapter 2.1.1 --- Assay development --- p.31 / Chapter 2.1.2 --- Dose-dependent study --- p.32 / Chapter 2.1.3 --- Reversibility of the enzyme inhibition --- p.32 / Chapter 2.1.4 --- Lineweaver-Burk plots --- p.33 / Chapter 2.2 --- Lipid peroxidation inhibition assay of mouse liver microsomes --- p.34 / Chapter 2.2.1 --- Preparation of mouse liver microsomes --- p.34 / Chapter 2.2.2 --- Basis of assay --- p.34 / Chapter 2.2.3 --- Assay procedures --- p.35 / Chapter 2.3 --- AAPH-induced hemolysis inhibition assay --- p.36 / Chapter 2.3.1 --- Preparation of RBC --- p.36 / Chapter 2.3.2 --- Basis of assay --- p.36 / Chapter 2.3.3 --- Assay procedures --- p.37 / Chapter 2.4 --- Lipid peroxidation inhibition assay of RBC membrane --- p.38 / Chapter 2.4.1 --- Preparation of RBC membrane --- p.38 / Chapter 2.4.2 --- Basis of assay --- p.39 / Chapter 2.4.3 --- Assay procedures --- p.40 / Chapter 2.5 --- ATPase protection assay --- p.41 / Chapter 2.5.1 --- Preparation of RBC membrane --- p.41 / Chapter 2.5.2 --- Preparation of malachite green (MG) reagent --- p.41 / Chapter 2.5.3 --- Basis of assay --- p.41 / Chapter 2.5.4 --- Assay procedures --- p.42 / Chapter 2.5.5 --- Determination of ATPase activities --- p.43 / Chapter 2.5.6 --- Assay buffers --- p.43 / Chapter 2.6 --- Sulfhydryl group protection assay --- p.44 / Chapter 2.6.1 --- Preparation of RBC membrane --- p.44 / Chapter 2.6.2 --- Basis of assay --- p.45 / Chapter 2.6.3 --- Assay procedures --- p.45 / Chapter 2.7 --- Lipid peroxidation inhibition assay of LDL by the AAPH method --- p.46 / Chapter 2.7.1 --- Basis of assay --- p.46 / Chapter 2.7.2 --- Assay procedures --- p.46 / Chapter 2.8 --- Lipid peroxidation inhibition assay of LDL by the hemin method --- p.47 / Chapter 2.8.1 --- Basis of assay --- p.47 / Chapter 2.8.2 --- Assay procedures --- p.47 / Chapter 2.9 --- Protein assay --- p.48 / Chapter 2.10 --- Statistical analysis --- p.48 / Chapter 2.11 --- Test compounds --- p.48 / Chapter Chapter 3 --- Xanthine oxidase inhibition assay: results and discussion --- p.49 / Chapter 3.1 --- Introduction --- p.49 / Chapter 3.2 --- Results --- p.54 / Chapter 3.3 --- Discussion --- p.59 / Chapter Chapter 4 --- Lipid peroxidation inhibition in mouse liver microsomes: results and discussion --- p.64 / Chapter 4.1 --- Introduction --- p.64 / Chapter 4.2 --- Results --- p.64 / Chapter 4.3 --- Discussion --- p.69 / Chapter Chapter 5 --- Assays on protection of RBC from oxidative damage: results and discussion --- p.71 / Chapter 5.1 --- Introduction --- p.71 / Chapter 5.2 --- Results --- p.75 / Chapter 5.2.1 --- AAPH-induced hemolysis inhibition assay --- p.75 / Chapter 5.2.2 --- Lipid peroxidation inhibition assay of RBC membranes --- p.82 / Chapter 5.2.3 --- Ca2+-ATPase protection assay --- p.88 / Chapter 5.2.4 --- Na+/K+-ATPase protection assay --- p.95 / Chapter 5.2.5 --- Sulfhydryl group protection assay --- p.100 / Chapter 5.3 --- Discussion --- p.110 / Chapter 5.3.1 --- AAPH-induced hemolysis inhibition assay --- p.110 / Chapter 5.3.2 --- Lipid peroxidation inhibition assay of RBC membranes --- p.111 / Chapter 5.3.3 --- Ca2+-ATPase protection assay --- p.113 / Chapter 5.3.4 --- Na+/K+-ATPase protection assay --- p.114 / Chapter 5.3.5 --- Sulfhydryl group protection assay --- p.115 / Chapter 5.3.6 --- Chapter summary --- p.117 / Chapter Chapter 6 --- Lipid peroxidation inhibition assay of LDL: results and discussion --- p.118 / Chapter 6.1 --- Introduction --- p.118 / Chapter 6.2 --- Results --- p.118 / Chapter 6.3 --- Discussion --- p.134 / Chapter Chapter 7 --- General discussion --- p.137 / References --- p.142
542

Effect of phytoestrogens on low-density- lipoprotein receptor and apolipoprotein A-I expression in HepG2 cells.

January 2005 (has links)
Yuen Yee Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 108-125). / Abstracts in English and Chinese. / TITLE PAGE --- p.1 / ACKNOWLEGDEMENTS --- p.2 / ABSTRACT --- p.3 / 摘要 --- p.5 / table of contents --- p.7 / list of figures and tables --- p.13 / CHAPTER 1 GENERAL INTRODUCTION --- p.16 / Chapter 1.1 --- role of PHYTOESTROGENS in soy and red WINE the PREVENTION OF CARDIOVASCULAR DISEASES (CVD) --- p.17 / Chapter 1.1.1 --- INTRoduction and Classification of Phytoestrogens --- p.17 / Chapter 1.1.2 --- estrogenic1ty of phytoestrogens and theIr abundancesin Plasma --- p.18 / Chapter 1.1.3 --- phytoestrogens as one of the active components In cvd Protection --- p.21 / Chapter 1.1.4 --- effects of Phytoestrogens on LDL Receptor and Apolipoprotein A-1 --- p.22 / Chapter 1.2 --- role of estrogen receptors (ers) in gene regulation --- p.24 / Chapter 1.2.1 --- "structure, Classification and tissue distribution of ERS" --- p.24 / Chapter 1.2.2 --- ligands for ERS --- p.25 / Chapter 1.2.3 --- mechaniSMS OF LIgands-ERS complex in GENE regulation --- p.27 / Chapter 1.2.4 --- ligand-independent ER activation --- p.28 / Chapter 1.3 --- aims and scopes of investigation --- p.29 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.30 / Chapter 2.1 --- chemicals and materials --- p.30 / Chapter 2.1.1 --- Chemicals --- p.30 / Chapter 2.1.2 --- Plasmids --- p.30 / Chapter 2.2 --- mammalian cell culture maintainence --- p.30 / Chapter 2.2.1 --- Maintenance of Cells --- p.31 / Chapter 2.2.2 --- Preparation of Cell Stock --- p.31 / Chapter 2.2.3 --- Cell Recovery from Liquid Nitrogen Stock --- p.31 / Chapter 2.3 --- manipulation of dna --- p.31 / Chapter 2.3.1 --- isolation of HEPG2 cells genonmic DNA --- p.31 / Chapter 2.3.2 --- separation and purification of dna from agarose gel --- p.31 / Chapter 2.3.3 --- Restriction digestionof DNA --- p.32 / Chapter 2.3.4 --- Ligation of DNA Fragments --- p.32 / Chapter 2.3.5 --- Transformation of --- p.32 / Chapter 2.3.6 --- Small Scale Plasmids Purification from DH5a --- p.32 / Chapter 2.4 --- construction of expression and reporter plasmids --- p.33 / Chapter 2.4.1 --- Construction of Estrogen Receptorα (Erα) Expression Vectors --- p.33 / Chapter 2.4.2 --- construction of reporter vectors of LDLR promoter and the Respective Mutants --- p.33 / Chapter 2.4.3 --- Construction of Reporter Vectors of APOAI Promoter and the Respective Mutants --- p.33 / Chapter 2.5 --- determination of promoter transcrtiption activities --- p.34 / Chapter 2.5.1 --- Transient Transfection of Cell with ERa Expression Vector and Promoter Reporter using Lipofectamine PLUS Reagent --- p.34 / Chapter 2.5.2 --- Dual Luciferase Assay --- p.34 / Chapter 2.6 --- semi-quantitative and quantitative rt-pcr assay --- p.34 / Chapter 2.6.1 --- Transient transfection of Cell with ERa Expression Vector Using Lipofectamine PLUS Reagent --- p.34 / Chapter 2.6.2 --- "Isolation of RNA using TRIzol® Reagent (Life Technology, USA)" --- p.35 / Chapter 2.6.3 --- Quantitation of RNA --- p.35 / Chapter 2.6.4 --- First Strand cDNA Synthesis --- p.35 / Chapter 2.6.5 --- Sem卜Quantitative PCR Reactions --- p.35 / Chapter 2.6.6 --- Quantitative PCR Reactions --- p.36 / Chapter 2.7 --- western blotting analysis --- p.36 / Chapter 2.8 --- statistical methods --- p.36 / Chapter CHAPTER 3 --- REGULATION BY PHYSIOLOGICAL LEVEL OF 17B-ESTRADIOL ON APOLIPOPROTEIN A-I AND LOW-DENSITY- LIPOPROTEIN RECEPTOR IN HEPG2 CELLS --- p.37 / Chapter 3.1 --- introduction --- p.37 / Chapter 3.2 --- results --- p.39 / Chapter 3.2.1 --- Determination of transient transfection functionality of estrogen receptors in hepg2 cells --- p.39 / Chapter 3.2.2 --- Effect of 17β-Estradiolon LDLR promoter transcription activity --- p.39 / Chapter 3.2.3 --- Effect of 17β-Estradiol on apoai promoter transcription activity --- p.40 / Chapter 3.2 --- discussion --- p.47 / Chapter CHAPTER 4 --- SOY ISOFLAVONES AND RESVERATROL DISPLAY DIFFERENT MECHANISM IN THE UP-REGULATION OF LOVV-DENSITY-LIPOPROTEIN RECEPTOR IN HEPG2 CELLS --- p.49 / Chapter 4.1 --- introduction --- p.49 / Chapter 4.2 --- results --- p.54 / Chapter 4.2.1 --- Association of ERα and isoflavones or resveratrol on LDLR promoter transcription activity --- p.54 / Chapter 4.2.2 --- Association of ERβ and isoflavones or resveratrol on LDLR promoter transcription activity --- p.54 / Chapter 4.2.3 --- "Role of MAP Kinase, PKA and PKC in isoflavones and resveratrol induced LDLR promoter transcription" --- p.55 / Chapter 4.2.4 --- Identification of promoter regions responsible for induction of LDLR transcription by isoflavones in the presence OF ERα --- p.55 / Chapter 4.2.5 --- Identification of promoter regions responsible for induction of LDLR TRANSCRIPTION BY resveratrol IN THE ABSENCE OF ERα --- p.56 / Chapter 4.3 --- DISCUSSION --- p.75 / Chapter CHAPTER 5 --- SOY ISOFLAVONES AND RESVERATROL UP-REGULATE APOLIPOPROTEIN A-I SIMILAR TO 17B-ESTRADIOL IN HEPG2 CELLS --- p.80 / Chapter 5.1 --- INTRODUCTION --- p.80 / Chapter 5.2 --- RESULTS --- p.84 / Chapter 5.2.1 --- Association of ERα phytoestrogens on APCAI gene expression --- p.84 / Chapter 5.2.2 --- Association of ERβ and isoflavones or resveratrol on APOAI promoter transcription activity --- p.85 / Chapter 5.2.3 --- "Role of MAP Kinase, PKA and PKC in isoflavones and resveratrol in APOAI promoter transcription in the presence of ERα" --- p.85 / Chapter 5.2.4 --- Identification of promoter regions responsible for induction of APOAI transcription by isoflavones and resveratrol in the presence of ERα --- p.85 / Chapter 5.3 --- DISCUSSION --- p.100 / Chapter CHAPTER 6 --- GENERAL DISCUSSION --- p.103 / Chapter CHAPTER 7 --- SUMMARY --- p.106 / BIBLIOGRAPHY --- p.108 / APPENDIX 1 ABBREVIATIONS --- p.126 / APPENDIX 2 MATERIALS AND METHODS --- p.129 / APPENDIX 3 PRIMER LISTS --- p.145 / APPENDIX 4 REAGENTS AND BUFFERS --- p.147
543

Effects of tetrandrine on hepatocarcinoma cell lines.

January 2011 (has links)
Yu, Wai Lam. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 79-88). / Abstracts in English and Chinese. / Acknowledgements --- p.IV / Abstract --- p.V / 論文摘要 --- p.VII / Table of Contents --- p.IX / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Cancer --- p.1 / Chapter 1.2 --- Hepatocellular Carcinoma (HCC) --- p.2 / Chapter 1.2.1 --- Risk factors causing HCC --- p.3 / Chapter 1.2.2 --- Molecular mechanism of HCC --- p.7 / Chapter 1.2.3 --- Treatment of HCC --- p.8 / Chapter 1.3 --- Tetrandrine (Tet) - A Natural Compound Derived from Traditional Chinese Medicine (TCM) --- p.10 / Chapter 1.3.1 --- Traditional Chinese Medicine (TCM) --- p.10 / Chapter 1.3.2 --- Tetrandrine (Tet) --- p.12 / Chapter 1.4 --- Molecular View of Apoptosis --- p.14 / Chapter 1.4.1 --- Overview of apoptosis --- p.14 / Chapter 1.4.2 --- Caspase cascade --- p.15 / Chapter 1.4.3 --- Bcl-2 protein family --- p.18 / Chapter 1.4.4 --- The role of mitochondria in apoptosis --- p.20 / Chapter 1.5 --- Anti-cancer Agents Inducing Apoptosis Are New Targets --- p.22 / Chapter 1.6 --- Aim of Study --- p.26 / Chapter Chapter 2 --- Materials and Methods --- p.27 / Chapter 2.1 --- Cell Culture And Treatment --- p.27 / Chapter 2.1.1 --- Cell lines used --- p.27 / Chapter 2.1.2 --- Tetrandrine (Tet) --- p.28 / Chapter 2.1.3 --- Chemicals and reagents 2 --- p.83 / Chapter 2.1.4 --- Solution preparation --- p.29 / Chapter 2.1.5 --- Procedures --- p.30 / Chapter 2.2 --- Cell viability --- p.32 / Chapter 2.2.1 --- Chemicals and reagents . --- p.32 / Chapter 2.2.2 --- Solution preparation --- p.32 / Chapter 2.2.3 --- Procedures --- p.32 / Chapter 2.3 --- Apoptosis detection --- p.34 / Chapter 2.3.1 --- Chemicals and reagents --- p.34 / Chapter 2.3.2 --- Solution preparation --- p.35 / Chapter 2.3.3 --- Procedures --- p.36 / Chapter 2.4 --- Gene expression in tet-induced apoptotic cells --- p.39 / Chapter 2.4.1 --- Chemicals and reagents --- p.39 / Chapter 2.4.2 --- Solution preparation --- p.40 / Chapter 2.4.3 --- Procedures --- p.40 / Chapter 2.5 --- Protein expression in tet-induced apoptotic cells --- p.44 / Chapter 2.5.1 --- Chemicals and reagents --- p.44 / Chapter 2.5.2 --- Solution preparation --- p.45 / Chapter 2.5.3 --- Procedures --- p.48 / Chapter 2.6 --- Cell cycle analysis of tet-treated cells --- p.54 / Chapter 2.5.1 --- Chemicals and reagents --- p.54 / Chapter 2.5.2 --- Solution preparation --- p.54 / Chapter 2.5.3 --- Procedures --- p.54 / Chapter Chapter 3 --- Result --- p.56 / Chapter Chapter 4 --- Discussion --- p.70 / Chapter 4.1 --- Dose- and Time- Dependent Inhibitory Effects of Tet were found on HuH-7 And JHH-4 Cell Lines --- p.70 / Chapter 4.2 --- Tet Is More Selective Towards Liver Cancer Cells --- p.71 / Chapter 4.3 --- The Cell Death in HuH-7 Cells Induced by Tet is Mediated Through Apoptosis --- p.72 / Chapter 4.4 --- Hepatocellular Carcinoma (HCC)Tet Induces G1 Phase Cell Cycle Arrest as Part of Its Mechanism in Inducing Apoptosis in HuH-7 Cells --- p.73 / Chapter 4.5 --- Tet Could Probably Induce G1 Phase Cell Cycle Arrest in JHH-4 Cells --- p.75 / Chapter 4.6 --- "Tet-induced Apoptosis Involves the Intrinsic, Caspase-Dependent Pathway in Both the HuH-7 and JHH-4 Cell Lines" --- p.75 / Chapter 4.7 --- Proteins in Bcl-2 Family are Involved in the Inhibitory Mechanism of Tet --- p.77 / Reference --- p.79
544

Antifungal activities of metergoline, purpurin and baicalein on Candida species. / CUHK electronic theses & dissertations collection

January 2010 (has links)
Baicalein is known to be a potent antifungal agent and induces programmed cell death in Candida albicans. In the present study, we found that baicalein also inhibited the growth of C. krusei isolates. The minimal inhibitory concentrations of baicalein against eight C. krusei isolates were 1.35--2.70 microg/ml. One-hour exposure to baicalein elicited a consistent and moderate post-antifungal effect on the C. krusei isolates. Further flow cytometric study demonstrated a depolarization of mitochondrial membrane potential. However, both the levels of reactive oxygen species and DNA fragmentation were not significantly changed after baicalein treatment in C. krusei. It can be concluded that the antifungal activity of baicalein was mitochondria-dependent in both C. krusei and C. albicans, but the antifungal mechanism was different. Reactive oxygen species may not play a direct role and baicalein does not initiate programmed cell death or apoptosis in C. krusei. The structure-activity relationship study showed that the three hydroxyl groups in baicalein were essential for its antifungal potency. / Candidiasis has become a serious infection with very high mortality and morbidity in the world if not providing effective treatments. However, due to clinical limitation and resistance of the current antifungal agents, there is an urgent need to search for novel antifungals. In this study, after screening a compound library (n=400) for antifungal activity, three members (metergoline, purpurin and baicalein) were chosen for further study. Their antifungal characteristics and the antifungal mechanisms were investigated. / Metergoline, a serotonin receptor antagonist, was found to have potent antifungal activity against the intrinsically fluconazole-resistant human fungal pathogen Candida krusei. The minimal inhibitory concentration and minimal fungicidal concentration of metergoline against C. krusei were 4 microg/ml and 8 microg/ml respectively. Metergoline induced post-antifungal effect. Significant synergism was found in combination of metergoline with amphotericin B by a checkerboard assay, which may be due to the perturbation of cell permeability and increase in the intracellular accumulation of antifungal agents. Metergoline also inhibited extracellular phospholipase production in C. krusei. To gain insights into the mechanisms, intracellular changes that accompany apoptosis were examined by flow cytometry and spectrophotometry. The results showed an increase in the level of reactive oxygen species, depolarization of mitochondrial membrane potential, phosphatidylserine externalization, and positive terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labelling in the metergoline-treated C. krusei . Taken together, we conclude that metergoline may promote apoptosis in C. krusei through reactive oxygen species production and perturbation in mitochondrial homeostasis, implying its antifungal potential to treat candidiasis. / The antifungal activity of purpurin, a natural red anthraquinone pigment in madder root (Rubia tinctorum L.), was evaluated against Candida isolates by a broth microdilution assay. The minimal inhibitory concentrations of purpurin against Candida species isolates were 1.28--5.12 microg/ml. Mechanistic studies indicated that purpurin inhibited energy-dependent efflux pumps of Candida isolates. Furthermore, purpurin demonstrated a depolarization of mitochondrial membrane potential, suggesting a possible linkage of the antifungal mechanism of purpurin to Candida apoptosis. / Kang, Kai. / Adviser: Fong Wing Ping. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 98-123). / 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.
545

Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and mitochondrial dysfunction. / CUHK electronic theses & dissertations collection

January 2010 (has links)
Additionally, cyclosporin A, an inhibitor of the mitochondrial permeability transition (MPT) pore, failed to prevent hIAPP-induced DeltaPsim collapse, cytochrome c and AIF release and caspase-3 activation, indicating that the MPT pore was not involved in hIAPP-induced apoptosis. On the other hand, potential crosstalk between the extrinsic and intrinsic apoptotic pathways was demonstrated by cleavage of Bid by caspase-8 in the apoptotic process triggered by hIAPP. / It is widely accepted that human islet amyloid polypeptide (hIAPP) aggregation plays an important role in the loss of insulin-producing pancreatic beta cells. Insulin secretion impairment and cell apoptosis can be due to mitochondrial dysfunction in pancreatic beta cells. hIAPP-induced cytotoxicity is mediated by the generation of reactive oxygen species (ROS). Phycocyanin (PC) is a natural compound from blue-green algae that is widely used as food supplement. Currently, little information is available about the effect of hIAPP on mitochondrial function of beta cells and protection of PC against hIAPP-induced cytotoxicity. In this thesis, I hypothesize that hIAPP may impair beta cell function with the involvement of mitochrondrial dysfunction, and this effects could be attenuated by PC. Therefore, the aim of this study was to investigate the role of mitochondria in hIAPP-induced apoptosis, the in vitro protective effects of PC and explore the underlying mechanisms. / It was found that hIAPP induced apoptosis in INS-1E cells with the disruption of mitochondrial function, as evidenced by ATP depletion, mitochondrial mass reduction, mitochondrial fragmentation and loss of mitochondrial membrane potential (DeltaPsim). Further molecular analysis showed that hIAPP induced changes in the expression of Bcl-2 family members, release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria into cytosol, activation of caspases and cleavage of poly (ADP-ribose) polymerase. Interestingly, the hIAPP-induced mitochondrial dysfunction in INS1-E cells was effectively restored by co-treatment with PC. / Our results showed that hIAPP inhibited the INS-1E cell growth in a dose-dependent manner. However, cytotoxicity of hIAPP was significantly attenuated by co-incubation of the cells with PC. hIAPP induced DNA fragmentation and chromatin condensation, which were key characteristics of cell apoptosis. These changes were inhibited by PC as examined by TUNEL assay and DAPI staining. Moreover, PC significantly prevented the hIAPP-induced overproduction of intracellular ROS and malonaldehyde (MDA), as well as changes of activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Furthermore, hIAPP triggered the activation of mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinase (JNK) and p38 kinase, and these effects were effectively suppressed by PC. / Taken together, I have demonstrated for the first time the involvement of mitochondrial dysfunction in hIAPP-induced INS-1E cell apoptosis, which was attenuated by PC through attenuating oxidative stress, modulating JNK and p38 pathways and reducing mitochondrial dysfunction. / Li, Xiaoling. / Adviser: Juliana Chung Ngor Chan. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 150-159). / 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.
546

Cardioprotective effects of Chinese medicinal materials in rat model systems. / CUHK electronic theses & dissertations collection

January 2004 (has links)
Woo Yiu Ho Anthony. / "August 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 176-198). / 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.
547

Studies of the active constituents of Angelica sinensis and Garcinia hanburyi on colon cancer. / 當歸及藤黃的活性成分對大腸癌的抗癌作用研究 / CUHK electronic theses & dissertations collection / Dang gui ji teng huang de huo xing cheng fen dui da chang ai de kang ai zuo yong yan jiu

January 2010 (has links)
Colorectal cancer is the second leading cause of cancer-related mortality in Hong Kong and lack of selectivity has limited the success of conventional chemotherapy. Given the recent interest in the anti-cancer effects of traditional Chinese medicine (TCM), there are two approaches to studying its bioactivity: as a mixture of ingredients or as single compounds. The objective of the present study is to examine the anti-tumor effects of Angelicae Sinensis Radix (DG) and Garcinia hanburyi resin (TH) using both approaches, respectively, as they are traditionally used to treat inflammation. In the present study, their anti-cancer effects and the mechanisms of actions were examined for the development of potential novel chemotherapeutic drugs for colon cancer since inflammation is a predisposing factor for colon cancer. / DG extract and its three main bioactive phtbalides: n-butylidenephthalide, senkyunolide A and z-ligustilide (LGT), were found to be cytotoxic to HT-29 cells with IC50 values (24 h) of 20.70 +/- 0.85, 72.51 +/- 8.65, 18.74 +/- 1.14 and 41.98 +/- 3.64 mug/ml, respectively. The results evidenced that LGT induced G0/G 1 arrest and apoptosis, triggering cleavage of PARP, pro-caspases-3, -8 and -9 and nuclear fragmentation. LGT and cisplatin synergistically reduced the viability of HT-29 cells. More interestingly, DG extract was more potent than individual phthalides, suggesting that there are other bioactive components and/or synergistic interactions. / Individual compounds purified from TH were investigated because gambogic acid isolated from this herb has been used clinically to treat cancer, 30-Epicambogin (EPC) and guttiferone K (GUTK) showed the highest cytotoxic selectivity and potency on HT-29 cells among 15 isolated compounds. IC50 values (24 h) for EPC and GUTK in HT-29 cells were 5.36+/-0.25 and 5.39+/-0.22 muM, respectively, and both induced G0/G1 arrest by down-regulation of cyclins D1, D3, CDK4 and CDK6, while up-regulation of p21Waf1/CiP1 and p27KiP1. Both compounds triggered the activation of caspases-3, -8 and -9 in apoptosis. The in vivo anti-tumor effects of GUTK were further investigated by using a subcutaneous Colon-26 mouse tumor model. GUTK (10 mg/kg i.p.) reduced tumor volume by 33.6% and potentiated the anti-tumor effects of 5-fluorouracil when administered concurrently. / Our findings revealed that DG rather than individual phthalides, is worthy for further study as a potential anti-cancer drug, due to the synergistic interactions among multi-components in the herb. On the other hand, EPC and GUTK, isolated from TH have potential to be developed as novel anti-tumor candidates for combination use with 5-fluorouracil. The results strongly support the use of different approaches to study TCM for chemotherapy, according to its traditional and empirical use. / Subsequently, the anti-proliferative effects of DG and Chuanxiong Rhizoma (CX) extracts and mixtures containing three phthalides in the proportions similar to their presence in both extracts were examined, since CX also contains the same phthalides, but in different proportions. DG extract was significantly more potent than its corresponding phthalide mixture to inhibit cancer cell proliferation and synergistic interaction was observed among the phthalides and other bioactive components, while the phthalides in CX extract interacted antagonistically with other components. / Kan, Lai Ting Winnie. / Adviser: Ge Lin. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 267-311). / 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.
548

The anti-cancer activities of paeoniae radix extracts on human hepatocellular carcinoma cell-line HepG2 and multidrug resistant human hepatocellular carcinoma cell-line R-HepG2 and their action mechanisms. / CUHK electronic theses & dissertations collection

January 2004 (has links)
Li Lok Yee Mandy. / "June 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 155-165). / 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.
549

Chemical, pharmacological and intestinal absorption studies of stemona alkaloids from radix stemonae. / CUHK electronic theses & dissertations collection

January 2006 (has links)
Finally, intestinal absorption of compounds A and H were also investigated by Caco-2 monolayer cell model. These results demonstrated, for the first time, that these stemona alkaloids were well absorbed in a gastrointestinal cell culture model. Furthermore, compound A was demonstrated to have a marked preference in the basolateral to apical transport direction, and such efflux (basolateral to apical) transport was inhibited by both verapamil and cyclosporine A, P-glycoprotein (P-gp) inhibitors, but not by probenecid and MK371, multidrug resistant-associated protein (MRP) inhibitors. The results suggested that compound A transported through active efflux mechanisms via P-gp but not MRP pathway. / High performance liquid chromatography (HPLC) coupled with evaporative laser scattering detector (ELSD) was developed to qualitatively and quantitatively determine the chemical profiles of Radix Stemonae. The results demonstrated that the type and quantity of the main bioactive ingredients, stemona alkaloids, present in various herbal samples varied significantly. Compound A (neotuberostemonine) was identified as a predominant alkaloid in two commercial Radix Stemonae samples, whereas compound F (croomine), compound H (tuberostemonine) and compound G (oxoneotuberostemonine) were identified as the major alkaloids present in other three commercial samples, respectively. Chemical variations were observed in several fresh Radix Stemona samples collected in mainland China. These chemical variations might be due to species and/or environmental differences. / In addition to the antitussive activities, it was found that a high dose of compound A caused markedly behavioral changes, including head and body shaking via both intraperitoneal and intracerebroventricular administration. Such adverse effect was abolished by a centrally acting dopamine D2 antagonist haloperidol, suggesting that a central dopaminergic effect might contribute to the behavioral activities produced by compound A. Moreover, compound A was found, for the first time, to dose-dependently and competitively inhibit monoamine oxidase (MAO)-B and compound A was identified to be a weak and non-competitively inhibitor on MAO-A. It was further demonstrated that compound A increased the intercellular concentration of dopamine in the cultured PC12 cells and prevented MPTP-induced cell death in PC12 cells via inhibition of MAO. Therefore, the behavioral changes induced by compound A was suggested to be involved with dopaminergic pathway via reduction of dopamine metabolism caused by inhibition of MAO. / On the other hand, compound F was demonstrated to cause acute lethal toxicity via intraperitoneal but not via oral administration. The results suggested that compound F might have a low oral bioavaiIability. Further absorption study by Caco-2 model demonstrated that this alkaloid had a good intestinal absorption, thus its low oral bioavailability could be due to extensive first-pass effects in the gastrointestinal tract. / Pharmacological properties of stemona alkaloids were studied in vivo using the citric acid-induced guinea pig cough model. The three stemona alkaloids present in different Radix Stemonae samples were all found to be antitussive. Compounds A and H were both orally active and had similar antitussive potencies via both oral and intraperitoneal (i.p.) administrations. Compound F was demonstrated to be antitussive via i.p. administration only. The mechanism of antitussive activity of the representative stemona alkaloid, compound A, was further investigated. However, none of the currently known antitussive pathways were identified to be involved in compound A. Thus, compound A and also other stemona alkaloids are likely to produce their antitussive activity via a novel pathway. / Radix Stemonae is derived from the root tubes of three different species of Stemona genus (Stemonaceae). This herb has been prescribed in traditional Chinese medicine (TCM) as an antitussive agent for over thousands of years. To date, over fifty stemona alkaloids have been identified from various Stemona species. However, there is a lack of direct evidence to link stemona alkaloids to the effectiveness of the herb in the treatment of cough. The aim of the present study is to investigate Stemona species used as plant sources for Radix Stemonae, the chemical and pharmacological properties in relation to antitussive activity of the herb, and the intestinal absorption of the main bioactive constituents, stemona alkaloids, in the herb. / The identity of fresh Radix Stemonae samples was investigated using a DNA based polymorphism assay. 5S-rRNA, ITS-1 and ITS-2 are highly conserved spacer regions; thus, the diversity of these spacer regions was used for the identification of Radix Stemonae samples. The amplified spacer regions of different Radix Stemona samples collected from different geographical locations in Mainland China were sequenced and compared. The result demonstrated that there were at least three different DNA patterns among seven samples examined and this DNA sequential assay could distingue species in Stemona genus from species in other genera. However, the findings suggested that the variation in chemical profiles of different Radix Stemonae samples was not directly related to their DNA sequences. DNA sequential method could be used to authenticate the correct plant sources for Radix Stemonae but it can not to provide information on chemical profiles of the herb. / The overall results demonstrated that the quantities and types of stemona alkaloids varied significantly depending upon plant sources. Furthermore, these stemona alkaloids differed considerably in pharmacological activities, toxicological effects and absorption profiles. Therefore, these variations in different Radix Stemonae samples may lead to different therapeutic outcomes, including efficacies, adverse effects, and potential herb-drug and herb-herb interactions. Nevertheless, the present study provided a scientific basis for the therapeutic use of Radix Stemonae and illustrated a potential for the development of herbal Radix Stemonae or pure stemona alkaloids into a new class of antitussive TCM herbal products or TCM-based agents in the future. / Leung Pak Ho Henry. / "January 2006." / Adviser: Ge Lin. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6328. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 179-197). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
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Avaliação da taxa de acesso à prescrição médica do tratamento preventivo de tuberculose com isoniazida em serviço especializado de HIV/aids / Evaluation of the rate of access to prescription of preventive treatment of tuberculosis with isoniazid in a specialized HIV/AIDS outpatient clinic

Picone, Camila de Melo 13 March 2014 (has links)
Introdução: O Tratamento Preventivo com Isoniazida (TPI) é indicado para os pacientes com HIV/aids e infecção latente por Micobacterium tuberculosis (ILMTb) para os quais não haja contraindicação à Isoniazida. Entretanto, barreiras de acesso podem impedir que os pacientes realizem este tratamento. Objetivos: O presente estudo avaliou a taxa de acesso à prescrição médica do TPI em sujeitos com HIV/aids e ILMTb em seguimento em um serviço especializado de HIV/aids no período de fevereiro de 2005 a dezembro de 2009. Para os sujeitos que não tiveram acesso à prescrição do TPI, buscou-se, em prontuário, justificativas para esta conduta. Também foi identificado o perfil epidemiológico, clínico e demográfico dos sujeitos com HIV/aids e ILMTb e foi descrita a característica do médico que solicitou o teste tuberculínico (TT) e do que prescreveu o TPI. Métodos: No período de 02 de fevereiro de 2005 a 31 de dezembro de 2009 que estavam em seguimento no SEAP HIV/Aids foram incluídos sujeitos com HIV/Aids e ILMTB, diagnosticada através do Teste Tuberculínico (TT). Informações referentes às variáveis analisadas foram coletadas nos prontuários médicos e através de consulta ao Sistema de Informação e Gestão Hospitalar (SIGH) - Módulo Farmácia. Resultados: Foram incluídos 238 sujeitos dentre os 310 que tiveram TT > 5 mm no período do estudo. Destes, 70,6% (168) eram do sexo masculino; a média de idade foi de 42,6 anos; 88,2% (210) dos sujeitos tiveram acesso à prescrição do TPI. O acesso à prescrição do TPI foi associado à idade, ao tamanho da resposta ao TT, ao nadir de Linfócitos TCD4+ dos sujeitos em TARV e à presença de cicatriz de BCG. Sujeitos mais jovens, com resposta ao TT igual ou maior do que 10 mm e com cicatriz de BCG tiveram maior acesso à prescrição do TPI. Uma das questões a ser explorada em futuros estudos se refere aos fatores que influenciam, ou não, a decisão do profissional de introduzir este tratamento na situação em que o mesmo está recomendado tecnicamente. Conclusão: Os sujeitos mais jovens, com melhor situação imunológica de base, maior valor de resposta ao TT e com presença da cicatriz de BCG, tiveram maior acesso ao TPI. Neste estudo foi evidenciada a necessidade de que as instituições de saúde invistam em educação continuada de seus profissionais para elevarem a cobertura de ações programáticas, como é o tratamento da ILMTB, previsto nos programas nacionais de tuberculose e de HIV/aids. Além disso, é necessário que as equipes interdisciplinares atuem de forma integrada e harmônica, para garantir o acesso às ações de saúde. É possível identificar, porém muitas barreiras que restam para a serem rompidas de modo que os cidadãos que vivem com HIV/aids tenham acesso a este e aos demais tratamentos de que tenham necessidade / Background: Isoniazid Preventive Treatment (IPT) is recommended for patients with HIV/AIDS and Latent Infection by Mycobacterium tuberculosis (ILMTb) and no contraindication to isoniazid. However, access barriers may prevent patients to undergo to this treatment. Objectives: This study evaluated the rate of access to the prescription of IPT in subjects with HIV/aids and ILMTb followed up in a specialized HIV/aids from February 2005 to December 2009. For subjects who did not have access to the prescription of IPT, we sought, on records, justification for this conduct. Also, the epidemiological, clinical and demographic profile of individuals with HIV/AIDS and ILMTb and the characteristic of the doctor who requested the tuberculin skin test (TST) and prescribed IPT were identified. Methods: from 02 February 2005 to 31 December 2009 subjects followed up at SEAP HIV/aids with HIV/aids and ILMTB, diagnosed by Tuberculin Test (TST) were included. Information was collected from the medical records and from the Hospital Information and Management System (SIGH) - Pharmacy Module. Results: 238 subjects were included, among the 310 who had TST > 5 mm during the study period. Of these, 70.6 % (168) were male and the average age was 42.6 years, 88.2 % (210) had access to the prescription of IPT. Access to IPT prescription was associated with age , size of response to TST, nadir of lymphocytes CD4 + in subjects on ART and presence of BCG scar: younger subjects with response to TST equal to or greater than 10 mm and BCG scar had higher access rate to IPT prescription. An issue to be explored in the future refers to variables that influence the professional\'s decision to prescribe this treatment when it is technically recommended. Conclusion: younger subjects with better immune status at baseline, greater response to TST and presence of BCG scar, had more access to IPT. This study highlighted the need of educational programs for health professionals, in order to improve the coverage of activities devoted to reduce morbidity and mortality in HIV/aids patients, as is the treatment of ILMTB, recommended in national tuberculosis and HIV/AIDS programs. Furthermore, it is crucial, for interdisciplinary health teams, to operate in an integrated and harmonious way, to ensure, for HIV/aids patients, a healthy and longer life

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