Yang, Hao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 53-57). / Abstract also in Chinese. / Title Page --- p.i / Thesis Committee --- p.ii / Abstract (English version) --- p.iv / Abstract (Chinese version) --- p.vi / Acknowledgment --- p.vii / Table of Contents --- p.viii / List of Tables --- p.xi / List of Figures --- p.xii / List of Abbreviations and Symbols --- p.xv / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- DNA Methylation --- p.1 / Chapter 1.2 --- DNA Methylation Repair --- p.2 / Chapter 1.3 --- Objectives of This Work --- p.2 / Chapter 1.4 --- DNA Structure --- p.3 / Chapter 1.4.1 --- Nomenclature Scheme for DNA --- p.3 / Chapter 1.4.2 --- Base Pair Scheme --- p.4 / Chapter 1.4.3 --- Sugar Conformation --- p.5 / Chapter 1.4.4 --- Backbone Conformation --- p.5 / Chapter 2 --- Materials and Methods --- p.7 / Chapter 2.1 --- Sample Design --- p.7 / Chapter 2.2 --- Sample Preparation --- p.7 / Chapter 2.3 --- UV Optical Melting Study --- p.8 / Chapter 2.4 --- NMR Study --- p.9 / Chapter 2.4.1 --- NMR Melting Study --- p.10 / Chapter 2.4.2 --- Resonance Assignment --- p.10 / Chapter 2.4.3 --- Determination of Sugar Conformation --- p.12 / Chapter 2.4.4 --- Determination of Backbone Conformation --- p.13 / Chapter 3 --- Effect of 1-Methyladenine on Double-Helical DNA Structures --- p.14 / Chapter 3.1 --- NMR Resonance Assignments --- p.14 / Chapter 3.1.1 --- TA-oligo Resonance Assignments --- p.14 / Chapter 3.1.2 --- TmlA-oligo Resonance Assignments --- p.16 / Chapter 3.2 --- DNA Double-Helical Structures upon 1-Methylation of Adenine --- p.18 / Chapter 3.2.1 --- Base Pairing Mode --- p.18 / Chapter 3.2.2 --- Sugar Puker --- p.21 / Chapter 3.2.3 --- Backbone Conformation --- p.22 / Chapter 3.3 --- Summary --- p.24 / Chapter 4 --- Effect of 1-Methyladenine on Double-Helical DNA Stabilities --- p.25 / Chapter 4.1 --- Thermodynamic Studies --- p.26 / Chapter 4.1.1 --- Influence of m6A on UV Melting Studies --- p.26 / Chapter 4.1.2 --- Thermodynamics by NMR Melting Studies --- p.28 / Chapter 4.2 --- "NMR Structural Studies on Gm1A-, Am1A- and Cm1A-oligo" --- p.33 / Chapter 4.2.1 --- Gml A-oligo --- p.33 / Chapter 4.2.1.1 --- Gm1A-oligo Resonance Assignments --- p.33 / Chapter 4.2.1.2 --- Base Pair Structures of Gm1A-oligo --- p.35 / Chapter 4.2.2 --- AmiA-oligo --- p.37 / Chapter 4.2.2.1 --- Am1A-oligo Resonance Assignments --- p.37 / Chapter 4.2.2.2 --- Base Pair Structures of Am1A-oligo --- p.39 / Chapter 4.2.3 --- Cm1A-oligo --- p.43 / Chapter 4.2.3.1 --- Cm1A-oligo Resonance Assignments --- p.43 / Chapter 4.2.3.2 --- Base Pair Structures of Cm1A-oligo --- p.45 / Chapter 4.3 --- Summary --- p.46 / Chapter 5 --- Conclusion and Future work --- p.47 / Appendix I Proton chemical shift values of TA-oligo --- p.48 / Appendix II Proton chemical shift values of TmlA-oligo --- p.49 / Appendix III Proton chemical shift values of GmlA-oligo --- p.50 / Appendix IV Proton chemical shift values of Am1A-oligo --- p.51 / Appendix V Proton chemical shift values of CmlA-oligo --- p.52 / References --- p.53

Cyclic guanosine 3', 5'-monophosphate (cGMP) has recently emerged as an endogenous regulator for controlling or reversing cardiac hypertrophy. Increased protein accumulation is a key feature of cardiac hypertrophy; thus, our study investigates the effects of a cGMP analog on protein accumulation in primary culture of adult rat cardiomyocytes and dissects out the mechanisms involved. We confirmed that a cGMP analog, 8-bromo-cGMP, inhibits phenylephrine (PE)-increased accumulation of newly synthesized proteins in cultured adult rat ventricular cardiomyocytes. Firstly, we have obtained data showing that 8-bromo-cGMP does not inhibit phosphorylation of S6K1 by PE during short time treatment (10 min to 2 h), but blocks phosphorylation of S6K1 by PE at 6 h; moreover this blocking effect is completely abolished by phosphatase inhibitor Tautomycin. Then, we have demonstrated that PE and cGMP induce sustained and transient increased phosphorylation of ERK, respectively. Moreover, cGMP inhibits PE-induced phosphorylation of ERK during long term treatment (3 and 6h). We have also shown that 8-bromo-cGMP inhibits ROS generation induced by PE. Other effects of PE that could be related to hypertrophy (i.e. increased concentration of upstream binding factor mRNA and decreased concentration of the mRNAs of Atrogin and muscle specific RING finger) were not abolished by 8-bromo-cGMP. We conclude that cGMP analog blocks protein accumulation by inhibiting the sustained phosphorylation of S6K1 via the activation of phosphatases.

No description available.

A perda da função das células beta acelera a deterioração do controle metabólico em pessoas com diabetes tipo 2. Além da lipo- e da glicotoxicidade, os AGEs parecem contribuir para esse processo, promovendo a apoptose das ilhotas pancreáticas. Em outros tecidos, os AGEs interagem com seu receptor específico (RAGE), produzindo espécies reativas de oxigênio (ROS) e ativando o NF-kB. Para investigar o efeito temporal dos AGEs sobre a apoptose de ilhotas, bem como o potencial de compostos antioxidantes para diminuir danos causados pelos AGEs, ilhotas pancreáticas de ratos foram tratadas durante 24, 48, 72, 96 e 120 h com AGEs gerados a partir de co-incubação de albumina de soro bovino (BSA) com Dgliceraldeído (GAD, 5 mg/mL) ou tampão fostato (controle). A apoptose foi avaliada pela quantificação do DNA fragmentado (ELISA), atividade de caspase 3 e detecção da permeabilidade da membrana mitocondrial (MitoProbe JC-1). O estresse oxidativo foi avaliado pela detecção de espécies de oxigênio (Image-iT LIVE Green) e a atividade da NADPH oxidase foi mensurada pelo método de quimioluminescência da lucigenina. A expressão dos genes Bax, Bcl2 e Nfkb1 foi avaliada por reação em cadeia da polimerase quantitativa após transcrição reversa (RT-qPCR). Em um dos tempos em que foi detectado o aumento da apoptose, o efeito de dois compostos antioxidantes foi avaliado: benfotiamina (350 M), uma vitamina B1 lipossolúvel, e Mito Q (1 M), um derivado da ubiquinona com alvo seletivo para a mitocôndria. Em 24 e 48 h, os AGES promoveram um aumento do índice de apoptose em relação ao controle, concomitantemente com o aumento na expresssão do gene Bcl2 (gene anti-apoptótico) e uma redução na expressão do gene Nfkb1. Em contraste, após 72, 96 h e 120 h, os AGEs promoveram um aumento do índice de apoptose em comparação com a condição de controle, concomitantemente com uma diminuição na expressão do gene Bcl2 e um aumento na expressão do gene Nfkb1. Em 24 h, os AGEs promoveram uma diminuição do conteúdo de ROS nas ilhotas, enquanto que nos tempos de 48 e 72 h, os AGEs promoveram um efeito oposto. A benfotiamina e o Mito Q foram capazes de diminuir o índice de apoptose e o estresse oxidativo de ilhotas expostas aos AGEs por 72 h. Em conclusão, os AGEs exerceram um duplo efeito em cultura de ilhotas pancreáticas, sendo de proteção contra a apoptose após exposição curta, mas pró-apoptótica após exposição prolongada. O Mito Q e e a benfotiamina merecem ser adicionalmente estudados como drogas com o potencial de oferecer proteção às ilhotas pancreáticas em condições de hiperglicemia crônica / Loss of beta cell function hastens the deterioration of metabolic control in people with type 2 diabetes. Besides lipo- and glucotoxicity, AGEs seem to contribute to this process by promoting islet apoptosis. In other tissues, AGEs interact with their specific receptors (RAGE) and elicit reactive oxygen species (ROS) generation and NF-kB activation. In order to investigate the temporal effect of AGEs on islet apoptosis as well as the potential of antioxidant compounds to decrease islet damage caused by AGEs, rat pancreatic islets were treated for 24, 48, 72, 96 and 120 h with either AGEs generated from co-incubation of bovine serum albumin (BSA) with D-glyceraldehyde (GAD, 5 mg/mL) or phosphate-buffered saline (PBS, control). Apoptosis was evaluated by quantification of DNA fragmentation (ELISA), caspase-3 enzyme activity and detection of mitochondrial permeability transition (MitoProbe JC-1). Oxidative stress was evaluated by oxygen species detection (Image-iT LIVE Green) and the activity of NADPH oxidase was measured by the lucigenin-enhanced chemiluminescence method. The expression of the genes Bax, Bcl2 and Nfkb1 was evaluated by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). In one of the time points at which increased apoptosis was detected, the effect of two antioxidant compounds was evaluated: benfotiamine (350 M), a liposoluble vitamin B1, and Mito Q (1 M), a derivative of ubiquinone targeted to mitochondria. In 24 and 48 h, AGEs elicited a significant decrease in the apoptosis rate in comparison to the control condition concomitantly with a significant increase in the RNA expression of the antiapoptotic gene Bcl2 and a significant decrease in the Nfkb1 RNA expression. In contrast, after 72 and 96 h, AGEs promoted a significant increase in the apoptosis rate in comparison to the control condition concomitantly with a significant decrease in Bcl2 RNA expression and a significant increase in Nfkb1 RNA expression. In 24 h, AGEs elicited a significant decrease in the islet content of ROS while after 48 and 72 h, AGEs promoted an opposite effect. Benfotiamine and Mito Q were able to decrease the apoptosis rate and the ROS content in islets exposed to AGEs for 72 h. In conclusion, AGEs exerted a dual effect in cultured pancreatic islets, being protective against apoptosis after short exposition but proapoptotic after prolonged exposition. Mito Q and benfotiamine deserve further evaluation as drugs that could offer islet protection in conditions of chronic hyperglycemia

A perda da função das células beta acelera a deterioração do controle metabólico em pessoas com diabetes tipo 2. Além da lipo- e da glicotoxicidade, os AGEs parecem contribuir para esse processo, promovendo a apoptose das ilhotas pancreáticas. Em outros tecidos, os AGEs interagem com seu receptor específico (RAGE), produzindo espécies reativas de oxigênio (ROS) e ativando o NF-kB. Para investigar o efeito temporal dos AGEs sobre a apoptose de ilhotas, bem como o potencial de compostos antioxidantes para diminuir danos causados pelos AGEs, ilhotas pancreáticas de ratos foram tratadas durante 24, 48, 72, 96 e 120 h com AGEs gerados a partir de co-incubação de albumina de soro bovino (BSA) com Dgliceraldeído (GAD, 5 mg/mL) ou tampão fostato (controle). A apoptose foi avaliada pela quantificação do DNA fragmentado (ELISA), atividade de caspase 3 e detecção da permeabilidade da membrana mitocondrial (MitoProbe JC-1). O estresse oxidativo foi avaliado pela detecção de espécies de oxigênio (Image-iT LIVE Green) e a atividade da NADPH oxidase foi mensurada pelo método de quimioluminescência da lucigenina. A expressão dos genes Bax, Bcl2 e Nfkb1 foi avaliada por reação em cadeia da polimerase quantitativa após transcrição reversa (RT-qPCR). Em um dos tempos em que foi detectado o aumento da apoptose, o efeito de dois compostos antioxidantes foi avaliado: benfotiamina (350 M), uma vitamina B1 lipossolúvel, e Mito Q (1 M), um derivado da ubiquinona com alvo seletivo para a mitocôndria. Em 24 e 48 h, os AGES promoveram um aumento do índice de apoptose em relação ao controle, concomitantemente com o aumento na expresssão do gene Bcl2 (gene anti-apoptótico) e uma redução na expressão do gene Nfkb1. Em contraste, após 72, 96 h e 120 h, os AGEs promoveram um aumento do índice de apoptose em comparação com a condição de controle, concomitantemente com uma diminuição na expressão do gene Bcl2 e um aumento na expressão do gene Nfkb1. Em 24 h, os AGEs promoveram uma diminuição do conteúdo de ROS nas ilhotas, enquanto que nos tempos de 48 e 72 h, os AGEs promoveram um efeito oposto. A benfotiamina e o Mito Q foram capazes de diminuir o índice de apoptose e o estresse oxidativo de ilhotas expostas aos AGEs por 72 h. Em conclusão, os AGEs exerceram um duplo efeito em cultura de ilhotas pancreáticas, sendo de proteção contra a apoptose após exposição curta, mas pró-apoptótica após exposição prolongada. O Mito Q e e a benfotiamina merecem ser adicionalmente estudados como drogas com o potencial de oferecer proteção às ilhotas pancreáticas em condições de hiperglicemia crônica / Loss of beta cell function hastens the deterioration of metabolic control in people with type 2 diabetes. Besides lipo- and glucotoxicity, AGEs seem to contribute to this process by promoting islet apoptosis. In other tissues, AGEs interact with their specific receptors (RAGE) and elicit reactive oxygen species (ROS) generation and NF-kB activation. In order to investigate the temporal effect of AGEs on islet apoptosis as well as the potential of antioxidant compounds to decrease islet damage caused by AGEs, rat pancreatic islets were treated for 24, 48, 72, 96 and 120 h with either AGEs generated from co-incubation of bovine serum albumin (BSA) with D-glyceraldehyde (GAD, 5 mg/mL) or phosphate-buffered saline (PBS, control). Apoptosis was evaluated by quantification of DNA fragmentation (ELISA), caspase-3 enzyme activity and detection of mitochondrial permeability transition (MitoProbe JC-1). Oxidative stress was evaluated by oxygen species detection (Image-iT LIVE Green) and the activity of NADPH oxidase was measured by the lucigenin-enhanced chemiluminescence method. The expression of the genes Bax, Bcl2 and Nfkb1 was evaluated by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). In one of the time points at which increased apoptosis was detected, the effect of two antioxidant compounds was evaluated: benfotiamine (350 M), a liposoluble vitamin B1, and Mito Q (1 M), a derivative of ubiquinone targeted to mitochondria. In 24 and 48 h, AGEs elicited a significant decrease in the apoptosis rate in comparison to the control condition concomitantly with a significant increase in the RNA expression of the antiapoptotic gene Bcl2 and a significant decrease in the Nfkb1 RNA expression. In contrast, after 72 and 96 h, AGEs promoted a significant increase in the apoptosis rate in comparison to the control condition concomitantly with a significant decrease in Bcl2 RNA expression and a significant increase in Nfkb1 RNA expression. In 24 h, AGEs elicited a significant decrease in the islet content of ROS while after 48 and 72 h, AGEs promoted an opposite effect. Benfotiamine and Mito Q were able to decrease the apoptosis rate and the ROS content in islets exposed to AGEs for 72 h. In conclusion, AGEs exerted a dual effect in cultured pancreatic islets, being protective against apoptosis after short exposition but proapoptotic after prolonged exposition. Mito Q and benfotiamine deserve further evaluation as drugs that could offer islet protection in conditions of chronic hyperglycemia

According to the results, Pa-PDT showed inhibitory effect on MDA-MB-231 cells in vitro with an IC50 value of 0.5 muM at 24 h. Pa-PDT was demonstrated to activate intracellular mitogen activated protein kinases (MAPK) pathways via reactive oxygen species (ROS) production. Pa-PDT IS also believed to induce extracellular signal-regulated kinase (ERK)-mediated autophagy and endoplasmic reticulum stress. Pa-PDT in combination with Tamoxifen is demonstrated to exert a synergetic effect in inhibiting cancer growth. The combination treatment induces both intrinsic and extrinsic apoptosis. Regarding the direct cancer cell killing activity, two dimensional gel electrophoresis screening revealed that Pa-PDT regulates proteins which involve in human leukocyte antigen (HLA) class I-restricted antigen-processing machinery. This activation of antigen presentation was confirmed by Western blot analysis and immunostaining. Furthermore, a cross-presentation of antigen with HLA class I proteins and 70-kDa heat shock protein was found in Pa-PDT-treated cells, as shown by the fluorescent microscopic observation and immunoprecipitation assay. Moreover, the immunogenicity of breast cancer cells was increased by Pa-PDT treatment that triggered phagocytic activity by human macrophages. Our findings provide the first evidence that Pa-PDT can trigger both apoptosis and anti-tumour immunity. / Cancer is one of the most lethal diseases worldwide. Treatments of cancer comprise surgical intervention, radiotherapy or chemotherapy; however, their side effects are still need to be overcome. In order to search for anti-cancer treatments with milder side effects and higher efficiency, traditional Chinese medicine (TCM) has been investigated. Previous study in our laboratory reported that pheophorbide a (Pa), an active compound purified from Scutellaria barbata, combined with photodynamic therapy (PDT) approach produces anti-tumour effect in a wide range of human cancers. Because of the lack of protocols for curing late phase breast cancer, my project is to investigate the therapeutic potential of Pa-PDT and its action mechanism on human breast cancer. A human breast cancer cell line MDA-MB-231, which is estrogen receptor nude and resistant to a conventional breast cancer drug tamoxifen, was used as an in vitro tumour model in my study to mimic the late stage of breast cancer. / Pheophorbide a (Pa) has been proposed to be a potential photosensitizer for the photodynamic therapy of human cancer. However, the immunomodulatory effect of Pa, in the absence of irradiation, has not yet been investigated. The present study revealed that Pa possessed immunostimulating effect on a murine macrophages cell line RAW 264.7. Pa could stimulate the growth of RAW 264.7 cells with the maximal effect at 0.5 muM after 48 h of treatment, where MAPK family including c-Jun N-tenninal kinase (JNK), ERK and p38 MAPK were activated by Pa treatment in a dose-dependent manner. Moreover, the induction of interleukin-6 and tumour necrosis factor-a secretion, and the enhancement of phagocytic activity were observed in Pa-treated RAW 264.7 cells. The results were similar in Pa-treated human immune competent cells (e.g. CD4+ and CD14+ cells) at higher Pa concentrations (from 1 to 10 muM). The present work is the first report to demonstrate the potential immunomodulatory effects of Pa on immune competent cells, apart from its well-known anti-tumour activity. / Bui Xuan, Ngoc Ha. / "December 2010." / Advisers: Fung Kwok Pui; Wong Chun Kwok. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 123-144). / 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.

Hoi, Wan Heng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 212-245). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Zou Wei. / Thesis submitted in: December 2001. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 98-119). / Abstracts in English and Chinese. / Declaration --- p.i / Acknowledgements --- p.ii / Publication lists --- p.iii / Abstract --- p.ix / Abbreviations --- p.xiii / List of tables and figures --- p.xiv / Chapter Chapter 1: --- General Introduction --- p.1 / Chapter 1.1. --- Endothelium-dependent relaxation in coronary and pulmonary circulation --- p.1 / Chapter 1.1.1. --- Endothelium-derived relaxing factors --- p.2 / Chapter 1.1.1.1. --- Nitric Oxide --- p.3 / Chapter 1.1.1.2. --- PGI2 --- p.5 / Chapter 1.1.1.3. --- EDHF --- p.6 / Chapter 1.1.2. --- EDHF in coronary and pulmonary circulation --- p.8 / Chapter 1.1.2.1. --- EDHF in coronary circulation --- p.8 / Chapter 1.1.2.2. --- EDHF in pulmonary circulation --- p.9 / Chapter 1.2. --- Effect of hyperkalemia on EDHF-mediated relaxation --- p.10 / Chapter 1.3. --- Organ Preservation Solutions --- p.13 / Chapter 1.3.1. --- Euro-Collins solution --- p.14 / Chapter 1.3.2. --- University of Wisconsin solution --- p.15 / Chapter Chapter 2: --- Objectives and research approaches --- p.16 / Chapter 2.1. --- Objectives --- p.16 / Chapter 2.1.1. --- "Endothelium-dependent relaxation resistant to INDO, L-NNA, and HbO in porcine and pulmonary coronary micro-arteries" --- p.16 / Chapter 2.1.2. --- "EET11,12 and EDHF-mediated function in porcine coronary micro-arteries" --- p.17 / Chapter 2.1.3. --- "Comparison of EC or UW solution on endothelium-dependent relaxation resistant to INDO, l-NNA, and HbO in porcine pulmonary arteries" --- p.17 / Chapter 2.2. --- Research approaches --- p.18 / Chapter 2.2.1. --- "Endothelium-dependence of the relaxation by BK or EET11,12" --- p.18 / Chapter 2.2.2. --- Effect of hypothermic storage with EC and UW solution on EDHF-related relaxation --- p.18 / Chapter 2.2.3. --- Time-dependent alteration of endothelium-dependent relaxation in pulmonary micro-arteries by EC and UW solution --- p.19 / Chapter 2.2.4. --- Effect of HbO in endothelium-dependent relaxation --- p.19 / Chapter Chapter 3: --- Material and Methods --- p.21 / Chapter 3.1. --- General Methods --- p.21 / Chapter 3.1.1. --- Porcine heart and lung collection and transportion / Chapter 3.1.2. --- Myograph --- p.21 / Chapter 3.1.3. --- Myosight --- p.24 / Chapter 3.1.4. --- Anatomizing blood vessel --- p.24 / Chapter 3.1.5. --- Mounting --- p.24 / Chapter 3.1.6 --- Normalization --- p.26 / Chapter 3.1.6.1. --- Normalization of coronary micro-artery --- p.27 / Chapter 3.1.6.2. --- Normalization of pulmonary micro-artery --- p.28 / Chapter 3.1.7. --- Precontraction --- p.30 / Chapter 3.1.8. --- Endothelium-dependent relaxation --- p.31 / Chapter 3.2. --- Coronary artery studies --- p.32 / Chapter 3.2.1. --- Porcine heart harvest and anatomy --- p.32 / Chapter 3.2.2. --- Characteristic of histology of porcine coronary micro-artery --- p.32 / Chapter 3.3. --- Pulmonary artery studies --- p.35 / Chapter 3.3.1. --- Porcine lung harvest and anatomy --- p.35 / Chapter 3.3.2. --- Characteristic of histology of porcine pulmonary micro- artery --- p.36 / Chapter 3.4. --- Drugs --- p.41 / Chapter 3.4.1. --- Drugs --- p.41 / Chapter 3.4.2. --- Preparation of oxyhemoglobin solution --- p.41 / Chapter 3.5. --- Statistical Analysis --- p.42 / Chapter 3.5.1. --- Calculation of EC50 --- p.42 / Chapter 3.5.2. --- Statistical analysis --- p.42 / Chapter Chapter 4: --- "Epoxyeicosatrienoic Acids (EET11,12) May Partially Restore EDHF-Mediated Function in Coronary Micro-Arteries" --- p.43 / Chapter 4.1. --- Abstract --- p.43 / Chapter 4.2. --- Introduction --- p.44 / Chapter 4.3. --- Experimental Protocol --- p.45 / Chapter 4.3.1. --- Precontraction --- p.45 / Chapter 4.3.2. --- "EDHF-mediated (INDO, L-NNA, and HbO-resistant) relaxation" --- p.45 / Chapter 4.3.3. --- "EET11,12-mediated relaxation after exposure to hyperkalemia" --- p.46 / Chapter 4.3.4. --- "The effect of incubation with EET11,12 on the BK-induced, EDHF-mediated relaxation" --- p.46 / Chapter 4.4. --- Results --- p.47 / Chapter 4.4.1. --- Resting force --- p.47 / Chapter 4.4.2. --- HbO and U46619-induced contraction force --- p.48 / Chapter 4.4.3. --- "EET11,12-induced relaxation in coronary micro-arteries after exposure to hyperkalemia" --- p.49 / Chapter 4.4.4. --- "The EDHF-mediated relaxation to BK resistant to INDO, l- NNA,and HbO" --- p.51 / Chapter 4.4.4.1. --- Incubated in either hyperkalemic solution (K+ 20mmol/L) or Krebs' solution (control) --- p.51 / Chapter 4.4.4.2. --- "Incubated in either hyperkalemic solution (K+ 20mmol/L) plus EET11,12 or Krebs' solution (control)" --- p.53 / Chapter 4.5. --- Discussion --- p.57 / Chapter 4.5.1. --- EDHF plays an important role in the coronary micro-arteries --- p.57 / Chapter 4.5.2. --- "EDHF-mediated (INDO, l-NNA, and HbO-resistant) relaxation in the coronary micro-arteries" --- p.58 / Chapter 4.5.3. --- "EET11,12 may partially mimic the EDHF-mediated relaxation in the porcine coronary micro-artery" --- p.59 / Chapter 4.5.4. --- "Effect of EET11,12 added in hyperkalemia may partially restore the EDHF-mediated relaxation in the porcine coronary micro-arteries" --- p.59 / Chapter Chapter 5: --- Impaired EDHF-Mediated Relaxationin Porcine Pulmonary Micro-arteries by Cold Store with Euro-Collin's and University of Wisconsin Solution --- p.61 / Chapter 5.1. --- Abstract --- p.61 / Chapter 5.2. --- Introduction --- p.62 / Chapter 5.3. --- Experimental Protocol --- p.64 / Chapter 5.3.1. --- Precontraction --- p.64 / Chapter 5.3.2. --- "Role of EDHF-mediated (INDO, L-NNA and HbO-resistant) relaxation in porcine pulmonary micro-arteries by BK orA23187" --- p.64 / Chapter 5.3.3. --- Effect of hyperkalemia or preservation solutions (EC or UW) on the EDHF-mediated relaxation by BK or A23187 --- p.65 / Chapter 5.3.3.1. --- The effect of hyperkalemia --- p.65 / Chapter 5.3.3.2. --- Effect of EC solution on the EDHF-mediated relaxation --- p.65 / Chapter 5.3.3.3. --- Effect of UW solution on the EDHF-mediated relaxation --- p.66 / Chapter 5.3.3.4. --- The effect of UW and EC solutions on the contractility of the pulmonary micro-artery --- p.66 / Chapter 5.4. --- Results --- p.66 / Chapter 5.4.1. --- Resting force --- p.66 / Chapter 5.4.2. --- U46619-induced contraction force --- p.67 / Chapter 5.4.3. --- Role of EDHF-mediated relaxation induced by BK or A23187 --- p.67 / Chapter 5.4.4. --- The effect of hyperkalemia --- p.71 / Chapter 5.4.5. --- Effect of EC solution on the EDHF-mediated relaxation --- p.72 / Chapter 5.4.6. --- Effect of UW solution on the EDHF-mediated relaxation --- p.73 / Chapter 5.4.7. --- The effect of UW and EC solution on the contractility of the pulmonary micro-artery --- p.73 / Chapter 5.5. --- Discussion --- p.77 / Chapter 5.5.1. --- EDHF-mediated endothelial function exists in the pulmonary micro-circulation --- p.77 / Chapter 5.5.2. --- Hyperkalemia exposure reduces EDHF-related relaxation and possible mechanism --- p.78 / Chapter 5.5.3. --- The effect of EC and UW solutions on the EDHF-media relaxation in the pulmonary micro-arteries --- p.79 / Chapter Chapter 6: --- General Discussion --- p.82 / Chapter 6.1. --- Endothelium-dependent vasodilators: BK and A23187 --- p.82 / Chapter 6.2. --- EDHF in porcine coronary and pulmonary micro-arteries --- p.84 / Chapter 6.2.1. --- EDHF in porcine coronary micro-arteries --- p.84 / Chapter 6.2.2. --- EDHF in porcine pulmonary micro-arteries --- p.87 / Chapter 6.2.3. --- Vascular stretch and release of endothelium-derived vasodilators --- p.87 / Chapter 6.2.4. --- "EET11,12" --- p.88 / Chapter 6.3. --- "Endothelium-dependent relaxation resistant to INDO, L- NNA, and HbO in porcine coronary and pulmonary microcirculation" --- p.89 / Chapter 6.4. --- "Alteration of endothelium-dependent relaxation resistant to INDO, l-NNA, and HbO after exposure to hyperkalemia" --- p.90 / Chapter 6.5. --- "Alteration of endothelium-dependent contraction resistant to INDO, L-NNA, and HbO after exposure to EC or UW solutions" --- p.91 / Chapter 6.6. --- Clinical implications --- p.92 / Chapter 6.7. --- Limitations --- p.93 / Chapter 6.7.1. --- Common limitations --- p.93 / Chapter 6.7.2. --- Limitation of in vitro study --- p.93 / Chapter 6.8. --- Future work --- p.94 / Chapter Chapter 7: --- Conclusion --- p.96 / References --- p.98 / Appendies / "Wei Zou, Qin Yang, Anthony PC Yim, & Guo-Wei He Epoxyeicosatrienoic acids (EET11,12) may partially restore endothelium- derived hyperpolarizing factor-mediated function in coronary micro- arteries. Annals of Thoracic Surgery. 2001; 72(12): 1970~1976."

Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 218-235). / 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.

Tong Hoi Yee. / "July, 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 237-253). / 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.