Gamma-thujaplicin (GT) and beta-hydroxy thujaplicin (BHT) are two of the isopropyl derivatives of tropolone found in the heartwood of western red cedar (Thuja plicata D. Don). Several of the tropolones are effective inhibitors of the enzyme catechol-O-methyltransferase (COMT). In this work, the isolated, spirally-cut rabbit thoracic aorta preparation has been used to study possible COMT inhibition as well as other pharmacological properties of the sodium salts of GT and BHT. It was found that GT, BHT and pyrogallol, a known COMT inhibitor, all potentiated the response of the aortic strip to norepinephrine (NE). However, since it was shown that the chelating agent EDTA also potentiated the NE response, the potentiation by GT and BHT could not be attributed to COMT inhibition without further evidence. GT and BHT were found to have a stimulatory effect of their own on aortic smooth muscle tissue. BHT was a more potent agonist than GT. Phenoxybenzamine blocked the stimulatory effects of BHT and GT. This suggested alpha-adrenergic receptor involvement although the halogenoalkylamine blocking agents are not absolutely specific in their action. Cocaine produces a small potentiation of the contraction produced by GT and BHT. This potentiation suggests the involvement of endogenous NE. Cocaine does not cause relaxation of the GT and BHT responses which indicates that GT and BHT differ in mode and perhaps site of action from tyramine. BHT potentiates the tyramine response on the rabbit aortic strip. This may be due to COMT inhibition, increased NE release or merely additive effects. GT was found to produce relaxation of a histamine-induced contraction. This relaxant effect was not prevented by beta-adrenergic blockade and is likely due to a nonspecific depressant effect by GT. Both GT and BHT have produced non-specific blocking effects against NE and histamine as well as acetylcholine throughout this work. In reserpinized preparations, GT no longer produced a contraction of the aortic strip. Instead, a relaxation below normal tone was produced. It would seem that the presence of endogenous NE is required in the tissue stores before GT can cause the strips to contract. GT causes relaxation of tyramine-induced contractions in reserpinized strips. The isolated rabbit thoracic aorta was found not to be a suitable preparation for the pharmacological investigation of COMT inhibition by GT and BHT due to their own agonistic effects on this tissue as well as their nonspecific chelating properties. However, this tissue was useful in providing information on other pharmacological actions of these compounds. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

lsoflurane interacts with cytochrome P-450 in rat and human hepatic microsomes and the Δ6- and Δ5-desaturases in rat hepatic microsomes. The interaction of isoflurane with cytochrome P-450 results in its metabolism to fluoride ion and organofluorine metabolites. The cytochrome P-450 isozymes catalysing the defluorination of isoflurane were assessed in hepatic microsomes from phenobarbital-, β-naphthoflavone- and pregnenolone-16α-carbonitrilepretreated and untreated rats. One or more of the cytochrome P-450 isozymes induced by phenobarbital and pregnenolone-16α-carbonitrile appear to defluorinate isoflurane, but those induced by β-naphthoflavone do not. From a comparison of the extent of defluorination of isoflurane in hepatic microsomes from phenobarbital- and pregnenolone-16α-carbonitrile-pretreated rats, and their Kₘ and Vₘₐₓ values, it appears that isoflurane is defluorinated by one or more isozymes induced by both phenobarbital and pregnenolone-16α-carbonitrile. The major isozyme is probably cytochrome P-450PCN1. The metabolites of isoflurane were identified in human and phenobarbital-induced rat hepatic microsomes. In microsomes from phenobarbital-pretreated rats, isoflurane is metabolised to fluoride ion and trifluoroacetaldehyde; trifluoroacetic acid is not produced in measureable amounts. The trifluoroacetaldehyde produced binds to microsomal constituents. In human hepatic microsomes, the organofluorine metabolite is identified as trifluoroacetic acid. It is proposed that isoflurane is metabolised by different pathways in human and phenobarbital-induced rat hepatic microsomes. The interaction of isoflurane with the cyanide-sensitive factors was assessed by several criteria. Firstly, using the reoxidation of cytochrome b₅ as an index of fatty acid desaturase activity, isoflurane appears to interact with the Δ6- and/or Δ5-desaturases, but not the Δ9-desaturase. Secondly, these results were confirmed and clarified by the use of direct assays to measure the fatty acid desaturase activity. Using the direct assay, we confirmed that isoflurane did not inhibit the Δ9-desaturase and inhibited Δ6-desaturation of linoleic acid, but not the Δ6-desaturation of α-linolenic acid. The inhibition of the Δ6-desaturation of linoleic acid occurred at low millimolar concentrations of isoflurane. lsoflurane inhibits the Δ5-desaturation of eicosa-8, 11, 14-trienoic acid to a small extent which is only apparent at much higher concentrations of isoflurane than that which inhibits the Δ6-desaturase. Further studies focussed on measurement of the activity of Δ6-desaturase in order to attempt to study the kinetics of the inhibition of the Δ6-desaturase by isoflurane: Δ6-desaturase activity was assessed using hepatic microsomes as the source of the enzyme and linoleic acid as substrate precursor. In the course of these studies, we identified a number of factors that affected the apparent activity of the Δ6-desaturase in hepatic microsomes. These included significant levels of endogenous substrate and competing reactions in the hepatic microsomes. Endogenous substrate levels were quantified and corrected for. We then resorted to computer modelling to extract the kinetics of the Δ6-desaturase free of contributions from acyl-CoA synthetase and lysophospholipid acyltransferase, as well as enzyme decay. The kinetics of isoflurane inhibition of the Δ6-desaturase were then superimposed and studied by computer modelling.

No description available.

by Ai-Dong Qi. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 219-256). / 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.

by Ho Iok Ieng Yolanda. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 116-132). / 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.

by Ho Ka-Pong, Bosco. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 81-100). / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter CHAPTER 2: --- PURIFICATION OF HUMAN CLASS I LIVER ADH --- p.19 / Chapter CHAPTER 3: --- DISSOCIATION AND REASSOCIATION OF HUMAN CLASS I ADH BY FREEZE/THAW TECHNIQUE --- p.36 / Chapter CHAPTER 4: --- "DISSOCIATION AND REASSOCIATION OF HUMAN CLASS I ADH BY USING UREA, GdmCl,HIGH SALT AND LOW pH" --- p.51 / Chapter CHAPTER 5: --- GENERAL DISCUSSION --- p.77 / REFERENCES --- p.81

by Lam Heung-wah, Angora. / Thesis (M. Phil.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 124-131). / ACKNOWLEDGEMENTS --- p.iv / ABSTRACT --- p.v / LIST OF ABBREVIATIONS --- p.vii / LIST OF TABLES --- p.viii / LIST OF FIGURES --- p.ix / INTRODUCTION --- p.1 / LITERATURE REVIEW --- p.4 / Chapter A. --- Some Aspects of Cardiovascular Physiology and Pharmacology --- p.4 / Chapter I. --- Fundamental Principles Governing regulation of Arterial Pressure --- p.4 / Chapter II. --- Hypertension --- p.12 / Chapter III. --- Antihypertensive Substances --- p.16 / Chapter B. --- Mushrooms and Their Medicinal Values --- p.29 / Chapter I. --- "The Straw Mushroom, V. volvacea" --- p.29 / Chapter II. --- "Mushrooms, Blood Pressure, and Related Changes" --- p.32 / MATERIALS AND METHODS --- p.39 / Chapter A. --- Basic Preparative Procedures --- p.39 / Chapter I. --- Preparation of Straw Mushroom Extract (SME) --- p.39 / Chapter II. --- Purification of SME by Dialysis --- p.40 / Chapter III. --- Preparation for In vivo Blood Pressure Measurement in Rats --- p.40 / Chapter IV. --- preparation of Right Atrium for In vitro Studies --- p.41 / Chapter V. --- Preparation of Artery Strip for In vitro Studies --- p.42 / Chapter B. --- Experiments Done --- p.43 / Chapter Experiment 1. --- Toxicity of SME --- p.43 / Chapter Experiment 2. --- Hypotensive Effect of SME and Dialyzed Samples --- p.44 / Chapter Experiment 3. --- Pharmacological Antagonist Studies --- p.45 / Chapter Experiment 4. --- Effect of Autonomic Ganglion Blocker and Alpha Blocker on Hypotensive Changes Induced by SME --- p.47 / Chapter Experiment 5. --- Study on Renin-Angiotensin and Kinin Systems --- p.48 / Chapter Experiment 6. --- Urinary and Sodium Excretion in Water-loaded Rats --- p.48 / Chapter Experiment 7. --- Chronotropic and Inotropic Studies on Isolated Right Atria --- p.49 / Chapter Experiment 8. --- Contractile Responses of SME & Its Dialyzed Samples on Rat Tail Artery Strips --- p.50 / Chapter Experiment 9. --- Effect of Adrenergic Blockers in SME Preconstricted Strips --- p.51 / Chapter Experiment 10. --- Acute Oral Effect of DUL8000 and DLL8000 from SME on Blood Pressure --- p.51 / Chapter Experiment 11. --- "Chronic Oral Effect of SME on Blood Pressure, Total Free Cholesterol and Triglyceride Levels" --- p.52 / Chapter C. --- Statistics --- p.55 / RESULTS --- p.56 / Chapter A. --- Toxicity of Straw Mushroom Extract (SME) --- p.56 / Chapter B. --- Effects of SME in Normotensive Rats --- p.56 / Chapter I. --- Blood Pressure Changes --- p.56 / Chapter II. --- Pharmacological Antagonists Studies --- p.58 / Chapter III. --- Converting Enzyme Activity --- p.60 / Chapter IV. --- Urinary and Sodium Excretion --- p.60 / Chapter V. --- In vitro Arterial and Cardiac Effects --- p.61 / Chapter C. --- Cardiovascular Effects of Dialyzed Samples of SME (Molecular Mass cutoffl2000) in Spontaneously Hypertensive Rats (SHR) and Normotensive Rats --- p.61 / Chapter I. --- Blood Pressure Changes --- p.61 / Chapter II. --- In vitro Arterial and Cardiac Effects --- p.62 / Chapter D. --- Cardiovascular Effects of Dialyzed Samples (DUL8000 and DLL8000) in Spontaneously Hypertensive Rats (SHR) and Normotensive Rats --- p.63 / Chapter I. --- Blood Pressure Changes --- p.63 / Chapter II. --- In vitro Arterial and Cardiac Effects --- p.65 / Chapter E. --- The Acute Oral Effect of SME on Blood Pressure --- p.68 / Chapter F. --- "Chronic Dietary Effect of SME on Blood Pressure, Total Free Serum Cholesterol and Triglyceride Levels" --- p.68 / DISCUSSION --- p.109 / Chapter A. --- The Hypotensive Effect of SME --- p.109 / Chapter B. --- The Hypotensive Action of SME: Mechanism of Action --- p.110 / Chapter C. --- The Cardiovascular Active Fractions in SME --- p.113 / Chapter D. --- "The Cardiovascular Effect of DUL8000 and DLL8000 in Rats with Reference to Age, Sex and Strains" --- p.115 / Chapter E. --- The Oral Effect of SME on Blood Pressure and on Serum Cholesterol and Triglyceride Levels --- p.118 / SUMMARY --- p.121 / REFERENCES --- p.124 / APPENDIXES --- p.132

by Yeung, Sai-mo, Simon. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 189-207.

by Fong Wing-ping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1987. / Bibliography: leaves 186-198.