by Ng Ka On. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 100-122). / Abstract --- p.i / Acknowledgement --- p.vi / Chapter 1. --- Introduction / Chapter 1.1 --- Testicular vasculature --- p.1 / Chapter 1.1.1 --- Structural organization --- p.1 / Chapter 1.1.2 --- Peculiar structural organization pertinent to the Consideration of function --- p.3 / Chapter 1.2 --- Importance of the blood flow to testicular function --- p.6 / Chapter 1.3 --- Measurement of testicular blood flow --- p.8 / Chapter 1.4 --- Control of testicular blood flow --- p.16 / Chapter 1.5 --- Adrenergic control in the testis --- p.18 / Chapter 1.5.1 --- Adrenergic innervation and source of catecholamines --- p.18 / Chapter 1.5.2 --- Regulation of testicular function --- p.20 / Chapter 1.5.3 --- Effect on testicular blood flow --- p.22 / Chapter 1.6 --- Serotonergic control in the testis --- p.23 / Chapter 1.6.1 --- Serotonergic innervation and source of serotonin --- p.23 / Chapter 1.6.2 --- Regulation of testicular function --- p.24 / Chapter 1.6.3 --- Effect on testicular blood flow --- p.25 / Chapter 1.7 --- Cholinergic control in the testis --- p.26 / Chapter 1.7.1 --- Cholinergic innervation and source of acetylcholine --- p.26 / Chapter 1.7.2 --- Regulation of testicular function --- p.28 / Chapter 1.7.3 --- Effect on testicular blood flow --- p.29 / Chapter 1.8 --- Aims of the study --- p.30 / Chapter 2. --- Materials and methods / Chapter 2.1 --- Animals --- p.31 / Chapter 2.2 --- Drugs and chemicals --- p.32 / Chapter 2.3 --- In vivo videomicroscopy method --- p.33 / Chapter 2.4 --- Hydrogen gas clearance method --- p.37 / Chapter 2.5 --- Data and statistical analyses --- p.45 / Chapter 3. --- Results / Chapter 3.1 --- Adrenergic control --- p.46 / Chapter 3.1.1 --- Response of the testicular subcapsular artery to adrenergic agonists and antagonists --- p.46 / Chapter 3.1.2 --- Effect of adrenergic agonists on testicular capillary blood flow --- p.57 / Chapter 3.2 --- Serotonergic control --- p.60 / Chapter 3.2.1 --- Response of the testicular subcapsular artery to serotonergic agonists and antagonists --- p.60 / Chapter 3.2.2 --- Effect of serotonergic agonists on testicular capillary blood flow --- p.69 / Chapter 3.3 --- Cholinergic control --- p.76 / Chapter 3.3.1 --- Response of the testicular subcapsular artery to serotonergic agonists and antagonists --- p.76 / Chapter 3.3.2 --- Effect of serotonergic agonists on testicular capillary blood flow --- p.79 / Chapter 4. --- Discussion / Chapter 4.1 --- Adrenergic control --- p.86 / Chapter 4.2 --- Serotonergic control --- p.90 / Chapter 4.3 --- Cholinergic control --- p.96 / Chapter 4.4 --- General discussion --- p.98 / Chapter 5. --- References --- p.100

Quantitative structure-activity relationships (OSAR) constitute empirical analogy models connecting chemical structure and biological activity. The analogy approach to QSAR assume that the factors important in the biological system also are contained in chemical model systems. The development of a QSAR can be divided into subproblems: 1. to quantify chemical structure in terms of latent variables expressing analogy, 2. to design test series of compounds, 3. to measure biological activity and 4. to construct a mathematical model connecting chemical structure and biological activity. In this thesis it is proposed that many possibly relevant descriptors should be considered simultaneously in order to efficiently capture the unknown factors inherent in the descriptors. The importance of multivariately and multipositionally varied test series is discussed. Multivariate projection methods such as PCA and PLS are shown to be appropriate far QSAR and to closely correspond to the analogy assumption. The multivariate analogy approach is applied to a beta- adrenergic agents, b haloalkanes, c halogenated ethyl methyl ethers and d four different families of peptides. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1986, härtill 8 uppsatser</p> / digitalisering@umu

BACKGROUND: Right ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT's unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT. METHODS: We conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics. RESULTS: We found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (=0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (=0.034) and partially reversed action potential duration at 80% repolarization shortening (=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT. CONCLUSIONS: Human RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.