Thesis (Ph.D.)--University of Nevada, Reno, 2004. / Includes bibliographical references. Online version available on the World Wide Web.

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Thesis (Ph. D.)--University of Missouri--Columbia, 2005. / "July 2005." Typescript. Vita. Includes bibliographical references (leaves 152-167). Also issued on the Internet.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 71-91).

Avaliou-se prospectivamente 19 pacientes com obstrução infravesical por hiperplasia prostática benigna selecionados pra prostatectomia transvesical. Obteve-se um fragmento da parede da bexiga e quantificou-se o colágeno no epimísio, perimísio e endomísio do detrusor. Amostra vesicais de oito doadores cadavéricos de órgãos serviram como controles. Observou-se padrão focal de aumento do colágeno na camada muscular da bexiga dos pacientes com obstrução. Demonstrou-se que a idade correlaciona-se positivamente com o aumento da quantidade de colágeno com a diminuição da complacência vesical, o aumento da prevalência de hiperatividade detrusora e a maior chance de retenção urinária / We prospectively evaluated 19 patients with bladder outlet obstruction by benign prostatic hyperplasia selected for transvesical prostatectomy. A sample of the bladder wall was obtained and the collagen was measured at the level of epimysium, premysium and endomysium. Bladder samples from eight cadaveric organ donors were used as controls. A focal pattern of collagen increase was observed at the bladder smooth muscle layer of obstructed patients. Age was shown to correlate with increased collagen quantity. Increased collagen quantity also correlated with decreased bladder compliance, higher prevalence of detrusor overactivity and of urinary retention

Diazoxide, a non-diuretic benzothiadiazlne antihypertensive agent, is thought to act directly upon the vascular smooth muscle of the resistance vessels to exert its therapeutic effects in hypertension. Diazoxide may exert its antihypertensive action by antagonizing calcium in vascular smooth muscle. Wohl et al. (1967 and 1968) have suggested such an interaction based on experiments conducted with isolated rabbit aortae. The present experiments were designed to investigate the possible cellular locus of the postulated interaction of diazoxide with calcium using the isolated anterior mesenteric vein of the rabbit as a model of vascular smooth muscle. This vein is spontaneously motile and possesses characteristics similar to those observed for vessels of the microcirculation. Diazoxide at 10ˉ⁴ M inhibited spontaneous motility and its associated membrane electrical activity, and caused hyperpolarization in rabbit anterior mesenteric veins examined with a sucrose gap apparatus. Diazoxide also inhibited spontaneous electrical and contractile activity in guinea-pig taenia coli and in estrogen dominated rabbit uterus. In all these tissues, calcium is believed to play an important role in spontaneous electrical membrane activity. Diazoxide failed to affect contractility, rate of spontaneous contractions, or action potential configurations in isolated rabbit heart, even though the action potential in heart tissues possesses a definite calcium current component. Diazoxide reduced contractions induced in the mesenteric vein by electrical stimulation of the smooth muscle itself or by excitation of the nerve endings within the vein. Various drugs were chosen for their ability to contract the mesenteric vein in different ways. Noradrenaline contracts vascular smooth muscle even when the tissue Is depolarized with ouabain Diazoxide failed to inhibit noradrenaline contractions in the depolarized vein, but showed the characteristics of a competitive inhibitor of noradrenaline in normally polarized veins. Diazoxide was also capable of inhibiting contractions to serotonin and procaine, agents which require membrane polarization to initiate contraction. The inhibitory effect of diazoxide was not observed to be modified in solutions containing high concentrations of calcium. Diazoxide was tested upon the contractile responses to calcium In veins depolarized in K⁺ Ringer solution. Examination of the resultant dose response curves showed that diazoxide inhibited calcium contractions ln a reversible, non surmountable manner. Hydrochlorothiazide had no effect upon calcium induced contractions. Diazoxide antagonizes drug induced contractions only if a polarized membrane is present. Calcium Induced contractions in depolarizing solutions were inhibited in an apparently Insurmountable manner, while drug responses in polarizing solutions were inhibited by diazoxide in a surmountable manner. In addition, action potentials from rabbit heart were unchanged whereas, the apparently calcium spike mediated electrical activity of certain smooth muscles is inhibited. It is concluded that diazoxide affects the membrane of vascular smooth muscle to reduce excitability of the tissue to drugs or electrical stimuli. It is possible that cell membrane bound calcium could be the locus of action of diazoxide and that this agent modifies membrane calcium to cause increased membrane stability. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

The purpose of this work was to determine whether arachidonic acid and other fatty acids might directly regulate the behavior of ion channels. Arachidonic acid is known to be liberated from plasma membrane phospholipid upon activation of cell surface receptors, and to subsequently act as a precursor to biologically active metabolites. This study was based on the rationale that the liberated arachidonic acid itself was a potential regulator of plasma membrane ion channels. The effects of arachidonic acid and other fatty acids on the behavior of ion channels were examined in two preparations of isolated smooth muscle cells. In both cell types, K+-selective ion channels were activated both by arachidonic acid and by fatty acids that are not converted to metabolites through the cyclooxygenase and lipoxygenase metabolic pathways for arachidonic acid. These results indicate that metabolites of these pathways did not mediate the fatty acid response. Further, fatty acids were effective in cell-free patches of membrane in the absence of nucleotides and Ca++, showing that signal transduction mechanisms requiring these and other cytosolic factors were not required. Such signaling mechanisms include those involving phosphorylation, cyclic nucleotides, GTP-dependent proteins, and the NADPH-dependent cytochrome P450 metabolic pathway. Thus fatty acids themselves appear to directly activate K+ channels, much as they directly activate several enzymes, and may constitute a new class of messenger molecules acting on ion channels. The two preparations of cells used were gastric smooth muscle cells from the toad, Bufo Marinus, and pulmonary artery smooth muscle cells from the New Zealand White Rabbit. In gastric smooth muscle cells, a previously undescribed K+ channel was activated by a variety of fatty acids. This channel exhibited a conductance of approximately 50 pS, weak voltage-dependence, and K+ selectivity. The fatty acid structural features required for activation of this channel were examined by testing numerous fatty acids. Further, the same K+ channel was found to be endogenously active in the presence of Ca++ at the extracellular surface of the membrane. In pulmonary artery smooth muscle cells, fatty acids activated K+ channels of a recognizable large-conductance type that is activated by Ca++ at the intracellular membrane surface. This channel type has been widely studied but has not been reported in this preparation. Characteristic of the large-conductance, calcium-activated K+ (CAK) channel type, the channels activated by fatty acids exhibited a conductance of approximately 260 pS, strong voltage-dependence, K+ selectivity, and activation by low concentrations of Ca++ (10-7-10-6 M) at the cytosolic surface of the membrane. Lastly, these CAK channels were found to be activated by membrane stretch.

No description available.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 147-164.

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / "May 2001." Typescript. Vita. Includes bibliographical references (leaves 176-195). Also available on the Internet.