Thesis (M.S.)--University of Wisconsin--Madison, 1963. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 28-30).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The effects of tetrodotoxin (TTX) and other neurotropic drugs on anaerobic glycolysis, and on transport processes, of incubated cerebral cortex slices have been studied in an effort to understand more fully cerebral metabolic processes during anoxia, and the mode of action of certain neurotropic drugs. The general approach has been to study the action of various drugs on the rates of anaerobic glycolysis of incubated brain slices under a variety of conditions. The cation (Na⁺, K⁺) contents were also studied under these conditions and the changes in these contents were related to concomitant changes in cerebral metabolism. Experiments were also carried out on the cerebral transport of amino acids and glucose under a variety of incubation conditions. Measurement of the rates of anaerobic glycolysis in the presence of TTX showed that the drug, at low concentrations such as 2 μM, enhances the rate of anaerobic glycolysis of cerebral cortex slices two to three fold, the effects being greater in the absence of Ca⁺⁺. Such an effect of TTX is far greater than that obtained on the aerobic metabolism of the cerebral cortex slices. The anaerobic glycolysis of kidney medulla slices, 2-day old rat brain slices or of acetone powder extracts from brain are not affected by the drug, indicating that the effects of TTX on the anaerobic glycolysis are specific for mature cerebral tissue, and requires integrity of the brain cells for its action. TTX has little or no effect in increasing rate of anaerobic glycolysis when it is added 10 minutes, or later, after the onset of anoxia, or when high K⁺, protoveratrine, L-glutamate or NH₄⁺ are present in the incubation medium. Under these conditions, there is either an influx of Na⁺ into, or loss of K⁺ from, the incubated cerebral tissue. In the presence of TTX under anoxic conditions, a much slower decline in the K⁺ /Na⁺ ratio of the cerebral cortex slices is observed. These and other experiments lead to the conclusion that the effects of TTX on anaerobic glycolysis are due to its action at the brain cell membrane resulting in the prevention of the changes in brain cell permeabilities to Na⁺ and K⁺ brought about by the onset of anoxia. In the presence of TTX, the initial high rate of glycolysis tends to be maintained due to only a slow decline in the cellular K⁺/Na⁺ ratio. The effects of K⁺ and Na⁺ on the anaerobic glycolysis are thought to be mediated largely by changes in the pyruvate kinase activity, which is enhanced by K⁺ and diminished by Na⁺. TTX appears to affect the aerobic and anaerobic metabolism of brain in vitro in the same way as it affects the generation action potentials i.e. by diminishing the influx of Na⁺ and efflux of K⁺ . These results lead to the conclusion that action potentials are generated in the incubated cerebral tissue at the onset of anoxia. These are blocked by TTX which manifests its effect by a higher rate of anaerobic glycolysis. The effect of TTX on the Na⁺ and K⁺ contents may be greater in the neurons than in glial cells because the former are the site of action of TTX. Consequently, the changes in the neuronal K⁺/Na⁺ ratio brought about by TTX are probably much greater than those of the K⁺/ Na⁺ ratio found in the tissue as a whole. In addition to its effects on the Na⁺ and K⁺ fluxes, TTX also prevents the efflux of amino acids from the incubated cerebral cortex slices that occurs at the onset of anoxia. This effect of TTX is independent of the activity of the transport processes normally operating on the amino acid uptake into the brain. Local anesthetics, ouabain, amytal and reserpine also increase the rate of anaerobic glycolysis of cerebral cortex slices. Local anesthetics act in a manner similar to TTX, although much higher concentrations are required. The effects of ouabain in a Ca⁺⁺-free medium are much greater than in a Ca⁺⁺-containing medium. It is suggested that the increase in the rate of anaerobic glycolysis due to ouabain is possibly mediated by an increase in cell ATP concentration under anoxia, as a result of inhibition of Na⁺ , K⁺-ATPase. The actions of amytal and reserpine on the anaerobic glycolysis of cerebral cortex slices are possibly mediated by membrane cation changes, but further work is necessary to support this conclusion. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

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Thesis (M.S.)--University of British Columbia, 2004. / Includes bibliographical references (leaves 113-121). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--University of British Columbia, 2004. / Includes bibliographical references (leaves 113-121).

Publicación a texto completo no autorizada por el autor. / Describe la controversia respecto al papel que puede jugar la hipoxia asociada a grandes alturas (> 3000 msnm) en las vías de producción de especies reactivas de oxígeno (EROs). Asimismo se desconoce el papel de Mieloperoxidasa (MPO) y Ceruloplasmina (CP) en la generación de estrés oxidativo. En el presente estudio se postula que existe diferencia entre las actividades de MPO, CP y estrés oxidativo en grandes alturas y a nivel del mar. Para ello se evaluó la actividad enzimática de MPO, CP y el nivel de estrés oxidativo en pulmón, cerebro y corazón de cobayos nativos de grandes alturas (Cerro de Pasco, 4330 msnm) en comparación con un grupo control de nivel del mar (Lima, 150 msnm). Asimismo se determinó la asociación que existe entre los niveles de MPO, CP y estrés oxidativo mediante correlaciones de sus valores a grandes alturas y a nivel del mar. El estrés oxidativo se evaluó mediante la determinación de Malondialdehído (MDA) y Productos avanzados de oxidación protéica (AOPP) en pulmón, cerebro y corazón de cobayos. En esta investigación se encontró que no existe diferencia significativa entre los niveles de MPO, CP y estrés oxidativo en cerebro y corazón de cobayos nativos de grandes alturas y de nivel del mar. Sin embargo si se encontró diferencia significativa (p<0.05) entre los niveles de MPO en pulmón de cobayos de grandes alturas y de nivel del mar. Además los niveles de MDA y AOPP en corazón difieren significativamente (p<0.05) a grandes altura y a nivel del mar. Por lo tanto se concluyó que la actividad enzimática de MPO y CP en cerebro y corazón de cobayos tanto de nivel del mar como de grandes alturas son similares. Además el nivel de estrés oxidativo en corazón de cobayos es diferente a los niveles de sus similares a nivel del mar. No obstante estos niveles (MDA, AOPP) en pulmón y cerebro a grandes alturas y a nivel del mar no difieren. Por último existe diferencia entre los niveles de MDA y AOPP en corazón de cobayos de grandes alturas y de nivel del mar. / Tesis

Thesis (Ph.D.)--University of Delaware, 2006. / Principal faculty advisor: George W. Luther, III., College of Marine and Earth Studies. Includes bibliographical references.

Title from PDF of title page (University of Missouri--Columbia, viewed on March 8, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Michael J. Petris. Vita. Includes bibliographical references.

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