Thèse (M.Sc.)--Université Laval, 2004. / Sur la p. de t. "v" est en indice. Bibliogr.: f. 77-93. Publié aussi en version électronique.

Thesis (M.Res.(Med.))--University of Hong Kong, 2003. / Includes bibliographical references (leaves 76-92) Also available in print.

Thesis (Ph. D.) -- Lincoln University, 2004.

Th. 3e cycle--Physiol. animale et cell.--Nice, 1986.

Orientador: Hérida Regina Nunes Salgado / Banca: Maria José Vieira Fonseca / Banca: Maria Virginia Costa Scarpa / Resumo: O azumoleno sódico é um fármaco desenvolvido para combater a hipertermia maligna, que é caracterizada por predisposição genética e desencadeada pelo uso de agentes anestésicos inalatórios em processos cirúrgicos podendo levar a óbito 70% dos enfermos. Este fármaco mostra-se como congênere do dantroleno sódico, e devido à sua solubilidade ser 30 vezes maior, apresenta vantagens durante seu uso emergencial. Por tratar-se de um novo fármaco, há poucos estudos relacionados às suas características físicoquímicas, impurezas e métodos de análises. Os objetivos são desenvolver e validar métodos analíticos eficazes na identificação e na quantificação de azumoleno sódico. A análise qualitativa foi realizada por análise térmica, espectrofotometria de absorção na região do ultravioleta, espectroscopia na região do infravermelho e espectrofotometria de absorção na região do visível com utilização de ácido cloranílico 0,1% como reagente, permitindo a identificação do azumoleno sódico. Os métodos de análise quantitativos desenvolvidos e validados envolveram: (i) espectrofotometria no UV, com comprimento de onda a 340 nm, que apresentou resposta linear entre a faixa de concentração de 7,0 e 12,0 Ng/mL, na qual foram analisados satisfatoriamente os parâmetros de precisão, exatidão, robustez, limite de detecção e limite de quantificação, com teor médio de 98,86% e CV de 0,62 %; (ii) espectrofotometria na região visível, com utilização de ácido cloranílico 0,1% como reagente e acetonitrila como solvente, com comprimento de onda a 507 nm e faixa de concentração linear de 8,0 a 13,0 Ng/mL, com avaliação dos parâmetros de precisão, exatidão, robustez, limite de detecção... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Azumolene sodium is a drug designed to fight malignant hyperthermia, which is characterized by genetic predisposition and triggered by the use of inhalational anesthetics in surgical procedures can lead to death 70% of patients. This drug is shown as a congener of dantroleno sodium, and due to its solubility is 30 times larger, has advantages for its emergency use. As this is a new drug, there are few studies related to their physical and chemical characteristics, impurities and methods of analysis. The objectives are to develop and validate analytical methods effective in the identification and quantification of azumolene sodium. Qualitative analysis was performed by thermal analysis, absorption spectrophotometry in ultraviolet and visible region using 0.1% chloranilic acid as reagent and spectroscopy infrared absorption, allowing the identification of azumolene sodium. The methods of analysis developed and validated involved: (i) UV spectrophotometry, with wavelength at 340 nm, which showed linear response the concentration range of 7.0 and 12.0 Ng/mL, which were analyzed satisfactorily the parameters of precision, accuracy, robustness, limit of detection and limit of quantitation, with percentage average of 98.86% and CV 0.62%, (ii) visible spectrophotometry, using 0.1% chloranilic acid reagent and acetonitrile as solvent, at 507 nm and linear concentration range from 8.0 to 13.0 mg/mL, with evaluation of precision, accuracy, robustness, limit of detection and limit of quantification, showed the percentage average of 98.15% and CV 0.66%, (iii) high performance liquid chromatography, which used reverse-phase column C18 and a mobile phase consisting of methanol: water... (Complete abstract click electronic access below) / Mestre

The polarographic method has been described, and an attempt made to describe the difficulty of the simultaneous deposition of sodium and potassium. Various methods have been examined, of which precipitation of potassium with magnesium dipicrylaminate seems the most promising. The quantitative results were unsatisfactory, and possible sources of error are discussed. The method, while very convenient, rapid and labour-saving, is not sufficiently standardised to be trustworthy.

Activities of sodium in alumina-saturated cryolite-aluminum melts have been measured by the equilibration of a three phase system of cryolite, aluminum and lead. An approximate linear increase in the activity of sodium was noted on a log plot of activity as a function of NaF-A1F₃ weight ratios over the range pertinent to commercial reduction cell operation. Activities of sodium in cryolite-aluminum melts have been calculated by employing the equilibrium reaction between cryolite and aluminum metal and the thermodynamic data from-an analysis of the NaF-A1F₃ phase diagram. Differences between the reversible deposition potential for aluminum and sodium at one atmosphere partial pressure were calculated from the measured equilibrium sodium activities. The values obtained were of the order of .15 to .4O volts, increasing with decreasing NaF-A1F₃, ratio. / Applied Science, Faculty of / Materials Engineering, Department of / Graduate

Extracellular action potentials and isometric contractile tension have been recorded simultaneously in vitro from uterine longitudinal smooth muscle of the pregnant cat, pregnant rabbit, estrogen-treated rabbit, and estrogen-treated rat. Action potentials were recorded from the surface of the muscle strips with glass electrodes having a large tip diameter. Tension was recorded with an RCA transducer. Spontaneous contractions are associated with a series of action potentials. During relaxation no electrical activity is observed. Electrical and mechanical activities were first recorded in Kreb's Ringer medium and then in sodium-poor media (replacement of sodium chloride with choline chloride or sucrose). Sufficient reduction in the external sodium concentration resulted in increased amplitude (peak to peak) of the biphasic action potential spikes. The duration of the peak to peak deflection and the maximum rate of potential, change remained unchanged. However, decrease in the external sodium concentration reduced the frequency of the action potentials, considerably in the cat, and less so in the rabbit and rat. The external sodium concentration was reduced in stepwise ; fashion to ½, ¼ , ⅛ its initial value. Each successive decrease in the external sodium concentration was accompanied by a prompt initial contraction, followed by very slow relaxation and subsequent resumption of spontaneous contractions accompanied by action potentials. With cat uteri reduction of the sodium concentration of the medium to a level of 15-20 mEq/1 resulted in a greatly prolonged contraction with eventual relaxation when tissues failed to contract. This paralysis was associated with cessation of action potentials. The electrical responses of uteri of the other two species (rabbit and rat) during exposure to sodium-poor media were similar to those observed with the cat uterus. However, the mechanical activity of rat and rabbit uteri in sodium poor media was different from that of the cat uterus. Decrease in the external sodium concentration below 25-30 mEq/1 usually resulted in prolonged contractions, and finally to complete failure of the tissue to relax (even after 2-2½ hours). Outbursts of action potentials at irregular intervals were seen in the initial stages of this persistent contraction but eventually action potentials also disappeared. It was difficult to reconcile these facts with the "Sodium Hypothesis". A selective inward flow of sodium ions probably cannot account for the initiation of action potentials in uterine smooth muscle since considerable reduction of the external sodium concentration (down to 15-20 mEq/1 in cat and 25-30 mEq/1 in the other two species) did not affect the characteristics of the action potentials in the expected manner. However, further reduction in sodium did result in electrical and mechanical inactivity. The view that an outward flow of intracellular anions might be responsible for depolarization (14) receives further support from the present studies. In addition to many differences from other types of excitable tissue (nerve, cardiac and skeletal muscle), uterine smooth muscle also shows considerable intra- and inter-species variation. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

The crystallization kinetics of sodium sulphate from 9N sulphuric acid was studied under cooling conditions. The crystal growth and nucleation rates were determined using the Population Balance concept in a continuous mixed-suspension mixed-product-removal (MSMPR) crystallizer. The effects of supersaturation, crystal suspension density and temperature on the crystallization kinetics were all investigated. The study was conducted at crystallizer temperatures of 45, 50, 55, and 60 °C. The crystal growth rate data were correlated to the supersaturation with a power-law, G = KGSg. The crystal nucleation rate data were fitted to both primary (B° = KBSb) and secondary (B° = KNMTjSu) nucleation models. Growth and nucleation rate data were correlated according to the primary (B° = KbGi) and secondary (B° = KnMTjGv) relative kinetic models. The study determined that the growth rate data fit the expression, (G = KGS⁰‧⁸⁷ ), and that secondary nucleation was the dominant mode of nuclei generation (B° = KNMT⁰‧⁸⁴S¹‧²⁷). The sodium sulphate crystallizes from solution as the acid salt, sodium sesqui-sulphate (Na₃HSO₄) . The rate constants, KG and KN, were both functions of temperature and were fitted to Arrhenius type expressions : [formula omitted] / Applied Science, Faculty of / Chemical and Biological Engineering, Department of / Graduate

Cation sensitive glass microelectrodes were inserted into single striated muscle fibers of the giant barnacle, Balanus nubilus, to measure directly the activities of sodium and potassium in the myoplasm. The total sodium and potassium content of the individual experimental fibers was determined by flame photometry. From these measurements, the percentage of sodium in the fiber which did not affect the microelectrodes and the percentage of water in the fiber which was not available to act as solvent for the potassium ions were calculated. The minimal percentages of "bound" sodium and water were 84% and 42% respectively. It was hypothesized that a significant fraction of this "bound" sodium was involved in ion pair formation with carboxyl moieties on the myosin molecules which comprise the thick filaments, and experiments were designed to test this hypothesis. In the second series of experiments, the activities of sodium, potassium and hydrogen in the myoplasm were measured as the temperature of the solution bathing the fibers was increased from 7 to 40°C. An irreversible shortening occurred in all fibers between 37 and 40°C. When the fibers shortened in a sodium free Ringer solution, the mean activity of sodium increased by 130%, the mean activity of potassium remained relatively constant, and the pH decreased from 7.17 to 6.77. These experiments provided strong evidence that sodium is bound to myosin in the living fiber, for extracted myosin is known to denature at 37°C and release its associated alkali metal cations. In the third series of experiments, the optical density, O.D., of the single striated muscle fibers was measured at 50 mµ intervals between 450 and 850 mµ. At all wavelengths, the O.D. decreased markedly when the normal Ringer bathing solution was replaced by sodium free sucrose Ringer. For example, at 850 mµ the O.D. of the fibers, relative to the initial value in normal Ringer, decreased from 1 to 0.21 ± 0.06 in 25 minutes. The corresponding increase in the transmittance, T, (O.D. = -log T) was from 5% to 55%. This change in O.D. could be reversed by returning the normal Ringer bathing solution to the bath. Large, reversible decreases in O.D. were also observed when potassium and tris were used as substitutes for sodium. These changes in O.D. are explained by the theory of light scattering if it is assumed that sodium is bound to the main scattering centers in the myoplasm, the thick filaments. When the fibers were bathed in sodium free, lithium substituted Ringer, a small reversible increase in the O.D. was observed, which may indicate that lithium is complexed more strongly than sodium to the binding sites on the thick filaments. In the final series of experiments, the number of sodium and potassium ions "bound" to the contractile proteins in a glycerinated fiber was measured. The free concentrations of hydrogen, sodium and potassium were maintained at values similar to those found in an intact fiber. The results indicated that substantial binding of both sodium and potassium occurred, and that proportionally more sodium than potassium ions were "bound". If the results are extrapolated to the intact fiber, they imply that about as much sodium is "bound" to the contractile proteins as is free in the myoplasm. This amount of "bound" sodium is sufficient to explain the results of the denaturation and light scattering experiments, but insufficient to account for the anomalously low activity of sodium in the myoplasm, as measured by a sodium sensitive microelectrode. Thus, it was concluded that either some factor must enhance the binding of sodium to the contractile proteins in a living cell, or that sodium must be sequestered in organelles which are destroyed by the glycerination process. / Medicine, Faculty of / Graduate