Isolated Langendorff-perfused rat hearts, after 30 min of preperfusion, were submitted to increasing times of global normothermic ischemia (1, 2, 5, 10, 20 and 30 min) or to the same times of ischemia followed by 30 min of reperfusion. Analysis of malondialdehyde, ascorbic acid, oxypurines, nucleosides, nicotinic coenzymes and high-energy phosphates was carried out by HPLC on neutralized perchloric acid extracts of freeze-clamped tissues. In addition, maximum rate of intraventricular pressure development and cardiac output of malondialdehyde, lactate dehydrogenase, oxypurines and nucleosides were monitored during both preperfusion and reperfusion. Besides decreasing energy metabolites and nicotinic coenzyme pool, prolonged ischemia produced oxidation of significant amounts of hypoxanthine and xanthine to uric acid and generation of detectable levels of malondialdehyde (0.002 micromol/g dry weight). After oxygen and substrate readmission, tissue and perfusate malondialdehyde increased only if previous ischemia was longer than 5 min, while lactate dehydrogenase was detected in perfusate of reperfused hearts following 10, 20, and 30 min of ischemia. Highest values of tissue malondialdehyde and total malondialdehyde output were recorded in reperfused hearts subjected to 30 min of ischemia (0.043 micromol/g dry weight and 0.069 micromol/30 min/g dry weight, respectively). Since tissue malondialdehyde was observed without detectable lactate dehydrogenase release in perfusate, it might be stated that malondialdehyde generation (i.e., lipid peroxidation) temporally preceded lactate dehydrogenase release (i.e., tissue necrosis). In reperfused hearts, evaluation of myocardial energy state and of mechanical recovery allowed us to determine times of ischemia beyond which reperfusion did not positively affect these metabolic and functional parameters. Main findings are that, under these experimental conditions, lipid peroxidation might be the cause and not the consequence of tissue necrosis and that duration of ischemia might be the factor deciding effectiveness of reperfusion.

No abstract

The three-dimensional structure of tomato P31 and T10 Cu,Zn superoxide dismutases (SODs) were computer modelled using the structure of the bovine enzyme as a template. The structure-essential residues retain in the models the position occupied in the other Cu,Zn SODs of known 3D structure and the overall packing of the beta-barrel is maintained. Formation of 'aromatic pairs' occurs between newly inserted aromatic residues. The number of total charges changes in the two variants and some charged residues located in the proximity of the active site in most Cu,Zn SODs disappear in tomato enzymes. Calculation of the electrostatic potential field, carried out by numerically solving the Poisson-Boltzmann equation, indicates that in both variants a negative potential field surrounds all the protein surface except the active site areas, characterized by positive potential values, as already observed in the bovine enzyme. This result confirms that coordinated mutations of charged residues have occurred in the evolution of this enzyme giving rise to a peculiar electrostatic potential distribution common to all members of this protein family.

No abstract

RESUMENObjetivo Evaluar mediante un modelo de simulación la utilidad de un programa organizado de cribado mamográfi co en Bogotá, Colombia. Material y Métodos Diseño análisis de costo-efectividad usando el modelo Markov. Se compara la realización de cribado mamográfi co bienal en mujeres de 50 a 69 años con respecto al statu quo en el cual no existe este programa. Se evalúa sobrevida, costos e incrementos en la tasa de costo-efectividad. Resultados El modelo muestra una reducción de la tasa de mortalidad por cáncer de mama en el esquema de cribado mamográfi co de ciclo bienal. Se observa que hay un incremento lineal de los años de vida acumulados desde el tercer ciclo con un ahorro acumulado de costos de tratamiento en las diferentes tasas de cribado generando ahorros al sistema de salud.La Razón de costo por año de vida ganado y Producto interno bruto se hace menor de 3 por encima del 50 % de cobertura (indicando que es una intervención costo-efectiva). El costo medio del programa experimenta una disminución porcentual del 40 % cuando se llega al ciclo 10. De allí la disminución de este costo es menor. Conclusiones Según el modelo desarrollado es costo-efectivo adelantar un programa de cribado mamográfi co bienal con cobertura mayor al 50 %, obteniéndose reducción en la mortalidad que se hace más notoria desde el tercer ciclo del esquema evaluado, obteniendo un ahorro en los recursos queelsistema de salud destina al cáncer de mama.Palabras Clave: Evaluación de costo-efectividad, cribado, mamografía, mama, neoplasias de la mama (fuente: DeCS, BIREME).