Purificación del benzoil-mercaptoacetil triglicina, complementado con evaluaciones biológicas / Purification of benzoil-mercaptoacetil triglicine, complemented with biological evaluations

La síntesis se realiza por la técnica de W. Brandau. La purificación se realizó por cristalización fraccionada en metanol: agua (80:20), monitoreada por HPLC. Se obtienen varios precipitados, con los cuales se preparan minilotes de prueba, que se marcan con Tc 99m y se realizaron los controles radioquímicos y las evaluaciones biológicas. Los resultados obtenidos son los siguientes: la pureza química del Bz-MAG3 se incrementa de un 70 por ciento a un 98,12 por ciento del compuesto activo, con un rendimiento del 25 por ciento aproximadamente; la pureza radioquímica de los precipitados puros es mayor del 98 por ciento y el porcentaje de dosis de inyección en riñones se incrementa de un 8 por ciento a un 30 por ciento a los 5 minutos post-inyección en ratones sanos. El porcentaje de excreción renal promedio a los 60 minutos es mayor del 90 por ciento, porcentaje que garantizará una buena calidad de imágenes gammagráficas renales.

Radiation damage to glucose concentrating capacity and cell survival in kidney tubule cells: effects of fractionation.

The glucose concentrating capacity of cultured LLC-PK1 kidney epithelial cells has been measured after single and fractionated doses of X-rays. Steady-state glucose concentrating capacity (ratio of glucose concentration inside to outside cell) can be measured using radiolabelled analogues of glucose which are actively transported but not metabolized. These cells can be stimulated to increase their glucose concentrating capacity (up-regulation) by a reduction in the glucose concentration of the growth medium. However, after X-ray irradiation the cells have a reduced capacity to respond to up-regulation. This effect can be measured 7 days after irradiation and before radiation-induced cell killing affects the cell population. The previously reported radiosensitivity of this function to single doses of X-rays (in the range 1-16 Gy) was confirmed. Surprisingly, no significant sparing of this effect could be measured by fractionation of the X-ray dose into two or four fractions. However, the cells showed a significant fractionation effect if clonogenic survival was measured using the standard cell survival assay. These early effects have different fractionation response from the later phases of tissue damage, measured months to years after irradiation, which do show sparing due to fractionation and are thought to be mainly due to changes in cell survival. The lack of sparing by fractionation to the functional damage may suggest a different target from that which determines cell survival. These results support the hypothesis that radiation damages cellular functions, separately from cell replication.

Absorption and biokinetics of U in rats following an oral administration of uranyl nitrate solution.

The absorption of U within the male Wistar rat was determined following oral gavage with uranyl nitrate solutions at seven different dosages. Gavage levels ranged from 0.003 to 45 mg U per kilogram body weight. Uranium tissue burdens were determined at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 96 and 240 h following gavage. Blood, kidney, liver and bone were analyzed for U content using neutron activation followed by delayed neutron counting. Uranium rapidly localized in the kidneys and bone following ingestion. Bone was found to be the primary tissue of deposition. Skeletal and kidney burdens closely paralleled each other from 15 min to 10 d after oral gavage. Uranium burdens in the blood reached a maximum within 30 min but declined rapidly thereafter. Burdens of all tissues were well correlated with each other and with dosage at all dose levels. Equations relating body burdens with blood levels were developed and found to be useful for predicting body burdens for the initial 8 h following gavage. Gastrointestinal absorption (f1) was 0.6-2.8% over the range of U administered. Movement of U through the GI tract was assessed at two dosages. The transit time of U through the GI tract was approximately 48 h. Uranium loss from the stomach was described as a power function of time. The maximum value in the small intestine was attained within 2 h, and thereafter its rapid loss was linear up to 8 h. A minor residual loss component from the small intestine was evident beyond 8 h post-gavage.