Captopril methylation in human liver and kidney: interindividual variability.

1. The methylation of captopril was studied in the microsomal fraction obtained from 87 specimens of human liver and 70 specimens of human renal cortex. 2. The rate captopril methylation ranged over one order of magnitude in the liver and kidney. In the human liver, the mean (+/- SD) rate of captopril methylation (pmol/min/mg) was significantly (p < 0.001) greater in women (199 +/- 97) than in men (126 +/- 88), whereas in the kidney no sex-difference was observed, and the mean (+/- SD) of all cases was 47 +/- 23 pmol/min/mg. 3. In the kidney, the statistical analysis revealed the presence of two subgroups in the rate of captopril methylation and their mean (+/- SD) estimates were 42.5 +/- 13.9 and 90.3 +/- 12.0 pmol/min/mg (p < 0.05). Of the population, 84% fell in the former and the remaining 16% in the latter subgroup. 4. Captopril is mainly eliminated by metabolism and its bioavailability is 65%. Methylation is one of the metabolic routes of captopril and its variability may contribute, to some extent, to modulate the intracellular concentration of this drug.

Variability in the rate of 6-mercaptopurine methylation in the erythrocytes, liver and kidney in an Italian population.

OBJECTIVE: The polymorphism of erythrocyte thiopurine methyltransferase (TPMT) is genetically regulated as an autosomal codominant trait, and so should be congenital. RESULTS: We tested this hypothesis by measuring TPMT activity in erythrocyte preparations from adults and newborns and observed polymorphic distribution of TPMT activity in the adult and newborn erythrocytes. The activity of TPMT was higher in red cells from the newborns than adults. The frequency distribution of TPMT activity was also investigated in the liver and kidney. In the kidney, TPMT activity fell into two subgroups, whereas in the liver the distribution pattern was more complex. The activity of TPMT in erythrocytes and liver from the same subject was correlated, but the values of only half the cases fell within the 95% confidence limits, suggesting that the control of hepatic and/or erythrocyte TPMT is multifactorial.

Human liver budesonide sulphotransferase is inhibited by testosterone and correlates with by testosterone sulphotransferase.

Budesonide, a corticosteroid used in the treatment of asthma and allergic reactions, is almost entirely cleared by metabolism in man. We describe the sulphation of budesonide in human liver and lung and provide evidences that the sulphation of budesonide is catalysed by testosterone sulphotransferase. A rapid and reproducible radiometric assay for budesonide sulphotransferase is described. Liver specimens were obtained from 35 men and 65 women and lung specimens from 2 women and 17 men. The average hepatic budesonide sulphation rate was significantly higher in men (41.1 pmol.min-1.ml-1) than women (28.2 pmol.min-1.mg-1). In the lung, the mean budesonide sulphation rate was 5.0 pmol.min-1.mg-1. Testosterone strongly inhibited the hepatic sulphation of budesonide, whereas p-nitrophenol and dopamine were poor inhibitors; the IC50 was 7.0 uM (testosterone), 320 uM (p-nitrophenol) and 510 uM (dopamine). The hepatic rates of testosterone, p-nitrophenol and dopamine sulphation were measured in the same samples assayed for budesonide sulphotransferase. There was a correlation between the hepatic rates of budesonide and testosterone sulphation (P < 0.001; r = 0.810). The activity of testosterone sulphotransferase was significantly greater in men than women (22.0 vs. 17.2 pmol.min-1.mg-1), whereas those of dopamine and p-nitrophenol sulphotransferase were not sex dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Food habits and the apparent nature and extent of dietary nutritional deficiencies in the Peruvian Andes.

Food patterns, and energy and nutrient intake of a sample of rural and urban families in the Peruvian Andes are analyzed and compared with requirements and recommended figures of nutrient allowances. It is concluded that, with the exception of vitamin A, there is very little nutrient deficiency where calorie requirements are met. About half the population in the region suffers from some degree of calorie deficiency in the sense that the total quantity of food available to the family is insufficient to satisfy energy needs of all family members. The incidence of calorie deficiency is about equally distributed between rural and urban areas and there is strong evidence that calorie intake is positively correlated with the proportion of home-produced to total (home-produced and purchased) food.

Food habits and the apparent nature and extent of dietary nutritional deficiencies in the Peruvian Andes.

Se analizan los patrones de ingesta de alimentos y nutrientes en una muestra de familias urbanas y rurales de los Andes Peruanos, y se comparan con los requerimientos establecidos. Se concluye que, con excepcion de vitamina A, existe poca deficiencia nutricional en los casos en que se satisfacen los requerimientos caloricos.Cerca de la mitad de la poblacion en la region padece de cierto grado de deficiencia calorica en el sentido de que la cantidad total de alimentos disponibles para la familia, es insuficiente para satisfacer las necesidades energeticas de todos sus miembros. La incidencia de deficiencia calorica es mas o menos la misma en las areas rurales que en las urbanas, y existe evidencia fuertemente indicativa de que la ingesta calorica esta correlacionada positivamente con la proporcion de alimentos que se producen a nivel del hogar a alimentos totales (producidos en el hogar mas los comprados en el mercado)