Biochemical medicine最新文献

Sake, a rice wine, induced hepatic collagen accumulation in rats. This was noted after 16 weeks of a liquid diet containing 35% ethanol by caloric content. However, under similar experimental conditions, whiskey and ethanol did not produce any changes. Hepatic collagenase activities in sake-fed rats were slightly, but significantly, higher than in the whiskey group. The central and pericellular liver fibrosis in sake-fed rats was caused possibly by either accelerated collagen synthesis or maturation, exceeding the increased collagen degradation. Mechanisms of enhanced fibrogenesis in sake-fed rats were discussed.

Carbamazepine, a drug which is widely used in neurological diseases, has a porphyrogenic effect in chick embryo liver cells in culture. It increased the concentration of cellular porphyrins by 80-fold and δ-aminolevulinate synthase activity by 4-fold. The increase in the accumulation of porphyrins preceded that of ALAS activity. Measurements of the activities of aminolevulinate dehydrase, porphobilinogen deaminase, and uroporphyrinogen decarboxylase showed that C inhibits UROD up to nearly 50% and PBGD activity up to 20%, but does not affect the activity of ALAD.

The pattern of accumulation of porphyrins, mainly uro- and heptacarboxylporphyrin, is compatible with an inhibition of UROD. We may, therefore, conclude that the porphyrogenic effect of C in monolayers of chick embryo liver cells is the sesult of its inhibitory effect on the activity of UROD.

Muscle biopsies from 35 patients referred for possible malignant hyperthermia were subjected to contracture testing with halothane, caffeine, and the combined agents, histopathological and fiber-type-distribution analysis, and quantitative assay of three major muscle enzymes: adenylate deaminase, adenylate kinase, and creatine kinase. Adenylate kinase and creatine kinase were in the normal range in all biopsies and each averaged 92% of expected normal value when corrected for their fiber-type distribution. Of the 14 cases with a positive halothane test, 2 had primary myoadenylate deaminase deficiency, and 5 others had low levels of this enzyme (less than one-third normal). In contrast, only 3 of 21 cases negative to halothane testing had low adenylate deaminase levels, and none were deficient. This association was significant by several statistical tests, although it would not be highly predictive for an individual case. A positive halothane test also correlated wth a high type 2 fiber contribution, but this was probably secondary, since cases with low enzyme levels had significantly higher type 2 fiber areas. Caffeine contractures did not correlate with either low enzyme levels or with fiber-type distribution. Sixty percent of the biopsies were entirely normal histologically, and showed a significant correlation with a negative combined contracture test. Data on the one family included in this study suggest separate inheritance of the trait for myoadenylate deaminase deficiency and the trait for positive contracture tests. The present findings suggest that patients with myoadenylate deaminase deficiency (and the carrier state as well) may be at increased risk of malignant hyperthermia when subjected to anesthesia.

The pattern of acid proteinase zymogens, seven pepsinogens (Pg) and slow moving protease (SMP), in normal human gastric mucosa has been reported. No significant differences were found in appearance of individual pepsinogens in oxyntic mucosa in the two sexes, but in pyloric mucosa, Pg 3 occurred significantly more often in men. Rapidly migrating pepsinogens (constituents of Group I pepsinogens) were seen in pyloric mucosa as well as in oxyntic mucosa. The duodenal mucosa contained small amounts of proteinases, the activity being largely confined to the slower moving proteinases (constituents of Group II pepsinogens).

The macromolecular AGAG in the urine of patients with Werner's syndrome were analyzed by enzymatic methods after digestion with chondroitinases and Streptomyces hyaluronidase. The molecular weight-dependent distribution of the urinary AGAG has been determined by gel filtration on a Sephadex G-100 column.

The distribution of HA and HS was predominant in the macromolecular fractions. Chondroitin sulfate isomers were prominent in the low molecular weight fractions but the ratio of the 4-type to the 6-type increased with decreasing molecular weight. These observations indicated that Werner's syndrome is a metabolic disorder of the molecular weight-dependent AGAG composition.

The influence of diet on the excretion of catecholamines, some of their metabolites, and pHPG, an octopamine metabolite, was examined. Two groups of rats were fed either a cereal-containing standard laboratory Purina rat chow or a cereal-free casein diet. Use of the standard chow resulted in significant increases in the urinary values for total MHPG, pHPG, DHPE, MHPE, and free and total DOPAC by the seventh day in comparison to the casein diet. No changes were noted in the excretion of free and total NE, DA, and HVA. The data indicate that it is necessary to place the animals on the casein diet several days before determining the excretion of the aforementioned metabolites.

The effects of endotoxin administration on glycolytic and tricarboxylic acid cycle intermediates in dog livers were studied. Changes in metabolite concentrations were expressed graphically as percentages of controls using “crossover” plots in order to identify transitory rate-controlling steps. The results show that endotoxin administration increased glycolytic flux through pyruvate kinase, inhibited gluconeogenic flux through phosphoenolpyruvate carboxykinase, decreased glycogen storage, shifted cytosolic and mitochondrial redox state from a relatively oxidized to a more reduced state, decreased the extra- and intramitochondrial malate-aspartate and glutamate-α-ketoglutarate shuttle activities, depleted ATP, ADP, and NADP concentrations, and decreased energy charge. Based on these data, it is concluded that pyruvate kinase plays the major role in the control of glycolysis, while phosphoenolpyruvate carboxykinase is the major controlling step for the regulation of gluconeogenesis in dog livers during endotoxic shock. In addition, the major factor in the regulation of metabolic pathways that produce and utilize high-energy phosphates in the livers was impaired in endotoxic shock.

A biochemical study has been undertaken on the mothers of children with a major neurodevelopmental disability, without known etiology (study group), and an appropriate control group. Two hundred seventy-four mothers were studied, 137 in each group. Social and environmental details were recorded in earch of the two major groups.

Biochemical studies included the assay of plasma and urinary amino acids and appropriate screening tests for carbohydrate and organic acid abnormalities. To introduce an element of standardization and also to enhance the opportunities for identifying possible biochemical heterozygote states, a 50-g protein mean was given to all subjects approximately three-quarters of an hour before blood and urine samples were taken.

Difference of means tests on 22 amino acids revealed 9 significant t values at the 0.05 level and all means were significantly lower in the study groups. Because of the differences noted a discriminant analysis was carried out which demonstrated an extremely high proportion of correctly classified subjects (98%) when biochemical parameters were used to attempt to classify subjects into the study or control group.