Effects of ethanol treatment and castration on liver alcohol dehydrogenase activity.

Induction of alcohol dehydrogenase (ADH) activity by chronic ethanol treatment and castration has previously been reported to occur in Sprague-Dawley rats. In the present study, no induction was found following chronic ethanol treatment and only a low level of induction was found with castration. However the activity of ADH was high in control animals compared with those used in other studies. The activity of ADH in control animals was not decreased by testosterone administration, which has been shown to reverse induction of the enzyme produced by chronic ethanol treatment or castration in other studies. It is concluded that the male Sprague-Dawley rat is not necessarily a suitable animal for the study of ADH induction by chronic ethanol treatment and that further unknown factors must be identified before the regulation of ADH activity in vivo is fully understood.

Increased malate dehydrogenase activity in blood from non-drinking alcoholics.

Since cytosolic malate dehydrogenase has been shown to play a role in the regulation of liver cytosolic [NAD+]/[NADH] redox state during ethanol metabolism, it is possible that differences in this enzyme could cause differences in response to ethanol. The present study demonstrates that the isozyme pattern of this cytosolic enzyme in whole blood samples is the same as that in liver and that the pattern does not differ in alcoholic and control subjects. A marginally significant elevation of activity of malate dehydrogenase in blood from alcoholic subjects is reported. Further studies are needed to confirm this latter finding and to assess fully its possible significance.

Factors influencing rates of ethanol oxidation in isolated rat hepatocytes.

The stimulation of ethanol oxidation by fructose which has frequently been observed in isolated hepatocytes was found to occur only in unsupplemented cells. In the presence of other substrates (lactate, pyruvate) which accelerate ethanol oxidation, fructose had no additional effect. Acceleration of ethanol oxidation by fructose was not directly related to the ATP demand created by fructose. The effects of fructose on ethanol oxidation rates were not due to changes in acetaldehyde concentration. In cells from fed animals, acetaldehyde concentrations rose as high as 200 microM in some incubations, and therefore became a significant factor limiting ethanol oxidation rates. In hepatocytes isolated from starved rats incubated with pyruvate, where acetaldehyde concentrations were very low, (1-2 microM) it was possible to assess the effect of changes in [lactate]/[pyruvate] (and hence free cytosolic NADH) on rates of ethanol oxidation. The results showed that the increase in free cytosolic [NADH] usually found during ethanol oxidation in vivo would inhibit rates of ethanol clearance by a maximum of 20%.

Kinetics of malate dehydrogenase and control of rates of ethanol metabolism in rats.

The theory that the rate of ethanol oxidation is governed by rates of NADH reoxidation is based in part on the observation that the ratio of free cytosolic [NADH]/[NAD+] increases during ethanol metabolism. However, it has recently been suggested that the amount of alcohol dehydrogenase governs rates of ethanol metabolism, which then leaves the change in cytosolic redox state unexplained. In this paper the kinetic parameters for rat liver malate dehydrogenase, determined at 37 degrees C and pH 7.4, are used to provide an explanation for the change in cytosolic redox state that is compatible with rate control by alcohol dehydrogenase.

Total body water volumes for adult males and females estimated from simple anthropometric measurements.

Individual total body water volumes for 458 adult males and 265 adult females obtained from dilution studies, together with their height, weight, and age have been selected from the literature. These values were used to derive total body water prediction equations for adults of any age. The equations that gave the best fit were for males: formula (see text) and for females: formula (see text). Numerous other linear regression equations to predict total body water from anthropometric measurements have been reported in the literature. Most apply only to restricted age groups. These, and the equations from the present study were tested on completely independent data. In all cases the equations from the present study gave the best overall results, though for women one equation designed for a specific age group, gave for that age group a marginally better fit.

Inhibition of RNA synthesis in Chlorella pyrenoidosa and Bacillus megaterium by the pine-blight toxin, dothistromin.

Dosthistromin, an anthraquinone derivative produced by the pine-blight fungus, Dothistroma pini, inhibits the growth of Chlorella pyrenoidosa and Bacillus megaterium. At growth inhibitory concentrations, dothistromin strongly inhibits incorporation of [3H]uridine into RNA of both species. With B. megaterium, marked inhibition of [3H]uridine incorporation is apparent within 5 min of addition of dothistromin, but only a slight inhibition of [3H]thymidine incorporation into the DNA-containing fraction or of [14C]leucine incorporation into protein is detectable after 10 min.

Deficiency of alpha-mannosidase in Angus cattle. An inherited lysosomal storage disease.

A disease of Angus cattle previously known as pseudolipidosis has been shown to be an inherited lysosomal storage disease, in which an oligosaccharide containing mannose and glucosamine is the storage substance. Diseased animals have a near-absolute deficiency of the lysosomal enzyme, alpha-mannosidase, whereas heterozygotes have a partial deficiency of this enzyme. The condition is analogous to the human disease known as mannosidosis.