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Metabolic acidosis severely complicates methanol and ethylene glycol intoxications. Acidosis is caused by acid metabolites and can be intensified by lactate elevation. Lactate concentration depends on the NADH(2)/NAD ratio. Lactate dehydrogenase (LDH, E.C.1.1.1.27.) supplies more lactate when the level of NADH(2) is elevated. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH) inhibitors and substrates: cimetidine, EDTA, 4-methylpyrazole (4-MP), Ukrain and ethanol on LDH activity. The activity of LDH was determined spectrophotometrically in human liver homogenates incubated with cimetidine, EDTA, 4-MP and Ukrain at concentrations of 2 x 10(-6), 10(-5) and 5 x 10(-5) m as well as ethanol at concentrations of 12.50, 25.00, 50.00 mm. The LDH activity was significantly increased by 10(-5) and 5 x 10(-5) m concentrations of cimetidine and 4-MP, and by all concentrations of ethanol. The most effective change of LDH activity of about 26% (P<0.01) was observed at the highest concentration of ethanol. Ukrain inhibited LDH activity at both concentrations, i.e. 10(-5) and 5 x 10(-5) m (P<0.05). However, EDTA did not significantly influence LDH activity. The data showed that ethanol and 4-MP, the main antidotes in methanol or ethylene glycol poisoning, may increase liver LDH activity - an undesirable effect during the therapy of patients intoxicated with these alcohols. On the other hand, the decrease of LDH activity in the presence of Ukrain is a promising finding but definitely requires further investigation.

The aim of this study was to establish if the changes in the ultrastructure of the exocrine part of the pancreas are correlated with changes in serum glucose, cholesterol and lipoprotein fractions during the progression of diabetes in rabbits. Diabetes mellitus was induced in male New Zealand rabbits by a single injection of alloxan into the auricular vein. On the day 7th the glucose level in the whole blood was measured and this day was designated as the first day of diabetes. Rabbits were divided into 5 groups: untreated control, 21-day diabetes, 42-day diabetes, 90-day diabetes and 180-day diabetes. The cholesterol, HDL (high-density lipoprotein) and LDL (low-density lipoprotein) levels were examined in the serum. The total pancreatic lipase activity was measured spectrophotometrically in the pancreatic homogenate. Histological specimens were examined under an electron microscopy. The glucose level increased significantly in all of the alloxan exposed animals. The significant elevation of cholesterol level was observed on day 21 and 180. The HDL level was increased (P<0.05) only on the day 21st. The LDL level and the total activity of pancreatic lysosomal lipase increased significantly on day 21, 42 and 90. Further dilation of granular endoplasmic reticular ducts and decrease in the number of zymogen granules were observed amongst exocrine cells. Fragmented mitochondrial and translucent matrix were also seen. Intensification of the pancreatic fibrosis was found on day 90. Microvascular changes were reported in exocrine cells after 180 days. Their nuclei were smaller with large bulges on the nuclear membrane, and the number of heterogeneous electron granules of zymogen further declined. We concluded that the intensification of ultrastructural changes of the exocrine part of the pancreas correlated with the changes of the pancreatic lipase activity, and glucose and lipoprotein levels.