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Seventy patients with primary liver cell carcinoma (PLC) were studied for the occurrence and relative incidence of paraneoplastic syndromes (PNS) between 1985 and 1990. Here we communicate results of the study involving hypercholesterolaemia, hypercalcemia, hypoglycaemia, gynaecomastia and polycythaemia. Hypercholesterolaemia occurred in 20% of our patients and is the most common PNS in our series; polycythaemia occurred in 15.6%, hypoglycaemia in 8.6% and hypercalcaemia in 7%. It is noteworthy that hypoglycaemia, which is one of the commonest and certainly the most dangerous PNS associated with PLC, occurred in few of our patients. The occurrence and incidence of PNS as obtained in the present study slightly differ from those in developed countries. The pathophysiological mechanisms underlying these systemic manifestations are discussed.

Alcohol dehydrogenase isoenzymes were isolated from the liver of patients with hepatoma and healthy control individuals. Whereas only a single form of the enzyme was obtained in healthy control liver, two distinct forms of the enzyme were found in hepatoma liver. These two forms were named AD-I and AD-II according to their elution pattern in CM-cellulose chromatography and mobility towards the anode in polyacrylamide gel electrophoresis. Both isoenzymes resembled normal liver enzyme with respect to their molecular properties. However, the two forms had distinct kinetic properties, although AD-I had some properties similar to the normal liver enzyme. The Km values of AD-I for ethanol, n-butanol and m-nitrobenzyl alcohol were 61 microM, 90 microM and 292 microM, respectively, as against the values for AD-II which were 473 microM, 100 microM and 60 microM for the respective substrates. Pyrazole inhibited the activity of AD-II but not that of AD-I. These kinetic properties of alcohol dehydrogenase in patients with hepatoma could be of clinical importance particularly in the tropics where the disease is prevalent.

The serum activity of alcohol dehydrogenase was determined in healthy controls and in patients with liver diseases. The mean activity in hepatoma (6.4 +/- 1.0U/L) was significantly higher (P less than 0.05) than the mean values in liver cirrhosis (2.7 +/- 0.5U/L); hepatitis (4.3 +/- 1.0U/L), obstructive jaundice (2.9 +/- 0.5U/L) and healthy controls (0.7 +/- 0.1U/L). Alcohol dehydrogenase purified by CM-cellulose chromatography from the sera of patients with hepatoma had a higher affinity for butanol long chain saturated and unsaturated alcohols than the purified enzyme from healthy controls. Similarly, hepatoma alcohol dehydrogenase oxidized ethanol very poorly (KM = 154 microM) when compared with that from healthy controls (KM = 40.2 microM). Hepatoma alcohol dehydrogenase was inhibited by pyrazole while those of other liver diseases and the healthy controls were not. These properties of serum alcohol dehydrogenase may prove useful in the early diagnosis of hepatoma since biochemical changes occur before morphological changes in the development of cancer.

Gentamicin has been shown to induce renal tubular damage in man and laboratory animals and to result in elevated urinary excretion of some enzymes associated with specific cell regions in the kidney. In the present investigation, the possible protective effect of selenium against gentamicin-induced renal damage was tested by measuring the urinary excretion of some enzymes in the presence and absence of selenium. Our results show that a prior subcutaneous injection of selenium to rats for two days followed by a simultaneous S.C. injection of gentamicin and selenium resulted in a marked reduction in the excretion of such biochemical systems as the urine volume, urinary proteins, alkaline and acid phosphatases, beta-glucuronidase, muramidase, and glutamate dehydrogenase. Renal functional studies revealed that selenium-treated rats suffered less adverse effects compared to rats treated with gentamicin alone. Urinary acid phosphatase, beta-glucuronidase and muramidase, the three lysosomal enzymes tested, appeared to respond most readily to protection by selenium.

The labilizing effect of gentamicin, an aminoglycoside antibiotic, on isolated rat kidney lysosomes was investigated. The light-scattering behavior of lysosomal suspensions and the release of lysosomal acid hydrolase enzymes (acid phosphatase, beta-glucuronidase and muramidase) from incubated lysosomal suspensions, in the presence of gentamicin, were used as indices of lysosomal membrane labilization. Gentamicin was found to cause a decrease in light absorbance and a release of lysosomal acid hydrolases, which indicate lysosomal membrane swelling. In the presence of selenium, in the form of potassium selenate, the decrease in light absorbance of lysosomal suspensions and the release of lysosomal acid hydrolases from isolated lysosome particles were reduced markedly. This suggests that selenium protects against gentamicin-induced lysosomal membrane labilization. The possible mechanisms of protection by selenium are discussed.