Hepatorenal failure induced by tetracycline in dogs with portacaval shunt.

The aim of the present investigation was to determine whether tetracycline accelerated the hepatic toxicity of portacaval anastomosis and whether this could be reflected by changes in pharmacokinetics of the drug. Side-to-side portacaval shunts were constructed and converted to end-to-side by ligating the hepatic side of the portal vein in dogs. The results of this study showed that the i.v. infusion of tetracycline (50 mg/kg) to shunted animals caused rapid deterioration in hepatic and renal functions followed by the eventual transition of these animals from stage I to stage II liver disease. This was reflected by a 3- to 6-fold increase in the serum level of bilirubin, alkaline phosphatase, serum glutamic-oxalacetic transaminase, blood urea nitrogen and creatinine as compared with the levels of those produced in serum of dogs before and after the construction of the shunt before the administration of tetracycline. Kinetic analysis revealed a significant prolongation in the elimination half-life (38.2 +/- 4.2 hr) of the shunted dogs as compared with controls (14.5 +/- 1.5 hr) after the i.v. administration of tetracycline. This was accompanied by an appreciable reduction of elimination rate constant. In contrast to shunted animals, control animals exhibited no behavioral side effects after the administration of tetracycline.

Melanoma detection by enzyme-radioimmunoassay of L-dopa, dopamine, and 3-O-methyldopamine in urine.

This enzyme-radioimmunoassay for the measurement of L-dopa, dopamine, and 3-O-methyldopamine is based on the incubation of urine in the presence of catechol-O-methyltransferase, aromatic-L-amino-acid decarboxylase, and S-adenosylmethionine. The O-methylated dopamine metabolite formed, 3-O-methyldopamine, was characterized by radioimmunoassay. To evaluate the role of L-dopa metabolism in melanoma, we used the enzyme-radioimmunoassay to assess concentrations of L-dopa, dopamine, and 3-O-methyldopamine in urine from 10 healthy subjects, 10 hospitalized patients without melanoma and 28 patients with different degrees of melanoma. The effect of surgery for melanoma on urinary output of these catechols of melanoma patients was also evaluated. No significant difference in urinary L-dopa, dopamine, and 3-O-methyldopamine excretion rates was seen between normal subjects (L-dopa 1.3 +/- 0.3, dopamine 147 +/- 38, and 3-O-methyldopamine 31.4 +/- 13.6 microgram/24 h), hospitalized patients without melanoma, and amelanotic melanoma patients. However, the excretion rates for these metabolites in melanotic melanoma (L-dopa 5.6 +/- 1.2, dopamine 555 +/- 121, and 3-O-methyldopamine 178 +/- 40.3 microgram/24 h) were significantly (p < 0.005) higher than in control or amelanotic melanoma subjects. After surgery, there was a substantial decrease in urinary output of L-dopa and its metabolites by these patients.