Euroitalia (Italy)

The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-beta-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-beta-hydroxycortisol, but the magnitude of the effects was significantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.

The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

A strain ofClaviceps purpurea, labelled 231 F.I., produced in submerged culture 1200 μ/ml of a mixture of peptidic alkaloids composed for 30% by β-ergokryptine. Cultural media, conditions of culture and development features of a typic fermentation are reported.

Adriamycin was given by an infra-arterial route as part of a planned program of combined modality therapy in 10 patients with regionally advanced neoplasms. Doses ranged from 45–107 mg/m2 given as a continuous infusion over 1.5–3.0 days. Adriamycin was followed by radiation therapy and/or radical surgical excision of the tumor in most cases, making long-term evaluation of response difficult. However, 4 of 7 evaluable patients had prompt partial responses prior to subsequent treatment. We conclude that adriamycin can be administered by the intra-arterial route and that it may be useful as part of a program of combined modality therapy in selected patients. Cancer 33:1485–1490, 1974.

The effect of 1,6-dimethyl-8β-carbobenzyloxy-aminomethyl-10α-er-goline (MCE), a potent anti-5-hydroxytryptamine (5-HT) agent with a prolonged effect, was studied.