Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: an experimental in vivo study.

The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.

In-vitro studies of two 5-nitroimidazole derivatives.

This paper reports the findings obtained using two new compounds belonging to the 5-nitroimidazole family: sulphuridazole (V1) and sulphonidazole (V2). We first assessed their antimicrobial activity on Clostridia spp. and then extended the study to Gram-positive and Gram-negative aerobic microorganisms and to Candida albicans. Their MICs were compared with those of metronidazole. The findings show that the antibacterial and antimycotic activity of sulphonidazole is greater than that of sulphuridazole, while metronidazole is not active against any aerobic organism. It also emerges that the NO2 group is indispensable for all the microorganisms assayed and that sulphuridazole and sulphonidazole are the first two 5-nitroimidazoles active against C. albicans. The redox potentials of the 5-nitroimidozoles studied suggest that their action mechanism is mainly based on redox processes.

Role of chemotherapeutic antagonism in opportunistic infections.

The most widely-known anti-tumor drugs often induce marked immunosuppression which can give rise to one or more sepses. Anti-infection measures immediately applied can sometimes prove largely ineffective or even useless, the patient dying not as a result of the spread of the tumour but as a direct consequence of opportunistic infection. We postulate that antagonism between anti-tumour and antimicrobial drugs may also play an important part in this. By way of illustration of this hypothesis, we have studied the action of a number of known inhibitors of peptidoglycan synthesis and of DNA-gyrases on certain strains of Gram-positive and Gram-negative microorganisms cultured in medium containing various concentrations of some of the best-known anti-tumour antimetabolites. The experimental data show that antimicrobial and anti-tumour drugs can sometimes induce synergic or indifferent chemotherapeutic interactions with many bacteria, while in others the effect is antagonistic. In practice, the action of the drugs could lead to bacterial selectivity, which, in conjunction with immunosuppression and the presence of resistant strains, could favour the evolution of opportunistic infection.

Influence of antimalarials chloroquine, quinine, primaquine and mepacrine on the evolution of Ehrlich ascites tumour.

Substances like imidazoles, benzimidazoles and also quinolines, whose chemical structure includes a heterocyclic nitrogen, are known to interfere with the microsomal oxidation and, in some cases, with the metabolism of drugs. Since chloroquine and primaquine exert this effect in vivo and in vitro, we studied the influence of other antimalarials (quinine and mepacrine) in mice with induced Ehrlich ascites tumour (EAT) to find out whether variations in oxygen consumption affected the course of the disease. In vitro data, obtained by a polarographic technique, indicate that primaquine and, in particular, mepacrine increase EAT-cell oxygen consumption, while in vivo data, obtained in mice injected with an inoculum of about 1 x 10(6) tumour cells per mouse, show that both drugs, but notably mepacrine, accelerate tumour growth, as monitored by Cox's statistical method for body weight, and lead to earlier death. In cases of existing neoplasia, therefore, the potentially toxic effects of certain antimalarials must be borne in mind.

In vitro activity of trimethoprim in association with sulfimidazole against aerobic gram-negative and gram-positive microorganisms and Clostridia.

The in vitro activity of a chemotherapeutic agent, sulfimidazole (SIZ), obtained by combining two molecules belonging to groups of extremely different antibacterial drugs, p-aminobenzene sulfonamide and a derivative with a 5-nitroimidazole ring, was studied. In association with trimethoprim, SIZ induces an intense synergistic antibacterial effect on gram-negative and gram-positive aerobic microorganisms and Clostridia. The results show that, in SIZ, the activity of each starting molecule remains unchanged providing that its structure-action relationship is kept intact.

Influence of glycyrrhizin on the evolution and respiration of Ehrlich ascites tumour cells.

It has been demonstrated that 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid and glycyrrhizin effectively inhibit the inception and growth of skin tumours. Moreover, glycyrrhizin and its aglycone act on the growth and differentiation of mouse melanoma cells in culture. In this study we investigated the effect of glycyrrhizin, 18 alpha- and 18 beta-glycyrrhetinic acids on the evolution of Ehrlich ascites tumour in mice. A prolonged glycyrrhizin treatment proved to be effective in modifying the animals' survival pattern.

Glycyrrhizin and 18 beta-glycyrrhetinic acid: a comparative study of the pharmacological effects induced in the rat after prolonged oral treatment.

Recent clinical and toxicological studies have investigated the mineralcorticoid-like and hypertensive effects of liquorice, and we therefore set out to identify the active component responsible for these effects. We conducted a 30-day comparative analysis of glycyrrhizin and 18 beta-glycyrrhetinic acid and found that the latter causes significant variations both in systolic blood pressure and in the excretion in the urine of Ca++. The effects were fully reversible on suspension of treatment.

In vitro activity of sulphimidazole alone and in association with trimethoprim against enteric pathogens.

Sulphimidazole is a new sulphonamide belonging to the class of intestinal sulphonamides and characterized by the fact that it is active even in vitro. It has the heterocyclic ring of 5-nitroimidazoles on amidic nitrogen. Its antibacterial activity is similar to that of the classical sulphonamides but differs in that it also combats certain anaerobic bacteria such as Clostridium botulinum. This effect is completely absent in the case of sulphadiazine and sulphamethoxazole. Also, since p-amino-benzene-sulphonamide is present in the molecule, the drug acts in synergism with trimethoprim against certain aerobic or facultative strains of enteric pathogens.