Fungal morphology after treatment with itraconazole as a single oral dose in experimental vaginal candidosis in rats.

The therapeutic effect of a single, oral dose of itraconazole was studied in rats inoculated intravaginally with Candida albicans and in which an established vaginal infection was present. We used light microscopy, transmission and scanning electron microscopy to document the structural alterations in the 3 days after treatment. The most important observations include the speed (within 24 hours) with which itraconazole inhibits the further penetration of the fungus into the vaginal squamous epithelium, the ability of the drug to reach and structurally alter intracellularly located fungal elements, and the prolonged drug effect of a single dose leading to complete eradication of the fungus from the vagina within 3 days.

In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis.

Ketoconazole, an orally active antimycotic drug, is a potent inhibitor of ergosterol biosynthesis in Candida albicans when added to culture media which support yeast or mycelial growth or to cultures containing outgrown mycelium. This inhibition coincides with accumulation of sterols with a methyl group at C-14 and can thus be attributed to an interference with one of the reactions involved in the removal of the 14 alpha-methyl group of lanosterol. When administered to rats infected with C. albicans, ketocanazole also inhibits fungal synthesis of ergosterol. A six-times-higher dose is required to effect cholesterol synthesis by rat liver.

Synthesis and antimyoctic properties of 1-(2-alkyl-2-phenylethyl)-1H-imidazoles.

The synthesis of 1-(2-alkyl-2-phenylethyl)-1H-imidazoles was accomplished starting from the corresponding phenylacetonitriles. Via alkylation, esterification, and sodium borohydride reduction-in the presence of lithium iodide-beta-phenylalconols were obtained. Mesylation of these alcohols and refluxing with imidazole in dimethylformamide furnished title compounds, which were active in vitro against dermatophytes, yeasts, other fungi, and gram-positive bacteria and in vivo as well as in vitro against Candida albicans.

The action of miconazole of the growth of Candida albicans.

The growth of Candida albicans was studied in control cultures and in the presence of miconazole or clotrimazole. Each drug prolonged the lag phase and reduced the total final population. Although miconazole, at the low concentrations used, was a less potent inhibitor than clotrimazole in the main logarithmic phase, it was more fungicidal. The antifungal activity of miconazole on C. albicans was inversely proportional to the number of cells inoculated in the media. The effects of miconazole on growth depended on the nutrients in the medium and were most pronouncedwhen it was added to cultures of C. albicans in the lag and main logarithmic phase of growth. The growth inhibitory effects of sub-fungicidal doses of micronazole (smaller than or equal to 10-6 M) on C. albicans seemed to be reversible.