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The in vitro fungicidal properties of Visco-gel, alone and combined with nystatin and amphotericin B.

The in vitro effect of the tissue conditioner Visco-gel, with or without the inclusion of nystatin and amphotericin B, upon Candida albicans, Candida krusei and Candida tropicalis, has been studied. Visco-gel alone was completely inert and would therefore not be used without nystatin in the treatment of a denture stomatitis where a yeast infection was present. Amphotericin B became completely ineffective when mixed with Visco-gel, but in control tests remained very active.

Amphotericin B↗

Ultrastructural investigations of Candida albicans after in vitro treatment with the new fungicidal agent rilopirox.

Candida albicans was maintained in various culture media and incubated with different concentrations of the antifungal agent rilopirox. After fixation, dehydration and embedding in Spurr's medium, the cells were analysed at the ultrastructural level to investigate morphological aspects of the antifungal mode of action of this new hydroxpyridone compound. All untreated or sham-treated control cells exhibited a normal ultrastructural appearance. The cells were surrounded by a multilayered cell wall of typical structure, and the plasmalemma was in close contact with the cell wall. Also, the cell organelles of the protoplast corresponded well with the findings of other authors. After treatment with rilopirox, a variety of ultrastructural changes were seen, and the extent of damage was dependent on the specific culture condition, drug concentration and incubation time. After only 6 h and 1-10 micrograms ml-1 rilopirox, the plasmalemma exhibited elongated invaginations, the number and size of the lipid droplets had increased and greatly enlarged mitochondria containing electron-dense deposits became visible. The vacuolar system was strongly expanded and occupied nearly the whole cell. Exposure to higher concentrations of the antifungal agent and prolonged incubation times resulted in complete cytoplasmic autolysis and membrane breakdown, while the fungal cell wall remained unaffected. After treatment with 0.5% rilopirox suspension gel on agar cultures, the extent of cellular damage was clearly enhanced and included all cell types of a treated yeast colony, i.e. single blastospores and pseudohyphae.

Antifungal Agents↗

Terbinafine induces the PMNL priming effect and enhances in vitro PMNL fungicidal activity against Candida albicans blastospores.

Terbinafine, a new antifungal drug of the allylamine category, has been shown not to interfere with some polymorphonuclear leucocyte (PMNL) functions such as chemotaxis and chemiluminescence. The aim of the present study was to elucidate the effects of terbinafine on PMNL respiratory burst activation and killing of Candida albicans blastospores by PMNLs at the biochemical and ultrastructural level by means of scanning electron microscopy (SEM). Terbinafine is shown to enhance the respiratory burst and superoxide anion release in human PMNLs stimulated by phorbol esters or chemotactic peptides, and to have a priming effect on PMNL functions. Moreover, in our experiments we found that terbinafine does not interfere with PMNL killing of C. albicans blastospores but, in fact, at the concentration found in tissues after oral administration, slightly increases it. As PMNLs play a key role in the early stages of fungal infections we suggest that in vivo terbinafine induces priming of PMNLs, and that this effect is related to enhanced candidacidal activity independent of direct drug damage to fungal particles.

Antifungal Agents↗

Fungicidal activity of latex sap from Carica papaya and antifungal effect of D(+)-glucosamine on Candida albicans growth.

Carica papaya latex sap inhibits the growth of Candida albicans when added to a culture during the exponential growth phase. Approximately 60% was achieved. This fungistatic effect is the result of cell wall degradation due to a lack of polysaccharidic constituents in the outermost layers of the fungal cell wall and release of cell debris into the culture medium. When C. albicans was cultured on medium supplemented with D(+)-glucosamine, an inhibitor of N-acetyl-beta-D-glucosaminidase, growth was inhibited (34%) in a similar manner. Addition of D(+)-glucosamine during the exponential growth phase also had a fungistatic effect (26%). The modes of action of C. papaya latex and of D(+)-glucosamine in cell wall breakdown are discussed.

Acetylglucosaminidase↗

Amino- and aminomethylcholesterol derivatives with fungicidal activity.

Among a series of aminocholesterol derivatives synthesized, 7-aminocholesterol is the strongest inhibitor of yeast cell growth. Using sterol auxotrophic mutant strains, we showed that this compound inhibits cell proliferation by interfering with ergosterol biosynthesis. The sterol pattern of treated cells revealed that 7-aminocholesterol inhibits delta 8-->delta 7-sterol isomerase and delta 14-sterol reductase as morpholine inhibitors. However, the novel feature of this compound is a strong cytotoxicity to yeast.

Cholesterol↗