Extracellular phospholipase production of oral Candida albicans isolates from smokers, diabetics, asthmatics, denture wearers and healthy individuals following brief exposure to polyene, echinocandin and azole antimycotics

Abstract Objective Candida albicans is the primary causative agent of oral candidosis, and one of its key virulent attributes is considered to be its ability to produce extracellular phospholipases that facilitate cellular invasion. Oral candidosis can be treated with polyenes, and azoles, and the more recently introduced echinocandins. However, once administered, the intraoral concentration of these drugs tend to be sub-therapeutic and rather transient due to factors such as the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, the pathogenic yeasts may undergo a brief exposure to antifungal drugs. We, therefore, evaluated the phospholipase production of oral C. albicans isolates following brief exposure to sub-therapeutic concentrations of the foregoing antifungals. Materials and methods Fifty C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sub-therapeutic concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for one hour. Thereafter the drugs were removed and the phospholipase production was determined by a plate assay using an egg yolk-agar medium. Results The phospholipase production of these isolates was significantly suppressed with a percentage reduction of 10.65, 12.14, 11.45 and 6.40% following exposure to nystatin, amphotericin B, caspofungin and ketoconazole, respectively. This suppression was not significant following exposure to fluconazole. Conclusions Despite the sub-therapeutic, intra oral, bioavailability of polyenes, echinocandins and ketoconazole, they are likely to produce a persistent antifungal effect by suppressing phospholipase production, which is a key virulent attribute of this common pathogenic yeast.

Leishmanicidal activity of nystatin [mycostatin]: a potent polyene compound

The susceptibility of promastigote of Leishmania major to Nystatin in vitro was examined. L. major [MHOM/PK/88/DESTO] promastigote were cultured in medium 199 supplemented with 10% heat inactivated foetal bovine serum and 2% urine. The growth of the promastigote was monitored in the absence and presence of the experimental compound [Nystatin] for upto 5 days post-inoculation. The EC50 value [the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value] obtained for Nystatin against the promastigote of L. major was less than 9.76 iu ml. Certain polyene compounds like Amphotericin-B and Nystatin [mycostatin] are familiar for their fungicidal activity. Amphotericin-B is used since long as antileishmanial drug as well. Results obtained suggest that Nystatin has a very good anti leishmanial activity in vitro. The mode of action proposed for this drug is same as for Amphotericin-B as both of these polyene compounds interact with the various sterols present on the surface of the parasite, thus unusual gaps and pores are formed on the surface that results in the leakage of the ions. This leakage finally leads to the destruction of the parasite

Antifungal activity (invitro) of certain polyene macrolide antibiotics against various plant pathogens.

Certain polyene macrolides were developed from different actinomycetes at Research and Development of Hindustan Antibiotics Limited. These antibiotics were screened for the antifungal activity against various plant pathogens. IC50 and MIC of each of the antibiotic against the plant pathogens was found out and is being reported.

Reduction of Sephadex-induced lung inflammation and bronchial hyperreactivity by rapamycin

Rapamycin is a macrolide antibiotic whose potent immunosuppressor activity was recently described in vivo and in vitro. The aim of the present work was to determine if rapamycin could affect an established inflammatory response. Conscious pathogen-free Dunkin-Hartley guinea pigs (300-400 g) were injected intravenously with Sephadex beads (G50, superfine, 10 to 40 microns, 24 mg/kg) to induce lung inflammation and bronchial hyperreactivity. Bronchoalveolar lavage (BAL) fluid was collected 2, 12 and 24 h after Sephadex administration and the cells were counted. Bronchial tissue was used to construct dose-response (contraction, g) curves to histamine and acetylcholine 24 h after the Sephadex injection, using a cascade system. Results are presented as area under the log dose-response curves. Test animals were injected with rapamycin (5 mg/kg) or its vehicle by the intramuscular route either 2 or 12 h after Sephadex injection and BAL fluid collected 24 h after Sephadex administration. Rapamycin administration 2 h after Sephadex reduced eosinophil and lymphocyte numbers in BAL by 52 and 55 per cent , respectively, but not ex vivo bronchial hyperreactivity induced by Sephadex injection. However, rapamycin administration 12 h after Sephadex reduced BAL eosinophil and lymphocyte numbers (55 and 62 per cent , respectively) and bronchial hyperreactivity. The increase in neutrophil numbers in BAL induced by Sephadex injection was not modified by rapamycin. Since lymphocyte numbers in BAL were significantly increased in Sephadex-treated animals at 12 h but not at 2 h after Sephadex injection, the present results suggest that the inhibition of bronchial hyperreactivity by rapamycin may be dependent on the presence of lymphocytes elicited into the airways by Sephadex injection

Leveduras isoladas de pacientes com câncer: incidência e sensibilidade a antibióticos poliênicos

Foram estudadas as incidências de leveduras isoladas de pacientes com câncer e submetidos a radioterapia ou a quimioterapia e a sensibilidade destes fungos a antibióticos poliênicos. De 227 desses pacientes, também com suspeita clínica de micose, foram desses pacientes, também com suspeita clínica de micose, foram isoladas 200 cepas que incluiam apenas espécies de Candida. C. albicans foi a espécie de maior incidência (87.5%), seguindo-se C. tropicalis (9.0%), C. parapsilosis (6.0%), C. brusei (4,0%), C. guilliermondii, C. pseudotropicalis (3,0% e C. famata (1,0%). Em concentracöes dos antibióticos consideradas eficazes para amostras sensíveis, todas as leveduras foram inibidas pela nistatina (8 microng/ml) e 97,4% o foram pela anfotericina B (2 microng/ml) e pela pimaricina (10microng/ml). Nessas concentraçöes, 10,6% das leveduras mostraram-se resistentes a açäo letal da nistatina, 32,6% a da anfotericina B e 38,7% a da pimaricina