Influence Of Fluconazole Research Articles

Unveiling the roles of CaSDH8 in Candida albicans: Implications for virulence and azole resistance

ABSTRACT Candida albicans is the most common pathogen in systemic fungal diseases, exhibits a complex pathogenic mechanism, and is increasingly becoming drug tolerant. Therefore, it is particularly important to study the genes associated with virulence and resistance of C. albicans. Here, we identified a gene (orf19.1588) that encodes a conserved mitochondrial protein known as CaSDH8, upon deletion of CaSdh8, the deleted strain (Casdh8Δ/Δ) experienced impaired growth, hyphal development, and virulence. Casdh8Δ/Δ displayed a reduced capacity to utilize alternative carbon sources, along with detrimental alterations in reactive oxygen species (ROS), mitochondrial membrane potential (MMP) depolarization, and adenosine triphosphate (ATP) levels. Interestingly, Casdh8Δ/Δ demonstrated resistance to azole drugs, and under the influence of fluconazole, the cell membrane permeability and mitochondrial function of Casdh8Δ/Δ were less compromised than those of the wild type, indicating a reduction in the detrimental effects of fluconazole on Casdh8Δ/Δ. These findings highlight the significance of CaSDH8 as a crucial gene for the maintenance of cellular homoeostasis. Our study is the first to document the effects of the CaSDH8 gene on the virulence and azole resistance of C. albicans at both the molecular and animal levels, providing new clues and directions for the antifungal infection and the discovery of antifungal drug targets.

Evaluation of the antifungal activity of Iranian propolis against Candida albicans

Propolis is a resinous substance which has many pharmaceutical and biological effects such as antimicrobial activities. In this study, antifungal aspect of ethanolic solution of propolis was investigated. Candida albicans isolates were obtained from patients attending the Mycology Laboratory of Veterinary Faculty of the University of Tehran. BALB/c mice were used for the second part of the study. They were divided into eight groups and infected with different strains of Candida. Then, the influence of fluconazole and propolis for prevention of infection was assessed. All of them were treated with different dilutions of fluconazole and propolis samples in microdilution plates. Only two isolates were susceptible to fluconazole. However, they showed significant susceptibility to propolis. Groups of mice which were treated with propolis showed increased resistance to Candidiasis when compared with those that received fluconazole. Results indicate that natural substances like propolis should be used instead of drugs in medicine, because they lack side effects or for its prevention of microbial resistance. Propolis has several chemical constituents, so it seems impossible that microbial strains would be able to resist it. Key words: Propolis, fluconazole, Candida albicans, MIC, mice.

Effects of Antifungal Agents in Sap Activity of Candida albicans Isolates

Some antifungal agents have shown to exert effects on expression of virulent factors of Candida as the production of secretory aspartyl proteinase (Sap). In this study, we sought to determine and to compare the influence of fluconazole and voriconazole in proteinase activity of this microorganism. Thirty-one isolates obtained from oral mucosa of human immunodeficiency virus positive (HIV) patients were used in this study. The minimal inhibitory concentrations (MIC) of fluconazole and voriconazole were determined using the broth microdilution method with RPMI 1640 medium and with yeast carbon base-bovine serum albumin (YCB-BSA) medium. The Sap activity following by digestion of BSA as substrate was determined for four Candida albicans strains arbitrarily chosen according to susceptibility (susceptible or resistant) to fluconazole or voriconazole. Besides, the SAP1 to SAP7 genes were screened by PCR for the same isolates that were determined by the Sap activity. In vitro susceptibility testing using the two media presented similar MIC values. Increased Sap activity was observed in resistant isolates on presence of drugs, but the Sap activity by susceptible isolates to azoles showed different behavior on the presence of drug. We detected the presence of SAP1 to SAP7 genes from all susceptible or resistant C. albicans isolates. The present study provides important data about the proteinase activity and the presence of genes of SAP family in fluconazole and voriconazole susceptible or resistant C. albicans isolates.

Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers

Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers

Influence of fluconazole at subinhibitory concentrations on cell surface hydrophobicity and phagocytosis of Candida albicans

Cell surface hydrophobicity (CSH) status influences virulence of Candida albicans and decreases the susceptibility of yeast cells to phagocytic killing. We tested whether subinhibitory concentrations of fluconazole, which is widely used in the treatment and prophylaxis of candidiasis, affect CSH and the susceptibility of C. albicans to enzymatic digestion by glucanase and to phagocytic killing. Treatment of yeast cells with subinhibitory fluconazole concentrations resulted in greater phagocytosis. This effect was independent of CSH but may be related to increased cell wall porosity resulting from alterations in the cell envelope. The use of subinhibitory concentrations of fluconazole in patients with competent phagocytes may contribute to resistance to candidiasis regardless of yeast CSH status.

The continuous flow culture as an in vitro model in experimental mycology.

We used the model of continuous flow culture (cfc) to study the growth of Candida species. This model allows special test conditions: a long generation time of 15-20 hs, controlled limitation of nitrogen sources and carbohydrates, comparison of the growth under aerobic and anaerobic conditions simultaneously. These conditions were used to study the effect of antimycotic drugs, mainly during a long time of 7 to 10 days. Germ tube formation as a virulence factor was more abundant and faster in cfc of strains with a stronger adherence to buccal epithelium cells. Co-cultivation of C. albicans and C. glabrata allowed conclusions for their colonization in vivo. A biofilm on the glass wall of the culture vessel led to mycelium formation by C. albicans. Concomitantly the growth of C. glabrata was favoured. Growth of C. albicans in the gastrointestinal flora was reduced by masses of bacteria and their multiple metabolic activities. A remarkable growth of C. albicans was only to be seen if the ecosystem was destroyed e.g. by antibacterial antibiotics. The influence of fluconazole in a long-term follow up study under anaerobic conditions showed an inhibition of C. albicans in 99.9 %. This means fungicidal efficacy.

Influence of fluconazole on antipyrine kinetics in rats.

The present study was undertaken to examine the effect of fluconazole on in vivo drug metabolism in rats, using the model substrate antipyrine. Oral doses of fluconazole, 20 mg/kg, were administered once (acutely) or twice daily for 4 days (chronically). Control animals received oral drug vehicle. Antipyrine kinetics were determined following an intravenous dose of 20 mg/kg given either 1 or 12 h after the single or last dose of fluconazole respectively. Acute fluconazole treatment significantly increased antipyrine half-life by 250% and reduced its clearance by 50%, without affecting its volume of distribution. Chronic treatment with fluconazole failed to affect antipyrine pharmacokinetics. This study demonstrates that acute fluconazole inhibits the metabolism of antipyrine in rats.

Possible Potentiation of Warfarin by Fluconazole

Fluconazole, a new triazole antifungal agent, interacts with a number of drugs. Only one study to date has examined the potentiation of warfarin's anticoagulant effect by fluconazole. To our knowledge, this is the first published case report of this interaction in the clinical setting. The patient had received a stable dosage regimen of warfarin for a number of months. Fluconazole 100 mg bid was added for a candidal wound infection. The prothrombin time increased from 19 to 65 seconds eight days later and the patient experienced a gastrointestinal bleeding episode. Fresh-frozen plasma was administered and warfarin was discontinued while the patient completed a planned 21-day course of fluconazole. The patient eventually resumed the original warfarin dosage with stable coagulation parameters. Until the influence of fluconazole on the anticoagulant effect of warfarin is studied in further detail, careful monitoring of coagulation parameters is recommended for all patients receiving the combination.