The Candida albicans CDR1 gene, encoding an ABC transporter that functions as an efflux pump, is thought to be involved in pathogenic adaptation and uses mammalian hormones and other environmental cues to regulate its activity. Exposure of several clinical isolates of C. albicans to 1 × 10 −8 M 17β-oestradiol increased CDR1 expression and the isolates showed a positive correlation between oestrogen induction of CDR1 and growth in the presence of oestrogen. A reporter strain carrying the GFP gene under the control of the CDR1 promoter was used to analyse the effect of steroid hormones and antifungal drugs on CDR1 expression by flow cytometry. We found that among the many hormones tested, only oestradiol and progesterone induce CDR1 expression. CDR1 induction requires hormone concentrations greater than 10 −8 M, a threshold reached in vivo only by progesterone. Using the GFP-reporter strain, we show CDR1 induction by female but not male human serum and demonstrate that exposure of C. albicans to physiological concentrations of progesterone measurably increases resistance to fluconazole, miconazole and 5-fluorouracil. Simultaneous exposure of C. albicans to hormones and antifungal drugs provided evidence that both agents induce CDR1 expression via different mechanisms with different saturation points.
Background. Previous studies have associated alopecia areata (AA) with a number of comorbidities. However, the timing between AA and the development of such comorbidities remains poorly understood. Aim. To examine the temporal relationship between AA diagnosis and comorbidity development in Denmark. Methods. A Danish nationwide register-based cohort study was performed on all individuals diagnosed with AA between 2007 and 2016 (n = 1843), and each patient was matched for age and sex with 10 healthy controls (HCs). Time between AA and comorbidity development was assessed, and incidence rate ratios (IRRs) were calculated to assess risk of comorbidity following initial AA diagnosis. Results. Use of antidepressant and anxiolytic drugs were mostly started prior to AA diagnosis, and these drugs were used more frequently before than after diagnosis with AA. Additional frequent comorbidities included thyroid disease, hyperlipidaemia, type 2 diabetes and asthma. Most comorbidities occurred prior to AA diagnosis; however, among those that occurred after AA diagnosis, antidepressants
Candida antibody tests for systemic candidiasis were conducted on 53 sera from patients with the disease and 170 sera from control patients by agar gel diffusion, counterimmunoelectrophoresis (CIE), latex agglutination, and whole-cell agglutination. The agar gel diffusion test and CIE had sensitivity, specificity, and efficiency of approximately 90%. The whole-cell agglutination test scored significantly lower, whereas the latex test scored in between. The agar gel diffusion test had the highest reproducibility and the whole-cell agglutination test the lowest in tests of identical sera by six independent laboratories. The agar gel diffusion and CIE tests make significant contributions to the diagnosis of systemic candidiasis.
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