Curcumin enhances the activity of fluconazole against Cryptococcus gattii-induced cryptococcosis infection in mice.

AIM: The aim of this study was to investigate the in vitro and in vivo activities of pure curcumin, as well as its combination with fluconazole, against Cryptococcus gattii. METHODS AND RESULTS: The minimal inhibitory concentrations (MIC) of curcumin and its interactions with fluconazole against C. gattii were assessed in vitro using standard methods. This same combination was used to treat C. gattii-induced cryptococcosis in mice. The behavioural and functional assessment of the mice during treatment was also performed. The average MIC for curcumin was 19·8 µg ml(-1) . Its combination with fluconazole resulted in FICΣ (fractional inhibitory concentration index) values between 0·79 and 2·29. Curcumin (alone or combined with fluconazole) significantly reduced pulmonary damage and fungal burden in the brain. No colonies were found in the brain following combination treatment, which was also confirmed by the improved behaviour of mice. CONCLUSIONS: The combination therapy with curcumin and fluconazole was the most effective among the treatments tested, as in addition to reducing the fungal burden and damage on lung tissues, it was able to eliminate the fungal burden in the brain, enhancing the survival of mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points to the possibility of using curcumin in combination with fluconazole as a clinical treatment of cryptococcosis.

The effectiveness of relative dose response to retinol intake as an evaluation of vitamin A status of cirrhotic patients.

BACKGROUND: The liver is the main organ involved in homeostasis, metabolism and the storage of retinol. During the fibrotic process, hepatic stellate cells lose their lipid drops, and retinol reserves may deplete. Thus, the present study aimed to evaluate serum retinol levels (RL), hepatic retinol storage and dietary vitamin A intake in cirrhotic patients. METHODS: RL were measured by high-performance liquid chromatography in fifty-eight cirrhotic patients. Fasting RL <1.05 µmol L⁻¹ indicates vitamin A deficiency (VAD). A relative dose response (RDR) to oral retinol ≥20% indicates an inadequate hepatic retinol reserve (positive test). Severe malnutrition was defined as a mid-arm muscle circumference (MAMC) and/or triceps skinfold thickness (TSF) below the 5th percentile and moderate malnutrition as MAMC and/or TSF below the 10th percentile. Vitamin A daily intake was estimated by a specific questionnaire. The Child-Pugh classification of liver disease severity and the Model for End-Stage Liver Disease were used. RESULTS: Low RL were found in 60% of the patients. Twenty-three cirrhotic patients had adequate fasting RL (RL = 1.34; 1.05-2.12 µmol L⁻¹) and negative RDR, indicating efficient liver stores. Among thirty-five cirrhotic patients with low RL, 43% had negative RDR (RL = 0.42; 0.06-0.82 µmol L⁻¹) and 57% had positive RDR (RL = 0.45; 0.09-0.93 µmol L⁻¹). Malnutrition (36%) and inadequate vitamin A intake (55%) were not associated with fasting RL or RDR. CONCLUSIONS: VAD was highly prevalent in cirrhotic patients. However, in those with low serum RL and negative RDR, factors other than inadequate vitamin A intake, such as impaired hepatic vitamin A mobilization and intestinal vitamin A malabsorption, which were not examined in the present study, could have influenced the negative results obtained by the RDR method.