Exploring the antifungal, antibiofilm and antienzymatic potential of Rottlerin in an in vitro and in vivo approach.

Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB50) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC50) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans. Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin's multipotentiality against these fungal infections.

Effectiveness of a resistance exercise program for lower limbs in chronic renal patients on hemodialysis: A randomized controlled trial.

INTRODUCTION: Physical inactivity in hemodialysis patients is associated with increased mortality. The objective of this study was evaluated the effect of an intradialytic resistance exercise program on chronic kidney disease (CKD) patients on hemodialysis. METHODS: One hundred seven patients were included in the study. They were aged 18-60 years, of both sexes, had undergone hemodialysis treatment for at least 1 year, sedentary. Patients were randomly divided into two groups: stretching (STG) and resistance exercise (REG). Intervention programs were performed for 8 weeks, three times a week. The evaluations were performed before and after the training programs. The primary outcome was functional capacity using the 6-minute walk test (6MWT). Secondary outcomes were peripheral muscle strength, respiratory muscle strength, spirometric respiratory function, and laboratory data. FINDINGS: Comparisons between groups revealed the following clinically relevant results in favor of REG: lower limb muscle strength (mean difference [MD] = -1.99, 95% confidence interval [CI] = -2.77 to -1.21; d = -0.53), distance walked in the 6MWT (MD = -26.27, 95% CI = -45.40 to -7.14; d = -0.46), creatinine (MD = -1.52, 95% CI = -2.49 to -0.54; d = -0.66), and calcium (MD = -0.44, 95% CI = -0.78 to -0.10; d = -0.49). DISCUSSION: CKD patients on hemodialysis have reduced functional capacity compared to healthy sedentary individuals. In turn, this reduction appears to be associated with a lower survival rate and affects the performance of their daily living activities. Thus, resistance exercise performed in the intradialytic phase is an effective therapeutic strategy for CKD patients, mainly because it increases functional capacity and lower limb muscle strength.

Insulin but not phlorizin treatment induces a transient increase in GLUT2 gene expression in the kidney of diabetic rats.

BACKGROUND/AIMS: Increases in the renal glucose transporter gene expression are involved in renal tubule-glomerular diseases. Here we investigate the GLUT2 gene expression changes in the kidney of diabetic rats, by using insulin or phlorizin treatment. METHODS: Rats were rendered diabetic and studied 20 days later: 4-12 h after one single injection of insulin or phlorizin, and 1-6 days after insulin or phlorizin injection twice a day, comparing with diabetic rats injected with placebo. GLUT2 was investigated by Northern and Western analysis. RESULTS: In 20-day diabetic rats, acute treatment with insulin lowered the plasma glucose and increased the GLUT2 mRNA ( approximately 100%, p < 0.001) without changes in the protein content, while phlorizin lowered the plasma glucose, but changed neither the GLUT2 mRNA nor the protein expression. Twenty-four hours of insulin treatment increased both GLUT2 mRNA ( approximately 100%, p < 0.001) and protein ( approximately 50%, p < 0.01), but no effects of phlorizin were observed. After 6 days, insulin and phlorizin similarly reduced glycemia, with opposite effects upon plasma insulin and urinary glucose, and both treatments decreased GLUT2 mRNA and protein (p < 0.05). CONCLUSION: In kidney of diabetic rats, an initial and transient upregulation of GLUT2 was induced specifically by insulin only. The 6-day normalization of GLUT2, however, was induced by both insulin and phlorizin treatment, which seems to be related to the plasma glucose lowering.