Plant products with antifungal activity. From field to biotechnology strategies

In this chapter, informations on the recent advances regarding antifungal activity of natural products obtained from plants collected directly from their natural habitat or from plant cell and organ, cultures have been reported. The biotechnological approaches could increase uniformity and predictability of the extracts and overcome problems associated with geographical, seasonal, and environmental variations. Human fungal pathogens are the cause of severe diseases associated with high morbidity and mortality. The major human fungal pathogens are Candida species, dermatophytes, Aspergillus species, and Cryptococcus neoformans. Side effects and resistance are frequently attributed to the current antifungal agents. Moreover, the treatments often require long-term therapy and are not resolving. Plants represent a source of antifungal agents, but up to date, the number of new phytochemicals reaching the market is very low. This review attempts to summarize the current status of botanical screening efforts, as well as in vitro and in vivo studies on antifungal activity of plant products. Despite the currently non-uniform regulatory framework in all the states, the plant-derived products are increasingly in demand for their effectiveness. The basic conclusion from these studies is that rigorous, well-designed clinical trials are needed to validate the effectiveness and safety of plant extracts for their use as antifungals

Liraglutide and Renal Outcomes in Type 2 Diabetes.

BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .)