High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism

The essential trace element selenium has long been considered to exhibit anti-diabetic and insulin-mimetic properties, but recent epidemiological studies indicated supranutritional selenium intake and high plasma selenium levels as possible risk factors for development of type 2 diabetes, pointing to adverse effects of selenium on carbohydrate metabolism in humans. However, increased plasma selenium levels might be both a consequence and a cause of diabetes. We summarize current evidence for an interference of selenium compounds with insulin-regulated molecular pathways, most notably the phosphoinositide-3-kinase/protein kinase B signaling cascade, which may underlie some of the pro- and anti-diabetic actions of selenium. Furthermore, we discuss reports of hyperinsulinemia, hyperglycemia and insulin resistance in mice overexpressing the selenoenzyme glutathione peroxidase 1. The peroxisomal proliferator-activated receptor gamma coactivator 1α represents a key regulator for biosynthesis of the physiological selenium transporter, selenoprotein P, as well as for hepatic gluconeogenesis. As proliferator-activated receptor gamma coactivator 1α has been shown to be up-regulated in livers of diabetic animals and to promote insulin resistance, we hypothesize that dysregulated pathways in carbohydrate metabolism and a disturbance of selenium homeostasis are linked via proliferator-activated receptor gamma coactivator 1α

Is Paromomycin an Effective and Safe Treatment against Cutaneous Leishmaniasis? A Meta-Analysis of 14 Randomized Controlled Trials

Millions of people worldwide are suffering from cutaneous leishmaniasis that is caused by parasites of the genus Leishmania. Although pentavalent antimony compounds are the treatment of choice, their use is limited by high cost, poor compliance, and systemic toxicity. Paromomycin was developed to overcome such limitations. However, there is no consensus on its efficacy. This meta-analysis assessed the efficacy and safety of paromomycin compared with placebo and pentavalent antimony compounds. Fourteen randomized controlled trials, including 1,221 patients, met our selection criteria. Topical paromomycin appeared to have therapeutic activity against the old world and new world cutaneous leishmaniasis, with increased local reactions, when combined with methylbenzethonium chloride. Topical paromomycin was not significantly different from intralesional pentavalent antimony compounds in treating the old world form, whereas it was inferior to parenteral pentavalent antimony compounds in treating the new world form. However, a similar efficacy was found between parenteral paromomycin and pentavalent antimony compounds in treating the new world form. Fewer systemic side effects were observed with topical and parenteral paromomycin than pentavalent antimony compounds. These results suggest that topical paromomycin with methylbenzethonium chloride could be a therapeutic alternative to pentavalent antimony compounds for selected cases of the old world cutaneous leishmaniasis