Activity of the antiarrhythmic drug amiodarone against Leishmania (L.) infantum: an in vitro and in vivo approach

<div><p>Abstract Background: Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market. Methods: In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.)infantum and its in vitro and in vivo activity. Results: The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC50 value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC50 value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum-infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR. Conclusions: Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL.</p></div

Understanding unsuccessful attempts to quit smoking: a social phenomenology approach

Abstract OBJECTIVE The aim of this paper is to understand the experience of smokers in view of unsuccessful attempts to quit smoking. METHOD This study is based on social phenomenology. Between November and December of 2014, nine interviews were conducted with people that had attempted to quit smoking. The content of these interviews was analyzed and discussed based on the related literature. RESULTS Unsuccessful attempts to quit smoking are related to tobacco addiction; cigarettes are seen as a support to cope with everyday stressful situations. Attempts to quit the smoking habits were based on the need of health improvement and insistence of family and friends. Smokers reported the use of habit cessation strategies learned in support groups, but they also express expectation of specialized psychological support. CONCLUSION The study points out the need to expand the strategies of approaching smokers, and reinforcing psychological support in order to achieve success in the attempt to quit smoking