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Background: Leishmaniasis comprises several infectious diseases caused by protozoa parasites of Leishmania genus. In recent years, there has been a growing interest in the therapeutic use of natural products to treat parasitic diseases. Among them Croton cajucara Benth. (Euphorbiaceae) is a plant found in the Amazonian region with a history of safe use in folk medicine.Purpose: The purpose of this study was to investigate the effects of clerodane diterpenes, trans-dehydrocrotonin (DCTN), trans-crotonin (CTN) and acetylaleuritolic acid (AAA) obtained from powdered bark of C. cajucara against promastigotes, axenic and intracellular amastigotes of Leishmania amazonensis. Furthermore, the effects of DCTN and CTN on the trypanotiona reductase enzyme were also investigated. The extraction of the terpenes was carried out as previously reported (Maciel et al., 1998; 2003).Methods: The effect of the isolated compounds (DCTN, CTN and AAA) from the bark of C. cajucara was assessed in vitro against promastigotes, axenic amastigotes and intracellular amastigotes of L. amazonensis by counting of remaining parasites in a Neubauer chamber in comparison to pentamidine used as standard drug. The action of natural products on trypanothione reductase was assessed using soluble protein fraction of promastigotes. The assays were performed by incubation with HEPES, EDTA, NADPH and trypanothione disulfide to quantify the NAPH consumption by TryR.Results: The results showed very high efficacy, especially of the diterpene DCTN, against promastigotes (IC50 = 6.30 ± 0.06 µg/ml) and axenic amastigotes (IC50 = 19.98 ± 0.05 µg/ml) of L. amazonenesis. The cytotoxic effect of the best active natural product was evaluated on mouse peritoneal infected macrophages (IC50 = 0.47 ± 0.03 µg/ml in 24 h of culture), and the treatment revealed that DCTN never reaches toxic concentrations while reducing the infection and, most importantly, with no toxicity (>100 µg/ml with 0% of macrophage kill) when compared to pentamidine (37.5 µg/ml with 100% of macrophage kill). Furthermore, all of the natural products assayed on the trypanothione reductase enzyme inhibited the enzyme activity compared to the control.Conclusion: Clerodane diterpenes from C. cajucara showed promising in vitro antileishmanial effects against L. amazonensis, specially the DCTN with no macrophage toxicity up to the assayed concentration. In addition, the action on trypanothione reductase enzyme revealed a possible mechanism of action. [ABSTRACT FROM AUTHOR]

A proper professional lighting design implies in a continuous search for the best compromise between both low power consumption and better lighting quality. This search converts this design into a hard to solve multi-objective optimization problem. Evolutionary algorithms are widely used to attack that type of hard optimization problems. However, professionals could not benefit from that kind of assistance since evolutionary algorithms have been unexplored by several commercial lighting design computer-aided softwares. This work proposes a system based on evolutionary algorithms which implement a computer-automated exterior lighting design both adequate to irregular shaped areas and able to respect lighting pole positioning constraints. The desired lighting design is constructed using a cluster of computers supported by a web client, turning this application into an efficient and easy tool to reduce project cycles, increase quality of results and decrease calculation times. This ELCAutoD-EA system consists in a proposal for a parallel multi-objective evolutionary algorithm to be executed in a cluster of computers with a Java remote client. User must choose lighting pole heights, allowed lamps and fixtures, as well as the simplified blue print of the area to be illuminated, marking the sub-areas with restrictions to pole positioning. The desired average illuminance must also be informed as well as the accepted tolerance. Based on user informed data, the developed application uses a dynamic representation of variable size as a chromosome and the cluster executes the evolutionary algorithm using the Island model paradigm. Achieved solutions comply with the illumination standards requirements and have a strong commitment to lighting quality and power consumption. In the present case study, the evolved design used 37.5% less power than the reference lighting design provided by a professional and at the same time ensured a 227.3% better global lighting uniformity. A better lighting quality is achieved because the proposed system solves multi-objective optimization problems by avoiding power wastes which are often unclear to a professional lighting engineer in charge of a given project. [ABSTRACT FROM AUTHOR]