Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it?

AbstractLeishmaniasis is one of the most neglected tropical disease in terms of drug discovery and development. Most antileishmanial drugs are highly toxic, present resistance issues or require hospitalization, being therefore not adequate to the field. Recently improvements have been achieved by combination therapy, reducing the time and cost of treatment. Nonetheless, new drugs are still urgently needed.In this review, we describe the current visceral leishmaniasis (VL) treatments and their limitations. We also discuss the new strategies in the drug discovery field including the development and implementation of high-throughput screening (HTS) assays and the joint efforts of international teams to deliver clinical candidates

Approach of Passive Filters using NSGA II in industrial installations: Part I

The optimization of passive filters in industrial systems has been presented by different computational methods. The objective of this paper is to develop a computational algorithm with NSGA II to select the configuration and design parameters of a set of passive filters for industrial installations. As a methodology, the optimization problem was addressed using three independent objective functions of innovative character for compensation of harmonics through passive filters as a multiobjective problem. The results were the computational solution to this problem that determines a set of Pareto optimal solutions (Frontier). In addition, the computational tool has several new features such as: calculates the parameters that characterize the filters, but also selects the type of configuration and the number of branches of the filter in each candidate bar according to a set of pre-established configurations according to PRODIST-M8 (Brazilian Standard) and IEEE 519-2014. Also determine solutions with good power quality indicators (THD, TDD and NPV) for several characteristic and non-characteristic scenarios of the system that allow to represent: daily variations of the load, and variations of system parameters and filters. It evaluates the cost of energy bills in an industrial power grid that has different operating conditions (characteristic scenarios) and evaluates the economic effect of harmonic filters as reactive power compensators

Seletividade e eficácia de herbicidas em cultivares de feijão-caupi (Vigna unguiculata (L.) Walp.).

Objetivou-se avaliar a seletividade e eficácia de herbicidas para a cultura do feijão-caupi, através de um experimento fatorial 2 x 13, delineamento de blocos casualizados. Foram avaliados dois cultivares de feijão-caupi (BRS Xiquexique e BRS Guariba) e 13 estratégias de manejo de plantas daninhas (1: S-metolachlor, 2: metribuzin+fluazyphop-p-buthyl, 3: mazamox+fluazyphop-p-buthyl, 4: bentazon +fluazyphop-p-buthyl, 5: imazamox+bantazon +fluazyphop-p-buthyl, 6: imazetapyr +fluazyphop-p-buthyl, 7: fomesafen+fluazyphop-p-buthyl, 8: lactofen+fluazyphop-p-buthyl, 9: clorimuron-ethyl+fluazyphop-p-buthyl, 10: clorimuron-ethyl+lactofen+fluazyphop-pbuthyl, 11: capina+fluazyphop-p-buthyl, 12: testemunha capinada e 13: testemunha sem capina). Aos 07, 15 e 30 dias após a aplicação (DAA) foram realizadas avaliações visuais de intoxicação na cultura e aos 15 e 30 DAA avaliações de controle das espécies presentes na área. Por ocasião da colheita, determinou-se a produtividade em Kg ha-¹. As duas variedades comportaram-se de forma semelhante com relação à seletividade dos herbicidas. As estratégias 2, 9 e 10 causaram morte das plantas de feijão-caupi, enquanto que as misturas 7 e 8 causaram intoxicação severa na cultura, ocasionando aumento do ciclo e redução na produtividade, já as estratégias de controle 1, 3, 4, 5, e 6 causaram apenas sintomas leves de intoxicação na cultura. As principais espécies de plantas infestantes foram Tallinum paniculatum, Cleome affinis, Amaranthus spinosus e Commelina bengalensis, sendo todas controladas com eficiência pelas misturas 5 e 6. Já as estretégias 1, 4 e 5 não exerceram controle eficiente. Assim, os herbicidas das estratégias 1, 3, 4, e 5 foram seletivos para a cultura do feijão-caupi.CONAC 2012. Disponível em: http://www.conac2012.org/resumos/pdf/185a.pdf. Acesso em: 06 ago. 2013

Comparações ambientais de Bothrops atrox na Amazônia Oriental.

A região de Santarém (PA) está relacionada com 92% dos acidentes ofídicos, dos quais 20% foram considerados graves. Através do uso da metodologia dos isótopos estáveis do carbono-13 (13C) e do nitrogênio-15 (15N), pretende-se verificar se as variações dos hábitos e fontes alimentares existentes nos diferentes ambientes e usos de solo na Amazônia, neste caso áreas de floresta, savana e pastagem, influenciam na composição isotópica das serpentes encontradas nestes ambientes, de forma a auxiliar estudos de correlação, com a variabilidade de seus venenos. As serpentes, assim como as suas possíveis presas, foram coletadas nos três ambientes, através de três métodos de coleta ? encontro ocasional, busca ativa e armadilhas de interceptação e queda ? e tiveram os seus tecidos analisados isotopicamente. Ainda serão realizadas mais coletas de serpentes e de suas fontes alimentares e essas amostras dos diferentes ambientes também serão analisadas isotopicamente. Supõe-se que as diferentes fontes alimentares nos diferentes ambientes serão isotopicamente distintas, com reflexo na composição isotópica dos tecidos das serpentes. Caso se confirme tais hipóteses este estudo contribuirá para o conhecimento da ecologia da serpente e seu uso dos ambientes, ainda pouco relatados, como para o aprimoramento futuro dos soros antiofídicos e diminuição das seqüelas geradas pelos acidentes

Current and future chemotherapy for Chagas disease

Luís Gaspar is thankful to FCT for funding (scholarship reference: SFRH/BD/81604/2011). The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED) and No. 603240 (Project NMTrypI).American trypanosomiasis, commonly called Chagas disease, is one of the most neglected illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with thousands of new cases every year. The only treatments available have been introduced five decades ago. They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease – a characteristic and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This fragility has been recently exposed by the failure of two candidates, posaconazole and E1224, to sterilely cure patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug discovery and development efforts to discover better and safer treatments. In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by academic research groups, industry and other research organizations over the last half century. We will also analyze the current research landscape that is now better placed than ever to deliver alternative treatments for Chagas disease in the near futurePostprintPeer reviewe

Dammarane Triterpenoids from Carnauba, Copernicia prunifera (Miller) H. E. Moore (Arecaceae), Wax

Phytochemical investigation from carnauba (Copernicia prunifera) wax led to the identification of sixteen dammarane-type triterpenes, including thirteen new characterized as: (24R*)-methyldammara-20,25-dien-3 alpha-ol and a mixture of alkyl (24R*)-methyldammar-25-en- 20-ol-3 beta-carboxylates, together with three previously described triterpenes: carnaubadiol, (24R*)-methyldammara-20,25-dien-3 beta-ol and (24R*)-24-methyldammara-20,25-dien-3-one. Moreover, four fatty alcohols (eicosanol, docosanol, tetracosanol and hexacosanol) as well as four sterols (cholesterol, campesterol, stigmasterol, and sitosterol) were also obtained. These compounds were isolated using classical chromatographic methods and their structures were determined by spectroscopic and chemical methods.Univ Fed Piaui, Dept Quim, BR-64049550 Teresina, PI, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210180 Santo Andre, SP, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 Diadema, SP, BrazilWeb of Scienc