Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor.

Using machine learning, targets were identified for β-lapachone. Resorting to biochemical assays, β-lapachone was validated as a potent, ligand efficient, allosteric and reversible modulator of 5-lipoxygenase (5-LO). Moreover, we provide a rationale for 5-LO modulation and show that inhibition of 5-LO is relevant for the anticancer activity of β-lapachone. This work demonstrates the power of machine intelligence to deconvolute complex phenotypes, as an alternative and/or complement to chemoproteomics and as a viable general approach for systems pharmacology studies

Diagnóstico molecular da taxa de infecção natural de flebotomíneos (Psychodidae, Lutzomyia) por Leishmania sp na Amazônia maranhense Molecular diagnosis of the natural infection rate due to Leishmania sp in sandflies (Psychodidae, Lutzomyia) in the Amazon region of Maranhão, Brazil

A taxa de infecção natural de três diferentes espécies de flebotomíneos por Leishmania foi estudada usando a técnica de reação em cadeia da polimerase. Primers específicos para Leishmania foram designados para examinar se os pools de flebotomíneos estavam infectadas. Um total de 1.100 fêmeas separadas em pools de 10 indivíduos foram examinados, consistindo de 50 Lutzomyia whitmani, 43 Lutzomyia triacantha e 17 Lutzomyia choti. De todos os pools analisados, 4 de Lutzomyia whitmani estavam positivos, mas nenhum pool das duas espécies restantes estava infectado. Deste modo, uma taxa de infecção de 0,4% foi verificada neste estudo. Esta taxa de infecção associada a estudos anteriores sugere que Lutzomyia whitmani transmite Leishmania aos mamíferos em Buriticupu, Maranhão.<br>The natural infection rate due to Leishmania was studied in three different sandfly species using the polymerase chain reaction technique. Leishmania specific primers were designed to examine whether sandfly pools were infected. In total 1,100 female sandflies separated into pools of 10 individuals, consisting of 50 pools of Lutzomyia whitmani, 43 of Lutzomyia triacantha and 17 of Lutzomyia choti, were analyzed. Among all the pools examined, four pools of Lutzomyia whitmani were positive, but none of the pools of the other two species were infected. Thus, a total infection rate of 0.4% was established in this study. A similar infection rate was found in previous studies, suggesting that Lutzomyia whitmani transmits Leishmania to mammals in Buriticupu, Maranhão

Clinical epidemiological profile of American tegumentary leishmaniasis at the Pinto Sugar Mill in Moreno Municipality, Greater Metropolitan Recife, Pernambuco State, Brazil Perfil clínico-epidemiológico da leishmaniose tegumentar americana no Engenho Pinto, Município de Moreno, Região Metropolitana do Recife, Pernambuco, Brasil

American tegumentary leishmaniasis (ATL) is present in all regions of Pernambuco State, Brazil, where it is spreading, with the emergence of foci in new areas like the Municipality (County) of Moreno in Greater Metropolitan Recife. The objective of the current study was to assess the prevalence of infection and identify autochthonous cases of ATL. In April 2006 a population survey was performed using a questionnaire and the Montenegro skin test (MST) in 481 individuals from the Pinto Sugar Mill, of whom 47% were males and 74% were younger than 30 years. One hundred forty-four individuals (30%) showed a positive MST. Of these, five presented active lesions, 41 were cured after meglumine antimoniate treatment, and one showed a spontaneous cure. Indirect immunofluorescence (IIF) was performed on sera from 89 individuals and showed a 36% positive rate. The high ATL prevalence demonstrates the epidemiological spread of the disease in Greater Metropolitan Recife, a worrisome development since there are no effective measures for ATL control except ecological awareness raising to minimize the risk of infection.<br>A leishmaniose tegumentar americana incide em todas as regiões do Estado de Pernambuco, Brasil, onde se apresenta em expansão, com o surgimento de focos em novas áreas, como o Município de Moreno, na região metropolitana do Recife. O objetivo deste estudo foi avaliar a prevalência da infecção e identificar os casos autóctones de leishmaniose tegumentar americana. Em abril de 2006, realizou-se um inquérito populacional por meio da aplicação de um questionário e do teste de intradermoreação de Montenegro a 481 indivíduos do Engenho Pinto, dos quais 47% eram do sexo masculino e 74% menores de 30 anos. Cento e quarenta e quatro (30%) indivíduos apresentaram reação positiva ao teste. Dentre estes, cinco apresentaram lesões ativas, 41 foram curados após quimioterapia e um curado espontaneamente. A RIFI realizada nos soros de 89 indivíduos apresentou 36% de positividade. A alta prevalência aponta para a expansão epidemiológica da doença nessa área da região metropolitana, fato preocupante, pois não há medidas eficazes para o controle da leishmaniose tegumentar americana, a não ser uma conscientização ecológica para minimizar o risco de infecção