The effects of nitric oxide on the immune system during Trypanosoma cruzi infection

Trypanosoma cruzi infection triggers substantial production of nitric oxide (NO), which has been shown to have protective and toxic effects on the host's immune system. Sensing of trypomastigotes by phagocytes activates the inducible NO-synthase (NOS2) pathway, which produces NO and is largely responsible for macrophage-mediated killing of T. cruzi. NO is also responsible for modulating virtually all steps of innate and adaptive immunity. However, NO can also cause oxidative stress, which is especially damaging to the host due to increased tissue damage. The cytokines IFN-³ and TNF-±, as well as chemokines, are strong inducers of NOS2 and are produced in large amounts during T. cruzi acute infection. Conversely, TGF-² and IL-10 negatively regulate NO production. Here we discuss the recent evidence describing the mechanisms by which NO is able to exert its antimicrobial and immune regulatory effects, the mechanisms involved in the oxidative stress response during infection and the implications of NO for the development of therapeutic strategies against T. cruzi.FAPESPFRSGTWPMPMMGThe Millennium Institute for Vaccine Development and TechnologyCNP

Global and decomposition evolutionary support vector machine approaches for time series forecasting

Multi-step ahead Time Series Forecasting (TSF) is a key tool for support- ing tactical decisions (e.g., planning resources). Recently, the support vector machine emerged as a natural solution for TSF due to its nonlinear learning capabilities. This paper presents two novel Evolutionary Support Vector Machine (ESVM) methods for multi-step TSF. Both methods are based on an Estimation Distribution Algorithm (EDA) search engine that automatically performs a simultaneous variable (number of inputs) and model (hyperparameters) selection. The Global ESVM (GESVM) uses all past patterns to fit the support vector machine, while the Decomposition ESVM (DESVM) separates the series into trended and stationary effects, using a distinct ESVM to forecast each effect and then summing both predictions into a sin- gle response. Several experiments were held, using six time series. The proposed approaches were analyzed under two criteria and compared against a recent Evolu- tionary Artificial Neural Network (EANN) and two classical forecasting methods, Holt-Winters and ARIMA. Overall, the DESVM and GESVM obtained competitive and high quality results. Furthermore, both ESVM approaches consume much less computational effort when compared with EANN.The authors wish to thank Ramon Sagarna for introducing the subject of EDA. The work of P. Cortez was supported by FEDER (program COMPETE and FCT) under project FCOMP-01-0124-FEDER-022674

Valores de referência para plumbemia em população urbana

INTRODUCTION: The lead reference values for blood used in Brazil come from studies conducted in other countries, where socioeconomic, clinical, nutritional and occupational conditions are significantly different. In order to guarantee an accurate biomonitoring of the population which is occupationally exposed to lead, a major health concern of the studied community, reference values for individuals who are not occupationally exposed and who live in the southern region of the city were established. MATERIAL AND METHOD: The sample was composed of 206 subjects of at least 15 years of age. Various strategies were employed to assure good-quality sampling. Subjects who presented values outside clinical or laboratory norms were excluded, as well as those whose specific activities might interfere with the results. RESULTS: Lead reference values for blood were found to be from 2.40 to 16.6 µg.dL-1, obtained by the interval ; ± 2s (where ; is the mean and s is the standard deviation form observed values) and the median was 7.9 µg.dL-1.INTRODUÇÃO: Os valores de referência utilizados no Brasil, para chumbo em sangue, advêm de estudos realizados em outros países onde as condições socioeconômicas, clínicas, nutricionais e ocupacionais diferem bastante das brasileiras. Para garantir uma correta biomonitorização da população ocupacionalmente exposta ao chumbo, um dos principais problemas identificados no município estudado, foram estabelecidos valores de referência na população não exposta ocupacionalmente da região sul do município. MATERIAL E MÉTODO: Diferentes estratégias foram utilizadas para assegurar a qualidade de amostragem, que foi dimensionada em 206 sujeitos acima de 15 anos. Sujeitos que apresentaram valores clínicos e laboratoriais fora da faixa de normalidade foram excluídos, bem como os que apresentaram atividades específicas que pudessem interferir nos valores de plumbemia. RESULTADOS: Foram encontrados valores de referência para chumbo em sangue de 2,4 a 16,6 mg.dL-1, obtidos através do intervalo ; ± 2s (onde ; é o valor médio e s é o desvio-padrão dos valores observados) e mediana = 7,9 µg.dL-1

IL-17 Produced during Trypanosoma cruzi Infection Plays a Central Role in Regulating Parasite-Induced Myocarditis

Chagas disease is caused by the intracellular parasite Trypanosoma cruzi. This infection has been considered one of the most neglected diseases and affects several million people in the Central and South America. Around 30% of the infected patients develop digestive and cardiac forms of the disease. Most patients are diagnosed during the chronic phase, when the treatment is not effective. Here, we showed by the first time that IL-17 is produced during experimental T. cruzi infection and that it plays a significant role in host defense, modulating parasite-induced myocarditis. Applying this analysis to humans could be of great value in unraveling the elements involved in the pathogenesis of chagasic cardiopathy and could be used in the development of alternative therapies to reduce morbidity during the chronic phase of the disease, as well as clinical markers of disease progression. The understanding of these aspects of disease may be helpful in reducing the disability-adjusted life years (DALYs) and costs to the public health service in developing countries

Evaluation of a Rapid Immunochromatographic ODK-0901 Test for Detection of Pneumococcal Antigen in Middle Ear Fluids and Nasopharyngeal Secretions

Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901) that detects pneumococcal antigens using 264 middle ear fluids (MEFs) and 268 nasopharyngeal secretions (NPSs). A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM). In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs

The Guinea-Bissau Family of Mycobacterium tuberculosis Complex Revisited

The Guinea-Bissau family of strains is a unique group of the Mycobacterium tuberculosis complex that, although genotypically closely related, phenotypically demonstrates considerable heterogeneity. We have investigated 414 M. tuberculosis complex strains collected in Guinea-Bissau between 1989 and 2008 in order to further characterize the Guinea-Bissau family of strains. To determine the strain lineages present in the study sample, binary outcomes of spoligotyping were compared with spoligotypes existing in the international database SITVIT2. The major circulating M. tuberculosis clades ranked in the following order: AFRI (n = 195, 47.10%), Latin-American-Mediterranean (LAM) (n = 75, 18.12%), ill-defined T clade (n = 53, 12.8%), Haarlem (n = 37, 8.85%), East-African-Indian (EAI) (n = 25, 6.04%), Unknown (n = 12, 2.87%), Beijing (n = 7, 1.68%), X clade (n = 4, 0.96%), Manu (n = 4, 0.97%), CAS (n = 2, 0.48%). Two strains of the LAM clade isolated in 2007 belonged to the Cameroon family (SIT61). All AFRI isolates except one belonged to the Guinea-Bissau family, i.e. they have an AFRI_1 spoligotype pattern, they have a distinct RFLP pattern with low numbers of IS6110 insertions, and they lack the regions of difference RD7, RD8, RD9 and RD10, RD701 and RD702. This profile classifies the Guinea-Bissau family, irrespective of phenotypic biovar, as part of the M. africanum West African 2 lineage, or the AFRI_1 sublineage according to the spoligtyping nomenclature. Guinea-Bissau family strains display a variation of biochemical traits classically used to differentiate M. tuberculosis from M. bovis. Yet, the differential expression of these biochemical traits was not related to any genes so far investigated (narGHJI and pncA). Guinea-Bissau has the highest prevalence of M. africanum recorded in the African continent, and the Guinea-Bissau family shows a high phylogeographical specificity for Western Africa, with Guinea-Bissau being the epicenter. Trends over time however indicate that this family of strains is waning in most parts of Western Africa, including Guinea-Bissau (p = 0.048)

Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein–protein and protein–immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of protein–protein and protein–immobilized ligand interactions are discussed. Presently, this field of research is often called interactomics or interaction proteomics. A slightly different approach that will be discussed, chemical proteomics, allows one to analyze selectivity profiles of ligands for multiple drug targets and off-targets. Additionally, of particular interest is the use of surface plasmon resonance technologies coupled with MS for the study of protein interactions. The review addresses the principle of each of the methods with a focus on recent developments and the applicability to lead compound generation in drug discovery as well as the elucidation of protein interactions involved in cellular processes. The review focuses on the analysis of bioaffinity interactions of proteins with other proteins and with ligands, where the proteins are considered as the bioactives analyzed by MS