Unveiling Lovastatin's Anti-Inflammatory Potential in Mouse's Brain during Acute Trypanosoma cruzi Infection.

Neurological commitment is a neglected manifestation of Chagas disease (CD). Meningoencephalitis mainly affects children and immunosuppressed patients, while stroke can occur with or without cardiac compromise. One of the possible causes of stroke development is microvascular commitment. Our group previously described that experimental Trypanossoma cruzi acute infection leads to cerebral microvasculopathy. This condition is characterized by decreased capillary density, increased leukocyte rolling and adhesion, and endothelial dysfunction. CD was discovered 114 years ago, and until today, only two drugs have been available for clinical treatment: benznidazole and nifurtimox. Both present a high cure rate for the acute phase (80%) and small cure rate for the chronic phase (20%). In addition, the high occurrence of side-effects, without proper medical follow-up, can result in treatment abandonment. Therefore, the search for new therapeutic schemes is necessary. Statins are drugs already used in the clinic that have several pleiotropic effects including endothelial function improvement, anti-inflammatory action, as well as trypanocidal effects, making them a potential alternative treatment for brain microvasculopathy in CD. Here, we investigate the effect of lovastatin (LOV) on brain microvasculopathy and inflammatory parameters. Swiss Webster mice were intraperitoneally inoculated with the Y strain of T. cruzi. Treatment with lovastatin (20 mg/kg/day) was initiated 24 h after the infection and continued for 14 consecutive days. We observed that LOV treatment did not affect parasitemia, brain microcirculation alterations, or the reduction in cerebral blood flow caused by T. cruzi infection. Also, LOV did not prevent the increased number of CD3+ cells and eNOS levels in the T. cruzi-infected brain. No alterations were observed on VCAM-1 and MCP-1 expressions, neither caused by infection nor LOV treatment. However, LOV prevented the increase in F4/80+ cells and ICAM-1 levels in the brain caused by acute infection with T. cruzi. These results suggest an anti-inflammatory activity of LOV, but more studies are needed to elucidate the role of LOV in CD acute infection.

Tuberculosis in adolescence: an integrative review focusing on patient-centered care / Tuberculose na adolescência: uma revisão integrativa com foco no cuidado centrado no paciente

ABSTRACT Objective: To identify how patient-centered care has been addressed in tuberculosis studies with adolescents. Data source: We searched for articles published in Portuguese, Spanish and English in the Virtual Health Library (LILACS), PubMed (MedLine), and Scopus (Elsevier) databases, from 2000 to 2020, using descriptors (DeCS, MeSH) in Portuguese and English. Data synthesis: 1,322 studies were identified, of which 18 were selected. The main themes found were related to adherence to tuberculosis treatment, knowledge, attitudes and practices, health education, and public policies. Conclusions: We observed that both the number of researchers dedicated to the topic and the presence of a truly person-centered view are still scarce elements in tuberculosis among adolescents research.

RESUMO Objetivo: Identificar, por meio de uma revisão integrativa, como o cuidado centrado no paciente tem sido abordado nos estudos de tuberculose com adolescentes. Fontes de dados: Buscamos artigos publicados em português, espanhol e inglês nas bases de dados da Biblioteca Virtual em Saúde - BVS (LILACS), PubMed (MedLine) e Scopus (Elsevier), de 2000 a 2020, utilizando descritores (DeCS, MeSH) em português e inglês. Síntese dos dados: Foram identificados 1.322 estudos, dos quais 18 foram selecionados. Os principais temas encontrados foram relacionados à adesão ao tratamento da tuberculose, conhecimentos, atitudes e práticas, educação em saúde e políticas públicas. Conclusões: Observamos que tanto o número de pesquisadores dedicados ao tema quanto a presença de uma visão verdadeiramente centrada na pessoa ainda são elementos escassos na pesquisa da tuberculose entre adolescentes.

Contribuições para a mobilização social, comunicação e educação em saúde sobre a doença de Chagas no YouTube ­ percurso e notas sobre o canal Falamos de Chagas / Contributions to social mobilization, communication and health education on Chagas disease on YouTube ­ route and notes on the channel Falamos de Chagas / Aportes a la movilización social, comunicación y educación en salud sobre la enfermedad de Chagas en YouTube ­ trayectoria y notas en el canal Falamos de Chagas

A doença de Chagas crônica afeta seis milhões de pessoas em regiões endêmicas, com 30 mil novos casos anuais ­ logo, espaços de divulgação científica são muito importantes para ofertar informações de qualidade à população. As iniciativas envolvendo o controle da doença de Chagas não podem se limitar às pesquisas com enfoque biológico. Este estudo objetiva apresentar um panorama sobre o processo de construção do canal Falamos de Chagas, no YouTube, sua importância para a comunicação, a informação, a educação em saúde e a mobilização social, bem como refletir sobre a qualidade de uma subamostra de vídeos do canal. Trata-se de um estudo qualitativo, dividido em duas fases: criação do canal e análise qualitativa dos vídeos sobre a doença disponíveis no YouTube. Observamos que existe potencial nas redes sociais, enquanto recurso de comunicação, contudo é preciso cautela, uma vez que se faz necessária a certificação da qualidade do material

Chronic Chagas disease affects six million people in endemic regions, with 30,000 new infected cases an-nually ­ thus, initiatives involving science diffusion are relevant to offer qualified information to the people. Chagas disease control initiatives cannot be limited to the level of biological focused research. This study aims to present an overview of the construction process of the YouTube channel Falando de Chagas, its importance for communication, information, health education and social mobilization, as well as to reflect on the quality of a subsample of videos present in the channel. Qualitative in nature, the study was divided into two stages: construction of the channel and qualitative analysis of videos about the disease available on YouTube. We observed that there is potential for social networks as communication resources, but caution is needed in their use, since the quality of the material needs certification

La enfermedad de Chagas crónica afecta seis millones de personas en regiones endémicas, con 30.000 nuevos casos anuales ­ los espacios de divulgación científica son muy importantes para ofrecer información a la población. Las iniciativas de control de la enfermedad de Chagas no pueden limitarse al nivel de investigación con enfoque biológico. El estudio tiene como objetivo presentar un panorama del proceso de construcción del canal Falando de Chagas, en YouTube, su importancia para la comunicación, información, educación en salud y movilización social, así como reflexionar sobre la calidad de una submuestra de videos presentes en la canal. De naturaleza cualitativa, el estudio se dividió en dos fases: construcción del canal y análisis cualitativo de videos sobre la enfermedad disponibles en YouTube. Observamos que existe potencial para las redes sociales como recurso de comunicación, sin embargo, se requiere cautela en su uso, ya que se requiere certificar la calidad del material

Effect of benznidazole on cerebral microcirculation during acute Trypanosoma cruzi infection in mice.

Central nervous system alterations was described in Chagas disease in both human and experimental models, leading to meningoencephalitis, stroke and cognitive impairment. Recently, our group demonstrated that acute infection by Trypanossoma cruzi leads to cerebral microvasculophaty in mice with endothelial dysfunction, capillary rarefaction, increased rolling and leukocyte adhesion. Only benznidazole and nifurtimox are available for clinical treatment, they have an efficiency of 80% in the acute phase and less than 20% in chronic phase. However, the effect of these drugs on brain microcirculation has not yet been evaluated. We hypothesized that early treatment with benznidazole could protect brain microcirculation during acute experimental Chagas disease. Swiss Webster mice were inoculated with 104 trypomastigotes forms of T. cruzi, and after 24 h they were treated with 50 or 100 mg/kg/day of benznidazole for 14 consecutive days. In untreated infected mice, we observed cerebral microvascular rarefaction, increase in leukocyte rolling and adhesion, reduced cerebral blood flow, and increased CD3+ and F4-80+ cells in brain tissue. Early treatment with benznidazole at 100 mg/kg/day and 50 mg/kg/day prevented the occurrence of the alterations mentioned. Here, we show that BZ is able to protect the microcirculation and reduced brain inflammation in acute experimental Chagas disease.

[Chagas disease: tackling the invisibility through the analysis of life histories of chronic patients]. / Doença de Chagas: enfrentando a invisibilidade pela análise de histórias de vida de portadores crônicos.

The scope of this article is to analyze the life histories of Chagas disease (CD) patients, searching for elements in their narratives that might present possibilities for coping with this problem. Caused by the protozoan Trypanosoma cruzi, Chagas disease combines conditions of infection and/or progression to disease, in accordance with biological and social determinants and affects around 6 to 7 million people infected with T. cruzi. More than 6,000 people die each year due to complications in the chronic CD phase. This is a qualitative study using the life history technique that was used in open interviews. We collected a wealth of material with which we can work on the context of the disease in multiple dimensions. We associate sensitive listening with the needs of people living with the CD to give strength to their voice, valuing their own life story, transforming them into masters of their history and knowledge. Visibility emerged and prevailed, exposing the disease itself as a central theme and two general sub-themes: their perceptions about the disease and their own life, in the context of the disease. We identified the need to (re)think the problem of Chagas disease as something visible and present.

O artigo tem por objetivo analisar as histórias de vida de portadores de doença de Chagas (DC), para evidenciar em suas narrativas elementos e possibilidades de enfrentamento dessa problemática. Causada pelo protozoário Trypanosoma cruzi, a DC combina condições de infecção assintomática e/ou de progressão para doença de acordo com determinantes biológicos e sociais e afeta 6 a 7 milhões de pessoas infectadas. No mundo anualmente 6 mil pessoas em consequência das complicações na fase crônica da DC. Realizamos um estudo qualitativo com uso da técnica de história de vida coletadas em entrevistas abertas, coletando um material riquíssimo para trabalhar o contexto da doença em múltiplas dimensões. Associamos uma escuta sensível com a necessidade das pessoas vivendo com a DC darem força à sua voz, valorizando sua própria história de vida, transformando-as em detendoras de sua história e de seu conhecimento. A visibilidade emergiu e prevaleceu, expondo a própria doença como tema central e dois subtemas gerais: suas percepções sobre a doença e a sua própria vida, no contexto da doença. Identificamos a necessidade de (re)pensar a problemática da doença de Chagas como algo visível e presente.

Doença de Chagas: enfrentando a invisibilidade pela análise de histórias de vida de portadores crônicos / Chagas disease: tackling the invisibility through the analysis of life histories of chronic patients

Resumo O artigo tem por objetivo analisar as histórias de vida de portadores de doença de Chagas (DC), para evidenciar em suas narrativas elementos e possibilidades de enfrentamento dessa problemática. Causada pelo protozoário Trypanosoma cruzi, a DC combina condições de infecção assintomática e/ou de progressão para doença de acordo com determinantes biológicos e sociais e afeta 6 a 7 milhões de pessoas infectadas. No mundo anualmente 6 mil pessoas em consequência das complicações na fase crônica da DC. Realizamos um estudo qualitativo com uso da técnica de história de vida coletadas em entrevistas abertas, coletando um material riquíssimo para trabalhar o contexto da doença em múltiplas dimensões. Associamos uma escuta sensível com a necessidade das pessoas vivendo com a DC darem força à sua voz, valorizando sua própria história de vida, transformando-as em detendoras de sua história e de seu conhecimento. A visibilidade emergiu e prevaleceu, expondo a própria doença como tema central e dois subtemas gerais: suas percepções sobre a doença e a sua própria vida, no contexto da doença. Identificamos a necessidade de (re)pensar a problemática da doença de Chagas como algo visível e presente.

Abstract The scope of this article is to analyze the life histories of Chagas disease (CD) patients, searching for elements in their narratives that might present possibilities for coping with this problem. Caused by the protozoan Trypanosoma cruzi, Chagas disease combines conditions of infection and/or progression to disease, in accordance with biological and social determinants and affects around 6 to 7 million people infected with T. cruzi. More than 6,000 people die each year due to complications in the chronic CD phase. This is a qualitative study using the life history technique that was used in open interviews. We collected a wealth of material with which we can work on the context of the disease in multiple dimensions. We associate sensitive listening with the needs of people living with the CD to give strength to their voice, valuing their own life story, transforming them into masters of their history and knowledge. Visibility emerged and prevailed, exposing the disease itself as a central theme and two general sub-themes: their perceptions about the disease and their own life, in the context of the disease. We identified the need to (re)think the problem of Chagas disease as something visible and present.

[Collective interest cycles and trends in Google searches related to institutional campaigns on prostate cancer: promoting health or illness?] / Ciclos de interesse coletivo e tendências das buscas no Google relacionadas a campanhas institucionais sobre o câncer de próstata: promovendo saúde ou doenças?

Google algorithms record trends in interest on topics relevant to public health. WEB searches were analyzed (2014-2019) to identify patterns linked to prostate cancer. Relative Search Volumes (RSV) were analyzed by Google Trends on "prostate cancer" (PC), "prostate examination" (PE) and "PSA"; 260-week time series; Brazil region; Health category; Trend lines (degree 2 polynomials) to identify patterns; Averages compared by ANOVA; Sudden increase in November searches; Searches on PC greatly surpass PE and PSA; Stable annual PC averages; Discreet reduction in PE; Marked increase in PSA. In campaign months: Discreet increase in PC; stability in PE; Marked increase in PSA. "Blue November" campaigns encourage early identification of prostate cancer, although interest is seen to be focused on the disease per se with a lack of interest in diagnosis throughout the year. Differences in relation to "Pink October" are discussed - tenuous relation to educational level on prevention habits and the influence of celebrities. The conclusion drawn is that RSV analysis might be useful in tracking trends in prostate cancer screening to provide input for campaign developers.

Algoritmos do Google registram tendências no interesse sobre temas relevantes à saúde coletiva. Analisamos buscas na web (2014-2019) para identificar padrões ligados ao câncer de próstata. Analisamos volumes de pesquisa relativos (VPR) pelo Google Trends sobre "câncer de próstata" (CAP), "exame de próstata"(EP) e "PSA"; séries temporais de 260 semanas; região Brasil; categoria "saúde" e linhas de tendência (polinomiais ordem 2) para identificar padrões; médias comparadas por ANOVA. Identificamos crescimentos súbitos nas buscas nos meses de novembro; buscas sobre CAP superam largamente EP e PSA; médias anuais CAP estáveis; EP com discreta queda; PSA com marcada ascensão. Nos meses de campanhas: elevação discreta de CAP; estabilidade em EP; marcada elevação de PSA. O "Novembro Azul" incentiva a identificação precoce do câncer de próstata, embora observe-se interesse focado na doença e desinteresse sobre o diagnóstico ao longo do ano. Diferenças em relação ao "Outubro Rosa" são discutidas - fraca interferência do nível de escolaridade sobre os hábitos de prevenção e influência de celebridades. Concluiu-se que análises de VPR podem ser úteis ao acompanhamento de tendências sobre o rastreio do câncer de próstata para fornecer subsídios aos desenvolvedores das campanhas.

Perceptions and Feelings of Brazilian Health Care Professionals Regarding the Effects of COVID-19: Cross-sectional Web-Based Survey.

BACKGROUND: The importance of health professionals has been recognized in COVID-19 pandemic-affected countries, especially in those such as Brazil, which is one of the top 3 countries that have been affected in the world. However, the workers' perception of the stress and the changes that the pandemic has caused in their lives vary according to the conditions offered by these affected countries, including salaries, individual protection equipment, and psychological support. OBJECTIVE: The purpose of this study was to identify the perceptions of Brazilian health workers regarding the COVID-19 pandemic impact on their lives, including possible self-contamination and mental health. METHODS: This cross-sectional web-based survey was conducted in Brazil by applying a 32-item questionnaire, including multiple-choice questions by using the Google Forms electronic assessment. This study was designed to capture spontaneous perceptions from health professionals. All questions were mandatory and divided into 2 blocks with different proposals: personal profile and COVID-19 pandemic impact. RESULTS: We interviewed Brazilian health professionals from all 5 Brazilian regions (N=1376). Our study revealed that 1 in 5 (23%) complained about inadequate personal protective equipment, including face shields (234/1376, 17.0%), masks (206/1376, 14.9%), and laboratory coats (138/1376, 10.0%), whereas 1 in 4 health professionals did not have enough information to protect themselves from the coronavirus disease. These professionals had anxiety due to COVID-19 (604/1376, 43.9%), difficulties in sleep (593/1376, 43.1%), and concentrating on work (453/1376, 32.9%). Almost one-third experienced traumatic situations at work (385/1376, 28.0%), which may have led to negative feelings of fear of COVID-19 and sadness. Despite this situation, there was hope and empathy among their positive feelings. The survey also showed that 1 in 5 acquired COVID-19 with the most classic and minor symptoms, including headache (274/315, 87.0%), body pain (231/315, 73.3%), tiredness (228/315, 72.4%), and loss of taste and smell (208/315, 66.0%). Some of their negative feelings were higher than those of noninfected professionals (fear of COVID-19, 243/315, 77.1% vs 509/1061, 48.0%; impotence, 142/315, 45.1% vs 297/1061, 28.0%; and fault, 38/315, 12.1% vs 567/1061, 53.4%, respectively). Another worrying outcome was that 61.3% (193/315) reported acquiring an infection while working at a health facility and as expected, most of the respondents felt affected (344/1376, 25.0%) or very affected (619/1376, 45.0%) by the COVID-19. CONCLUSIONS: In Brazil, the health professionals were exposed to a stressful situation and to the risk of self-contamination-conditions that can spell future psychological problems for these workers. Our survey findings showed that the psychological support for this group should be included in the future health planning of Brazil and of other hugely affected countries to assure a good mental health condition for the medical teams in the near future.

Highly aggressive behavior induced by social stress is associated to reduced cytochrome c oxidase activity in mice brain cortex.

Violence and aggression represent severe social problems, with profound impacts on public health. Despite the development of experimental models to study aggressive behavior is highly appreciated, the underlying mechanisms remain poorly understood. Given the key contribution of mitochondria to central nervous system bioenergetics, we hypothesized that mitochondrial function in brain would be altered by social stress. Using a model of spontaneous aggression, we investigated here the effects of social stress on brain mitochondrial function in prefrontal cortex of Swiss mice. Animals were categorized as highly aggressive, subordinate and non-aggressive (harmonic) after stress induced by regrouping and compared them with non-regrouped animals. Despite social stress did not affect brain cortex oxygen consumption rates and NADH:cytochrome c oxidoreductase activity, cytochrome c oxidase expression and activity were significantly lower in highly aggressive animals compared to non-regrouped ones. These changes were not observed in ATP synthase and adenine nucleotide translocator content suggesting a selective effect of social stress on cytochrome c oxidase. Therefore, aggressive behavior generated upon social stress associates to selective reduction in cytochrome c oxidase activity, with potential detrimental effects on brain bioenergetics and function.

A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC) trial.

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov, NCT00875173 . Registered on 20 October 2008.

TGF-ß Polymorphisms Are a Risk Factor for Chagas Disease.

Transforming growth factor ß1 (TGF-ß1) is an important mediator in Chagas disease. Furthermore, patients with higher TGF-ß1 serum levels show a worse clinical outcome. Gene polymorphism may account for differences in cytokine production during infectious diseases. We tested whether TGFB1 polymorphisms could be associated with Chagas disease susceptibility and severity in a Brazilian population. We investigated five single-nucleotide polymorphisms (-800 G>A, -509 C>T, +10 T>C, +25 G>C, and +263 C>T). 152 patients with Chagas disease (53 with the indeterminate form and 99 with the cardiac form) and 48 noninfected subjects were included. Genotypes CT and TT at position -509 of the TGFB1 gene were more frequent in Chagas disease patients than in noninfected subjects. Genotypes TC and CC at codon +10 of the TGFB1 gene were also more frequent in Chagas disease patients than in noninfected subjects. We found no significant differences in the distribution of the studied TGFB1 polymorphisms between patients with the indeterminate or cardiac form of Chagas disease. Therefore, -509 C>T and +10 T>C TGFB1 polymorphisms are associated with Chagas disease susceptibility in a Brazilian population.

Ambiente, saúde e trabalho: temas geradores para ensino em saúde e segurança do trabalho no Acre, Brasil / Ambiente, salud y trabajo: temas generadores para la enseñanza en salud y seguridad del trabajo en Acre, Brasil / Environment, health and work: generating subjects for education in health and safety at work in Acre, Brazil

O artigo apresenta ambiente, saúde e trabalho como temas geradores necessários à construção de uma tecnologia social para educação profissional, considerando a ergologia como perspectiva de análise, e, o diálogo, como estratégia de ensino em Saúde e Segurança no Trabalho para Agentes de Combate a Endemias em Rio Branco, Acre, Brasil. A definição dos temas geradores é resultado do diálogo entre pesquisadores de diferentes áreas, trabalhadores que atuam ou atuaram no combate às endemias, bem como de discentes e docentes do Curso Técnico em Segurança do Trabalho no Instituto Federal do Acre (IFAC), mediante exercício de atividades de ensino, pesquisa e extensão. As pesquisas histórica e documental permitiram que se estabelecessem os nexos entre os projetos de desenvolvimento que impactaram significativamente o ambiente e as relações de trabalho na saúde daí resultantes.

Este artículo presenta ambiente, salud y trabajo como temas generadores necesarios a la construcción de una tecnología social para la educación profesional, considerando la ergología como perspectiva de análisis y el diálogo como estrategia de enseñanza en Salud y Seguridad en el Trabajo para los Agentes de Combate a Endemias, en Rio Branco, Acre, Brasil. La definición de los temas resulta del diálogo entre investigadores de distintas áreas, trabajadores que actúan o actuaron en el combate a endemias, así como entre los discentes y docentes del Curso Técnico en Seguridad del Trabajo en el Instituto Federal de Acre (IFAC), mediante actividades de enseñanza, investigación y extensión. Las investigaciones históricas y documentales posibilitaron que se establecieran nexos entre los proyectos de desarrollo, que resultaron significativos en el ambiente y en las relaciones laborales en el área de la salud.

The paper proposes that environment, health and work are generating subjects, necessary to build a social technology for professional education, considering ergology as the perspective for analysis and dialogue as a teaching strategy in Health and Safety at Work for Agents that fight endemic diseases in Rio Branco, Acre, Brazil. The definition of these main generating subjects is the result of a dialogue between researchers from different areas, workers in the fight against endemic diseases, teachers and students of the Technical Course in Occupational Safety at the Federal Institute of Acre (IFAC). The historical and documentary research allowed to establish the links between the development projects that impacted significantly with outcomes in the environment and labor relations in health.

TGF-ß receptor type II costameric localization in cardiomyocytes and host cell TGF-ß response is disrupted by Trypanosoma cruzi infection.

Transforming growth factor beta (TGF-ß) cytokine is involved in Chagas disease establishment and progression. Since Trypanosoma cruzi can modulate host cell receptors, we analysed the TGF-ß receptor type II (TßRII) expression and distribution during T. cruzi - cardiomyocyte interaction. TßRII immunofluorescent staining revealed a striated organization in cardiomyocytes, which was co-localized with vinculin costameres and enhanced (38%) after TGF-ß treatment. Cytochalasin D induced a decrease of 45·3% in the ratio of cardiomyocytes presenting TßRII striations, demonstrating an association of TßRII with the cytoskeleton. Western blot analysis showed that cytochalasin D significantly inhibited Smad 2 phosphorylation and fibronectin stimulation after TGF-ß treatment in cardiomyocytes. Trypanosoma cruzi infection elicited a decrease of 79·8% in the frequency of cardiomyocytes presenting TßRII striations, but did not interfere significantly in its expression. In addition, T. cruzi-infected cardiomyocytes present a lower response to exogenous TGF-ß, showing no enhancement of TßRII striations and a reduction of phosphorylated Smad 2, with no significant difference in TßRII expression when compared to uninfected cells. Together, these results suggest that the co-localization of TßRII with costameres is important in activating the TGF-ß signalling cascade, and that T. cruzi-derived cytoskeleton disorganization could result in altered or low TGF-ß response in infected cardiomyocytes.

Proteins involved on TGF-ß pathway are up-regulated during the acute phase of experimental Chagas disease.

Studies developed by our group in the last years have shown the involvement of TGF-ß in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-ß cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-ß is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-ß signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-ß receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-ß. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-ß activity in the heart, we found that serum levels of total TGF-ß were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-ß pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection.

Use of haloperidol and risperidone in highly aggressive Swiss Webster mice by applying the model of spontaneous aggression (MSA).

Aggression is defined as the act in which an individual intentionally harms or injures another of their own species. Antipsychotics are a form of treatment used in psychiatric routine. They have been used for decades in treatment of patients with aggressive behavior. Haloperidol and risperidone promote the control of psychiatric symptoms, through their respective mechanisms of action. Experimental models are obtained by behavioral, genetic, and pharmacological manipulations, and use a reduced number of animals. In this context, we applied the model of spontaneous aggression (MSA), originating the presence of highly aggressive mice (AgR) when reassembled in adulthood. We administered haloperidol and risperidone in escalating doses, for ten consecutive days. Using positive and negative control groups, we evaluated the effectiveness of these drugs and the reversal of the aggressive behavior, performing the tail suspension test (TST) and open field test (OFT) on 10th day of treatment and 10 days after its discontinuation. The results showed that both antipsychotic drugs were effective in AgR and reversed the aggressive phenotype, reducing the number of attacks by AgR and the extent of lesions in the subordinate mice (AgD) exposed to the pattern of aggressive behavior (PAB) of the aggressors. This conclusion is based on the reduction in the animals' motor and exploratory activity, and on the reversal of patterns of aggressive behavior. The association between the MSA and experiments with other therapeutic protocols and different antipsychotics can be an important methodology in the study of aggressive behavior in psychiatric patients.

Cruzipain Activates Latent TGF-ß from Host Cells during T. cruzi Invasion.

Several studies indicate that the activity of cruzipain, the main lysosomal cysteine peptidase of Trypanosoma cruzi, contributes to parasite infectivity. In addition, the parasitic invasion process of mammalian host cells is described to be dependent on the activation of the host TGF-ß signaling pathway by T. cruzi. Here, we tested the hypothesis that cruzipain could be an important activator of latent TGF-ß and thereby trigger TGF-ß-mediated events crucial for the development of Chagas disease. We found that live epimastigotes of T. cruzi, parasite lysates and purified cruzipain were able to activate latent TGF-ß in vitro. This activation could be inhibited by the cysteine peptidase inhibitor Z-Phe-Ala-FMK. Moreover, transfected parasites overexpressing chagasin, a potent endogenous cruzipain inhibitor, prevented latent TGF-ß activation. We also observed that T. cruzi invasion, as well as parasite intracellular growth, were inhibited by the administration of Z-Phe-Ala-FMK or anti-TGF-ß neutralizing antibody to Vero cell cultures. We further demonstrated that addition of purified cruzipain enhanced the invasive activity of trypomastigotes and that this effect could be completely inhibited by addition of a neutralizing anti-TGF-ß antibody. Taken together, these results demonstrate that the activities of cruzipain and TGF-ß in the process of cell invasion are functionally linked. Our data suggest that cruzipain inhibition is an interesting chemotherapeutic approach for Chagas disease not only because of its trypanocidal activity, but also due to the inhibitory effect on TGF-ß activation.

A Imunologia no segundo segmento do Ensino Fundamental Brasileiro / The Immunology in Brazilian Middle School

O presente trabalho apresenta uma pesquisa bibliográfica documental sobre a Imunologia no 2º segmento do Ensino Fundamental (EF) brasileiro. Foram realizados levantamentos emquatro bases de dados e no site de busca Google acadêmico. Ademais, foram realizadas análises interpretativas da Lei de Diretrizes e Bases da Educação e dos Parâmetros Curriculares Nacionais(PCN), visando à identificação da inserção do tema Imunologia nos documentos oficiais que norteiama educação brasileira. Foram encontrados 21 artigos relacionados ao ensino de Imunologia. Contudo, somente um desses tratava do ensino de Imunologia no EF. Nos PCN, foi verificada a presença da recomendação do ensino do tema com uma abordagem “bélica”. Consideramos que, apesar da contemporaneidade e relevânciado tema para a formação do cidadão, há pouca investigação sobre a inserção da Imunologia no contexto investigado e sobre o ensino e a aprendizagem do tema (AU)

This paper presents a literature search ofdocuments about Immunology in the Brazilian Middle School (MS). Surveys were conducted by using the databases SciELO, PubMed, Science Direct and BVS and the search web site Google scholar, aiming at identifying scientific papersrelated to the teaching of Immunology and the approach given to this fi eld of knowledge in the literature. Further analyses of the Brazilian law and basic guidelines and the Nati onal CurricularParameters (NCP) were conducted, in order to identify the insertion of the topic in the documents that guide the Brazilian education. We found 21 items related to the teaching of immunology. However, only one of these was about the teachingof Immunology in MS. In PCN, we found the recommendation of the teaching of this subject by means of a “war” attitude. Such approach becomes as an epistemological obstacle preventing a broad understanding of immunology in the context ofthe whole organism. We conclude that, despite the contemporary aspect and the importance of the theme for citizenship development, there is scare research on the inserti on of immunology in the investi gated context and in the context of teaching and learning of this subject (AU)

A Imunologia no segundo segmento do Ensino Fundamental Brasileiro / The Immunology in Brazilian Middle School

O presente trabalho apresenta uma pesquisa bibliográfica documental sobre a Imunologia no 2º segmento do Ensino Fundamental (EF) brasileiro. Foram realizados levantamentos em quatro bases de dados e no site de busca Google acadêmico. Ademais, foram realizadas análises interpretativas da Lei de Diretrizes e Bases da Educação e dos Parâmetros Curriculares Nacionais(PCN), visando à identificação da inserção do tema Imunologia nos documentos oficiais que norteiam a educação brasileira. Foram encontrados 21 artigos relacionados ao ensino de Imunologia. Contudo, somente um desses tratava do ensino de Imunologia no EF. Nos PCN, foi verificada a presença da recomendação do ensino do tema com uma abordagem "bélica". Consideramos que, apesar da contemporaneidade e relevância do tema para a formação do cidadão, há pouca investigação sobre a inserção da Imunologia no contexto investigado e sobre o ensino e a aprendizagem do tema

This paper presents a literature search ofdocuments about Immunology in the Brazilian Middle School (MS). Surveys were conducted by using the databases SciELO, PubMed, Science Direct and BVS and the search web site Google scholar, aiming at identifying scientific papersrelated to the teaching of Immunology and the approach given to this fi eld of knowledge in the literature. Further analyses of the Brazilian law and basic guidelines and the Nati onal CurricularParameters (NCP) were conducted, in order to identify the insertion of the topic in the documents that guide the Brazilian education. We found 21 items related to the teaching of immunology. However, only one of these was about the teachingof Immunology in MS. In PCN, we found the recommendation of the teaching of this subject by means of a "war" attitude. Such approach becomes as an epistemological obstacle preventing a broad understanding of immunology in the context ofthe whole organism. We conclude that, despite the contemporary aspect and the importance of the theme for citizenship development, there is scare research on the inserti on of immunology in the investi gated context and in the context of teaching and learning of this subject

O PalhaSUS e a Saúde em Movimento nas Ruas: relato de um encontro / The PalhaSUS and the Family Health Strategy for Homeless People: a report of the meeting / PalhaSUS y salud en movimiento por las calles: informe de una unión

Relatamos a experiência gerada pelo encontro entre os projetos PalhaSUS e Estratégia Saúde da Família para População em Situação de Rua (ESF POP RUA), identificando (i) sua afinidade metodológica com a Educação Popular em Saúde e (ii) a singularidade do território de atuação, a rua, ambiente propício para esse casamento. O encontro foi mediado, por um lado, pela Coordenação de Saúde da Família e pelo Núcleo de Cultura, Ciência e Saúde, da Secretária Municipal de Saúde e Defesa Civil do Rio de Janeiro, e, por outro lado, pelo PalhaSUS desenvolvido no Instituto Oswaldo Cruz, introduzido no processo formativo da primeira equipe da ESF POP RUA. Após as atividades, os agentes de saúde assumiram um segundo papel, como palhaços mediadores da promoção da saúde com alegria, confirmando o potencial de integração da Dialogia do Riso nas ações e políticas de combate à miséria...

We report the experience generated by the union between the projects PalhaSUS and Family Health Strategy for Homeless People (ESF POP RUA), identifying (i) their methodological affinity with popular health education and (ii) the singularity of the street, which is the best environment for this union. The encounter was mediated, by one side, by the Coordination of Family Health and the Center for Culture, Science and Health, from the city government of Rio de Janeiro, and by the other side, by the PalhaSUS project developed at Oswaldo Cruz Institute, which was introduced in the formative process of the first ESF POP RUA team. After the activities, Health Agents have aggregated a new role: clowns mediating health promotion with joy, confirming the potential of integrating Dialogy of Laughter in actions and policies to fight poverty...

Relatamos la experiencia entre el encuentro de los proyectos PalhaSUS y la Estrategia de Salud de la Familia para Indigentes (ESF POP RUA), identificando (i) la afinidad metodológica con la educación popular en salud y (ii) la singularidad del território, ambiente propicio para esta unión. El encuentro fue mediado por la Coordinación de Salud de la Familia y por el Centro de Cultura, Ciencia y Salud de la Secretaría Municipal de Salud y Defensa Civil de Río de Janeiro y por PalhaSUS, proyecto desarrollado en el Instituto Oswaldo Cruz e introducido en el proceso de formación del primer equipo de ESF POP RUA. Después de las actividades, los profesionales de esta área tuvieran un papel en la promoción de la salud como payasos-agentes de alegría, confirmando el potencial de la risa en las acciones y políticas para combatir la pobreza...

Selenium Treatment and Chagasic Cardiopathy (STCC): study protocol for a double-blind randomized controlled trial.

BACKGROUND: Heart disease progression occurs in 30% of patients with chronic Trypanosoma cruzi infection. Supplementation with selenium (Se) in animal model of T. cruzi infection produced promising results. There is evidence that patients with Chagas heart disease have lower Se levels than healthy individuals and patients with T. cruzi infection without of cardiac disease. The aim of this investigation is to estimate the effect of Se treatment on prevention of heart disease progression in patients with chagasic cardiopathy. METHODS: The Selenium Treatment and Chagasic Cardiopathy trial is a superiority, double-blind, placebo-controlled, randomized clinical trial. The eligibility criteria are as follows: (1) a Chagas disease diagnosis confirmed by serology; (2) segmental, mild or moderate global left ventricular systolic dysfunction; and (3) age between 18 and 65 years. The exclusion criteria are as follows: (1) pregnancy, (2) diabetes mellitus, (3) tobacco use, (4) alcohol abuse, (5) evidence of nonchagasic heart disease, (6) depression, (7) dysphagia with evidence of food residues in the esophagus, (8) dysphagia with weight loss higher than 15% of usual weight in the last four months and/or (9) conditions that may result in low protocol adherence. The intervention will be 100 µg of sodium selenite once daily for 365 consecutive days compared to placebo. The following are the primary outcomes to be measured: (1) the trajectories of the left ventricular ejection fraction in the follow-up period; (2) reduction of heart disease progression rates, with progression defined as a 10% decrease in left ventricular ejection fraction; and (3) rate of hospital admissions attributable to dysrhythmia, heart failure or stroke due to Chagas disease. One hundred thirty patients will be randomly allocated into either the intervention or placebo group at a ratio of 1:1. The sequence allocation concealment and blinding were planned to be conducted with the strategy of numbered boxes. Both patients and health-care providers will remain blinded to the intervention groups during the 5 years of follow-up. DISCUSSION: If Se treatment reduces the progression of Chagas cardiopathy, the inclusion of this micronutrient in the daily diet can improve the therapeutic regimen for this neglected tropical disease at low cost. TRIAL REGISTRATION: Clinical Trials.gov ID: NCT00875173 (registered 20 October 20 2008).