Trypanosoma cruzi interaction with host tissues modulate the composition of large extracellular vesicles.

Trypanosoma cruzi is the protozoan that causes Chagas disease (CD), an endemic parasitosis in Latin America distributed around the globe. If CD is not treated in acute phase, the parasite remains silent for years in the host's tissues in a chronic form, which may progress to cardiac, digestive or neurological manifestations. Recently, studies indicated that the gastrointestinal tract represents an important reservoir for T. cruzi in the chronic phase. During interaction T. cruzi and host cells release extracellular vesicles (EVs) that modulates the immune system and infection, but the dynamics of secretion of host and parasite molecules through these EVs is not understood. Now, we used two cell lines: mouse myoblast cell line C2C12, and human intestinal epithelial cell line Caco-2to simulate the environments found by the parasite in the host. We isolated large EVs (LEVs) from the interaction of T. cruzi CL Brener and Dm28c/C2C12 and Caco-2 cells upon 2 and 24 h of infection. Our data showed that at two hours there is a strong cellular response mediated by EVs, both in the number, variety and enrichment/targeting of proteins found in LEVs for diverse functions. Qualitative and quantitative analysis showed that proteins exported in LEVs of C2C12 and Caco-2 have different patterns. We found a predominance of host proteins at early infection. The parasite-host cell interaction induces a switch in the functionality of proteins carried by LEVs and a heterogeneous response depending on the tissues analyzed. Protein-protein interaction analysis showed that cytoplasmic and mitochondrial homologues of the same parasite protein, tryparedoxin peroxidase, were differentially packaged in LEVs, also impacting the interacting molecule of this protein in the host. These data provide new evidence that the interaction with T. cruzi leads to a rapid tissue response through the release of LEVs, reflecting the enrichment of some proteins that could modulate the infection environment.

Sérgio Arouca na Faculdade de Ciências Médicas da Unicamp / Sérgio Arouca at the UNICAMP School of Medical Sciences

RESUMO Este trabalho resgatou a passagem do médico sanitarista e professor universitário Antônio Sérgio da Silva Arouca pela Universidade Estadual de Campinas (Unicamp), entre 1967 e 1975, mediante estudo de três documentos importantes conservados nessa instituição, a saber, seu Processo de Vida Funcional, a Revista Comemorativa dos 25 anos do Departamento de Medicina Preventiva e Social da Faculdade de Ciências Médicas, onde consta depoimento seu, e o Relatório Final da Comissão da Verdade e Memória "Octávio Ianni". No Departamento de Medicina Preventiva e Social da Unicamp, encontrou ambiente propício para atuar conforme suas convicções. Integrou-se à disciplina de Ciências Sociais Aplicadas à Medicina, cujo conteúdo teórico dialogava com ações extramuros desenvolvidas pelos alunos em bairro pobre da cidade, com o intuito de lhes propiciar a oportunidade de reconhecer a importância e a influência dos fatores sociais sobre o estado de saúde dos indivíduos e das populações. Tal experiência, muito provavelmente, influenciou sobremaneira o jovem docente que, anos depois, produziria uma tese de extrema relevância para formulação e consolidação da saúde coletiva brasileira e presidiria a VIII Conferência Nacional de Saúde, que estabeleceu as bases do Sistema Único de Saúde.

ABSTRACT This work recovers the passage of the public health physician and university professor Antônio Sérgio da Silva Arouca through the State University of Campinas (UNICAMP), between 1967 and 1975, through the study of three important documents kept in this institution, namely, his Functional Life File, the Commemorative Magazine of the 25th anniversary of the Department of Preventive and Social Medicine of the Faculty of Medical Sciences, where his statement is included, and the Final Report of the "Octávio Ianni" Truth and Memory Commission. At the UNICAMP's Department of Preventive and Social Medicine, he found a favorable environment to act according to his convictions. He joined the discipline of Social Sciences Applied to Medicine, whose theoretical content dialogued with extramural actions developed by students in poor neighborhoods of the city, in order to give them the opportunity to recognize the importance and influence of social factors on the health status of individuals and populations. This experience probably had a great influence on the young professor who, years later, would produce a thesis of extreme relevance for the formulation and consolidation of Brazilian Public Health, and preside over the 8th National Health Conference, which established the bases for the Unified Health System.

Non-histone protein methylation in Trypanosoma cruzi epimastigotes.

Post-translational methylation of proteins, which occurs in arginines and lysines, modulates several biological processes at different levels of cell signaling. Recently, methylation has been demonstrated in the regulation beyond histones, for example, in the dynamics of protein-protein and protein-nucleic acid interactions. However, the presence and role of non-histone methylation in Trypanosoma cruzi, the etiologic agent of Chagas disease, has not yet been elucidated. Here, we applied mass spectrometry-based-proteomics (LC-MS/MS) to profile the methylproteome of T. cruzi epimastigotes, describing a total of 1252 methyl sites in 824 proteins. Functional enrichment and protein-protein interaction analysis show that protein methylation impacts important biological processes of the parasite, such as translation, RNA and DNA binding, amino acid, and carbohydrate metabolism. In addition, 171 of the methylated proteins were previously reported to bear phosphorylation sites in T. cruzi, including flagellar proteins and RNA binding proteins, indicating that there may be an interplay between these different modifications in non-histone proteins. Our results show that a broad spectrum of functions is affected by methylation in T. cruzi, indicating its potential to impact important processes in the biology of the parasite and other trypanosomes.

The impact of COPD on the private healthcare system in Brazil: an economic analysis / Impacto da DPOC no sistema de saúde privado no Brasil: uma análise econômica

Objective: To assess healthcare resource utilization and hospitalization costs of patients with chronic obstructive pulmonary disease (COPD) exacerbations in the Brazilian private healthcare system. Methods: A retrospective cohort study, considering data from an administrative database of a private company (Orizon). Patients aged ≥40 years old and with at least one COPD-related claim identified by the ICD-10 code (J40 to J44) at any time during the eligibility period (January/2010 to December/2013) were included in the analysis. Follow-up was performed until December/2014, death or inactivation of a health plan. Sociodemographic characteristics, number of emergency visits, hospital admissions (number and length of stay), length of hospital stay in an intensive care unit (ICU), number of severe COPD exacerbations, therapeutic approach, and hospitalization costs were assessed. Results: The analysis included 8,254 COPD patients. Emergency visits, hospital admission, and exacerbation rates were 0.4, 0.2, and 0.1 per person-year, respectively. The mean length of hospital stays and the length of stay of patients requiring or not ICU stay were 16.6 (SD = 77.0), 8.7 (SD = 36.9), and 27.6 (SD = 109.7), respectively. Mean costs associated to emergency department visits and hospitalizations were 258.2 BRL (SD = 383.1) and 38,165.4 BRL (SD = 124,683.5), respectively. Hospitalizations costs without ICU stay were 11,810.1 BRL (SD = 31,144.1) and 74,585.3 BRL (SD = 182,808.1) for those with ICU utilization. Conclusion: Costs for COPD management during disease exacerbation are very high and may reach almost 75 thousand BRL per hospitalization. The prevention of COPD exacerbations and better disease control may reduce the economic burden on the private healthcare system in Brazil.

Objetivo: Avaliar a utilização de recursos e custos de pacientes com exacerbação da doença pulmonar obstrutiva crônica (DPOC) no sistema de saúde suplementar (SSS) do Brasil. Métodos: Estudo de coorte retrospectiva, considerando banco de dados administrativo de uma empresa privada (Orizon). Pacientes com ≥40 anos e pelo menos um registro de admissão relacionado à DPOC identificado com CID-10 J40-J44, entre janeiro/2010 e dezembro/2013, foram incluídos e acompanhados até dezembro/2014, morte ou inativação no plano. Características sociodemográficas, número de visitas de emergência, admissões hospitalares (número e tempo de hospitalização), tempo de hospitalização em unidade de terapia intensiva (UTI), número de exacerbações graves, estratégias terapêuticas e custos hospitalares foram as variáveis analisadas. Resultados: A análise incluiu 8.254 pacientes com DPOC. As taxas de visita à emergência, internação hospitalar e exacerbação da doença foram de 0,4, 0,2 e 0,1 por pessoa-ano, respectivamente. Os tempos médios de hospitalização, hospitalização sem utilização de UTI e hospitalização com necessidade de UTI foram de 16,6 (DP = 77,0), 8,7 (DP = 36,9) e 27,6 (DP = 109,7) dias, respectivamente. Os custos médios relacionados à visita de emergência e por hospitalização foram de 258,2 BRL (DP = 383,1) e 38.165,4 BRL (DP = 124.683,5), respectivamente. Os custos para pacientes que não utilizaram UTI foram de 11.810,1 BRL (DP = 31.144,1) e de 74.585,3 BRL (DP = 182.808,1) para aqueles com necessidade desse serviço. Conclusão: Os custos para o manejo dos pacientes com exacerbação da DPOC são muito elevados, podendo chegar a 75.000 BRL por hospitalização. A prevenção de exacerbações e o melhor controle da doença podem reduzir esse impacto econômico no SSS.

Effect of continuous positive airway pressure on atrial remodeling and diastolic dysfunction of patients with obstructive sleep apnea and metabolic syndrome: a randomized study.

OBJECTIVE: The aim of this study was to evaluate the role of obstructive sleep apnea (OSA) treatment on heart remodeling and diastolic dysfunction in patients with metabolic syndrome (MS). METHODS: This study is a prespecified analysis of a randomized placebo-controlled trial that enrolled patients with a recent diagnosis of MS and moderate-to-severe OSA to undergo continuous positive airway pressure (CPAP) or nasal dilators (placebo) for 6 months. Patients were invited to perform a transthoracic echocardiogram by a single investigator blinded to treatment assignment. RESULTS: A total of 99 (79% men; mean [SD], age: 48 [9] years; BMI: 33 [4] kg/m2 ) completed the study. At follow-up, in the placebo group, patients had a significant increase in atrial diameter: from 39.5 (37.0-43.0) mm to 40.5 (39.0-44.8) mm (p = 0.003). CPAP prevented atrial enlargement: from 40.0 (38.0-44.0) to 40.0 (39.0-45.0) mm (p = 0.194). In patients with diastolic dysfunction at baseline, almost half had diastolic dysfunction reversibility with CPAP (in comparison with only two patients in the placebo group, p = 0.039). In the regression analysis, the chance of diastolic dysfunction reversibility by CPAP was 6.8-fold (95% CI: 1.48-50.26, p = 0.025) compared with placebo. CONCLUSIONS: In patients with MS and OSA, 6 months of CPAP therapy prevented atrial remodeling and increased the chance of diastolic dysfunction reversibility.

Impact of asthma control on quality of life in an outpatient setting in Brazil.

INTRODUCTION: The goal of asthma therapy is asthma control. As a chronic disease, asthma may cause considerable physical, emotional and social restrictions impacting quality of life. The aim of this study was to analyze control of asthma symptoms in an outpatient setting in Brazil and its impact on quality of life. METHODS: A pilot cross-sectional study was performed in two public centers in the metropolitan region of São Paulo, Brazil. Control of asthma symptoms was assessed according to GINA guidelines, and quality of life was analyzed by the Mini Quality of Life Questionnaire (mini-AQLQ). RESULTS: A total of 47 adult patients with asthma were analyzed. Asthma was controlled in 8 patients (17.0%), partially controlled in 26 patients (55.3%) and uncontrolled in 13 patients (27.7%). Patients with controlled asthma showed better mini-AQLQ scores (4.99 ± 1.10) as compared to those with partly controlled (3.66 ± 1.10) and uncontrolled asthma (2.59 ± 0.64; p < 0.001 for both). Most patients (85.1%) were taking inhaled corticosteroids (ICS) and long-acting bronchodilators (LABA) as controller treatment. CONCLUSIONS: Better asthma control had a positive impact on Health-Related Quality of Life (HRQoL) contributing to a better disease management. Few patients reached full asthma control in our specialty ambulatory center, suggesting further initiatives are required to improve the quality of asthma care in Brazil.

Effects of CPAP on Metabolic Syndrome in Patients With OSA: A Randomized Trial.

BACKGROUND: OSA is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with CPAP can revert MS. RESEARCH QUESTION: Does OSA treatment with CPAP per se have effects on the MS reversibility and the associated metabolic, adiposity and vascular parameters? STUDY DESIGN AND METHODS: The TREATOSA-MS trial is a randomized placebo-controlled trial that enrolled adult patients with a recent diagnosis of MS and moderate or severe OSA (apnea-hypopnea index [AHI], ≥ 15 events/h) to undergo therapeutic CPAP or nasal dilator strips (placebo group) for 6 months. Before and after each intervention, we measured anthropometric variables, BP, glucose, and lipid profile. To control potential-related mechanisms and consequences, we also measured adiposity biomarkers (leptin and adiponectin), body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic fat), and endothelial function. RESULTS: One hundred patients (79% men; mean age, 48 ± 9 years; BMI, 33 ± 4 kg/m2; AHI, 58 ± 29 events/h) completed the study (n = 50 per group). The mean CPAP adherence was 5.5 ± 1.5 h/night. After 6 months, most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group (18% vs 4%; OR, 5.27; 95% CI, 1.27-35.86; P = .04). In the secondary analysis, CPAP did not promote significant reductions in the individual components of MS, weight, hepatic steatosis, lipid profile, adiponectin, and leptin, but did promote a very modest reduction in visceral fat and improved endothelial function (all analyses were adjusted for baseline values). INTERPRETATION: Despite the higher rate of MS reversibility after CPAP therapy as compared with placebo, most patients retained this diagnosis. The lack of significant or relevant effects on adiposity biomarkers and depots supports the modest role of OSA in modulating MS. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02295202; URL: www. CLINICALTRIALS: gov.

An updated map of Trypanosoma cruzi histone post-translational modifications.

In humans and other eukaryotes, histone post-translational modifications (hPTMs) play an essential role in the epigenetic control of gene expression. In trypanosomatid parasites, conversely, gene regulation occurs mainly at the post-transcriptional level. However, our group has recently shown that hPTMs are abundant and varied in Trypanosoma cruzi, the etiological agent of Chagas Disease, signaling for possible conserved epigenetic functions. Here, we applied an optimized mass spectrometry-based proteomic workflow to provide a high-confidence comprehensive map of hPTMs, distributed in all canonical, variant and linker histones of T. cruzi. Our work expands the number of known T. cruzi hPTMs by almost 2-fold, representing the largest dataset of hPTMs available to any trypanosomatid to date, and can be used as a basis for functional studies on the dynamic regulation of chromatin by epigenetic mechanisms and the selection of candidates for the development of epigenetic drugs against trypanosomatids.

Proteomics analysis reveals the role of ubiquitin specific protease (USP47) in Epithelial to Mesenchymal Transition (EMT) induced by TGFß2 in breast cells.

Epithelial to Mesenchymal Transition (EMT) is a normal cellular process that is also triggered during cancer progression and metastasis. EMT induces cellular and microenviromental changes, resulting in loss of epithelial features and acquisition of mesenchymal phenotypes. The growth factor TGFß and the transcription factor SNAIL1 (SNAIL) have been described as inducers of EMT. Here, we carried out an EMT model with non-tumorigenic cell line MCF-10A induced with the TGFß2 specific isoform of TGF protein family. The model was validated by molecular, morphological and functional experiments and showed correlation with the up-regulation of SNAIL. In order to identify additional regulators of EMT in this non-tumorigenic model, we explored quantitative proteomics, which revealed the Ubiquitin carboxyl-terminal hydrolase 47 (USP47) as one of the top up-regulated proteins. USP47 has a known role in cell growth and genome integrity, but not previously correlated to EMT. After validating USP47 alterations using MRM and antibody-based assays, we demonstrated that the chemical inhibition of USP47 with the inhibitor P5091 reduced expression of EMT markers and reverted morphological changes in MCF-10A cells undergoing EMT. These results support the involvement of USP47 in our EMT model as well as potential applications of deubiquitinases as therapeutic targets for cancer progression management. BIOLOGICAL SIGNIFICANCE: Metastasis is responsible for most cancer-associated mortality. Additionally, metastasis requires special attention, as the cellular transformations make treatment at this stage very difficult or occasionally impossible. Early steps in cancer metastasis involve the ability to detach from the solid tumor mass and invade the surrounding stromal tissues through cohesive migration, or a mesenchymal or amoeboid invasion. One of the first steps for metastatic cascade is denominated epithelial to mesenchymal transition (EMT), which can be triggered by different factors. Here, our efforts were directed to better understand this process and identify new pathways that contributes for acquisition of EMT, mainly focused on post translational modifications related to ubiquitin proteasome system. Our model of EMT induction by TGFß2 mimics early stage of metastatic cancer in epithelial breast cells and a proteomic study carried out for such model demonstrates that the deubiquitinase enzyme USP47 acts in SNAIL stabilization, one of the most important transcription factors for EMT phenotype acquisition and consequent metastasis. In addition, the inhibiton of USP47 with P5091, reverted the EMT phenotype. Together the knowledge of such processes of cancer progression and regulation can help in designing new strategies for combined therapies for control of cancer in early stages.

Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation.

PURPOSE: Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. METHODS: We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group (n = 6), mild OSA group (n = 12), moderate OSA group (n = 15), and severe OSA group (n = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). RESULTS: The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 (ß = 68.4; EP = 29.8; p = 0.02) and miR-320e (ß = 76.1; EP = 31.3; p = 0.02). CONCLUSION: Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.

Quantitative phosphoproteome and proteome analyses emphasize the influence of phosphorylation events during the nutritional stress of Trypanosoma cruzi: the initial moments of in vitro metacyclogenesis.

Phosphorylation is an important event in cell signaling that is modulated by kinases and phosphatases. In Trypanosoma cruzi, the etiological agent of Chagas disease, approximately 2% of the protein-coding genes encode for protein kinases. This parasite has a heteroxenic life cycle with four different development stages. In the midgut of invertebrate vector, epimastigotes differentiate into metacyclic trypomastigotes in a process known as metacyclogenesis. This process can be reproduced in vitro by submitting parasites to nutritional stress (NS). Aiming to contribute to the elucidation of mechanisms that trigger metacyclogenesis, we applied super-SILAC (super-stable isotope labeling by amino acids in cell culture) and LC-MS/MS to analyze different points during NS. This analysis resulted in the identification of 4205 protein groups and 3643 phosphopeptides with the location of 4846 phosphorylation sites. Several phosphosites were considered modulated along NS and are present in proteins associated with various functions, such as fatty acid synthesis and the regulation of protein expression, reinforcing the importance of phosphorylation and signaling events to the parasite. These modulated sites may be triggers of metacyclogenesis.

Metabolomic and lipidomic profile in men with obstructive sleep apnoea: implications for diagnosis and biomarkers of cardiovascular risk.

The use of metabolomic and lipidomic strategies for selecting potential biomarkers for obstructive sleep apnoea (OSA) has been little explored. We examined adult male patients with OSA (defined by an apnoea-hypopnoea index ≥15 events/hour), as well as age-, gender-, and fat-composition-matched volunteers without OSA. All subjects were subjected to clinical evaluation, sleep questionnaires for detecting the risk of OSA (Berlin and NoSAS score), metabolomic analysis by gas chromatography coupled to mass spectrometry and lipidomic analysis with liquid chromatography followed by detection by MALDI-MS. This study included 37 patients with OSA and 16 controls. From the 6 metabolites and 22 lipids initially selected, those with the best association with OSA were glutamic acid, deoxy sugar and arachidonic acid (metabolites), and glycerophosphoethanolamines, sphingomyelin and lyso-phosphocholines (lipids). For the questionnaires, the NoSAS score performed best with screening for OSA (area under the curve [AUC] = 0.724, p = 0.003). The combination of the NoSAS score with metabolites or lipids resulted in an AUC for detecting OSA of 0.911 and 0.951, respectively. In conclusion, metabolomic and lipidomic strategies suggested potential early biomarkers in OSA that could also be helpful in screening for this sleep disorder beyond traditional questionnaires.

Accumulation of prohibitin is a common cellular response to different stressing stimuli and protects melanoma cells from ER stress and chemotherapy-induced cell death.

Melanoma is responsible for most deaths among skin cancers and conventional and palliative care chemotherapy are limited due to the development of chemoresistance. We used proteomic analysis to identify cellular responses that lead to chemoresistance of human melanoma cell lines to cisplatin. A systems approach to the proteomic data indicated the participation of specific cellular processes such as oxidative phosphorylation, mitochondrial organization and homeostasis, as well as the unfolded protein response (UPR) to be required for the survival of cells treated with cisplatin. Prohibitin (PHB) was among the proteins consistently accumulated, interacting with the functional clusters associated with resistance to cisplatin. We showed PHB accumulated at different levels in melanoma cell lines under stressing stimuli, such as (i) treatment with temozolomide (TMZ), dacarbazine (DTIC) and cisplatin; (ii) serum deprivation; (iii) tunicamycin, an UPR inducer. Prohibitin accumulated in the mitochondria of melanoma cells after cisplatin and tunicamycin treatment and its de novo accumulation led to chemoresistance melanoma cell lines. In contrast, PHB knock-down sensitized melanoma cells to cisplatin and tunicamycin treatment. We conclude that PHB participates in the survival of cells exposed to different stress stimuli, and can therefore serve as a target for the sensitization of melanoma cells to chemotherapy.

Towards the phosphoproteome of trypanosomatids.

The identification and localization of protein phosphorylation sites provide clues to what proteins or pathways might be activated in a given condition, helping to improve our understanding about signaling networks. Advances in strategies for enrichment of phosphorylated peptides/proteins, mass spectrometry (MS) instrumentation, and specific MS techniques for identification and quantification of post-translational modifications have allowed for large-scale mapping of phosphorylation sites, promoting the field of phosphoproteomics. The great promise of phosphoproteomics is to unravel the dynamics of signaling networks, a layer of the emerging field of systems biology. Until a few years ago only a small number of phosphorylation sites had been described. Following large-scale trends, recent phosphoproteomic studies have reported the mapping of thousands of phosphorylation sites in trypanosomatids. However, quantitative information about the regulation of such sites in different conditions is still lacking. In this chapter, we provide a historical overview of phosphoproteomic studies for trypanosomatids and discuss some challenges and perspectives in the field.

Quantitative proteomics of Trypanosoma cruzi during metacyclogenesis.

Trypanosoma cruzi is the etiologic agent of Chagas disease, which is estimated to affect over eight million people around the world. Trypanosoma cruzi has a complex life cycle, involving insect and mammalian hosts and four distinct developmental stages: epimastigotes, metacyclic trypomastigotes, amastigotes, and bloodstream trypomastigotes. Metacyclogenesis is the process by which T. cruzi epimastigotes differentiate into metacyclic trypomastigotes and acquire infectivity, and involves differential gene expression associated with acquisition of virulence. In T. cruzi, gene expression regulation is achieved mainly posttranscriptionally. Therefore, proteomics-based approaches are extremely useful for gaining a better understanding of the changes that occur in the stage-regulated gene expression program of the parasite at the molecular level. Here, we performed an in-depth quantitative MS-based proteomic study of T. cruzi metacyclogenesis and quantified almost 3000 proteins expressed during the process of differentiation. To the best of our knowledge, this work is the most comprehensive quantitative proteomics study of different cell populations of T. cruzi available so far. We identified relevant proteins and pathways involved in the parasite's differentiation and infectivity acquisition, opening new perspectives for further studies that could, ultimately, lead to the identification of new targets for chemotherapy.

Organic additives in concentrate supplementation of beef cattle grazing / Aditivos orgânicos no suplemento concentrado de bovinos de corte mantidos em pastagem

Organic additives have relevant potential for substitution of antibiotic or ionophorus used in supplements of beef cattle on grazing to increase the heard efficiency and also to avoid sanitary and environmental problems. Thirty zebu cattle of Nellore breed with average initial body weight of 228 +/- kg and approximately 12 months of age were designed in a total random experiment, remaining groups of five animals in six areas of 1.0 ha each of Brachiaria brizantha grass to evaluate the performance in grazing beef cattle with the use of organic additives in the protein-energy supplementation. The treatments were three types of supplements (600 g/animal/d): SC = Control supplement, comprehending a commercial supplement, Premiphos Campo Extra; AGE = SC added an organic mix of commercial essential fatty acids, the Fator Premium and AGEF = AGE supplement added with phosphatidylcholine. The experiment was conducted during the rainy season in 87 d with 28 d earlier as adjustment period. There was no significant difference in average weight gain among the animals supplemented with AGE (826.4 g /d) and AGEF (863.2 g /d), but they had superior performance (P

Aditivos orgânicos apresentam relevante potencial para a substituição de antibióticos ou ionóforos usados em suplementos de bovinos de corte criados em pastagens, visando aumentar a eficiência do rebanho e, também, evitar problemas sanitários e ambientais. Trinta bovinos da raça Nelore com peso vivo inicial médio de 228 kg (228,6 +/- 9,7) e aproximadamente 12 meses de idade foram distribuídos em experimento inteiramente casualizado, mantendo-se grupos de cinco animais em seis piquetes de capim Brachiaria brizantha com 1,0 ha cada, objetivando-se avaliar o desempenho animal em pastagens com uso de aditivos orgânicos em suplementação protéico-energética. Os tratamentos consistiram em três diferentes tipos de suplementos, fornecidos em 600 g/animal/dia: SC = Suplemento controle, compreendendo o suplemento comercial, Premiphós Campo Extra; AGE = Suplemento controle adicionado de mistura orgânica comercial de ácidos graxos essenciais, o Fator Premium; AGEF = Suplemento AGE enriquecido com fosfatidilcolina. O experimento foi realizado durante o período das águas em 87 dias com 28 dias iniciais de adaptação. Não houve diferença significativa no ganho de peso médio entre animais suplementados com AGE (826,4 g/dia) e AGEF (863,2 g/dia), mas esses apresentaram desempenhos superiores (P

Evaluation of turnip forage residue extracted from biodiesel production as supplement for grazing beef cattle / Avaliação do resíduo de nabo forrageiro extraído da produção de biodiesel como suplemento para bovinos de corte em pastagens

Two experiments were performed to evaluate the use of the turnip forage residue extracted from biodiesel production as alternative protein source for grazing zebu cattle. At the first experiment, the performance of Nellore zebu cattle was evaluated on grazing grass. Twenty four animals were distributed in three treatments and allocated on six paddocks, with four animals each and two repetitions. Treatments consisted of supplements with two levels of turnip forage residue (7.5 and 15.0% dry matter) and without turnip forage (control). Pasture availability and quality were also evaluated. At the second trial, degradability of the residue turnip forage was measured in six rumen fistulated zebu cattle fed basal diet composed by grass coast-cross hay and concentrate (35% CP) with 15% of turnip forage. No difference was observed among the treatments for the animal performance, but the steers fed 7.5% of turnip forage residue showed the highest daily gain weight (0.575 kg DGW). The turnip forage residue showed high and fast ruminal effective degradability of the dry matter (83.8%), crude protein (88.9%) and neutral detergent fiber (52.1%). In conclusion, the turnip forage residue can be used as protein source in supplement diet for cattle, shifting the conventional protein sources up to 15% in supplement with 35% of total crude protein.

Dois experimentos foram realizados visando avaliar o uso do resíduo de nabo forrageiro extraído da produção de biodiesel como fonte de proteína alternativa de suplementos para bovinos de corte em pastejo de gramíneas. No primeiro experimento, avaliou-se o desempenho de bovinos Nelore a pasto (ganho diário de peso), utilizando-se 24 animais, distribuídos em três tratamentos em seis piquetes com quatro animais cada e duas repetições. Os tratamentos consistiram de suplementos com dois níveis do resíduo de nabo forrageiro (7,5 e 15,0% na matéria seca) e sem nabo forrageiro (testemunha). A disponibilidade e qualidade da pastagem foram também avaliadas. No segundo experimento determinou-se a degradabilidade ruminal do resíduo de nabo forrageiro em seis bovinos fistulados no rúmen recebendo dieta basal com feno de gramínea e concentrado com 15% de nabo forrageiro. Durante todo o período experimental não houve diferença significativa entre os tratamentos, mas observou-se melhor desempenho nos animais suplementados com 7,5% de resíduo de nabo forrageiro. O resíduo de nabo forrageiro apresentou alta e rápida degradabilidade ruminal da matéria seca, proteína bruta e fibra em detergente neutro.

Evaluation of turnip forage residue extracted from biodiesel production as supplement for grazing beef cattle / Avaliação do resíduo de nabo forrageiro extraído da produção de biodiesel como suplemento para bovinos de corte em pastagens

Two experiments were performed to evaluate the use of the turnip forage residue extracted from biodiesel production as alternative protein source for grazing zebu cattle. At the first experiment, the performance of Nellore zebu cattle was evaluated on grazing grass. Twenty four animals were distributed in three treatments and allocated on six paddocks, with four animals each and two repetitions. Treatments consisted of supplements with two levels of turnip forage residue (7.5 and 15.0% dry matter) and without turnip forage (control). Pasture availability and quality were also evaluated. At the second trial, degradability of the residue turnip forage was measured in six rumen fistulated zebu cattle fed basal diet composed by grass coast-cross hay and concentrate (35% CP) with 15% of turnip forage. No difference was observed among the treatments for the animal performance, but the steers fed 7.5% of turnip forage residue showed the highest daily gain weight (0.575 kg DGW). The turnip forage residue showed high and fast ruminal effective degradability of the dry matter (83.8%), crude protein (88.9%) and neutral detergent fiber (52.1%). In conclusion, the turnip forage residue can be used as protein source in supplement diet for cattle, shifting the conventional protein sources up to 15% in supplement with 35% of total crude protein.

Dois experimentos foram realizados visando avaliar o uso do resíduo de nabo forrageiro extraído da produção de biodiesel como fonte de proteína alternativa de suplementos para bovinos de corte em pastejo de gramíneas. No primeiro experimento, avaliou-se o desempenho de bovinos Nelore a pasto (ganho diário de peso), utilizando-se 24 animais, distribuídos em três tratamentos em seis piquetes com quatro animais cada e duas repetições. Os tratamentos consistiram de suplementos com dois níveis do resíduo de nabo forrageiro (7,5 e 15,0% na matéria seca) e sem nabo forrageiro (testemunha). A disponibilidade e qualidade da pastagem foram também avaliadas. No segundo experimento determinou-se a degradabilidade ruminal do resíduo de nabo forrageiro em seis bovinos fistulados no rúmen recebendo dieta basal com feno de gramínea e concentrado com 15% de nabo forrageiro. Durante todo o período experimental não houve diferença significativa entre os tratamentos, mas observou-se melhor desempenho nos animais suplementados com 7,5% de resíduo de nabo forrageiro. O resíduo de nabo forrageiro apresentou alta e rápida degradabilidade ruminal da matéria seca, proteína bruta e fibra em detergente neutro.

Organic additives in concentrate supplementation of beef cattle grazing / Aditivos orgânicos no suplemento concentrado de bovinos de corte mantidos em pastagem

Organic additives have relevant potential for substitution of antibiotic or ionophorus used in supplements of beef cattle on grazing to increase the heard efficiency and also to avoid sanitary and environmental problems. Thirty zebu cattle of Nellore breed with average initial body weight of 228 +/- kg and approximately 12 months of age were designed in a total random experiment, remaining groups of five animals in six areas of 1.0 ha each of Brachiaria brizantha grass to evaluate the performance in grazing beef cattle with the use of organic additives in the protein-energy supplementation. The treatments were three types of supplements (600 g/animal/d): SC = Control supplement, comprehending a commercial supplement, Premiphos Campo Extra; AGE = SC added an organic mix of commercial essential fatty acids, the Fator Premium and AGEF = AGE supplement added with phosphatidylcholine. The experiment was conducted during the rainy season in 87 d with 28 d earlier as adjustment period. There was no significant difference in average weight gain among the animals supplemented with AGE (826.4 g /d) and AGEF (863.2 g /d), but they had superior performance (P

Aditivos orgânicos apresentam relevante potencial para a substituição de antibióticos ou ionóforos usados em suplementos de bovinos de corte criados em pastagens, visando aumentar a eficiência do rebanho e, também, evitar problemas sanitários e ambientais. Trinta bovinos da raça Nelore com peso vivo inicial médio de 228 kg (228,6 +/- 9,7) e aproximadamente 12 meses de idade foram distribuídos em experimento inteiramente casualizado, mantendo-se grupos de cinco animais em seis piquetes de capim Brachiaria brizantha com 1,0 ha cada, objetivando-se avaliar o desempenho animal em pastagens com uso de aditivos orgânicos em suplementação protéico-energética. Os tratamentos consistiram em três diferentes tipos de suplementos, fornecidos em 600 g/animal/dia: SC = Suplemento controle, compreendendo o suplemento comercial, Premiphós Campo Extra; AGE = Suplemento controle adicionado de mistura orgânica comercial de ácidos graxos essenciais, o Fator Premium; AGEF = Suplemento AGE enriquecido com fosfatidilcolina. O experimento foi realizado durante o período das águas em 87 dias com 28 dias iniciais de adaptação. Não houve diferença significativa no ganho de peso médio entre animais suplementados com AGE (826,4 g/dia) e AGEF (863,2 g/dia), mas esses apresentaram desempenhos superiores (P

Relationship between the cattle tick Boophilus microplus and the occurence of myiasis in a crossbred cattle / Nota Científica. Relação entre infestação pelo carrapato Boophilus microplus e ocorrência de miíase em bovinos mestiços

The authors report a relationship between the Boophilus microplus tick infestation and the occurence of myiasis in a crossbred dairy cattle.

Os autores comunicam a existência de uma relação entre infestações de carrapato Boophilus microplus e a ocorrência de miíase em animais de um rebanho mestiço leiteiro.