RESUMEN
Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF-ß (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast Green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-ß inhibitor, IC50 114.3 µM), losmapimod (p38 inhibitor, IC50 17.6 µM) and SP600125 (c-Jun inhibitor, IC50 3.9 µM). This effect was independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the hearts of the patients.
Asunto(s)
Cardiomiopatía Chagásica , Fibrosis , Ratones Endogámicos C57BL , Piridonas , Animales , Piridonas/farmacología , Piridonas/uso terapéutico , Cardiomiopatía Chagásica/tratamiento farmacológico , Cardiomiopatía Chagásica/parasitología , Cardiomiopatía Chagásica/metabolismo , Cardiomiopatía Chagásica/patología , Ratones , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/parasitología , Miocardio/patología , Miocardio/metabolismo , Colágeno/metabolismo , Trypanosoma cruzi/efectos de los fármacos , Humanos , Enfermedad Crónica , Factor de Crecimiento Transformador beta/metabolismo , Modelos Animales de Enfermedad , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Masculino , AntracenosRESUMEN
As tecnologias educacionais podem ser utilizadas como instrumentos para disseminar informação em período de isolamento social. A pesquisa buscou descrever a experiência de produzir vídeos de avaliação cognitiva para pessoas idosas tendidas na Atenção Primária à Saúde. Método: Trata-se de um relato de experiência sobre a produção de vídeos animados contendo informações a respeito da utilização de instrumentos de avaliação cognitiva em idosos na Atenção Primária à Saúde do município de Coari-AM. Resultados: Os vídeos foram confeccionados e distribuídos para os gestores das Unidade Básicas de Saúde. Foram abordados um total de 13 gestores que tiveram acesso ao material produzido. Conclusão: A produção e divulgação dos vídeos de avaliação cognitiva em idosos possibilitou a educação continuada de maneira remota entre os gestores.
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Mollusc rearing is a relevant global socioeconomic activity. However, this activity has faced severe problems in the last years in southeast Brazil. The mariculture scallop production dropped from 51,2 tons in 2016 to 10,2 tons in 2022 in the Baia da Ilha Grande (BIG; Rio de Janeiro). However, the possible causes of this collapse are unknown. This study aimed to analyze decadal trends of water quality in Nodipecten nodosus spat and adult production in BIG. We also performed physical-chemical and biological water quality analyses of three scallop farms and two nearby locations at BIG in 2022 to evaluate possible environmental stressors and risks. Scallop spat production dropped drastically in the last five years (2018-2022: mean ± stdev: 0.47 ± 0.45 million). Spat production was higher in colder waters and during peaks of Chlorophyll a in the last 13 years. Reduction of Chlorophyll a coincided with decreasing spat production in the last five years. Warmer periods (>27 °C) of the year may hamper scallop development. Counts of potentially pathogenic bacteria (Vibrios) and Escherichia coli were significantly higher in warmer periods which may further reduce scallop productivity. Shotgun metagenomics of seawater samples from the five studied corroborated these culture-based counts. Vibrios and fecal indicator bacteria metagenomic sequences were abundant across the entire study area throughout 2022. The results of this study suggest the collapse of scallop mariculture is the result of a synergistic negative effect of global warming and poor seawater quality.
Asunto(s)
Calentamiento Global , Pectinidae , Animales , Clorofila A , Brasil , Contaminación del AguaRESUMEN
Objetivo: Descrever a presença da prática de exercício físico e de função física em um grupo de idosos durante a pandemia por COVID-19 no interior do Amazonas. Métodos: Trata-se de um estudo transversal realizado com idosos ativos que realizavam exercício físico por pelo menos 3 vezes na semana por 50 minutos no interior do Amazonas. Avaliou-se a prática de exercício físico antes e durante a pandemia e aplicaram-se duas questões investigativas referente a COVID-19. Para avaliar a capacidade funcional e física aplicou-se o Short Physical Performance Battery (SPPB). Resultados: A amostra foi composta por 63 idosos ativos da comunidade. Destes, 31,8% (21) eram analfabetos, 74,2% (49) aposentados e 75,8 % (50) de baixa renda. No SPPB 27,3% (18) apresentaram total de 10 pontos e 14,29% (9) dos idosos realizam exercício físico acima dos minutos recomendados pela Organização Mundial da Saúde (OMS). Conclusão: Neste estudo nenhum fator durante a pandemia interferiu na prática de exercício físico e nem na capacidade funcional dos idosos que residem no interior do Amazonas.
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Chagas' Disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for up to 41% of the heart failures in endemic areas in South America and is an emerging infection in regions of North America, Europe, and Asia. Treatment is suboptimal due to two factors. First, the lack of an adequate biomarker to predict disease severity and response to therapy; and second, up to 120-days treatment course coupled with a significant incidence of adverse effects from the drug currently used. Because the disease can manifest itself clinically a few years to decades after infection, controversy remains concerning the suitability of current drug treatment (benznidazole), and the efficacy of alternative drugs (e.g. posaconazole). We therefore followed the clinical course, and PCR detection of parasite burden, in a mouse model of infection for a full year following treatment with benznidazole or posaconazole. Efficacy of the two drugs depended on whether the treatment was performed during the acute model or the chronic model of infection. Posaconazole was clearly superior in treatment of acute disease whereas only benznidazole had efficacy in the chronic model. These results have important implications for the design and analysis of human clinical trials, and the use of specific drugs in specific clinical settings.
Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Nitroimidazoles/farmacología , Triazoles/farmacología , Trypanosoma cruzi/efectos de los fármacos , Administración Oral , Animales , Enfermedad de Chagas/parasitología , Modelos Animales de Enfermedad , Estudios de Seguimiento , Masculino , Ratones Endogámicos C57BL , Nitroimidazoles/administración & dosificación , Reacción en Cadena de la Polimerasa , Triazoles/administración & dosificación , Tripanocidas/farmacología , Trypanosoma cruzi/aislamiento & purificaciónRESUMEN
Introdução: As lesões nos tendões flexores (FTI) atingem as mãos e apresentam um desafio para a equipe multidisciplinar. Objetivo: Buscou-se em ensaios clínicos a aplicação da cinesioterapia em recuperar a função das mãos após lesão tendinosa. Métodos: Para a construção deste estudo foi realizada uma revisão da literatura baseada em artigos, que abordavam a temática de cinesioterapia aplicada a cirurgia no tendão da mão. Resultados: Os estudos encontrados aplicaram a cinesioterapia com programas de exercícios e mobilização articular em jovens e adultos que passaram por cirurgia no tendão da mão, auxiliando na recuperação funcional de acordo com a zona acometida. Conclusão: A cinesioterapia deve ser aplicada para recuperação funcional da mão após lesões tendinosas, no entanto, há uma enorme escassez quanto às publicações de ensaios clínicos bem conduzidos que direcionem o trabalho do fisioterapeuta. (AU)
Introduction: Flexor tendon injuries of the hands is a challenge to the multidisciplinary team. Objective: The aim of the clinical trials was to apply kinesiotherapy to recover hand function after tendon injury. Methods: A literature review was performed based on articles that addressed the theme of kinesiotherapy applied to hand tendon surgery. Results: The studies found applied kinesiotherapy with exercise programs and joint mobilization in young and adults who underwent surgery on the tendons of the hand, assisting in functional recovery according to the affected area. Conclusion: Kinesiotherapy should be applied for functional recovery of the hand after tendon injuries, however, there is a huge shortage of publications on well-conducted clinical trials that guide the physiotherapist's work. (AU)
Asunto(s)
Humanos , Cirugía General , Tendones , Rehabilitación , Modalidades de Fisioterapia , ManoRESUMEN
Chagas disease, the clinical presentation of T. cruzi infection, is a major human health concern. While the acute phase of Chagas disease is typically asymptomatic and self-resolving, chronically infected individuals suffer numerous sequelae later in life. Cardiomyopathies in particular are the most severe consequence of chronic Chagas disease and cannot be reversed solely by parasite load reduction. To prioritize new therapeutic targets, we unbiasedly interrogated the host signaling events in heart tissues isolated from a Chagas disease mouse model using quantitative, multiplexed proteomics. We defined the host response to infection at both the proteome and phospho-proteome levels. The proteome showed an increase in the immune response and a strong repression of several mitochondrial proteins. Complementing the proteome studies, the phospho-proteomic survey found an abundance of phospho-site alterations in plasma membrane and cytoskeletal proteins. Bioinformatic analysis of kinase activity provided substantial evidence for the activation of NDRG2 and JNK/p38 kinases during Chagas disease. A significant activation of DYRK2 and AMPKA2 and the inhibition of casein family kinases were also predicted. We concluded our analyses by linking the diseased heart proteome profile to known therapeutic interventions, uncovering a potential to target mitochondrial proteins, secreted immune effectors and core kinases for the treatment of chronic Chagas disease. Together, this study provides molecular insight into host proteome and phospho-proteome responses to T. cruzi infection in the heart for the first time, highlighting pathways that can be further validated for functional contributions to disease and suitability as drug targets.
Asunto(s)
Cardiomiopatía Chagásica/metabolismo , Animales , Cardiomiopatía Chagásica/genética , Cardiomiopatía Chagásica/inmunología , Cardiomiopatía Chagásica/parasitología , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Proteoma/genética , Proteoma/metabolismo , Proteómica , Transducción de Señal , Trypanosoma cruzi/fisiologíaRESUMEN
Transforming growth factor beta (TGF-ß) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of Trypanosoma cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF), and L6E9 skeletal myoblasts to TGF-ß. Cultures of CM, CF, and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-ß (1-10 ng/mL, 1 h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-ß, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 was less stimulated in CF than CM and L6E9. T. cruzi infection resulted in localized FN disorganization in CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-ß showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-ß after T. cruzi infection.
Asunto(s)
Enfermedad de Chagas/metabolismo , Enfermedad de Chagas/parasitología , Matriz Extracelular/metabolismo , Interacciones Huésped-Patógeno , Factor de Crecimiento Transformador beta/metabolismo , Trypanosoma cruzi/fisiología , Animales , Biomarcadores , Línea Celular , Células Cultivadas , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Miocitos Cardíacos/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: Both acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart. CONCLUSIONS/SIGNIFICANCE: The positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life.
Asunto(s)
Inhibidores de 14 alfa Desmetilasa/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Pirimidinas/uso terapéutico , Tripanocidas/uso terapéutico , Trypanosoma cruzi/efectos de los fármacos , Inhibidores de 14 alfa Desmetilasa/efectos adversos , Animales , Enfermedad de Chagas/parasitología , Modelos Animales de Enfermedad , Descubrimiento de Drogas , Femenino , Corazón/efectos de los fármacos , Plomo/química , Plomo/uso terapéutico , Masculino , Ratones , Ratones Endogámicos BALB C , Miocardio/patología , Parasitemia/parasitología , Pirimidinas/efectos adversos , Esterol 14-Desmetilasa/metabolismo , Esteroles/biosíntesis , Tripanocidas/efectos adversosRESUMEN
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.
Asunto(s)
Enfermedad de Chagas/fisiopatología , Costameras/metabolismo , Interacciones Huésped-Parásitos/fisiología , Miocitos Cardíacos/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Animales , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Interacciones Huésped-Parásitos/efectos de los fármacos , Ratones , Miocitos Cardíacos/parasitología , Transporte de Proteínas/efectos de los fármacos , Transporte de Proteínas/fisiología , Receptor Tipo II de Factor de Crecimiento Transformador beta , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Trypanosoma cruzi/fisiologíaRESUMEN
Telemental Health Care has reported very good results and is included within mental health priorities by the World Health Organization. Objective To provide an overview of the current situation of the integration of Brazilian telemedicine activities into primary health care. Methods Critical review based on MEDLINE database, using the keywords telemedicine, primary health care mental health and telemental health, on websites of the Brazilian Ministry of Health and Brazilian Telehealth Network Program, and on personal communication. Results The Brazilian Telehealth Network Program is well positioned and connects primary health care with academic centers. Regulations standards allow a broader scope of activities for psychologists, however, are more restrictive for physicians. In Brazil most of telemental health activities are focused on education and second opinion consulting. A huge challenge must be overcome considering the regional differences and the telehealth implementation experience. Research initiatives have been initiated both in the implementation and evaluation of the mental health assistance into primary health care. Discussion Brazilian Telemental Health initiatives into Primary Care are aligned with other examples around the world, have a great potential for improving mental health care service delivery, and access to proper mental health care, especially if articulated in a national program and coordinated research...
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Humanos , Atención a la Salud , Salud Mental , Telemedicina , Servicios de Salud MentalRESUMEN
OBJETIVO: Descrever a relação entre a frequência de insatisfação com a imagem corporal e a presença de sintomas de transtornos alimentares em adolescentes. MÉTODOS: O estudo foi realizado com uma amostra de 300 adolescentes, de ambos os sexos, na faixa etária de 10 a 17 anos, estudantes de uma escola pública estadual da cidade do Recife, Brasil. Foram utilizadas as versões brasileiras para adolescentes de três escalas autoaplicativas (EAT-26, BITE e BSQ), além de um questionário contendo dados biodemográficos. RESULTADOS: A frequência de sintomas de transtornos alimentares detectada pelo EAT-26 foi de 32,3%; 2,3% para comportamentos sugestivos de bulimia nervosa, por meio da escala BITE, tendo 36,67% dos alunos apresentado padrão alimentar não usual; 5,6% apresentaram insatisfação com a imagem corporal; 8,6% demonstraram tendência à preocupação com a insatisfação com a imagem corporal e 17,6% apresentaram leve insatisfação, além de 66,3%, que mostraram normalidade em relação à sua forma corporal. CONCLUSÃO: Os adolescentes apresentaram níveis de alteração na autoimagem corporal, com alta frequência de insatisfação da imagem corporal, podendo apresentar associação com comportamentos alimentares inadequados.
OBJECTIVE: To describe the relationship between frequency of body dissatisfaction and symptoms of eating disorders in adolescents. METHODS: The study was conducted with a sample of 300 adolescents of both sexes, aged from 10 to 17 years-old, students from a state school in Recife, Brazil. Authors used the Brazilian version of three self-report questionnaires for adolescents (EAT-26, BITE and BSQ), and a questionnaire containing biodemographical data. RESULTS: The frequency of symptoms of eating disorders detected by the EAT-26 was 32.3%; 2.3% for suggestive behaviors of bulimia nervosa, through BITE, and 36.67% of the students presented an unusual eating pattern; 5.6% showed body dissatisfaction, and 66.3%, showed normality in relation to its body form. CONCLUSION: These adolescents had higher levels of change in body self-image, with high frequency of body dissatisfaction, that suggest and association with inappropriate eating behaviors.
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O objetivo deste trabalho foi realizar um levantamento das plantas medicinais utilizadas pela população urbana de Três Barras do Paraná. A coleta de dados ocorreu com uma amostragem de 370 questionários. Os resultados demonstraram que 98% da população fazer uso de plantas medicinais. A maioria dos entrevistados possui renda entre 2-4 salários mínimos (47%), idade entre 18-28 anos (23%), sendo donas de casa (48%) que não concluíram o Ensino Fundamental (54%). O principal motivo pelo qual as utilizam está relacionado a serem naturais (36%). Apenas 4% dos entrevistados citaram tO objetivo deste trabalho foi realizar um levantamento das plantas medicinais utilizadas pela população urbana de Três Barras do Paraná. A coleta de dados ocorreu com uma amostragem de 370 questionários. Os resultados demonstraram que 98% da população fazer uso de plantas medicinais. A maioria dos entrevistados possui renda entre 2-4 salários mínimos (47%), idade entre 18-28 anos (23%), sendo donas de casa (48%) que não concluíram o Ensino Fundamental (54%). O principal motivo pelo qual as utilizam está relacionado a serem naturais (36%). Apenas 4% dos entrevistados citaram ter passado por reação adversa. A forma mais significativa de obtenção das plantas foi o cultivo próprio (44%) e a orientação sobre o uso foi pelas informações com familiares (63%). A parte mais utilizada foi a folha (60%), preparada por infusão (40%). Conclui-se que, devido ? facilidade de obtenção associada ao baixo custo, as plantas estão inseridas no dia-a-dia da população. er passado por reação adversa. A forma mais significativa de obtenção das plantas foi o cultivo próprio (44%) e a orientação sobre o uso foi pelas informações com familiares (63%). A parte mais utilizada foi a folha (60%), preparada por infusão (40%). Conclui-se que, devido ? facilidade de obtenção associada ao baixo custo, as plantas estão inseridas no dia-a-dia da população.
The objective of this work was to survey medicinal plants used by the urban population from the city of Três Barras do Paraná. Data collection encompass a sampling of 370 interviews. The results demonstrated that 98% of the population uses medicinal plants. The majority of the users have their income between 2-4 minimum wages (47%), are aged between 18-28 (23%), are housewives (48%), and have not concluded the Ensino Fundamental (1st to 8th grade) (54%). The main reason why these people use medicinal plants is the fact that these are natural (36%). Just 4% of the interviewee mentioned that they had undergone some sort of adverse reaction. The way to obtain the most significant plants was from own cultivation (44%). The orientation about the way to use these plants was through relatives (63%). The mostly used part was the leaf (60%), being prepared by infusion (40%). Conclusion points that these plants have been included in population?s day-by-day due to the fact that they are easy to obtain associated with low cost.