Polysaccharide-rich extract of Genipa americana leaves protects seizures and oxidative stress in the mice model of pentylenetetrazole-induced epilepsy.

Plant polysaccharides have biological activities in the brain and those obtained from Genipa americana leaves present antioxidant and anticonvulsant effects in the mice model of pentylenetetrazole (PTZ)-induced acute seizures. This study aimed to evaluate the polysaccharide-rich extract of Genipa americana leaves (PRE-Ga) in the models of acute seizures and chronic epilepsy (kindling) induced by PTZ. In the acute seizure model, male Swiss mice (25-35 g) received PRE-Ga (1 or 9 mg/kg; intraperitoneal- IP), alone or associated with diazepam (0.01 mg/kg), 30 min before induction of seizures with PTZ (70 mg/kg; IP). In the chronic epilepsy model, seizures were induced by PTZ (40 mg/kg) 30 min after treatment and in alternated days up to 30 days and evaluated by video. Brain areas (prefrontal cortex, hippocampus, striatum) were assessed for inflammatory and oxidative stress markers. Diazepam associated to PRE-Ga (9 mg/kg; i.p.) increased the latency of seizures in acute (222.4 ± 47.57 vs. saline: 62.00 ± 4.709 s) and chronic models (6.267 ± 0.502 vs. saline: 4.067 ± 0.407 s). In hippocampus, PRE-Ga (9 mg/kg) inhibited TNF-α (105.9 ± 5.38 vs. PTZ: 133.5 ± 7.62 pmol/g) and malondialdehyde (MDA) (473.6 ± 60.51) in the chronic model. PTZ increased glial fibrillar acid proteins (GFAP) and Iba-1 in hippocampus, which was reversed by PRE-Ga (GFAP: 1.9 ± 0.23 vs PTZ: 3.1 ± 1.3 and Iba-1: 2.2 ± 0.8 vs PTZ: 3.2 ± 1.4). PRE-Ga presents neuroprotector effect in the mice model of epilepsy induced by pentylenetetrazole reducing seizures, gliosis, inflammatory cytokines and oxidative stress.

Correlation between ABO blood type, susceptibility to SARS-CoV-2 infection and COVID-19 disease severity: A systematic review

ABSTRACT Objectives: To verify the association between the ABO blood type and the risk of SARS-CoV-2 infection and COVID-19 disease severity. Methods: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the 2020 PRISMA Checklist and flow diagram, and articles selected for review were analyzed using the Newcastle-Ottawa Quality Rating Scale. The research question was: "Would the ABO blood group influence the risk of infection and clinical course of patients infected with SARS-CoV-2?", The following databases were used: Embase, PubMed, Virtual Health Library (VHL), Web of Science, Science-Direct and Scopus. The protocol for this review was registered in the Prospective Register of Systematic Reviews (PROSPERO), number CRD42021245945. Results: We found 798 articles across PubMed, Embase, Scopus, Web of Science, Science Direct and Virtual Health Library and 54 articles were included in the final analysis. Among 30 studies evaluating the risk of COVID-19 infection, 21 found significant correlations with ABO blood groups, 14 of them revealing an increased risk in blood group A and 15 studies showing a decreased risk in blood group O. Most studies found no significant correlation with disease severity or mortality. Conclusion: The qualitative assessment of available information suggests that blood group A may be a risk factor for COVID-19 infection and that blood group O may have a protective effect. We were unable to determine a clear association between the ABO blood group and mortality. These conclusions are based on highly heterogenous evidence.

Effects of whey protein supplementation on gut microbiota of Wistar rats with valproic acid-induced autism symptoms.

Aim: To evaluate the effects of whey protein (WP) supplementation (1.24 mg/g, 24 days) in rats with autism spectrum disorder (ASD) induced by valproic acid (400 mg/kg, single dose). Materials & methods: Wistar rats (14 days old) were divided into four groups: control, ASD, ASD plus WP and WP. Results: WP increased bacterial diversity and the number of colonies. Bacteria from the Firmicutes phylum were predominantly found in the supplemented groups (p < 0.05). WP also improved the animals' memory in the Y-maze test and decreased the time that male animals spent in the 'solitary chamber' (p < 0.05). Conclusion: WP supplementation positively influenced gut microbiota, along with memory.

Thousands of bacteria live in the human intestine. These bacteria help with many functions in the body and are so important that they can communicate with the brain. When the types and abundance of these bacteria change, brain activity can also change. This may be the case in some children with autism spectrum disorder (ASD), who may have an increase in harmful types of bacteria and a decrease in beneficial types of bacteria in the gut. Whey protein is a commonly used protein supplement for muscle growth. However, many studies have shown its benefits for gut bacteria. The authors investigated the effects of whey protein in animals with symptoms of ASD and showed that supplementation with whey protein increased the number of beneficial bacteria. In addition, the rats given whey protein had better memory. ASD-induced rats were less sociable, spending more time by themselves. However, male animals treated with whey protein spent less time alone. Supplementation with whey protein was beneficial for gut bacteria and memory in rats.

Correlation between ABO blood type, susceptibility to SARS-CoV-2 infection and COVID-19 disease severity: A systematic review.

OBJECTIVES: To verify the association between the ABO blood type and the risk of SARS-CoV-2 infection and COVID-19 disease severity. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the 2020 PRISMA Checklist and flow diagram, and articles selected for review were analyzed using the Newcastle-Ottawa Quality Rating Scale. The research question was: "Would the ABO blood group influence the risk of infection and clinical course of patients infected with SARS-CoV-2?", The following databases were used: Embase, PubMed, Virtual Health Library (VHL), Web of Science, ScienceDirect and Scopus. The protocol for this review was registered in the Prospective Register of Systematic Reviews (PROSPERO), number CRD42021245945. RESULTS: We found 798 articles across PubMed, Embase, Scopus, Web of Science, Science Direct and Virtual Health Library and 54 articles were included in the final analysis. Among 30 studies evaluating the risk of COVID-19 infection, 21 found significant correlations with ABO blood groups, 14 of them revealing an increased risk in blood group A and 15 studies showing a decreased risk in blood group O. Most studies found no significant correlation with disease severity or mortality. CONCLUSION: The qualitative assessment of available information suggests that blood group A may be a risk factor for COVID-19 infection and that blood group O may have a protective effect. We were unable to determine a clear association between the ABO blood group and mortality. These conclusions are based on highly heterogenous evidence.

Behavioral and neuroinflammatory changes caused by glyphosate: Base herbicide in mice offspring.

BACKGROUND: Glyphosate is a pesticide considered of low toxicity, but scientific evidences show it can be harmful to health. This study aimed to evaluate the toxicity in mice offspring exposed to glyphosate-based herbicide (GBH) during the intrauterine period. METHODS: Female matrices received glyphosate 0.3 mg/kg daily per oral throughout the gestational period, which was variable between 18 and 22 days. From the 25th until the 28th days post-birth, mice offspring were subjected to behavioral tests, and the prefrontal cortex was processed for immunohistochemical analysis. RESULTS: Two significant behavioral changes were observed: anxiety in the GLIF0.3 group, increase in the behavior burying marbles in the marble-burying test and hyperactivity, expressed by the significant increase of the crossing number in the open field test. The increased microglia, TNF-alpha, and astrocyte expression were also observed in the prefrontal cortex of offspring treated with GLIF0.3. CONCLUSION: Exposure to GBH during mice intrauterine development induces hyperactive and anxious behavior, evidencing neuroinflammation.

Bumetanide in autism spectrum disorder / Bumetanida no transtorno do espectro autista / Bumetanida en el trastorno del espectro autista

Objectives: This study aimed to make a bibliographic update on the already published data on bumetanide, addressing the main information on its use in Autism Spectrum Disorder (ASD). Methods: This was an integrative narrative review in which the following databases were used: Web of Science, MEDLINE, ScienceDirect, and Scielo. The descriptors used were: Autism Spectrum Disorder, Autistic Disorder and Bumetanide. It was considered only articles published in English and French. Original articles, randomized clinical trials, case reports, and review articles were included. Results: The results show that the use of bumetanide alters regions of the brain linked to the positive development of language, improvement of visual contact, improvement in social interactions, among others. Studies are also concerned about the safety and efficacy of bumetanide in ASD since several adverse effects have been reported. The most frequent were hypokalemia, polyuria, and loss of appetite. Conclusion: Bumetanide has proven as effective in improving some important symptoms in ASD, especially linked to language and social interaction, however, studies with larger groups of patients and with longer treatment and observation time are needed to confirm the efficacy and clarify the safety profile in use for people with ASD.

Objetivo: O objetivo deste trabalho foi fazer uma atualização bibliográfica sobre os dados já publicados da bumetanida, abordando as principais informações sobre seu uso no Transtorno do Espectro Autista (TEA). Metodologia: Foi realizada uma revisão do tipo narrativa integrativa, da qual foram utilizadas as bases de dados: Web of Science, MEDLINE, ScienceDirect e Scielo, com a utilização dos seguintes descritores: Autism Spectrum Disorder, Autistic Disorder e Bumetanide. Foram considerados apenas artigos publicados nas línguas inglesa e francesa. Foram incluídos artigos originais, ensaios clínicos randomizados e relatos de caso. Foram excluídos artigos de revisão. Resultados: Os resultados mostram que o uso da bumetanida altera regiões do cérebro ligadas ao desenvolvimento positivo da linguagem, melhora do contato visual, melhora nas interações sociais, entre outros. Os estudos também se preocupam em relacionar a segurança e a eficácia da bumetanida no TEA, do qual foram relatados diversos efeitos adversos, sendo os mais frequentes a hipocalemia, a poliúria e a perda de apetite. Conclusão: A bumetanida mostrou ser eficaz na melhoria de alguns importantes sintomas no TEA, especialmente ligados à linguagem e interação social, entretanto, estudos com grupos maiores de pacientes e com maior tempo de tratamento e observação são necessários para confirmar a eficácia e esclarecer o perfil de segurança no uso para pessoas com TEA.

: Este estudio tuvo como objetivo realizar una actualización bibliográfica sobre los datos ya publicados sobre la bumetanida, abordando la principal información sobre su uso en el Trastorno del Espectro Autista (TEA). Métodos: Se trata de una revisión narrativa integradora en la que se utilizaron las siguientes bases de datos: Web of Science, MEDLINE, ScienceDirect y Scielo. Los descriptores utilizados fueron: Trastorno del Espectro Autista, Trastorno Autista y Bumetanida. Se consideraron sólo los artículos publicados en inglés y francés. Se incluyeron artículos originales, ensayos clínicos aleatorios, informes de casos y artículos de revisión. Resultados: Los resultados muestran que el uso de la bumetanida altera regiones del cerebro relacionadas con el desarrollo positivo del lenguaje, la mejora del contacto visual, la mejora de las interacciones sociales, entre otros. Los estudios también se preocupan por la seguridad y eficacia de la bumetanida en el TEA, ya que se han reportado varios efectos adversos. Los más frecuentes fueron la hipocalemia, la poliuria y la pérdida de apetito. Conclusiones: La bumetanida ha demostrado ser eficaz en la mejora de algunos síntomas importantes en el TEA, especialmente vinculados al lenguaje y la interacción social, sin embargo, se necesitan estudios con grupos más grandes de pacientes y con mayor tiempo de tratamiento y observación para confirmar la eficacia y aclarar el perfil de seguridad en el uso para personas con TEA.

Percepção dos acadêmicos de Enfermagem sobre Autismo / Nursing students' perception of autism / Percepción de los académicos de enfermería sobre el autismo

Objetivo: analisar o nível de conhecimento dos acadêmicos do curso de Enfermagem de uma universidade pública sobre o Transtorno do Espectro Autista (TEA). Método: Trata-se de estudo quantitativo, descritivo, realizado entre outubro de 2020 a janeiro de 2021, utilizando um questionário on-line. Responderam ao questionário 60 estudantes dos últimos semestres do curso. Resultados: A maioria dos acadêmicos não conheciam a faixa etária mais provável para identificar os primeiros sinais de autismo, mas conseguiram identificar os sintomas nucleares do TEA. 65% negaram haver correlação entre o nível socioeconômico e TEA. De acordo com 4% dos estudantes, todos os autistas são superdotados, e para 98% o autismo não é causado por vacina. A maioria dos acadêmicos afirmaram não ter recebido conhecimento suficiente na graduação sobre o tema. Todos concordaram na falta de conscientização sobre o TEA entre profissionais da saúde. Apenas 37% participaram de eventos sobre TEA e todos demonstraram interesse em conhecer mais sobre o assunto. Considerações finais: Pode-se perceber algumas lacunas no conhecimento de estudantes de enfermagem acerca do TEA, devendo ser encorajado a inserção desta temática nos cursos de graduação, possibilitando a formação de enfermeiros capacitados para uma abordagem profissional específica aos pacientes com TEA. (AU)

Objective: To verify the level of knowledge of nursing students at a public university about Autistic Spectrum Disorder. Methods: This is a quantitative, descriptive study, carried out between October 2020 and January 2021, using an online questionnaire. Sixty students from the last semesters of the course answered the questionnaire. Results: Most academics did not know the age group most likely to identify the first signs of autism, but they were able to identify the core symptoms of Autism Spectrum Disorder. 65% denied having a correlation between socioeconomic status and the disorder. According to 4% of students, all autistic people are gifted, and for 98% autism is not caused by a vaccine. Most academics stated that they did not receive enough knowledge about the subject at graduation. All agreed on the lack of awareness about Autistic Spectrum Disorder among health professionals. Conclusión: there were some gaps in the knowledge of nursing students about Autistic Spectrum Disorder, and the inclusion of this theme in undergraduate courses should be encouraged. (AU)

Objetivo: Verificar el nivel de conocimientos de dos académicos del curso de Enfermería de una universidad pública sobre el Trastorno del Espectro Autista. Métodos: Se trata de un estudio cuantitativo, descriptivo, realizado entre octubre de 2020 y enero de 2021, mediante un cuestionario online. 60 alumnos responderán al cuestionario en los dos últimos semestres del curso. Resultados: La mayoría de los dos académicos no conocen cuál es el mejor grupo de edad para identificar los primeros síntomas del autismo, pero podrán identificar los síntomas centrales del trastorno del espectro autista. El 65% niega tener una correlación entre el nivel socioeconómico y el trastorno. Según el 4% de dos estudiantes, todos los autistas son superdotados, y para el 98% el autismo no es causado por la vacunación. Además, dos académicos afirman que no han recibido suficiente conocimiento de la graduación en la materia. Todos coinciden en la falta de conciencia sobre el trastorno del espectro autista entre los profesionales de la salud. Conclusión: Verificar algunas lagunas en el conocimiento de los estudiantes enfermos sobre el Trastorno del Espectro Autista, se me debe animar a insertar este tema en los cursos de graduación. (AU)

Whey protein supplementation and its potentially adverse effects on health: a systematic review.

Whey protein comprises soluble whey proteins and its benefits are well described in the literature. However, there are not many studies investigating the potential adverse effect of a diet with indiscriminate use of this supplement. The aim of this study was to perform a systematic review of papers that addressed this theme. A search was conducted in Medline, LILACS, TOXNET, Web of science, and Scopus electronic databases. In the end, 11 documents comprised this review. The majority of the papers associated the damaging effect with the chronic and abusive use of whey protein, with the kidneys and liver being the main organs affected. The other studies related whey protein to aggravation of aggression, presence of acne, and modification of the microbiota. Therefore, excessive consumption over a long period of protein supplementation may have some adverse effects on the body, which is aggravated when associated with sedentary lifestyle. PROSPERO registration no.: CRD42020140466. Novelty: A systematic review of experimental and randomized studies about the use of whey proteins supplements and its impact on physical health. Analysis revealed that chronic and without professional guidance use of whey protein supplementation may cause some adverse effects specially on kidney and liver function. Presented data support a need for future studies co-relating the use of different types of whey protein with and without exercise to better see the impact on human physical health.

Ethanolic Extract of the Red Algae Meristiella echinocarpa (Areschoug) Confers Neuroprotection in Mice / Extrato Etanólico da Alga Vermelha Meristiella echinocarpa (Areschoug) Confere Neuroproteção em Camundongos

Objectives: This study aimed to investigate the neuroprotective effects of the ethanolic extract obtained from red algae marine Meristiella echinocarpa (Areschougiaceae) ­ EEMe. Methods: EEMe was used in doses ranging from 10 to 40 mg/kg, administered intraperitoneally in mice. Behavioral tests were performed to assess locomotor activity (open field), anxiety (elevated plus maze), depression (tail suspension), and motor coordination (rota-rod). The anticonvulsant effect of the algae extract was evaluated in two models of seizures induced by strychnine and pentylenetetrazol. The level of oxidative stress was also evaluated in the following brain areas: the prefrontal cortex, hippocampus, and striatum. Statistical analysis was performed applying ANOVA followed by the Bonferroni test. Results: EEMe reduced significantly the number of crossing (36%) and rearing (54%) in the open field test and increased 1.3x the immobility time in the tail suspension test. In brain areas EEMe also reduced significantly malondialdehyde levels (striatum: 45%, hippocampus: 38%, prefrontal cortex: 37%) and nitrite levels (striatum: 72%, hippocampus: 79%, prefrontal cortex: 63%), and increased the reduced-glutathione levels (striatum: 72%, hippocampus: 73%, prefrontal cortex: 42%). In addition, the extract significantly prolonged the latency of seizures induced by strychnine (38%) or pentylenetetrazol (57%), and the latency of death induced by pentylenetetrazol (6.1x). Conclusion: EEMe exhibits antioxidant and anticonvulsant effects, probably involving GABAergic and glycinergic pathways.

Objetivos: este estudo teve como objetivo investigar os efeitos neuroprotetores do extrato etanólico da alga marinha vermelha Meristiella echinocarpa (Areschougiaceae) - EEMe. Métodos: EEMe foi utilizado em doses que variaram de 10 a 40 mg/kg, administrados via intraperitoneal em camundongos. Foram realizados testes comportamentais que avaliaram a atividade locomotora (campo aberto), a ansiedade (labirinto em cruz elevado), a depressão (suspensão em cauda) e a coordenação motora (rota-rod). O efeito anticonvulsivante do extrato da alga foi avaliado em dois modelos de convulsões por estricnina e pentilenotetrazol. Foi também realizada a avaliação do nível de estresse oxidativo nas seguintes áreas cerebrais: córtex pré-frontal, hipocampo e corpo estriado. A análise estatística foi realizada, aplicando a ANOVA seguida do teste de Bonferroni. Resultados: o EEMe reduziu, significativamente, o número de cruzamentos (36%) e o número de rearing (54%) no teste de campo aberto e aumentou, em 1,3x, o tempo de imobilidade no teste de suspensão pela cauda. Nas áreas cerebrais, o EEMe também reduziu, significativamente, os níveis de malondialdeído (estriado: 45%, hipocampo: 38%, córtex pré-frontal: 37%) e os níveis de nitrito (estriado: 72%, hipocampo: 79%, córtex pré-frontal: 63%) e aumentou a glutationa reduzida (estriado: 72%, hipocampo: 73%, córtex pré-frontal: 42%). Além disso, o EEMe prolongou, significativamente, a latência das convulsões induzidas por estricnina (38%) ou pentilenotetrazol (57%), e a latência da morte induzida por pentilenetetrazol (6,1x). Conclusão: o EEMe apresenta efeitos antioxidantes e anticonvulsivantes, provavelmente envolvendo as vias GABAérgica e glicinérgica.

Could autism spectrum disorders be a risk factor for COVID-19?

The coronavirus SARS-CoV-2 pandemia is infecting millions of people and some studies relate conditions that might increase the risk of developing a fatal course for the disease, such as diabetes, cardiovascular diseases and obesity. In COVID-19 physiopathology, one of the main inflammation mechanisms is the "cytokine storm", causing a pro-inflammatory state, related to cardiac and pulmonary damage. There is also a less effective role of lymphocyte B and T in the humoral immunity due to the reduction of their proliferative response. The physiopathology of ASD (Autism Spectrum Disorder) involves several modifications at the genetic and at the immune level, such as the increase of inflammatory cytokines and abnormal immune response in several levels. We hypothesize that ASD could be a risk-factor as the other conditions are.

A via das quinureninas e suas implicações na esquizofrenia / Kynurenine pathway and its implications in schizophrenia

Introdução: a esquizofrenia é uma doença mental grave heterogênea, de extrema complexidade, manifestada por vários distúrbios de cognição, pensamento, memória, comportamento e afeto. Sua fisiopatologia, apesar dos avanços, continua de difícil compreensão. Objetivo: realizar uma revisão da literatura a respeito da relação entre a via das quinureninas e a fisiopatologia da esquizofrenia. Metodologia: foi conduzida a busca de artigos através das bases de dados Medline e Lilacs, utilizando os descritores schizophrenia/ esquizofrenia e as palavras-chave kynurenine pathways/via das quinureninas. Por meio desta busca, foram selecionados 38 artigos publicados entre os anos de 1990 e 2018. Resultados: estudos mais recentes vêm demonstrando que anormalidades no metabolismo do triptofano por meio da via das quinureninas poderiam estar relacionadas com os mecanismos neurofisiopatológicos da esquizofrenia. Os metabólitos gerados pela via das quinureninas possuem propriedades neuroativas. Dentre eles, destaca-se o ácido quinurênico, antagonista endógeno do receptor N-metil-D-aspartato. Seus níveis cerebrais estão aumentados em pacientes esquizofrênicos, provavelmente devido a uma condição pró-inflamatória, resultando dessa forma, em possíveis alterações neurológicas responsáveis pelo desenvolvimento da esquizofrenia. Conclusão: não somente uma melhor compreensão da fisiopatologia da esquizofrenia, como também o desenvolvimento de novos alvos terapêuticos, poderão ser obtidos a partir de um melhor entendimento da relação entre anormalidades na via das quinureninas e a gênese da esquizofrenia.

Introduction: Schizophrenia is a severe heterogeneous mental illness of extreme complexity, manifested by various disorders of cognition, thought, memory, behavior and affection. Its pathophysiology, despite advances, remains difficult to understand. Objective: to review the literature on the relationship between the kynurenine pathway and the pathophysiology of schizophrenia. Methodology: a literature review was carried out using the descriptors kynurenine pathways/via das quinureninas and the keywords kynurenine pathways/via das quinureninas using Medline and Lilacs databases. Through this search, were selected 38 articles published between the years of 1990 and 2018. Results: recent studies have shown that abnormalities in tryptophan metabolism through the kynurenine pathway may be related to the neuropathophysiological mechanisms of schizophrenia. The metabolites generated by the kynurenine pathway have neuroactive properties. Among them, kynurenic acid, an endogenous antagonist of the N-methyl-D-aspartate receptor, stands out. Their brain levels are increased in schizophrenic patients, probably due to a pro-inflammatory condition, resulting in possible neurological changes responsible for the development of schizophrenia. Conclusion: not only a better knowledge of pathophysiology, but also the development of new therapeutic targets will be obtained with a better understanding of the relationship between abnormalities in the kynurenine pathway and the genesis of schizophrenia.

Uso de fármacos anticorpos monoclonais, imunomoduladores e anti-inflamatórios no tratamento da infecção por COVID-19 / Use of monoclonal antibodies, immunomodulators, and anti-inflammatory drugs in the treatment of COVID-19

O objetivo deste estudo foi realizar o levantamento bibliográfico de artigos científicos e ensaios clínicos sobre a utilização de anticorpos monoclonais, imunomoduladores e anti-inflamatórios como possíveis alternativas terapêuticas para uso em pacientes com COVID-19, com ênfase nos mecanismos de ação e resultados de ensaios clínicos. Foram analisados artigos obtidos na base de dados MEDLINE® e ensaios clínicos disponíveis no site ClinicalTrials no período de 6 de abril a 6 de maio de 2020. Os ensaios realizados com os fármacos apresentados nesta revisão bibliográfica sugerem a viabilidade de uso de algumas dessas drogas como alternativas para tratamento da COVID-19. No entanto, observou-se que, em função do número reduzido de participantes dos estudos disponíveis, é indispensável a continuidade de pesquisas e dos ensaios clínicos com esses medicamentos, para estimar a eficácia dessas drogas no tratamento do SARS-CoV-2, contra o qual ainda não há terapia específica

The objective of this study was to carry out a bibliographic survey of scientific articles and current clinical trials on the use of monoclonal antibodies, immunomodulators, and anti-inflammatories as possible therapeutic alternatives for use in patients with COVID-19, highlighting their mechanisms of action and results of clinical trials. Articles from the MEDLINE® database and clinical trials available on the ClinicalTrials website were analyzedThe tests performed with the drugs presented in this bibliographic review suggest the feasibility of using some of these drugs as treatment alternatives for COVID-19. However, it was observed that the small samples evaluated in these tests make it imperative to proceed with research and clinical trials with these drugs to provide greater evidence of the effectiveness of these drugs in the treatment of the disease caused by SARS-CoV-2, for which there is no specific therapy so far.

Jogo de cartas como estratégia para o ensino de doenças autoimunes na graduação médica / Card game as strategy for the teaching of autoimmune diseases in medical graduation / Juego de cartas como estrategia para la enseñanza de enfermedades autoinmunes en la graduación médica

A experiência relatada neste artigo envolveu a elaboração e aplicação do ImunoDAI, um jogo de cartas desenvolvido por alunos e professores do curso de Medicina para abordar o conteúdo técnico de vinte Doenças Autoimunes (DAI). As DAI compreendem numerosas doenças com diferentes apresentações clínicas que compartilham uma etiologia complexa, porém comum, representada pela resposta imunológica contra autoantígenos. O ImunoDAI trata-se de um jogo produzido coletivamente que, enquanto recurso pedagógico, possibilitou o trabalho com as DAI por meio da elaboração de quatro cartas contendo informações sobre as principais causas da doença; imunopatogênese; sinais e sintomas; diagnóstico e tratamento. A utilização do jogo facilitou a fixação dos conteúdos e favoreceu o processo de ensino-aprendizagem ao permitir múltiplas interações, promover a aprendizagem dos conteúdos, desenvolver autonomia, criatividade, cooperação mútua, discussões e tomadas de decisões, habilidades indispensáveis aos futuros médicos.

The experience reported in this article involved the development and application of ImmunoDAI, a card game developed by students and professors of the medical course to address the technical content of twenty autoimmune diseases (DAI). The DAI comprise numerous diseases with different clinical presentations that share a complex but common etiology represented by the immune response against autoantigens. The ImunoDAI is a collectively produced game that, as a pedagogical resource, made possible the work with the DAI through the elaboration of four letters containing information about the main causes of the disease; immunopathogenesis; signals and symptoms; diagnosis and treatment. The use of the game facilitated the fixing of contents and favored the teaching-learning process by allowing multiple interactions, promoting content learning, developing autonomy, creativity, cooperation, discussions and decision making, skills that are indispensable for future doctors.

A experiencia relatada en este artículo involucró la elaboración y aplicación del ImunoDAI, un juego de cartas desarrollado por alumnos y profesores del curso de Medicina para abordar el contenido técnico de veinte Enfermedades autoinmunes (DAI). Las DAI comprenden numerosas enfermedades con diferentes presentaciones clínicas que comparten una etiología compleja, pero común, representada por la respuesta inmunológica contra autoantígenos. El ImunoDAI es un juego producido colectivamente que, en cuanto recurso pedagógico, posibilitó el trabajo con las DAI por medio de la elaboración de cuatro cartas conteniendo informaciones sobre las principales causas de la enfermedad; inmunopatogenia; signos y síntomas; diagnóstico y tratamiento. La utilización del juego facilitó la fijación de los contenidos y favoreció el proceso de enseñanza-aprendizaje al permitir múltiples interacciones, promover el aprendizaje de los contenidos, desarrollar autonomía, creatividad, cooperación, discusiones y tomas de decisiones, habilidades indispensables para los futuros médicos.

Guillain-Barre syndrome and its correlation with dengue, Zika and chikungunya viruses infection based on a literature review of reported cases in Brazil.

Guillain-Barre syndrome (GBS) is one of the main neurologic manifestations of arboviruses, especially Zika virus infection. As known, the prevalence of these diseases is high, so the risk of having an increase on GBS is relevant. The study purposes making a comparative survey between the involvement of dengue, Zika and chikungunya infections in the development of the GBS in Brazil, as well as search in literature resemblances and distinctions between beforehand reported cases. It was performed an electronic search in online databases, with articles published between the years of 2004-2018. A total of 729 articles about the proposed search were found, and 10 were selected according to inclusion and exclusion criteria. The medium age found in Brazilian studies was 429. The time lapse for the neurological symptoms manifest was 6,5-11 days. Facial palsy, paresthesia and member weakness were the main symptoms related. Pediatric cases are rare. There are many studies that implicated the association of GBS and arboviruses and point it to one of the main neurological manifestation of these infections. More research and consistent data are needed to clarify unanswered questions and guide public health measures.

Protective effects of ethanolic extract from the red algae Amansia multifida on experimental inflammation, nociception and seizure experimental models / Efeito protetor do extrato etanólico da alga marinha vermelha Amansia multifida em modelos experimentais de inflamação, nocicepção e convulsão

This study aimed to investigate the EEAm effect in mice models of nociception, inflammation and in behavioral tests evaluating the central nervous system. EEAm had inhibitory effects in the following tests: acetic acid-induced writhing (78%); formalin (62% - inflammatory phase); open field (46%). EEAm increased the nociceptive latency (56%) in tail flick test and increased the death-latency by 36% in the pentylenetetrazole-induced seizure model. Moreover, EEAm inhibited paw edema (82%) and peritonitis (45%) induced by carrageenan. In conclusion, EEAm presents antinociceptive, anti-inflammatory and anticonvulsant effects involving peripheral and central-acting mechanisms in mice.

Neste estudo objetivou-se investigar o efeito do EEAm em modelos de nocicepção e inflamação, e em testes comportamentais que avaliam o sistema nervoso central em camundongos. EEAm exibiu efeitos inibitórios nos testes comportamentais de contorções abdominais induzidas por ácido acético (78%); formalina (62% - fase inflamatória) e campo aberto (46%). EEAm aumentou a latência de nocicepção no teste de retirada da cauda (56%) e a latência de morte 36% no modelo de convulsões induzidas por pentilenetetrazol. Além disso, EEAm inibiu o edema de pata (82%) e a peritonite (45%) induzidos por carragenana. Como conclusão, EEAm apresenta efeitos antinociceptivo, anti-inflamatório e anticonvulsivante em camundongos por mecanismos periféricos e centrais.

Alterations in brain amino acid metabolism and inhibitory effects on PKC are possibly correlated with anticonvulsant effects of the isomeric mixture of α- and ß-amyrin from Protium heptaphyllum.

CONTEXT: α- and ß-Amyrin (AMY) from Protium heptaphyllum (Aubl) March (Burseraceae) is found in Brazil and used in diverse inflammation-related diseases. This species presents a central action, as previously described. OBJECTIVE: The objectives were to evaluate the anticonvulsant effect of AMY in mice and to verify the mechanism of action. MATERIAL AND METHODS: Seizures were induced by pentylenetetrazole followed by acute or subchronic treatments (5-25 mg/kg, p.o. and i.p.) and determination of brain amino acids (10 and 25 mg/kg, i.p., 7 d). RESULTS: In the acute treatment, AMY (10, 25, and 50 mg/kg, p.o.) increased the latency to the first convulsion (FC) by 30, 44, and 40% and time to death (TD) by 36, 52, and 42%, respectively. When administered intraperitoneally, the same doses increased FC by 62, 75, and 73% and TD by 76, 82, and 119%, respectively. Combined with polymixin or staurosporine, AMY (25 mg/kg, i.p.) increased TD by 61 and 63%, respectively, as related to each drug alone. When subchronically administered (25 and 50 mg/kg, i.p.) increased FC by 75 and 101% and TD by 86 and 124%, respectively. AMY increased taurine (116 and 76%) and tyrosine concentrations (135 and 110%) in basal ganglia and hippocampus, respectively, and decreased by 68, 65, and 62% glutamate, aspartate, and GABA in basal ganglia. CONCLUSION: Thus, the AMY anticonvulsant activity is related to the GABAergic system and may be linked to the inhibition of the signaling cascade of PKC as well as to alterations in amino acids metabolism.

Edematogenic activity of a sulfated galactan from the red marine algae Gelidium crinale.

CONTEXT: The red algae Gelidium crinale (Turner) Gaillon (Gelidiaceae), encountered along the Southeast and Northeast Brazilian sea coast, contains a sulfated galactan presenting a similar saccharide backbone compared to λ carrageenan. Inflammatory effects of other galactans were reported, but not for that obtained from G. crinale (SG-Gc). OBJECTIVE: To investigate the in vivo edematogenic effect of SG-Gc in comparison to λ carrageenan. METHODS: SG-Gc was isolated by ion exchange chromatography. Paw edema was induced by subcutaneous (s.c.) intraplantar injection of SG-Gc or λ carrageenan and evaluated by hydroplethysmometry. Data were expressed as the increase in paw volume subtracted from the basal volume or area under curve-AUC. To investigate the participation of early and late-phase inflammatory mediators, rats were treated with pyrilamine, compound 48/80, indomethacin, NG-nitro-L-arginine methyl ester (L-NAME), or pentoxifylline before SG-Gc. RESULTS: SG-Gc edematogenic effect was initiated at 0.5 h, peaked at 2 h (1.26 ± 0.05 mL) and lasted until 6 h (0.21 ± 0.03 mL), whereas the carrageenan-induced edema started at 1 h. The first phase (1-3 h) of SG-Gc-induced edema was 176 ± 15 (AUC) versus carrageenan (114.5 ± 14), whereas the second phase (3-5 h) was 95 ± 12 (AUC) versus carrageenan (117.5 ± 11). Treatment with compound 48/80, pyrilamine, indomethacin, L-NAME, and pentoxifylline inhibited the effect of SG-Gc by 32, 40, 69, 72, and 49%, respectively. DISCUSSION AND CONCLUSION: SG-Gc and λ carrageenan induce different profile of inflammatory response in the paw edema model, that involves histamine, cytokines, prostaglandins, and nitric oxide (NO), but with different degree of participation.

Efeitos dos triterpenos a- e ß-amirina e de seus derivados acetilados no sistema nervoso central [manuscrito] / Effects of a- and ß-amyrin triterpenes and its acetylated derivatives in the central nervous system [manuscript]

A mistura triterpênica de α- e β-amirina (AMI) é obtida da planta Protium heptaphyllum Aubl March (Família Burseraceae), comum em vários estados brasileiros e conhecida popularmente como breu branco, também é utilizada na prática da medicina popular para tratar várias enfermidades. O acetato de α- e β-amirina (AcAMI) é a forma acetilada desta mistura triterpênica. Vários estudos experimentais já foram feitos utilizando estes triterpenos, mas estudos da ação destes no Sistema Nervoso Central (SNC) ainda são escassos. O objetivo deste trabalho foi avaliar o efeito da administração destes compostos naturais em camundongos e verificar uma possível atividade sedativa, ansiolítica, antidepressiva e anticonvulsivante, procurando ainda esclarecer por que mecanismos estes compostos agem. A metodologia utilizada foi utilizando testes farmacológicos já descritos na literatura e estudos de doseamento de monoaminas e aminoácidos através de HPLC. Os resultados mostraram que tanto a AMI como o AcAMI mostraram-se bastante ativos farmacologicamente. No teste da Campo Aberto ambas misturas (AMI e AcAMI) administradas por via aguda e sub-crônica demonstraram efeitos sedativos, nas doses de 10, 25 50 mg/kg, após a constatação da diminuição do movimento exploratório dos animais e do número de grooming e de rearing, utilizando o diazepam como controle positivo. No Teste do Plus Maze também ambas as misturas demonstraram atividade ansiolítica aumentando o número de entradas e o tempo de permanência nos braços abertos...

Analgesic and anti-inflammatory activities of the isomeric mixture of alpha- and beta-amyrin from Protium heptaphyllum (Aubl.) march.

In the present work, we demonstrated that the mixture of alpha- and beta-amyrin (AMI) from Protium heptaphyllum has antinociceptive activity as was evident from the writhing and formalin tests in mice. AMI (10 and 50 mg/kg, i.p.) inhibited writhing in 73 and 94%, respectively, while preferentially inhibiting the 2nd phase of the response (37 and 51; and 60 and 73% inhibitions of the 1st and 2nd phases, respectively) to the formalin test. Naloxone, an opioid antagonist, did not reverse the antinociceptive effect. AMI (50 mg/kg, i.p.) was also active in the hot plate test, increasing the reaction time to thermal stimulus after 30 and 60 min, by 62 and 71%, respectively. A preventive antiedematogenic effect was observed in mice that had a carrageenan-induced paw edema. Paw volume was significantly and dose-dependently decreased by 39, 42 and 53%, three hours after administration of 10, 25 and 50 mg/kg doses, i.p., respectively. AMI (25 and 50 mg/kg, i.p.) was also able to reverse the edema already induced by carrageenan (curative effect). AMI (10 and 25 mg/kg, i.p.) was equally effective in the dextran- induced paw edema (preventive effect), reducing the paw volume by 50 and 60% at the 2nd hour, and by 63 and 73% at the third hour post-dose. AMI (50 mg/kg, i.p.) reverted the edema already formed after the dextran injection (curative effect). In conclusion, AMI demonstrated peripheral and central analgesic effects independent of the opioid system, and also showed a potent anti-inflammatory activity. The antiinflammatory activity was potentiated by both indomethacin and thalidomide, suggesting a potential involvement of prostaglandins and TNFalpha inhibitions.