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Resumo Objetivo Mapear as evidências disponíveis sobre as ações do óxido nítrico na fisiopatologia da sepse e sua relação com a gravidade de pacientes sépticos. Método Revisão de escopo de acordo com a metodologia do Joanna Briggs Institute. Realizou-se busca por estudos que evidenciaram as ações do óxido nítrico na sepse e se o seu aumento está associado à gravidade de pacientes sépticos. Dois revisores independentes fizeram o mapeamento das informações utilizando um instrumento de extração de dados previamente elaborado. Os dados foram analisados quanto à sua relevância, sendo posteriormente extraídos e sintetizados. Resultados De 1342 estudos, 11 foram incluídos na revisão. O primeiro foi publicado em 2017 e o último, em 2022. A maioria foi desenvolvida nos Estados Unidos, na China e na Alemanha. Os estudos apresentaram informações referentes as ações do óxido nítrico, sintetizando sua biodisponibilidade e os inibidores endógenos relacionados a sua produção, além de abordarem a relação do óxido nítrico com a gravidade da sepse. Conclusão A produção de óxido nítrico fisiológico durante a sepse atua como protetor vascular, principalmente na microcirculação, porém, em altas concentrações, contribui para a disfunção vascular, que subverte a fisiologia da regulação da pressão arterial, causando profunda vasodilatação e hipotensão refratária e aumentando a gravidade de pacientes sépticos.
Resumen Objetivo Mapear las evidencias disponibles sobre las acciones del óxido nítrico en la fisiopatología de la sepsis y su relación con la gravedad de pacientes sépticos. Métodos Revisión de alcance de acuerdo con la metodología del Joanna Briggs Institute. Se realizó una búsqueda de estudios que evidenciaron las acciones del óxido nítrico en la sepsis y si su aumento estaba asociado a la gravedad de pacientes sépticos. Dos revisores independientes hicieron el mapeo de la información utilizando un instrumento de extracción de datos previamente elaborado. Los datos se analizaron respecto a su relevancia, para luego extraerlos y sintetizarlos. Resultados De 1342 estudios, se incluyeron 11 en la revisión. El primero fue publicado en 2017 y el último en 2022. La mayoría se realizó en Estados Unidos, China y Alemania. Los estudios presentaron información referente a las acciones del óxido nítrico, sintetizando su biodisponibilidad y los inhibidores endógenos relacionados con su producción, además de abordar la relación del óxido nítrico con la gravedad de la sepsis. Conclusión La producción de óxido nítrico fisiológico durante la sepsis actúa como protector vascular, principalmente en la microcirculación. Sin embargo, en altas concentraciones, contribuye a la disfunción vascular, que subvierte la fisiología de la regulación de la presión arterial, causa una profunda vasodilatación e hipotensión refractaria y aumenta la gravedad de pacientes sépticos. Registro da revisão de escopo no Open Science Framework: https://doi.org/10.17605/OSF.IO/MXDK2
Abstract Objective Map the available evidence on the actions of nitric oxide in the pathophysiology of sepsis and its relationship with the severity of sepsis in patients. Method Scoping review following the Joanna Briggs Institute methodology. A search was carried out for studies that highlighted the actions of nitric oxide in sepsis, informing whether its increase is associated with the severity of sepsis in patients. Two independent reviewers mapped the information using a previously designed data extraction instrument. The data was analyzed for its relevance and then extracted and synthesized. Results Eleven of 1342 studies were included in the review. The first of them was published in 2017 and the last in 2022. Most of them were developed in the USA, China, and Germany. Studies have reported the actions and bioavailability of nitric oxide and endogenous inhibitors related to its production, and related nitric oxide to the severity of sepsis. Conclusion The physiological production of nitric oxide during sepsis acts as a vascular protector, mainly in the microcirculation but contributes to vascular dysfunction in high concentrations, subverting the regulation of blood pressure, causing deep vasodilation and refractory hypotension, and increasing the severity of sepsis in patients. Registration of the scoping review in the Open Science Framework: https://doi.org/10.17605/OSF.IO/MXDK2
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Sepsis is associated with numerous physiological and biochemical abnormalities that result in a life-threatening condition. The involvement of the Central Nervous System (CNS) during sepsis has received considerable attention, especially the hippocampus which plays a key role in the learning and memory processes. The increased interest in this limbic region during systemic inflammation (SI) is related to the number of sepsis survivor patients who have cognitive impairments. A single injection of lipopolysaccharide (LPS)-induced systemic inflammation is the most commonly used murine endotoxemia model because it replicates several pathophysiological changes observed in severe sepsis. Molecular hydrogen (H2) has been used as an anti-inflammatory therapeutic strategy to prevent neuroinflammation. However, the mechanisms by which inhaled H2 mitigate memory loss during SI remains unknown. To understand how H2 acts in the hippocampus, the current study focused on specific mechanisms that may be involved in reducing neuroinflammation in rats during SI. We hypothesized that inhaled H2 decreases LPS-induced hippocampal pro-inflammatory cytokines surges and this effect is associated with reduced memory loss. Using different and integrative approaches, i.e., from hippocampal cells electrophysiology to animal behavior, we report that inhaled H2 decreased LPS-induced peripheral and hippocampal inflammation, decreased microglial and astrocytic activation, lessen memory loss without affecting long-term potentiation (LTP). To our knowledge, this is the first evidence showing that inhaled H2 reduces hippocampal microglial and glial cells inflammation, which may be associated with a reduced memory impairment induced by SI.
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The aim of this study was to evaluate the participation of nitric oxide (NO) in the hypotensive and vasorelaxation effect induced by PBM using an aluminum gallium arsenide (AlGaAs) diode laser (660 nm). Male Wistar rats were treated with the inhibitor of nitric oxide synthase (L-NAME). A red laser (660 nm; 63 J/cm2; 56 s/point) was applied to the abdominal region at six different points. Thoracic aorta was dissected for vascular reactivity study, and a laser (660 nm; 96 J/cm2; 56 s) was applied after incubation with the NO donor DETA-NO, PBS, or hydroxicobalamin. Endothelial cells (HUVEC) were treated with DETA-NO or CuSO4, and then, PBM (63 J/cm2) was applied, and the nitric oxide was detected. Hypertensive L-NAME rats did not exhibit a decrease in blood pressure after PBM. PBM promoted vasodilation in the aorta isolated from normotensive rats, and less effect in the aorta of L-NAME rats and the addition of the NO donor, DETA-NO, promoted greater vasodilation by PBM in the aorta of L-NAME rats. In endothelial cells, an increase in NO, after PBM, was detected; however, with the addition of CuSO4, which catalyzes the decomposition of NO storage, there was no detection of NO after PBM. The results of this study demonstrate that the hypotensive and vasodilatory effect of PBM with a red laser at 660 nm is modulated by the release of nitric oxide from the storage.
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Hipotensão , Vasodilatação , Alumínio/farmacologia , Animais , Arsenicais , Células Endoteliais , Gálio , Lasers Semicondutores/uso terapêutico , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico , Doadores de Óxido Nítrico/farmacologia , Ratos , Ratos WistarRESUMO
OBJECTIVE: To verify researchers-nurses' knowledge about trends in scientific publishing and good research practices. METHOD: A descriptive study carried out through an online survey with 197 nurses holding master's and/or doctoral degrees from all Brazilian regions. To raise knowledge, a validated, self-administered and anonymous questionnaire with 18 questions on the subject was used. Descriptive and inferential analyzes were performed on researchers' scores (Mann-Whitney test). RESULTS: Among the specific questions, the mean of correct answers was 7.1: 6.4 for master's and 7.4 for doctoral degree holders. There was a significant difference in the mean of correct answers between masters and doctors (p = 0.025), and between productivity scholarship holders and non-scholarship holders (p = 0.021), according to mean difference tests. Questions about predatory editorial practices were those in which researchers had the worst knowledge. CONCLUSION: We identified that, regardless of the education level (master's or doctoral degree), nurses have little knowledge about the topics studied, which can compromise the quality of production and the scientific vehicles used to disseminate this knowledge.
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Enfermeiras e Enfermeiros , Médicos , Brasil , Competência Clínica , Humanos , Inquéritos e QuestionáriosRESUMO
Abstract Objective: To verify researchers-nurses' knowledge about trends in scientific publishing and good research practices. Method: A descriptive study carried out through an online survey with 197 nurses holding master's and/or doctoral degrees from all Brazilian regions. To raise knowledge, a validated, self-administered and anonymous questionnaire with 18 questions on the subject was used. Descriptive and inferential analyzes were performed on researchers' scores (Mann-Whitney test). Results: Among the specific questions, the mean of correct answers was 7.1: 6.4 for master's and 7.4 for doctoral degree holders. There was a significant difference in the mean of correct answers between masters and doctors (p = 0.025), and between productivity scholarship holders and non-scholarship holders (p = 0.021), according to mean difference tests. Questions about predatory editorial practices were those in which researchers had the worst knowledge. Conclusion: We identified that, regardless of the education level (master's or doctoral degree), nurses have little knowledge about the topics studied, which can compromise the quality of production and the scientific vehicles used to disseminate this knowledge.
RESUMEN Objetivo: Verificar el conocimiento de investigadores-enfermeros sobre las tendencias en la publicación científica y las buenas prácticas de investigación. Método: Estudio descriptivo, realizado a través de una encuesta en línea con 197 enfermeros con maestría y/o doctorado de todas las regiones brasileñas. Para aumentar el conocimiento se utilizó un cuestionario validado, autoadministrado y anónimo con 18 preguntas sobre el tema. Sobre la puntuación de los investigadores, se realizaron análisis descriptivos e inferenciales (prueba de Mann-Whitney). Resultados: Entre las preguntas específicas, la media de aciertos fue de 7,1, siendo 6,4 para los másteres y 7,4 para los médicos. Hubo diferencia significativa en la media de aciertos entre maestros y doctores (p = 0,025), y entre becarios de productividad y no académicos (p = 0,021), según pruebas de diferencia de medias. Las preguntas sobre prácticas editoriales depredadoras eran aquellas en las que los investigadores tenían el peor conocimiento. Conclusión: Identificamos que, independientemente del nivel de formación (maestría o doctorado), los enfermeros tienen poco conocimiento sobre los temas estudiados, lo que puede comprometer la calidad de la producción y los vehículos científicos utilizados para difundir este conocimiento.
RESUMO Objetivo: Verificar o conhecimento de pesquisadores-enfermeiros sobre tendências em editoração científica e boas práticas em pesquisa. Método: Estudo descritivo, realizado por inquéritoonlinecom 197 enfermeiros com título de mestre e/ou doutor de todas as regiões brasileiras. Para levantar o conhecimento, utilizou-se um questionário validado, autoaplicável e anônimo com 18 questões sobre o assunto. Sobre o escore dos pesquisadores, realizaram-se análises descritivas e inferenciais (Teste de Mann-Whitney). Resultados: Entre as questões específicas, a média de acertos foi de 7,1, sendo 6,4 para mestres e 7,4 para doutores. Houve diferença significativa na média de acertos entre mestres e doutores (p = 0,025), e entre bolsistas e não bolsistas de produtividade (p = 0,021), segundo testes de diferença de médias. As questões sobre práticas editoriais predatórias foram aquelas em que os pesquisadores apresentaram pior conhecimento. Conclusão: Identificamos que, independente do grau de formação (mestrado ou doutorado), os enfermeiros têm baixo conhecimento sobre os temas estudados, o que pode comprometer a qualidade da produção e dos veículos científicos utilizados para disseminação desse conhecimento.
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Editoração , Enfermagem , Pesquisa , Pesquisadores , Conhecimento , Comunicação AcadêmicaRESUMO
OBJECTIVE: to analyze variations in body temperature and in plasma nitrate and lactate concentrations in rats submitted to the experimental sepsis model. METHOD: a total of 40 rats divided equally into five groups. The induction of endotoxemia was performed with intravenous administration of lipopolysaccharide, 0.5 mg/Kg, 1.5 mg/Kg, 3.0 mg/Kg, and 10 mg/Kg, respectively. The control group received 0.5 mL of saline solution. The experiment lasted six hours, with evaluations performed at 0 (baseline data), 2nd, 4th, and 6thhours. RESULTS: The animals that received doses up to 3.0 mg/kg showed a significant increase in body temperature compared to the group with 10 mg/kg, which showed a decrease in these values. The increase in plasma nitrate and lactate concentrations in the groups with lipopolysaccharide was significantly higher than in the group that received the saline solution and was correlated with the increase in body temperature. CONCLUSION: the variations in body temperature observed in this study showed the dose-dependent effect of lipopolysaccharide and were correlated with the increase in the concentrations of nitrate and plasma lactate biomarkers. The implications of this study are the importance of monitoring body temperature, together with the assessment of these pathophysiological markers, which suggest worsening in the prognosis of sepsis.
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Endotoxemia , Sepse , Animais , Biomarcadores , Modelos Animais de Doenças , Lipopolissacarídeos , RatosRESUMO
Sepsis-associated encephalopathy causes brain dysfunction that can result in cognitive impairments in sepsis survivor patients. In previous work, we showed that simvastatin attenuated oxidative stress in brain structures related to memory in septic rats. However, there is still a need to evaluate the long-term impact of simvastatin administration on brain neurodegenerative processes and cognitive damage in sepsis survivors. Here, we investigated the possible neuroprotective role of simvastatin in neuroinflammation, and neurodegeneration conditions of brain structures related to memory in rats at 10 days after sepsis survival. Male Wistar rats (250-300 g) were submitted to cecal ligation and puncture (CLP, n = 42) or remained as non-manipulated (naïve, n = 30). Both groups were treated (before and after the surgery) by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline and observed for 10 days. Simvastatin-treated rats that survived to sepsis showed a reduction in the levels of nitrate, IL1-ß, and IL-6 and an increase in Bcl-2 protein expression in the prefrontal cortex and hippocampus, and synaptophysin only in the hippocampus. Immunofluorescence revealed a reduction of glial activation, neurodegeneration, apoptosis, and amyloid aggregates confirmed by quantification of GFAP, Iba-1, phospho Ser396-tau, total tau, cleaved caspase-3, and thioflavin-S in the prefrontal cortex and hippocampus. In addition, treated animals presented better performance in tasks involving habituation memory, discriminative, and aversive memory. These results suggest that statins exert a neuroprotective role by upregulation of the Bcl-2 and gliosis reduction, which may prevent the cognitive deficit observed in sepsis survivor animals.
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Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/prevenção & controle , Doenças Neurodegenerativas/tratamento farmacológico , Sepse/tratamento farmacológico , Sinvastatina/uso terapêutico , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Ratos , Ratos Wistar , Sepse/metabolismo , Sepse/patologia , Sinvastatina/farmacologiaRESUMO
Objective: to analyze variations in body temperature and in plasma nitrate and lactate concentrations in rats submitted to the experimental sepsis model. Method: a total of 40 rats divided equally into five groups. The induction of endotoxemia was performed with intravenous administration of lipopolysaccharide, 0.5 mg/Kg, 1.5 mg/Kg, 3.0 mg/Kg, and 10 mg/Kg, respectively. The control group received 0.5 mL of saline solution. The experiment lasted six hours, with evaluations performed at 0 (baseline data), 2nd, 4th, and 6thhours. Results: The animals that received doses up to 3.0 mg/kg showed a significant increase in body temperature compared to the group with 10 mg/kg, which showed a decrease in these values. The increase in plasma nitrate and lactate concentrations in the groups with lipopolysaccharide was significantly higher than in the group that received the saline solution and was correlated with the increase in body temperature. Conclusion: the variations in body temperature observed in this study showed the dose-dependent effect of lipopolysaccharide and were correlated with the increase in the concentrations of nitrate and plasma lactate biomarkers. The implications of this study are the importance of monitoring body temperature, together with the assessment of these pathophysiological markers, which suggest worsening in the prognosis of sepsis.
Objetivo: analisar as variações na temperatura corporal e nas concentrações de nitrato e lactato plasmáticos em ratos submetidos ao modelo de sepse experimental. Método: foram utilizados 40 ratos divididos igualmente em cinco grupos. A indução da endotoxemia foi realizada com administração endovenosa de lipopolissacarídeo, respectivamente 0,5 mg/Kg, 1,5 mg/Kg, 3,0 mg/Kg e 10 mg/Kg. O grupo controle recebeu 0,5 mL de solução salina. O experimento teve duração de seis horas, com avaliações realizadas na 0 (dados basais), 2a, 4a e 6a hora. Resultados: os animais que receberam doses de até 3,0 mg/Kg apresentaram aumento significativo na temperatura corporal em relação ao grupo com 10 mg/Kg, que apresentou diminuição nesses valores. O aumento nas concentrações de nitrato e lactato plasmáticos nos grupos com lipopolissacarídeo foi significativamente superior ao grupo que recebeu salina e esteve correlacionado com o aumento na temperatura corporal. Conclusão: as variações na temperatura corporal observadas neste estudo mostraram efeito dose dependentes de lipopolissacarídeo e estiveram correlacionadas com o aumento nas concentrações dos biomarcadores nitrato e lactato plasmáticos. O estudo traz como implicações, a importância no monitoramento da temperatura corporal, em conjunto com a avaliação destes marcadores fisiopatológicos, os quais sugerem agravamento no prognóstico da sepse.
Objetivo: analizar las variaciones de la temperatura corporal y de las concentraciones de nitrato y lactato en plasma en ratones sometidos a un modelo de sepsis experimental. Método: se utilizaron 40 ratones divididos en cinco grupos iguales. La inducción de la endotoxemia se realizó mediante administración intravenosa de 0,5 mg/Kg, 1,5 mg/Kg, 3,0 mg/Kg y 10 mg/Kg de lipopolisacárido, respectivamente. El grupo de control recibió 0,5 mL de solución salina. El experimento duró seis horas, con evaluaciones realizadas a la hora 0 (datos de referencia) y a la 2a, 4a y 6ahora. Resultados: los animales que recibieron dosis de hasta 3,0 mg/kg presentaron un aumento significativo de la temperatura corporal, en comparación con el grupo al que se le administró 10 mg/kg, que presentó una disminución de dichos valores. En los grupos a los que se les administró lipopolisacárido, el aumento en las concentraciones de nitrato y lactato en plasma fue significativamente mayor que en el grupo al que se le administró la solución salina y estuvo correlacionado con el aumento de la temperatura corporal. Conclusión: las variaciones de la temperatura corporal observadas en este estudio mostraron que los efectos dependieron de la dosis de lipopolisacárido, y estuvieron correlacionadas con el aumento en la concentración de biomarcadores, como el nitrato y lactato en plasma. El estudio reveló la importancia del control de la temperatura corporal, junto con la evaluación de estos marcadores fisiopatológicos, que sugieren un empeoramiento en el pronóstico de la sepsis.