Lung-brain crosstalk: Behavioral disorders and neuroinflammation in septic survivor mice.

Although studies have suggested an association between lung infections and increased risk of neuronal disorders (e.g., dementia, cognitive impairment, and depressive and anxious behaviors), its mechanisms remain unclear. Thus, an experimental mice model of pulmonary sepsis was developed to investigate the relationship between lung and brain inflammation. Male Swiss mice were randomly assigned to either pneumosepsis or control groups. Pneumosepsis was induced by intratracheal instillation of Klebsiella pneumoniae, while the control group received a buffer solution. The model's validation included assessing systemic markers, as well as tissue vascular permeability. Depression- and anxiety-like behaviors and cognitive function were assessed for 30 days in sepsis survivor mice, inflammatory profiles, including cytokine levels (lungs, hippocampus, and prefrontal cortex) and microglial activation (hippocampus), were examined. Pulmonary sepsis damaged distal organs, caused peripheral inflammation, and increased vascular permeability in the lung and brain, impairing the blood-brain barrier and resulting in bacterial dissemination. After sepsis induction, we observed an increase in myeloperoxidase activity in the lungs (up to seven days) and prefrontal cortex (up to 24 h), proinflammatory cytokines in the hippocampus and prefrontal cortex, and percentage of areas with cells positive for ionized calcium-binding adaptor molecule 1 (IBA-1) in the hippocampus. Also, depression- and anxiety-like behaviors and changes in short-term memory were observed even 30 days after sepsis induction, suggesting a crosstalk between inflammatory responses of lungs and brain.

Toxicological and pharmacological effects of Eugenia brasiliensis Lam. (Myrtaceae) leaves in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia brasiliensis Lam., popularly known as "grumixama" or "Brazilian cherry", is widely used in folk medicine with astringent, diuretic, energizing, anti-rheumatic, and anti-inflammatory properties. AIM OF THE STUDY: Despite its traditional use, detailed toxicological studies of Eugenia brasiliensis are few. Thus, in the current study, we evaluate the toxicological effects of hydroalcoholic extract of Eugenia brasiliensis (HEEb) and its antinociceptive and anti-inflammatory activity. MATERIALS AND METHODS: We used male, and female Swiss mice. Acute toxicity study was performed following the Organization for Economic Cooperation and Development (OECD) guideline 425, and subacute toxicity was assessed following OECD guideline 407. We observed behavioral responses, in addition to hematological, biochemical, and histological evaluations. The antinociceptive and anti-inflammatory activity of HEEb were assessed using the Carrageenan-induced mechanical allodynia and paw edema model. Mechanical allodynia, levels of inflammatory cytokines, and oxidative damage were evaluated. RESULTS: The treatment with HEEb was not able to generate important toxicological alterations. Moreover, doses of 100 and 300 mg/kg of HEEb were able to reduce mechanical allodynia, paw edema, and inflammatory cytokines (TNF-α, IL-1ß, and IL-6), decrease malondialdehyde and increase superoxide dismutase enzyme activity in the paw. CONCLUSIONS: This study demonstrated that HEEb does not present important toxic effects. Additionally, an important antinociceptive, anti-inflammatory, and antioxidant potential were observed.

Aerobic Exercise Attenuates Kidney Injury, Improves Physical Performance, and Increases Antioxidant Defenses in Lungs of Adenine-Induced Chronic Kidney Disease Mice.

The association between chronic kidney disease (CKD) and pulmonary pathophysiological changes is well stablished. Nevertheless, the effects of aerobic exercise (AE) on lungs of CKD need further clarification. Thus, Swiss mice were divided in control, AE, CKD, and CKD + AE groups. CKD was induced by 0.2% adenine intake during 8 weeks (4 weeks of CKD induction and 4 weeks of AE). AE consisted in running on treadmill, at moderate intensity, 30 min/day, 5 days/week, during 4 weeks. Twenty-four hours after the last training day, functional capacity test was performed, and 48 h after the test, mice were euthanized. CKD mice showed a significant increase in urine output, serum urea, and creatinine concentrations, and decreased body weight and urine density, besides oxidative damage (p = 0.044), edema area (p < 0.001), leukocyte infiltration (p = 0.040), and collagen area in lung tissue (p = 0.004). AE resulted in an increase of distance traveled (p = 0.049) and maximum speed (p = 0.046), increased activity of catalase (p = 0.031) and glutathione peroxidase (p = 0.048) in lungs, increased levels of nitric oxide (NOx) in serum (p = 0.001) and bronchoalveolar lavage fluid (p = 0.047), and decreased kidney histological injury (p = 0.018) of CKD mice. However, AE also increased oxidative damage (p = 0.003) and did not change collagen content or perivascular edema in lungs (p > 0.05) of CKD mice. Therefore, AE attenuated kidney injury and improved antioxidants defenses in lungs. Despite no significant changes in pulmonary damage, AE significantly improved physical performance in CKD mice.

Tradução e adaptação cultural para a língua portuguesa falada no Brasil da Canadian survey of mobilization of ICU patients / Traducción y adaptación cultural al portugués brasileño de Canadian survey of mobilization of ICU patients / Translation into Portuguese and cross-cultural adaptation for use in Brazil of the Canadian survey of mobilization of ICU patients

RESUMO Este estudo teve como objetivo traduzir e adaptar culturalmente o questionário Canadian survey of mobilization of intensive care unit patients para a língua portuguesa falada no Brasil. Este instrumento avalia profissionais de unidade de terapia intensiva (UTI) em relação aos conhecimentos sobre a mobilização precoce (MP) e sua importância, as percepções sobre barreiras e as práticas de reabilitação com o paciente crítico. O protocolo incluiu as etapas: autorização e cessão de direitos de uso; tradução do instrumento para a língua portuguesa; reconciliação; retrotradução para a língua original; revisão e harmonização da retrotradução; aprovação da autora principal do questionário original; revisão da versão em português; desdobramento cognitivo; e reconciliação e elaboração da versão final. Devido a algumas diferenças conceituais e culturais entre os dois países, algumas dúvidas foram discutidas com a autora principal do instrumento, a qual concordou com as alterações sugeridas. No desdobramento cognitivo, os 10 profissionais selecionados testaram a clareza, compreensão e aceitabilidade do questionário, e demonstraram suas dificuldades quanto ao conteúdo deste. Muitos entrevistados evidenciaram que o instrumento desperta reflexões importantes sobre as práticas diárias e os benefícios com a realização da MP. O questionário intitulado Pesquisa de mobilização de pacientes em unidade de terapia intensiva: conhecimento, perspectivas e práticas atuais encontra-se traduzido e adaptado culturalmente para a língua portuguesa falada no Brasil, podendo ser utilizado para avaliar aspectos da MP por profissionais que participam deste processo em UTIs adulto e pediátricas. Estudos futuros utilizando esta versão serão necessários para verificar se o questionário fornece medidas reprodutíveis e válidas.

RESUMEN Este estudio tuvo como objetivo traducir y adaptar culturalmente el cuestionario Canadian survey of mobilization of intensive care unit patients al portugués de Brasil. Este instrumento evalúa a los profesionales de la unidad de cuidados intensivos (UCI) en cuanto al conocimiento sobre la movilización temprana (MT) y su importancia, las percepciones sobre las barreras y las prácticas de rehabilitación con pacientes críticos. El protocolo incluyó las siguientes etapas: autorización y cesión de derechos de uso; traducción del instrumento al portugués brasileño; reconciliación; retrotraducción al idioma original; revisión y armonización de la retrotraducción; aprobación de la autora principal al cuestionario original; revisión de la versión al portugués; despliegue cognitivo; y reconciliación y preparación de la versión final. Debido a algunas diferencias conceptuales y culturales entre los dos países, se discutieron algunas dudas con la autora principal del instrumento, quien estuvo de acuerdo con los cambios sugeridos. En el despliegue cognitivo, los 10 profesionales seleccionados probaron la claridad, la comprensión y la aceptabilidad del cuestionario, y demostraron las dificultades de los contenidos. Numerosos entrevistados manifestaron que el instrumento suscita importantes reflexiones sobre las prácticas cotidianas y beneficios de llevar a cabo la MT. El cuestionario titulado Investigación en movilización de pacientes en unidades de cuidados intensivos: conocimientos, perspectivas y prácticas actuales está traducido y adaptado culturalmente al portugués de Brasil, y puede ser utilizado para evaluar aspectos de MT por parte de profesionales que participan en este proceso en UCI de adultos y pediátrica. Se necesitarán estudios futuros que utilicen esta versión para verificar que el cuestionario proporciona la reproducibilidad y la validez de las medidas.

ABSTRACT This study aimed to translate and culturally adapt the "Canadian survey of mobilization of intensive care unit patients" questionnaire to Brazilian Portuguese. This instrument evaluates intensive care unit (ICU) professionals' knowledge about early mobilization and its importance, their perceptions about barriers and rehabilitation practices with critically ill patients. The protocol includes the following steps: authorization and assignment of rights of use; translation of the instrument into Portuguese; reconciliation; back-translation to the original language; revision and harmonization of back-translation; approval from the main author of the original questionnaire; revision of the Portuguese version; cognitive debriefing; reconciliation; and preparation of the final version. Due to some conceptual and cultural differences between the two countries, some questions were discussed with the author of the original instrument, who agreed with the suggested alterations. During cognitive debriefing, the 10 selected professionals tested the questionnaire's clarity, understanding, and acceptability, indicating any difficulties they had regarding its content. Many interviewees reported that the instrument raises important reflections on daily practices and the benefits of early mobilization. The questionnaire entitled "Pesquisa de mobilização de pacientes em unidade de terapia intensiva: conhecimento, perspectivas e práticas atuais" was translated and culturally adapted to Brazilian Portuguese and can be used to evaluate aspects of early mobilization by professionals who participate in this process in adult and pediatric ICUs. Future studies using this version will be necessary to verify that the questionnaire provides reproducible and valid measurements.

Effects of physical exercise on lung inflammation in animal models of chronic allergic lung inflammation: a systematic review.

We performed a systematic review to identify and summarize the effects of distinctive aerobic exercise (AE) protocols on chronic allergic lung inflammation reported in asthma animal models. We identified 255 preclinical studies of asthma and AE protocols by comprehensive searches in PubMed, ScienceDirect and LILACS for peer-reviewed journals, using the search components "exercise," "lung inflammation," and "asthma," without restrictions on publication date. Twenty-two studies were selected that met all eligibility criteria. Most studies used an ovalbumin experimental model and performed experiments with BALB/c mice. Most studies performed treadmill AE, using protocols of 30 to 60 minutes, 3 to 5 times/week, for 4 to 8 weeks. The results showed that the effects of AE on lungs were protocol dependent, but generaly, there was a decrease in inflammatory cell influx and Th2 cytokines, as well as an increase in anti-inflammatory defenses. However, the immunoregulation of globulins and nitric oxide levels in asthma seemed to be associated with the onset of AE. The results suggest that AE plays an important immunoregulatory role in animal models of asthma, with effects mainly mediated by increased anti-inflammatory defenses and reduced Th2 response. In parallel, prophylactic and therapeutic AE also played important roles in decreasing bronchial responsiveness and attenuating lung remodeling in animal models of asthma, secondary outcomes in this systematic review. The review protocol was published for free access in October 2017 on the Systematic Review Facility (SyRF) platform (http://syrf.org.uk/protocols/).

Ventilação não invasiva na unidade de terapia intensiva de um hospital universitário: características relacionadas ao sucesso e insucesso / Ventilación no invasiva en la unidad de terapia intensiva de un hospital universitario: características relacionadas con el éxito y el fracaso / Non-invasive ventilation in a university hospital intensive care unit: aspects related to success and failure

RESUMO O objetivo deste estudo foi descrever características de sucesso e insucesso do uso da ventilação não invasiva (VNI) na unidade de terapia intensiva (UTI) de um hospital universitário. Trata-se de um estudo observacional prospectivo no qual foram incluídos 75 pacientes, com idade média de 58,3±18,8 anos. Desses, doze necessitaram do uso da VNI por mais de uma vez, totalizando 92 utilizações. Evidenciou-se que, delas, a taxa de sucesso foi de 60,9% (56). O grupo insucesso apresentou mais indivíduos do sexo masculino (p=0,006) e número maior de pacientes com diagnóstico de infecção extrapulmonar (p=0,012). Não foram encontradas diferenças entre os grupos de sucesso e insucesso nos quesitos de modo, modelo, máscara, tempo total de permanência e razões para a instalação da VNI. No grupo insucesso, a pressão positiva inspiratória nas vias aéreas (Ipap) e o volume corrente (VC) foram superiores (p=0,029 e p=0,011, respectivamente). A saturação periférica de oxigênio (p=0,047), o pH (p=0,004), base excess (p=0,006) e o bicarbonato (p=0,013) apresentaram valores inferiores. Concluiu-se que os indivíduos do sexo masculino com diagnóstico de infecção extrapulmonar e que evoluíram com acidose metabólica evoluíram com mais insucesso na utilização da VNI. Esses, necessitaram de parâmetros elevados de Ipap e VC.

RESUMEN El objetivo de este estudio fue desarrollar las características del éxito y del fracaso con el uso de la ventilación no invasiva (VNI) en la unidad de terapia intensiva (UTI) de un hospital universitario. Se trata de un estudio observacional prospectivo en el cual fueron incluidos 75 pacientes, con edad media de 58,3±18,8 años. De estos, 12 necesitaron utilizar la VNI por más de una vez, que totalizó 92 utilizaciones. Se evidenció que, de estas, el índice de éxito fue del 60,9% (56). El grupo que no obtuvo el éxito esperado presentó más individuos del sexo masculino (p=0,006) y número mayor de pacientes con diagnóstico de infecciones extrapulmonares (p=0,012). No fueron encontradas diferencias entre los grupos con éxito y sin éxito en las cuestiones de modo, modelo, máscara, tiempo total de permanencia y razones para la instalación de la VNI. En el grupo sin éxito, la presión positiva inspiratoria en las vías aéreas (Ipap) y el volumen corriente (VC) fueron superiores (p=0,029 y p=0,011, respectivamente). La saturación periférica de oxígeno (p=0,047), el pH(p=0,004), base excess (p=0,0006) y el bicarbonato (p=0,013) presentaron valores inferiores. De este modo, se concluye que los individuos del sexo masculino con diagnóstico de infecciones extrapulmonares y que progresaron con acidose metabólica avanzaron más sin tener éxito en la utilización de la VNI. Además, necesitaron de parámetros elevados de Ipap y VC.

ABSTRACT The objective of this study was to describe the aspects of success and failure of the use of non-invasive ventilation (NIV) in the intensive care unit (ICU) of a university hospital. This is a prospective observational study that included 75 patients, with 58.3±18.8 years as the mean age. Of these, 12 required the use of NIV more than once, for 92 uses in total. Among these, the success rate was 60.9% (56). The failure group had more males (p=0.006) and a higher number of patients diagnosed with extrapulmonary infection (p=0.012). No differences were found between success and failure groups for the variables mode, model, mask, total length of stay and reasons for NIV installation. In the failure group, inspiratory positive airways pressure (Ipap) and flow volume (FV) were higher (p=0.029 and p=0.011, respectively). Peripheral oxygen saturation (p=0.047), pH (p=0.004), base excess (p=0.006) and bicarbonate (p=0.013) presented lower values. This study concluded that male individuals diagnosed with extrapulmonary infection and whose picture evolved with metabolic acidosis evolved with more failure in NIV use. These patients required higher Ipap and FV parameters.

High-Intensity Exercise Prevents Disturbances in Lung Inflammatory Cytokines and Antioxidant Defenses Induced by Lipopolysaccharide.

In this study, we evaluated the effects of high-intensity swimming in an experimental model of acute lung injury (ALI) induced by lipopolysaccharide (LPS) on lung inflammation and antioxidant defenses. Balb/C male mice were submitted to exercise (30 min/day, 5 days/week, for a period of 3 weeks) prior to LPS instillation in the lung. Twenty-four hours after delivery of LPS (10 µg/animal), mice were euthanized and bronchoalveolar fluid (BALF) was obtained for cell counting and analysis of cytokines by ELISA. Lung tissue was used to evaluate antioxidant defenses. LPS instillation resulted in an increase in total and mononuclear cells, IL-1ß, TNF-α, and IL-6 in BALF. LPS instillation also altered IL-10 and IL-ra levels in BALF and induced antioxidant defenses (glutathione, superoxide dismutase, catalase, and glutathione peroxidase) in the lung. Protein carbonyl increased in the LPS-treated animals. High-intensity swimming prevented all these changes induced by LPS. Significance: Therefore, this experimental protocol of high-intensity swimming showed a protective effect on ALI, decreasing inflammatory processes and preventing disturbances in antioxidant defenses into the lungs.

Effects of High-Intensity Swimming on Lung Inflammation and Oxidative Stress in a Murine Model of DEP-Induced Injury.

Studies have reported that exposure to diesel exhaust particles (DEPs) induces lung inflammation and increases oxidative stress, and both effects are susceptible to changes via regular aerobic exercise in rehabilitation programs. However, the effects of exercise on lungs exposed to DEP after the cessation of exercise are not clear. Therefore, the aim of this study was to evaluate the effects of high-intensity swimming on lung inflammation and oxidative stress in mice exposed to DEP concomitantly and after exercise cessation. Male Swiss mice were divided into 4 groups: Control (n = 12), Swimming (30 min/day) (n = 8), DEP (3 mg/mL-10 µL/mouse) (n = 9) and DEP+Swimming (n = 8). The high-intensity swimming was characterized by an increase in blood lactate levels greater than 1 mmoL/L between 10th and 30th minutes of exercise. Twenty-four hours after the final exposure to DEP, the anesthetized mice were euthanized, and we counted the number of total and differential inflammatory cells in the bronchoalveolar fluid (BALF), measured the lung homogenate levels of IL-1ß, TNF-α, IL-6, INF-Ï«, IL-10, and IL-1ra using ELISA, and measured the levels of glutathione, non-protein thiols (GSH-t and NPSH) and the antioxidant enzymes catalase and glutathione peroxidase (GPx) in the lung. Swimming sessions decreased the number of total cells (p<0.001), neutrophils and lymphocytes (p<0.001; p<0.05) in the BALF, as well as lung levels of IL-1ß (p = 0.002), TNF-α (p = 0.003), IL-6 (p = 0.0001) and IFN-Ï« (p = 0.0001). However, the levels of IL-10 (p = 0.01) and IL-1ra (p = 0.0002) increased in the swimming groups compared with the control groups, as did the CAT lung levels (p = 0.0001). Simultaneously, swimming resulted in an increase in the GSH-t and NPSH lung levels in the DEP group (p = 0.0001 and p<0.002). We concluded that in this experimental model, the high-intensity swimming sessions decreased the lung inflammation and oxidative stress status during DEP-induced lung inflammation in mice.