OBJECTIVES: The aim of this study was to evaluate systemic inflammatory factors and their relation to success or failure in a spontaneous ventilation test. METHODS: This cross-sectional study included a sample of 54 adult patients. Demographic data and clinical parameters were collected, and blood samples were collected in the first minute of the spontaneous ventilation test to evaluate interleukin (IL)-1β, IL-6, IL-8, and IL-10, tumour necrosis factor alpha (TNFα) and C-reactive protein. RESULTS: Patients who experienced extubation failure presented a lower rapid shallow breathing index than those who passed, and these patients also showed a significant increase in C-reactive protein 48 hours after extubation. We observed, moreover, that each unit increase in inflammatory factors led to a higher risk of spontaneous ventilation test failure, with a risk of 2.27 (1.001 - 4.60, p=0.049) for TNFα, 2.23 (1.06 - 6.54, p=0.037) for IL-6, 2.66 (1.06 - 6.70, p=0.037) for IL-8 and 2.08 (1.01 - 4.31, p=0.04) for IL-10, and the rapid shallow breathing index was correlated with IL-1 (r=-0.51, p=0.04). CONCLUSIONS: C-reactive protein is increased in patients who fail the spontaneous ventilation test, and increased ILs are associated with a greater prevalence of failure in this process; the rapid shallow breathing index may not be effective in patients who present systemic inflammation.

Objetivo: Investigar o efeito da hipóxia intermitente com um modelo de apneia obstrutiva do sono (AOS) sobre a expressão de uncoupling protein-2 (UCP2), assim como sobre perfis glicêmicos e lipídicos, em camundongos C57BL. Métodos: Camundongos C57BL machos foram expostos a hipóxia intermitente ou hipóxia simulada (grupo controle) 8 h/dia durante 35 dias. A condição de hipóxia intermitente envolveu a exposição dos camundongos a uma atmosfera de 92% de N e 8% de CO2 por 30 s, com redução progressiva de fração de O2 inspirado até 8 ± 1%, seguida por exposição a ar ambiente por 30 s e repetições do ciclo (480 ciclos no período experimental de 8 h). Os pâncreas foram dissecados para isolar as ilhotas. Foi realizada PCR em tempo real utilizando o método TaqMan. Resultados: A expressão do mRNA da UCP2 nas ilhotas pancreáticas foi 20% maior no grupo controle que no grupo hipóxia (p = 0,11). A insulina sérica de jejum foi maior no grupo hipóxia do que no grupo controle (p = 0,01). O modelo de avaliação da homeostase de resistência à insulina indicou que, em comparação com os camundongos controle, aqueles expostos à hipóxia intermitente apresentaram 15% menor resistência à insulina (p = 0,09) e 21% maior função das células beta (p = 0,01). A coloração das ilhotas pancreáticas por imuno-histoquímica não mostrou diferenças significativas entre os grupos em termos da área ou da intensidade das células alfa e beta, marcadas por insulina e glucagon. Conclusões: Segundo nosso conhecimento, esta é a primeira descrição do efeito da hipóxia intermitente sobre a expressão da UCP2. Nossos achados sugerem que UCP2 regula a produção de insulina na AOS. Futuras investigações sobre o papel da UCP2 no controle glicêmico em pacientes com AOS são justificadas.

Objective: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA)-on pancreatic expression of uncoupling protein-2 (UCP2), as well as on glycemic and lipid profiles, in C57BL mice. Methods: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group) or to a sham procedure (normoxia group). The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period). Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. Results: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11). Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01). The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09) and 21% higher pancreatic β-cell function (p = 0.01). Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and β-cell staining for insulin and glucagon. Conclusions: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted.

OBJECTIVE: Most lung transplants are obtained from brain-dead donors. The physiopathology of brain death involves hemodynamics, the sympathetic nervous system, and inflammatory mechanisms. Administering methylprednisolone 60 min after inducing brain death in rats has been shown to modulate pulmonary inflammatory activity. Our objective was to evaluate the effects of methylprednisolone on transplanted rat lungs from donors treated 60 min after brain death. METHODS: Twelve Wistar rats were anesthetized, and brain death was induced. They were randomly divided into two groups (n = 6), namely a control group, which was administered saline solution, and a methylprednisolone group, which received the drug 60 min after the induction of brain death. All of the animals were observed and ventilated for 2 h prior to being submitted to lung transplantation. We evaluated the hemodynamic and blood gas parameters, histological score, lung tissue levels of thiobarbituric acid-reactive substances, level of superoxide dismutase, level of tumor necrosis factor-alpha, and level of interleukin-1 beta. RESULTS: After transplantation, a significant reduction in the levels of tumor necrosis factor-alpha and IL-1β was observed in the group that received methylprednisolone (p = 0.0084 and p = 0.0155, respectively). There were no significant differences in tumor necrosis factor-alpha and superoxide dismutase levels between the control and methylprednisolone groups (p = 0.2644 and p = 0.7461, respectively). There were no significant differences in the blood gas parameters, hemodynamics, and histological alterations between the groups. CONCLUSION: The administration of methylprednisolone after brain death in donor rats reduces inflammatory activity in transplanted lungs but has no influence on parameters related to oxidative stress.

OBJETIVO: Avaliar os efeitos da administração sistêmica precoce e tardia de metilprednisolona nos pulmões em um modelo de morte encefálica em ratos. MÉTODOS: Vinte e quatro ratos Wistar machos foram anestesiados e randomizados em quatro grupos (n = 6 por grupo): sham, somente morte encefálica (ME), metilprednisolona i.v. (30 mg/kg) administrada 5 min após a morte encefálica (MP5) e 60 min após a morte encefálica (MP60). Os grupos ME, MP5 e MP60 foram submetidos à morte encefálica por insuflação de um balão no espaço extradural. Todos os animais foram observados e ventilados durante 120 min. Foram determinadas variáveis hemodinâmicas e gasométricas, relação peso úmido/seco, escore histológico, thiobarbituric acid reactive substances (TBARS, substâncias reativas ao ácido tiobarbitúrico), atividade de superóxido dismutase (SOD) e de catalase, assim como contagem diferencial de células brancas, proteína total e nível de desidrogenase lática no LBA. A atividade da mieloperoxidase, peroxidação lipídica e níveis de TNF-α foram avaliados no tecido pulmonar. RESULTADOS: Não foram observadas diferenças significativas nas variáveis hemodinâmicas e gasométricas, relação peso úmido/seco, análises do LBA, escore histológico, SOD, mieloperoxidase e catalase entre os grupos. Os níveis de TBARS foram significativamente maiores nos grupos MP5 e MP60 do que nos grupos sham e ME (p < 0,001). Os níveis de TNF-α foram significativamente menores nos grupos MP5 e MP60 do que no grupo ME (p < 0,001). CONCLUSÕES: Neste modelo de morte cerebral, a administração precoce e tardia de metilprednisolona apresentou efeitos semelhantes sobre a inflamação e a peroxidação lipídica no tecido pulmonar.

OBJECTIVE: To evaluate the effects that early and late systemic administration of methylprednisolone have on lungs in a rat model of brain death. METHODS: Twenty-four male Wistar rats were anesthetized and randomly divided into four groups (n = 6 per group): sham-operated (sham); brain death only (BD); brain death plus methylprednisolone (30 mg/kg i.v.) after 5 min (MP5); and brain death plus methylprednisolone (30 mg/kg i.v.) after 60 min (MP60). In the BD, MP5, and MP60 group rats, we induced brain death by inflating a balloon catheter in the extradural space. All of the animals were observed and ventilated for 120 min. We determined hemodynamic and arterial blood gas variables; wet/dry weight ratio; histological score; levels of thiobarbituric acid reactive substances (TBARS); superoxide dismutase (SOD) activity; and catalase activity. In BAL fluid, we determined differential white cell counts, total protein, and lactate dehydrogenase levels. Myeloperoxidase activity, lipid peroxidation, and TNF-α levels were assessed in lung tissue. RESULTS: No significant differences were found among the groups in terms of hemodynamics, arterial blood gases, wet/dry weight ratio, BAL fluid analysis, or histological score-nor in terms of SOD, myeloperoxidase, and catalase activity. The levels of TBARS were significantly higher in the MP5 and MP60 groups than in the sham and BD groups (p < 0.001). The levels of TNF-α were significantly lower in the MP5 and MP60 groups than in the BD group (p < 0.001). CONCLUSIONS: In this model of brain death, the early and late administration of methylprednisolone had similar effects on inflammatory activity and lipid peroxidation in lung tissue.

CONTEXTO: A esteatohepatite não-alcoólica é uma doença com alta incidência, difícil diagnóstico e tratamentos ainda não efetivos. Com isso, o uso de modelos experimentais para indução da esteatohepatite não-alcoólica e o estudo das rotas de desenvolvimento desta doença vem sendo empregado. OBJETIVO: Desenvolver um modelo experimental de esteatohepatite não-alcoólica a partir do uso de uma dieta deficiente de metionina e colina fabricada no Brasil e avaliar as alterações hepáticas decorrentes da doença. MÉTODO: Foram utilizados 30 camundongos machos da linhagem C57BL6, onde a metade foi alimentada com dieta deficiente em metionina e colina desenvolvida no Brasil e o restante com dieta controle no período de duas semanas. Após, os animais foram mortos por exaguinação e foi realizada laparotomia com hepatectomia total e preparo do material para análise histológica, coleta de sangue para análises bioquímicas sistêmicas. O nível de significância foi 5%. RESULTADOS: Os ratos que receberam a dieta deficiente em metionina e colina apresentaram perda de peso e aumento significativo das enzimas de integridade hepática e diminuição dos níveis bioquímicos sistêmicos de glicemia, triglicerídeos, colesterol total, HDL e VLDL. Todos os animais com esteatohepatite não-alcoólica mostraram, pelo menos, algum grau de esteatose macrovesicular. O diagnóstico de esteatohepatite não-alcoólica foi realizado em 100% dos camundongos que receberam a dieta deficiente em metionina e colina e nenhum dos animais que recebeu dieta controle apresentou alterações histológicas. Os animais com esteatohepatite não-alcoólica apresentaram aumento de lipoperoxidação e da enzima antioxidante GSH. CONCLUSÃO:A dieta deficiente de metionina e colina desenvolvida neste estudo apresenta índices elevados de indução de esteatose e esteatohepatite em modelo animal, apresentando comportamento patológico semelhante ao humano, com custo adequado e facilidade na sua aquisição.

CONTEXT: Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied. OBJECTIVES: This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder. METHODS: Thirty male C57BL6 mice divided in two groups (n = 15) were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5%. RESULTS: The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100% of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity. CONCLUSION: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in inducing steatosis and steatohepatitis in animal model, alterations that are similar to those observed in human livers.

Avaliamos o efeito da aminoguanidina sobre o estresse oxidativo pulmonar e a estrutura pulmonar em um modelo experimental de diabetes mellitus. Foram determinados thiobarbituric acid reactive substances (TBARS, substâncias reativas ao ácido tiobarbitúrico), histologia e gasometria arterial em animais com diabetes mellitus (DM), animais com diabetes mellitus tratados com aminoguanidina (DM+AG) e controles. O nível de TBARS foi significativamente maior no grupo DM que nos grupos controle e DM+AG (2,90 ± 1,12 vs. 1,62 ± 0,28 e 1,68 ± 0,04 nmol/mg proteína, respectivamente), o mesmo ocorrendo com PaCO2 em relação ao grupo controle (49,2 ± 1,65 vs. 38,12 ± 4,85 mmHg), e PaO2 foi significativamente maior no grupo controle (104,5 ± 6,3 vs. 69,48 ±16,30 e 97,05 ± 14,02 mmHg, respectivamente). Neste modelo experimental de diabetes mellitus, a aminoguanidina reduziu o estresse oxidativo, alterações estruturais teciduais pulmonares e a troca gasosa no modelo experimental.

We evaluated the effect of aminoguanidine on pulmonary oxidative stress and lung structure in an experimental model of diabetes mellitus. Thiobarbituric acid reactive substances (TBARS), histology and arterial blood gases were evaluated in animals with diabetes mellitus (DM group), animals with diabetes mellitus treated with aminoguanidine (DM+AG group), and controls. The TBARS levels were significantly higher in the DM group than in the control and DM+AG groups (2.90 ± 1.12 vs. 1.62 ± 0.28 and 1.68 ± 0.04 nmol/mg protein, respectively), as was PaCO2 when compared with that of the control group (49.2 ± 1.65 vs. 38.12 ± 4.85 mmHg), and PaO2 was significantly higher in the control group (104.5 ± 6.3 vs. 16.30 ± 69.48 and 97.05±14.02 mmHg, respectively). In this experimental model of diabetes mellitus, aminoguanidine reduced oxidative stress, structural tissue alterations, and gas exchange.