Effects of propofol on inflammatory response and activation of p38 MAPK signaling pathway in rats with ventilator-induced lung injury

ABSTRACT Purpose: To investigate the effects of propofol on inflammatory response and activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with ventilator-associated lung injury (VALI). Methods: Thirty-six Sprague Dawley (SD) rats were divided into control, VALI and VALI+propofol groups. The VALI group received the mechanical ventilation for 2 h. The VALI+propofol group received the mechanical ventilation for 2 h, which was accompanied by intravenous injection of propofol with dose of 8 mg·kg-1·h-1. At the end, the mean arterial pressure (MAP) and blood gas indexes were measured, and the lung wet/dry mass ratio (W/D) and biochemical indexes of lung tissue and bronchoalveolar lavage fluid (BALF) were determined. Results: Compared with VALI group, in VALI+propofol group the blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and MAP were increased, the lung W/D, lung tissue myeloperoxidase activity and total protein concentration, white blood cell count, and tumor necrosis factor α, interleukin 1β and interleukin 6 levels in BALF were decreased, and the p-p38 MAPK protein expression level and phosphorylated p38 MAPK (p-p38 MAPK)/p38 MAPK ratio were decreased. Conclusions: Propofol treatment may alleviate the VALI in rats by reducing the inflammatory response and inhibiting the activation of p38 MAPK signaling pathway.

Imágenes diagnósticas en el estudio del compromiso pulmonar de la discinesia ciliar primaria en niños / Chest imaging in study of primary ciliary dyskinesia in children

The diagnosis of primary ciliary dyskinesia (PCD) is complex and requires high clinical suspicion. The findings in the diagnostic images are nonspecific and can be seen in other conditions of the airway. In this review, we will describe the findings of PCD in chest radiography and computed tomography, with emphasis on some of the characteristics that differentiate it from cystic fibrosis and we will review the role of CT in the monitoring of changes of the PCD, since the CT findings correlate very well with the structural changes that occur in the course of PCD, especially bronchiectasis. However, using serial CTs should be decided on a case-by-case basis to avoid unnecessary radiation because they are pediatric patients.

El diagnóstico de la Discinesia ciliar primaria (DCP) es complejo y requiere alta sospecha clínica. Los hallazgos en la imágenes diagnósticas son inespecíficos y se pueden ver en otras afecciones de la vía aérea. En esta revisión describiremos los hallazgos de la DCP en Radiología simple y en Tomografía computada (TC), con énfasis en algunas de las características que permiten diferenciarla de la Fibrosis quística (FQ) y revisaremos el rol de la TC en la monitorización de la DCP ya que los hallazgos en la TC se correlacionan muy bien con los cambios estructurales que ocurren en el curso de la DCP, en especial las bronquiectasias. Sin embargo usar TC seriadas se debe decidir caso por caso para evitar la radiación innecesaria por ser pacientes pediátricos.

Oferta de oxigênio, remoção de dióxido de carbono, transferência de energia aos pulmões e comportamento da hipertensão pulmonar durante o suporte com oxigenação por membrana extracorpórea: um modelo matemático / Oxygen delivery, carbon dioxide removal, energy transfer to lungs and pulmonary hypertension behavior during venous-venous extracorporeal membrane oxygenation support: a mathematical modeling approach

RESUMO Objetivo: Descrever a transferência de energia do ventilador mecânico para os pulmões; o acoplamento entre a transferência de oxigênio por oxigenação por membrana extracorpórea venovenosa (ECMO-VV) e o consumo de oxigênio do paciente; a remoção de dióxido de carbono com ECMO; e o efeito potencial da oxigenação venosa sistêmica na pressão arterial pulmonar. Métodos: Modelo matemático com cenários hipotéticos e utilização de simulações matemáticas por computador. Resultados: A transição de ventilação protetora para ventilação ultraprotetora em um paciente com síndrome da angústia respiratória aguda grave e complacência respiratória estática de 20mL/cmH2O reduziu a transferência de energia do ventilador para os pulmões de 35,3 para 2,6 joules por minuto. Em um paciente hipotético, hiperdinâmico e ligeiramente anêmico com consumo de oxigênio de 200mL/minuto, é possível atingir saturação arterial de oxigênio de 80%, ao mesmo tempo em que se mantém o equilíbrio entre a transferência de oxigênio pela ECMO e o consumo de oxigênio do paciente. O dióxido de carbono é facilmente removido e a pressão parcial de dióxido de carbono normal é facilmente obtida. A oxigenação do sangue venoso, por meio do circuito da ECMO, pode direcionar o estímulo da pressão parcial de oxigênio na vasoconstrição pulmonar por hipóxia para valores normais. Conclusão: A ventilação ultraprotetora reduz amplamente a transferência de energia do ventilador para os pulmões. A hipoxemia grave no suporte com ECMO-VV pode ocorrer, a despeito do acoplamento entre a transferência de oxigênio, por meio da ECMO, e o consumo de oxigênio do paciente. A faixa normal de pressão parcial de dióxido de carbono é fácil de atingir. O suporte com ECMO-VV potencialmente alivia a vasoconstrição pulmonar hipóxica.

ABSTRACT Objective: To describe (1) the energy transfer from the ventilator to the lungs, (2) the match between venous-venous extracorporeal membrane oxygenation (ECMO) oxygen transfer and patient oxygen consumption (VO2), (3) carbon dioxide removal with ECMO, and (4) the potential effect of systemic venous oxygenation on pulmonary artery pressure. Methods: Mathematical modeling approach with hypothetical scenarios using computer simulation. Results: The transition from protective ventilation to ultraprotective ventilation in a patient with severe acute respiratory distress syndrome and a static respiratory compliance of 20mL/cm H2O reduced the energy transfer from the ventilator to the lungs from 35.3 to 2.6 joules/minute. A hypothetical patient, hyperdynamic and slightly anemic with VO2 = 200mL/minute, can reach an arterial oxygen saturation of 80%, while maintaining the match between the oxygen transfer by ECMO and the VO2 of the patient. Carbon dioxide is easily removed, and normal PaCO2 is easily reached. Venous blood oxygenation through the ECMO circuit may drive the PO2 stimulus of pulmonary hypoxic vasoconstriction to normal values. Conclusion: Ultraprotective ventilation largely reduces the energy transfer from the ventilator to the lungs. Severe hypoxemia on venous-venous-ECMO support may occur despite the matching between the oxygen transfer by ECMO and the VO2 of the patient. The normal range of PaCO2 is easy to reach. Venous-venous-ECMO support potentially relieves hypoxic pulmonary vasoconstriction.

Asma: uso adecuado de dispositivos para inhalación / Asthma: correct use of inhalation drug-delivery devices

Resumen La terapia inhalada se considera la piedra angular del manejo del asma. Sin embargo, a pesar de ser la forma ideal de administración de estos medicamentos, solamente el 70% de los pacientes cumple el tratamiento adecuadamente y sólo del 39 al 67% de los médicos conocen y pueden explicar de forma adecuada las distintas técnicas de inhalación. La terapia inhalada tiene características muy particulares. El depósito pulmonar de un medicamento inhalado a través del tracto respiratorio es más complejo que cuando se administra por vía oral, y varía dependiendo de varios factores, tanto inherentes al medicamento como a la forma de administrarlo. Para que la terapia inhalada sea exitosa, se requiere que se generen partículas del medicamento de un tamaño apropiado que penetren más allá de la orofaringe y la laringe, y que puedan depositarse en los pulmones. Existen múltiples dispositivos para la administración de medicamentos en la vía respiratoria baja. Cada uno ha probado tener una eficacia similar, siempre y cuando se utilicen con la técnica correcta. La decisión para su uso se realiza con base en la edad del paciente, la capacidad de coordinar entre la inhalación y la activación del dispositivo y la presencia de síntomas agudos. La elección del dispositivo a utilizar siempre deberá hacerse de forma conjunta, evaluando pros y contras de cada uno de los dispositivos y siempre de forma individualizada.

Abstract Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.

Videothermometry to evaluate metabolic activity in real time during pneumectomy in rats

Abstract Purpose: To evaluate, in rats, the open field videothermometry in real time while performing left pneumonectomy for early diagnosis of cardiopulmonary changes. Methods: Twelve non-specific pathogen-free Wistar rats were randomly allocated into two groups; pneumectomy group (GP) and sham surgery group (GS). Mean arterial pressure, videothermometry in real time, of the right lung, and histopathological analysis of the remaining lung were evaluated in all animals. Results: Videothermometry in real time allowed identification of temperature variance of right lung after pneumectomy, indicating a significant decrease in temperature during evaluation. There was a statistical difference between M0 and M1, M1 and M2 and M0 and M2 (p<0.004) in GS, and significant difference between M0 and M1, M1 and M2, and M2 and M0 with p<0.0001 in GP. Conclusions: Left pneumonectomy in rats shows initial histopathological changes after 60 minutes of its completion, indicating a possible compensation beginning. The open-field videothermometry in real time proved to be efficient identifying the temperature changes of the remaining lung.

Protein from Hevea brasiliensis "Hev b 13" latex attenuates systemic inflammatory response and lung lesions in rats with sepsis / Proteína do latex de Hevea brasiliensis "Hev b 13" atenua resposta inflamatória sistêmica e lesão pulmonar de ratos com sepse

Abstract Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.

Resumo Sepse induz uma resposta inflamatória sistêmica grave podendo resultar em disfunção de múltiplos órgãos e morte. Pesquisas utilizando uma proteína derivada do látex natural de Hevea brasiliensis (seringueira), denominada Hev b 13 tem demonstrado importantes efeitos anti-inflamatórios, mas nenhum dado foi publicado dos seus efeitos na sepse. O objetivo deste estudo foi investigar os efeitos da Hev b 13 na resposta inflamatória e na lesão pulmonar de ratos com sepse. Ratos machos da linhagem Wistar foram submetidos a ligação e perfuração do ceco (LPC), randomizados em grupos e tratados com as doses 0,5/2,0/3,0 mg/Kg de Hev b 13 subcutâneo. Após subdividiu-se os animais em três pontos diferentes de tempo (1, 6 e 24 horas após os tratamentos) para coleta de amostras sanguíneas e eutanásia com remoção dos órgãos. Contagem total e diferencial de leucócitos, dosagem de citocinas e avaliação histológica foram analisadas. O tratamento com a Hev b 13 resultou em diminuição significativa de leucócitos totais e diferenciais bem como suprimiu a produção de TNF-α e IL-6, associado ao aumento de IL-10 e IL-4 no plasma e tecido pulmonar. Além disso, reduziu as alterações morfológicas e patológicas encontradas nos pulmões, incluindo infiltrado de neutrófilos, edema e espessamento alveolar. Este estudo concluiu que a Hev b 13 tem efeitos anti-inflamatórios e atenua lesões pulmonares em ratos com sepse, apresentando potencialidades para aplicabilidade clínica.

Effect of hyperbaric oxygenation on the expression of glutathione peroxidase 4 and lactoperoxidase genes in the lung of isogenic mice after ischemia/reperfusion injury in the small bowel

Abstract Purpose: To evaluate the effect of hyperbaric oxygenation (HBO) on the expression of the genes antioxidant glutathione peroxidase 4 (Gpx4) and lactoperoxidase (Lpo) in the lung of mice subjected to intestinal ischemia and reperfusion (IIR). Methods: Control group (CG) in which were subjected to anesthesia, laparotomy and observation for 120 minutes; an ischemia and reperfusion group (IRG) subjected to anesthesia, laparotomy, small bowel ischemia for 60 minutes and reperfusion for 60 minutes; and three groups treated with HBO during ischemia (HBOG + I), during reperfusion (HBOG + R) and during ischemia and reperfusion (HBOG + IR). Studied 84 genes of oxidative stress by the method (RT-qPCR). Genes with expression levels three times below or above the threshold cycle were considered significantly hypoexpressed or hyperexpressed, respectively (Student's t-test p<0.05). Results: Gpx4 and Lpo were hiperexpressed on IRG, showing a correlation with these genes with lung oxidative stress. Treated with HBO, there was a significant reduction on genic expression on HBOG+I. Conclusion: Hyperbaric oxygenation showed to be associated with decreased expression of these antioxidant genes, suggesting a beneficial effect on the mechanism of pulmonary oxidative stress whenever applied during the ischemia.

Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats

Abstract Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28thand 35thdays of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p<0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p<0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.

Pulmonary oxidative stress in diabetic rats exposed to hyperoxia

Abstract Purpose: To evaluate the pulmonary oxidative stress in diabetic rats exposed to hyperoxia for 90 minutes. Methods: Forty male Wistar rats were divided into four groups, each one containing 10 animals, according to the oxygen concentration to which they were exposed: 21%, 50%, 75% and 100% (hyperoxia). In each group five animals were randomly induced to diabetes by means of at a dose of 55 mg/kg of streptozotocin (STZ). Results: Seventy two hours after diabetes induction, a significant difference was seen in blood glucose in the experimental groups in comparison with the control. In the experimental groups a significant difference was observed in the concentration of malondialdehyde (MDA) in lung tissue and blood plasma (p<0.05), except the 50% group. In the control group, significant differences in the MDA concentration in plasma and lung tissue were also observed (p<0.05), except the 75% group. The MDA concentration in lung tissue in comparison with the diabetic and non-diabetic groups showed a significant difference in the 21% group; however, no difference was seen in the 75 and 100% groups. Conclusion: In diabetic animals high oxygen concentrations (75 and 100%) do not appear to exert deleterious effects on lipid peroxidation in lung tissue.

Expression dynamics of caveolin-1 in fibroblasts of newborn rats with chronic lung disease and its impact on lung fibroblast proliferation

Abstract Purpose: To evaluate the changes of caveolin-1 in lung fibroblasts in newborn Wistar rats when exposed to hyperoxic conditions, as well as lung fibroblasts cell cycle. Methods: One hundred newborn Wistar rats were randomly divided (50 rats/group) into experimental and control groups, exposed to hyperoxic conditions or normal air, respectively. The fraction of inspired oxygen (FiO2) in the experimental group was 90%, whereas this value was 21% in the control group. Lung fibroblasts were collected on days 3, 7, and 14 of the experiment. Caveolin-1 expression dynamics in lung fibroblasts was assayed in each group by immunofluorescence and Western blot analyses. Flow cytometry (FCM) was used to assess the proportions of lung fibroblasts at different stages of the cell cycle. Results: On day 3, no significant difference in caveolin-1 expression was observed between the hyperoxic and control groups; however, on days 7 and 14, caveolin-1 expression was significantly lower in the hyperoxic group than in the control (P<0.05). No apparent differences were observed in caveolin-1 expression in the control group at the different time points. Using FCM analysis, we showed that the proportion of lung fibroblasts in G0/G1 phase in the hyperoxic group decreased compared to that of the control group on day 7, while the proportion of S-phase cells increased (P<0.05). These differences were more significant when the groups were compared on day 14 (P<0.01). Conclusion: After seven days the exposure to hyperoxic conditions, lung fibroblasts proliferated and caveolin-1 expression decreased.

microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells

microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.

Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals / Efeitos da pressão expiratória positiva na depuração pulmonar do ácido dietilenotriaminopentacético marcado com tecnécio-99m em aerossol em indivíduos saudáveis

ABSTRACT Objective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects.

RESUMO Objetivo: Avaliar os efeitos da pressão expiratória positiva (PEP) na permeabilidade da membrana epitelial pulmonar em indivíduos saudáveis. Métodos: Foi avaliada uma coorte de 30 indivíduos saudáveis (15 homens e 15 mulheres), com média de idade de 28,3 ± 5,4 anos, média da relação VEF1/CVF de 0,89 ± 0,14 e média de VEF1 de 98,5 ± 13,1% do previsto. Os indivíduos foram submetidos a cintilografia pulmonar por inalação de radioaerossol de ácido dietilenotriaminopentacético marcado com tecnécio-99m (99mTc-DTPA em inglês) em dois estágios: durante respiração espontânea e durante respiração com uma máscara de PEP de 10 cmH2O (n = 10), 15 cmH2O (n = 10) ou 20 cmH2O (n = 10). O 99mTc-DTPA foi nebulizado por 3 min, e sua depuração foi registrada por cintilografia por um período de 30 min durante respiração espontânea e por um período de 30 min durante a respiração com uma máscara de PEP. Resultados: A depuração pulmonar do 99mTc-DTPA foi significativamente menor quando PEP foi aplicada a 10 cmH2O (p = 0,044), 15 cmH2O (p = 0,044) e 20 cmH2O (p = 0,004), em comparação com a observada durante a respiração espontânea. Conclusões: Nossos achados indicam que o uso de PEP nos níveis testados pode induzir um aumento na permeabilidade da membrana epitelial pulmonar e no volume pulmonar em indivíduos saudáveis.

Repercussões da hiperinsuflação manual em recém-nascidos pré-termo sob ventilação mecânica / Effects of manual hyperinflation in preterm newborns under mechanical ventilation

RESUMO Objetivo: Avaliar as repercussões da hiperinsuflação manual, realizada com ressuscitador manual com e sem válvula de pressão positiva expiratória final, sobre a função respiratória de recém-nascidos pré-termo em ventilação mecânica. Métodos: Estudo transversal com recém-nascidos pré-termo com idade gestacional inferior a 32 semanas, em ventilação mecânica e dependentes desta aos 28 dias de vida, estáveis hemodinamicamente. A hiperinsuflação manual foi aplicada de forma randomizada, alternando o uso ou não uso da válvula de pressão positiva expiratória final, seguida de aspiração intratraqueal finalizando a manobra. Para os dados nominais, foi aplicado o teste de Wilcoxon com hipótese bilateral ao nível de significância de 5% e poder de teste de 80%. Resultados: Foram estudados 28 recém-nascidos pré-termo com peso médio de nascimento 1.005,71 ± 372.16g, idade gestacional média 28,90 ± 1,79 semanas, idade corrigida média de 33,26 ± 1,78 semanas, tempo médio de ventilação mecânica de 29,5 (15 - 53) dias. Ocorreu aumento dos volumes inspiratório e expiratório entre os momentos A5 (antes da manobra) e C1 (imediatamente após aspiração intratraqueal) tanto na manobra com válvula (p = 0,001 e p = 0,009) como sem válvula (p = 0,026 e p = 0,001), respectivamente. Também houve aumento da resistência expiratória entre os momentos A5 e C1 com p = 0,044. Conclusão: Os volumes pulmonares aumentaram na manobra com e sem válvula, havendo diferença significativa no primeiro minuto após a aspiração. Houve diferença significativa na resistência expiratória entre os momentos A5 (antes da manobra) e C1 (imediatamente após aspiração intratraqueal) no primeiro minuto após a aspiração dentro de cada manobra.

ABSTRACT Objective: To assess the effects of manual hyperinflation, performed with a manual resuscitator with and without the positive end-expiratory pressure valve, on the respiratory function of preterm newborns under mechanical ventilation. Methods: Cross-sectional study of hemodynamically stable preterm newborns with gestational age of less than 32 weeks, under mechanical ventilation and dependent on it at 28 days of life. Manual hyperinflation was applied randomly, alternating the use or not of the positive end-expiratory pressure valve, followed by tracheal aspiration for ending the maneuver. For nominal data, the two-tailed Wilcoxon test was applied at the 5% significance level and 80% power. Results: Twenty-eight preterm newborns, with an average birth weight of 1,005.71 ± 372.16g, an average gestational age of 28.90 ± 1.79 weeks, an average corrected age of 33.26 ± 1.78 weeks, and an average mechanical ventilation time of 29.5 (15 - 53) days, were studied. Increases in inspiratory and expiratory volumes occurred between time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in both the maneuver with the valve (p = 0.001 and p = 0.009) and without the valve (p = 0.026 and p = 0.001), respectively. There was also an increase in expiratory resistance between time-points A5 and C1 (p = 0.044). Conclusion: Lung volumes increased when performing the maneuver with and without the valve, with a significant difference in the first minute after aspiration. There was a significant difference in expiratory resistance between the time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in the first minute after aspiration within each maneuver.

Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats

ABSTRACT PURPOSE: To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injury METHODS: Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels. RESULTS: Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups. CONCLUSION: The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury.

Hiperinsuflação pulmonar com ventilador mecânico versus aspiração traqueal isolada na higiene brônquica de pacientes submetidos à ventilação mecânica / Lung hyperinflation by mechanical ventilation versus isolated tracheal aspiration in the bronchial hygiene of patients undergoing mechanical ventilation

RESUMO Objetivo: Determinar a eficácia da manobra de hiperinsuflação pulmonar com o ventilador mecânico, em comparação à aspiração traqueal isolada, para remover secreções, normalizar a hemodinâmica e melhorar a mecânica pulmonar em pacientes em ventilação mecânica. Métodos: Ensaio clínico randomizado cruzado incluindo pacientes em ventilação mecânica por mais de 48 horas internados na unidade de terapia intensiva. Os pacientes foram randomizados para receber a aspiração traqueal isolada (Grupo Controle) e hiperinsuflação pulmonar por meio do ventilador mecânico (Grupo HVM). Mensuraram-se parâmetros hemodinâmicos e de mecânica respiratória, assim como a quantidade de secreção aspirada. Resultados: Foram incluídos 50 pacientes. A média de idade dos pacientes foi de 44,7 ± 21,6 anos, sendo 31 do sexo masculino. O Grupo HVM apresentou maior quantidade de secreção aspirada (3,9g versus 6,4g; p = 0,0001), variação na média da complacência dinâmica (-1,3 ± 2,3 versus -2,9 ± 2,3; p = 0,008), volume corrente expirado (-0,7 ± 0,0 versus -54,1 ± 38,8; p = 0,0001) e diminuição significativa da pressão inspiratória de pico (0,2 ± 0,1 versus 2,5 ± 0,1; p = 0,001), em comparação com o Grupo Controle. Conclusão: Na amostra estudada, a técnica de HVM apresentou maior quantidade de secreção aspirada, aumento significativo da complacência dinâmica e volume corrente expirado, além de diminuição significativa da pressão de pico inspiratória.

ABSTRACT Objective: To determine the efficacy of lung hyperinflation maneuvers via a mechanical ventilator compared to isolated tracheal aspiration for removing secretions, normalizing hemodynamics and improving lung mechanics in patients on mechanical ventilation. Methods: This was a randomized crossover clinical trial including patients admitted to the intensive care unit and on mechanical ventilation for more than 48 hours. Patients were randomized to receive either isolated tracheal aspiration (Control Group) or lung hyperinflation by mechanical ventilator (MVH Group). Hemodynamic and mechanical respiratory parameters were measured along with the amount of aspirated secretions. Results: A total of 50 patients were included. The mean age of the patients was 44.7 ± 21.6 years, and 31 were male. Compared to the Control Group, the MVH Group showed greater aspirated secretion amount (3.9g versus 6.4g, p = 0.0001), variation in mean dynamic compliance (-1.3 ± 2.3 versus -2.9 ± 2.3; p = 0.008), and expired tidal volume (-0.7 ± 0.0 versus -54.1 ± 38.8, p = 0.0001) as well as a significant decrease in peak inspiratory pressure (0.2 ± 0.1 versus 2.5 ± 0.1; p = 0.001). Conclusion: In the studied sample, the MVH technique led to a greater amount of aspirated secretions, significant increases in dynamic compliance and expired tidal volume and a significant reduction in peak inspiratory pressure.

Ischemic preconditioning modifies mortality and inflammatory response

PURPOSE: To evaluate the effect of ischemic preconditioning on mortality, inflammatory mediators and oxidative stress after intestinal ischemia and reperfusion. METHODS: Male Wistar rats were allocated according to the period of ischemia with or without ischemic preconditioning which consist on clamping the superior mesenteric artery for 10 minutes followed by reperfusion for 10 minutes before the sustained ischemia period. Mortality was assessed in Phase 1 study, and the CINC-1, CINC-2 and MDA levels in the lungs were analyzed in Phase 2. RESULTS: Mortality was lower in the ischemic preconditioning group subjected to 90 minutes of ischemia compared to the group without ischemic preconditioning (I-90: 50% and IPC-90: 15%, p=0.018), and it was lower in the ischemic preconditioning group as a whole compared to the groups without ischemic preconditioning (IPC-14% and I=30%, p=0.006). Lower levels of MDA, CINC-1, and CINC-2 were observed in the animals that were subjected to ischemic preconditioning compared to the animals that were not (MDA: I-45=1.23 nmol/mg protein, and IPC-45=0.62 nmol/mg protein, p=0.0333; CINC-1: I-45=0.82 ng/mL and IPC-45=0.67 ng/mL, p=0.041; CINC-2: I-45=0.52 ng/mL and IPC-45=0.35 ng/mL, p=0.032). CONCLUSION: Ischemic preconditioning reduces mortality, inflammatory process and oxidative stress in rats subjected to intestinal ischemia and reperfusion.

Galantamine protects against lipopolysaccharide-induced acute lung injury in rats

Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.

Artificial gait in complete spinal cord injured subjects: how to assess clinical performance / Marcha artificial em indivíduos com lesão medular completa: como avaliar desempenho clínico

Objective Adapt the 6 minutes walking test (6MWT) to artificial gait in complete spinal cord injured (SCI) patients aided by neuromuscular electrical stimulation. Method Nine male individuals with paraplegia (AIS A) participated in this study. Lesion levels varied between T4 and T12 and time post injured from 4 to 13 years. Patients performed 6MWT 1 and 6MWT 2. They used neuromuscular electrical stimulation, and were aided by a walker. The differences between two 6MWT were assessed by using a paired t test. Multiple r-squared was also calculated. Results The 6MWT 1 and 6MWT 2 were not statistically different for heart rate, distance, mean speed and blood pressure. Multiple r-squared (r2 = 0.96) explained 96% of the variation in the distance walked. Conclusion The use of 6MWT in artificial gait towards assessing exercise walking capacity is reproducible and easy to apply. It can be used to assess SCI artificial gait clinical performance. .

Objetivo Adaptar o teste de caminhada dos 6 minutos (TC6) para marcha artificial de pacientes com lesão medular completa associado a eletroestimulação neuromuscular. Método Nove participantes do sexo masculino com paraplegia (AIS A) participaram do estudo. O nível de lesão variou entre T4 e T12 , tempo de lesão variou entre 4 e 13 anos. Os pacientes realizaram dois TC6 (TC6-1 e TC6-2). Os participantes usaram eletroestimulação neuromuscular e foram auxiliados por andador. As diferenças entre os dois TC6 foram avaliadas pelo teste t pareado e calculado o r2. Resultados Não foi encontrada diferença estatística entre TC6-1 e TC6-2 para frequência cardíaca, distância, velocidade média e pressão arterial. O r2 = 0,96 explica 96% da variação na distância caminhada. Conclusão O uso do TC6 em marcha artificial para avaliação da capacidade de exercício de caminhada é reprodutível e fácil de aplicar. Esse teste pode ser utilizado para avaliar o desempenho clínico da marcha artificial de indivíduos com lesão medular. .

Neurology at Escola Paulista de Medicina (1933-1995). From Fausto Guerner to José Geraldo Camargo Lima / Neurologia na Escola Paulista de Medicina (1933-1995). De Fausto Guerner a José Geraldo Camargo Lima.

Escola Paulista de Medicina (EPM) was founded in 1933 and the first Professor of Neurology was Fausto Guerner, who could not effectively assume the teaching activities due to his premature death in 1938. Professor Guerner had had his neurological training at Paris. Professor Longo was his successor. Longo was one of the founders of Arquivos de Neuro-Psiquiatria the foremost journal of neurosciences in Latin American. Longo died in 1967 and Professor Paulo Pupo succeeded him. Pupo introduced electroencephalography in Brazil. After his death in 1970, Professor Dante Giorgi succeeded him until 1974. Professor José Geraldo Camargo Lima took over the position after Giorgi’s death. He created the Neurological Emergency unit, initiated the Post-Graduation in Neurology and divided the Discipline in specialized units. During the 1980’s and until his retirement in 1995, EPM had become one of most important centers of Brazil training neurologists and researchers in neurological sciences.

A Escola Paulista de Medicina foi fundada em 1933 e o primeiro Professor de Neurologia foi Fausto Guerner, que morreu prematuramente em 1938, antes do início das aulas. O Professor Paulino Longo foi o seu sucessor. Longo, juntamente com outros, fundou os Arquivos de Neuro-Psiquiatria e a Academia Brasileira de Neurologia. Professor Paulo Pupo, seu sucessor, introduziu a eletroencefalografia no Brasil. O Professor José Geraldo Camargo Lima tornou-se chefe da Neurologia em 1974. Criou o Pronto-Socorro de Neurologia, iniciou a Pós-Graduação e dividiu a disciplina em setores especializadas. A partir dos anos 1980, a Neurologia da EPM tornou-se um dos centros acadêmicos mais importantes do Brasil.