A plant proteinase inhibitor from Enterolobium contortisiliquum attenuates airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma.

INTRODUCTION: Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for asthma. PURPOSE: The aim of the present study was to evaluate the effects of Enterolobium contortisiliquum trypsin inhibitor (EcTI) on pulmonary mechanical function, eosinophilic recruitment, inflammatory cytokines, remodeling and oxidative stress in an experimental model of chronic allergic pulmonary inflammation. METHODS: BALB/c mice were divided into 4 groups: C (saline i.p and inhalations with saline), OVA (ovalbumin i.p and inhalations with ovalbumin); C+EC (saline i.p, inhalations with s aline and treatment with EcTI); OVA+EC (ovalbumin i.p, inhalations with ovalbumin and treatment with EcTI). On day 29, we performed the following tests: resistance (Rrs) and elastance (Ers) of the respiratory system; (b) quantify eosinophils, 8-ISO-PGF2α, collagen and elastic fiber volume fractions; (c) IFN-γ, IL-4, IL-5, IL-13, MMP-9, TIMP-1, TGF-ß, iNOS and p65-NFκB-positive cells in the airway and alveolar walls. RESULTS: In OVA+EC group, there was an attenuation of the Rrs and Ers, reduction of eosinophils, IL-4, IL-5, IL-13, IFN-γ, iNOS and p65-NFκB-positive cells compared to OVA group. The 8-ISO-PGF2α, elastic and collagen fibers volume fractions as well as the positive cells for MMP-9, TIMP-1 and TGF-ß positive cells were decreased in OVA+EC compared to the OVA group. CONCLUSION: EcTI attenuates bronchial hyperresponsiveness, inflammation, remodeling and oxidative stress activation in this experimental mouse model of asthma.

A Plant Proteinase Inhibitor from Enterolobium contortisiliquum Attenuates Pulmonary Mechanics, Inflammation and Remodeling Induced by Elastase in Mice.

Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for emphysema. Our aim was to evaluate the effects of a plant Kunitz proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on several aspects of experimental elastase-induced pulmonary inflammation in mice. C57/Bl6 mice were intratracheally administered elastase (ELA) or saline (SAL) and were treated intraperitoneally with EcTI (ELA-EcTI, SAL-EcTI) on days 1, 14 and 21. On day 28, pulmonary mechanics, exhaled nitric oxide (ENO) and number leucocytes in the bronchoalveolar lavage fluid (BALF) were evaluated. Subsequently, lung immunohistochemical staining was submitted to morphometry. EcTI treatment reduced responses of the mechanical respiratory system, number of cells in the BALF, and reduced tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-12 (MMP-12), tissue inhibitor of matrix metalloproteinase (TIMP-1), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS)-positive cells and volume proportion of isoprostane, collagen and elastic fibers in the airways and alveolar walls compared with the ELA group. EcTI treatment reduced elastase induced pulmonary inflammation, remodeling, oxidative stress and mechanical alterations, suggesting that this inhibitor may be a potential therapeutic tool for chronic obstructive pulmonary disease (COPD) management.

Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation.

Several studies have demonstrated the importance of Rho-kinase in the modulation of smooth muscle contraction, airway hyperresponsiveness, and inflammation. However, the effects of repeated treatment with a specific inhibitor of this pathway have not been previously investigated. We evaluated the effects of repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on airway hyperresponsiveness, oxidative stress activation, extracellular matrix remodeling, eosinophilic inflammation, and cytokine expression in an animal model of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or saline exposures. The treatment with Y-27632 (1 mM) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the animals' pulmonary mechanics were evaluated, and exhaled nitric oxide (E(NO)) was collected. The lungs were removed, and histological analysis was performed using morphometry. Treatment with Y-27632 in sensitized animals reduced E(NO) concentrations, maximal responses of resistance, elastance of the respiratory system, eosinophil counts, collagen and elastic fiber contents, the numbers of cells positive for IL-2, IL-4, IL-5, IL-13, inducible nitric oxide synthase, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming growth factor-ß, NF-κB, IFN-γ, and 8-iso-prostaglandin F2α contents compared with the untreated group (P < 0.05). We observed positive correlations among the functional responses and inflammation, remodeling, and oxidative stress pathway activation markers evaluated. In conclusion, Rho-kinase pathway activation contributes to the potentiation of the hyperresponsiveness, inflammation, the extracellular matrix remodeling process, and oxidative stress activation. These results suggest that Rho-kinase inhibitors represent potential pharmacological tools for the control of asthma.

Chest physiotherapy during immediate postoperative period among patients undergoing upper abdominal surgery: randomized clinical trial.

CONTEXT AND OBJECTIVE: Abdominal surgical procedures increase pulmonary complication risks. The aim of this study was to evaluate the effectiveness of chest physiotherapy during the immediate postoperative period among patients undergoing elective upper abdominal surgery. DESIGN AND SETTING: This randomized clinical trial was performed in the post-anesthesia care unit of a public university hospital. METHODS: Thirty-one adults were randomly assigned to control (n = 16) and chest physiotherapy (n = 15) groups. Spirometry, pulse oximetry and anamneses were performed preoperatively and on the second postoperative day. A visual pain scale was applied on the second postoperative day, before and after chest physiotherapy. The chest physiotherapy group received treatment at the post-anesthesia care unit, while the controls did not. Surgery duration, length of hospital stay and postoperative pulmonary complications were gathered from patients' medical records. RESULTS: The control and chest physiotherapy groups presented decreased spirometry values after surgery but without any difference between them (forced vital capacity from 83.5 +/- 17.1% to 62.7 +/- 16.9% and from 95.7 +/- 18.9% to 79.0 +/- 26.9%, respectively). In contrast, the chest physiotherapy group presented improved oxygen-hemoglobin saturation after chest physiotherapy during the immediate postoperative period (p < 0.03) that did not last until the second postoperative day. The medical record data were similar between groups. CONCLUSIONS: Chest physiotherapy during the immediate postoperative period following upper abdominal surgery was effective for improving oxygen-hemoglobin saturation without increased abdominal pain. Breathing exercises could be adopted at post-anesthesia care units with benefits for patients.

Chest physiotherapy during immediate postoperative period among patients undergoing upper abdominal surgery: randomized clinical trial / Fisioterapia respiratória no pós-operatório imediato em pacientes submetidos a cirurgia abdominal alta: ensaio clínico aleatório

CONTEXT AND OBJECTIVE: Abdominal surgical procedures increase pulmonary complication risks. The aim of this study was to evaluate the effectiveness of chest physiotherapy during the immediate postoperative period among patients undergoing elective upper abdominal surgery. DESIGN AND SETTING: This randomized clinical trial was performed in the post-anesthesia care unit of a public university hospital. METHODS: Thirty-one adults were randomly assigned to control (n = 16) and chest physiotherapy (n = 15) groups. Spirometry, pulse oximetry and anamneses were performed preoperatively and on the second postoperative day. A visual pain scale was applied on the second postoperative day, before and after chest physiotherapy. The chest physiotherapy group received treatment at the post-anesthesia care unit, while the controls did not. Surgery duration, length of hospital stay and postoperative pulmonary complications were gathered from patients' medical records. RESULTS: The control and chest physiotherapy groups presented decreased spirometry values after surgery but without any difference between them (forced vital capacity from 83.5 ± 17.1 percent to 62.7 ± 16.9 percent and from 95.7 ± 18.9 percent to 79.0 ± 26.9 percent, respectively). In contrast, the chest physiotherapy group presented improved oxygen-hemoglobin saturation after chest physiotherapy during the immediate postoperative period (p < 0.03) that did not last until the second postoperative day. The medical record data were similar between groups. CONCLUSIONS: Chest physiotherapy during the immediate postoperative period following upper abdominal surgery was effective for improving oxygen-hemoglobin saturation without increased abdominal pain. Breathing exercises could be adopted at post-anesthesia care units with benefits for patients.

CONTEXTO E OBJETIVO: Cirurgias abdominais podem aumentar o risco de complicações pulmonares. O objetivo foi avaliar a eficácia da fisioterapia respiratória precoce no pós-operatório imediato em pacientes submetidos a cirurgia abdominal alta. TIPO DE ESTUDO E LOCAL: O estudo foi do tipo ensaio clínico aleatório, realizado na sala de recuperação pós-anestésica de um hospital público universitário. MÉTODO: 31 adultos foram selecionados aleatoriamente em dois grupos, controle (n = 16) e grupo de fisioterapia respiratória (n = 15). Espirometria, oximetria de pulso e anamnese foram realizadas no pré-operatório e no segundo dia pós-operatório. A escala visual analógica foi aplicada no segundo dia pós-operatório e antes e depois da fisioterapia respiratória. O grupo da fisioterapia respiratória recebeu fisioterapia na sala de recuperação pós-anestésica e o grupo controle, não. Tempo cirúrgico, tempo de internação e as complicações pulmonares pós-operatórias foram analisados nos prontuários dos pacientes. RESULTADOS: Os grupos apresentaram uma diminuição dos valores espirométricos após a cirurgia, porém, não houve diferença entre eles (capacidade vital forçada, CVF 83.5 ± 17.1 por cento versus 62.7 ± 16.9 por cento grupo controle pré versus pós-operatório e 95.7 ± 18.9 por cento versus 79.0 ± 26.9 por cento grupo fisioterapia). Em contraste, o grupo da fisioterapia respiratória apresentou uma melhora na saturação de oxi-hemoglobina após a fisioterapia no pós-operatório imediato (p < 0,03), mas esta não se manteve até o segundo dia pós-operatório. CONCLUSÕES: A fisioterapia respiratória é efetiva na melhora da saturação de oxi-hemoglobina em pacientes observados na sala de recuperação pós-anestésica em cirurgia abdominal alta, e não provoca dor durante os exercícios.