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

Possa SS, Charafeddine HT, Righetti RF, da Silva PA, Almeida-Reis R, Saraiva-Romanholo BM, Perini A, Prado CM, Leick-Maldonado EA, Martins MA, Tiberio ID. Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation. Am J Physiol Lung Cell Mol Physiol 303: L939-L952, 2012. First published September 21, 2012; doi:10.1152/ajplung.00034.2012.-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-beta, NF-kappa B, IFN-gamma, and 8-iso-prostaglandin F2 alpha 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Sch Med, Dept Med, BR-01246903 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilWeb of Scienc

Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice

Introduction: T helper 17 (Th17) has been implicated in a variety of inflammatory lung and immune system diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI). We investigated the mechanisms involved in the effect of anti-IL17 in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods: Mice were pre-treated with anti-IL17, 1h before saline/LPS intratracheal administration alongside non-treated controls and levels of exhaled nitric oxide (eNO), cytokine expression, extracellular matrix remodeling and oxidative stress, as well as immune cell counts in bronchoalveolar lavage fluid (BALF), and respiratory mechanics were assessed in lung tissue.Results: LPS instillation led to an increase in multiple cytokines, proteases, nuclear factor-κB, and Forkhead box P3 (FOXP3), eNO and regulators of the actomyosin cytoskeleton, the number of CD4+ and iNOS-positive cells as well as the number of neutrophils and macrophages in BALF, resistance and elastance of the respiratory system, ARG-1 gene expression, collagen fibers, and actin and 8-iso-PGF2α volume fractions. Pre-treatment with anti-IL17 led to a significant reduction in the level of all assessed factors.Conclusions: Anti-IL17 can protect the lungs from the inflammatory effects of LPS-induced ALI, primarily mediated by the reduced expression of cytokines and oxidative stress. This suggests that further studies using anti-IL17 in a treatment regime would be highly worthwhile

Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS

Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-kappa B, and Rho kinase 1-and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)National Council of Scientific and the Technological Development (CNPq)Laboratory of Medical InvestigationsUniv Sao Paulo, Sch Med, Dept Med Sci, Sao Paulo, Brazil|Hosp Sirio Libanes, Sao Paulo, BrazilUniv Fed Sao Paulo, Inst Biomed Sci, Dept Biol Sci, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Sao Paulo, BrazilUniv Fed Sao Paulo, Inst Biomed Sci, Dept Biol Sci, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Sao Paulo, BrazilFAPESP: 2013/17944-1Laboratory of Medical Investigations: LIM-20 FMUSPWeb of Scienc

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

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% 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.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% versus 62.7 ± 16.9% grupo controle pré versus pós-operatório e 95.7 ± 18.9% versus 79.0 ± 26.9% 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

Resilience Improves the Quality of Life and Subjective Happiness of Physiotherapists during the COVID-19 Pandemic

Resilience is an individual characteristic that protects mental health. However, its impact on the lives of Brazilian physiotherapists during COVID-19 is not known. This study aimed to analyze whether resilience modulates the perceived quality of life (QoL) and subjective happiness (SH) of physiotherapists who work with COVID-19 patients, compared with those who do not. A cross-sectional study was conducted between 22 August and 22 October 2020. Physiotherapists working in critical and non-critical hospital sectors were invited to participate in the study. The participants completed sociodemographic questionnaires and were graded on the 14-item Resilience Scale, 36-item Short-Form Health Survey (SF-36), and the Subjective Happiness Scale. In total, 519 physiotherapists were enrolled in the study. Physiotherapists with low resilience who worked with COVID-19 patients reported lower scores on the SF-36 subscales (except for social functioning) and the Subjective Happiness Scale, compared with those with high resilience who did not work with COVID-19 patients. These responses were modulated by age, sex, absence from work, receipt of personal protective equipment, host leadership, and practice and maintenance of regular physical activity. In conclusion, physiotherapists with low resilience who worked with COVID-19 patients presented lower perceptions of QoL and SH, compared with the other study participants

Longitudinal study of lung function in pregnant women: Influence of parity and smoking

OBJECTIVES: To evaluate pulmonary function in the first and third trimesters of pregnancy and analyze the influence of parity and smoking on spirometry parameters. METHODS: This longitudinal prospective study included a cohort of 120 pregnant women. The inclusion criteria were as follows: singleton pregnancy, gestational age less than 13.86 weeks, and no preexisting maternal diseases. The exclusion criteria were as follows: change of address, abortion, and inadequate spirometry testing. ClinicalTrials.gov: NCT02807038. RESULTS: A decrease in values of forced vital capacity and forced expiratory volume were noted in the first second from the first to third trimester. In the first and third trimesters, multiparous women demonstrated lower absolute forced vital capacity and forced expiratory volume values in the first second compared with nulliparous women (p<0.0001 and p=0.001, respectively). Multiparous women demonstrated reduced forced expiratory flow in 25% to 75% of the maneuver compared with nulliparous women in the first (p=0.005) and third (p=0.031) trimesters. The absolute values of forced expiratory flow in 25% to 75%, forced expiratory volume in the first second and predicted peak expiratory flow values in the third trimester were higher in smokers compared with nonsmokers (p=0.042, p=0.039, p=0.024, and p=0.021, respectively). CONCLUSION: There was a significant reduction in forced vital capacity and forced expiratory volume values in the first second during pregnancy. Parity and smoking significantly influence spirometric variables