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The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma-COPD overlap-ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-ß), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t-tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-ß, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1ß, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-ß, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.
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Asma , Doença Pulmonar Obstrutiva Crônica , Animais , Camundongos , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Ovalbumina/metabolismo , Interleucina-13/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Interleucina-6/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Asma/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Pulmão/patologia , Inflamação/metabolismo , Inibidores de Proteases/farmacologia , Líquido da Lavagem Broncoalveolar , Estresse Oxidativo , Colágeno/metabolismo , Elastase Pancreática/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Dexametasona/farmacologia , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
(1) There are several patients with asthma-COPD overlap (ACO). A peptide derived from the primary sequence of a kallikrein inhibitor isolated from Bauhinia bauhinioides (pep-BbKI) has potent anti-inflammatory and antioxidant effects. Purpose: To investigate the effects of pep-BbKI treatment in an ACO model and compare them with those of corticosteroids. (2) BALB/c mice were divided into groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep-BbKI (treated with inhibitor), ACO-DX (dexamethasone treatment), ACO-DX-pep-BbKI (both treatments), and SAL-pep-BbKI (saline group treated with inhibitor). We evaluated: hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), exhaled nitric oxide (eNO), IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, MMP-9, MMP-12, TGF-ß, collagen fibers, iNOS, eNO, linear mean intercept (Lm), and NF-κB in airways (AW) and alveolar septa (AS). (3) ACO-pep-BbKI reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, neutrophils, IL-5, IL-10, IL-17, IFN-γ, TNF-α, MMP-12 (AW), collagen fibers, iNOS (AW), and eNO (p > 0.05). ACO-DX reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, total cells and differentials, IL-1ß(AS), IL-5 (AS), IL-6 (AS), IL-10 (AS), IL-13 (AS), IFN-γ, MMP-12 (AS), TGF-ß (AS), collagen fibers (AW), iNOS, and eNO (p > 0.05). SAL was similar to SAL-pep-BbKI for all comparisons (p > 0.05). (4) Pep-BbKI was similar to dexamethasone in reducing the majority of alterations of this ACO model.
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Asma , Bauhinia , Doença Pulmonar Obstrutiva Crônica , Animais , Camundongos , Interleucina-10 , Interleucina-17 , Ovalbumina , Interleucina-13 , Interleucina-5 , Interleucina-6 , Metaloproteinase 12 da Matriz , Fator de Necrose Tumoral alfa , Proteínas de Plantas/farmacologia , Peptídeos/farmacologia , Líquido da Lavagem Broncoalveolar , Asma/tratamento farmacológico , Calicreínas , Elastase Pancreática , Dexametasona , Colágeno , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Modelos Animais de Doenças , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Studies in adult severe treatment-resistant asthma (STRA) have demonstrated heterogeneous pathophysiology. Studies in the pediatric age group are still scarce, and few include bronchial tissue analysis. OBJECTIVE: We investigated 6-18-year-old patients diagnosed with STRA in Sao Paulo, Brazil, by characterizing the different lung compartments and their correlations with asthma control and lung function. METHODS: Inflammatory profiles of 13 patients with a confirmed diagnosis of STRA were analyzed using blood, induced sputum, bronchoalveolar lavage, viral and bacterial screens and endobronchial biopsy. Inflammatory cells, cytokines, and basement membrane thickening were tested for correlations with the asthma control test (ACT) and spirometry and plethysmography parameters. RESULTS: Endobronchial biopsy specimens from 11 patients were viable for analysis. All biopsies showed eosinophilic infiltration. Submucosal (SM) eosinophils and neutrophils were correlated with worse lung function (pre-BD FEV1), and SM neutrophils were correlated with fixed obstruction (post-BD FEV1). Intraepithelial (IE) neutrophils were positively correlated with lung function (pre-BD sGaw). CD8 + T cells had the highest density in the IE and SM layers and were positively correlated with ACT and negatively correlated with the cytokines IL1ß, IL2, IL5, IL7, IL10, IL12, IL17, GCSF, MCP-1, INF-δ, and TNFα in sputum supernatant. The ASM chymase + mast cell density correlated positively with quality-of-life score (pAQLQ) and ACT. CONCLUSION: Eosinophils and SM neutrophils correlated with worse lung function, while IE neutrophils correlated with better lung function. Most importantly, CD8 + T cells were abundant in bronchial biopsies of STRA patients and showed protective associations, as did chymase + mast cells.
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Asma , Eosinófilos , Adolescente , Adulto , Humanos , Criança , Brasil/epidemiologia , Eosinófilos/patologia , Neutrófilos/patologia , Escarro , Pulmão , Linfócitos T/patologiaRESUMO
BACKGROUND: Cleaning workers represent a significant proportion of the active population worldwide, with poor remuneration, particularly in developing countries. Despite this, they remain a relatively poorly studied occupational group. They are constantly exposed to agents that can cause symptoms and respiratory problems. This study aimed to evaluate upper airway inflammation in professional cleaning workers in three different occupational settings by comparing nasal cytology inflammation and clinical profiles. METHODS: We performed a cross-sectional study on the prevalence of upper airway inflammation and symptoms of asthma/rhinitis related to cleaning work, according to workplace. A total of 167 participants were divided into four groups: hospital, university, housekeeper and control. A nasal swab was collected for upper airway inflammation evaluation. Clinical profiles and respiratory symptom employee evaluations were performed using specific questionnaires (European Community Respiratory Health Survey-ECRS and the International Study of Asthma and Allergies in Childhood-ISAAC). RESULTS: Cleaning workers showed increased neutrophils and lymphocytes; the hospital and university groups showed increased macrophages compared to the housekeeper and control groups. The hospital and housekeeper groups showed increased eosinophils when they performed cleaning services for up to one year and reported having more asthma symptoms than the control group. Cleaning workers showed increased rhinitis symptoms. The university group showed increased rhinitis symptoms aggravated by the workplace compared with the hospital and housekeeper groups. Cleaning workers showed an increased affirmative response when directly asked about rhinitis symptoms compared to the control group. CONCLUSIONS: Cleaning workers showed airway inflammation, asthma symptoms and rhinitis, regardless of the occupational environment to which they were exposed, as well as showed increased rhinitis and asthma symptoms. Hospital cleaning workers showed increased macrophages, lymphocytes and eosinophils compared to the others. The length of time spent performing cleaning work was not related to nasal inflammation or respiratory symptoms in this population. However, there were differences in workplaces. Registered on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT03311048. Registration date: 10.16.2017. Retrospectively registered.
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Asma , Doenças Profissionais , Rinite , Asma/complicações , Estudos Transversais , Humanos , Inflamação/epidemiologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia , Rinite/complicações , Rinite/epidemiologia , Local de TrabalhoRESUMO
Chronic obstructive pulmonary disease (COPD) is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti-interleukin (IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE + PREVENTIVE ANTI-IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI-IL-17 (ET). On the 29th day, animals were anesthetized with thiopental, tracheotomized, and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti-IL-17 decreased respiratory resistance and elastance, airway resistance, elastance of pulmonary parenchyma, eNO, and Lm compared with EC. There was reduction in total cells and macrophages in ET compared with EC. Both treatments decreased nuclear factor-кB, inducible nitric oxide synthase, matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor-ß, tumor necrosis factor-α, neutrophils, IL-1ß, isoprostane, and IL-17 in airways and alveolar septa; collagen fibers, decorin and lumican in airways; and elastic fibers and fibronectin in alveolar septa compared with EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP and a reduction of eNO synthase in airways in ET. In conclusion, both treatments with anti-IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.
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Interleucina-17/metabolismo , Lesão Pulmonar/metabolismo , Pulmão/metabolismo , Elastase Pancreática/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismoRESUMO
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.
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Remodelação das Vias Aéreas/efeitos dos fármacos , Fabaceae/química , Elastase Pancreática/metabolismo , Extratos Vegetais/farmacologia , Pneumonia/metabolismo , Pneumonia/fisiopatologia , Inibidores de Proteases/farmacologia , Animais , Biomarcadores , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Masculino , Camundongos , Mucinas/biossíntese , Estresse Oxidativo , Pneumonia/tratamento farmacológico , Pneumonia/patologiaRESUMO
The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.
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INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system. RESULTS: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress. CONCLUSIONS: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.
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Prolonged exposure to iron powder and other mineral dusts can threaten the health of individuals, especially those with COPD. The goal of this study was to determine how environmental exposure to metal dust from two different mining centers in Brazil affects lung mechanics, inflammation, remodeling and oxidative stress responses in healthy and elastase-exposed mice. This study divided 72 male C57Bl/6 mice into two groups, the summer group and the winter group. These groups were further divided into six groups: control, nonexposed (SAL); nonexposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, macrophage iron and alveolar wall alterations (mean linear intercept-Lm). The Lm was increased in the ELA, ELA-L1 and ELA-L2 groups compared to the SAL group (p < 0.05). There was an increase in the total number of cells and macrophages in the ELA-L1 and ELA-L2 groups compared to the other groups (p < 0.05). Compared to the ELA and SAL groups, the exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) exhibited increased expression of IL-1ß, IL-6, IL-10, IL-17, TNF-α, neutrophil elastase, TIMP-1, MMP-9, MMP-12, TGF-ß, collagen fibers, MUC5AC, iNOS, Gp91phox, NFkB and iron positive macrophages (p < 0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between inflammation remodeling, oxidative stress and NFkB with elastance, resistance of lung tissue and iron positive macrophages (p < 0.05). Environmental exposure to iron, confirmed by evaluation of iron in alveolar macrophages and in air, exacerbated inflammation, initiated remodeling, and induced oxidative stress responses in exposed mice with and without emphysema. Activation of the iNOS, Gp91phox and NFkB pathways play a role in these changes.
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Exposição Ambiental , Ferro , Elastase Pancreática , Animais , Masculino , Camundongos , Líquido da Lavagem Broncoalveolar/química , Exposição Ambiental/efeitos adversos , Inflamação/metabolismo , Inflamação/induzido quimicamente , Ferro/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Elastase Pancreática/metabolismo , Elastase Pancreática/farmacologia , Pós/toxicidadeRESUMO
Background: IL-17 is a modulator of the inflammatory response and is implicated in lung remodeling in both asthma and chronic obstructive pulmonary disease (COPD). Well as and probably in patients with asthma-COPD overlap (ACO). Methods: In this study, we evaluated the response of the airways and alveolar septa to anti-IL-17 treatment in an ACO model. Fifty-six male BALB/c mice were sensitized with ovalbumin (OVA group), received porcine pancreatic elastase (PPE group), or both (ACO group). Mice were then treated with either anti-IL-17 monoclonal antibody or saline. We evaluated hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and mean alveolar diameter. We quantified inflammatory, response, extracellular matrix remodeling, oxidative stress markers, and signaling pathway markers. Results: Anti-IL-17 treatment in the ACO anti-IL-17 group reduced the maximum response of respiratory system Rrs, Ers, Raw, Gtis, this when compared to the ACO group (p<0.05). There was a reduction in the total number of inflammatory cells, neutrophils, and macrophages in the BALF in the ACO anti-IL-17 group compared to the ACO group (p<0.05). There was attenuated dendritic cells, CD4+, CD8+, FOXP3, IL-1ß, IL-2, IL-6, IL-13, IL-17, IL-33 in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p<0.05). We observed a reduction of MMP-9, MMP-12, TIMP-1, TGF-ß, collagen type I in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p < 0.05). We also observed a reduction of iNOS and 8-iso-PGF2α in the airways and in the alveolar septum was reduced in the ACO anti-IL-17group compared to the ACO group (p < 0.05). Regarding the signaling pathways, NF-kB, ROCK-1, and ROCK-2 in the airway and alveolar septum were attenuated in the ACO anti-IL-17 group when compared to the ACO group (p<0.05). Conclusions: Our results suggest that inhibiting IL-17 modulates cell-associated cytokine production in lung tissue, extracellular matrix remodeling, and oxidative stress in ACO through the modulation of NF-kB and FOXP3.
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Asma , Doença Pulmonar Obstrutiva Crônica , Animais , Masculino , Camundongos , Fatores de Transcrição Forkhead , Interleucina-17 , NF-kappa B , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , SuínosRESUMO
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.
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Amidas/farmacologia , Antiasmáticos/farmacologia , Matriz Extracelular/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piridinas/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Remodelação das Vias Aéreas/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Amidas/uso terapêutico , Animais , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Asma/fisiopatologia , Colágeno/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Avaliação Pré-Clínica de Medicamentos , Tecido Elástico/metabolismo , Elasticidade , Eosinófilos/imunologia , Eosinófilos/patologia , Eosinófilos/fisiologia , Cobaias , Inalação/efeitos dos fármacos , Interleucina-2/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Piridinas/uso terapêutico , Quinases Associadas a rho/metabolismoRESUMO
OBJECTIVE: To analyze whether resilience modulates the levels of depression, anxiety, stress and the impact of events in physiotherapists who work with COVID-19 patients with those who do not. METHODS: A cross-sectional study was conducted from August 2020 up to October 2020. A total of 519 physiotherapists were enrolled and divided according to resilience and whether they worked with COVID-19 patients. Volunteers answered sociodemographic questionnaires, rating their depression, anxiety, and stress on a scale (DASS-21). The impact of event scale revised (IES-R) and 14-item resilience scale (14-RS) were also used. RESULTS: Physiotherapists with low resilience present scores significantly high of depression, anxiety, stress and impact of event compared to the high resilience group (P < .001). Additionally, working with COVID-19 patients also resulted in increased levels of depression, anxiety, stress, and impact of event compared with the NO COVID-19 group (P < .001). These responses were modulated by age, sex, number of absences from work, whether or not personal protective equipment was received, host leadership, and the practice and maintenance of regular physical activity. LIMITATIONS: The responses to the questionnaires were anonymous and self-administered. We cannot assess whether these people had a previous diagnosis of depression, anxiety and stress. CONCLUSIONS: Low resilience and work with COVID-19 patients were associated with high levels of depression, anxiety, and stress and worse psychological impacts of events. Several aspects modulate these responses and can contribute to improving the resilience and mental health of physiotherapists who are responsible for the care of COVID-19 patients.
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COVID-19 , Fisioterapeutas , Resiliência Psicológica , Ansiedade/epidemiologia , Ansiedade/psicologia , Brasil/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Humanos , Saúde Mental , Pandemias , SARS-CoV-2RESUMO
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.
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COVID-19 , Fisioterapeutas , COVID-19/epidemiologia , Estudos Transversais , Felicidade , Humanos , Pandemias , Qualidade de Vida/psicologia , Inquéritos e QuestionáriosRESUMO
Pulmonary irritants, such as cigarette smoke (CS) and sodium hypochlorite (NaClO), are associated to pulmonary diseases in cleaning workers. We examined whether their association affects lung mechanics and inflammation in Wistar rats. Exposure to these irritants alone induced alterations in the lung mechanics, inflammation, and remodeling. The CS increased airway cell infiltration, acid mucus production, MMP-12 expression, and alveolar enlargement. NaClO increased the number of eosinophils and macrophages in the bronchoalveolar lavage fluid, with cells expressing IL-13, MMP-12, MMP-9, TIMP-1, and iNOS in addition to increased IL-1ß and TNF-α levels. Co-exposure to both irritants increased epithelial and smooth muscle cell area, acid mucus production, and IL-13 expression in the airways, while it reduced the lung inflammation. In conclusion, the co-exposure of CS with NaClO reduced the pulmonary inflammation, but increased the acidity of mucus, which may protect lungs from more injury. A cross-resistance in people exposed to multiple lung irritants should also be considered.
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Fumar Cigarros , Lesão Pulmonar , Pneumonia , Animais , Líquido da Lavagem Broncoalveolar , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-13/metabolismo , Irritantes/metabolismo , Irritantes/farmacologia , Pulmão/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Pneumonia/metabolismo , Ratos , Ratos Wistar , Hipoclorito de Sódio/metabolismo , Hipoclorito de Sódio/farmacologia , NicotianaRESUMO
Some clinical situations require the use of oxygen therapy for a few hours without hypoxemia. However, there are no literature reports on the effects of acute oxygen therapy on the nasal mucosa. This study aimed to evaluate the acute effects of cold bubble humidification or dry oxygen on nasal Inflammation, oxidative stress, mucociliary clearance, and nasal symptoms. This is a randomized controlled cross-sectional study in which healthy subjects were randomly allocated into four groups: (1) CA + DRY (n = 8): individuals receiving dry compressed air; (2) OX + DRY (n = 8): individuals receiving dry oxygen therapy; (3) CA + HUMID (n = 7): individuals receiving cold bubbled humidified compressed air; (4) OX + HUMID (n = 8): individuals receiving cold bubbled humidified oxygen therapy. All groups received 3 L per minute (LPM) of the oxygen or compressed air for 1 h and were evaluated: total and differential cells in the nasal lavage fluid (NLF), exhaled nitric oxide (eNO), 8-iso-PGF2α levels, saccharin transit test, nasal symptoms, and humidity of nasal cannula and mucosa. Cold bubble humidification is not able to reduced nasal inflammation, eNO, oxidative stress, mucociliary clearance, and nasal mucosa moisture. However, subjects report improvement of nasal dryness symptoms (P < 0.05). In the conclusion, cold bubble humidification of low flow oxygen therapy via a nasal cannula did not produce any effect on the nasal mucosa and did not attenuate the oxidative stress caused by oxygen. However, it was able to improve nasal symptoms arising from the use of oxygen therapy.
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Inflamação/metabolismo , Mucosa Nasal/metabolismo , Adulto , Estudos Transversais , Feminino , Humanos , Macrófagos/metabolismo , Masculino , Mucosa Nasal/patologia , Neutrófilos/metabolismo , Estresse Oxidativo/fisiologia , Adulto JovemRESUMO
AIM: To explore the different consequences of acute and chronic exposure to chlorine gas (Cl2) on the functional and histological parameters of health mice. MAIN METHODS: Firstly, male BALB/c mice were acute exposed to 3.3 or 33.3 or 70.5 mg/m3 Cl2. We analyzed the lung function, the inflammatory cells in the bronchoalveolar lavage, cell influx in the peribrochoalveolar space and mucus production. In a second phase, mice were chronic exposed to 70.5 mg/m3 Cl2. Besides the first phase analyses, we also evaluated the epithelial cells thickness, collagen deposition in the airways, immunohistochemistry stain for IL-1ß, iNOS, IL-17 and ROCK-2 and the levels of IL-5, IL-13, IL-17, IL-1ß and TNF-α in lung homogenate. KEY FINDINGS: Acute exposure to chlorine impaired the lung function, increased the number of inflammatory cells in the BALF and in the airways, also increased the mucus production. Furthermore, when chlorine was exposed chronically, increased the airway remodeling with collagen deposition and epithelial cells thickness, positive cells for IL-1ß, iNOS, IL-17 in the airways and in the alveolar walls and ROCK-2 in the alveolar walls, lung inflammation with increased levels of IL-5, IL-13, IL-1ß and TNF-α in the lung homogenate, and also, induced the acid mucus production by the nasal epithelium. SIGNIFICANCE: Acute and chronic exposure to low dose of chlorine gas worsens lung function, induces oxidative stress activation and mucus production and contributes to augmenting inflammation in health mice.
Assuntos
Cloro/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/patologia , Células Epiteliais Alveolares/efeitos dos fármacos , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Cloro/metabolismo , Inflamação/patologia , Exposição por Inalação , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Adjuvants, such as bacterial lipopolysaccharides, have been studied to improve the efficacy of allergen-specific immunotherapy. The Bordetella pertussis (Pw) vaccine has been shown to have a protective role in ovalbumin-induced asthma models. However, its role in allergy to mites is unknown. We evaluated the effects of the diphtheria-tetanus-pertussis (DTPw) vaccine on a murine model of respiratory allergy induced by Dermatophagoides pteronyssinus (Derp). METHODS: In a 30-day protocol, BALB/c mice were immunized subcutaneously with saline or Derp, alone or in combination with diphtheria-tetanus (DT) or DTPw vaccines (days 0, 7 and 14). Subsequently, they underwent a daily intranasal challenge with saline or Derp (days 22-28) and were then sacrificed (day 29). We evaluated serum-specific immunoglobulins, bronchoalveolar lavage (BAL) cellularity, remodelling of the lower airways, density of polymorphonuclear leukocytes (PMNs) and acidic nasal mucus content. RESULTS: The animals sensitized with Derp produced high levels of specific immunoglobulins, increased density of PMNs and nasal mucus content, and elevated BAL cellularity and remodelling. Vaccines led to a reduction in IgE levels, with the Derp-DTPw group being similar to the saline groups. The vaccinated groups had reductions of BAL cellularity and remodelling, with more expressive results in the Derp-DTPw group compared to the Derp-DT group. The DT and DTPw vaccines inhibited the nasal PMN infiltrate, and DTPw modulated the production of acidic nasal mucus. CONCLUSIONS: The DTPw vaccine reduced serum specific IgE, nasal and pulmonary inflammation and remodelling of the lower airways.
Assuntos
Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Pyroglyphidae/imunologia , Administração Intranasal , Animais , Modelos Animais de Doenças , Hipersensibilidade/metabolismo , Hipersensibilidade/prevenção & controle , Imunoglobulina E/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pyroglyphidae/metabolismoRESUMO
OBJECTIVES: This study aimed to analyze the efficiency of physiotherapy techniques in sputum induction and in the evaluation of pulmonary inflammation in asthmatic children and adolescents. Although hypertonic saline (HS) is widely used for sputum induction (SI), specific techniques and maneuvers of physiotherapy (P) may facilitate the collection of mucus in some asthmatic children and adolescents. METHODS: A randomized crossover study was performed in patients with well-controlled asthma, and 90 sputum samples were collected. Children and adolescents were assessed using spirometry and randomized at entry into one of three sputum induction techniques: (i) 3% hypertonic saline - HS technique; (ii) physiotherapy (oscillatory positive expiratory pressure, forced expiration, and acceleration of expiratory flow) - P technique; and (iii) hypertonic saline + physiotherapy - HSP technique. ClinicalTrials.gov: NCT03136042. RESULTS: The total cells (mL) and the percentage (%) of differential inflammatory cells were similar in all techniques. The sputum weight (g) in the HSP technique was significantly higher than that in the HS technique. In all techniques, the percentage of viable cells was >50%, and there was no difference between the HS and P techniques. Moreover, sputum induction did not cause any alterations in the pulmonary function of patients. CONCLUSION: The physiotherapy sputum collection technique was effective in obtaining viable cells from mucus samples and yielded the same amount of sputum as the gold standard technique (hypertonic saline). In addition, the physiotherapy maneuvers were both safe and useful for sputum induction in asthmatic children and adolescents with well-controlled asthma.
Assuntos
Asma/complicações , Modalidades de Fisioterapia , Solução Salina Hipertônica , Escarro , Adolescente , Criança , Estudos Cross-Over , Volume Expiratório Forçado , HumanosRESUMO
Many cities fail to meet air quality standards, which results in increased risk for pulmonary disorders, including asthma. Human and experimental studies have shown that diesel exhaust (DE) particles are associated with worsening of allergic asthma. Biodiesel (BD), a cleaner fuel from renewable sources, was introduced in the eighties. Because of the reduction in particulate matter (PM) emissions, BD was expected to cause fewer adverse pulmonary effects. However, only limited data on the effect of BD emissions in asthma are available. OBJECTIVE: Determine whether BD exhaust exposure in allergic sensitized mice leads to different effects on inflammatory and functional responses compared to DE exposure. METHODS: Balb/C mice were orotracheally sensitized with House Dust Mite (HDM) or a saline solution with 3 weekly instillations. From day 9 until day 17 after sensitization, they were exposed daily to filtered air (FA), DE and BD exhaust (concentration: 600⯵g/m3 PM2.5). Lung function, bronchoalveolar lavage fluid (BALF) cell counts, cytokine levels (IL-2, IL-4, IL-5, IL-17, TNF-α, TSLP) in the BALF, peribronchiolar eosinophils and parenchymal macrophages were measured. RESULTS: HDM-sensitized animals presented increased lung elastance (pâ¯=â¯0.046), IgG1 serum levels (pâ¯=â¯0.029), peribronchiolar eosinophils (pâ¯=â¯0.028), BALF levels of total cells (pâ¯=â¯0.020), eosinophils (pâ¯=â¯0.028), IL-5 levels (pâ¯=â¯0.002) and TSLP levels (pâ¯=â¯0.046) in BALF. DE exposure alone increased lung elastance (pâ¯=â¯0.000) and BALF IL-4 levels (pâ¯=â¯0.045), whereas BD exposure alone increased BALF TSLP levels (pâ¯=â¯0.004). BD exposure did not influence any parameters after HDM challenge, while DE exposed animals presented increased BALF levels of total cells (pâ¯=â¯0.019), lymphocytes (pâ¯=â¯0.000), neutrophils (pâ¯=â¯0.040), macrophages (pâ¯=â¯0.034), BALF IL-4 levels (pâ¯=â¯0.028), and macrophagic inflammation in the lung tissue (pâ¯=â¯0.037), as well as decreased IgG1 (pâ¯=â¯0.046) and IgG2 (pâ¯=â¯0.043) levels when compared to the HDM group. CONCLUSION: The results indicate more adverse pulmonary effects of DE compared to BD exposure in allergic sensitized animals.
Assuntos
Biocombustíveis/toxicidade , Emissões de Veículos/toxicidade , Alérgenos , Animais , Asma/induzido quimicamente , Biocombustíveis/análise , Líquido da Lavagem Broncoalveolar , Citocinas , Modelos Animais de Doenças , Humanos , Inflamação/induzido quimicamente , Interleucina-17 , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos , Material Particulado/efeitos adversos , Testes de Toxicidade , Emissões de Veículos/análiseRESUMO
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.