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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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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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Objective Evaluate the results of the implementation of the Fast Track Protocol (FTP), a medical practice based on scientific evidence, for elective total hip arthroplasty surgery, mainly comparing the National Average Hospital Admission Rate of 7.1 days. Methods 98 patients who underwent elective total hip arthroplasty surgery via the direct anterior approach, anterolateral approach and posterior approach were included in the FTP from December 2018 to March 2020, being followed up preoperatively, intraoperatively and immediately postoperatively. Results The average length of hospital stay was 2.8 days, being 2.1 days for the direct anterior approach, 3.0 days for the anterolateral access approach and 4.1 days for the posterior access approach. The average surgery time was 90 minutes, 19 (19.39%) of the patients were referred to the ICU in the postoperative period, however, none of them underwent surgery using the direct anterior approach. We had no cases of deep vein thrombosis (DVT), pulmonary embolism (PTE) or neurological injury, 19 (19.39%) patients had postoperative bleeding requiring dressing change, 4 (4.08%) needed blood transfusion, 2 (2.04%) patients had implant instability, 1 (1.02%) patient had a fracture during surgery and 1 (1.02%) patient died of cardiac complications. Conclusion FTP may be a viable alternative to reduce the length of stay and immediate postoperative complications for elective total hip arthroplasty surgery decreasing the length of stay of patients by 2 to 3 times when compared to the national average of 7.1 days.
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Abstract Objective Evaluate the results of the implementation of the Fast Track Protocol (FTP), a medical practice based on scientific evidence, for elective total hip arthroplasty surgery, mainly comparing the National Average Hospital Admission Rate of 7.1 days. Methods 98 patients who underwent elective total hip arthroplasty surgery via the direct anterior approach, anterolateral approach and posterior approach were included in the FTP from December 2018 to March 2020, being followed up preoperatively, intraoperatively and immediately postoperatively. Results The average length of hospital stay was 2.8 days, being 2.1 days for the direct anterior approach, 3.0 days for the anterolateral access approach and 4.1 days for the posterior access approach. The average surgery time was 90 minutes, 19 (19.39%) of the patients were referred to the ICU in the postoperative period, however, none of them underwent surgery using the direct anterior approach. We had no cases of deep vein thrombosis (DVT), pulmonary embolism (PTE) or neurological injury, 19 (19.39%) patients had postoperative bleeding requiring dressing change, 4 (4.08%) needed blood transfusion, 2 (2.04%) patients had implant instability, 1 (1.02%) patient had a fracture during surgery and 1 (1.02%) patient died of cardiac complications. Conclusion FTP may be a viable alternative to reduce the length of stay and immediate postoperative complications for elective total hip arthroplasty surgery decreasing the length of stay of patients by 2 to 3 times when compared to the national average of 7.1 days.
Resumo Objetivo Avaliar os resultados da implantação do Protocolo de Recuperação Rápida (PRR), prática médica baseada em evidências científicas, para cirurgia eletiva de artroplastia total do quadril principalmente comparando à Taxa Média de Internação Hospitalar nacional de 7.1 dias. Métodos 98 pacientes submetidos a cirurgia eletiva de artroplastia total do quadril pela via direta anterior, via anterolateral e via posterior foram incluídos no PRR no período de dezembro de 2018 a março de 2020 sendo acompanhados no pré-operatório, intraoperatório e pós-operatório imediato. Resultados a Taxa Média de Permanência Hospitalar foi de 2,8 dias, sendo 2,1 dias para a Via de Acesso Anterior, 3,0 dias para via de acesso anterolateral e 4,1 dias para via de acesso posterior. O tempo médio de cirurgia foi de 90 minutos, 19 (19,39%) dos pacientes foram encaminhados à UTI no pós-operatório, no entanto nenhum deles operado pela via direta anterior. Não tivemos casos de trombose venosa profunda (TVP), embolia pulmonar (TEP) ou lesão neurológica, 19 (19,39%) pacientes tiveram sangramento pós-operatório com necessidade de troca de curativo, 4 (4,08%) necessidade de transfusão sanguínea, 2 (2,04%) pacientes apresentaram instabilidade do implante, 1(1,02%) paciente teve fratura durante a cirurgia e 1(1,02%) paciente faleceu por complicações cardíacas. Conclusão O PRR pode ser uma alternativa viável para diminuir o tempo de internação e as complicações pós-operatórias imediatas para a cirurgia eletiva de artroplastia total do quadril diminuindo 2 a 3 vezes o tempo de internação dos pacientes quando comparado com a média nacional de 7,1 dias.
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Humanos , Masculino , Feminino , Brasil , Protocolos Clínicos , Artroplastia de Quadril/reabilitação , Artroplastia do Joelho/reabilitação , Hospitais PúblicosRESUMO
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
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
Clinical studies demonstrate the impact of smoking on bone tissue fragility and higher incidence of fractures. However, it is not totally understood which physiological mechanisms could be involved in these events. Previously, we showed important changes in bone tissue components in experimental model of cigarette smoke (CS) exposure. CS exposure induces worsening in bone mineralization and a decrease in collagen type I deposition, leading to bone fragility. Considering that the majority of clinical studies described bone structural changes by radiographic images, in this study we performed analyses "in situ" using tissue samples from smokers, former smokers and non-smokers to better understand how the increase in inflammatory mediators induced by smoking exposure could interfere in bone cells activity leading bone structural changes. We observed increased levels of IL-1ß, IL-6 and TNF-α in bone tissue homogenates with a concomitant increase in osteoblast apoptosis in smokers and former smokers compared with non-smokers. Histological changes in both smokers and former smokers were characterized by reduction in collagen type I. Only in smokers, it was observed decrease in trabecular area, suggesting increased bone resorption and increase in collagen type V. These results showed that osteoblasts apoptosis in association with increased bone resorption leads bone structural changes in smokers.
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Reabsorção Óssea , Colágeno Tipo I , Humanos , Matriz Óssea , Osteoblastos , Apoptose , Fumar/efeitos adversosAssuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Linfócitos T Reguladores , Células Th17RESUMO
Asthma is a respiratory allergic disease presenting a high prevalence worldwide, and it is responsible for several complications throughout life, including death. Fortunately, asthma is no longer recognized as a unique manifestation but as a very heterogenic manifestation. Its phenotypes and endotypes are known, respectively, as pathologic and molecular features that might not be directly associated with each other. The increasing number of studies covering this issue has brought significant insights and knowledge that are constantly expanding. In this review, we intended to summarize this new information obtained from clinical studies, which not only allowed for the creation of patient clusters by means of personalized medicine and a deeper molecular evaluation, but also created a connection with data obtained from experimental models, especially murine models. We gathered information regarding sensitization and trigger and emphasizing the most relevant phenotypes and endotypes, such as Th2-high asthma and Th2-low asthma, which included smoking and obesity-related asthma and mixed and paucigranulocytic asthma, not only in physiopathology and the clinic but also in how these phenotypes can be determined with relative similarity using murine models. We also further investigated how clinical studies have been treating patients using newly developed drugs focusing on specific biomarkers that are more relevant according to the patient's clinical manifestation of the disease.