Exercise Prevents Diaphragm Wasting Induced by Cigarette Smoke through Modulation of Antioxidant Genes and Metalloproteinases

Background. The present study aimed to analyze the effects of physical training on an antioxidant canonical pathway and metalloproteinases activity in diaphragm muscle in a model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD). Methods. Male mice were randomized into control, smoke, exercise, and exercise + smoke groups, which were maintained in trial period of 24 weeks. Gene expression of kelch-like ECH-associated protein 1nuclear factor erythroid-2 like 2and heme-oxygenase1 by polymerase chain reaction was performed. Metalloproteinases 2 and 9 activities were analyzed by zymography. Exercise capacity was evaluated by treadmill exercise test before and after the protocol. Results. Aerobic training inhibited diaphragm muscle wasting induced by cigarette smoke exposure. This inhibition was associated with improved aerobic capacity in those animals that were submitted to 24 weeks of aerobic training, when compared to the control and smoke groups, which were not submitted to training. The aerobic training also downregulated the increase of matrix metalloproteinases (MMP-2 and MMP-9) and upregulated antioxidant genes, such as nuclear factor erythroid-2 like 2 (NRF2) and heme-oxygenase1 (HMOX1), in exercise + smoke group compared to smoke group. Conclusions. Treadmill aerobic training protects diaphragm muscle wasting induced by cigarette smoke exposure involving upregulation of antioxidant genes and downregulation of matrix metalloproteinases.CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)Sao Paulo Research Foundation (FAPESP) Grant [2012/15165-2]Univ Brasilia, Phys Therapy Div, Brasilia, DF, BrazilUniv Paulista, Dept Phys Therapy, Brasilia, DF, BrazilUniv Sao Paulo, Sch Med, Dept Med LIM 20, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Av Ana Costa 95, BR-11060001 Santos, SP, BrazilUniv Fed Sao Carlos, Dept Phys Therapy, Sao Carlos, SP, BrazilUniv Brasil, Postgrad Program Bioengn, Rua Carolina Fonseca 235, BR-08230030 Sao Paulo, SP, BrazilBrazilian Inst Teaching & Res Pulm & Exercise Imm, Rua Pedro Ernesto 240, BR-12245520 Sao Jose Dos Campos, SP, BrazilUniv Brasilia, Phys Therapy Div, Brasilia, DF, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Av Ana Costa 95, BR-11060001 Santos, SP, BrazilFAPESP [2012/15165-2]Web of Scienc

Nasal and systemic inflammatory profile after short term smoking cessation

SummaryIntroductionSmoking cessation promotes health benefits and, despite cigarette smoking be an important pro inflammatory stimulus, there are few studies concerning the nasal and systemic inflammation; as well as the mucociliary clearance behavior in smokers after short period of smoking cessation.AimTo evaluate the nasal and systemic inflammatory markers and mucociliary clearance behavior after 30 days of cigarette smoking abstinence.MethodsTwenty-five smokers were included and divided into two groups: abstinent smokers (n = 14) and current smokers (n = 11). Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10 were measured on nasal lavage and blood serum samples by ELISA at baseline and after 30 days. The mucociliary clearance, exhaled carbon monoxide (exCO) and carboxyhemoglobin (HbCO) were also measured at the same moments.ResultsThere was a decrease of TNF-α level only in blood serum at 30 days of abstinence compared to current smokers. The mucociliary clearance improved and there was a reduction in exCO and HbCO (p < 0.05 for all) after 30 days of smoking cessation.ConclusionThe short term smoking abstinence decreased systemic inflammation and improved nasal mucociliary clearance, despite not having changed the nasal inflammation

Como cuidar do seu coração na pandemia do COVID-19: exercícios respiratórios

The disease caused by the new coronavirus (COVID-19) mainly affects the respiratory system, and may progress in the most severe cases to pneumonia and acute respiratory distress syndrome. COVID-19 is caused by the SARS-CoV-2 coronavirus and the first cases were reported in December 2019 in Wuhan Province (China). As a result, COVID-19 reached European countries and infected 2,159,791 people until June 1, 2020. On that same date (June 1, 2020), the global epicenter is concentrated in the Americas, with the United States of America have 1,734,040 confirmed cases with 102,640 deaths. In this context, in the world, there are already 6,057,853 confirmed cases with 341,166 deaths (WHO, 2020). In Brazil, the first case of COVID-19 was officially notified on March 4, 2020 with the first death on March 18, 2020. On June 1, 2020, 514,849 people were infected and 29,314 Brazilians lost the fight against disease and their deaths were confirmed (2). According to the recommendations of the World Health Organization (WHO), as of the third week of March, most Brazilian states and municipalities started to adopt measures of social distancing, from which citizens were instructed to stay at their homes , being allowed the circulation of only people of essential services (health, safety, food professionals...) as a strategy to face COVID-19. In April, WHO began to guide the use of masks to avoid contamination when circulating on the streets. In this sense, the great majority of Brazilian cities have adopted the use of masks as a protection strategy in circulation by public transport and spaces. However, starting a sudden state of quarantine implies a radical change in the lifestyle of the population. In many cases, it can impact physical fitness and, essentially, increase psychological impacts. In this context, individuals are subjugated to post-traumatic stress, symptoms of confusion and anger. In addition, stressors that have become more prevalent with the longest quarantine duration have been identified, including: (i) fear of infection; (ii) frustration; (iii) boredom; (iv) lack of supplies; (v) inadequate information; (vi) financial losses; and, (vii) stigmas (3). In this context, adopting strategies that may be available to part of the population that is restricted to their homes and that can have a positive impact on mental health and still help to maintain pulmonary function, seems appropriate and welcome at a critical moment.A doença causada pelo novo coronavírus (COVID-19) afeta principalmente o sistema respiratório, podendo progredir nos casos mais graves para pneumonia e síndrome do desconforto respiratório agudo. A COVID-19 é provocada pelo coronavírus SARS-CoV-2 e os primeiros casos foram notificados em dezembro de 2019 na Província de Wuhan (China). Na sequência, a COVID-19 alcançou os países europeus e infectou 2.159.791 pessoas até o dia 01 de junho de 2020. Nessa mesma data (01/06/2020), o epicentro mundial se concentra nas Américas, sendo que os Estados Unidos da América apresentam 1.734.040 casos confirmados com 102.640 mortes. Neste contexto, no mundo, já são 6.057.853 de casos confirmados com 341.166 mortes (WHO, 2020). No Brasil, o primeiro caso da COVID-19 foi notificado oficialmente em 04 de março de 2020 com a primeira morte no dia 18 de março de 2020. Em 01 de junho de 2020, 514.849 pessoas estavam infectadas e 29.314 brasileiros perderam a luta contra a doença e estiveram seus óbitos confirmados (2). De acordo com as recomendações da Organização Mundial da Saúde (OMS), a partir da terceira semana do mês de março, a maioria dos estados e municípios brasileiros passaram a adotar medidas de distanciamento social, da qual os cidadãos foram orientados a ficarem em suas casas, sendo permitida a circulação apenas de pessoas de serviços essenciais (profissionais da saúde, da segurança, da área de alimentação...) como estratégia de enfrentamento a COVID-19. Em abril, a OMS passou a orientar o uso de máscaras para evitar a contaminação ao circular pelas ruas. Neste sentido, a grande maioria das cidades brasileiras adotaram a utilização de máscaras como estratégia de proteção em circulação por transportes e espaços públicos.Todavia, iniciar um estado repentino de quarentena implica em uma mudança radical no estilo de vida da população. Em muitos casos, pode impactar na aptidão física e, essencialmente, aumentar os impactos psicológicos. Neste contexto, os indivíduos estão subjugados ao estresse pós-traumático, sintomas de confusão e raiva. Além disso, foram identificados fatores estressores que podem se tornar mais prevalentes com a maior duração da quarentena, entre eles foram identificados: (i) medo de infecção; (ii) frustração; (iii) tédio; (iv) falta de suprimentos; (v) informações inadequadas; (vi) perdas financeiras; e, (vii) estigmas (3). Neste contexto, adotar estratégias que possam estar ao alcance de parte da população que está restrita as suas casas e que possam ter impacto positivo sobre a saúde mental e ainda possam auxiliar na manutenção da função pulmonar, parece adequada e bem vinda num momento crítico

Eu quero saber: 60 perguntas e respostas sobre a COVID-19

COVID-19 is caused by the new coronavirus SARS-CoV-2 and the first cases were reported in December 2019 in Wuhan Province in China. Subsequently, the virus quickly reached Europe, the United States and landed in Brazil. Even after four months of the first confirmed case in the city of São Paulo (March 4, 2020), many doubts remain or arise as researchers learn more about COVID-19 and the rate at which the disease progresses. Interestingly, the concern about seeking to know more about the new disease and about the measures to combat it began to appear in the speeches and questions of patients and visitors of our Laboratory of the Research Group on Cardiorespiratory Evaluation and Rehabilitation (GECARE) of the Department of Physiotherapy at the Federal University of Rio de Janeiro (UFRJ). This allowed us to exercise a fundamental approach in the context of health care, to inform from listening to patients' doubts. Break the logic of imposing information. In this sense, GECARE's scientific initiation, master's and doctoral students began to catalog doubts about COVID-19. This happened based on groups of messages maintained with patients during the period of social distance for guidance and monitoring of health conditions. Then, we set up a multiprofessional health team to answer the questions and compiled this 3rd E-book on COVID-19 from our group. We believe that our patients' doubts and the quick question and answer format will allow people in general to know more about the context of COVID-19.A COVID-19 é provocada pelo novo coronavírus SARS-CoV-2 e os primeiros casos foram notificados em dezembro de 2019 na Província de Wuhan na China. Na sequência, rapidamente o vírus alcançou a Europa, Estados Unidos e desembarcou no Brasil. Mesmo depois de quatro meses do primeiro caso confirmado na cidade de São Paulo (04 de março de 2020), muitas dúvidas permanecem ou surgem à medida que os pesquisadores conhecem mais sobre a COVID-19 e na proporção que a doença avança. Interessantemente, a inquietação pela busca em saber mais sobre a nova doença e sobre as medidas para combatê-la começou a surgir nas falas e perguntas dos pacientes e frequentadores do nosso Laboratório do Grupo de Pesquisa em Avaliação e Reabilitação Cardiorrespiratória (GECARE) do Departamento de Fisioterapia da Universidade Federal do Rio de Janeiro (UFRJ). Isso nos permitiu exercitar uma abordagem fundamental no contexto do cuidado em saúde, informar a partir da escuta das dúvidas dos pacientes. Quebrar a lógica da imposição da informação. Neste sentido, os alunos de iniciação científica, mestrado e doutorado do GECARE começaram a catalogar as dúvidas sobre a COVID-19. Isso aconteceu a partir dos grupos de mensagens mantidos com os pacientes durante o período de distanciamento social para orientações e acompanhamento das condições de saúde. Na sequência, montamos um time multiprofissional de saúde para responder as questões e compilamos neste 3º E-book sobre COVID-19 do nosso grupo. Acreditamos que as dúvidas dos nossos pacientes e o formato rápido de perguntas e respostas permitirão que as pessoas em geral possam conhecer mais sobre o contexto da COVID-19

In vivo evaluation of the airway epithelium in a murine model of allergic airway disease: effects of inhalatory drugs on ciliary beat frequency

O objetivo do presente trabalho foi propiciar o acesso in vivo ao epitélio respiratório e estudar a frequência de batimento ciliar (FBC) e a diferença de potencial transepitelial (DP) em um modelo murino de doença alérgica das vias aéreas induzida por ovoalbumina. Camundongos Swiss foram sensibilizados com ovoalbumina (OVA) através de duas injeções intraperitoneais de alérgico com o adjuvante hidróxido de alumínio (dias 0 e 14) e quatro inalações de OA 1% (dias 22, 24, 26 e 28). O grupo controle (S) foi tratado com salina 0,9 % seguindo o mesmo protocolo. Após 48h da última inalação, os camundongos foram anestesiados, a traquéia foi exposta longitudinalmente (1x4 mm) e o epitélio pode ser visualizado. A FBC foi mensurada pela técnica estroboscópica antes (basal) e logo após a administração inalatória das drogas (salbutamol e brometo de ipratrópio). A DP foi mensurada nos grupos S e OVA. Foram avaliados o lavado broncoalveolar e o remodelamento do epitélio da cavidade nasal, traquéia e vias aéreas distais. Nenhuma diferença foi encontrada na FBC basal entre os grupos (OVA e S), no entanto o grupo OVA mostrou uma DP basal significativamente menor. A inalação de salbutamol (3.5.10-3M ou 3.5.10-4M) elevou a FBC nos grupos estudados (p<0,05). O brometo de ipratrópio (10- 4M e 6.10-4M) não influenciou a FBC basal. Nossos resultados mostraram que é possível avaliar a FBC e a DP in vivo em um modelo murino de doença pulmonar alérgica crônica, e indicam que o processo inflamatório não afeta a FBC, mas contribui para o aumento de muco nas vias aéreas com conseqüências deletérias ao transporte mucociliar facilitando a retençãoThe aim of the present work was to propitiate the in vivo assessment of the respiratory epithelium. The effects of salbutamol and ipratropium bromide on ciliary beat frequency (CBF) in a murine model of allergic airway disease were addressed. Transepithelial electric potential difference (PD) was also measured in order to verify the integrity of the epithelial barrier. Mice were sensitized with ovalbumin (OVA) by two intraperitoneal injections of allergen (days 0 and 14) and four inhalations of OVA 1% (days 22, 24, 26 and 28). The control group was treated with saline following the same procedures. After 48 hs of the last inhalation, mice were anesthetized, trachea was opened longitudinally (1 x 4 mm) and the ciliated epithelium could be visualized. CBF was measured by a modification on the videoscopic technique. We measured the CBF before and just after the administration of aerosolized substances. The PD was also measured on groups OVA and S. Additionally, the eosinophil cell count was measured on broncoalveolar lavage (BAL) in order to access the magnitude of airway inflammation. No difference on baseline CBF was noticed between groups (OVA and S), however the OVA group had a significantly lower PD. The administration of aerosolized capsaicin (3.10-9M) and salbutamol (3.5.10-3M or 3.5.10-4M) increased CBF in all groups studied. Ipratropium bromide (10-4M and 6.10- 4M) did not influence the CBF. The eosinophil cell count in broncoalveolar lavage was higher in OVA group compared to S group. CBF and PD results indicate that the inflammatory process does not affect the ciliary beat frequency but augments the amount of mucus in the airway, with deleterious consequences to the mucociliary transport facilitating mucus retention. Our results demonstrated for the first time the possibiliy of studying airway epithelium in an in vivo murine model of allergic airway diseas

In vivo evaluation of the airway epithelium in a murine model of allergic airway disease: effects of inhalatory drugs on ciliary beat frequency

O objetivo do presente trabalho foi propiciar o acesso in vivo ao epitélio respiratório e estudar a frequência de batimento ciliar (FBC) e a diferença de potencial transepitelial (DP) em um modelo murino de doença alérgica das vias aéreas induzida por ovoalbumina. Camundongos Swiss foram sensibilizados com ovoalbumina (OVA) através de duas injeções intraperitoneais de alérgico com o adjuvante hidróxido de alumínio (dias 0 e 14) e quatro inalações de OA 1% (dias 22, 24, 26 e 28). O grupo controle (S) foi tratado com salina 0,9 % seguindo o mesmo protocolo. Após 48h da última inalação, os camundongos foram anestesiados, a traquéia foi exposta longitudinalmente (1x4 mm) e o epitélio pode ser visualizado. A FBC foi mensurada pela técnica estroboscópica antes (basal) e logo após a administração inalatória das drogas (salbutamol e brometo de ipratrópio). A DP foi mensurada nos grupos S e OVA. Foram avaliados o lavado broncoalveolar e o remodelamento do epitélio da cavidade nasal, traquéia e vias aéreas distais. Nenhuma diferença foi encontrada na FBC basal entre os grupos (OVA e S), no entanto o grupo OVA mostrou uma DP basal significativamente menor. A inalação de salbutamol (3.5.10-3M ou 3.5.10-4M) elevou a FBC nos grupos estudados (p<0,05). O brometo de ipratrópio (10- 4M e 6.10-4M) não influenciou a FBC basal. Nossos resultados mostraram que é possível avaliar a FBC e a DP in vivo em um modelo murino de doença pulmonar alérgica crônica, e indicam que o processo inflamatório não afeta a FBC, mas contribui para o aumento de muco nas vias aéreas com conseqüências deletérias ao transporte mucociliar facilitando a retençãoThe aim of the present work was to propitiate the in vivo assessment of the respiratory epithelium. The effects of salbutamol and ipratropium bromide on ciliary beat frequency (CBF) in a murine model of allergic airway disease were addressed. Transepithelial electric potential difference (PD) was also measured in order to verify the integrity of the epithelial barrier. Mice were sensitized with ovalbumin (OVA) by two intraperitoneal injections of allergen (days 0 and 14) and four inhalations of OVA 1% (days 22, 24, 26 and 28). The control group was treated with saline following the same procedures. After 48 hs of the last inhalation, mice were anesthetized, trachea was opened longitudinally (1 x 4 mm) and the ciliated epithelium could be visualized. CBF was measured by a modification on the videoscopic technique. We measured the CBF before and just after the administration of aerosolized substances. The PD was also measured on groups OVA and S. Additionally, the eosinophil cell count was measured on broncoalveolar lavage (BAL) in order to access the magnitude of airway inflammation. No difference on baseline CBF was noticed between groups (OVA and S), however the OVA group had a significantly lower PD. The administration of aerosolized capsaicin (3.10-9M) and salbutamol (3.5.10-3M or 3.5.10-4M) increased CBF in all groups studied. Ipratropium bromide (10-4M and 6.10- 4M) did not influence the CBF. The eosinophil cell count in broncoalveolar lavage was higher in OVA group compared to S group. CBF and PD results indicate that the inflammatory process does not affect the ciliary beat frequency but augments the amount of mucus in the airway, with deleterious consequences to the mucociliary transport facilitating mucus retention. Our results demonstrated for the first time the possibiliy of studying airway epithelium in an in vivo murine model of allergic airway diseas

The effects of elastic tubing-based resistance training compared with conventional resistance training in patients with moderate chronic obstructive pulmonary disease: a randomized clinical trial

To investigate the effects of elastic tubing training compared with conventional resistance training on the improvement of functional exercise capacity, muscle strength, fat-free mass, and systemic inflammation in patients with chronic obstructive pulmonary disease.status: publishe

The effects of elastic tubing-based resistance training compared with conventional resistance training in patients with moderate chronic obstructive pulmonary disease: a randomized clinical trial

Objective: To investigate the effects of elastic tubing training compared with conventional resistance training on the improvement of functional exercise capacity, muscle strength, fat-free mass, and systemic inflammation in patients with chronic obstructive pulmonary disease.Design: A prospective, randomized, eight-week clinical trial.Setting: The study was conducted in a university-based, outpatient, physical therapy clinic.Subjects: A total of 49 patients with moderate chronic obstructive pulmonary disease.Interventions: Participants were randomly assigned to perform elastic tubing training or conventional resistance training three times per week for eight weeks.Main measures: The primary outcome measure was functional exercise capacity. The secondary outcome measures were peripheral muscle strength, health-related quality of life assessed by the Chronic Respiratory Disease Questionnaire (CRDQ), fat-free mass, and cytokine profile.Results: After eight weeks, the mean distance covered during six minutes increased by 73 meters (69) in the elastic tubing group and by 42 meters (+/- 59) in the conventional group (p < 0.05). The muscle strength and quality of life improved in both groups (P < 0.05), with no significant differences between the groups. There was a trend toward an improved fat-free mass in both groups (P = 0.05). After the first and last sessions, there was an increase in interleukin 1 (IL-1) and interleukin 10 (IL-10) in both groups, while tumour necrosis factor alpha (TNF-) was stimulated only in the conventional training group.Conclusion: Elastic tubing training had a greater effect on functional exercise capacity than conventional resistance training. Both interventions were equally effective in improving muscle strength and quality of life

Moderate treadmill training induces limited effects on quadriceps muscle hypertrophy in mice exposed to cigarette smoke involving metalloproteinase 2

Background: Long-term cigarette smoke (CS) induces substantive extrapulmonary effects, including musculoskeletal system disorders. Exercise training seems to protect long-term smokers against fiber atrophy in the locomotor muscles. Nevertheless, the extracellular matrix (ECM) changes in response to aerobic training remain largely unknown. Thus, we investigated the effects of moderate treadmill training on aerobic performance, crosssectional area (CSA), fiber distribution, and metalloproteinase 2 (MMP-2) activity on quadriceps muscle in mice exposed to chronic CS. Methods: Male mice were randomized into four groups: control or smoke (6 per group) and exercise or exercise+smoke (5 per group). Animals were exposed to 12 commercially filtered cigarettes per day (0.8 mg of nicotine, 10 mg of tar, and 10 mg of CO per cigarette). The CSA, fibers distribution, and MMP-2 activity by zymography were assessed after a period of treadmill training (50% of maximal exercise capacity for 60 min/day, 5 days/week) for 24 weeks. Results: The CS exposure did not change CSA compared to the control group (p>0.05), but minor fibers in the frequency distribution (<1000 µm2 ) were observed. Long-term CS exposure attenuated CSA increases in exercise conditions (smoke+exercise vs exercise) while did not impair aerobic performance. Quadriceps CSA increased in mice nonsmoker submitted to aerobic training (p = 0.001). There was higher pro-MMP-2 activity in the smoke +exercise group when compared to the smoke group (p = 0.01). Regarding active MMP-2, the exercise showed higher values when compared to the control group (p = 0.001). Conclusion: Moderate treadmill training for 24 weeks in mice exposed to CS did not modify CSA, despite inducing higher pro-MMP-2 activity in the quadriceps muscle, suggesting limited effects on ECM remodeling. Our findings may contribute to new insights into molecular mechanisms for CS conditions