Exercise Physiology for undergraduates: the use of teaching strategies basead on the dialectical method

A metodologia dialética propõe um ensino de dupla mão (professor-aluno) que provoque a aprendizagem por meio de tarefas contínuas dos sujeitos. Para isso, o professor assume o papel de mediador e dirige as diferentes atividades. Nesse contexto, a Fisiologia do Exercício é uma disciplina academicamente orientada que está inserida em um ambiente dinâmico, e a utilização de estratégias de ensino se faz necessária para otimizar a apropriação do conhecimento de forma ativa, além de contribuir para a maior autonomia dos estudantes universitários. Portanto, o objetivo do presente estudo foi o de utilizar diferentes estratégias de ensinagem por meio de atividades propostas aos alunos na disciplina de Fisiologia da Atividade Motora I da Escola de Educação Física e Esporte da Universidade de São Paulo e correlacionar o desempenho do aluno com a sua participação nessas atividades propostas. Nossos principais achados demonstram correlações significativas e positivas entre a presença nas aulas e o desempenho nas avaliações (p < 0,0001; r = 0,84), bem como entre a realização das atividades propostas e o desempenho nas avaliações (p < 0,0001; r = 0,69). Em conjunto, esses dados sugerem que a utilização de diferentes estratégias de ensinagem baseadas na metodologia dialética com a ativa participação dos alunos é essencial para um bom rendimento acadêmico, sendo altamente recomendada para o ensino da Fisiologia do Exercício.The dialectic method proposes a two-way teaching (teacher-student) that causes learning through ongoing task of the subjects. For this, the teacher assumes the role of mediator and directs several activities. In line with the above, Exercise Physiology is an academically oriented discipline undergoing in a dynamic environment, and the use of different teaching strategies is needed to optimize the appropriation of knowledge in an active way and contribute to the greater autonomy of university students. Therefore, the aim of this study was apply different strategies in the course entitled "Physiology of the Motor Activity I" at School of Physical Education and Sport of University of Sao Paulo and assess a correlation between students participation and students performance. We used teaching strategies such as exposition and dialogue classes, practical classes, conversations with experts, directed study, study of scientific texts, concept mapping, case study and study of the environment in order to optimize the appropriation of the concepts of exercise physiology with emphasis on neuromuscular and cardiovascular physiology exercise. Our main findings show significant and positive correlations between the presence in classes and the performance evaluations (p < 0.0001, r = 0.84) as well as between the tasks proposed and the performance evaluations (p < 0.0001; r = 0.69). Altogether, these data suggest that using different teaching strategies based on the dialectic method associated with the participation of students is essential for a good academic performance in Exercise Physiology

Increased Clearance of Reactive Aldehydes and Damaged Proteins in Hypertension-Induced Compensated Cardiac Hypertrophy: Impact of Exercise Training

Background. We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). Methods and Results. SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. Conclusion. Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control

Exercise Training Restores Cardiac Protein Quality Control in Heart Failure

Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF) animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H2O2 release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H2O2 resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca2+-induced permeability transition and reduced H2O2 release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a nonpharmacological tool for heart failure therapy.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Sao Paulo - SP (FAPESP) [2009/18546-4, 2010/00028-4, 2012/05765-2]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Sao Paulo SP (FAPESP)Conselho Nacional de Pesquisa e Desenvolvimento - Brasil (CNPq) [479407/2010-0]Conselho Nacional de Pesquisa e Desenvolvimento Brasil (CNPq)Instituto Nacional de Ciencia e TecnologiaInstituto Nacional de Ciencia e TecnologiaNucleo de Apoio a Pesquisa de Processos Redox em BiomedicinaNucleo de Apoio a Pesquisa de Processos Redox em BiomedicinaFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2009/12349-2

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

Characterization of mitochondrial metabolism and dynamics in cardiac dysfunction-induced myocardial infarction in rats: effects of exercise training

O infarto do miocárdio é atualmente considerado a etiologia que mais contribui para o aparecimento de insuficiência cardíaca (IC) em humanos. Em detrimento a hiperativação de fatores neuro-humorais, a progressão da IC é caracterizada por uma série de anormalidades celulares associadas à disfunção ventricular. Dentre estas anormalidades, alterações na função e dinâmica mitocondrial merecem destaque, uma vez que a homeostase da organela é essencial para a viabilidade celular e o bom funcionamento da bomba cardíaca. No presente estudo, caracterizamos em modelo animal de disfunção cardíaca associada ao infarto do miocárdio: a) fenótipo cardíaco; b) função mitocondrial; c) equilíbrio redox; e d) dinâmica mitocondrial. Nossos resultados nos permitem afirmar que doze semanas após a cirurgia de infarto do miocárdio, os animais desenvolveram importantes alterações fenotípicas como aumento da massa cardíaca, dilatação ventricular, hipertrofia do cardiomiócito e maior deposição de tecido fibroso cardíaco, que contribuíram para o estabelecimento da disfunção ventricular. Além disso, foi possível confirmar a instalação do quadro de disfunção mitocondrial cardíaca, representada pela redução na capacidade respiratória e perda da homeostase redox. Por fim, encontramos um aumento no número de mitocôndrias cardíacas com menor diâmetro, alterações que vieram acompanhadas de uma menor atividade das enzimas relacionadas à fusão mitocondrial. Uma vez caracterizada a função e a dinâmica mitocondrial na disfunção cardíaca, avaliamos o efeito do treinamento físico aeróbico (TF) nessas variáveis. O TF, atualmente utilizado como um adjuvante no tratamento das doenças cardiovasculares, foi eficaz em promover o remodelamento cardíaco reverso e melhorar a função cardíaca nos animais infartados. Além disso, melhorou a capacidade respiratória e reduziu o estresse oxidativo, restaurando a função mitocondrial. Aliado a esses achados, o TF normalizou a atividade das enzimas relacionadas à dinâmica mitocondrial, fato associado à normalização do número e tamanho da organela. Esses resultados demonstram que a disfunção cardíaca induzida por infarto do miocárdio está associada à um quadro de mitocondriopatia em ratos, com alterações tanto na função quanto estrutura mitocondrial, e que o TF desencadeia efeitos benéficos na manutenção da integridade/função mitocondrial e melhora da função contrátil cardíacaMyocardial infarction is considered the etiology that most contributes to the onset of heart failure in humans. Among the ventricular dysfunction-associated cellular abnormalities, changes in mitochondrial function and dynamics are critical, since the organelle homeostasis is crucial in maintaining the metabolic, electrical and mechanical properties of the heart. In the present study, we characterized in cardiac dysfunction- induced myocardial infarction in rats: a) cardiac phenotype; b) mitochondrial metabolism; c) redox balance, and d) mitochondrial dynamics. Our results show that twelve weeks after myocardial surgery, the animals developed pathological cardiac remodeling-associated ventricular dysfunction. Furthermore, we observed a reduced mitochondrial respiratory capacity and loss of redox homeostasis. Finally, we found a lower activity of enzymes related to mitochondrial fusion, these changes were accompanied by an increase in the number of small mitochondria. Once characterized mitochondrial function and dynamics, we evaluated the effect of exercise training in these variables in rats with cardiac dysfunction. The exercise training, currently established as an important non-pharmacological treatment for cardiovascular diseases, reversed the pathological cardiac remodeling and minimized the ventricular dysfunction in infarcted animals. Furthermore, exercise training restored the mitochondrial function by increasing respiratory capacity and reducing oxidative stress. Finally, exercise training restored the activity of mitochondrial dynamics-related enzymes and morphology. Taken together, our findings uncover the potential benefits of exercise training in reversing the cardiac mitochondriopathy observed in failing hearts, reinforcing the importance of this intervention as a non-pharmacological tool for heart failure therap

Protein quality control in skeletal muscle weakness/wasting: role of &#946;2-adrenoceptor.

O Controle de qualidade de proteína (CQP) consiste na supervisão e no processamento de proteínas danificadas por meio de processos catalíticos (proteassoma e autofagia). Nesse estudo, caracterizamos o CQP, bem como os benefícios da ativação &#946;2-adrenérgica (&#946;2-AR) modulador positivo do CQP, em modelo animal de disfunção/atrofia muscular induzida por constrição crônica do nervo isquiático (CCI). Observamos que, apesar de um aumento na atividade catalítica, a atrofia está associada à um CQP insuficiente, detectado por um acúmulo de proteínas citotóxicas nessa musculatura. O tratamento com Formoterol (agonista &#946;2-AR) aumentou a atividade proteassomal e restaurou o fluxo de degradação via autofagia, resultando na melhora do CQP e da miopatia esquelética. A inibição da autofagia, mas não do proteassoma, foi capaz de abolir os efeitos do Formoterol na CCI. Nossos resultados sugerem uma nova contribuição da sinalização &#946;2-AR no quadro de miopatia esquelética, no qual sua ativação foi capaz de restaurar o CQP, contribuindo para a melhora do trofismo e função muscular.The protein quality control (PQC) detects, repairs and disposes cytotoxic proteins through different proteolytic systems (proteasome and autophagy). Here, we characterized the PQC profile as well as the benefits of sustained &#946;2-adrenoceptor activation (&#946;2-AR) a positive PQC modulator, during skeletal muscle atrophy in a rat model of sciatic nerve constriction (SNC). PQC is disrupted in SNC rats, demonstrated by elevated proteasomal and lysosomal activities along with accumulation of cytotoxic proteins and pro-apoptotic factors. The &#946;2-AR activation (Formoterol) promotes a further increase in proteasomal activity, along with autophagic flux reestablishment. Of interest, sustained autophagy inhibition, but not proteasomal inhibition, is sufficient to abolish Formoterol effects on skeletal muscle PQC, mass and strength. These findings suggest a new contribution of &#946;2-AR signalling pathway to the pathophysiology of skeletal muscle where &#946;2-AR restores the impaired PQC, therefore contributing to a better skeletal muscle morphology and function

Impact of exercise training on redox signaling in cardiovascular diseases

Reactive oxygen and nitrogen species regulate a wide array of signaling pathways that governs cardiovascular physiology. However, oxidant stress resulting from disrupted redox signaling has an adverse impact on the pathogenesis and progression of cardiovascular diseases. In this review, we address how redox signaling and oxidant stress affect the pathophysiology of cardiovascular diseases such as ischemia-reperfusion injury, hypertension and heart failure. We also summarize the benefits of exercise training in tackling the hyperactivation of cellular oxidases and mitochondrial dysfunction seen in cardiovascular diseasesFundação de Amparo a Pesquisa do Estado de São Paulo (2012/05765-2)Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico (470880/2012-0)Fundação de Amparo a Pesquisa do Estado de São Paulo (2012/14416-1

Increased Clearance of Reactive Aldehydes and Damaged Proteins in Hypertension-Induced Compensated Cardiac Hypertrophy: Impact of Exercise Training

Background. We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). Methods and Results. SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. Conclusion. Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control

β2-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise

The molecular mechanisms underlying skeletal muscle mitochondrial adaptations induced by aerobic exercise (AE) are not fully understood. We have previously shown that AE induces mitochondrial adaptations in cardiac muscle, mediated by sympathetic stimulation. Since direct sympathetic innervation of neuromuscular junctions influences skeletal muscle homeostasis, we tested the hypothesis that &beta;2-adrenergic receptor (&beta;2-AR)-mediated sympathetic activation induces mitochondrial adaptations to AE in skeletal muscle. Male FVB mice were subjected to a single bout of AE on a treadmill (80% Vmax, 60 min) under &beta;2-AR blockade with ICI 118,551 (ICI) or vehicle, and parameters of mitochondrial function and morphology/dynamics were evaluated. An acute bout of AE significantly increased maximal mitochondrial respiration in tibialis anterior (TA) isolated fiber bundles, which was prevented by &beta;2-AR blockade. This increased mitochondrial function after AE was accompanied by a change in mitochondrial morphology towards fusion, associated with increased Mfn1 protein expression and activity. &beta;2-AR blockade fully prevented the increase in Mfn1 activity and reduced mitochondrial elongation. To determine the mechanisms involved in mitochondrial modulation by &beta;2-AR activation in skeletal muscle during AE, we used C2C12 myotubes, treated with the non-selective &beta;-AR agonist isoproterenol (ISO) in the presence of the specific &beta;2-AR antagonist ICI or during protein kinase A (PKA) and G&alpha;i protein blockade. Our in vitro data show that &beta;-AR activation significantly increases mitochondrial respiration in myotubes, and this response was dependent on &beta;2-AR activation through a G&alpha;s-PKA signaling cascade. In conclusion, we provide evidence for AE-induced &beta;2-AR activation as a major mechanism leading to alterations in mitochondria function and morphology/dynamics. &beta;2-AR signaling is thus a key-signaling pathway that contributes to skeletal muscle plasticity in response to exercise

Fisiologia do Exercício para alunos de graduação: uso de estratégias de ensino baseadas na metodologia dialética

A metodologia dialética propõe um ensino de dupla mão (professor-aluno) que provoque a aprendizagem por meio de tarefas contínuas dos sujeitos. Para isso, o professor assume o papel de mediador e dirige as diferentes atividades. Nesse contexto, a Fisiologia do Exercício é uma disciplina academicamente orientada que está inserida em um ambiente dinâmico, e a utilização de estratégias de ensino se faz necessária para otimizar a apropriação do conhecimento de forma ativa, além de contribuir para a maior autonomia dos estudantes universitários. Portanto, o objetivo do presente estudo foi o de utilizar diferentes estratégias de ensinagem por meio de atividades propostas aos alunos na disciplina de Fisiologia da Atividade Motora I da Escola de Educação Física e Esporte da Universidade de São Paulo e correlacionar o desempenho do aluno com a sua participação nessas atividades propostas. Nossos principais achados demonstram correlações significativas e positivas entre a presença nas aulas e o desempenho nas avaliações (p < 0,0001; r = 0,84), bem como entre a realização das atividades propostas e o desempenho nas avaliações (p < 0,0001; r = 0,69). Em conjunto, esses dados sugerem que a utilização de diferentes estratégias de ensinagem baseadas na metodologia dialética com a ativa participação dos alunos é essencial para um bom rendimento acadêmico, sendo altamente recomendada para o ensino da Fisiologia do Exercício