Formoterol reduces muscle wasting in mice undergoing doxorubicin chemotherapy.

Background: Even though doxorubicin (DOX) chemotherapy promotes intense muscle wasting, this drug is still widely used in clinical practice due to its remarkable efficiency in managing cancer. On the other hand, intense muscle loss during the oncological treatment is considered a bad prognosis for the disease's evolution and the patient's quality of life. In this sense, strategies that can counteract the muscle wasting induced by DOX are essential. In this study, we evaluated the effectiveness of formoterol (FOR), a ß2-adrenoceptor agonist, in managing muscle wasting caused by DOX. Methods and results: To evaluate the effect of FOR on DOX-induced muscle wasting, mice were treated with DOX (2.5 mg/kg b.w., i.p. administration, twice a week), associated or not to FOR treatment (1 mg/kg b.w., s.c. administration, daily). Control mice received vehicle solution. A combination of FOR treatment with DOX protected against the loss of body weight (p<0.05), muscle mass (p<0.001), and grip force (p<0.001) promoted by chemotherapy. FOR also attenuated muscle wasting (p<0.01) in tumor-bearing mice on chemotherapy. The potential mechanism by which FOR prevented further DOX-induced muscle wasting occurred by regulating Akt/FoxO3a signaling and gene expression of atrogenes in skeletal muscle. Conclusions: Collectively, our results suggest that FOR can be used as a pharmacological strategy for managing muscle wasting induced by DOX. This study provides new insights into the potential therapeutic use of FOR to improve the overall wellbeing of cancer patients undergoing DOX chemotherapy.

Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism.

Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation- and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.

Physical activity recommendations for cancer prevention and control: a Brazilian consortium

Objective: This article describes the development process and summarizes the results of the Brazilian physical activity recommendations for cancer prevention and control, which was prepared to support health-care professionals. Material and Methods: These recommendations were elaborated considering: (i) the effect of physical activity on cancer prevention in the general healthy population; and (ii) on all-cause and cancer-specific mortality in cancer survivors. The process of preparing the recommendations was systematized, transparent and reproducible, following the recommendations of the appraisal of guidelines for research and evaluation (AGREE-II). We appraised the certainty of evidence for breast, prostate, colorectal and lung cancers, which are among the most frequent in Brazil, using the grading of recommendations, assessment, development and evaluations (GRADE) approach. Results: Regarding the risk of cancer, we found high certainty of evidence supporting the association between moderate-to-vigorous physical activity and lower risk of breast and colon cancer, moderate certainty of evidence for lung cancer and low certainty of evidence for prostate and rectal cancer. We found moderate certainty of evidence supporting the association between moderate-to-vigorous physical activity and reduction of all-cause and cancer-specific mortality from breast, colon and rectal cancer, and cancer-specific mortality from prostate cancer, when physical activity was performed after the disease diagnosis. We found low certainty of evidence for the association between physical activity and lung cancer mortality. Based on our findings, physical activity recommendations were proposed, including a step-by-step guide to support health-care professionals when recommending physical activity for all adults (including elderly people), with or without a diagnosis of cancer. Conclusion: Our recommentations may be useful to support health-care professionals counselling for physical activity, which contribute to reductions in physical inactivity in the general population and in the growing population of cancer survivors

Cardiovascular physiology and autonomic heart control principles: the use of a station rotation strategy to recall basic cardiovascular knowledge among exercise science students

Abstract Aim: Cardiovascular physiology learned by exercise science students is often quickly forgotten. We tested whether a state rotation model would help students to recall key principles of Cardiovascular Physiology (CV). Methods: Seventy-one undergraduate students enrolled in the Exercise Physiology Course at the School of Physical Education and Sport, University of São Paulo, participated in the study. The students were randomly assigned into one of 4 stations, dedicated to recalling the concepts of the heart as a pump (e.g. preload, post-load, and contractility; station 1) and hemodynamics (e.g. serial and parallel conductance; station 2) by using the educational tool. Heart rate (HR) control by sympathetic nervous system activation (station 3) and HR control by vagal activation (station 4) were assessed by quantifying HR response to the Stroop color and word test and during face immersion in cold water, respectively. To evaluate the efficacy of the intervention, we used a Socrative app to launch eight multiple-choice questions before (PRE) and after (POST) the student's station rotation. The questions were related to the basic principles of exercise physiology and its consequences on the cardiovascular system. Results: The 4-station average score (% of corrected answers) achieved after the station rotation was higher than the score achieved before (71.21%, SD 14.50 vs. 31.07%, SD 18.04; for POST and PRE, respectively p < 0.005). Considering specific stations, the lowest score of corrected answers before the rotation was observed at station 2- hemodynamics when compared with station 1-heart as a pump and station 3/4 - autonomic control (18.9%, SD 0.9 vs. 46.5, SD 24.1 and 34.8, SD 2.1 for hemodynamics, heart as a pump and autonomic control, respectively). Interestingly, after the rotation, there was a significant increase in corrected scores for all stations (33.9, SD 9.8; 80.5, SD 4.6 and 90.2, SD 2.3, for hemodynamics, heart as a pump, and autonomic control, respectively). Conclusion: Our results suggest that the use of the educational tool was effective to recall CV principles that are essential to a better understanding of the CV responses to exercise and applying the concepts in exercise testing and prescription for different populations.

The influence of a supervised group exercise intervention combined with active lifestyle recommendations on breast cancer survivors' health, physical functioning, and quality of life indices: study protocol for a randomized and controlled trial.

BACKGROUND: Most cancer patients, under active treatment or not, are sedentary, despite increasing scientific and clinical understanding of the benefits of exercise and physical activity, such as improving quality of life, limiting disease symptoms, decreasing cancer recurrence, and increasing overall survival. Studies have shown that both supervised exercise and unsupervised physical activity programs have low adherence and limited long-term benefits among cancer survivors. Therefore, interventions focused on increasing physical activity levels have clinical and psychological relevance. The present study will examine the feasibility and efficacy of an intervention that combines supervised group exercise with active lifestyle recommendations, analyzing its clinical, psychological, physiological, functional, and immunological effects in breast cancer survivors. METHODS: Women aged 35-75 years who have completed chemotherapy, radiotherapy, and surgery for breast cancer will be recruited from the Cancer Institute of the State of Sao Paulo (ICESP) and take part in a 16-week, parallel-group, randomized, and controlled trial. They will receive a booklet with recommendations for achieving a physically active lifestyle by increasing overall daily movement and undertaking at least 150 min/week of structured exercise. Then, they will be randomized into two groups: the supervised group will take part in two canoeing group exercise sessions every week, and the unsupervised group will increase their overall physical activity level by any means, such as active commuting, daily activities, or home-based exercise. Primary outcome includes aerobic capacity. Secondary outcomes are physical activity, physical functioning, self-reported quality of life, fatigue, presence of lymphedema, body composition, immune function, adherence to physical activity guidelines, and perceptions of self-image. DISCUSSION: Results should contribute to advance knowledge on the impact of a supervised group exercise intervention to improve aspects related to health, physical functioning, and quality of life in female breast cancer survivors. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials Number: RBR-3fw9xf. Retrospectively Registered on 27 December 2018. Items from the World Health Organization Trial Registration Data Set can be accessed on http://www.ensaiosclinicos.gov.br/rg/RBR-3fw9xf/ .

Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice.

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.

Corrigendum: Determinants of Health and Physical Activity Levels Among Breast Cancer Survivors During the COVID-19 Pandemic: A Cross-Sectional Study.

[This corrects the article DOI: 10.3389/fphys.2021.624169.].

Respostas fisiológicas à caminhada máxima e submáxima em pacientes com doença arterial periférica sintomática / Physiological responses to maximal and submaximal walking in patients with symptomatic peripheral artery disease

Resumo Fundamento: Embora a caminhada máxima e submáxima sejam recomendadas para pacientes com doença arterial periférica (DAP), a realização desses exercícios pode induzir diferentes respostas fisiológicas. Objetivos: Comparar os efeitos agudos de caminhada máxima e submáxima na função cardiovascular, a regulação e os processos fisiopatológicos associados pós-exercício em pacientes com DAP sintomática. Métodos: Trinta pacientes do sexo masculino foram submetidos a 2 sessões: caminhada máxima (protocolo de Gardner) e caminhada submáxima (15 períodos de 2 minutos de caminhada separados por 2 minutos de repouso ereto). Em cada sessão, foram medidos a pressão arterial (PA), a frequência cardíaca (FC), a modulação autonômica cardíaca (variabilidade da FC), os fluxos sanguíneos (FS) do antebraço e da panturrilha, a capacidade vasodilatadora (hiperemia reativa), o óxido nítrico (ON), o estresse oxidativo (a peroxidação lipídica) e a inflamação (quatro marcadores), pré e pós-caminhada. ANOVAs foram empregadas e p < 0,05 foi considerado significativo. Resultados: A PA sistólica e a PA média diminuíram após a sessão submáxima, mas aumentaram após a sessão máxima (interações, p < 0,001 para ambas). A PA diastólica não foi alterada após a sessão submáxima (p > 0,05), mas aumentou após a caminhada máxima (interação, p < 0,001). A FC, o equilíbrio simpatovagal e os FS aumentaram de forma semelhante após as duas sessões (momento, p < 0,001, p = 0,04 e p < 0,001, respectivamente), enquanto a capacidade vasodilatadora, o ON e o estresse oxidativo permaneceram inalterados (p > 0,05). As moléculas de adesão vascular e intercelular aumentaram de forma semelhante após as sessões de caminhada máxima e submáxima (momento, p = 0,001). Conclusões: Nos pacientes com a DAP sintomática, a caminhada submáxima, mas não a máxima, reduziu a PA pós-exercício, enquanto a caminhada máxima manteve a sobrecarga cardíaca elevada durante o período de recuperação. Por outro lado, as sessões de caminhada máxima e submáxima aumentaram a FC, o equilíbrio simpatovagal cardíaco e a inflamação pós-exercício de forma semelhante, enquanto não alteraram a biodisponibilidade de ON e o estresse oxidativo pós-exercício.

Abstract Background: Although maximal and submaximal walking are recommended for patients with peripheral artery disease (PAD), performing these exercises may induce different physiological responses. Objectives: To compare the acute effects of maximal and submaximal walking on post-exercise cardiovascular function, regulation, and associated pathophysiological processes in patients with symptomatic PAD. Methods: Thirty male patients underwent 2 sessions: maximal walking (Gardner's protocol) and submaximal walking (15 bouts of 2 minutes of walking separated by 2 minutes of upright rest). In each session, blood pressure (BP), heart rate (HR), cardiac autonomic modulation (HR variability), forearm and calf blood flows (BF), vasodilatory capacity (reactive hyperemia), nitric oxide (NO), oxidative stress (lipid peroxidation), and inflammation (four markers) were measured pre- and post-walking. ANOVAs were employed, and p < 0.05 was considered significant. Results: Systolic and mean BP decreased after the submaximal session, but they increased after the maximal session (interactions, p < 0.001 for both). Diastolic BP did not change after the submaximal session (p > 0.05), and it increased after maximal walking (interaction, p < 0.001). HR, sympathovagal balance, and BF increased similarly after both sessions (moment, p < 0.001, p = 0.04, and p < 0.001, respectively), while vasodilatory capacity, NO, and oxidative stress remained unchanged (p > 0.05). Vascular and intercellular adhesion molecules increased similarly after both maximal and submaximal walking sessions (moment, p = 0.001). Conclusions: In patients with symptomatic PAD, submaximal, but not maximal walking reduced post-exercise BP, while maximal walking maintained elevated cardiac overload during the recovery period. On the other hand, maximal and submaximal walking sessions similarly increased post-exercise HR, cardiac sympathovagal balance, and inflammation, while they did not change post-exercise NO bioavailability and oxidative stress.

Determinants of Health and Physical Activity Levels Among Breast Cancer Survivors During the COVID-19 Pandemic: A Cross-Sectional Study.

Background: Increased exercise and physical activity levels are recommended throughout cancer therapy and survivorship. Nonetheless, the COVID-19 pandemic and consequent social distancing are likely to cause a decline in physical activity. Objective: to evaluate the level of unsupervised physical activity of breast cancer survivors during the COVID-19 pandemic, and the factors associated with difficulties in engaging and maintaining recommended physical activity levels. Methods: This is a cross-sectional epidemiological study with a sample of 37 breast cancer survivors. They participated in a canoeing training program (project Remama) at the University of São Paulo before the COVID-19 pandemic. Socioeconomic aspects, engagement in physical activity, motivation, and potential exposure to COVID-19 were investigated through an online survey, administered in September of 2020. Results: During the pandemic, participants increased their body weight (5 ± 3.4 kg); 90% reported decreasing physical activity levels associated with increased sedentary time. Twenty-one (58%) participants exhibited some COVID-19-related symptoms, most used public transportation (59%), or returned to work during the period of a high incidence of COVID-19. The only factor associated with perceived difficulty in engaging in physical activities was having had more than three cancer treatments (RR: 2.14; 95% CI: 1.07-4.27). Conclusion: The COVID-19 pandemic led to a group of previously active breast cancer survivors to decrease their physical activity, gain weight, and have sedentary behavior. Specific tailored-care interventions are needed to prevent these occurrences, as overweight and physical inactivity may impose an additional risk for breast cancer recurrence and a severe course of COVID-19 in cancer patients.

Adjustments in ß-Adrenergic Signaling Contribute to the Amelioration of Cardiac Dysfunction by Exercise Training in Supravalvular Aortic Stenosis.

BACKGROUND/AIMS: Aortic stenosis-induced chronic pressure overload leads to cardiac dysfunction and congestive heart failure. The pathophysiological mechanisms of the myocardial impairment are multifactorial and include maladaptive ß-adrenergic signaling. Exercise training (ET) has been used as a non-pharmacological therapy for heart failure management. The present study tested the hypothesis that exercise training attenuates diastolic dysfunction through ß-adrenergic signaling preservation. METHODS: Wistar rats were submitted to ascending aortic stenosis (AS) surgery, and after 18 weeks, a moderate aerobic exercise training protocol was performed for ten weeks. RESULTS: ET attenuated diastolic dysfunction, evaluated by echocardiogram and isolated papillary muscle (IPM) assay. Also, ET reduced features of heart failure, cross-sectional cardiomyocyte area, and exercise intolerance, assessed by treadmill exercise testing. The ß2 adrenergic receptor protein expression was increased in AS rats independently of exercise. Interestingly, ET restored the protein levels of phosphorylated phospholamban at Serine 16 and preserved the ß-adrenergic receptor responsiveness as visualized by the lower myocardial compliance decline and time to 50% tension development and relaxation during ß-adrenergic stimulation in the IPM than untrained rats. Additionally, AS rats presented higher levels of TNFα and iNOS, which were attenuated by ET. CONCLUSION: Moderate ET improves exercise tolerance, reduces heart failure features, and attenuates diastolic dysfunction. In the myocardium, ET decreases the cross-sectional area of the cardiomyocyte and preserves the ß-adrenergic responsiveness, which reveals that the adjustments in ß-adrenergic signaling contribute to the amelioration of cardiac dysfunction by mild exercise training in aortic stenosis rats.

Comparison betweent the effects of swimming and treadmill-based aerobic training protocols in diabetic rats / Comparação entre os efeitos de natação e protocolos de treinamento aeróbio em esteira em ratos diabéticos

Background: Type 1 diabetes mellitus (DM1) can cause damage to several physiological systems.Objectives: To compare and characterize the effects of aerobic exercise training (ET) performed by swimming with those of ET performed on a treadmill on the skeletal muscle and heart of rats with DM1. Methods: 41 male Wistar rats were randomized into four groups: nondiabetic control (CTR), diabetic control (DMC), diabetic trained on the treadmill (DMT), and diabetic trained by swimming (DMS). The trained groups performed aerobic exercise training for 8 weeks, 5 times a week, 60 min per day. Exercise tolerance, blood glucose, body weight, wet weight of the skeletal muscles and left ventricle (LV), muscle glycogen, cross-sectional area of skeletal muscles, and cross-sectional diameter and collagen volume fraction of the LV were evaluated.Results: The results were expressed as mean ± standard deviation of the mean and submitted to two-way ANOVA with post-hoc Bonferroni test. Aerobic ET protocols applied to animals with DM1, regardless of the ergometer, showed satisfactory results (p < 0.05) when compared to the control groups: improved exercise tolerance, increased glycogen content of the soleus and extensor digitorum longus (EDL) muscles and increased cross-sectional diameter of the left ventricular cardiomyocytes. In some variables, such as exercise tolerance and cross-sectional area of the soleus and EDL muscles, DMT showed better results than DMS (p < 0.05). On the other hand, DMS showed increased cross-sectional diameter of cardiomyocytes when compared with the DMT group. Conclusion: Both aerobic ET protocols offered benefits to animals with diabetes; however, due to the specific characteristics of each modality, different physiological adaptations were observed between the trained groups

Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice / Treinamento Aeróbico Contínuo de Intensidade Moderada Melhora a Contratilidade do Cardiomiócito em Camundongos com Nocaute para o Receptor B1-Adrenérgico

Abstract Background: The lack of cardiac β1-adrenergic receptors (β1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. Objective: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from β1 adrenergic receptor knockout (β1ARKO) mice. Methods: Four- to five-month-old male wild type (WT) and β1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β1ARKO control (β1ARKOc) and trained (β1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. Results: The β1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The β1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in β1ARKO mice. Conclusion: MCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.

Resumo Fundamento: A falta de receptores β1-adrenérgicos (β1-AR) cardíacos afeta negativamente a regulação de inotropismo e lusitropismo cardíacos, levando, no longo prazo, a insuficiência cardíaca (IC). Recomenda-se exercício aeróbico contínuo de intensidade moderada (EACM) como adjuvante no tratamento de pacientes com IC. Objetivo: Testar os efeitos do EACM nas propriedades contráteis de miócitos do ventrículo esquerdo (VE) de camundongos com nocaute para o receptor β1-adrenérgico (β1ARKO). Método: Camundongos machos com 4 a 5 meses de idade, wild-type (WT) e β1ARKO foram divididos em grupos: WT controle (WTc) e treinado (WTt); e β1ARKO controle (β1ARKOc) e treinado (β1ARKOt). Os grupos treinados foram submetidos a regime de EACM (60 min/dia; 60% da velocidade máxima, 5 dias/semana) em esteira rolante, por 8 semanas. Adotou-se P ≤ 0,05 como nível de significância em todas as comparações. Resultados: Os animais β1ARKO (β1ARKOc + β1ARKOt) correram uma distância maior do que os animais WT (WTc + WTt) (p < 0,05). Os camundongos β1ARKO apresentaram maiores pesos corporal (PC), do coração (PCo) e do ventrículo esquerdo (PVE), assim como PCo/PC e PVE/PC do que os camundongos WT. Entretanto, o EACM não afetou tais parâmetros. Os miócitos do VE de camundongos β1ARKO apresentaram maiores (p < 0,05) amplitude e velocidades de contração e relaxamento do que os dos camundongos WT. Além disso, o EACM aumentou (p < 0,05) a amplitude e as velocidades de contração e relaxamento nos camundongos β1ARKO. Conclusão: O EACM melhora a contratilidade do miócito do VE de camundongos β1ARKO. Tal achado confirma o valor terapêutico desse tipo de treinamento físico para o tratamento de doenças cardíacas envolvendo dessensibilização ou redução de β1-AR.

The importance of animal studies in exercise science

Abstract The validity and relevance of research with animals for the development of knowledge in Exercise Science have for long been discussed. Given the complexity of the biological systems, the use of animal models offers a significant contribution to uncover new findings about acute and chronic effects of exercise, particularly when these studies in humans have limitations and ethical implications. There have been notable findings using experimental animals either in basic sciences or in clinical studies involving physiology, pharmacology, genetic, biochemistry, urology, endocrinology and cancer. This article presents a brief review of scientific research using animal models with a focus on exercise training as an effective tool for the prophylaxis and treatment of different pathological processes, which are the basis of many concepts taught and used in undergraduate courses and graduate programs, as well as in new researches showed in scientific conference meetings in numerous areas of science.(AU)

Loss of strength capacity is associated with mortality, but resistance exercise training promotes only modest effects during cachexia progression.

AIMS: Resistance exercise training (RET) has been adopted as non-pharmacological anti-catabolic strategy. However, the role of RET to counteract cancer cachexia is still speculative. This study aimed to verify whether short-term RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. MAIN METHODS: Wistar rats were randomly allocated into four experimental groups; 1) untrained control rats (control), 2) rats submitted to RET (control+RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor+RET). KEY FINDINGS: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumor-bearing rats. Indeed, RET did not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats' survival (p=0.02; r=0.40), suggesting that loss of strength capacity might predict cancer mortality. SIGNIFICANCE: These results demonstrated that bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia, strength capacity is associated with cancer survival and short-term RET promotes only modest effects during cachexia progression.

Attenuated PGC-1α Isoforms following Endurance Exercise with Blood Flow Restriction.

INTRODUCTION: Exercise performed with blood flow restriction simultaneously enhances the acute responses to both myogenic and mitochondrial pathways with roles in training adaptation. We investigated isoform-specific gene expression of the peroxisome proliferator-activated receptor gamma coactivator 1 and selected target genes and proteins regulating skeletal muscle training adaptation. METHODS: Nine healthy, untrained males participated in a randomized, counterbalanced, crossover design in which each subject completed a bout of low-intensity endurance exercise performed with blood flow restriction (15 min cycling at 40% of V˙O2peak, BFR-EE), endurance exercise (30 min cycling at 70% of V˙O2peak, EE), or resistance exercise (4 × 10 repetitions of leg press at 70% of one-repetition maximum) separated by at least 1 wk of recovery. A single resting muscle biopsy (vastus lateralis) was obtained 2 wk before the first exercise trial (rest) and 3 h after each bout. RESULTS: Total PGC-1α mRNA abundance, along with all four isoforms, increased above rest with EE only (P < 0.05) being higher than BFR-EE (P < 0.05). PGC-1α1, 2, and 4 were higher after EE compared with resistance exercise (P < 0.05). EE also increased vascular endothelial growth factor, Hif-1α, and MuRF-1 mRNA abundance above rest (P < 0.05), whereas COXIV mRNA expression increased with EE compared with BFR-EE (P < 0.05). CONCLUSION: The attenuated expression of all four PGC-1α isoforms when EE is performed with blood flow restriction suggests this type of exercise provides an insufficient stimulus to activate the signaling pathways governing mitochondrial and angiogenesis responses observed with moderate- to high-intensity EE.

Aerobic exercise training as therapy for cardiac and cancer cachexia.

Aerobic exercise training (AET) induces several skeletal muscle changes, improving aerobic exercise capacity and health. Conversely, to the positive effects of AET, the cachexia syndrome is characterized by skeletal muscle wasting. Cachexia is a multifactorial disorderassociated with other chronic diseases such as heart failure and cancer. In these diseases, an overactivation of ubiquitin-proteasome and autophagy systems associated with a reduction in protein synthesis culminates in severe skeletal muscle wasting and, in the last instance, patient's death. In contrast, AET may recycle and enhance many protein expression and enzyme activities, counteracting metabolism impairment and muscle atrophy. Therefore, the aim of the current review was to discuss the supposed therapeutic effects of AET on skeletal muscle wasting in both cardiac and cancer cachexia.

Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1.

Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg) in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX). The group submitted to exercise before cisplatin administration (CIS-EX) exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS). Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.

Efeito da suplementação de creatina, associada ou não ao treinamento de força, sobre a peroxidação lipídica em mulheres idosas / Effects of creatine supplementation associated or not with strength training upon lipid peroxidation in elderly women

O objetivo desse trabalho foi avaliar o efeito da suplementação de creatina associada ou não ao treinamento de força sobre a peroxidação lipídica em mulheres idosas. Foi conduzido um estudo clínico, randomizado, duplo-cego e controlado por placebo, no qual mulheres idosas foram randomizadas para compor quatro grupos: 1) suplementação com placebo (PL; n = 10); 2) suplementação com creatina (CR; n = 10); 3) suplementação com placebo associado ao treinamento de força (PL+TR; n = 6); e 4) suplementação com creatina associado ao treinamento de força (CR+TR; n = 8). Antes (PRE) e após 24 semanas (POS) de intervenção, foram coletadas amostras de sangue para posterior análise das concentrações plasmáticas de hidroperóxidos lipídicos por espectrofotometria. Nenhuma diferença estatística foi observada na concentração de hidroperóxidos lipídicos entre os grupos (PL: PRE = 48,7 ± 36,9; POS = 29,3 ± 18,8; delta = -13,0 ± 26,8; CR: PRE = 51,0 ± 46,0; POS = 54,2 ± 51,6; delta = -8,6 ± 30,2; PL+TR: PRE = 33,0 ± 11,2; POS = 47,3 ± 31,6; Δ = 14,3 ± 39,2; CR+TR: PRE = 18,5 ± 10,1; POS = 28,1 ± 17,9; delta = 9,7 ± 16,4 pmol.mg-1 de proteína total; p = 0,17). A suplementação de creatina associada ou não ao treinamento de força não afetou a peroxidação lipídica, um importante marcador de estresse oxidativo no plasma, em mulheres idosas.

The aim of this study was to evaluate the effects of creatine supplementation associated or not with strength training upon lipid peroxidation in older women. This was a clinical, randomized, double-blind, placebo-controlled trial. Older women were randomly allocated into four groups: 1) placebo supplementation (PL, n = 10), 2) creatine supplementation (CR; n = 10), 3) placebo supplementation associated with strength training (PL + RT, n = 6) and 4) creatine supplementation associated with strength training (CR + RT, n = 8). Before (PRE) and after 24 weeks (POST), blood samples were collected to measure lipid hydroperoxides concentration by spectrophotometry. No statistical difference was observed on the lipid hydroperoxides concentration between groups (PL: PRE = 48.7 ± 36.9; POST = 29.3 ± 18.8; Δ = -13.0 ± 26.8; CR : PRE = 51.0 ± 46.0; POST = 54.2 ± 51.6; Δ = -8.6 ± 30.2; + PL TR: PRE = 33.0 ± 11.2; POST = 47.3 ± 31.6, Δ = 14.3 ± 39.2; CR + TR: PRE = 18.5 ± 10.1; POST = 28.1 ± 17.9, Δ = 9.7 ± 16.4 pmol.mg-1 of total protein, p = 0.17). Creatine supplementation associated or not with strength training did not affect the lipid peroxidation, an important plasmatic marker of oxidative stress, in elderly women.

Treatment with nebivolol combined with physical training promotes improvements in the cardiovascular responses of hypertensive rats.

The aim of this study was to determine whether exercise training combined with beta-blocker treatment promotes additional cardiovascular benefits compared with either intervention on its own. For this we used 76 Wistar rats distributed among different groups: normotensive sedentary (NS), normotensive trained (NT), normotensive sedentary treated with beta-blocker (NS_BB), normotensive trained treated with beta-blocker (NT_BB), hypertensive sedentary (HS), hypertensive trained (HT), hypertensive sedentary treated with a beta-blocker (HS_BB), and hypertensive trained rats treated with beta-blocker (HT_BB). Exercise training consisted of 4 weeks of swimming for 60 min a day, 5 days a week. Hypertension was induced with l-NAME (4 weeks), whereas the control rats received saline, and both the control and test rats received nebivolol. The animals underwent surgery to directly record their blood pressure. The HS group showed higher mean arterial pressure (MAP) (P = 0.000), systolic arterial pressure (P = 0.000), and diastolic arterial pressure (P = 0.000) compared with NS. MAP was higher in the HS compared with the HT (P = 0.002), HS_BB (P = 0.018), and HT_BB (P = 0.015) groups. Hearts from the HS group had a higher percentage of collagen compared with the NS and HS_BB groups. The HT_BB and HT groups only had a higher percentage of cardiac collagen by comparison with the HS_BB group. The HT_BB group showed higher levels of macrophages and neutrophils by comparison with the HT and HS_BB groups. Thus, treatment with a beta-blocker combined with physical training was associated with increased cardiovascular benefits over either intervention alone.