Phytomodulatory proteins isolated from Calotropis procera latex promote glycemic control by improving hepatic mitochondrial function in HepG2 cells.

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.

Regulation of Lin28a-miRNA let-7b-5p pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta.

Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPARδ) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPARδ in the skeletal muscle, where it impacts mitochondrial respiration.

Fenofibrate reverses changes induced by high-fat diet on metabolism in mice muscle and visceral adipocytes.

The effect of fenofibrate on the metabolism of skeletal muscle and visceral white adipose tissue of diet-induced obese (DIO) mice was investigated. C57BL/6J male mice were fed either a control or high-fat diet for 8 weeks. Fenofibrate (50 mg/Kg BW, daily) was administered by oral gavage during the last two weeks of the experimental period. Insulin-stimulated glucose metabolism in soleus muscles, glucose tolerance test, insulin tolerance test, indirect calorimetry, lipolysis of visceral white adipose tissue, expression of miR-103-3p in adipose tissue, and miR-1a, miR-133a/b, miR-206, let7b-5p, miR-23b-3p, miR-29-3p, miR-143-3p in soleus muscle, genes related to glucose and fatty acid metabolism in adipose tissue and soleus muscle, and proteins (phospho-AMPKα2, Pgc1α, Cpt1b), intramuscular lipid staining, and activities of fatty acid oxidation enzymes in skeletal muscle were investigated. In DIO mice, fenofibrate prevented weight gain induced by HFD feeding by increasing energy expenditure; improved whole body glucose homeostasis, and in skeletal muscle, increased insulin dependent glucose uptake, miR-1a levels, reduced intramuscular lipid accumulation, and phospho-AMPKα2 levels. In visceral adipose tissue of obese mice, fenofibrate decreased basal lipolysis rate and visceral adipocytes hypertrophy, and induced the expression of Glut-4, Irs1, and Cav-1 mRNA and miR-103-3p suggesting a higher insulin sensitivity of the adipocytes. The evidence is presented herein that beneficial effects of fenofibrate on body weight, glucose homeostasis, and muscle metabolism might be related to its action in adipose tissue. Moreover, fenofibrate regulates miR-1a-3p in soleus and miR-103-3p in adipose tissue, suggesting these microRNAs might contribute to fenofibrate beneficial effects on metabolism.

Role of NCoR1 in mitochondrial function and energy metabolism.

Mitochondrial number and shape are constantly changing in response to increased energy demands. The ability to synchronize mitochondrial pathways to respond to energy fluctuations within the cell is a central aspect of mammalian homeostasis. This dynamic process depends on the coordinated activation of transcriptional complexes to promote the expression of genes encoding for mitochondrial proteins. Recent evidence has shown that the nuclear corepressor NCoR1 is an essential metabolic switch which acts on oxidative metabolism signaling. Here, we provide an overview of the emerging role of NCoR1 in the transcriptional control of energy metabolism. The identification and characterization of NCoR1 as a central, evolutionary conserved player in mitochondrial function have revealed a novel layer of metabolic control. Defining the precise mechanisms by which NCoR1 acts on energy homeostasis will ultimately contribute towards the development of novel therapies for the treatment of metabolic diseases such as obesity and type 2 diabetes.

Anti-contractile effects of perivascular adipose tissue in thoracic aorta from rats fed a high-fat diet: role of aerobic exercise training.

The aim of the present study was to evaluate the effects of aerobic exercise training on perivascular adipose tissue (PVAT) function in thoracic aorta from rats fed a high-fat diet. Aortic vascular reactivity was performed in sedentary (SD), trained (TR), sedentary high-fat diet (SD-HF), and trained high-fat diet (TR-HF) male Wistar rats in the absence (PVAT-) or in the presence (PVAT+) of thoracic PVAT. We also measured circulatory concentrations of leptin and tumour necrosis factor alpha (TNF-α), as well as the protein expressions of TNF-α receptor 1 (TNFR1) and inducible nitric oxide synthase (iNOS) on PVAT. In the SD-HF group, the body weight, epididymal fat pad, thoracic PVAT, circulatory triglycerides, insulin, leptin and TNF-α were increased when compared with the SD group, whereas exercise training reduced these values in TR-HF group. The relaxing response curves to acetylcholine and sodium nitroprusside were not modified by either intervention (high-fat diet or exercise training) or the presence of PVAT. The presence of PVAT had an anti-contractile effect in response to serotonin in all groups. In SD-HF group, the increased magnitude of anti-contractile effects was in parallel with an up-regulation of iNOS protein expression in PVAT without alteration in TNFR1. Exercise training was effective in normalizing the vascular reactivity in rings PVAT+ and in reducing the iNOS protein expression. Exercise training prevented the PVAT-induced alteration in thoracic aorta from rats fed a high-fat diet.

Role of microRNAs on the Regulation of Mitochondrial Biogenesis and Insulin Signaling in Skeletal Muscle.

Mitochondria play a critical role in several cellular processes and cellular homeostasis. Mitochondrion dysfunction has been correlated with numerous metabolic diseases such as obesity and type 2 diabetes. MicroRNAs are non-coding RNAs that have emerged as key regulators of cell metabolism. The microRNAs act as central regulators of metabolic gene networks by leading to the degradation of their target messenger RNA or repression of protein translation. In addition, vesicular and non-vesicular circulating miRNAs exhibit a potential role as mediators of the cross-talk between the skeletal muscle and other tissues/organs. In this review, we will focus on the emerging knowledge of miRNAs controlling mitochondrial function and insulin signaling in skeletal muscle cells. J. Cell. Physiol. 232: 958-966, 2017. © 2016 Wiley Periodicals, Inc.

Circulating Concentrations of Adipocytokines and Their Receptors in the Isolated Corpus Cavernosum and Femoral Artery from Trained Rats on a High-Fat Diet.

BACKGROUND: The aim of the present study was to evaluate different signaling pathways by which exercise training would interfere in endothelial function in obesity. Therefore, we examined adipocytokine levels and their receptors in the corpus cavernosum and femoral artery from trained rats on a high-fat diet. METHODS: Functional experiments were performed in control sedentary and trained rats, and sedentary (h-SD) and trained male Wistar rats on a high-fat diet (h-TR). Nitric oxide (NO) and reactive oxygen species (ROS) were evaluated in vascular tissue. Circulating adipocytokines and their receptors were analyzed. RESULTS: In the h-SD group, the maximal responses to acetylcholine (ACh) were reduced in the femoral artery and corpus cavernosum as well as the electrical field stimulation, accompanied by an increase in circulating insulin, leptin, TNF-α, MCP-1, and PAI-1. Downregulation of ObR protein expression in the femoral artery was observed without alterations in AdipoR1 and TNFR1 in both preparations. A positive effect was observed in the h-TR group regarding the relaxation response to ACh and circulating adipocytokines, resulting in increased NO production and reduced ROS generation. Exercise restored the ObR protein expression only in the femoral artery. CONCLUSION: Aerobic exercise training ameliorated the inflammatory adipocytokines and restored the relaxation responses in the corpus cavernosum and femoral artery in rats on a high-fat diet.

Cross-talk between TRPC-1, mTOR, PGC-1α and PPARδ in the dystrophic muscle cells treated with tempol.

Background Ca2+ dysregulation and oxidative damage appear to have a central role in Duchenne muscular dystrophy (DMD) progression. The current study provides muscle cell-specific insights into the effect of Tempol on the TRPC 1 channel; on the positive and negative regulators of muscle cell differentiation; on the antioxidant enzymatic system; on the activators of mitochondrial biogenesis; and on the inflammatory process in the dystrophic primary muscle cells in culture. METHODS: Mdx myotubes were treated with Tempol (5 mM) for 24 h. Untreated mdx myotubes and C57BL/10 myotubes were used as controls. RESULTS: The Trypan Blue, MTT and Live/Dead Cell assays showed that Tempol (5 mM) presented no cytotoxic effect on the dystrophic muscle cells. The Tempol treated-mdx muscle cells showed significantly lower levels in the fluorescence intensity of intracellular calcium; TRPC-1 channel; MyoD; H2O2 and O2•- production; 4-HNE levels; SOD2, CAT and GPx levels; and TNF levels. On the other hand, SOD, CAT and GR mRNA relative expression were significantly higher in Tempol treated-mdx muscle cells. In addition, higher levels of Myogenin, MHC-Slow, mTOR, PGC-1α and PPARδ were also observed in Tempol treated-mdx muscle cells. CONCLUSION: Our findings demonstrated that Tempol decreased intracellular calcium and oxidative stress in primary dystrophic muscle cells, promoting a cross-talk between TRPC-1, mTOR, PGC-1α and PPARδ.

Offspring from trained male mice inherit improved muscle mitochondrial function through PPAR co-repressor modulation.

Aim Investigate whether inheritance of improved skeletal muscle mitochondrial function and its association with glycemic control are multigenerational benefits of exercise. MAIN METHODS: Male Swiss mice were subjected to 8 weeks of endurance training and mated with untrained females. KEY FINDINGS: Trained fathers displayed typical endurance training-induced adaptations. Remarkably, offspring from trained fathers also exhibited higher endurance performance, mitochondrial oxygen consumption, glucose tolerance and insulin sensitivity. However, PGC-1α expression was not increased in the offspring. In the offspring, the expression of the co-repressor NCoR1 was reduced, increasing activation of PGC-1α target genes. These effects correlated with higher DNA methylation at the NCoR1 promoter in both, the sperm of trained fathers and in the skeletal muscle of their offspring. SIGNIFICANCE: Higher skeletal muscle mitochondrial function is inherited by epigenetic de-activation of a key PGC-1α co-repressor.

Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice.

The role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle.

The MicroRNA miR-696 is regulated by SNARK and reduces mitochondrial activity in mouse skeletal muscle through Pgc1α inhibition.

OBJECTIVE: MicroRNAs (miRNA) are known to regulate the expression of genes involved in several physiological processes including metabolism, mitochondrial biogenesis, proliferation, differentiation, and cell death. METHODS: Using "in silico" analyses, we identified 219 unique miRNAs that potentially bind to the 3'UTR region of a critical mitochondrial regulator, the peroxisome proliferator-activated receptor gamma coactivator (PGC) 1 alpha (Pgc1α). Of the 219 candidate miRNAs, miR-696 had one of the highest interactions at the 3'UTR of Pgc1α, suggesting that miR-696 may be involved in the regulation of Pgc1α. RESULTS: Consistent with this hypothesis, we found that miR-696 was highly expressed in the skeletal muscle of STZ-induced diabetic mice and chronic high-fat-fed mice. C2C12 muscle cells exposed to palmitic acid also exhibited a higher expression of miR-696. This increased expression corresponded with a reduced expression of oxidative metabolism genes and reduced mitochondrial respiration. Importantly, reducing miR-696 reversed decreases in mitochondrial activity in response to palmitic acid. Using C2C12 cells treated with the AMP-activated protein kinase (AMPK) activator AICAR and skeletal muscle from AMPKα2 dominant-negative (DN) mice, we found that the signaling mechanism regulating miR-696 did not involve AMPK. In contrast, overexpression of SNF1-AMPK-related kinase (SNARK) in C2C12 cells increased miR-696 transcription while knockdown of SNARK significantly decreased miR-696. Moreover, muscle-specific transgenic mice overexpressing SNARK exhibited a lower expression of Pgc1α, elevated levels of miR-696, and reduced amounts of spontaneous activity. CONCLUSIONS: Our findings demonstrate that metabolic stress increases miR-696 expression in skeletal muscle cells, which in turn inhibits Pgc1α, reducing mitochondrial function. SNARK plays a role in this process as a metabolic stress signaling molecule inducing the expression of miR-696.

MicroRNA miR-222 mediates pioglitazone beneficial effects on skeletal muscle of diet-induced obese mice.

Pioglitazone belongs to the class of drugs thiazolidinediones (TZDs) and is an oral hypoglycemic drug, used in the treatment of type 2 diabetes, which improves insulin sensitivity in target tissues. Adipose tissue is the main target of pioglitazone, a PPARg and PPARa agonist; however, studies also point to skeletal muscle as a target. Non-PPAR targets of TZDs have been described, thus we aimed to study the direct effects of pioglitazone on skeletal muscle and the possible role of microRNAs as targets of this drug. Pioglitazone treatment of obese mice increased insulin-mediated glucose transport as a result of increased fatty acid oxidation and mitochondrial activity. PPARg blockage by treatment with GW9662 nullified pioglitazone's effect on systemic and muscle insulin sensitivity and citrate synthase activity of obese mice. After eight weeks of high-fat diet, miR-221-3p expression in soleus muscle was similar among the groups and miR-23b-3p and miR-222-3p were up-regulated in obese mice compared to the control group, and treatment with pioglitazone was able to reverse this condition. In vitro studies in C2C12 cells suggest that inhibition of miR-222-3p protects C2C12 cells from insulin resistance and increased non-mitochondrial respiration induced by palmitate. Together, these data demonstrate a role of pioglitazone in the downregulation of microRNAs that is not dependent on PPARg. Moreover, miR-222 may be a novel PPARg-independent mechanism through which pioglitazone improves insulin sensitivity in skeletal muscle.

Opposing action of NCoR1 and PGC-1α in mitochondrial redox homeostasis.

The ability to respond to fluctuations of reactive oxygen species (ROS) within the cell is a central aspect of mammalian physiology. This dynamic process depends on the coordinated action of transcriptional factors to promote the expression of genes encoding for antioxidant enzymes. Here, we demonstrate that the transcriptional coregulators, PGC-1α and NCoR1, are essential mediators of mitochondrial redox homeostasis in skeletal muscle cells. Our findings reveal an antagonistic role of these coregulators in modulating mitochondrial antioxidant induction through Sod2 transcriptional control. Importantly, the activation of this mechanism by either PGC-1α overexpression or NCoR1 knockdown attenuates mitochondrial ROS levels and prevents cell death caused by lipid overload in skeletal muscle cells. The opposing actions of coactivators and corepressors, therefore, exert a commanding role over cellular antioxidant capacity.

Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice.

The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60-70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe.

Post-exercise cold water immersion does not alter high intensity interval training-induced exercise performance and Hsp72 responses, but enhances mitochondrial markers.

This study aims to evaluate the effect of regular post-exercise cold water immersion (CWI) on intramuscular markers of cellular stress response and signaling molecules related to mitochondria biogenesis and exercise performance after 4 weeks of high intensity interval training (HIIT). Seventeen healthy subjects were allocated into two groups: control (CON, n = 9) or CWI (n = 8). Each HIIT session consisted of 8-12 cycling exercise stimuli (90-110 % of peak power) for 60 s followed by 75 s of active recovery three times per week, for 4 weeks (12 HIIT sessions). After each HIIT session, the CWI had their lower limbs immersed in cold water (10 °C) for 15 min and the CON recovered at room temperature. Exercise performance was evaluated before and after HIIT by a 15-km cycling time trial. Vastus lateralis biopsies were obtained pre and 72 h post training. Samples were analyzed for heat shock protein 72 kDa (Hsp72), adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) assessed by western blot. In addition, the mRNA expression of heat shock factor-1 (HSF-1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 and 2 (NRF1 and 2), mitochondrial transcription factor A (Tfam), calcium calmodulin-dependent protein kinase 2 (CaMK2) and enzymes citrate synthase (CS), carnitine palmitoyltransferase I (CPT1), and pyruvate dehydrogenase kinase (PDK4) were assessed by real-time PCR. Time to complete the 15-km cycling time trial was reduced with training (p < 0.001), but was not different between groups (p = 0.33). The Hsp72 (p = 0.01), p38 MAPK, and AMPK (p = 0.04) contents increased with training, but were not different between groups (p > 0.05). No differences were observed with training or condition for mRNA expression of PGC-1α (p = 0.31), CPT1 (p = 0.14), CS (p = 0.44), and NRF-2 (p = 0.82). However, HFS-1 (p = 0.007), PDK4 (p = 0.03), and Tfam (p = 0.03) mRNA were higher in CWI. NRF-1 decrease in both groups after training (p = 0.006). CaMK2 decreased with HIIT (p = 0.003) but it was not affected by CWI (p = 0.99). Cold water immersion does not alter HIIT-induced Hsp72, AMPK, p38 MAPK, and exercise performance but was able to increase some markers of cellular stress response and signaling molecules related to mitochondria biogenesis.

Effect of aerobic exercise training on cGMP levels and blood pressure in treated hypertensive postmenopausal women

Abstract The second messenger cGMP has been largely studied as a therapeutic target in a variety of disorders such as erectile dysfunction, arterial hypertension and heart failure. Evidence has shown thatcGMP activators are less efficient in estrogen-deficiency animals, but no studies exist involving non-pharmacological approacheson NO/cGMP signaling pathway in hypertensive postmenopausal women. The aim of this study is to examine NO/cGMP pathway, redox state and blood pressure in trained treatedhypertensive (HT) postmenopausal women comparing with normotensive (NT) group. The rationale for that is most of HT patients is encouraged by physician to perform exercise associated with pharmacological treatments.Aerobic exercise training (AET) consisted of 24 sessions, 3 times/week.Parameters were evaluated at baseline and after AET for both groups (HT=28; NT=33).In treatedHT group, AET was significantly effective in increasing cGMP concentrations (28%) accompanied by an up-regulation of SOD (97%) and catalase activity (37%). In NT group, we found an increasein SOD activity (58%). TreatedHT postmenopausal women were still responsive to AET increasing cGMP levels and up-regulating antioxidant system. It should also be emphasized that these findings provide information on the circulating biomarkers that might delay the developing of cardiovascular events in this particular population.(AU)

EFEITO DO EXERCÍCIO FÍSICO SOBRE A SAÚDE E SOBRECARGA DE MÃES DE CRIANÇAS E ADOLESCENTES COM PARALISIA CEREBRAL / EFFECT OF EXERCISE ON HEALTH AND BURDEN OF MOTHERS OF CHILDREN AND ADOLESCENTS WITH CEREBRAL PALSY / EFECTO DEL EJERCICIO SOBRE LA SALUD Y SOBRECARGA DE LAS MADRES DE NIÑOS Y ADOLESCENTES CON PARÁLISIS CEREBRAL

RESUMO Introdução: A paralisia cerebral (PC) é considerada a incapacidade física mais comum na infância. Essa doença afeta profundamente a saúde e o bem-estar dos indivíduos acometidos e também pode influenciar múltiplos aspectos da vida de seus cuidadores, especialmente as mães. Objetivo: Avaliar o efeito de um programa de exercício resistido sobre a qualidade de vida relacionada à saúde (QVRS) de mães de crianças e adolescentes com PC. Método: Vinte e duas mães sedentárias cuidadoras de crianças e adolescentes com PC, aptas à prática de exercício resistido, participaram de um programa de exercício resistido de intensidade moderada, em 2 sessões semanais durante 12 semanas. Todos os participantes responderam ao questionário de QVRS, Short Form Questionnaire (SF-36), à escala de sobrecarga Caregiver Burden Scale (CBS) e ao Inventário de Depressão de Beck (BDI) antes e após o programa de intervenção. Os escores dos questionários pré e pós-intervenção foram comparados pelo teste de Wilcoxon e a magnitude das diferenças foi medida pelo tamanho do efeito. Resultados: A mediana de idade das mães foi de 41 anos e variou de 18 a 58 anos. A mediana da idade das crianças/adolescentes foi de 14 anos, variando 3 a 21 anos. Após a intervenção foram encontrados aumentos significativos nos escores do SF-36 (p < 0,05), exceto nos domínios aspectos físicos e aspectos emocionais, que já obtiveram pontuação máxima pré-intervenção. Os escores do CBS e do BDI tiveram redução significativa pós-intervenção (p < 0,05). Conclusão: A prática regular de exercícios resistidos tem impacto positivo sobre a QVRS, a percepção de sobrecarga e a intensidade de sintomas depressivos de mães cuidadoras de crianças e adolescentes com PC.

ABSTRACT Introduction: Cerebral palsy (CP) is considered the most common physical disability in childhood. This disease profoundly affects the health and well-being of affected individuals and can influence multiple aspects of the life of their caregivers, especially mothers. Objective: To evaluate the effect of a resistance training program on health-related quality of life (HRQoL) of mothers of children and adolescents with CP. Methods: Twenty-four sedentary mothers caregivers of children and adolescents with CP, able to practice resistance training, participated in a resistance training program of moderate intensity of 2 sessions per week for 12 weeks. All participants answered to HRQoL questionnaire, SF-36, Caregiver Burden Scale (CBS) and Beck Depression Inventory (BDI) before and after the intervention program. The scores of the questionnaires before and after the intervention were compared using the Wilcoxon test and the magnitude of the differences was measured by effect size. Results: The median age of the mothers was 41 years, ranging from 18 to 58 years. The median age of children and adolescents was 14 years, ranging from 3 to 21 years. The SF-36 scores were significantly higher after the intervention (p<0.05), except in the domains physical aspects and emotional aspects, which already scored the highest value before the intervention. CBS and BDI scores were significantly reduced after intervention (p<0.05). Conclusion: The regular practice of resistance training has a positive impact on HRQoL, burden perception and intensity of depressive symptoms of mothers caregivers of children and adolescents with CP.

RESUMEN Introducción: La parálisis cerebral (PC) es considerada la discapacidad física más común en la infancia. Esta enfermedad afecta profundamente la salud y el bienestar de los individuos afectados y también puede influir en muchos aspectos de la vida de sus cuidadores, especialmente las madres. Objetivo: Evaluar el efecto de un programa de ejercicios de resistencia en la calidad de vida relacionada con la salud (CVRS) de las madres de niños y adolescentes con parálisis cerebral. Método: Veinte y dos madres sedentarias cuidadoras de niños y adolescentes con PC, aptas para la práctica de ejercicios de resistencia, participaron en un programa de ejercicios de resistencia de intensidad moderada, de 2 sesiones por semana durante 12 semanas. Todos los participantes respondieron el cuestionario CVRS, el Short Form Questionnaire (SF-36), la escala de sobrecarga del cuidador Caregiver Burden Scale (CBS) y el Inventario de Depresión de Beck (BDI) antes y después de la intervención. Las puntuaciones de los cuestionarios antes y después de la intervención se compararon mediante la prueba de Wilcoxon y la magnitud de las diferencias fue medida por el tamaño del efecto. Resultados: La edad mediana de las madres fue de 41 años, con un rango de 18 a 58 años. La mediana de edad de los niños/adolescentes fue de 14 años, con rango 3 a 21 años. Después de la intervención se encontró un aumento significativo en los resultados de SF-36 (p < 0,05), excepto en los dominios aspectos físicos y aspectos emocionales, que han obtenido la máxima puntuación antes de la intervención. Las puntuaciones de la CBS y la BDI tuvieron una reducción significativa después de la intervención (p < 0,05). Conclusión: La práctica regular de ejercicios de resistencia tiene un impacto positivo en la CVRS, la percepción de la sobrecarga y la intensidad de los síntomas depresivos de las madres cuidadoras de niños y adolescentes con PC.

Effect of swimming training on stress-related metabolic parameters of diabetic and non-diabetic rats / Efeito do treinamento de natação sobre estresse metabólico de ratos diabéticos e não diabéticos

Physical training can be an useful strategy to attenuate the stress markers concentrations and hyperglycemia on type 1 diabetic rats. Thus, the purpose of the present study was to investigate the effects of swimming training on metabolic parameters and stress markers in diabetic and non-diabetic rats. Twenty-four adult male Wistar rats were recruited. The rats were randomly divided into four groups, sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). The diabetic rats received alloxan monohydrate and the trained rats swam for 60 minutes five times per week. The training load was 3.5% and 5% of body weight to diabetic and non-diabetic rats, respectively. After the euthanasia, blood samples for determination of corticosterone, insulin, and glucose levels were collected, and the adrenal weight, adrenal cholesterol concentration, gastrocnemius glycogen concentration, and muscle total protein content were also determined. To compare the groups, a variance analysis was used with Tukey´s post-hoc. The significance level of 5% was adopted. The adrenal weight was higher in SD (17.2±0.6g) than the other groups (SC: 12.2±0.8g; TC: 13.7±0.6g; TD: 14.3±0.8g), and TD had similar values of TC. The corticosterone level of SD was higher than SC and TC. The serum glucose was higher in the diabetic groups and insulin was lower in these groups. Six weeks of swimming training was efficient to reduce stress markers concentration in type 1 rats. Training may be a good tool to avoid the reduction on muscle protein content in type 1 diabetic rats.

Treinamento físico pode ser uma estratégia útil para atenuar as concentrações de marcadores de estresse e hiperglicemia em ratos diabéticos tipo 1. Assim, objetivo do estudo foi investigar o efeito do treinamento de natação sobre os parâmetros metabólicos e marcadores de estresse em ratos diabéticos e não diabéticos. Foram selecionados vinte e quatro ratos machos Wistar divididos em quatro grupos, controle sedentário (SC), controle treinado (TC), diabético sedentário (SD) e diabético treinado (TD). A indução de diabetes foi por aloxana monoidratada. Os ratos foram submetidos a 60 minutos de natação cinco vezes por semana com carga de 3,5% e 5% do peso corporal para ratos diabéticos e não diabéticos, respectivamente. Depois da eutanásia, foram determinados corticosterona, insulina, glicose, peso da adrenal, concentração de colesterol da adrenal e glicogênio do músculo gastrocnêmio e conteúdo proteico total muscular também foram determinados. Foi aplicada análise de variância e Post Hoc de Tukey, com significância estatística menor que 5%. Peso da adrenal foi maior em SD (17.2±0.6g) que nos outros grupos (SC: 12.2 ±0.8g; TC: 13.7±0.6g; TD: 14.3±0.8g) e TD apresentou valores similares de TC. A corticosterona de SD foi maior do que SC e TC. Glicose sérica foi elevada no grupo diabético e a insulina foi menor neste grupo. Seis semanas de treinamento de natação foram eficientes para reduzir a concentração de marcadores de estresse em ratos diabéticos tipo 1. O treinamento de natação pode ser uma ferramenta útil para evitar a redução do conteúdo proteico muscular em ratos diabéticos tipo 1.

Use of sample size calculation in scientific research in Brazilian Physical Education journals / Emprego do cálculo amostral em pesquisas científicas de periódicos nacionais de Educação Física

The mistaken use of biostatistics in scientific research involves methodological errors both in the research itself as in its analyses. Among these, the lack of sample size calculation, considered essential for validation and credibility of results, is often found. The aim of the study was to determine how often sample size calculation is used in articles published in Physical Education national journals. The study included only national scientific journals ranked as A1 and B2 by the Coordination of Improvement of Higher Education Personnel (CAPES), which analyzed only articles available in full and published in the period from 2010 to 2012. Review articles, letter to the editor, points of view and original articles that did not perform any statistical analysis were excluded. Approximately 15 % of articles analyzed performed sample size calculation and no difference between these proportions over the years were identified. Differences between Physical Education subareas (education, health and sport) were observed, being lower in sport (p = 0.001) compared to other subareas. Journals classified as B2 showed higher use of sample size calculation in relation to those classified as B1 (p = 0.013) and A2 (p = 0.007). The use of sample size calculation in scientific research published in Physical Education national journals in the period from 2010 to 2012 was not satisfactory, especially in sport subarea. Moreover, no evolution on the use of sample size calculation over the years analyzed was observed.

O emprego equivocado da bioestatística nas pesquisas científicas implica em erros metodológicos tanto na condução quanto nas análises das mesmas. Dentre estes, a ausência do cálculo amostral, considerado primordial para validação e credibilidade dos resultados, é frequentemente encontrado. O objetivo do estudo foi verificar com que frequência o cálculo amostral é empregado nos artigos publicados em periódicos nacionais de Educação Física. Foram incluídos no estudo somente periódicos científicos nacionais classificados entre A1 e B2 pela Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), dos quais foram analisados somente artigos originais disponíveis na íntegra e publicados no período de 2010 a 2012. Foram excluídos do estudo artigos de revisão, carta ao editor, ponto de vista e artigos originais que não realizaram nenhum tipo de análise estatística. Aproximadamente 15% dos artigos analisados realizaram cálculo amostral; não houve diferença entre as proporções destes ao longo dos anos. Observou-se diferença entre as subáreas da Educação Física (educação, saúde e esporte), sendo menor na subárea esporte (p = 0,001) em relação às demais. Os periódicos classificados como B2 apresentaram maior uso do cálculo amostral em relação àqueles classificados como B1 (p = 0,013) e A2 (p = 0,007). O emprego do cálculo amostral em pesquisas científicas publicadas em periódicos nacionais de Educação Física no período de 2010 a 2012 não foi satisfatório, especialmente na subárea esporte. Além disso, não foi observada uma evolução do uso do cálculo amostral ao longo dos anos analisados.