Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure

Background: Heart failure (HF) is known to lead to skeletal muscle atrophy and dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are not fully understood. We hypothesized that HF would increase oxidative stress and ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic hyperactivity mouse model. We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF. Methods/Principal Findings: Time-course evaluation of plantaris muscle cross-sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin-like proteasome activity was performed in a mouse model of sympathetic hyperactivity-induced HF. At the 7th month of age, HF mice displayed skeletal muscle atrophy, increased oxidative stress and UPS overactivation. Moderate-intensity AET restored lipid hydroperoxides and carbonylated protein levels paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like proteasome activity and plantaris trophicity. In human HF (patients randomized to sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like proteasome activity was also increased and AET restored it to healthy control subjects' levels. Conclusions: Collectively, our data provide evidence that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome activity paralleled by improved aerobic capacity in HF patients, which is not achieved by drug treatment itself. Altogether these findings strengthen the clinical relevance of AET in the treatment of HF.

Methods of body-mass reduction by combat sport athletes

The aim of this study was to investigate the methods adopted to reduce body mass (BM) in competitive athletes from the grappling (judo, jujitsu) and striking (karate and tae kwon do) combat sports in the state of Minas Gerais, Brazil. An exploratory methodology was employed through descriptive research, using a standardized questionnaire with objective questions self-administered to 580 athletes (25.0 +/- 3.7 yr, 74.5 +/- 9.7 kg, and 16.4% +/- 5.1% body fat). Regardless of the sport, 60% of the athletes reported using a method of rapid weight loss (RWL) through increased energy expenditure. Strikers tend to begin reducing BM during adolescence. Furthermore, 50% of the sample used saunas and plastic clothing, and only 26.1% received advice from a nutritionist. The authors conclude that a high percentage of athletes uses RWL methods. In addition, a high percentage of athletes uses unapproved or prohibited methods such as diuretics, saunas, and plastic clothing. The age at which combat sport athletes reduce BM for the first time is also worrying, especially among strikers.

Dilthey: The hermeneutics of life and the universal aspirations of pedagogy

Dilthey claimed that first psychology and then hermeneutics played the foundational role for his philosophy of life, whose main practical goal is to develop a pedagogy or theory of education. Pedagogy needs help from h ethics to establish its ends, and from psychology to indicate it means. This paper intends to show the relationship between Dilthey's hermeneutics of life and his pedagogy. Dilthey's philosophy of life, in so far it adopts the hermeneutical procedure, engages in the understanding of or the search for the meaning of human socio-historical creations, by adopting a special type of relationship between parts and whole. It is exactly within this hermeneutical balance that we propose to extinguish any indication of a rupture, breach, or contradiction between the quest for universal principles of human behavior and :Dilthey's defense of the impossibility of constructing human moral tasks by means of universal principles. Dilthey began his ethics lectures at the University of Berlin in 1890. These lectures, published in 1958 by Herman Nohl in volume X of Dilthey's collected works, indicate the direction of the trajectory by which formative or social ethics are consolidated as a historical solution for reaching universal principles that can guide human purposes. This trajectory is a result of the distinctively human exercise of self-reflection, by means of which we can fulfill our destiny of manifesting and exteriorizing in time the immanent energy of the absolute spirit. We wish to show that it is possible that such a pedagogy can respect its universal task of orienting the historical development of the younger generation without directing this process by means of fixed and rigid aims.

Frontal Plane Biomechanics in Males and Females with and without Patellofemoral Pain

NAKAGAWA, T. H., E. T. U. MORIYA, C. D. MACIEL, and F. V. SERRAO. Frontal Plane Biomechanics in Males and Females with and without Patellofemoral Pain. Med. Sci. Sports &ere., Vol. 44, No. 9, pp. 1747-1755, 2012. Purpose: The study's purpose was to compare trunk, pelvis, hip, and knee frontal plane biomechanics in males and females with and without patellofemoral pain syndrome (PFPS) during stepping. Methods: Eighty recreational athletes were equally divided into four groups: female PFPS, female controls, male PFPS, and male controls. Trunk, pelvis, hip, and knee frontal plane kinematics and activation of the gluteus medius were evaluated at 15 degrees, 30 degrees, 45 degrees, and 60 degrees of knee flexion during the downward and upward phases of the stepping task. Isometric hip abductor torque was also evaluated. Results: Females showed increased hip adduction and knee abduction at all knee flexion angles, greater ipsilateral trunk lean and contralateral pelvic drop from 60 degrees of knee flexion till the end of the stepping task (P = 0.027-0.001), diminished hip abductor torque (P < 0.001), and increased gluteus medius activation than males (P = 0.008-0.001). PFPS subjects presented increased knee abduction at all the angles evaluated; greater trunk, pelvis, and hip motion from 45 of knee flexion of the downward phase till the end of the maneuver; and diminished gluteus medius activation at 60 degrees of knee flexion, compared with controls (P = 0.034-0.001). Females with PFPS showed lower hip abductor torque compared with the other groups. Conclusions: Females presented with altered frontal plane biomechanics that may predispose them to knee injury. PFPS subjects showed frontal plane biomechanics that could increase the lateral patellofemoral joint stress at all the angles evaluated and could increase even more from 45 degrees of knee flexion in the downward phase untill the end of the maneuver. Hip abductor strengthening and motor control training should be considered when treating females with PFPS.

Swimming Training in Rats Increases Cardiac MicroRNA-126 Expression and Angiogenesis

DA SILVA, N. D. JR, T. FERNANDES, U. P. R. SOCI, A. W. A. MONTEIRO, M. I. PHILLIPS, and E. M. DE OLIVEIRA. Swimming Training in Rats Increases Cardiac MicroRNA-126 Expression and Angiogenesis. Med. Sci. Sports Exerc., Vol. 44, No. 8, pp. 1453-1462, 2012. Purpose: MicroRNA (miRNA)-126 is angiogenic and has two validated targets: Sprouty-related protein 1 (Spred-1) and phosphoinositol-3 kinase regulatory subunit 2 (PI3KR2), negative regulators of angiogenesis by VEGF pathway inhibition. We investigated the role of swimming training on cardiac miRNA-126 expression related to angiogenesis. Methods: Female Wistar rats were assigned to three groups: sedentary (S), training 1 (T1, moderate volume), and training 2 (T2, high volume). T1 consisted of 60 min.d(-1) of swimming, five times per week for 10 wk with 5% body overload. T2 consisted of the same protocol of T1 until the eighth week; in the ninth week, rats trained for two times a day, and in the 10th week, rats trained for three times a day. MiRNA and PI3KR2 gene expression analysis was performed by real-time polymerase chain reaction in heart muscle. We assessed markers of training, the cardiac capillary-fiber ratio, cardiac protein expression of VEGF, Spred-1, Raf-1/ERK 1/2, and PI3K/Akt/eNOS. Results: The cardiac capillary-fiber ratio increased in T1 (58%) and T2 (101%) compared with S. VEGF protein expression was increased 42% in T1 and 108% in T2. Cardiac miRNA-126 expression increased 26% (T1) and 42% (T2) compared with S, correlated with angiogenesis. The miRNA-126 target Spred-1 protein level decreased 41% (T1) and 39% (T2), which consequently favored an increase in angiogenic signaling pathway Raf-1/ERK 1/2. On the other hand, the gene expression of PI3KR2, the other miRNA-126 target, was reduced 39% (T1) and 78% (T2), and there was an increase in protein expression of components of the PI3K/Akt/eNOS signaling pathway in the trained groups. Conclusions: This study showed that aerobic training promotes an increase in the expression of miRNA-126 and that this may be related to exercise-induced cardiac angiogenesis, by indirect regulation of the VEGF pathway and direct regulation of its targets that converged in an increase in angiogenic pathways, such as MAPK and PI3K/Akt/eNOS.

Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age

Background: Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients. Design: Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45-59 years, and older, defined as 60-75 years) and exercise status (trained and untrained). Methods: MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm Blood Flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test. Results: Exercise training significantly and similarly increased FBF and peak VO2 in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients. Conclusion: Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.

Exercise Inhibits Allergic Lung Inflammation

Aerobic conditioning (AC) performed either during or after sensitization reduces allergic inflammation in mice; however, the effects of AC performed before and during allergic sensitization on airway inflammation are unknown. Mice were divided into Control, AC, OVA, and AC + OVA groups. Mice were trained in a treadmill followed by either ovalbumin (OVA) sensitization or saline administration. Peribronchial inflammation, OVA-specific IgE and IgG1 titers, the expression of Th1 and Th2 cytokines, and airway remodeling were evaluated, as well as the expression of Eotaxin, RANTES, ICAM-1, VCAM-1, TGF-beta and VEGF. Aerobic conditioning performed before and during allergic sensitization displayed an inhibitory effect on the OVA-induced migration of eosinophils and lymphocytes to the airways, a reduction of IgE and IgG1 titers and an inhibition of the expression of Th2 cytokines. The AC + OVA group also demonstrated reduced expression of ICAM-1, VCAM-1, RANTES, TGF-beta and VEGF, as well as decreased airway remodeling (p < 0.05). The effects of AC before and during the sensitization process inhibit allergic airway inflammation and reduce the production of Th2 cytokines and allergen-specific IgE and IgG1.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

Abstract Background Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. Results High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. Conclusion The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.

Involvement of the atrial natriuretic peptide in cardiovascular pathophysiology and its relationship with exercise

In this minireview we describe the involvement of the atrial natriuretic peptide (ANP) in cardiovascular pathophysiology and exercise. The ANP has a broad homeostatic role and exerts complex effects on the cardio-circulatory hemodynamics, it is produced by the left atrium and has a key role in regulating sodium and water balance in mammals and humans. The dominant stimulus for its release is atrial wall tension, commonly caused by exercise. The ANP is involved in the process of lipolysis through a cGMP signaling pathway and, as a consequence, reducing blood pressure by decreasing the sensitivity of vascular smooth muscle to the action of vasoconstrictors and regulate fluid balance. The increase of this hormone is associated with better survival in patients with chronic heart failure (CHF). This minireview provides new evidence based on recent studies related to the beneficial effects of exercise in patients with cardiovascular disease, focusing on the ANP.

Fructose and Galactose Enhance Post-Exercise Human Liver Glycogen Synthesis

Both liver and muscle glycogen stores play a fundamental role in exercise and fatigue, but the effect of different CHO sources on liver glycogen synthesis in humans is unclear. The aim was to compare the effect of maltodextrin (MD) drinks containing galactose, fructose, or glucose on postexercise liver glycogen synthesis.

REGULATION OF WHOLE-BODY ENERGY HOMEOSTASIS WITH GROWTH HORMONE REPLACEMENT THERAPY AND ENDURANCE EXERCISE

We hypothesized that network analysis is useful to expose coordination between whole body and myocellular levels of energy metabolism and can identify entities that underlie skeletal muscle's contribution to growth hormone-stimulated lipid handling and metabolic fitness. We assessed 112 metabolic parameters characterizing metabolic rate and substrate handling in tibialis anterior muscle and vascular compartment at rest, after a meal and exercise with growth hormone replacement therapy (GH-RT) of hypopituitary patients (n = 11). The topology of linear relationships (| r | ≥ 0.7, P ≤ 0.01) and mutual dependencies exposed the organization of metabolic relationships in three entities reflecting basal and exercise-induced metabolic rate, triglyceride handling, and substrate utilization in the pre- and postprandial state, respectively. GH-RT improved aerobic performance (+5%), lean-to-fat mass (+19%), and muscle area of tibialis anterior (+2%) but did not alter its mitochondrial and capillary content. Concomitantly, connectivity was established between myocellular parameters of mitochondrial lipid metabolism and meal-induced triglyceride handling in serum. This was mediated via the recruitment of transcripts of muscle lipid mobilization (LIPE, FABP3, and FABP4) and fatty acid-sensitive transcription factors (PPARA, PPARG) to the metabolic network. The interdependence of gene regulatory elements of muscle lipid metabolism reflected the norm in healthy subjects (n = 12) and distinguished the regulation of the mitochondrial respiration factor COX1 by GH and endurance exercise. Our observations validate the use of network analysis for systems medicine and highlight the notion that an improved stochiometry between muscle and whole body lipid metabolism, rather than alterations of single bottlenecks, contributes to GH-driven elevations in metabolic fitness.

Next-state comfort in learning a vertical stick transportation sequence

Over the last decade, the end-state comfort effect (e.g., Rosenbaum et al., 2006) has received a considerable amount of attention. However, some of the underlying mechanisms are still to be investigated, amongst others, how sequential planning affects end-state comfort and how this effect develops over learning. In a two-step sequencing task, e.g., postural comfort can be planned on the intermediate position (next state) or on the actual end position (final state). It might be hypothesized that, in initial acquisition, next state’s comfort is crucial for action planning but that, in the course of learning, final state’s comfort is taken more and more into account. To test this hypothesis, a variant of Rosenbaum’s vertical stick transportation task was used. Participants (N = 16, right-handed) received extensive practice on a two-step transportation task (10,000 trials over 12 sessions). From the initial position on the middle stair of a staircase in front of the participant, the stick had to be transported either 20 cm upwards and then 40 cm downwards or 20 cm downwards and then 40 cm upwards (N = 8 per subgroup). Participants were supposed to produce fluid movements without changing grasp. In the pre- and posttest, participants were tested on both two-step sequencing tasks as well as on 20 cm single-step upwards and downwards movements (10 trials per condition). For the test trials, grasp height was calculated kinematographically. In the pretest, large end/next/final-state comfort effects for single-step transportation tasks and large next-state comfort effects for sequenced tasks were found. However, no change in grasp height from pre- to posttest could be revealed. Results show that, in vertical stick transportation sequences, the final state is not taken into account when planning grasp height. Instead, action planning seems to be solely based on aspects of the next action goal that is to be reached.

Early repolarization, left ventricular diastolic function, and left atrial size in professional soccer players

Recent data have suggested a relation among long-term endurance sport practice, left atrial remodeling, and atrial fibrillation. We investigated the influence of an increased vagal tone, represented by the early repolarization (ER) pattern, on diastolic function and left atrial size in professional soccer players. Fifty-four consecutive athletes underwent electrocardiography, echocardiography, and exercise testing as part of their preparticipation screening. Athletes were divided into 2 groups according to presence or absence of an ER pattern, defined as a ST-segment elevation at the J-point (STE) > or =0.1 mm in 2 leads. For linear comparisons average STE was calculated. Mean age was 24 +/- 4 years. Twenty-five athletes (46%) showed an ER pattern. Athletes with an ER pattern had a significant lower heart rate (54 +/- 9 vs 62 +/- 11 beats/min, p = 0.024), an increased E/e' ratio (6.1 +/- 1.2 vs 5.1 +/- 1.0, p = 0.002), and larger volumes of the left atrium (25.6 +/- 7.3 vs 21.8 +/- 5.0 ml/m(2), p = 0.031) compared to athletes without an ER pattern. There were no significant differences concerning maximum workload, left ventricular dimensions, and systolic function. Univariate regression analysis revealed significant correlations among age, STE, and left atrial volume. In a stepwise multivariate regression analysis age, STE and e' contributed independently to left atrial size (r = 0.659, p <0.001). In conclusion, athletes with an ER pattern had an increased E/e' ratio, reflecting a higher left atrial filling pressure, contributing to left atrial remodeling over time.