Search

Background and objectives: Exercise can help ease withdrawal symptoms of smokers. However, there is little information about the physiological responses, such as cardiorespiratory and lactate (La) responses, during exercise from light to moderate intensity combined with transdermal nicotine patches (TNPs) in smokers. This study aimed to investigate the effect of TNPs on the cardiorespiratory and La responses during exercise at light to moderate intensity. Materials and Methods: Fourteen young men (8 non-smokers, 6 current smokers) aged 20 to 26 years participated in this study. They performed an incremental graded submaximal exercise test using an electromagnetic cycle ergometer set from 30 to 210 W with (TNP condition) or without a TNP (control condition) in a random order. The TNP was applied to the left arm 8-10 h prior to starting the exercise to achieve the peak level of blood nicotine concentration. Heart rate (HR), rate of perceived exertion (RPE), oxygen consumption ( V O 2 ), ventilation ( V E), and blood La at rest and during exercise were measured and analyzed. Results: The HR at rest was significantly higher in the TNP condition than in the control condition (TNP; 74.7 ± 13.8 bpm, control; 65.3 ± 10.8 bpm, p < 0.001). There was no interaction (condition × exercise intensity) between any of the variables, and V O 2 , V E, RPE, and La during exercise were not significantly different between the conditions. However, HR during exercise was 6.7 bpm higher on average in the TNP condition. Conclusions: The HR during exercise was greater at light to moderate intensity with a TNP. Our study results will guide clinicians or health professionals when prescribing exercise programs combined with TNPs for healthy young smokers.

Limited information exists regarding the impact of different temperature stimuli on myosin heavy chain (MyHC) expression in skeletal muscle during recovery from injury. Therefore, this experiment investigated the impact of both cold and heat exposure on the MyHC isoform profile in the rat soleus during recovery from injury. Male Wistar rats were randomly divided into control, bupivacaine-injected (BPVC), BPVC with icing, and BPVC with heat stress groups. Muscle injury was induced by intramuscular injection of bupivacaine into soleus muscles of male Wistar rats. Icing treatment (0°C for 20 min) was performed immediately after the injury. Intermittent heat stress (42°C for 30 min on alternating days) was carried out during 2-14 days after bupivacaine injection. In response to injury, a transient increase in developmental, IId/x, and IIb MyHC isoforms, as well as various types of hybrid fibers, followed by the recovery of the MyHC profile toward the control level, was noted in the regeneration of the soleus. The restoration of the MyHC profile in the regenerating muscle at whole-muscle and individual myofiber levels was partially delayed by icing but facilitated by heat stress. In addition, the application of repeated heat stress promoted the recovery of soleus muscle mass toward the control level following injury. We conclude that compared with acute and immediate cold (icing) treatment, chronic and repeated heat stress may be a more appropriate treatment for the enhancement of both normalization of the MyHC profile and restoration of muscle mass following injury. NEW & NOTEWORTHY Cold exposure (icing), but not heat exposure, has been well accepted as a first-aid treatment for accidental and/or sports-related injuries. However, recent evidence suggests the negative impact of icing treatment on skeletal muscle regeneration following injury. Here, we demonstrated that acute/immediate icing treatment delayed the restoration of the myosin heavy chain (MyHC) profile, but intermittent hyperthermia, repeated for several days, facilitated the recovery of both muscle mass and the MyHC profile in the regeneration of skeletal muscle following injury.

Psoriasis is a chronic inflammatory skin disease characterized mainly by epidermal hyperplasia, scaling, and erythema; T helper 17 cells have a role in its pathogenesis. Although IL-26, known as a T helper 17 cytokine, is upregulated in psoriatic skin lesions, its precise role is unclear. We investigated the role of IL-26 in the imiquimod-induced psoriasis-like murine model using human IL-26 transgenic mice. Erythema symptoms induced by daily applications of imiquimod increased dramatically in human IL-26 transgenic mice compared with controls. Vascularization and immune cell infiltration were prominent in skin lesions of human IL-26 transgenic mice. Levels of fibroblast growth factor (FGF) 1, FGF2, and FGF7 were significantly upregulated in the skin lesions of imiquimod-treated human IL-26 transgenic mice and psoriasis patients. In vitro analysis demonstrated that FGF1, FGF2, and FGF7 levels were elevated in human keratinocytes and vascular endothelial cells following IL-26 stimulation. Furthermore, IL-26 acted directly on vascular endothelial cells, promoting proliferation and tube formation, possibly through protein kinase B, extracellular signal-regulated kinase, and NF-κB pathways. Moreover, similar effects of IL-26 were observed in the murine contact hypersensitivity model, indicating that these effects are not restricted to psoriasis. Altogether, our data indicate that IL-26 may be a promising therapeutic target in T cell-mediated skin inflammation, including psoriasis., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and objectives: The purpose of this study was to compare the energy expenditures (EE) of a single sit-to-stand (STS) movements with slow and normal speeds using a multi-stage exercise test. Materials and Methods: Twelve young males, aged 21⁻27 years (age, 23.0 ± 1.7 years; height, 171.2 ± 6.1 cm; weight, 64.3 ± 5.6 kg), performed repeated 3-s stand-up and 3-s sit-down (slow) or 1-s stand-up and 1-s sit-down (normal) movement on two different days with random order. All the participants completed multi-stage tests at different STS frequencies per minute. The slope and intercept of the linear regression relationship between the EE (kcal/min) and the STS frequency were obtained, and the slope of the regression was quantified as the EE of an STS. Results: The metabolic equivalents (METs) of the STS-slow was 4.5 METs for the frequency of 10 times/min (in total 1 min), and the net EE was 5.00 ± 1.2 kcal/min. The net EE of the STS-slow was 0.37 ± 0.12 kcal, which was significantly greater than that during the STS-normal (0.26 ± 0.06 kcal). The difference between the EEs of the STS-slow and STS-normal was significantly greater in taller and heavier subjects. Conclusions: We concluded that the intensity of STS-slow movement is moderate, and the EE during an STS-slow (0.37 ± 0.12 kcal) is higher than that during an STS-normal (0.26 ± 0.06 kcal). Our study results will help exercise and/or health professionals prescribe physical activity programs using STS movement for healthy young population groups.

We tested the hypothesis that there are sex differences in hindlimb unloading-induced activation of the forkhead box subfamily O3a (FoxO3a) signaling pathway in rat soleus muscle. Age-matched male and female Wistar rats were subjected to hindlimb unloading, and the soleus muscle was removed before or 1 or 7 days after unloading. Female rats showed greater percent changes in relative soleus muscle weight than males. FoxO3a phosphorylation was lower in females than in males and was associated with higher levels of protein ubiquitination 7 days after unloading. Heat shock protein 72 (Hsp72) levels were lower in female rats and increased in males during unloading. Female rats showed slightly higher myostatin levels, which showed a non-significant decline in male rats following unloading. Thus, males and females show different responses to the FoxO3a/ubiquitin-proteasome pathway following hindlimb unloading in rat soleus muscle, which may be associated with differences in Hsp72 expression and myostatin signaling.

We examined the effect of a combination of astaxanthin (AX) supplementation, repeated heat stress, and intermittent reloading (IR) on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats (8-week-old) were divided into control, hind-limb unweighting (HU), IR during HU, IR with AX supplementation, IR with repeated heat stress (41.0-41.5 °C for 30 min), and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soleus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.

[Purpose] This study aimed to identify the efficacy of a progressive walking program on the risk of developing locomotive syndrome among untrained elderly Japanese people. [Participants and Methods] Twenty-four untrained elderly individuals (68 ± 4 years) completed a 17-week progressive walking program. The stand-up, two-step tests and the 25-question geriatric locomotive function scale were used to assess the risk of locomotive syndrome at baseline, the 8-week midpoint (2 months), and the 17-week endpoint (4 months). Maximal isometric muscle strength of the knee extensors and flexors were measured using a dynamometer with the hip joint angle at 90° of flexion and physical function (the 30-s sit-to-stand, sit-up, 10-meter walk, and grip strength) were evaluated. [Results] The 4-month walking program significantly improved the two-step test and geriatric locomotive function scale scores. This may be attributable to the improvement in knee flexor strength and physical function. [Conclusion] A 4-month program of progressive walking effectively lowered the risk of developing locomotive syndrome in elderly Japanese people by improving knee flexor muscle strength and physical function.

We aimed to replicate, in a specific athletic event cohort (only track and field) and in two different ethnicities (Japanese and East European, i.e. Russian and Polish), original findings showing the association of the angiotensin-II receptor type-2 gene ( AGTR2 ) rs11091046 A>C polymorphism with athlete status. We compared genotypic frequencies of the AGTR2 rs11091046 polymorphism among 282 track and field sprint/power athletes (200 men and 82 women), including several national record holders and Olympic medallists (214 Japanese, 68 Russian and Polish), and 2024 control subjects (842 men and 1182 women) (804 Japanese, 1220 Russian and Polish). In men, a meta-analysis from the two combined cohorts showed a significantly higher frequency of the C allele in athletes than in controls (odds ratio: 1.62, P =0.008, heterogeneity index I 2 =0%). With regard to respective cohorts, C allele frequency was higher in Japanese male athletes than in controls (67.7% vs. 55.9%, P =0.022), but not in Russian/Polish male athletes (61.9% vs. 51.0%, P =0.172). In women, no significant results were obtained by meta-analysis for the two cohorts combination ( P =0.850). The AC genotype frequency was significantly higher in Russian/Polish women athletes than in controls (69.2% vs. 42.1%, P =0.022), but not in Japanese women athletes ( P =0.226). Our results, in contrast to previous findings, suggested by meta-analysis that the C allele of the AGTR2 rs11091046 polymorphism is associated with sprint/power track and field athlete status in men, but not in women., Competing Interests: The authors have no conflicts of interest to declare.

Background: There are several studies on the relationship between low back pain and physical activity. However, the results of these studies vary, and the relationship between them remains unclear. Therefore, we conducted a cross-sectional study to evaluate the association between objectively measured physical activity and low back pain in Japanese men., Methods: The study included 4022 Japanese men [average age: 47 (10) y]. Daily amount of moderate to vigorous physical activity and step counts were measured using an accelerometer. Low back pain, drinking and smoking, and lifestyle-related diseases were surveyed using a self-administered questionnaire. A logistic regression model was used to evaluate the relationship between physical activity and step counts with persistent low back pain after adjusting for confounders., Results: Persistent low back pain was reported in 428 participants. The multivariable-adjusted odds ratios of presenting persistent low back pain across quartiles of amount of moderate to vigorous physical activity were 1.00 (reference); 0.93 (95% confidence interval, 0.70-1.22); 0.97 (95% confidence interval, 0.74-1.28); and 0.67 (95% confidence interval, 0.50-0.90); P for linearity = .012., Conclusion: We found a significant inverse relationship between objectively measured physical activity and persistent low back pain.

Genetic polymorphisms and sex differences are suggested to affect muscle fiber composition; however, no study has investigated the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences. Therefore, the present study examined the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences in the Japanese population. The present study included 211 healthy Japanese individuals (102 men and 109 women). Muscle biopsies were obtained from the vastus lateralis to determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx). Moreover, we analyzed polymorphisms in α-actinin-3 gene ( ACTN3; rs1815739 ), angiotensin-converting enzyme gene ( ACE; rs4341 ), hypoxia-inducible factor 1 α gene ( rs11549465 ), vascular endothelial growth factor receptor 2 gene ( rs1870377 ), and angiotensin II receptor, type 2 gene ( rs11091046 ), by TaqMan single-nucleotide polymorphism genotyping assays. The proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%, respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID + DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE insertion/deletion (I/D) was significantly correlated with the proportion of MHC-I ( r = -0.23) and MHC-IIx ( r = 0.27) in men. In contrast, no significant correlation was observed between the examined polymorphisms and muscle fiber composition in women. These results suggest that the ACTN3 R577X and ACE I/D polymorphisms independently affect the proportion of human skeletal muscle fibers MHC-I and MHC-IIx in men but not in women. NEW & NOTEWORTHY In men, the RR + RX genotype of the α-actinin-3 gene ( ACTN3) R577X polymorphism was associated with a higher proportion of myosin heavy chain (MHC)-IIx. The ID + DD genotype of the angiotensin-converting enzyme gene ( ACE) insertion/deletion (I/D) polymorphism, in contrast to a previous finding, was associated with a higher proportion of MHC-I in men. In addition, the combined genotype of these polymorphisms was correlated with the proportion of MHC-I and MHC-IIx in men. Thus ACTN3 R577X and ACE I/D polymorphisms influence the muscle fiber composition in Japanese men.

Sakamoto, A, Naito, H, and Chow, C-M. Effects of hyperventilation on repeated pedaling sprint performance: short vs. long intervention duration. J Strength Cond Res 32(1): 170-180, 2018-Previously, hyperventilation (HV)-induced respiratory alkalosis, implemented during the last 30 seconds of each 60-second recovery that separated repeated pedaling sprints, has been shown to attenuate performance decrement. The present study investigated whether the ergogenic effects of HV would hold if the HV duration was shortened or extended. Seventeen power-trained athletes performed 10 seconds × 10 sets of standing pedaling sprints on a cycle ergometer, with a 60-second interset recovery and the load (kp) set at 0.075 × body mass, under 3 breathing conditions: control, HV of 15 seconds (HVshort), and HV of 45 seconds (HVlong). Subjects breathed spontaneously during each 60-second recovery for the control condition. Under HVshort and HVlong conditions, subjects hyperventilated at 60 breaths·min with near-maximum tidal volume during the last 15 or 45 seconds, respectively, of each recovery period. Peak and mean pedaling power outputs (POpeak and POmean) were documented for each sprint set to compare performance decrements between conditions. No significant condition effect or condition × time interaction was found for POpeak and POmean. The lack of ergogenic effects with HVlong may be ascribed to a complex interaction between the positive (augmented buffering effects) and negative effects of HV (decreased aerobic energy metabolism and exaggerated discomfort sensation of increased ventilatory work). For HVshort, the implemented duration may have been too short to yield positive physiological effects. A practical implication is that ergogenic effects may be impaired when HV is too short or too long, with the duration of around 30 seconds being the target for this exercise type.

Background: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population. A total of 1565 individuals were studied, subdivided into 822 middle-aged controls and 743 centenarians., Results: We found a FOXOA3 rs2802292 T-allele-dependent association of fibronectin type III domain-containing 5 (FDNC5) rs16835198 with EL: the frequency of carriers of the FOXOA3 rs2802292 T-allele among individuals with the rs16835198 GG genotype was significantly higher in cases than in controls (P < 0.05). On the other hand, among non-carriers of the APOE 'risk' ε4-allele, the frequency of the FDNC5 rs16835198 G-allele was higher in cases than in controls (48.4% vs. 43.6%, P < 0.05). Among carriers of the 'non-risk' APOE ε2-allele, the frequency of the rs16835198 G-allele was higher in cases than in controls (49% vs. 37.3%, P < 0.05)., Conclusions: The association of FDNC5 rs16835198 with EL seems to depend on the presence of the FOXOA3 rs2802292 T-allele and we report a novel association between FNDC5 rs16835198 stratified by the presence of the APOE ε2/ε4-allele and EL. More research on 'gene*gene' and 'gene*environment' effects is needed in the field of EL.

[Purpose] This study evaluated whether obesity is a risk factor for low back pain, by using body fat percentage (%FAT) and body mass index (BMI) as indices of obesity among Japanese males. [Subjects and Methods] This study included 1,152 males (average age: 28.0 ± 4.6 years). BMI was calculated from subject's height and weight, and %FAT was estimated by the thickness of two parts of skin. Low back pain, drinking and smoking were surveyed using a self-administered questionnaire, and maximal oxygen uptake was measured by a submaximal exercise test using a cycle ergometer. [Results] A significant positive dose-response relationship was shown between %FAT and persistent low back pain prevalence. Similarly, a significant positive dose-response relationship was confirmed between BMI and persistent low back pain. [Conclusion] This study suggests that both high %FAT and BMI are risk factors for persistent low back pain.

Heat shock proteins (HSPs) play an important role in insulin resistance and improve the cellular stress response via HSP induction by exercise to treat type 2 diabetes. In this study, the effects of exercise-induced HSP72 expression levels on whole-body insulin resistance in type 2 diabetic rats were investigated. Male 25-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into three groups: sedentary (Sed), trained in a thermal-neutral environment (NTr: 25 °C), and trained in a cold environment (CTr: 4 °C). Exercise training was conducted 5 days/week for 10 weeks. Rectal temperature was measured following each bout of exercise. An intraperitoneal glucose tolerance test (IPGTT) was performed after the training sessions. The serum, gastrocnemius muscle, and liver were sampled 48 h after the final exercise session. HSP72 and heat shock cognate protein 73 expression levels were analyzed by Western blot, and serum total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels were measured. NTr animals exhibited significantly higher body temperatures following exercise, whereas, CTr animals did not. Exercise training increased HSP72 levels in the gastrocnemius muscle and liver, whereas, HSP72 expression was significantly lower in the CTr group than that in the NTr group (p < 0.05). Glucose tolerance improved equally in both trained animals; however, insulin levels during the IPGTT were higher in CTr animals than those in NTr animals (p < 0.05). In addition, the TG and FFA levels decreased significantly only in NTr animals compared with those in Sed animals. These results suggest that attenuation of exercise-induced HSP72 expression partially blunts improvement in whole-body insulin resistance and lipid metabolism in type 2 diabetic rats.

Intracellular signaling exhibits circadian variation in the suprachiasmatic nucleus and liver. However, it is unclear whether circadian regulation also extends to intracellular signaling pathways in the cardiac and skeletal muscles. Here, we examined circadian variation in the intracellular mammalian target of rapamycin (mTOR)/70 kDa ribosomal protein S6 kinase 1 (p70S6K) and extracellular signal-regulated kinase (ERK) pathways, which regulate protein synthesis in rat cardiac and skeletal muscles. Seven-week-old male Wistar rats were assigned to six groups: Zeitgeber time (ZT) 2, ZT6, ZT10, ZT14, ZT18, and ZT22 (ZT0, lights on; ZT12, lights off). The cardiac, plantaris, and soleus muscles were removed after a 12-h fasting period, and signal transducers involved in protein synthesis (mTOR, p70S6K, and ERK) were analyzed by western blotting. Circadian rhythms of signal transducers were observed in both cardiac (mTOR, p70S6K, and ERK) and plantaris (p70S6K and ERK) muscles ( p <0.05), but not in the soleus muscle. In the cardiac muscle, the phosphorylation rate of mTOR was significantly higher at ZT6 (peak) than at ZT18 (bottom), and the phosphorylation rate of p70S6K was significantly higher at ZT2 (peak) than at ZT18 (bottom). In contrast, in the plantaris muscle, the phosphorylation rate of ERK was significantly lower at ZT2 (bottom) than at ZT18 (peak). Our data suggested that protein synthesis via mTOR/p70S6K and ERK signaling molecules exhibits circadian variation in rat cardiac and fast-type plantaris muscles.

Purpose: Low-load voluntary exercise can induce muscle hypertrophy and strength gain in working muscles when combined with blood flow restriction (BFR). However, it is unknown whether such hypertrophy and strength gain can be induced by involuntary muscle contractions triggered via low-intensity neuromuscular electrical stimulation (NMES) combined with BFR. The purpose of this article was to investigate whether low-intensity NMES combined with BFR (NMES-BFR) could elicit muscle hypertrophy and strength gain in the quadriceps., Methods: Eight untrained young male participants (mean ± SE; age, 26.2 ± 0.7 yr; height, 1.74 ± 0.02 m; body weight, 71.4 ± 4.8 kg) were subjected to 23 min of unilateral low-intensity (5%-10% of maximal voluntary contraction) NMES twice per day (5 d·wk⁻¹) for 2 wk: one leg received NMES-BFR and the other leg received NMES alone. Quadriceps muscle thickness and isometric and isokinetic strength were measured before and every week throughout the training and detraining periods., Results: In NMES-BFR legs, muscle thickness increased after 2 wk of training (+3.9%) and decreased after 2 wk of detraining (-3.0%). NMES-BFR training also increased maximal knee extension strength in isometric (+14.2%) and isokinetic (+7.0% at 90°·s⁻¹ and +8.3% at 180°·s⁻¹) voluntary contractions. In addition, maximal isometric strength decreased (-6.8%), whereas no large fall (-1.9% at 90°·s⁻¹ and -0.6% at 180°·s⁻¹) in isokinetic maximal strength was evident after 2 wk of detraining. In legs that received NMES alone, no prominent change was observed; there was a negligible effect on isometric strength., Conclusion: Low-intensity NMES-BFR induces muscle hypertrophy and strength gain in untrained young male participants.

Aims: To investigate the relationship between muscle oxygenation (specifically, the levels of oxygenated haemoglobin and myoglobin [oxyHb/Mb]) during maximal running and muscle fibre composition, and to determine whether muscle fibre composition can be non-invasively estimated from oxyHb/Mb levels during maximal running., Methods: Eight male runners ([Formula: see text], 60.9± 4.6 mL·kg -1 ·min -1 ) performed an incremental running test on a treadmill. OxyHb/Mb levels of the vastus lateralis during maximal running were measured by near-infrared spectroscopy (NIRS). Muscle fibre composition of the vastus lateralis was determined from muscle biopsy samples from the same region measured by NIRS, and the fibre types were classified as type I, type IIa, or type IIb fibres using traditional pH-sensitive ATPase staining. Type I and type IIa fibres together were defined as oxidative fibres., Results: OxyHb/Mb levels during running were lowest at exhaustion in all participants. OxyHb/Mb levels at exhaustion were positively correlated with the percentages of type I fibres (r=0.755, p<0.05) and oxidative fibres (r=0.944, p<0.01)., Conclusions: We conclude that higher oxyHb/Mb levels at exhaustion during maximal running are correlated with a higher percentage of oxidative fibres, indicating the potential importance of oxidative fibres in the maintenance of oxyHb/Mb levels during maximal running. Additionally, muscle fibre composition could be non-invasively estimated from oxyHb/Mb levels during maximal running tests in runners.

Skeletal muscles are composed of two major muscle fiber types: slow-twitch oxidative fibers and fast-twitch glycolytic fibers. The proteins in these muscle fibers are known to differ in their expression, relative abundance, and post-translational modifications. In this study, we report a previously unreported post-translational modification of α-skeletal muscle actin in the skeletal muscles of adult male F344 rats in vivo. Using two-dimensional electrophoresis (2D-PAGE), we first examined the differences in the protein expression profiles between the soleus and plantaris muscles. We found higher intensity protein spots at approximately 60 kDa and pH 9 on 2D-PAGE for the soleus muscle compared with the plantaris muscle. These spots were identified as α-skeletal muscle actin by liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry and western blot analyses. In addition, we found that the 60 kDa α-skeletal muscle actin is modified by small ubiquitin-like modifier (SUMO) 1, using 2D-PAGE and western blot analyses. Furthermore, we found that α-skeletal muscle actin with larger molecular weight was localized in the nuclear and cytosol of the skeletal muscle, but not in the myofibrillar fraction by the combination of subcellular fractionation and western blot analyses. These results suggest that α-skeletal muscle actin is modified by SUMO-1 in the skeletal muscles, localized in nuclear and cytosolic fractions, and the extent of this modification is much higher in the slow muscles than in the fast muscles. This is the first study to show the presence of SUMOylated actin in animal tissues.

Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation (MV) results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. We tested the hypothesis that repeated bouts of heat stress result in diaphragm resistance against CMV-induced atrophy and contractile dysfunction. Male Wistar rats were randomly divided into six experimental groups: 1) control; 2) single bout of whole body heat stress; 3) repeated bouts of whole body heat stress; 4) 12 h CMV; 5) single bout of whole body heat stress 24 h before CMV; and 6) repeated bouts of whole body heat stress 1, 3, and 5 days before 12 h of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear: this heat stress-induced protection against CMV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm., (Copyright © 2015 the American Physiological Society.)

Toe-out angle alternation is a potential tactic for decreasing the knee adduction moment during walking. Published reports have not examined the medial knee contact force during the toe-out gait, although it is a factor affecting knee articular cartilage damage. This study investigated the effects of increased toe-out angle on the medial knee contact force, using musculoskeletal simulation analysis. For normal and toe-out gaits in 18 healthy subjects, the muscle tension forces were simulated based on the joint moments and ground reaction forces with optimization process. The medial knee contact force during stance phase was determined using the sum of the muscle force and joint reaction force components. The first and second peaks of the medial knee contact force were compared between the gaits. The toe-out gait showed a significant decrease in the medial knee contact force at the second peak, compared with the normal gait. In contrast, the medial knee contact forces at the first peak were not significantly different between the gaits. These results suggest that the toe-out gait is beneficial for decreasing the second peak of the medial knee contact force.

There are several gene variants that are candidates to influence functional capacity in long-lived individuals. As such, their potential association with exceptional longevity (EL, i.e., reaching 100+ years) deserves analysis. Among them are rs7832552 in the thyrotropin-releasing hormone receptor (TRHR) gene, rs1800795 in the interleukin-6 (IL6) gene and rs6552828 in the coenzyme A synthetase long-chain 1 (ACSL1) gene. To gain insight into their functionality (which is yet unknown), here we determined for the first time luciferase gene reporter activity at the muscle tissue level in rs7832552 and rs6552828. We then compared allele/genotype frequencies of the 3 abovementioned variants among centenarians [n = 138, age range 100-111 years (114 women)] and healthy controls [n = 334, 20-50 years (141 women)] of the same ethnic and geographic origin (Spain). We also studied healthy centenarians [n = 79, 100-104 years (40 women)] and controls [n = 316, 27-81 years (156 women)] from Italy, and centenarians [n = 742, 100-116 years (623 women)] and healthy controls [n = 499, 23-59 years (356 women)] from Japan. The THRH rs7832552 T-allele and ACSL1 rs6552828 A-allele up-regulated luciferase activity compared to the C and G-allele, respectively (P = 0.001). Yet we found no significant association of EL with rs7832552, rs1800795 or rs6552828 in any of the 3 cohorts. Further research is needed with larger cohorts of centenarians of different origin as well as with younger old people.

Context: Intramyocellular lipid (IMCL) accumulation is observed in both insulin-resistant subjects and insulin-sensitive endurance athletes (athlete's paradox). We hypothesized that the expression pattern of fatty acid transporters may influence oxidative capacity and determine the association between IMCL and insulin resistance., Objective: The objective of the study was to investigate the muscle expression of fatty acid transporters and their function related to insulin sensitivity in IMCL-accumulated subjects., Design and Setting: The study subjects were 36 nonobese healthy men. Their IMCL levels were measured by (1)H-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by steady-state glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR. We compared the clinical phenotypes and the expression levels of genes involved in lipid metabolism in skeletal muscle between IMCL-accumulated high-GIR (H-GIR) subjects (n = 8) and low-GIR subjects (n = 9). The functions of candidate fatty acid transporters were determined by in vitro analyses., Results: Compared with the low-GIR group, body fat was lower and maximum oxygen uptake was higher in the H-GIR group. Several lipid oxidation genes in muscle were up-regulated in the H-GIR group, and this was associated with increased expression of higher plasma membrane-associated fatty acid-binding protein (FABPpm) and decreased expression of fatty acid transport protein (FATP)-1. Overexpression of FABPpm in C2C12 myotubes increased fatty acid oxidation coupled with the elevated expression of genes related to fatty acid oxidation. These changes were not observed in FATP1-overexpressed myotubes., Conclusions: Differences in the gene expression of fatty acid transporters may, at least in part, affect insulin sensitivity in IMCL-accumulated nonobese men.

In recent years, shoes having rounded soles in the anterior-posterior direction have been commercially introduced, which are commonly known as unstable shoes (US). However, physiological responses during walking in US, particularly at various speeds, have not been extensively studied to date. The purpose of this study was to investigate the effect of wearing unstable shoes while walking at low to high speeds on the rate of perceived exertion (RPE), muscle activation, oxygen consumption (VO2), and optimum speed. Healthy male adults wore US or normal walking shoes (WS), and walked at various speeds on a treadmill with no inclination. In experiment 1, subjects walked at 3, 4, 5, 6, and 7 km·h(-1) (duration, 3 min for all speeds) and were recorded on video from the right sagittal plane to calculate the step length and cadence. Simultaneously, electromyogram (EMG) was recorded from six different thigh and calf muscles, and the integrated EMG (iEMG) was calculated. In experiment 2, RPE, heart rate and VO2 were measured with the walking speed being increased from 3.6 to 7.2 km·h(-1) incrementally by 0.9 km·h(-1) every 6 min. The optimum speed, defined by the least oxygen cost, was calculated from the fitted quadratic relationship between walking speed and oxygen cost. Wearing US resulted in significantly longer step length and lower cadence compared with WS condition at any given speed. For all speeds, iEMG in the medial gastrocnemius and soleus muscles, heart rate, and VO2 were significantly higher in US than WS. However, RPE and optimum speed (US, 4.75 ± 0.32 km·h(-1); WS, 4. 79 ± 0.18 km·h(-1)) did not differ significantly between the two conditions. These results suggest that unstable shoes can increase muscle activity of lower legs and energy cost without influencing RPE and optimum speed during walking at various speeds.

Background: Limited data are available on the relationship between muscular and performance fitness (MPF) and the incidence of type 2 diabetes., Methods: A cohort of 3792 Japanese men completed a medical examination that included MPF and cardiorespiratory fitness tests. MPF index composite score was calculated using Z-scores from vertical jump, sit-ups, side step, and functional reach tests., Results: The mean follow-up period was 187 months (15.6 years). There were 240 patients who developed type 2 diabetes during follow-up. Relative risks and 95% confidence intervals (CI) for incidence of diabetes across baseline quartiles of MPF index composite score were obtained using the Cox proportional hazards model while adjusting for age, BMI, diastolic blood pressure, cigarette smoking, alcohol intake, and family history of diabetes. The relative risks for developing diabetes across quartiles of MPF index composite scores (lowest to highest) were 1.0 (referent), 1.15 (95% CI 0.83-1.60), 1.10 (0.78-1.55), and 0.57 (0.37-0.90) (P for trend = .061). These results were attenuated after adjustment for cardiorespiratory fitness (P for trend = .125)., Conclusions: This prospective study suggests that MPF is a predictor of type 2 diabetes, although its predictive ability was attenuated after adjusting for cardiorespiratory fitness.

This study aimed to determine whether high-intensity dumbbell exercise involving both concentric and eccentric contractions would provide a temporary alleviation of delayed-onset muscle soreness (DOMS). It also examined the effect of alleviated muscle soreness on dynamic muscle performance using a stretch-shortening cycle (SSC; peak angular acceleration and velocity of the elbow during both lowering and concentric phases) to provide indirect evidence that DOMS contributes to the dynamic performance decrement after eccentric injury. Thirteen untrained adults performed 30 maximal isokinetic eccentric contractions of the elbow flexors to induce eccentric damage. Five sets of arm curls using a dumbbell (equivalent to 70% of isometric maximal voluntary contraction) were then performed until failure on days 1, 2, 3, and 5 of recovery. Muscle soreness significantly decreased after each session of dumbbell exercise (p = 0.001). Isometric strength further decreased immediately after dumbbell exercise, indicating muscle fatigue (p < 0.001). Dynamic performance variables were less affected by fatigue, however, with performance being reduced only for peak lowering velocity (p < 0.001). Other measures of dynamic performance were relatively constant after dumbbell exercise, particularly on days 2 and 3 when soreness was greatest. It was concluded that high-intensity concentric/eccentric dumbbell exercise was able to temporarily alleviate DOMS and that this reduction in soreness served to counter the effect of peripheral muscle fatigue during dynamic activities. Practical applications of this study are that after eccentric damage, alleviation of muscle soreness through an optimal warm-up may be helpful to temporarily recover dynamic muscle performance. Free-weight loading is one suggested technique to temporarily manage DOMS.

This study examined whether the exercise-increased extracellular heat shock protein 72 (eHsp72) levels in rats was associated with body temperature elevation during exercise. In all, 26 female Sprague-Dawley rats (3 mo old) were assigned randomly to control (CON; n = 8), exercise under warm temperature (WEx; n = 9), or exercise under cold temperature (CEx; n = 9). The WEx and CEx were trained at 25 degrees C or 4 degrees C, respectively, for nine days using a treadmill. Before and immediately after the final exercise bout, the colonic temperatures were measured as an index of body temperature. The animals were subsequently anesthetized, and blood samples were collected and centrifuged. Plasma samples were obtained to assess their eHsp72 levels. Only the colonic temperature in WEx was increased significantly (P < 0.05) by exercise. The eHsp72 level in WEx was significantly higher (P < 0.05) than that of either the CON or CEx. However, no significant difference was found between CON and CEx. Regression analyses revealed that the eHsp72 level increased as a function of the body temperature. In another experiment, the eHsp72 level of animals with body temperature that was passively elevated through similar kinetics to those of the exercise was studied. Results of this experiment showed that mere body temperature elevation was insufficient to induce eHsp72 responses. Collectively, our results suggest that body temperature elevation during exercise is important for induction of exercise-increased eHsp72. In addition, the possible role of body temperature elevation is displayed when the exercise stressor is combined with it.

Introduction: Hyperthermia induced by microwave diathermy raises the temperature of deep tissues from 41 degrees C to 45 degrees C using electromagnetic power. Microwave diathermy is used in the management of superficial tumours with conventional radiotherapy and chemotherapy and, recently, its use has been successfully extended to physical medicine and sports traumatology in Central and Southern Europe., Methods: We searched the literature for relevant studies. Most of the published studies in these fields have used 434 and 915 microwave diathermy, as these wavelengths are most effective., Results: Hyperthermia induced by microwave diathermy into tissue can stimulate repair processes, increase drug activity, allow more efficient relief from pain, help in the removal of toxic wastes, increase tendon extensibility and reduce muscle and joint stiffness. Moreover, hyperthermia induces hyperaemia, improves local tissue drainage, increases metabolic rate and induces alterations in the cell membrane., Conclusions: The biological mechanism that regulates the relationship between the thermal dose and the healing process of soft tissues with low or high water content or with low or high blood perfusion is still under study. Microwave diathermy treatment at 434 and 915 MHz can be effective in the short-term management of musculo-skeletal injuries.

Previous studies have demonstrated that endurance exercise training increases the level of heat shock proteins (HSPs) in skeletal muscles. However, little attention has been drawn to the effects of high intensity-short duration exercise, or sprint- interval training (SIT) on HSP72 level in rat skeletal muscles. This study performed to test the hypothesis that the SIT would induce the HSP72 in fast and slow skeletal muscles of rats. Young male Wistar rats (8 weeks old) were randomly assigned to a control (CON) or a SIT group (n = 8/group). Animals in the SIT group were trained (1 min/sprint, 6~10 sets/day and 5~6 days/week) on a treadmill for 9 weeks. After the training period, HSP72 levels in the plantaris (fast) and soleus (slow) muscles were analyzed by Western blotting method. Enzyme activities (hexokinase, phosphofructokinase and citrate synthase) and histochemical properties (muscle fiber type compositions and cross sectional area) in both muscles were also determined. The SIT resulted in significantly (p < 0.05) higher levels of HSP72 in both the plantaris and soleus muscles compared to the CON group, with the plantaris producing a greater HSP72 increase than the soleus (plantaris; 550 ± 116%, soleus; 26 ± 8%, p < 0.05). Further, there were bioenergetic improvements, fast-to-slow shift of muscle fiber composition and hypertrophy in the type IIA fiber only in the plantaris muscle. These findings indicate that the SIT program increases HSP72 level of the rat hindlimb muscles, and the SIT-induced accumulation of HSP72 differs between fast and slow muscles. Key PointsThere is no study about the effects of high intensity but short duration exercise, or sprint-interval training (SIT) on heat shock protein 72 (HSP72) level in skeletal muscles.The SIT program (≤ 10 min·day(-1)) accumulated HSP72 in rat skeletal muscles.The SIT-induced accumulation of HSP72 in the plantaris (fast) muscle was drastic compared to the soleus (slow) muscle and accompanied with the improvements of enzyme activities, fast-to-slow shift within fast muscle fiber type and muscle hypertrophy.

Protein kinase B [PKB, also known as Akt (PKB/Akt)] and calcineurin (CaN) are postulated to play important roles in integrating intracellular signaling in skeletal muscle in response to disuse and increased muscle loading. These experiments investigated changes in signal transduction of the downstream pathways of PKB/Akt and CaN during recovery following disuse-induced muscle atrophy. A 10-day period of hindlimb unloading (HLU) via tail suspension (male rats) was used to produce soleus muscle atrophy. Muscle recovery was achieved by returning animals to normal ambulation for 3-10 days. HLU resulted in significant muscle atrophy and a slow-to-fast fiber transition as revealed by appearance of type IId/x and IIb myosin heavy chain (MHC) isoforms. Muscle mass in HLU animals recovered to control (Con) levels after 10 days of reloading, but the fast-to-slow shift in muscle MHC was incomplete, as indicated by the continued presence of type IId/x MHC. Ten days of HLU resulted in a significant decrease (-43%) in muscle levels of phosphorylated PKB/Akt. In contrast, muscle levels of phosphorylated PKB/Akt were greater (+56%) in HLU than in Con animals early after the onset of reloading (3 days). Soleus levels of phosphorylated p70S6K were significantly higher (+26%) in HLU animals after 3 days of muscle reloading. Muscle levels of phosphorylated PKB/Akt and phosphorylated p70S6K returned to Con levels by day 10 of recovery. Moreover, muscle CaN levels were significantly higher than Con levels after 10 days of muscle reloading. These findings are consistent with the hypothesis that PKB/Akt and its downstream mediators are active in the regrowth of muscle mass during the early periods of recovery from muscle atrophy. Our data support the concept that CaN is involved in muscle remodeling during the later phases of recovery from disuse muscle atrophy.

The combined effects of aging and regular physical exercise was investigated on the production of reactive oxygen species (ROS), lipid peroxidation, glutathione status, and the activity of nuclear factor-kappaB (NF-kappaB) in rat liver. A group of 24 male F344 rats was divided into the following categories: adult control (18 months), adult exercised (18 months), and aged control (28 months) and aged exercised (28 months). The ROS formation increased as a function of age and exercise training decreased the rate of ROS formation in the two age groups. Significant positive correlation was found between ROS production and lipid peroxidation (LIPOX). The reduced glutathione (GSH) level was higher and the oxidized glutathione (GSSG) level lower in exercised groups compared with the sedentary controls (P<0.05). An age-associated increase in NF-kappaB activity was attenuated by the regular exercise. The content of p50 and p65 subunits of NF-kappaB increased with age and decreased with exercise training. The content of inhibitory factor-kappaB was inversely related to NF-kappaB activation. Regular exercise-induced adaptive responses, including attenuation of an increase in ROS production, LIPOX level, NF-kappaB activation, and reduced GSH/GSSG ratio, appear to be capable, even in old age, of reducing increases in inflammatory and other detrimental consequences that are often associated with advancing age.

Regular physical exercise retards a number of age-associated disorders, in spite of the paradox that free radical generation is significantly enhanced with exercise. Eight weeks of treadmill running resulted in nearly a 40% increase in maximal oxygen uptake in both middle-aged (20-month-old) and aged (30-month-old) rats. The age-associated increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG) content was significantly attenuated in gastrocnemius muscle by exercise. The 8-OHdG repair, as measured by the excision of 32P-labeled damaged oligonucleotide, increased in muscle of exercising animals. The reactive carbonyl derivatives (RCD) of proteins did not increase with aging. However, when the muscle homogenate was exposed to a mixture of 1 mM iron sulfate and 50 mM ascorbic acid, the muscle of old control animals accumulated more RCD than that of the trained or adult groups. The chymotrypsin-like activity of proteasome complex increased in muscle of old trained rats. We suggest that regular exercise-induced adaptation attenuates the age-associated increase in 8-OHdG levels, and increases the activity of DNA repair and resistance against oxidative stress in proteins.