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Oxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p p 2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients. more...

Physical activity is considered a promising behavior to improve cognitive function and academic performance in adolescents. As evidence on the relationship of specific sports activity is not conclusive, this study aimed to determine the longitudinal relationships of different sports to academic performance in adolescents and evaluate the cardiorespiratory fitness mediation effect of these sports. We focused on the demands of complex motor skills and the differences between individual sports vs team sports. Four hundred and sixty-three 7th-grade students (227 girls and 236 boys) were followed up over 2 years. Data regarding participation in sports activities, types of sports activities, academic performance, and cardiorespiratory fitness were obtained at baseline and after a 2-year follow-up. Structural equation modeling revealed that participation in all sports activity was positively associated with improvement of academic performance from baseline to follow-up, and that these associations were mediated by cardiorespiratory fitness gains. Participation in sports activities that require more complex motor skills and individual sports activity was directly associated with an improvement of academic performance from baseline to follow-up. Furthermore, quitting sports activities was negatively associated with academic performance via a reversal in cardiorespiratory fitness gains. These findings indicate that participation in specific sports may have significant benefits for academic performance in adolescents. Although these relationships are presumably mediated by cardiorespiratory fitness, sports activities that require more complex motor skills and individual sports participation may be directly related to academic performance. Considering that quitting sports activities reversed these benefits, sustained participation in sports is important for academic success. more...

Objectives Heterogeneity and homogeneity in the flow-mediated dilation of the human body's individual extremities are not fully understood, and the relationship between flow-mediated dilation and local muscle activity is unclear. We assessed the flow-mediated dilation of four individual extremities and sought to determine the contribution of local muscle activity (evaluated as muscle strength) to the flow-mediated dilation in each extremity. Methods Thirteen healthy young right-handed nonactive males participated. The flow-mediated dilation in the brachial and popliteal arteries at both arms and legs was assessed by ultrasound Doppler. Muscle strength was evaluated as the grip strength and knee extension. Results There was a significant difference in the brachial artery (BA)-FMD values between the subjects' dominant and non-dominant sides (8.0 ± 2.8 vs. 5.5 ± 2.2%, p Conclusion These results demonstrated heterogeneity in the flow-mediated dilation of individual extremities. We observed that local muscle activity can affect the local vascular function. Measurements of vasodilatory function in individual extremities should thus be carefully considered. more...

Increases in muscle size and strength similar to those obtained with high resistance load can be achieved by combining lower loads with continuous blood flow restriction (BFR). However, high ratings for distress have been reported for continuous BFR. Therefore, we investigated the efficacy (metabolic stress) of BFR applied only during intervals in resistance exercise. Seven healthy men performed three 1-min sets of plantar flexion (30 reps/min) with 1-min rest intervals under 4 conditions: low-load resistance exercise (L, 20% 1-repetition maximum (1RM)) without BFR (L-noBFR), L with BFR during exercise sets (L-exBFR), L with BFR during rest intervals (L-intBFR), and L with continuous BFR during both exercise and rest intervals (L-conBFR). Based on the results of the first experiment, we performed additional protocols using a moderate load (M, 40% 1RM) with intermittent (exercise or rest intervals) BFR (M-exBFR and M-intBFR). Intramuscular metabolic stress, defined as decreases in phosphocreatine and intramuscular pH, was evaluated by 31P magnetic resonance spectroscopy. Rated perceived exertion (RPE) was also assessed. At the end of exercise, total decreases in phosphocreatine and intramuscular pH were similar among L-noBFR, L-intBFR, and L-exBFR and significantly less than those in L-conBFR (p < 0.05). In contrast, changes in these variables in M-intBFR but not in M-exBFR were similar to those in L-conBFR. Nevertheless, RPE was lower in M-intBFR than in both M-exBFR and L-conBFR (p < 0.05). The effect of intermittent BFR during exercise might be insufficient to induce metabolic stress when using a low load. However, effective metabolic stress for muscle adaptation could be obtained by moderate-load resistance exercise with BFR during intervals with less ischemic duration and discomfort. more...

Background Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients’ peak aerobic capacity. Methods We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF Results The mean peak oxygen uptake (VO2) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO2 was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of − 0.93 (− 1.82 to − 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of − 1.05 (− 1.96 to − 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO2 at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O2 pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO2 in CHF patients with non-reduced LVEF and those with reduced LVEF. Conclusions T2DM was associated with lowered peak VO2 in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients’ exercise capacity, and the degree of impact is partly dependent on their LV systolic function. more...

Background: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown.Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I–III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=−0.256), but not at rest (r=−0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER ( more...

The aim of this study was to determine, using structural equation modeling, the comprehensive relationships of achievement motivation (self-fulfillment achievement motivation [SFAM] and competitive achievement motivation [CAM]), daily behaviors (exercise habits, screen time, and learning duration), body mass index [BMI], and cardiorespiratory fitness [CRF]) with academic performance among schoolchildren. Three hundred twenty-five schoolchildren (172 males and 153 females; 12–13 years old) were recruited. Academic performance was assessed using the total grade points in 8 academic subjects (GP8); CRF using the 20-m shuttle run; and achievement motivation, daily behaviors, and socioeconomic status using questionnaires. Socioeconomic status was included as a control variable. In males, two cascade associations of achievement motivation to GP8 were detected: (1) SFAM → screen time/learning duration → GP8, and (2) CAM → exercise habit → CRF → GP8 (χ 2 = 8.72, p = .19, AGFI = .92). In females, two cascade associations were also detected: (1) SFAM → screen time/learning habit → GP8, and (2) exercise habit → BMI 2 → GP8 (χ 2 = 6.17, p = .41, AGFI = .93). Our results suggest that greater achievement motivation is associated with academic success via various physiological/behavioral factors, and that these associations differ by gender. more...

The purpose of this study was to determine, using structural equation modelling (SEM), the direct and indirect influence of daily behaviours (i.e. exercise/learning durations), weight status, and physical fitness on academic performance among seventh-grade schoolchildren, after controlling for socioeconomic status. We analysed cross-sectional data from 274 schoolchildren (159 males and 115 females; 12-13 years old). Academic performance was assessed using the total grade points in eight academic subjects. Physical fitness was evaluated using the total score of eight physical fitness tests and weight status using body mass index. The daily behaviours and socioeconomic status were assessed by the questionnaire. The SEM showed an adequate fit to the data (χ more...

Aims/Introduction Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). Here, we investigated the effects of pioglitazone treatment on whole-body aerobic capacity and skeletal muscle energy metabolism in MetS patients. Materials and Methods A total of 14 male patients with MetS received oral pioglitazone 15 mg/day for 4 months. To assess whole-body aerobic capacity, exercise testing with a bicycle ergometer was carried out before and after pioglitazone treatment. To assess skeletal muscle energy metabolism, intramyocellular lipid in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus magnetic resonance spectroscopy, respectively. Results Pioglitazone significantly increased peak oxygen uptake (25.1 ± 4.9 mL/kg/min pretreatment vs 27.2 ± 3.9 mL/kg/min post- treatment, P < 0.05) and anaerobic threshold (12.7 ± 1.9 mL/kg/min pretreatment vs 13.6 ± 1.6 mL/kg/min post-treatment, P < 0.05), although daily physical activity was comparable before and after the treatment. Intramyocellular lipid content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased the muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in anaerobic threshold; that is, submaximal aerobic capacity, closely correlated with the decrease in intramyocellular lipid content after pioglitazone treatment. Conclusions Pioglitazone significantly improved the MetS patients’ whole-body aerobic capacity and skeletal muscle energy metabolism. The beneficial effect of pioglitazone on whole-body aerobic capacity might be at least in part through improved fatty acid metabolism in the skeletal muscle. more...

Purpose Students who study intensively in one of Japan's ‘cram schools’ and/or spend excess time on electronic devices such as video games are in a sedentary state much of the time, and this may affect their physical fitness. We investigated whether there are relationships among obesity, physical fitness and academic achievement in Japanese students after controlling for socioeconomic and behavioral confounding factors. Methods The data of 315 students (152 females [48%], 163 males [52%]; 12–13 yrs old) were analyzed. Academic achievement was assessed by the total grade points on eight school subjects (GP8). Students with a body mass index at or above the 85th percentile of each gender were classified as the overweight/obese group. Physical fitness was evaluated by the total score on eight fitness tests. Socioeconomic and behavioral confounders including the mother's educational background, household income, cram school utilization and time spent on video games/mobile phones were used as covariates. Results The GP8 of the overweight/obese students was significantly lower than that of the normal weight students (27.2 vs. 29.0 points, respectively). After adjusting for the confounders, the physical fitness score was found to be a significant factor for determinants of GP8 in boys (β = 0.324), but not in girls. The obesity status was a factor for GP8 in the girls (β = − 0.160) but not in the boys. Conclusion These results suggest that physical fitness in boys and obesity status in girls could be important factors not only for health status but also for academic achievement, independent of socioeconomic and behavioral backgrounds. more...

Aims Exercise capacity is reduced in heart failure (HF) patients, due mostly to skeletal muscle abnormalities including impaired energy metabolism, mitochondrial dysfunction, fiber type transition, and atrophy. Glucagon-like peptide-1 (GLP-1) has been shown to improve exercise capacity in HF patients. We investigated the effects of the administration of a dipeptidyl peptidase (DPP)-4 inhibitor on the exercise capacity and skeletal muscle abnormalities in an HF mouse model after myocardial infarction (MI). Methods and Results MI was created in male C57BL/6J mice by ligating the left coronary artery, and a sham operation was performed in other mice. The mice were then divided into two groups according to the treatment with or without a DPP-4 inhibitor, MK-0626 (1 mg/kg body weight/day) provided in the diet. Four weeks later, the exercise capacity evaluated by treadmill test was revealed to be limited in the MI mice, and it was ameliorated in the MI+MK-0626 group without affecting the infarct size or cardiac function. The citrate synthase activity, mitochondrial oxidative phosphorylation capacity, supercomplex formation and their quantity were reduced in the skeletal muscle from the MI mice, and these decreases were normalized in the MI+MK-0626 group, in association with the improvement of mitochondrial biogenesis. Immunohistochemical staining also revealed that a shift toward the fast-twitch fiber type in the MI mice was also reversed by MK-0626. Favorable effects of MK-0626 were significantly inhibited by treatment of GLP-1 antagonist, Exendin-(9-39) (150 pmol/kg body weight/min, subcutaneous osmotic pumps) in MI+MK-0626 mice. Similarly, exercise capacity and mitochondrial function were significantly improved by treatment of GLP-1 agonist, Exendin-4 (1 nmol/kg/body weight/hour, subcutaneous osmotic pumps). Conclusions A DPP-4 inhibitor may be a novel therapeutic agent against the exercise intolerance seen in HF patients by improving the mitochondrial biogenesis in their skeletal muscle. more...

Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6 J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10 mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress. more...

Background: Brain-derived neurotropic factor (BDNF) is involved in cardiovascular diseases as well as skeletal muscle energy metabolism and depression. We investigated whether serum BDNF level was associated with prognosis in patients with heart failure (HF). Methods and Results: We measured the serum BDNF level in 58 patients with HF (59.2 6 13.7 years old, New York Heart Association functional class IeIII) at baseline, and adverse events, including all cardiac deaths and HF rehospitalizations, were recorded during the median follow-up of 20.3 months. In a univariate analysis, serum BDNF levels were significantly associated with peak oxygen capacity (b 5 0.547; P 5 .003), anaerobic threshold (b 5 0.929; P 5 .004), and log minute ventilation/ carbon dioxide production slope (b 5 � 10.15; P 5 .005), but not Patient Health Questionnaire scores (b 5 � 0.099; P 5 .586). A multivariate analysis demonstrated that serum BDNF level was an independent prognostic factor of adverse events (hazard ratio 0.41, 95% confidence interval 0.20e0.84; P 5 .003). The receiver operating characteristic curve demonstrated that low levels of BDNF (!17.4 ng/mL) were associated with higher rates of adverse events compared with high levels of BDNF ($17.4 ng/mL; log rank test: P ! .001). Conclusions: Decreased serum BDNF levels were significantly associated with adverse outcomes in HF patients, suggesting that these levels can be a useful prognostic biomarker. (J Cardiac Fail more...

New Findings What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus. Abstract We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented the decline in exercise capacity in HFD-induced diabetic mice via maintenance of mitochondrial function, fat oxidation and attenuation of oxidative stress in the skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for the treatment of diabetes mellitus. more...

We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, FLED I vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND I vehicle group. Pioglitazone normalized the insulin levels in RED fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP dependent mitochondrial respiration, complex l and Ill activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondria! function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus. (C) 2014 Elsevier B.V. All rights reserved. more...

We previously reported that insulin resistance was induced by the impairment of insulin signaling in the skeletal muscle from heart failure (HF) via NAD(P)H oxidase-dependent oxidative stress. (Pro)renin receptor [(P)RR] is involved in the activation of local renin-angiotensin system and subsequent oxidative stress. We thus examined whether (P)RR inhibitor, handle region peptide (HRP), could ameliorate insulin resistance in HF after myocardial infarction (MI) by improving oxidative stress and insulin signaling in the skeletal muscle. C57BL6J mice were divided into four groups: sham operated (Sham, n = 10), Sham treated with HRP (Sham+HRP, 0.1 mg·kg−1·day−1, n = 10), MI operated (MI, n = 10), and MI treated with HRP (MI+HRP, 0.1 mg/kg/day, n = 10). After 4 wk, MI mice showed left ventricular dysfunction, which was not affected by HRP. (P)RR was upregulated in the skeletal muscle after MI (149% of sham, P < 0.05). The decrease in plasma glucose after insulin load was smaller in MI than in Sham (21 ± 2 vs. 44 ± 3%, P < 0.05), and was greater in MI+HRP (38 ± 2%, P < 0.05) than in MI. Insulin-stimulated serine phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle from MI by 48 and 49% of Sham, both of which were ameliorated in MI+HRP. Superoxide production and NAD(P)H oxidase activities were increased in MI, which was inhibited in MI+HRP. HRP ameliorated insulin resistance associated with HF by improving insulin signaling via the inhibition of NAD(P)H oxidase-induced superoxide production in the skeletal muscle. The (P)RR pathway is involved in the development of insulin resistance, at least in part, via the impairment of insulin signaling in the skeletal muscle from HF. more...

Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus. more...

OBJECTIVE Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using 31P- and 1proton-magnetic resonance spectroscopy, respectively. RESULTS Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 μmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 μmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = −0.49 and r = −0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively). CONCLUSIONS Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS. more...

NAD(P)H oxidase-induced oxidative stress is at least in part involved with lowered exercise capacity and impaired mitochondrial function in high-fat diet (HFD)-induced diabetic mice. NAD(P)H oxidase can be activated by activation of the renin-angiotensin system. We investigated whether ANG II receptor blocker can improve exercise capacity in diabetic mice. C57BL/6J mice were fed a normal diet (ND) or HFD, and each group of mice was divided into two groups: treatment with or without olmesartan (OLM; 3 mg·kg−1·day−1in the drinking water). The following groups of mice were studied: ND, ND+OLM, HFD, and HFD+OLM ( n = 10 for each group). After 8 wk, HFD significantly increased body weight, plasma glucose, and insulin compared with ND, and OLM did not affect these parameters in either group. Exercise capacity, as determined by treadmill tests, was significantly reduced in HFD, and this reduction was ameliorated in HFD+OLM. ADP-dependent mitochondrial respiration was significantly decreased, and NAD(P)H oxidase activity and superoxide production by lucigenin chemiluminescence were significantly increased in skeletal muscle from HFD, which were attenuated by OLM. There were no such effects by OLM in ND. We concluded that OLM ameliorated the decrease in exercise capacity in diabetic mice via improvement in mitochondrial function and attenuation of oxidative stress in skeletal muscle. These data may have a clinical impact on exercise capacity in the medical treatment of diabetes mellitus. more...

Aim: Poor sleep has been shown to be associated with the development of cardiovascular risk factors, such as obesity, in both adults and children. This study aimed to investigate the relationship between sleep duration and arterial stiffness indices in Japanese children and early adolescents. Methods: The data on 102 students (56 males, 46 females; mean age, 11.9 ± 1.8 years) were analyzed. As non-invasive arterial stiffness parameters, the cardio-ankle vascular index (CAVI) and heart-ankle pulse wave velocity (haPWV) were evaluated. Their students' sleep habits (bedtime and wake times on a usual weekday) were investigated using questionnaires, and based on these, their sleep durations were calculated. Results: The CAVI values in the males and females were 4.8 ± 0.9 and 4.7 ± 0.9 (arbitrary unit), respectively. haPWV values in the males and females were 5.5 ± 0.6 and 5.4 ± 0.6 m/s, respectively. Sleep duration in the males, but not in the females, was negatively correlated with CAVI (r = −0.356) and haPWV (r = −0.356), suggesting that students with short sleep duration could have increased arterial stiffness. After adjusting for confounders, such as age, sex, systolic blood pressure, heart rate, adiposity, and physical fitness, the correlation of sleep duration with CAVI, but not with haPWV, was still significant (partial r = −0.253, p < 0.05). Conclusion: Our findings suggest that shorter sleep duration influences arterial stiffening even in childhood. more...

Objective To investigate the effects of arm-cranking exercise training on plasminogen activator inhibitor 1 (PAI-1) as a risk factor of deep vein thrombosis, along with general physical parameters such as muscle strength, aerobic capacity, and hemodynamics, in individuals with spinal cord injury (SCI) and control subjects. Design Longitudinal study. Setting Community-based supervised intervention. Participants Participants (N=17) comprised individuals with SCI (n=9) who volunteered for this study, and able-bodied individuals (n=8) matched for age, height, and body mass index who were assessed at baseline only. Intervention The arm-cranking exercise program was performed for 10 weeks with 4 sessions per week. Sessions consisted of 2 sets of warmup (5min) and arm crank exercises (25min) with a 10-minute recovery at an intensity of 50% to 70% of heart rate reserve. Main Outcome Measures Body mass (BM), waist circumference (WC), aerobic capacity (peak oxygen consumption [Vo 2 peak]), PAI-1, blood pressure, glucose metabolism, and lipids. Results PAI-1, BM, WC, systolic blood pressure, and triglycerides (TG) decreased, and Vo 2 peak increased after training ( P 2 peak, BM, WC, TG, and high-density lipoprotein cholesterol. Multiple linear regression analysis revealed that WC was the most sensitive factor for predicting changes in PAI-1 ( P =.038). Conclusions These results suggest that 10 weeks of arm-cranking exercise training for people with SCI may help to reduce the risk factors of cardiovascular disease. In addition, changes in abdominal fat may be related to changes in PAI-1 in the SCI population. more...

Background: It has been reported that skeletal muscle mass and strength are decreased in patients with heart failure (HF), and HF is associated with both reduced exercise capacity and adverse clinical outcomes. Myostatin has been known as a negative regulator of muscle growth, follistatin as the myostatin antagonist, maintaining tissue homeostasis. We thus determined serum myostatin levels in HF patients and whether they are associated with skeletal muscle wasting. Methods and results: Forty one consecutive HF patients (58 +/- 15 years old, New York Heart Association class I-III) and 30 age-matched healthy subjects as controls (53 +/- 8 years old) were studied. Serum myostatin levels were significantly lower in HF patients than controls (18.7 +/- 7.4 vs. 23.6 +/- 5.2 ng/mL, P < 0.001). Circumference of the thickest part of the right thigh was significantly small (468 +/- 72 vs. 559 +/- 37 mm, P = 0.001) and lower extremity muscular strength was lower in patients with HF (129 +/- 55 vs. 219 +/- 52 N × m, P < 0.001). Fourteen HF patients (34%) had muscle wasting. By univariate analysis, higher age, higher serum follistatin, and lower serum myostatin were significantly associated with the presence of muscle wasting. By multivariate analysis, serum myostatin levels were independently associated with muscle wasting (OR = 0.77, 95% CI [0.58, 0.93], P = 0.02). Conclusion: Serum myostatin levels were significantly decreased in HF patients and associated with lower extremity muscle wasting, suggesting that myostatin may be an important factor for maintaining skeletal muscle mass and strength in HF. more...

Our previous study reported that intramuscular metabolic stress during low-intensity resistance exercise was significantly enhanced by combining blood flow restriction (BFR); however, they did not reach the levels achieved during high-intensity resistance exercise. That study was performed using a single set of exercise; however, usual resistance exercise consists of multiple sets with rest intervals. Therefore, we investigated the intramuscular metabolic stress during multiple-set BFR exercises, and compared the results with those during multiple-set high-intensity resistance exercise. Twelve healthy young subjects performed 3 sets of 1-min unilateral plantar flexion (30 repetitions) with 1-min intervals under 4 different conditions: low intensity (L, 20 % 1 RM) and high intensity (H, 65 % 1 RM) without BFR, and L with intermittent BFR (IBFR, only during exercise) and with continuous BFR (CBFR, during rest intervals as well as exercise). Intramuscular metabolic stress, defined as intramuscular metabolites and pH, and muscle fiber recruitment were evaluated by 31P-magnetic resonance spectroscopy. The changes of intramuscular metabolites and pH during IBFR were significantly greater than those in L but significantly lower than those in H. By contrast, those changes in CBFR were similar to those in H. Moreover, the fast-twitch fiber recruitment, evaluating by a splitting Pi peak, showed a similar level to H. In conclusion, the multiple sets of low-intensity resistance exercise with continuous BFR could achieve with the same metabolic stress as multiple sets of high-intensity resistance exercise. more...

Skeletal muscle bulk and strength are becoming important therapeutic targets in medicine. To increase muscle mass, however, intensive, long-term mechanical stress must be applied to the muscles, and such stress is often accompanied by orthopedic and cardiovascular problems. We examined the effects of circulatory occlusion in resistance training combined with a very low-intensity mechanical load on enhancing muscular metabolic stress and thereby increasing muscle bulk. Muscular metabolic stress, as indicated by the increases in inorganic phosphate (Pi) and a decrease in intramuscular pH, was evaluated by31P-magnetic resonance spectroscopy during unilateral plantar-flexion at 20% of the one-repetition maximum (1-RM) with circulatory occlusion for 2 min in 14 healthy, male untrained participants (22 yr) at baseline. Participants performed two sets of the same exercise with a 30-s rest between sets, 2 times/day, 3 days/wk, for 4 wk. The muscle cross-sectional area (MCA) of the plantar-flexors and the 1-RM were measured at baseline and after 2 and 4 wk of training. MCA and 1-RM were significantly increased after 2 and 4 wk ( P < 0.05, respectively). The increase in MCA at 2 wk was significantly ( P < 0.05) correlated with the changes in Pi( r = 0.876) and intramuscular pH ( r = 0.601). Furthermore, the increases in MCA at 4 wk and 1-RM at 2 wk were also correlated with the metabolic stress. Thus enhanced metabolic stress in exercising muscle is a key mechanism for favorable effects by resistance training. Low-intensity resistance exercise provides successful outcomes when performed with circulatory occlusion, even with a short training period. more...

Insulin resistance or diabetes is associated with limited exercise capacity, which can be caused by the abnormal energy metabolism in skeletal muscle. Oxidative stress is involved in mitochondrial dysfunction in diabetes. We hypothesized that increased oxidative stress could cause mitochondrial dysfunction in skeletal muscle and make contribution to exercise intolerance in diabetes. C57/BL6J mice were fed on normal diet or high fat diet (HFD) for 8 wk to induce obesity with insulin resistance and diabetes. Treadmill tests with expired gas analysis were performed to determine the exercise capacity and whole body oxygen uptake (V̇o2). The work (vertical distance × body weight) to exhaustion was reduced in the HFD mice by 36%, accompanied by a 16% decrease of peak V̇o2. Mitochondrial ADP-stimulated respiration, electron transport chain complex I and III activities, and mitochondrial content in skeletal muscle were decreased in the HFD mice. Furthermore, superoxide production and NAD(P)H oxidase activity in skeletal muscle were significantly increased in the HFD mice. Intriguingly, the treatment of HFD-fed mice with apocynin [10 mmol/l; an inhibitor of NAD(P)H oxidase activation] improved exercise intolerance and mitochondrial dysfunction in skeletal muscle without affecting glucose metabolism itself. The exercise capacity and mitochondrial function in skeletal muscle were impaired in type 2 diabetes, which might be due to enhanced oxidative stress. Therapies designed to regulate oxidative stress and maintain mitochondrial function could be beneficial to improve the exercise capacity in type 2 diabetes. more...

Although recent studies have reported that low-intensity resistance training with blood flow restriction could stress the muscle effectively and provide rapid muscle hypertrophy and strength gain equivalent to those of high-intensity resistance training, the exact mechanism and its generality have not yet been clarified. We investigated the intramuscular metabolism during low-intensity resistance exercise with blood flow restriction and compared it with that of high-intensity and low-intensity resistance exercises without blood flow restriction using 31P-magnetic resonance spectroscopy. Twenty-six healthy subjects (22 ± 4 yr) participated and performed unilateral plantar flexion (30 repetitions/min) for 2 min. Protocols were as follows: low-intensity exercise (L) using a load of 20% of one-repetition maximum (1 RM), L with blood flow restriction (LR), and high-intensity exercise using 65% 1 RM (H). Intramuscular phosphocreatine (PCr) and diprotonated phosphate (H2PO4−) levels and intramuscular pH at rest and during exercise were obtained. We found that the PCr depletion, the H2PO4− increase, and the intramuscular pH decrease during LR were significantly greater than those in L ( P < 0.001); however, those in LR were significantly lower than those in H ( P < 0.001). The recruitment of fast-twitch fiber evaluated by inorganic phosphate splitting occurred in only 31% of the subjects in LR, compared with 70% in H. In conclusion, the metabolic stress in skeletal muscle during low-intensity resistance exercise was significantly increased by applying blood flow restriction, but did not generally reach that during high-intensity resistance exercise. This new method of resistance training needs to be examined for optimization of the protocol to reach equivalence with high-intensity resistance training. more...

Purpose: The effects of exercise in subjects with multiple cardiovascular risk factors (RF) have never been tested in a large-scale randomized controlled trial. The favorable results from our observational study led to this randomized controlled trial. Methods: The participants, recruited from a community, were overweight, with two of the following three risk factors: hypertension, hyperlipidemia, or glucose intolerance (N = 561; 44% male; mean age (SD) 67 (6); mean BMI 26.4 (2.0)). All participants received a standard health exam with counseling, followed by randomization. The intervention group (INT) was to exercise two to four times per week for 6 months at a fitness club. Results: Dropout rate was 11% for INT and 10% for the controls. INT exercised an average of 2.6 times per week. Among primary outcome measures, there was a marginally significant between-group difference in changes in systolic blood pressure (intervention minus control, -2.46 mm Hg). Reductions in LDL cholesterol (-1.9 mg·dL-1) and hemoglobin A1c (-0.042%) were not significant. Among secondary outcomes, between-group differences were significantly greater (P < 0.05) for INT in mean body weight (-1.60 kg), waist circumference (-1.8 cm), triglyceride (-7 mg·dL-1), hsCRP (-0.063 mg·L-1), and estimated V?O2peak (2.0 mL·kg-1·min-1). All directional mean RF changes consistently favored INT. A cardiovascular risk reduction estimated from the changes in RF was about 24%. A greater improvement was also found in health-related quality-of-life measures (SF-36) in INT. No difference was found in the adverse event rate. Conclusions: Exercising an average of 2.6 times per week for 6 months produced a significant improvement in cardiovascular risk profile in subjects with multiple cardiovascular risk factors through cumulative results of modest yet pervasive changes in all conventional risk factors, without increased adverse effects more...

a Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan b Department of Rehabilitation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan c Research Fellow of the Japan Society for the Promotion of Science, Japan d Translational Research and Clinical Trial Center, Hokkaido University Hospital, Sapporo, Japan e Graduate School of Program in Lifelong Learning Studies, Hokusho University, Ebetsu, Japan more...

Skeletal muscle atrophy is induced by an imbalance between protein synthesis and degradation. Our previous studies reported that angiotensin II (AII) directly induced muscle atrophy in mice. This study investigated the role of NAD(P)H oxidase 2 (Nox2) activation by AII in the induction of skeletal muscle atrophy. For 4 weeks, either saline (vehicle: V) or AII (1000 ng kg−1 min−1) was infused into male wild-type (WT) and Nox2 knockout (KO) mice via osmotic minipumps. Experiments were performed in the following 4 groups: WT + V, KO + V, WT + AII, and KO + AII. Body weight, muscle weight, and myocyte cross-sectional area were significantly decreased in WT + AII compared to WT + V mice, and these changes were not observed in KO + AII mice. Akt phosphorylation of Ser473 and p70S6K of Thr389 was decreased, gene expression levels of MuRF-1 and atrogin-1 were increased in WT + AII compared to WT + V, and these changes were significantly attenuated in KO + AII mice. The deletion of Nox2 prevented AII-induced skeletal muscle atrophy via improving the balance between protein synthesis and degradation. Therefore, Nox2 may be a therapeutic target for AII-induced skeletal muscle atrophy. more...

Purpose: We demonstrated that blood flow restriction (BFR) remarkably enhances muscular metabolic stress in resistance exercise, although there is a wide range of individual differences in the responses. It is possible that these differences could be due to training status and muscular physiological characteristics. We investigated intramuscular metabolic responses during low-intensity resistance exercise with BFR between two different types of track athletes. Methods: Twelve age-matched male track athletes (sprinter group, n = 6; endurance runner group, n = 6) were recruited and performed unilateral plantarflexion (30 repetitions per minute). The exercise protocols were as follows: low-intensity exercise at 20% of one-repetition maximum (1RM) (L), high-intensity exercise at 65% 1RM without BFR (1.3 times of systolic blood pressure), L with BFR for 2 min (L-BFR), and prolonged exercise time in L-BFR for 3 min (prolonged BFR). Metabolic stress, defined as phosphocreatine and intramuscular pH decrease, and muscle fiber recruitment were evaluated using 31P magnetic resonance spectroscopy. Results: Endurance runners showed higher peak oxygen uptake and lower muscle strength than sprinters. Phosphocreatine decreases in endurance runners during exercise with BFR protocols were significantly greater than those in sprinters (P < 0.05), although those occurring during L were significantly lower than those in sprinters (P < 0.05). The changes in intramuscular pH and the incidence of fast-twitch fiber recruitment did not show a statistical difference between the two groups. Phosphocreatine decreases in L-BFR were significantly correlated with peak oxygen uptake (P < 0.05). Conclusions: The effects of low-intensity resistance exercise with BFR are greater in endurance runners according to higher aerobic capacity more...

Muscular blood flow reduction (BFR) during multiple sets of low-intensity exercise training has been shown to elicit muscle hypertrophy and strength gain. Several hypotheses have been proposed to explain the hypertrophic adaptations to low-intensity BFR exercise, which include muscle fatigue with metabolic stress. However, the change in intramuscular inorganic phosphate (Pi, an index of muscle fatigue) during multiple sets of low-intensity exercise with BFR is poorly understood. Eight men performed four sets of unilateral plantar flexion exercise (20% 1-RM) on a (31)P-magnetic resonance spectroscopy. Each subject wore a cuff (5-cm wide) on the most proximal portion of the thigh; the cuff was inflated during the exercise session at three different pressures [0 mmHg as the control ± (CON), 180 mmHg as moderate restriction (BFR-M) and 230 mmHg as high restriction (BFR-H)]. During the first and second exercise sets, the increase in Pi was higher (P0·05) with BFR-H than with BFR-M and CON. On the other hand, the decrease in Pi was lower with BFR-H than with CON during the second and third rest periods between sets. As a result, the Pi concentration increased progressively (P0·05) with BFR-H, while the Pi was relatively constant with BFR-M and CON during the exercise session. Our results suggest that intramuscular Pi accumulation during multiple sets of low-intensity exercise can be produced only by a high level of BFR, but not by moderate reduction. The Pi accumulation was associated both with exercise and with the rest period between sets. more...

Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex-, and activity-matched control subjects to assess the aerobic capacity. We performed 31phosphorus-magnetic resonance spectroscopy (31P-MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton(1H)-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO2; 34.1 ± 6.2 vs. 41.4 ± 8.4 mL/kg/min, P < 0.05) and anaerobic threshold (AT; 18.0 ± 2.4 vs. 23.1 ± 3.7 mL/kg/min, P < 0.01) adjusted by lean body mass were lower in MetS patients than control subjects. Phosphocreatine (PCr) loss during exercise was 1.5-fold greater in MetS, suggesting reduced intramuscular oxidative capacity. PCr loss was inversely correlated with peak VO2 (r = -0.64) and AT (r = -0.60), respectively. IMCL content was 3-fold higher in MetS and was inversely correlated with peak VO2 (r = -0.47) and AT (r = -0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r = 0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism. more...

Our previous study reported that metabolic stress in skeletal muscle achieved by combining moderate blood flow restriction (BFR) with low-intensity resistance exercise at 20% of one repetition maximum (1 RM) could not reach the level achieved by high-intensity resistance exercise. Since the previous protocol is typical of current regimens of this type, we sought in this study to optimize the exercise protocol for low-intensity resistance exercise with BFR by examining the dose effects of exercise intensity and pressure. Twelve healthy subjects participated in this study. They were asked to perform unilateral plantar flexion for 2 min (30 repetitions/min) under six different conditions: two resistance exercises (20% 1 RM and 65% 1 RM) without BFR, and four BFR protocols. The four BFR protocols included three different exercise intensities (20, 30, and 40% 1 RM) with moderate pressure (MP) using 130% of systolic blood pressure (147 ± 17 mmHg, mean ± SD) and 20% 1 RM with high pressure at 200 mmHg. Intramuscular metabolites and pH were obtained by 31P-magnetic resonance spectroscopy. Significant dose effects on intramuscular metabolites and pH were observed for exercise intensity ( P < 0.001) but not for BFR pressure. The BFR protocol combining 30% 1 RM with MP had similar results as the high-intensity load at 65% 1 RM. Intramuscular metabolic stress during BFR exercise might be susceptible to increasing exercise intensity. To replace high-intensity resistance exercise, the BFR protocol might require an intensity of ≥30% 1 RM. more...

To investigate the effects of a 100-mg oral single-dose administration of sarpogrelate hydrochloride (SH) on saturation O(2) (StO(2)) of calf muscle in healthy subjects experiencing simulated peripheral arterial disease (0.6 ankle brachial pressure index). Ten subjects performed three kinds of plantar flexion exercises at a work rate of 50% of maximal volunteer contraction for 4 min by using cuff occlusion ischemia,. Subjects performed a control test (C) without ischemia and SH, an ischemia test (I) without SH, and an I + SH test with ischemia. StO(2), blood pressures (BP), and heart rate (HR) were measured through all experiments. At the end of the exercise, the decrease in StO(2) from baseline in the C and I + SH tests was significantly less than that in the I test (p0.05, respectively). However, there were no significant differences in mean BP or HR in any of the exercise conditions. These results indicated that an oral single-dose administration of SH might improve peripheral circulation independent of any changes in BP and HR. more...

The aim of this study was to determine if muscle energy metabolism, as measured by (31)P-magnetic resonance spectroscopy (MRS), is a metabolic marker for the efficacy of treatment of Machado-Joseph disease (MJD). We obtained (31)P-MRS in the calf muscle of 8 male patients with MJD and 11 healthy men before, during, and after a 4 minute plantar flexion exercise in a supine position. The data showed that there was a significant difference between the groups in terms of the PCr/(Pi + PCr) ratio at rest (P = 0.03) and the maximum rate of mitochondrial ATP production (V(max)) (P < 0.01). In addition, V(max) was inversely correlated with the scale for the assessment and rating of ataxia score (r = -0.34, P = 0.04). The MJD group also showed a reduction in V(max) over the course of 2 years (P < 0.05). These data suggest that this noninvasive measurement of muscle energy metabolism may represent a surrogate marker for MJD. more...

Background: Enriched blood vessels occur in the stroma of Barrett's esophagus and are related to the ease of tumor invasion in the early stage of the cancer. Hypoxia-inducible factor (HIF) is closely related with angiogenesis through expression of vascular endothelial growth factor. The aim of the present study was to determine the predictors for angiogenesis in Barrett's esophagus and evaluate their clinical significance. Methods: Between December 2003 and May 2004, 209 patients with endoscopically and histologically proven Barrett's esophagus were enrolled. Before endoscopic examination, all participants answered structured questionnaires for gastroesophageal reflux symptoms and drug usage. HIF-1α and COX-2 protein expressions, cellular proliferation, and apoptosis were investigated immunohistochemically in biopsy samples taken from the esophagus of each patient. The degree of angiogenesis was determined by CD34 immunostaining analysis. Predictors for angiogenesis were evaluated with multivariate logistic regression analysis. Results: Sixty (28.7%) of the 209 enrolled patients with Barrett's esophagus had a high CD34 score. Factors proven as positive predictors for a high CD34 score were presence of gastroesophageal reflux symptoms, reflux esophagitis, COX-2 protein expression, and the proliferating cell nuclear antigen (PCNA) index. Administration of proton-pump inhibitors and HIF-1α protein expression were not predictors. Conclusions: Reflux esophagitis and gastroesophageal reflux symptoms were positive predictors for enriched angiogenesis in the stromal portion of Barrett's esophagus, which has malignant potential because the epithelial cells express COX-2 and have accelerated cellular proliferation. more...

Barrett’s esophagus is a well-known acquired condition resulting from gastroesophageal reflux disease (GERD). However, it is still unknown whether Barrett’s esophagus develops gradually over time in patients with GERD. To address this issue, we investigated the change in the prevalence and length of short-segment Barrett’s esophagus (SSBE) over time. From January 2005 to March 2007, we enrolled 5338 patients who received upper gastrointestinal endoscopy. Prevalence and length of endoscopically identified SSBE were evaluated within groups divided on the basis of 10-year age intervals. The factors possibly influencing SSBE length such as symptoms, antacid use, and endoscopic findings were also evaluated. Additionally, the length change in 236 patients with histologically confirmed Barrett’s esophagus was evaluated over a 2-year follow-up. Of the 5338 enrolled patients, 1997 had SSBE. The prevalence of endoscopically identified SSBE was significantly higher and its length was significantly longer in elderly patients. Multiple regression analysis showed that age, presence of reflux esophagitis, reflux symptoms, and hiatal hernia were positively correlated with SSBE length. Analysis of the 2-year follow-up study of histologically confirmed SSBE revealed significant extension of Barrett’s length in 28.0% of 236 patients. Presence of reflux symptoms and hiatal hernia were identified as positive predictors and proton pump inhibitor administration as a negative predictor of SSBE elongation. Positive predictors for the extension of SSBE were presence of hiatal hernia and reflux symptoms, but not age. more...

Background and Aim: Colonoscopy plays an important role in the diagnosis and treatment of gastrointestinal illness in both Western countries and Japan. However, preparative bowel cleansing for colonoscopy is frequently troublesome for elderly and/or constipated patients, since they must drink larger volumes of lavage solution for adequate cleansing. We investigated the use of prokinetic agents for improving the efficacy and tolerability of bowel cleansing prior to colonoscopy. Methods: 613 patients were divided into two groups according to oral lavage solution used (polyethylene glycol or magnesium citrate), and were further randomized to receive either vehicle (100 ml water) alone, vehicle with 5 mg mosapride citrate, or vehicle with 50 mg itopride hydrochloride 30 min before administration of lavage solution. Experimental parameters included bowel cleansing quality, times to first defecation and completion of bowel cleansing, and incidence of uncomfortable abdominal symptoms during colonoscopy preparation. Results: Administration of mosapride citrate or itopride hydrochloride prior to oral lavage solution did not significantly improve bowel cleansing quality. However, statistically significantly fewer uncomfortable abdominal symptoms were found in patients who received mosapride citrate or itopride hydrochloride versus vehicle alone. Conclusion: Prokinetic agents effectively decreased the incidence of uncomfortable abdominal symptoms experienced during colonoscopy preparation. more...

with renal dysfunction in patients with heart failure Arata Fukushima , Shintaro Kinugawa ⁎, Tsuneaki Homma , Yoshihiro Masaki , Takaaki Furihata , Takahiro Abe , Tadashi Suga , Shingo Takada , Tomoyasu Kadoguchi , Koichi Okita , Shouji Matsushima , Hiroyuki Tsutsui a a Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan b Department of Rehabilitation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan c Research Fellow of the Japan Society for the Promotion of Science, Japan d Graduate School of Program in Lifelong Learning Studies, Hokusho University, Ebetsu, Japan more...

The annual health check followed by lifestyle recommendations has long been the standard national strategy to improve cardiovascular disease (CVD) risk factors in Japan. Exercise at fitness clubs, now widely accessible in major cities, has a novel appeal as a strategy with the additive effect of CVD risk reduction. The Sapporo Fitness Club Trial (SFCT) is a randomized controlled trial to compare the efficacy of the national standard alone (control) with the standard plus exercise at a fitness club (intervention) for the reduction of CVD risk factors.The SFCT has recruited and randomized 561 relatively inactive overweight men and women, aged 40-85 years, with elevated levels of 2 or more of the following: systolic blood pressure, fasting blood glucose, and low-density lipoprotein cholesterol. The intervention group was required to exercise at a fitness club 2-4 times per week. At the end of 6 months, risk factors, aerobic capacity, health-related quality of life measures, and adverse effects are to be compared.The SFCT is expected to have a major impact in Japan on public health recommendations on exercise for the reduction of lifestyle-related disease. more...

OKITA, K., K. YONEZAWA, H. NISHIJIMA, A. HANADA, T. NAGAI, T. MURAKAMI, and A. KITABATAKE. Muscle high-energy metabolites and metabolic capacity in patients with heart failure. Med Sci. Sports. Exerc., Vol. 33, No. 3, 2001, pp. 442-448.Various abnormalities in skeletal muscle have been demonstrated by biopsy in patients with chronic heart failure (CHF). In mammalian muscles, high-energy metabolite composition at rest (HEMC) provides data on important metabolic characteristics; however, the significance of HEMC has not been clarified in patients with CHF. Therefore, we investigated HEMC in normal subjects and patients with CHF and examined its relation to muscle metabolic capacity and exercise tolerance.High-energy metabolites (phosphocreatine (PCr), inorganic phosphate (Pi), and ATP) in resting calf muscle were measured by 31P-magnetic resonance spectroscopy (31P-MRS), and ratios of Pi to PCr, Pi to ATP, and PCr to ATP were calculated in 34 patients with CHF and 13 age- and size-matched normal subjects. Muscle metabolism was evaluated during local exercise of unilateral plantar flexion by 31P-MRS. Metabolic capacity was estimated by the rate of PCr breakdown in relation to the workload. Systemic exercise capacity was evaluated by a bicycle ergometer.The ratio of PCr to ATP was significantly increased in patients with CHF compared with controls (3.06 +/- 0.43 vs 2.72 +/- 0.36, P0.05) and was significantly correlated with metabolic capacity (r = -0.37, P0.01) and with peak oxygen uptake (r = -0.45, P0.01). There was a significant correlation between metabolic capacity and peak oxygen uptake (r = 0.53, P0.001).HEMC was altered in patients with CHF, and this change was related to metabolic capacity and exercise capacity. These findings provide new insight into the mechanism of impaired muscle metabolism in CHF. more...

Background —Several studies have indicated that skeletal muscle is important in determining the exercise capacity of patients with chronic heart failure (CHF). However, this theory has been investigated only in experiments based on local exercise involving a small muscle mass. We investigated skeletal muscle metabolism during maximal systemic exercise to determine whether muscle metabolism limits exercise capacity in patients with CHF. We also studied the relationship between muscle metabolic abnormalities during local and systemic exercise. Methods and Results —Skeletal muscle metabolism was measured during maximal systemic exercise on a bicycle ergometer by a combination of the metabolic freeze method and 31 P magnetic resonance spectroscopy in 12 patients with CHF and 7 age- and size-matched normal subjects. We also evaluated skeletal muscle metabolism during local exercise while subjects performed unilateral plantar flexion. Muscle phosphocreatine (PCr) was nearly depleted during maximal systemic exercise in patients with CHF and normal subjects (12.5±0.04% and 12.3±0.07%, respectively, of initial level). PCr depletion occurred at a significantly lower peak oxygen uptake (peak V̇ o 2 ) in patients with CHF than in normal subjects (CHF, 20.2±3.0 versus normal, 31.8±3.7 mL · min −1 · kg −1 , P o 2 during maximal systemic exercise in patients with CHF ( r =0.83, P r =0.76, P o 2 ( r =0.83, P Conclusions —These results suggest that impaired muscle metabolism associated with early metabolic limitation determines exercise capacity during maximal systemic exercise in patients with CHF. There was a significant correlation between muscle metabolic capacity during systemic and local exercise in patients with CHF. more...

Objective—To investigate whether localised skeletal muscle training, which does not have a great influence on the heart, improves abnormalities of calf muscle metabolism in patients with chronic heart failure. Methods—Seven cardiac patients in New York Heart Association class II and III undertook a random order crossover trial. Training consisted of unilateral calf plantar flexion exercise. Before and after training, the patients' metabolic responses were examined during the calf exercise test with phosphorus-31 nuclear magnetic resonance spectroscopy (31P-MRS) and calf blood flow with plethysmography. The new Borg scale was employed as a subjective fatigue scale. Results—In a constant load exercise test (70% of maximum load achieved during the incremental exercise), standardised phosphocreatine and intracellular pH decreased less after training (p more...