l-carnitine supplementation vs cycle ergometer exercise for physical activity and muscle status in hemodialysis patients: A randomized clinical trial.

Serum carnitine is decreased in hemodialysis patients, which induces muscle atrophy. Thus, we examined the different effects of l-carnitine and exercise on exercise activity and muscle status in hemodialysis patients. Twenty patients were divided into l-carnitine and cycle ergometer groups and were followed for 3 months. Muscle and fat mass, physical activities, and muscle status were evaluated by an impedance, physical function test, and magnetic resonance imaging, respectively. The l-carnitine significantly increased muscle mass (P = .023) and thigh circumference (P = .027), decreased fat mass (P = .007), and shortened chair stand-up time (P = .002) and 10-m walk test (P = .037). The fat fraction was improved by the l-carnitine (P = .047). Compared with the exercise group, l-carnitine improved the changes in 10-m walk test (P = .026), chair stand-up time (P = .014), and thigh circumference (P = .022). Baseline fibroblast growth factor-21 and myostatin levels predicted the l-carnitine-associated changes in exercise activities. l-carnitine, rather than exercise, improved physical activity and muscle status in hemodialysis patients.

Hybrid training of voluntary and electrical muscle contractions decreased fasting blood glucose and serum interleukin-6 levels in elderly people: a pilot study.

A new muscle-training method, "hybrid training", utilizing combined voluntary and electrical muscle contractions, is effective for increasing muscle mass and force on lower extremities in elderly people. Although skeletal muscle regulates glucose metabolism, partly by releasing interleukin (IL)-6, the effects of hybrid training on glucose metabolism remains unclear. The aim of this study was to investigate the effects of hybrid training on glucose metabolism and serum IL-6 levels in elderly people. Hybrid training was performed on 7 elderly subjects. Both quadriceps and hamstrings were contracted voluntarily or electrically at the same time for 19 min twice a week. The effects on glucose metabolism and serum IL-6 levels were evaluated after 12 weeks of hybrid training. All of the subjects completed the study, and no severe adverse events developed during the study period. There were no significant differences in body mass index, serum insulin levels, homeostasis model assessment for insulin resistance values, or hemoglobin A1c values after hybrid training. However, fasting blood glucose levels were significantly decreased after hybrid training (114 ± 13 vs. 103 ± 9 mg·dL(-1); p = 0.0340). In addition, all 7 subjects showed a decrease in serum IL-6 levels after hybrid training, and this decrease was statistically significant (44.0 ± 35.6 vs. 14.6 ± 10.5 pg·mL(-1); p = 0.0180). Furthermore, there was a significant correlation between changes in serum IL-6 levels and changes in fasting blood glucose levels (ρ = 0.883; p = 0.0306). In this study, we showed the safety and good adherence of hybrid training for lower extremities in elderly people. Furthermore, hybrid training decreased fasting blood glucose and serum IL-6 levels in elderly people.

Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study.

BACKGROUND: Physical inactivity is a risk factor for the development of non-alcoholic fatty liver disease (NAFLD). "Hybrid training", a training that involves both voluntary and electrical muscle contractions, causes beneficial alterations in muscles even after short durations of exercise. The aim of this study was to investigate the therapeutic efficacy of hybrid training in patients with NAFLD. METHODS: Thirty-five patients with NAFLD who were resistant to lifestyle counseling were assigned to a hybrid-training group (n = 12) or a control group (n = 23). In the hybrid-training group, quadriceps and hamstrings were contracted voluntarily or electrically for 19 min twice a week. In the control group, patients received lifestyle counseling. The therapeutic efficacy of the hybrid training was evaluated after 12 weeks of the intervention. RESULTS: Serum alanine aminotransferase (ALT) levels and hepatic steatosis grade were significantly decreased in the hybrid-training group compared to that of the control group (-14.1 ± 5.8 vs. 3.5 ± 5.4 IU/mL; P < 0.05, -0.67 ± 0.19 vs. 0.09 ± 0.06 grade; P < 0.01, respectively). No significant changes were seen between the two groups in skeletal muscle mass. The decreases in homeostasis model assessment of insulin resistance (HOMA-IR) value and in serum IL-6 levels were significantly greater in the hybrid-training group than in the control group (-6.2 ± 3.2 vs. 0.4 ± 0.6; P < 0.05, -3.1 ± 1.1 vs. 1.1 ± 0.5 pg/mL; P < 0.01, respectively). CONCLUSION: Hybrid training of voluntary and electrical muscle contractions improved hepatic steatosis and reduced insulin resistance and serum IL-6 levels in NAFLD patients who are resistant to lifestyle counseling.

Increasing muscle strength and mass of thigh in elderly people with the hybrid-training method of electrical stimulation and volitional contraction.

The "Hybrid training" (HYBT) method utilizing combined electrical stimulation and voluntary muscle contraction has been developed as a muscle training method. It has already been shown that the method is technically sound and clinically effective in healthy young subjects. The purpose of this study was to investigate the effect of the HYBT method on the knee extensor strength considering safety for elderly people. Twenty subjects were randomly divided into two groups: the HYBT group and the weight machine training (WMT) group. All the subjects performed knee flexion and extension for 19 min per session, twice a week for 12 weeks. At the baseline and after the training, the subjects' maximal isometric torque of knee extension and cross-sectional area (CSA) of quadriceps femoris muscle were measured. The subjects completed the study without adverse effects. The knee extension torque significantly increased in both groups (39% in HYBT group and 42% in WMT group, P < 0.05). The CSA of quadriceps whole significantly increased in both groups (9% in HYBT group and 14% in WMT group, P < 0.05). These results indicate that the HYBT method increases muscle strength and mass, and that this method is as effective as the WMT. In addition, unlike the WMT, the HYBT device, which is portable and not large in size, is so easy to handle that it can be placed at the bedside. Therefore, the HYBT has potential to become a safe, effective method of muscle training for elderly people.

[Comparison of basic imaging properties for digital radiographic systems based on a direct conversion type of flat panel detector].

The purpose of this study was to evaluate the basic imaging properties of the two latest digital radiographic X-ray systems, namely, the DynaDirect Winscope 6000 (abbr. as System A, Toshiba Medical Systems) and the Sonialvision Safire Multi (abbr. as System B, Shimadzu Corp.). These systems were based on a direct-conversion flat panel detector (FPD) of amorphous selenium. The basic imaging properties of the two systems were evaluated by measuring characteristic curves, presampled modulation transfer functions (MTFs), and noise power spectra (NPS) using DICOM images to which no resampling was performed with a matrix size of 2048x2048. In addition, noise equivalent quanta (NEQ) and detective quantum efficiency (DQE) calculated from the result of the basic imaging properties were evaluated. The characteristic curves of the two systems showed quite high linearity. The MTFs of the two systems indicated high-resolution properties, as is well known to be an advantage of the direct conversion FPD system. However, the NPS of System A showed better performance than System B under the same exposures. Therefore, the DQE of System A was higher than that of System B at all spatial frequencies.

Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea.

BACKGROUND: A dry powder inhaler of KP-496 is currently in clinical development in Japan as an anti-asthmatic agent. The aim of this study was to evaluate the in vitro pharmacological profile of KP-496. METHODS: The antagonistic activities of KP-496 for leukotriene (LT) D(4) and thromboxane (TX) A(2) receptors were examined using the LTD(4)- and U46619-induced contractions of the isolated guinea pig trachea. The selectivity of KP-496 was examined using various agonist-induced contractions in the isolated guinea pig trachea. RESULTS: KP-496 produced parallel rightward shifts of the LTD(4) and U46619 concentration-response curves in a concentration-dependent manner. Schild plot analyses of the antagonistic activities of KP-496 demonstrated that it is a competitive antagonist for LTD(4) and TXA(2) receptors with pA(2) values of 8.64 and 8.23, respectively. The LTD(4) antagonistic activity of KP-496 was comparable to that of pranlukast and zafirlukast but was more potent than that of montelukast. The TXA(2) antagonistic activity of KP-496 was comparable to that of seratrodast. KP-496 and seratrodast also inhibited the prostaglandin (PG) D(2)- and PGF(2alpha)-induced contractions of the isolated guinea pig trachea. KP-496 had no effect on the histamine-, acetylcholine-, serotonin- and substance P-induced contractions of the isolated guinea pig trachea. CONCLUSIONS: These results indicate that KP-496 is a selective dual antagonist for LTD(4) and TXA(2) receptors. LTD(4) and TXA(2) play important roles in asthma, and antagonists for these mediators are being used for the treatment of asthma. Thus, KP-496 is expected to become a novel potent therapeutic agent for asthma.

Rebamipide enema is effective for treatment of experimental dextran sulfate sodium induced colitis in rats.

We investigated therapeutic efficacy of rebamipide using dextran sulfate sodium (DSS) induced colitis model in rats. Three percent DSS solution was given to rats for 9 days. After that, we evaluated the drug efficacy on colitis sustained with continuous drinking of 1% DSS. Twice-daily treatment with 0.3% or 1% rebamipide for 14 days significantly ameliorated the stool abnormality in the colitis model, preferentially suppressed hematochezia. The colonic mucosal lesion, determined by Alcian blue staining on day 24, was significantly reduced by rebamipide enema in a dose-dependent manner. Either rebamipide or 5-aminosalycilic acid (5-ASA) enema treated once daily significantly ameliorated colitis. The minimum effective dose of rebamipide was 0.3% in once-daily treatment, and that of 5-ASA was 10%. In a mechanistic study, the epithelial cell sheet formation of the T84 colon cancer cell was measured as an increase in generation of trans-epithelial electrical resistance in vitro. Rebamipide accelerated the increase, while 5-ASA conversely suppressed it. These results suggest that rebamipide enema is effective for treatment of experimental ulcerative colitis (UC).

Thymosin alpha1 accelerates restoration of T cell-mediated neutralizing antibody response in immunocompromised hosts.

Thymosin alpha1 is a biological response modifier that has been used clinically for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracellular mechanisms have been postulated to explain the effect of thymosin alpha1 on hepatocytes infected with hepatitis B virus (HBV). Here, we established a new animal model and the related suitable conditions to access the thymosin activity by means of measuring the production of neutralizing antibody against hepatitis B surface antigen (HBsAg). We proved that chemically synthesized thymosin alpha1 restored the T cell-mediated antibody production following its suppression in mice by 5-fluorouracil (5-FU), and found that thymosin alpha1 showed activity at a low dose of 30 microg/kg. Further studies utilizing the flowcytometric analysis showed that thymosin alpha1 at this dose accelerated the replenishment and maturation of thymocytes while the expression of Smoothened (Smo) of the Hedgehog (Hh)-signaling in CD4-CD8- thymocytes, the potent negative regulator of proliferative responses, was not affected. The restoration of some of the defects in the host defense systems may facilitate elimination of infectious agents, and the present study provides a novel model to define the restoration of T cell-mediated immune responses to hepatitis B virus in vivo.