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The objective of this study was to evaluate the effect of Capacitive and Resistive electric transfer (CRet)-combined exercise therapy for participants with non-specific chronic low back pain (NSCLBP). Twenty-six received only the exercise program (E group, n = 15), or received both CRet and the same exercise program (E+CRet group, n = 11). Pain intensity, functional disability and trunk function were measured pre-, and post-intervention and there was also a 1-month follow-up period. Data analysis was performed for each index using the Mann-Whitney U test for comparisons between two groups at each time point, and the Wilcoxon signed-rank test for comparison between each time point within the group. The results of this study indicate that pain intensity was improved in both groups at post-intervention, also, the effect continued during follow-up period. In addition, functional disability was significantly improved in the E+CRet group at the post-intervention and during the follow-up period. The intervention effect on NSCLBP was higher in the E+CRet group than the E group. CRet, which is a form of deep thermotherapy, combined with exercise have a possibility of more effectiveness than exercise alone.

Context: The functional movement screen (FMS) is an assessment tool for movement dysfunction, which is used to reduce the risk of injury. Although the relationship between the FMS composite score and injuries has been extensively studied, the association between FMS scores and injuries in only college basketball players remains unknown. Objective: To examine the relationship between the FMS score and injuries in basketball players. Design: Cross-sectional study. Setting: University research laboratory. Participants: Eighty-one male college basketball players (average age 20.1 [1.3] y) participated. Main Outcome Measures: The FMS composite score was calculated from 7 movement tests. The incidence of injuries over a 1-year period prior to the test day was determined based on a questionnaire. Individuals were categorized into 2 groups: injury (with a serious basketball-related injury resulting in the loss of practice and game time for at least 4 wk) and noninjury groups. Mann–Whitney U and chi-square tests were used to evaluate group differences in the composite FMS and 7 movement scores, respectively. Furthermore, the scores significant on univariate analyses were submitted to a multivariate logistic analysis, adjusting for participant characteristics. Results: The composite FMS scores of the 2 groups were not significantly different (P = .38). Among the 7 tasks, only the deep squat and hurdle step showed significant group differences (P = .03 and P = .001, respectively). The multivariate logistic analysis revealed that deep squat (odds ratio, 6.48; 95% confidence interval, 1.23–34.01; P = .03) and hurdle step scores (odds ratio, 25.80; 95% confidence interval, 1.81–368.73; P = .02) were significantly associated with injuries, even after adjustment for participant characteristics. Conclusions: Deep squat and hurdle step scores may be associated with injuries in basketball players. Further research should be conducted to confirm that these 2 scores can predict the incidence of injuries in basketball players.

[Purpose] Few studies on the transverse arch (TA) in the forefoot have been conducted. The forefoot is where pains occur most frequently and is related to walking and balance; hence, paying attention to TA is vital. However, the relationship between TA and foot muscles has not been investigated. Therefore, this study aims to investigate muscles related to TA. [Subjects and Methods] Nineteen healthy young males were included. Measurements of their feet, excluding one foot with recent foot pain (n=37), were obtained. The height of TA (TAH) was measured in two ways: during 10% and 90% loading of body weight. The cross-sectional area and thickness of five muscles were measured: flexor digitorum longus, peroneus longus and brevis, flexor hallucis brevis, flexor digitorum brevis (FDB) and abductor hallucis (ABH). All measurements were performed with an ultrasound device. [Results] FDB and ABH were correlated with TAH during 10% and 90% loading after removing the effect of body mass index and age. The greater FDB and ABH, the higher TAH. [Conclusion] As FDB becomes larger, the second, third and fourth metatarsal heads are raised more. Furthermore, the height of the first metatarsal head is lowered by a larger ABH. These mechanisms may increase TAH.

[Purpose] The association between foot injuries and foot alignment, including the transverse arch height (TAH) and asymmetry, was examined in athletes participating in college track events. [Participants and Methods] This study included 55 male athletes participating in a college track and field club. Data including demographic information and the incidence of foot injuries within a year prior to participation in this study were obtained via questionnaires. TAH and the medial longitudinal arch height during 10 and 90% loading, leg-heel alignment, and the heel angle were measured before calculating the asymmetry of each alignment parameter measured. Participants were categorized into an injury or a normal group. Unpaired t-tests were used to perform between-group comparisons for each alignment parameter measured and asymmetry. Additionally, logistic regression analysis was performed to identify factors associated with foot injuries after adjustment for demographic data. [Results] TAH asymmetry during 10 and 90% loading was significantly greater in the injury group. Further logistic regression analysis performed showed that only TAH asymmetry during 90% loading was significantly associated with foot injuries after adjustment for demographic data. [Conclusion] With regard to track events, a greater asymmetry of forefoot TAH in a weight-bearing position was observed to be associated with foot injuries.

This study aimed to investigate the acute effects of capacitive and resistive electric transfer (CRet) on Achilles tendon elongation during muscle contraction, as well as the circulation in the peritendinous region. Sixteen healthy men participated in this study. All 16 participants underwent 2 interventions: (1) CRet trial and (2) CRet without power (sham trial). Tendon elongation was measured four times. Using near-infrared spectroscopy, the blood circulation (volume of total-hemoglobin (Hb), oxygenated hemoglobin (oxy-Hb), and deoxygenated hemoglobin (deoxy-Hb)) was measured for 5 min before the intervention and for 30 min after the intervention. The differences between the measurements obtained before and after intervention were compared between the two interventions. The changes in tendon elongation and deoxy-Hb were not significantly different between the interventions. Total- and oxy-Hb were significantly increased in the CRet trial compared with the sham trial. In addition, the increases in total-Hb and oxy-Hb lasted for 30 min after the CRet intervention (CRet vs. sham: oxy-Hb: F = 8.063, p = 0.001, total-Hb: F = 4.564, p = 0.011). In conclusion, CRet significantly improved blood circulation in the peritendinous region.

[Purpose] This study aimed to clarify the effects of Capacitive and Resistive electric transfer (CRet) on changes in muscle flexibility and lumbopelvic alignment after fatiguing exercise. [Subjects and Methods] Twenty-two healthy males were assigned into either the CRet (n=11) or control (n=11) group. Fatiguing exercise and CRet intervention were applied at the quadriceps muscle of the participants' dominant legs. The Ely test, pelvic tilt, lumbar lordosis, and superficial temperature were measured before and after exercise and for 30 minutes after intervention. Statistical analysis was performed using one-way analysis of variance, with Tukey's post-hoc multiple comparison test to clarify within-group changes and Student's t-test to clarify between-group differences. [Results] The Ely test and pelvic tilt were significantly different in both groups after exercise, but there was no difference in the CRet group after intervention. Superficial temperature significantly increased in the CRet group for 30 minutes after intervention, in contrast to after the exercise and intervention in the control group. There was no significant between-group difference at any timepoint, except in superficial temperature. [Conclusion] CRet could effectively improve muscle flexibility and lumbopelvic alignment after fatiguing exercise.

The potent and selective phosphodiesterase 4 inhibitor ASP3258 is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease (COPD). After a single oral administration to rats, ASP3258 is rapidly absorbed with a bioavailability of 106%. In situ absorption data indicated that ASP3258 is mainly absorbed in the small intestine. Tissue distribution data after oral administration of 14C-ASP3258 showed rapid and extensive distribution to various tissues. Excluding the gastrointestinal tract, the tissues with the highest concentrations were liver, heart and plasma. Liquid chromatography-nuclear magnetic resonance spectroscopy data revealed that O-glucuronidation of the carboxylic acid moiety of ASP3258 (formation of an acyl glucuronide) plays a key role in metabolism. No indication was found that the acyl glucuronide reacted with proteins in plasma or tissues. When 14C-ASP3258 was orally administered to intact rats, urinary and fecal excretion accounted for 1.3% and 100.6% of the administered radioactivity, respectively. After a single oral administration of 14C-ASP3258 to bile-cannulated rats, urinary and biliary excretion accounted for 0.7% and 93.8% of the administered radioactivity, respectively. These findings suggest that fecal excretion via bile plays an important role in the elimination of ASP3258-derived radioactivity. In vitro metabolic profiles were relatively similar among the species examined, suggesting that our findings in rats may help us to understand pharmacokinetics, efficacy and safety profiles in humans and other species. Copyright © 2014 John Wiley & Sons, Ltd.

[Purpose] Targeting university badminton players, this study investigated the relationship between agility, which is associated with performance in badminton, and lower limb muscle strength, and examined which muscles influence agility. [Subjects and Methods] A total of 23 male university badminton players were evaluated for side-shuffle test scores and lower limb strength. The relationships between agility, lower limb strength, and duration of experience playing badminton were evaluated using a correlation analysis. Moreover, the relationship between agility and lower limb strength was evaluated by partial correlation analysis, adjusting for the effects of experience of each badminton player. [Results] The agility score correlated with hip extension and ankle plantar flexion strength, with adjustment for badminton experience. [Conclusion] This study suggests that hip extension training and improvement in ankle plantar flexion strength may improve agility.

Background Forefoot structure is important to understand some foot problems such as hallux valgus and metatarsalgia. Ultrasonography (US) is a highly portable, noninvasive, low cost, and fast imaging method, especially when compared to magnetic resonance imaging (MRI), computed tomography (CT), and radiography. As the use of US for evaluating forefoot bony structure has not been validated, except for the presence of synovitis, erosions and bursitis within the forefoot in people with inflammatory arthritis, the purpose of this study was to determine whether US is a reliable method for evaluating forefoot structure. Methods Sixty feet (30 women, age = 40.1 ± 11.8 years) were examined by US and CT to assess agreement with CT and repeatability of US evaluation of the 2nd metatarsal head height, length between the medial sesamoid bone and 5th metatarsal head, transverse arch height, transverse arch index, sesamoid rotation angle, and area under the transverse arch. The measurement data were evaluated for agreement with CT using the intra-class correlation coefficient (ICC)3, 1, Pearson correlation coefficient, and Bland-Altman plot, and with ICC1, 1 for repeatability. Results The ICC3, 1 values of 0.78–0.89, Pearson correlation coefficient of 0.78–0.90, and Bland-Altman plots showed almost perfect agreements between the US and CT method for all parameters, except the area under the transverse arch (AUTA). The ICC1, 1 also showed perfect agreements (0.84–0.92) between two sets of US measurements in all parameters. Conclusions The US evaluation of forefoot structure in the coronal plane showed good agreement with CT and repeatability of two ultrasonograms in adult women. This reliable evaluation method of forefoot structure can contribute to a quick clinical assessment screening for risk factors of foot problems such as hallux valgus and metatarsalgia. However, because of some limitations such as a lack of inter-observer reliability, more research is needed to validate US evaluation of forefoot structure. Trial registration The current study (trial registration number: R0297) was approved by the Ethical Committee for Human Experiments of Kyoto University ( http://www.ec.med.kyoto-u.ac.jp ) on December 3, 2015. The first participant in this study was enrolled on November 17, 2015 and retrospectively registered.

Introduction: The differences between Capacitive and Resistive electric transfer (CRet) and hot pack (HP) in their effects on tissue temperature, muscle flexibility, and blood circulation are unknown. This study aimed to clarify the effect of CRet and HP on tissue temperature, muscle flexibility, and blood circulation. Methods: The participants were 13 healthy adults. They randomly performed three 15-minute interventions: (1) CRet, (2) HP, and (3) without powered CRet (sham). The intervention and measurement were applied to the right hamstring muscle. INDIBA® activ ProRecovery HCR902 was used in the CRet trial. The moist heat method was used in the HP trial. The measurement indexes were superficial temperature (ST), 10-mm deep temperature (DT), and 20-mm DT; the passive straight leg raise (SLR) test; and oxygenated (oxy), deoxygenated (deoxy), and total (total) hemoglobin (Hb) concentrations. Each index was measured for 30 minutes after the intervention and the amount of change (Δ) from the pre-intervention value was calculated. Results: ΔST, Δ10 mmDT, Δ20 mmDT, Δoxy-Hb, and Δtotal-Hb were significantly higher in the CRet and HP trials than in the sham trial for 30 minutes after the intervention (p

Objective: Most studies on arch biomechanics focus on the medial longitudinal arch (MLA) and its function; however, there are fewer studies on the forefoot transverse arch (FTA) biomechanics and its function is not well understood. This study aimed at investigating the function of FTA on foot kinetics and kinematics during gait. Methods: Nineteen healthy participants (10 men, 9 women) with a mean age of 25.8 years were recruited. Each measurement was performed with the participants’ dominant foot. For evaluating FTA, transverse arch index (TAI) was measured using ultrasonic diagnostic equipment, which represented the relative height of FTA. Measurements were performed in a two-stance condition: 90% of weight bearing (90% WB), and 10% of weight bearing (10% WB). For evaluating MLA, arch height ratio (AHR) were measured with a ruler. A three-dimensional motion analysis system was used to capture and analyze foot kinetics and kinematics. Participants were instructed to walk barefoot along a 7 m walkway at regular walking pace (110 steps/minute). To examine the function of FTA, spearman’s correlation coefficients were calculated for non-parametric variables (TAI at 10% WB with foot kinetics and kinematics), to examine the relationship between MLA and FTA, (TAI at 10% WB with AHR), to examine flexibility of FTA, (the difference between TAI in 90% and 10% WB with vertical ground reaction force (GRFV)in the terminal stance). Results: A significant positive correlation was observed between TAI and max GRFV in the terminal stance (r=0.50, P=0.03). There was no significant difference between TAI at 10% WB and AHR, A significant negative correlation was observed between the difference in TAI at 90% and 10% WB and, max GRFV in the terminal stance (r=-0.64, P=0.003). Conclusions: The present study showed that GRFV in the terminal stance was positively correlated with the height of FTA, and that flexibility of FTA has relative to GRFV in the terminal stance during gait. It is important to measure flexibility of FTA as well as height of FTA so as to predict the risk of forefoot injury.

Background/PurposeMeasures to prevent the development of muscle mass decline should be initiated from midlife. However, the impact of physical activity at midlife on muscle mass in old age remains uncertain. The aim of this cross-sectional study was to determine whether physical activity at midlife influences muscle mass and physical performance in old age.MethodsA total of 272 Japanese women aged 65 years and older were enrolled in the study. Information about physical activity levels at midlife and in old age were collected using a retrospective questionnaire. We calculated the skeletal muscle mass index in old age and recorded the participants' walking speed and hand grip strength in old age. We then classified the participants into four groups according to their physical activity levels at midlife and in old age and conducted multiple linear regression analysis to determine whether the physical activity levels at midlife and in old age were associated with skeletal muscle mass index and physical performance in old age.ResultsThe participants in the groups that were physically inactive at midlife had a significantly lower skeletal muscle mass index in old age than those who were physically active at midlife (p

Objective The purpose of this study was to examine the relationship between the number of participants partaking in fall prevention-related programs and fall rates in the community. Method A cross-sectional survey was conducted in Sakyo Ward, Kyoto City, Japan as part of the Japan Multi-center Aging Cohort for Care prevention study. Data from 6423 healthy community-dwelling elderly adults living in 20 districts were used to identify the districts with high fall rates. An alternate survey was conducted to collect information on fall prevention-related programs held in each district between April 2010 and March 2011. Using the Mantel-Haenszel chi-square test, we identified districts with high fall rates and compared the number of participants in each fall prevention-related program between districts with high fall rates and other districts using the Mann-Whitney U test and chi-square test. Results The districts determined as “non-high fall rate” had significantly more participants in exercise and education programs than the “high fall rate” districts (p = 0.02). The “non-high fall rate” districts also had more participants than the “high fall rate” districts in public group exercise, private volunteer-led group exercise, and pamphlet distribution; however, this number was not significant. Conclusion Interventions with exercise and educational aspects may be effective in preventing falls at the community level.

CKD is associated with impairments in health status, physical function, and frailty. The aim of the current prospective cohort study was to determine whether CKD predicted new LTCI need certification among community-dwelling older Japanese adults. This was a prospective cohort study. We analyzed the cohort data from a prospective study, The Japan Multicenter Aging Cohort for Care Prevention (J-MACC). We followed 8063 elderly adults for 2 years, and we analyzed the relationship between CKD and LTCI need. The outcome studied was new certification for LTCI service need during a 2-year period. We measured serum creatinine (the estimated glomerular filtration rate; eGFR), serum albumin, frailty checklist scores, and body mass index. During the 2-year follow-up, 536 subjects (6.6%) were newly certified as needing LTCI services. We stratified the cohort according to eGFR quartile and performed multivariate analyses using an eGFR value of 71.4-83.6 ml/min/1.73 m(2) as a reference. We found that subjects with eGFR values

Background In Japan, older adults are assessed by frailty checklist for care prevention. However, the effect of care prevention programs in community-dwelling frail older adults is still unclear. Objectives The purpose of this study was to investigate whether the care prevention program would reduce care and disability and to measure its cost-effectiveness in frail older adults. Design This is a prospective study using propensity score matching. Setting and subjects A total of 610 community-dwelling older adults were recruited in 2 cities of Japan. Intervention Subjects in the exercise group (n = 305) attended physical exercise sessions once a week for 16 consecutive weeks. The exercise sessions were in a standardized format consisting of moderate-intensity aerobic exercise, progressive strength training, flexibility and balance exercises, and cool-down activities. The control group (n = 305) received only screening evaluation. Measurements Primary outcome was long term care insurance requirement certification during the 1-year follow-up period. Secondary outcome measurements were changes of frailty checklist, and care and medical cost. Results Twenty-five subjects (8.1%) in the exercise group and 55 (18%) in the control group were newly certified for long-term care insurance service requirement in 1 year after the intervention (RR = 2.16, 95% CI = 1.46–3.20). Consequently, the health care cost for the subjects in the exercise group was significantly lower than in the control group (P < .001). Moreover, subjects in the exercise group had significant improvements in total scores of the frailty checklist compared with the control group that worsened after 1 year (exercise group: from 7.41 ± 3.98 to 7.11 ± 4.00, control group: from 7.34 ± 4.27 to 8.02 ± 4.81, F = 12.84, P < .001). Conclusion These results suggested that physical exercise is effective in preventing the progression of frailty and further disability in older adults living in the community. We could save heath care costs by our care prevention program.

YM155 monobromide is a novel small-molecule survivin suppressant. The pharmacokinetics, distribution and excretion of YM155/[14C]YM155 were investigated using males and pregnant or lactating female rats after a single intravenous bolus administration. For the 0.1, 0.3 and 1 mg/kg YM155 doses given to male rats, increases in area under the plasma concentration-time curves were approximately proportional to the increase in the dose level. After administering [14C]YM155, radioactivity concentrations in the kidney and liver were highest among the tissues in both male and pregnant rats: e.g. 14.8- and 5.24-fold, respectively, and higher than in plasma at 0.1 h after dosing to male rats. The YM155 concentrations in the brain were lowest: 25-fold lower than in plasma. The transfer of radioactivity into fetuses was low (about 2-fold lower than in plasma). In lactating rats, the radioactivity was transferred into milk at a level 8- to 21-fold higher than for plasma. Radioactivity was primarily excreted in feces (64.0%) and urine (35.2%). The fecal excretion was considered to have occurred mainly by biliary excretion and partly by secretion across the gastrointestinal membrane from the blood to the lumen.

Objective: Sarcopenia, the age-related loss of skeletal muscle mass, is highly prevalent in older adults. The aim of this study was to investigate the effects of the combination of resistance training and multinutrients supplementation (including vitamin D and protein) on muscle mass and physical performance in frail older adults. Methods: This trial was conducted in Japanese frail older adults (n=77), which underwent a standardized protocol of a 3-month physical exercise intervention. The sample population was divided into two groups, according to the adoption (S/Ex: n = 38) or not (Ex: n = 39) of the additional multinutrient supplementation. The outcome measures of interest for the present analyses were the skeletal muscle mass index (SMI) and several physical performance tests. Results: Participants in S/Ex group had significant improvements for the outcome measures, including SMI and maximum walking time (P

Recent studies suggested that pedometer-based walking programs are applicable to older adults. Objectives: The purpose of this study was to evaluate the use of pedometer in sedentary older adults to improve physical activity, fear of falling, physical performance, and leg muscle mass. Design: This was a pilot randomized controlled trial (RCT). Setting and participants: Eighty-seven community dwelling sedentary older adults living in Japan. Intervention: The intervention group (n=43) received a pedometer-based behavioural change program for 6 months, while the control group (n=44) did not. The participants in the intervention group were instructed to increase their mean daily steps by 10% each month. Thus, at the end of 6 months, participants in the intervention group were expected to have 77 % more daily steps than their baseline step counts. Written activity logs were monthly averaged to determine whether the participants were achieving their goal. Measurements: Outcome measures were physical activity, fear of falling, physical performances, and leg muscle mass. Results: In this 6-month trial 40 older adults (93%) completed the pedometer protocol with good adherence. In the intervention group, average daily steps were increased by 83.4% (from 20311323 to 3726 1607) during the study period, but not in the control group (from 20471698 to 22671837). The pedometer-based behavioral change program was more effective to improve their physical activity, fear of falling, locomotive function, and leg muscle mass than control (P

1. YM758 is a novel If channel inhibitor for the treatment of stable angina and atrial fibrillation. The absorption, distribution, and excretion of YM758 have been investigated in albino and non-albino rats after a single oral administration of (14)C-YM758 monophosphate. 2. YM758 was well absorbed from all segments of the gastrointestinal tract except for the stomach. After oral administration, the ratio of AUC(0-1 h) between the plasma concentrations of radioactivity and the unchanged drug was estimated to be 17.7%, which suggests metabolism. 3. The distribution of the radioactivity derived from (14)C-YM758 in tissues was evaluated both in albino and non-albino rats. The radioactivity concentrations in most tissues were higher than those in plasma, which indicates that the radioactivity is well distributed to tissues. Extensive accumulation and slower elimination of radioactivity were noted in the thoracic aorta of albino and non-albino rats as well as in the eyeballs of non-albino rats. The recovery rates of radioactivity in urine and bile after oral dosing to bile duct-cannulated albino rats were 17.8% and 57.3%, respectively. 4. These results suggest that YM758 was extensively absorbed, subjected to metabolism, and excreted mainly into the bile after oral administration to rats, and extensive accumulation of the unchanged drug and/or metabolites into tissues such as the thoracic aorta and eyeballs was observed.

The potent and selective phosphodiesterase 4 inhibitor ASP3258 is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease (COPD). After a single oral administration to rats, ASP3258 is rapidly absorbed with a bioavailability of 106%. In situ absorption data indicated that ASP3258 is mainly absorbed in the small intestine. Tissue distribution data after oral administration of (14)C-ASP3258 showed rapid and extensive distribution to various tissues. Excluding the gastrointestinal tract, the tissues with the highest concentrations were liver, heart and plasma. Liquid chromatography-nuclear magnetic resonance spectroscopy data revealed that O-glucuronidation of the carboxylic acid moiety of ASP3258 (formation of an acyl glucuronide) plays a key role in metabolism. No indication was found that the acyl glucuronide reacted with proteins in plasma or tissues. When (14)C-ASP3258 was orally administered to intact rats, urinary and fecal excretion accounted for 1.3% and 100.6% of the administered radioactivity, respectively. After a single oral administration of (14)C-ASP3258 to bile-cannulated rats, urinary and biliary excretion accounted for 0.7% and 93.8% of the administered radioactivity, respectively. These findings suggest that fecal excretion via bile plays an important role in the elimination of ASP3258-derived radioactivity. In vitro metabolic profiles were relatively similar among the species examined, suggesting that our findings in rats may help us to understand pharmacokinetics, efficacy and safety profiles in humans and other species.

The absorption, distribution, metabolism and excretion of radioactivity were investigated after a single oral administration of 30 mg/kg of 14C-YM992 to rats. 1. Blood and plasma radioactivity levels reached the Cmax at 30 min after administration, and then decreased bi-phasically with terminal half-lives (t1/2) of 7.2 and 5.5 hr, respectively. Plasma unchanged drug levels reached the Cmax 15 min after dosing, and then decreased bi-phasically with a t1/2 of 1.2 hr. The ratios of the unchanged drug to total radioactivity level in the plasma were 1.6% and 4.1% at 5 and 15 min after dosing, respectively, and subsequently decreased to 0.1% at 8 hr after dosing. 2. 14C-YM992 was well absorbed from the duodenum to the colon but not stomach. 3. Radioactivity was distributed quickly into various tissues, showing a peak level within 1 hr after dosing in most tissues. Radioactivity levels (excluding the gastrointestinal tract) at 1 hr after dosing were highest in the liver, followed by the kidney, lung, adrenal, bone marrow, spleen, submandibular gland, and pancreas. Radioactivity disappeared relatively rapidly from most tissues, reflecting a decrease in the plasma concentration. The ratio of the unchanged drug to total radioactivity level in the cerebrum was 62.8% at 15 min after dosing, and subsequently decreased time-dependently to 33.3% at 24 hr after dosing. 4. Within 168 hr after dosing, 61.3% and 37.7% of the dosed radioactivity were excreted in the urine and feces, respectively. In bile-duct cannulated rats, 58.0 % and 39.4% of the dosed radioactivity were excreted within 72 hr in the bile and urine, respectively. At least 70.6% of the radioactivity excreted in bile was reabsorbed. 5. At least 18 peaks of radioactivity were observed in the radio-chromatogram of plasma at 1 hr after dosing, and at least 10 peaks in the radio-chromatograms of urine and bile collected for 6 hr after dosing. Little or trace amount of unchanged drug was observed in these samples. In the radio-chromatogram of cerebrum at 1 hr after dosing, at least 9 peaks of radioactivity were observed, and the main peak corresponded to the unchanged drug.

Smartphones are very common devices in daily life that have a built-in tri-axial accelerometer. Similar to previously developed accelerometers, smartphones can be used to assess gait patterns. However, few gait analyses have been performed using smartphones, and their reliability and validity have not been evaluated yet. The purpose of this study was to evaluate the reliability and validity of a smartphone accelerometer. Thirty healthy young adults participated in this study. They walked 20 m at their preferred speeds, and their trunk accelerations were measured using a smartphone and a tri-axial accelerometer that was secured over the L3 spinous process. We developed a gait analysis application and installed it in the smartphone to measure the acceleration. After signal processing, we calculated the gait parameters of each measurement terminal: peak frequency (PF), root mean square (RMS), autocorrelation peak (AC), and coefficient of variance (CV) of the acceleration peak intervals. Remarkable consistency was observed in the test-retest reliability of all the gait parameter results obtained by the smartphone (p

YM155 monobromide is a novel small-molecule survivin suppressant. The pharmacokinetics, distribution and excretion of YM155/[14C]YM155 were investigated using males and pregnant or lactating female rats after a single intravenous bolus administration. For the 0.1, 0.3 and 1 mg/kg YM155 doses given to male rats, increases in area under the plasma concentration-time curves were approximately proportional to the increase in the dose level. After administering [14C]YM155, radioactivity concentrations in the kidney and liver were highest among the tissues in both male and pregnant rats: e.g. 14.8- and 5.24-fold, respectively, and higher than in plasma at 0.1 h after dosing to male rats. The YM155 concentrations in the brain were lowest: 25-fold lower than in plasma. The transfer of radioactivity into fetuses was low (about 2-fold lower than in plasma). In lactating rats, the radioactivity was transferred into milk at a level 8- to 21-fold higher than for plasma. Radioactivity was primarily excreted in feces (64.0%) and urine (35.2%). The fecal excretion was considered to have occurred mainly by biliary excretion and partly by secretion across the gastrointestinal membrane from the blood to the lumen.

YM466 is a novel factor Xa inhibitor for the treatment of thrombosis. The absorption, distribution, metabolism and excretion of YM466 were investigated in male Fisher rats after a single oral administration. YM466 was absorbed rapidly from all segments of the gastrointestinal tract except the stomach. After oral dosing, the plasma concentration of 14C-YM466 reached a maximum within 0.5h, and declined rapidly with an elimination half-life of 0.64h. The unchanged YM466 accounted for almost all of its radioactivity, suggesting a minimal metabolism in rats. This was also supported by the finding that no metabolites were observed in bile and urine after oral dosing of 14C-YM466. The distribution of 14C-YM466 in tissue was evaluated and the liver and kidney were the organs with radioactivity concentrations consistently higher than that of plasma. Cumulative biliary and urinary excretion of radioactivity in bile duct-cannulated rats was 29.5% and 7.6%, respectively, indicating prominent excretion into bile after oral dosing. This was consistent with the finding that 76.1% and 25.2% of radioactivity dosed were excreted to faeces and urine, respectively, after i.v. dosing. These results suggest that YM466 was rapidly absorbed and then subjected to biliary excretion with a minimal metabolism after oral dosing to rats. Copyright © 2004 John Wiley & Sons, Ltd.

1. Drug disposition of incadronate in the nude rat with bone metastases induced by A375 human melanoma cells was studied after intravenous administration. 2. The pharmacokinetics of incadronate (plasma concentration, urinary excretion and bone uptake) in rat with bone metastases was not markedly different from that in the control rat. This compound, however, was selectively taken up in the bone region around metastatic tumour nests. 3. Drug concentrations in the bone region around tumour nests were 3-10 micrograms/g, these levels being higher than the IC50 (0.35 microgram/ml) for the inhibitory effect of this drug on osteoclasts in vitro. 4. In contrast, concentrations in the tumour nest itself was0.7 microgram/g, being markedly lower than the IC50 (35 micrograms/ml) for the inhibitory effect on the proliferation of tumour cells in vitro. 5. These results strongly suggest that pharmacological action of incadronate in mouse with bone metastases (inhibitory effect on the growth of metastatic tumour in bone) is caused not by the direct action on the tumour cells but by the distribution of the drug in the perifocal bone region followed by inhibition of the activity of osteoclasts, resulting in inhibition of the osteolytic process, which is necessary for the progress of metastatic tumour.