Para-Sports could be categorized as 3 Stages.

Stage 1 = Rehabilitation sports (hospital): check the general and local conditions but also complications following accidents.

Stage 2 = Lifelong sports; check the concomitant symptoms and complications following impairments.

Stage 3 = Competitive sports; check the general and local conditions, especially abilities and performance in para-sports.

Medical Doctor should take care of medical condition, Classification, Anti-Doping Control, Mechanical analysis of performance and devices.

Although Boccia is a type of target sports, factors such as the ingenious form of pitching, ingenuity in handling the ball, tactics, techniques, and the rules make it a very exciting sports that let you think of the different layouts of the ball. Since Boccia is a Paralympic event, it is often percevied as a sport for people with disabilities, however, the essence of Boccia is that anyone including people without handicaps can genuinely enjoy the sport.

In Japan, jurisdiction of para-sports was transferred from the Ministry of Health, Labor and Welfare to the Ministry of Education, Culture, Sports, Science and Technology in 2014 and Japan Sports Agency (JSA) was established in October 2015. In March 2017, the Second Phase Sports Basic Plan based on the Basic Sports Act was formulated as a nation plan for the next five years. Para-sports is well emphasized in the plan. For example, one of the aim of the plan is to increase the sports practice rates for persons with disabilities from 19% to 40% in next 5 years. To achieve this, several approaches are required such as improvement of an environment to easily participate in para-sports in each area, enhancement of sports activities at special support schools and support for sports organizations with disabilities. Based on the current situation, in this lecture, we will introduce the policies and efforts to promote para-sports undertaken by JSA after referring to issues regarding para-sports in Japan.

Individuals with a spinal cord injury (SCI) are thermoregulatory impaired, due to their reduced heat loss capacity, as a result of a loss in sweating capacity and vasomotor control below their lesion level. Previous research has neglected to undertake studies that reflect real-world sporting scenarios for this population group, affecting the translation of these findings into meaningful performance enhancements. Thus, our work aimed to investigate the thermoregulatory responses of athletes with a SCI during real-world sporting scenarios, with particular focus on athletes with tetraplegia. Our work has shown that in indoor playing environments, representing wheelchair court sports, athletes with tetraplegia are under greater thermal strain than athletes with paraplegia and athletes with non-spinal related physical impairments. To reduce thermal strain in able-bodied athletes, cooling strategies have been shown to be effective, but research in this area is limited for athletes with a SCI. Our work demonstrates that a combination of current cooling strategies (pre-cooling using an ice vest and water sprays between quarters) used in wheelchair rugby were found to be effective at reducing thermal strain compared to no cooling or pre-cooling alone. Although neither cooling strategy improved performance. Recommendations for the use of cooling strategies for athletes with an SCI are to take an individualised approach and use in align with the practicalities and regulations of the sport.

The Paralympic Games in China started in the 1950s. In the 1980s, the Chinese Olympic Committee and the International Olympic Committee returned to normal relations. The Paralympic activities became an integral part of China’s sports and the development of disabled persons. The government attaches great importance and on it to promote it’s development. From 1983 to 2008, the Paralympic Games in China entered a stage of competitive development. During this period, the Paralympic movement gradually formed a standardized and scientific management system based on the strategy of giving priority to the development of competitive sports and promoting organizational construction, system construction, and reserve of human resources. Since then, the hosting of the 2008 Beijing Olympic Games has brought unprecedented opportunities for the development of Paralympic Games in China. The development of Paralympic Games in China has entered an all-round development stage. The trajectory of the development of Chinese Paralympic Games began a strategic shift from the priority of competitive sports to the comprehensive development of disabled sports. The main features of this period are the diversified development of sporting forms for persons with disabilities.

The purpose of this study was to investigate characteristics of the anaerobic performance in Japanese amputee soccer players compared with those reported in previous studies. Moreover, this study examined factors related to sprint performance. Subjects were 18 male Japanese amputee soccer players. The 30 m sprint test, countermovement jump (CMJ) test, and the push-up test were used to evaluate anaerobic performance. Assessments of anthropometric characteristics were body height and body weight. All measurements were performed while the participant was not wearing an artificial leg. In addition, the number of years of experience participating in competition and since amputation were investigated. Body height, body weight, and body mass index were 171.9±6.6 cm, 63.2±9.7 kg, and 21.4±3.3, respectively. Average age was 37.7±5.7 years. The number of years of experience participating in competition and since amputation were 4.3±2.4 years and 14.6±8.7 years, respectively. The average time for the 30 m sprint test was 6.66±0.38 seconds. The average CMJ height was 31.0±4.4 cm. The average number of push-ups was 52.3±16.1. There was a significant correlation between the duration of the 30 m sprint and the number of push-ups (r=-0.701, p<0.01). There was also a significant correlation between the duration of the 30 m sprint and the number of years since amputation (r=-0.565, p<0.01). The results of this study suggest the need to improve sprint performance to enhance competitive abilities.

Objective: The aim of this study was to investigate the influence of amputation on match performance in amputee soccer by comparing amputee and non-disabled soccer players.

Methods: We recruited 12 Japanese amputee soccer players and 12 Japanese non-disabled university soccer players in this study. Match performance data were collected across five matches. Total distance and high-intensity running (HIR: ≥13 km・h -1) were collected using global positioning systems technology. Heart rate (HR) was recorded using short-range radio telemetry. In addition, ratings of perceived exertion (RPE) were assessed immediately after the first and second halves of match play using the Borg RPE scale.

Results: The HR response and RPE were significantly different between the amputation group and non-disabled group (p<0.01). The mean HR, mean %HRmax, and RPE were 176.8±7.9 beats・min -1, 96.3±4.6%, and 15.8±1.3, respectively, in the amputation group and 144.4±15.6 beats・min -1, 72.2±7.8%, and 13.4±2.0, respectively, in the non-disabled group.

Conclusion: Results of this study indicate that HR response and RPE are affected by amputation. These findings would indicate that the energy cost of physical activities is higher in the amputation group than in the non-disabled group.

Purpose: The Japanese Orthopaedic Association (JOA) proposed the term Locomotive syndrome (LS) in 2007 to describe a condition in high-risk groups of patients with musculoskeletal disease who are highly likely to require nursing care. Subsequently, numerous studies about LS have been performed. However these studies are only designed for non-handicapped people. Lower amputees are apparently at a high risk for LS due to their physical features. Lower amputees have to be evaluated for LS. We decided to conduct a study on LS in lower amputees, and designed a comparative study with general orhopedic patients.

Methods: We surveyed 47 lower amputees who were treated in a clinic of the Prosthetic and Orthotic Care Center of the Tetsudo Kosaikai Foundation and 1,122 orthopedic patients who were treated in the orthopedic department of Juntendo University Hospital. A questionnaire that included the 25-question Geriatric Locomotive Function Scale (GLFS-25) was distributed to the participants. For the analysis, we recruited 47 amputees (46.3 years) as a lower amputee group (LA-Group) and 512 orthopedic patients (17.6 years) as a general orhopedic patients group (GOP-Group). The participants answered all of the questions on both the GLFS-25 and the Loco-check.

Results: The mean GLFS-25 score in the GOP-Group (17.2 points) was higher than that in the LA-Group (10.4 points) (p=0.049). However, after adjustment for differences in age and the sex ratio of the two groups, the gap closed: GOP-Group (11.3 points) and LA-Group (10.4) (p=0.130). Our study also revealed some of the unique risk factors for LS in lower amputees that were associated with the GLFS-25 score: amputation level (p=0.071), phantom pain (p=0.06), stump wound (p=0.057), frequent use of a wheel chair (p=0.007), exercise habit before amputation (p=0.801), and exercise habit after amputation (p=0.173).

Conclusion: Our results revealed the real risk of LS in lower amputees. The results of this study may be helpful in the treatment and prevention of LS in lower amputees.

In the world of sports, not only game results but the viewpoint of career is significant to the life of an athlete. In the “Sport Basic Plan” that was adopted in 2012, it revealed to the sports instructors and sports organizations that while securing the required environment for athlete life (such as performance and training) as a top athlete, they should enlighten awareness of “Dual Career” , which is educating and giving vocational training necessary for the athlete’s career after retirement as an athletic player to provide for the future, and policy objectives were set out to support career formation for the athletes. In the athlete career transition model by Wylleman and others (2004), it states that the career of a top athlete is analyzed not just from the athletic period, but from the whole life and whole character perspective. It states that not only performance but the influence of a plurality of each elements such as mental development, psychopathic development, academic development and career development, and financial basis develop the athlete’s individual careers.

Studies concerning non-disabled athletes have advanced and many career programs are offered. On the other hand, when it comes to Paralympians, there are often more uncertain points from the initial process of career development. Paralympians possess the equal “independence” as nondisabled persons, and there are actual situations where there are an extremely low number of people who advance to become able to consider the career of both occupation and competition. This research will focus on Paralympians and aim to clarify their individual career consciousness. In this research, a general survey was conducted to investigate the career of Paralympians.

To be more specific, qualitative survey (interview) was conducted to 10 active and retired Paralympian athletes (3 males, 7 women) for the purpose of researching the consciousness towards career in Japanese Paralympians and the obstructive factors upon selecting their career.

3 results were obtained from this interview survey, (1) Social Identity concerning the Paralympic Movement, (2) Aim to combine Sports and Career, and (3) The Importance of Education.

As the development of athletes has been becoming enthusiastic in preparation for the 2020 Tokyo Olympics, the athletes should continue to make use of the unique career techniques that they have achieved during this period and take advantage of it after the Olympic/Paralympic. There is a compelling need of an establishment of a human resources development system that reflects the concept of Olympic Legacy where athletes are required to contribute to society in a long term.

This research clarified the current situation of dual career support for Paralympians from an academic approach. The results of the main investigation using qualitative survey make it possible to clearly articulate and actualize the challenges of the dual career support, and lead to the challenges of the dual career support, and lead to specific measures. The improvement of an environment where Paralympians can concentrate on their competitions and the development of a program where they can seek career support after retirement are essential to sports organizations. Moreover, it is an urgent need to secure a place where beneficial information can be proactively offered and shared to Paralympians so that it can help solve the problems that Paralympians face upon making career decisions.

Introduction: In the twenty-first century, the Olympic Games and the Paralympic Games are held by the same organising committee, and both events are covered simultaneously by the media. Under these conditions, it can be observed that the preparations for the Paralympics are delayed in comparison to those for the Olympics. Furthermore, the medal count of the Paralympic games is much lower than that of the Olympic games. Therefore, the purpose of this study is to illustrate medal standings of the Olympics and the Paralympics and to analyze socio-economic indicators to clarify the characteristics of each participating country.

Methods: The subjects of this study were 47 countries which have received the medals from the Olympic Games or the Paralympic Games. The data was collected from both events since the 2000 summer games and the 2002 winter games. In the analysis, we use some socio-economic indicators such as GDP, GDP per capita, population, political system, health and welfare system, military situation (peace and order situation), national curriculum, etc.

Results and Conclusions: Here, we show a part of the results for the last two games. At the London Games, the number of medals in the Olympic Games was 962, and that of the Paralympic Games was 1,522. The ratio of the medals between the two games was 0.63 (Olympic per Paralympics) and the correlation coefficient was 0.669 (p<0.01) in countries which got medals from both events. Furthermore, at the Rio de Janeiro Games, the number of medals in the Olympic Games was 974, and in the Paralympic Games it was 1,597. The ratio of the medals of both games was 0.60 (Olympic per Paralympics), and the correlation coefficient was 0.552 (p<0.01). Therefore, a correlation is assumed between the Olympics and the Paralympics. At the same time, in many countries, the medal ratio shows a value smaller than 1 and the number of medals of the Paralympic Games is larger than that of the Olympic Games. However, in the case of Japan, the medal ratio at the London Games was 2.375. This was the highest among the OECD member countries. These show that the Japanese situation regarding sport is extremely biased toward the Olympic Games. At the London Games, it can be assumed that the medal ratio of each country has a roughly normal distribution. But the value of the ratio of Japan can be rejected by the Smirnov-Grubbs’ test. On the other hand, at the Rio Games, the medal ratio of Japan improved to 1.70; still, the bias towards the Olympic Games has remained. These facts clearly show the attitude toward the Paralympic Games in Japan.

Background: In the run-up to the 2020 Tokyo Olympic and Paralympic Games, various efforts are being made to raise awareness and interest in sports for the disabled. Enriching the sports curriculum in schools is an important step in promoting sports for the disabled. Furthermore, health/physical education (HPE) teachers also have a vital role to play in this area. This study explores how trainee HPE teachers’ attitudes toward students with special educational needs are affected by whether or not they attended classes on special support education as part of their HPE teacher-training curriculum.

Method: We surveyed 278 third-year university students who aspire to obtain an HPE teacher’s license. We conducted the survey after the students had undergone practical teacher training in their third year. We divided the students into two groups: those who only aspire to obtain an HPE teacher’s license (171 students) and those who additionally aspire to obtain a special needs school teacher’s license (107 students). We then analyzed the difference between the two groups.

Results: The students who additionally aspired to obtain a special needs school teacher’s license were more likely to have been involved in some way with a person with disabilities in the past. The two groups did not differ significantly in terms of specific special needs strategies, although the students who aspired to obtain a special needs license were more likely to show consideration to students with special educational needs during their HPE training, and they also exhibited a better overall understanding of terminology related to special needs education. On the other hand, the two groups did differ significantly in terms of their basic attitudes toward special needs education, with those aspiring to earn a special needs license being more aware of inclusive education and physical education.

Conclusion: Recently, children with various disabilities have been registered not only at special needs schools but also in regular elementary, junior high, and high schools. For this reason, a high level of expertise in special needs is required not only among those who teach in special needs schools, special needs classes, or special support classrooms but also among those who teach in regular classes. HPE is no exception; it is essential that HPE teachers learn about special needs education during their training process. In addition, there is also a need to consider ways in which to configure the teacher-training curriculum so as to ensure that trainee teachers will master not only the necessary knowledge but also specific special-needs strategies.

Background: Deaf football is the football for people with a handicap in hearing. Recently, although the deaf football comes to be spreading in Japan, the medical supports are not enough at all. There are few documents about sports injuries of the deaf football. Therefore there will be a lot of players who play while suffering from any symptoms.

Object: The aim of this case report is to describe the treatment course of a deaf footballer with the bilateral intractable patellar tendinopathy.

Case: The case is a 31 years old man. He is a member of the Japan national team of deaf football. He began deaf football at university student. He continued suffering from a symptom of the patellar tendinopathy since second grade at a high school. He became the first medical examination in our hospital in January 2017. On the first medical examination, he suffered from bilateral patellar tendinopathy. Both sides confirmed severe degenerative changes of the patellar tendon with ultrasonography (Fritschy classification pahse3). We started medical support to him. At first, we introduced physiotherapy as basic treatment to him and his athletic trainer for the improvement of his physical risk factors. With the start of the physiotherapy, we started platelet-rich plasma (PRP) therapy for the purpose of assisting for organization healing process. Both sides gave three times PRP therapy in total every two weeks. Just three months after starting supports, VAS and VISA-P score were improved (VAS: Lt 98 to 48 Rt 88 to 20, VISA-P: Lt 38 to 60 Rt 48 to 80). He participated in DEAFLYMPICS held in Turkey in July 2017.

Discussion: The deaf footballers seem to repeat contact injuries because of behind with noticing the existence of the opponents due to their handicaps of hearing. Besides, they are also forced to do more stop motions and cutting movements suddenly. So we think that their injuries are easy to become chronic. Although we were able to experienced good treatment course for a deaf footballer who suffered from the bilateral intractable patellar tendinopathy by the same treatment approaches as physically non-handicapped athletes in this case, there are any problems on medical supports of deaf football.

We propose that:

① The epidemiological studies about injuries of deaf football are required.

② The deaf footballers are athletes and should be treated like physically non-handicapped athletes.

③ We should provide more informations of the injury and environments of the care for them in Japan.

For the development of disabled sports, we think that it is essential and important to spread deaf football and provide more medical supports.

This study aims to research body compositions for long-term judo practitioners. Exercise habit effects good influence for health condition from many earlier studies’ results. By the way, judo is one of the Olympic sports and Japanese traditional sports. One of the judo’s characteristics is that there are many old-aged players who part in competition. They are considered to possess long-term exercise habits. Therefore, we think that they keep good health condition.

We conduct a survey for long-term judo practitioners body compositions by Inbody430 from Inbody Japan Inc. Subjects are competitors who part in 2017 Veterans Judo Championships held in Wakayama prefecture.

In results, 11 items are surveyed from Inbody430. Survey data was collected from 121 participants aged 30-81 years. Analysis consisted of one-way ANOVA analysis of variance in order to compare body compositions by age group. From ANOVA, judo players’ percent body fat is increasing as age level elevation older.

But, this old-aged players percent body fat is too lower than many similar studies’ results that surveyed old-aged person’s percent body fat. By this reason, long-term judo player may keep good health comdition. And, playing judo for a long time may have good effect of one’s health.

Background: Obesity and associated metabolic disorders are rapidly increased all over the world. However, metabolic syndrome and cardiovascular disease (CVD) are easily developed in Asian adults with normal body mass index (BMI), compared with BMI matched other ethnicities. Thus, slightly increased BMI level (>23 kg/m2) in adults is recognized as a risk for development of metabolic disorders and CVD in Asians. However, to date, it has not been investigated whether small increase in BMI level at young age is also a risk factor for development of metabolic disorders later in life in Asians.

Purpose: To investigate the impacts of BMI at young age on development of metabolic disorders (hypertension, diabetes and dyslipidemia) later in life in Japanese men.

Methods: The study subjects are male alumni who were graduated from Juntendo University from 1971 to 1991. From 2007 to 2011, a self-administered follow-up questionnaire was sent by mail to the subjects to ask their previous medical diagnosis of metabolic disorders, including hypertension, diabetes and dyslipidemia. This study included subjects with both BMI at the time of college and returned follow-up questionnaire were available. Then, we categorized the study subjects into quartile (Q1, Q2, Q3 and Q4) by BMI and compared the incident of metabolic disorder by Cox proportional hazards models.

Results: This study analyzed 636 male alumni and covered 26-year follow-up period (Interquartile Range: IQR: 22-30 years) that included 16,395 person-years of observation. The median BMI at young age of categories were Q1: 20.4 kg/m2 (IQR: 19.7-20.8 kg/m2), Q2: 21.6 kg/m2 (IQR: 21.3-21.8 kg/m2), Q3: 22.5 kg/m2 (IQR: 22.3-22.7 kg/m2) and Q4: 24.0 kg/m2 (IQR: 23.4-25.1 kg/m2). During the period, 194 men had developed more than one metabolic disorder. The prevalence rates of more than one metabolic disorder in Q1 to Q4 were 23.9%, 25.8%, 35.6%, and 36.7%, respectively (p=0.02) and their hazard ratios were 1.00 (reference), 1.21 (IQR: 0.78-1.89), 1.76 (IQR: 1.16-2.67) and 1.82 (IQR: 1.21-2.76), respectively (p=0.001 for trend). This trend was similar after adjustment for age, smoking and participation in college sports club.

Conclusion: Slightly elevated BMI at young age predicted the incidence of metabolic disorders later in life in Japanese men.

Introduction: Accumulating evidence suggests that, independent of physical activity levels, sedentary behaviors (SBs) are associated with increased risk of cardio-metabolic disease, all-cause mortality, and a variety of physiological and psychological problems (Carson et al: Appl Physiol Nutr Metab, 2016; 6 Suppl 3: S240-265). Understanding behavioral context of SBs is required for effective interventions. The purpose of the present study was to compare the domain-specific SBs of adolescents among major metropolitan cities in southeast Asia regions.

Methods: A total of 11,516 youths (aged 12-15 years; 5,540 boys and 5,976 girls) were recruited from eight Asian metropolitan cities, which were Hong Kong, Shanghai, Tokyo, Seoul, Kuala Lumpur, Taipei, Singapore and Bangkok. Time spent per day engaging in each specific sedentary behavior was assessed by self-report questionnaire, respectively; (1) television (TV) viewing, (2) internet or game use, (3) reading, (4) car travel, and (5) homework.

Results: There were significant differences in domain-specific SBs among Asian adolescents (all p<0.001). Youths in Kuala Lumpur spent greatest time in total sedentary behaviors (776.4±187.8 min/day), followed by Singapore (584.6±211.4 min/day), Hong Kong (547.9±218.8 min/day), Taipei (502.1±192.5 min/day), Tokyo (495.3±227.1 min/day), Shanghai (457.7±160.1 min/day), Bangkok (431.4±187.8 min/day), and Seoul (415.2±187.3 min/day). In addition, Kuala Lumpur youths (319.8±100.8 min/day) spent greatest time in screen-based SBs (i.e., TV viewing and internet or game use), followed by Hong Kong (292.1±147.4 min/day) and Tokyo (266.3±153.0 min/day). For non-screen based SBs (i.e., reading, car travel, and homework), youths in Kuala Lumpur also spent greatest time (456.6±133.9 min/day), followed by Singapore (313.4±155.6 min/day) and Shanghai (295.2 ±94.0 min/day).

Conclusions: The present study demonstrated that there were significant differences in domain-specific sedentary behaviors among Asian adolescents. It appears that each country has own strengths and weakness regarding the domain-specific SBs. The findings suggest that country-specific strategies are needed to decrease sedentary behaviors in Asian adolescents.

Objective: The aim of this study was to examine the relationship between locomotive syndrome (LS) and the physical characteristics of Taiwanese elderly people.

Materials and Methods: Seventy-six untrained Taiwanese elderly individuals (31 male; mean age, 70.0±7.1 years) were included in this study. Three functional tests, namely the Stand-Up test, Two-Step, and 25-question Geriatric Locomotive Function Scale, were used to assess the risk of LS. A total of 70 subjects were included in the LS group, while the other six subjects were included in the control (non-LS) group. Body composition (weight, body fat, muscle mass) was determined via bioelectrical impedance analysis using a domestic body composition analyzer. Body mass index and skeletal muscle mass index (SMI) were calculated. The binomial logistic regression analysis was performed with the presence/absence of LS as the dependent variable.

Results: The prevalence of LS was 92.1% (26 male and 44 female) in this study. Body weight, muscle mass, and SMI were significantly lower in the LS group compared with the non-LS group. The body fat percentage in the LS group was significantly higher than that in the non-LS group. Logistic regression analysis showed that muscle mass was significantly related to LS (odds ratio=0.824, p<0.05).

Conclusion: Community-dwelling Taiwanese elderly people who fulfill the diagnostic criteria for LS have lower muscle mass and higher body fat percentage. In particular, the decrease in muscle mass may be an effective indicator of increased risk of LS.

Introduction:Nurses have always been in high demand in Japan due to the advancement of aging society with falling child birthrates and decline of population of people. A growing need for nursing workforce has brought about the increase in male nurses and foreign nurses, and the introduction of entrance examination systems for adults working in society. Hence, nursing teams currently comprise nurses with various backgrounds. In particular, the number of new graduates with previous work experience has increased. With an increment in non- first career nurses, they are attracting attention, and contributing team medical care and the development of nurse organizations based on their diverse experiences. According to self-efficacy theory (Bandura, 1977) 1), self-efficacy and team efficacy are essential to develop closely-knit organization. In this study, we aimed to clarify the influence of previous work experiences on self-efficacy and team efficacy of nurses.

Methods: To clarify the influence of previous work experience on self-/team efficacy from the viewpoint of age, gender, and job position, a self-reported questionnaire was distributed to 784 nurses at 18 hospitals less than 300 beds in 2016. Valid responses were obtained from 417 nurses (valid response rate: 53.2%), 37 of which were head nurses and the others were staff nurses. They were all female nurses. The mean age was 37.89 years old (SD = 9.31). The questionnaire consisted of two sections, the first of which was a face sheet. The second section was designed to assess the degree of self-/team efficacy using the scale developed by Takahashi et al. (2010) based on CEQS scale.

Results and Future study: We hypothesized that staff nurses with previous work experience have high self-efficacy and head nurses with previous work have high team efficacy. However, contrary to our hypothesis, the results did not support this hypothesis (see Figure). In the field of sports research, it was found that high team effectiveness is positively correlated with team performance. However, for nurses with other professional experience, we think that there is a possibility that team performance cannot be fully achieved by high level of individual self-efficacy. In further endeavor, we need to proceed to research on factors enhancing the team's effectiveness consisted of diverse background.

Background: Exercise is known to have beneficial effects on therapy for heart failure (HF). However, the effects of exercise on patients with dilated cardiomyopathy (DCM), one of major causes of progressive HF, have not been established because DCM is associated with high risk of sudden death (SD) at compensated stage and deterioration in HF. Our aim is to examine the impacts of voluntary and forced exercise on cardiac function of DCM using a knock-in mouse model of DCM.

Methods: We used a knock-in mouse model having one of human inherited DCM mutation, TNNT2 Δ210, which decreases Ca2+ sensitivity of myofilaments and show enlarged heart and frequent SD with t1/2 of ~70 days (Du et al: Circ Res, 2007). Homozygous Δ210 mice (below are called DCM mice) in a voluntary exercise (V-Ex) group were housed with a wheel at 1 month of age and daily running distance was recorded. DCM mice in a forced exercise (F-Ex) group underwent a forced treadmill exercise every 1-2 days from 1 month of age. Following each exercise until 2 monthold, cardiac function was assessed by echocardiography and ECG. Heart, lung and lower extremity muscle (soleus, plantaris and gastrocnemius muscles) were excised and their weights were measured together with body weight (BW). Heart failure-related genes (ANP, αMHC, βMHC) were quantified by q-PCR analysis.

Results and Discussion: In case that DCM mice start running exercise before onset of detriorateion in HF, V-Ex significantly prolonged t1/2 of DCM mice, from 77 days to 128 days. At 2 month of age, after each exercise for a month, V-Ex group showed significantly attenuated deterioration of left ventricular systolic function and F-Ex group showed similar tendency. Gene expression of αMHC was consistently higher in F-Ex group. Though the relative soleus muscle weights were significantly greater in V-Ex group than in those of F-Ex group and control (V-Ex: 0.40±0.05 mg/g BW, F-Ex: 0.32±0.05 mg/g BW, control: 0.34±0.05 mg/g BW), the relative gastrocnemius muscle weights of V-Ex group were slightly smaller compared with F-Ex and control groups (V-Ex: 4.83±0.3 mg/g BW, F-Ex: 5.01±0.3 mg/g BW, control: 5.04±0.6 mg/g BW), suggesting the effects of both exercises on whole body may be somewhat different. These results suggest that voluntary and forced exercises are beneficial for cardiac function of DCM mice and would give different means for the future therapy of DCM patients.

Objective: We investigated the relationship between the Kihon Checklist (KCL) as a frailty index and plasma fatty acid levels in elderly patients undergoing cardiac rehabilitation (CR).

Subjects: Two hundred six consecutive elderly patients aged ≥65 years underwent CR (mean age, 75±6 years, 34% female) were enrolled.

Methods: We measured anthropometric parameters and performed a 6-min walk test (6MWT) at the beginning of CR. Patients were divided into frailty (F), pre-frailty (PF) and non-frailty (NF) groups according to KCL score.

Results: The F, PF and F groups comprised 100 patients (39%), 81 patients (32%), and 75 patients (29%) respectively. No significant differences in age were observed among the three groups. Gender, body mass index, lean body weight, skeletal muscle mass, 6MWT, hemoglobin levels, nutritional index, estimated glomerular filtration rate, and eicosapentaenoic acid (EPA/arachidonic acid (AA) ratio were significantly different among the three groups. Hemoglobin level, nutritional index, and EPA/AA ratios were significantly lower in the F and PF groups than in the NF group.

Conclusions: KCL can be used as a frailty index for patients undergoing CR. In addition, EPA/AA ratio may be a marker for assessing frailty.

Research purposes: Estrogen decreased levels in postmenopausal women, cause the body function changes significantly, and the special crowd obese postmenopausal women we should pay more attention. Therefore, this research observed the correlation between physical activity levels and vascular endothelial cell function of obese postmenopausal women. Explore the role of different physical activity intensity for vascular endothelial cell function of obese postmenopausal women.

Subject and Methods: 45-60 years old obese postmenopausal women, natural menopause more than five years, no malignant gynecological disease, no smoking, no cardiovascular disease, without taking antioxidants, involved in this experiment before fully understand the experiment content and experiment process, and signed the informed consent.

Methods: At the beginning, fill in the international physical activity questionnaire and self-made questionnaire; BMI according to 《the overweight and obesity prevention guide of Chinese adults》 BMI >28 kg/m 2 for obesity is divided into three groups, 20 people/group; Blood pressure test using blood pressure meter; FMD (flow mediated dilation), endothelial function test using UNEX EF detector; lipid test by fasting venous blood.

Results: age: Low intensity group (LG) 53±6.5 (years), moderate intensity group (MG) 54±4.2 (years), high intensity group (HG) 52±5.6 (years), height: low intensity group 154.3±4.0 (cm) and moderate intensity group 153.3±3.2 (cm), high intensity group 156.4±4.7 (cm). Weight: low intensity group 73.9±8.8 (kg), moderate intensity group 69.4±6.7 (kg), high intensity group 74.8±7.6 (kg). BMI: low intensity group 31.0±3.4 (kg/cm2) and moderate intensity group 29.5±4.6 (kg/cm2), high intensity group 30.6±3.7 (kg/cm2); Level of physical activity: low intensity group 417.3±156.5 (MET-min/week), moderate intensity group 2,417.3±546.5 (MET-min/week), high intensity group 7,417.3±878.9 (MET-min/week). Endothelial function: low intensity group 7.9±2.8 (%), moderate intensity group strength in the group of 7.8±2.8 (%), high intensity group 8.8±3.5 (%). Age, height, weight, BMI: we had a match between groups, so the groups does not appear significant difference. Correlation of physical activity levels and endothelial function: low intensity and high intensity group (p<0.05), there was no statistical significance between several other groups.

Conclusion: High intensity physical activity can have certain effect in obese postmenopausal women, low and moderate intensity physical activity does not show the obvious effect. So high intensity physical activity has certain effect on endothelial function in obese postmenopausal women, specific mechanism needs further research.

Introduction & Purpose: In the case of an excessive burden imposed on self, a person with vulnerability he/she perceives unprotected against the load. Vulnerability is defined as “a susceptibility to damage to self, a state that may be fragile or hurt.” University athletes may often experience psychological, physical, and social stressors, which may cause vulnerable athletes to exhibit stress responses. Our previous studies of vulnerability among athletes have revealed that women have higher scores than men. Therefore, this study aimed to examine the relationship between vulnerability and depression among Japanese university athletes by gender.

Method: Participants were 363 university athletes (men=193, women=170, mean age=19.0 years, SD=1.07). The Athletic Vulnerability Scale (AVS) and Self-Depression Scale (SDS) were used. We analyzed the relationships between these variables using the Pearson’s product-moment correlation coefficient by gender.

Result & Discussion: The results revealed a significant relationship between the total scores on the AVS and SDS in both men and women (r=0.26 and 0.32 respectively, p<0.01). Additionally, in both men and women, the subscale scores on the AVS and SDS were also significantly correlated (men: r=0.18-0.30, p<0.01 and 0.05, women: r=0.22-0.31, p<0.01).

Conclusion: We concluded that vulnerability and depression are closely associated in both men and women athletes, and its relationship differs by gender.

Objective: This study aimed to examine the effect of stressors and basic needs satisfaction on athlete engagement among Japanese soccer players.

Methods: We collected data from 1,610 Japanese soccer players (1,452 males, 158 females; M age=16.73, SD=2.23) who completed questionnaires including the Athlete Engagement Questionnaire (AEQ), Basic Needs Satisfaction in Sport Scale (BNSSS), and Daily and Competitive Stressor Scale (DCSS). We assessed the effect of the stressors and basic needs satisfaction (independent variable) on athlete engagement (dependent variable) using binomial logistic regression analysis.

Results: The adjusted analysis results indicated that the stressor score of internal and social change in each individual content of club activity and economic condition and academic record were suppressive factors for engagement (confidence: adjusted OR 0.54-0.67; dedication: adjusted OR 0.44-0.61; vigor: adjusted OR 0.46-0.65; Enthusiasm: adjusted OR 0.38-0.56). Furthermore, the basic needs satisfaction score of internal perceived locus of causality and volition were strong promotion factors for engagement (confidence: adjusted OR 3.27-5.68; dedication: adjusted OR 8.08-9.94; vigor: adjusted OR 7.36-9.22; Enthusiasm: adjusted OR 9.44-11.30).

Conclusions: We concluded that stressors and basic needs satisfaction have a considerable influence on athlete engagement. More specifically, there is a possibility that the basic needs satisfaction of internal perceived locus of causality promotes athlete engagement, and the stressors of internal and social change in each individual, content of club activity, and economic condition and academic record suppress athlete engagement.

Purpose: Eye movements are important factors for dynamic visual acuity (DVA) that refers to the ability to perceive fine details of a moving object. When tracking a moving visual stimulus, we often combine smooth eye movements with catch-up saccades. The velocity of saccade eye movements (up to 500-600 deg/s) is much faster than smooth pursuit (usually less than 50 deg/s). Tracking ability using these two kinds of eye movements is thought to play a critical role in DVA and better DVA is associated with an ability of catch-up saccades. However, it is still uncertain whether eye movements and speed perception have directional asymmetry when tracking a moving object. The purpose of this study was to quantitatively clarify the effects of visual target directions on training of DVA and concomitant eye movements. Therefore, we repetitively measured the eye movements during DVA training and attempted to determine the effects of visual target directions on saccade eye movements.

Methods: DVA was evaluated by a moving visual target (Landolt ring) that was projected on the front screen (HI-10; Kowa, Japan). Eye movements were detected using a video based eye tracking system (Eye Link1000; SR research, Canada). We have performed measuring DVA in eight subjects (mean age; 18.7±1.0, age range; 18 to 21 years old) and analyzed saccades eye movements quantitatively using custom analytical software (Matlab; Mathworks Inc., USA). Subjects were seated in front of a screen and put their jaw on a chin supporter of our device to stabilize the head. The subjects were asked to follow the Landolt ring moving across in front of their visual field and judge the direction of the slit. We defined a total of forty trials as one set of training and subjects were given three sets of training every other day. Thus, each subject performed 120 trials in total. We analyzed saccade latency (msec), peak velocity (deg/sec), error (deg) and a correct response rate (%). The Landolt ring moved either from right to left or left to right with constant speed of 300 deg/s.

A total of eight measurements were performed for each subject before and after vision training. We examined whether the visual target directions influence training effect of DVA and eye movements such as saccade latency, peak velocity, error.

Results: Our results demonstrated that saccade latency and error showed significant decreases and the correct response rate increased after training for eight subjects. In contrast, saccade peak velocity showed different results among subjects. There was no tendency in velocity after training. The ability of DVA did not show a statistical difference between the left-right direction and the right-left direction before training. Training effect of latency and error also showed no difference between the directions.

Conclusion: Our study provided several lines of evidence showing that saccade eye movements, such as latency, error and peak velocity changed after vision training. And the effects of vision training on DVA and eye movements were not differ in terms of the target directions. Our results suggest that DVA and eye movements may not be biased towards the target direction.

Introduction: Brain volume measurement is widely applied in many situations. High magnetic field magnetic resonance imaging (MRI) has an advantage in evaluating brain volume due to its high signal-to-noise ratio (SNR). However, many facilities only have low magnetic field MRI. The purpose of this study was to compare local brain volume scanned with 0.3 T MRI to that scanned with 3 T MRI.

Methods: Eighteen healthy volunteers (age 72.3±6.0 years) underwent whole-brain threedimensional (3D) T1-weighted image with 0.3 T clinical MRI system (AIRIS Vento, Hitachi)and 3 T clinical MRI system (Prisma, Siemens). The image of 0.3 T MRI was obtained using a 3D-gradient echo with inversion recovery sequence with the following parameters: TR=25 ms; TE=5.8 ms; IR=600 ms; NEX=1; FOV=200×250×250 mm²; resolution=0.98×2 mm³; total scan time=601 s.

The image of 3 T MRI was obtained using a magnetization prepared rapid gradient echo sequence with the following parameters: TR=2,300 ms; TE=2.32 ms; IR=900 ms; NEX=1; FOV=200×250×250 mm²; resolution=0.9×0.9×0.9 mm³; total scan time=321 s. The MRI data was processed using statistical parametric mapping 12 software implemented in MATLAB. The image was registered between subjects and normalized to Montreal Neurological Institute space. The signal intensity was converted to the volume. The brain was segmented to 116 regions of interest (ROIs) as listed in Automated Anatomical Labeling atlas. The volume of each ROI relative to the intracranial volume was calculated. The correlations between the local brain volume scanned with 0.3 T and that scanned with 3 T were analyzed by Pearson correlation coefficient analysis. The concordance rate of these images was also investigated.

Results: The local brain volume scanned with 0.3 T and that scanned with 3 T correlated very strongly (r=0.939). The concordance rate was higher than 80 percent in 111 out of 116 ROIs. Especially, caudate nucleus (86.98-99.92%, postcentral gyrus (78.39-99.52 %) and amygdala (90.53-99.62%) showed high concordance rates. All five ROIs with a concordance rate lower than 80 percent were in the cerebellum, and the volume of these ROIs were calculated larger in 0.3 T than in 3 T.

Conclusions: Brain volume measurement with 0.3 T MRI showed similar results to that with 3 T MRI except for some segments in the cerebellum.

Introduction: The hypothalamus is a small (approximately 1 cm3) structure important for the autonomic functions, and it contains numerous nuclei that implement different autonomic functions. However, due to its size, the precise functional architecture of the human hypothalamus is not well understood. In the present study, we utilized areal parcellation to discriminate individual nuclei in the human hypothalamus based on areal profiles of resting state functional connectivity by using functional MRI.

Methods: We collected high-resolution functional MRI images (1.25 mm cubic voxel) from twelve healthy human subjects using multi-band EPI (Siemens Skyra 3-T MRI scanner), and parcellated the hypothalamus (Figure-1). Analytical details of areal parcellation are described in Osada et al. (2017) ¹⁾. The parcellation method based on resting-state functional MRI has successfully delineated many functional areas in the cerebral cortex based on the changes in the spatial pattern of functional connectivity in the cerebral cortex when a seed point is moved from one voxel to another ^2)-5). In the present study, we extended such cortical parcellation methods, which have been applied to the 2D cortical surface, to the hypothalamus, a 3D structure, and the centers of parcellated areas in the hypothalamus were detected as hypothalamic foci.

Results: Ten bilateral pairs of foci were detected that were expected to represent hypothalamic nuclei, including the ventromedial hypothalamic nucleus (VMH), the arcuate nucleus (ARC), and the lateral hypothalamic area (LHA). The locations of the detected foci were consistent with those of the hypothalamic nuclei identified in a previous study ⁶⁾, in which hypothalamic nuclei in structural MRI images were validated using histological images. The regions of interest (ROI) analyses revealed contrasting activity changes following glucose ingestion: decrease in the VMH and increase in the LHA in parallel with blood glucose increase (p<0.001, two-way ANOVA, interaction, factor: foci [VMH and LHA]×conditions [glucose and water]). Furthermore, decreased activity in the ARC significantly predicted future increase in blood insulin during the first 10 min after glucose ingestion (p<0.05, t-test)(Figure-2).

Conclusion: The hypothalamic nuclei can be putatively determined by the high-resolution 3D parcellation procedure. The results suggest that the analysis of the human hypothalamus at the nucleus-level can be used to reveal the diverse autonomic functions for future scientific and clinical investigations.

Background: Physical exercise has been considered as an effective non-pharmaceutical measure for the treatment of Alzheimer’s disease (AD). In this report, we described the effect of long-term forced and voluntary exercise on tau protein modification using tauopathy model mice, Tg601.

Methods: 12-month-old non-transgenic and Tg601 mice were subjected to forced and voluntary exercise by means of treadmill (TD) and wheel running (WH), respectively. After 5 months, behavioral analysis was performed by Morris water Maze (MWM) and Y-Maze (YM) test. Tau modification was analyzed by using detergent soluble and insoluble tau fractions from brain homogenate. Neuroinflammation was analyzed by immunohistochemistry (IHC) and the cytokine profile by total cytokine microarray.

Results: The MWM and YM results indicated improvement of cognition only in WH. However, TD-treated mice were unaffected. A marked decrease in sarkosyl insoluble tau, and hyper phosphorylated tau was observed in the WH group. IHC data indicated Iba-1 positive microglia were reduced in WH mice. Cytokine microarray illustrated that IL-1α, IL-1r, IL-9, IL-15r, IFNγ, CRP, ICAM-1, CXCL-12, and TNFα were elevated in TD group, however WH was not altered.

Conclusion: Our findings indicated that voluntary exercise would be beneficial for AD in mice.

Motivation to do sports and physical exercise greatly differs among individuals, with some exercising daily, some once a month, and others not at all. Despite knowing that exercise improves and maintains our health, regular exercise is difficult for people who dislike exercising. It remains unclear why preference for sports and exercise differs among individuals or what innate and environmental factors are involved. To clarify this, we aimed to demonstrate whether physical exercise is rewarding for organisms. We placed four 4-week-old Long-Evans rats in an experimental cage comprising three rooms: one with a wheel (ExR), one is a locked wheel (NoExR), and one in the middle (PreR, connecting ExR and NoExR). Rats could freely move and enter these rooms for 15 min/day. The position of ExR and NoExR was fixed for several weeks. Therefore, rats could learn the association between room position (left or right) and possibility for exercise (ExR or NoExR) over several days (Figure-1 left; 5 days/weeks). To quantify preference for exercise, a conditioned place preference (CPP) test was performed every 4-5 days. In the CPP test, wheels in both rooms were locked to exclude time spent exercise on the wheel. Furthermore, we reversed the association between room position and exercise possibility after animals showed a bias to either ExR or NoExR. Two rats stayed longer in ExR than in NoExR, and they tracked the position of ExR after reversal of room position and possibility for exercise (Figure-1 right). In contrast, the other two rats did not exhibit tracking of possibility for exercise. These results suggest that even among rats, preference for exercise differs among individuals. Subsequently, we aim to elucidate the neuronal mechanisms underlying motivation to exercise and its individual differences. Previous studies have shown that both voluntary and forced exercise induce c-Fos expression as a marker of neuronal activation in the nigrostriatal pathway, including the midbrain dopamine system (containing known reward circuitry). However, considering that the dopamine system is known to be activated not only by reward but also by motor execution per se, it is difficult to dissociate which of these (reward or motor execution) induces c-Fos expression after exercise. To address this problem, we are now developing a new conditioning task to extend the results of this study.

Cardiovascular regulation during sports and physical exercise is controlled by the autonomic nervous system, which exerts sympathoexcitation to increase arterial pressure and support muscle activity. High-intensity exercise is often associated with negative emotions, physical pain, and mental stress. These negative emotions affect the autonomic nervous system. Based on these facts, we considered that vigorous exercise with negative emotions possibly induces “over-activation” of the sympathetic nerves, with subsequent abnormal hemodynamics that may affect exercise performance. Thus, overcoming this negative state could potentially improve performance. Nonetheless, the relationship between neuronal mechanisms underlying negative mental states and cardiovascular regulation determining exercise performance remains unclear. The insular cortex (IC) and amygdala (AMY), parts of the limbic system, are thought to mediate negative effects. We hypothesized that IC and AMY are involved in negative mental states and in maintaining performance by tuning autonomic activities during exhausting exercise. To test this hypothesis, we first examined whether activation of IC and AMY depends on the intensity of treadmill exercise using c-Fos immunostaining. We divided Wistar/ST rats into 3 groups: high-intensity exercise (n=3, 40 m/min for 1 hour on the treadmill), middle-intensity exercise (n=3, 20 m/min for 30 min), or 1 hout (n=3, placed on the treadmill for 30 min). We observed a stronger c-Fos expression in the caudal part of IC (cIC) and the central nucleus of AMY (CeA) in the high-intensity exercise group than in the middle-intensity and sedentary groups. Subsequently, we examined whether exercise-related regions of IC and AMY (cIC and CeA) regulated cardiovascular responses. Interestingly, the microstimulation of cIC and CeA in urethane-anesthetized rats evoked contrasting cardiovascular responses, with decreased arterial pressure (n=6, -5.53 ± 3.43 mmHg, p<0.05) and increased arterial pressure (n=10, 11.3 ± 3.4 mmHg, p<0.01) in response to cIC and CeA stimulation, respectively. Finally, to confirm the anatomical connections between these areas and the nucleus of the solitary tract (nTS; a cardiovascular control center), we microinjected a retrograde tracer (Fluorogold) into nTS (n=12). We observed expression of Fluorogold in cIC and CeA, indicating direct connections between these regions and nTS. These observations suggest that both cIC and CeA are activated during exhausting exercise, but they may have differential roles in cardiac autonomic regulation via their projection to nTS.

Introduction: Endurance training induces a fiber type shift from fast to slow, mitochondria biogenesis, and increased oxidative capacity, which together are known as the skeletal muscle adaptation. To understand how training induces the skeletal muscle adaptation, the study has generally been done an in vivo model because of the lack of an appropriate cell culture model representing these phenomena. Yet the underlying mechanism remains unknown. Therefore, an in vitro training model with skeletal muscle cells is required to elucidate the molecular mechanism of muscle adaptation induced by training. The purpose of this study is to establish a chronic muscle contraction model of cultured myotubes that mimic the in vivo endurance-training-induced adaptation.

Methods: Mouse primary myotubes derived from skeletal muscle satellite cells were used for this study. Mouse extensor digitorum longus was digested in DMEM supplemented with collagenase, and satellite cells were cultured in growth medium including 30% FBS. Satellite-cell-derived myoblasts were differentiated to myotubes by switching the differentiation medium (5% horse serum in DMEM). Three days after differentiation, the myotubes were stimulated with electric pulses at 10 Hz (twitch condition) for different periods (consecutively for 24 h, 72 h, or intermittently for 8 days) or 100 Hz (tetanic condition) for 48 h or 96 h. The myotubes were harvested after stimulation, and the protein expressions of myosin heavy chain (MyHC), MyHC II, hexokinase II, glucose transporter 4, myoglobin, and COX IV were quantified by immunoblotting.

Results: The contraction of cultured primary myotubes persisted for 8 days under the twitch condition without any visible changes. Contrary to expectations, the protein expressions were not changed by twitch contraction for 24 h, 72 h or 8 days. Under tetanic contraction for 48 h and 96 h, the protein expressions were unchanged.

Discussions: We successfully made primary myotubes that endured the twitch condition for 8 days and the tetanic condition for 96 h. However, the protein expressions induced by endurance training were not accompanied by either chronic twitch or tetanic contraction. We suggest two possible reasons that the protein expressions were unchanged after continuous contraction. First, the stimulus conditions adopted in this study were not sufficient to induce a change of protein expression. Second, the protein expression accompanied by endurance training is not only induced by physical contraction but also by other factors such as neurotransmitters and cytokines derived from immune cells.

Protein phosphorylation is one of the most common and well-studied post translational modification in eukaryotic and prokaryotic cells. Among phosphoamino acid, phosphohistidine (pHis) is mainly investigated in microorganisms and plants. However pHis containing proteins existed in vertebrates (especially in mammals), such as histone H4, trimeric G protein β1 chain, potassium-calcium channel KCa3.1, studies on invertebrates were limited. In contrast to acid-stable O-phosphorylation of Ser, Thr and Tyr residues, His residue forms heat and acid-liable phosphoramide bond, which is difficult to identify using conventional low pH reverse phased LC-MS/MS. In addition to its unstable nature, histidine residue has two phosphorylation sites on its imidazole nitrogen atoms (N1, N3), which complicates its analysis.

Recently T. Hunter and his colleagues developed antibodies against each N1-, N3-, specific pHis using stable each pHis analogues (Fuhs et al, 2015). To profile phosphorylation of histidine residue, we concentrated phosphohistidine containing peptides from tryptic digest of C2C12 mouse myoblast cell lysate with anti-pHis antibodies and peptide sequences were determined with Triple TOF 5600 (SCIEX). Candidate of histidine phosphorylated proteins were mainly categorized into actin cytoskeleton signaling, glycolysis and DNA binding protein. To elucidate the roles of histidine phosphorylation, cDNA encoding pHis phosphatase-1 (PHPT-1) which specifically dephosphorylates pHis was transfected into C2C12 cell. Quantitative analysis of immuno-purified peptides were performed with SWATH-MS, a data independent acquisition method, revealed peptides derived from glycolytic enzymes were markedly decreased in PHPT-1 transfected cell. These results raise the possibility that glycolysis would be regulated through histidine phosphorylation.

Objective: There is no convenient parameter for autophagic protein degradation. To ascertain specific marker(s) for autophagy, autophagic degradation products of liver autolysosomes as well as cultured cells were analyzed comprehensively.

Materials: Autolysosomes isolated from rat livers using Percoll density-gradient centrifugation and mouse embryonic fibroblasts (MEFs) in culture.

Methods: i) Autolysosomes were isolated from rat and mouse livers using Percoll-density gradient centrifugation. Lysosome-enriched fraction was separated by differential centrifugation from total lysate of MEFs that were cultured in starvation medium (Krebs-Ringer bicarbonate buffer) for 4 hr. ii) Free amino acids and degradation peptides in autolysosomes were determined using an amino acid analyzer (Hitachi L-8900FF) and a mass spectrometer (AB SCIEX, Triple TOF 5600).

Results: i) Peptides produced via autophagic degradation of some key metabolic enzymes were identified, using proteomic analyses of autolysosomes. These include argininosuccinate synthase and eukaryotic elongation factor 1A. Importantly, they were found excreted to culture media of MEFs. ii) In addition to 20 amino acids that were derived from autophagic degradation, β-alanine was found abundantly present in liver autolysosomes. It was also confirmed that β-alanine content in crude lysosomal fraction accounts for ～30% of total cellular β-alanine in cultured MEFs.

Conclusions: i) Antibodies raised against peptides derived from argininosuccinate synthase and eukaryotic elongation factor 1A can be used to trace autophagic degradation process or degradation markers. ii) Enrichment of β-alanine in autolysosomes suggests a mechanism for β-alanine transport into lysosomes. It is important to clarify the relationship between β-alanine accumulation in autolysosomes and autophagy.

Objective: Type 2 diabetes is characterized by reduced contractile force production and fatigability in skeletal muscle. While maintenance of Ca²⁺ homeostasis during muscle contraction is requisite for optimal contractile function, the mechanisms of muscle contractile dysfunction in type 2 diabetes are still unclear. Here, we hypothesized that muscle contractile dysfunction in type 2 diabetes is associated with impaired Ca²⁺ regulation in skeletal muscle.

Methods (or “Interventions”): To test this hypothesis, skeletal muscle contractile force and Ca²⁺ flux during contraction and pharmacological stimulation of db/db mice, type 2 diabetic model mice were assessed by electrical stimulation and calcium imaging, respectively. Furthermore, we also investigated the effect of exercise training by treadmill on the muscle contractile function.Results: Muscle contractile force and peak Ca²⁺ levels during tetanic stimulation in fast-twitch muscles of db/db mice were decreased and the Ca²⁺ accumulation after the stimulation was increased compared with the control mice. Whereas 6 weeks of exercise training did not improve glucose tolerance, the exercise improved muscle contractile dysfunction, peak Ca²⁺ levels and Ca²⁺ accumulation by stimulation in db/db mice.

Conclusions: These data suggest that dysfunction of Ca²⁺ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and exercise training may be promising therapeutic approach for the skeletal muscle contractile dysfunction.

Objective: The aim of this study was to determine the relationship between the mRNA expression of muscle-specific ubiquitin ligases (E3) and the degree of muscle atrophy in both slow-twitch and fast-twitch muscles, following immobilization.

Methods: Male C57BL/6 mice were subjected to cast immobilization for 0 (Control), 3, 7, 14, and 21 days. Based on the observed trends in the mRNA expression of muscle-specific E3s in our previous study, we analyzed the correlation between muscle mass (the percentage change from the control group per day) and muscle-specific E3 mRNA expression levels in the two types of muscles.

Results: In soleus muscles, MAFbx/Atrogin-1 mRNA levels correlated negatively with muscle mass in the late stage of immobilization (14 and 21 days of immobilization)(r=-0.80, p=0.03). However, this relationship was not observed in the early stage of immobilization (3 and 7 days of immobilization). MuRF1 mRNA expression levels also correlated negatively with muscle mass, but only in the late stage of immobilization (r=-0.82, p=0.02). In the plantaris muscles, these correlations were not found in both the early and late stages of immobilization.

Conclusions: These data suggest that protein degradation resulting from the effects of muscle-specific E3s may not be involved in the early stage of immobilization-induced atrophy in both muscle types, and that other proteolytic pathways are possibly responsible for the atrophy during this period.

Introduction: Skeletal muscle has a large plasticity in response to changes in extracellular stimuli. It has been well known that prolonged periods of muscle disuse due to chronic bed rest or immobilization lead to skeletal muscle atrophy and that the maintenance of muscle mass is one of key factors for Quality of Life (QOL). Recently, it has been reported that high-fat diet-obesity accelerates by 14 days denervation-induced muscle atrophy and protein degradation in mice. Furthermore, we have previously showed that immobilization for 3 day increased muscle RING finger 1 (MuRF1) and atrogin-1/muscle atrophy F-box (MAFbx) in high-fat diet-obesity compared with normal diet (unpublished data). It is notable that the amount of muscle mass decreased a few days after immobilization, but little is known about the acute change in the expression level of atrophy-related ubiquitin ligases (MuRF1 and atrogin-1/MAFbx) before an decrease in muscle mass in obesity mouse skeletal muscle. The purpose of this study was to investigate the short-term effect of immobilization on the expression levels of MuRF1 and atrogin-1/MAFbx in mice fed a high-fat diet.

Methods: This study was approved by the Juntendo University Animal Care Committee (H28- 14). Fourteen male C57BL/6J mice (6 weeks old) were randomly divided into two groups: 1) normal diet (ND, n=7), 2) high-fat diet (HFD, n=7). HFD were fed a high-fat diet (60% calories from fat) for 16 weeks, while ND received a chow diet (10% calories from fat). Following 16 weeks of each experimental diet intake, all mice were lightly anaesthetized with the inhalant isoflurane and attached the casting material. One hindlimb was immobilized (Imm) in the plantar flexion position with casting tape, non-immobilized leg served as an internal control (Con). After 6 h, animals were sacrificed and the soleus and plantaris muscles of both hindlimbs were removed and frozen in liquid nitrogen and stored at -80℃ for real-time RT-PCR. Statistical significance was analyzed by using two-way (diet and treatment) analysis of variance (ANOVA). Statistical significant level was set at p<0.05.

Results: Body weight and epididymal fat pad mass were significantly higher in the HFD compared with ND (p<0.05). The absolute soleus and plantaris muscle weight were significantly higher in the HFD compared with ND. On the other hand, the relative soleus and plantaris muscle weight to body weight were significantly lower in the HFD compared with ND. However, these parameters were not altered during immobilization in HFD and ND. The expression level of atrogin-1/MAFbx mRNA in soleus muscle was significantly lower during immobilization in HFD and ND, whereas there was no alteration in plataris. On the other hand, the expression level of MuRF1 mRNA in soleus and plantaris muscle were no changes during immobilization in HFD and ND.

Conclusion: Short-term immoblization for 6 h did not affect the expression levels of atrophyrelated ubiquitin ligase during immobilization in mice fed a high-fat diet.

This study was supported in part by President’s Grant for Interfaculty Collaboration, Juntendo University (A. Goto), Japan Society for the Promotion of Science Research Activity Start-up Grant number 16H07182 (A. Goto), the Descente Foundation for the Promotion of Sports Science (A. Goto).

Purpose: We recently confirmed that physical inactivity prior to hind limb unloading accelerated disuse-induced skeletal muscle atrophy thorough proteolytic signaling transducers upregulation. However, it is unknown that physical inactivity affects the protein synthesis-related signaling such as mTOR and MAPK pathways in response to muscle contraction. Therefore, the aim of this study was to investigate whether physical inactivity blunts muscle contraction-induced mTOR and MAPK signaling activation in rat skeletal muscle.

Methods: Twelve 4-week-old male Wistar rats were assigned randomly into control (CT, n=6) or physical inactivity (IN, n=6) groups. Rats in the IN group were housed in narrow cages with half of the usual floor space for 10 weeks to limit their range of movement. After 10 weeks, the lateral gastrocnemius muscles of both group rats were electrically stimulated at 100 Hz frequency (pulse duration, 1 ms; duty cycle, 3 s on/6 s off) under anesthesia with isoflurane. The individual stimulation intensity was determined by progressively increasing the stimulus intensity (mA) until there was no further peak twitch force increase. After the stimulation, gastrocnemius muscles were removed and the phosphorylation levels of the mTOR and MAPK signaling pathways were determined by using western blotting.

Results: The phosphorylation levels of Akt at Thr473 and its downstream target S6K1 at Thr389 have significantly increased in the CT and IN groups after NMES in comparison with each control leg. In addition, the phosphorylation of ERK1/2 at Thr202/Tyr204 and its downstream target S6K1 at Thr421/Ser424 have significantly increased in the CT and IN groups after NMES. However, there was no significant difference in these phosphorylation levels between the CT and IN groups.

Conclusion: Physical inactivity has not blunted muscle contraction-induced mTOR and MAPK signaling activation in rat skeletal muscle.

Objective: In response to both endogenous and exogenous stimuli, mammalian mitochondria undergo dynamic structural remodeling via fusion and fission events (mitochondrial dynamics), which support biogenesis, maintain functional integrity, and assist in the removal of dysfunctional organelles. However, whether the responses to high-fat diet change mitochondrial dynamics in both slow- and fast-twitch muscles remains unknown. The purpose of this study was to investigate the effects of a high-fat diet on the expression of mitochondrial fission-related protein Drp1 in both slow- and fast-twitch muscles.

Materials and Methods: Female Sprague-Dawley rats (4-weeks old) were assigned to either a high-fat diet or a sedentary control environment for 8 weeks. After 8 weeks of high-fat diet, the animals were sacrificed, and red and white portions of the gastrocnemius muscle were dissected. These muscles were prepared for western blotting analysis to quantify the protein level of Drp1, which regulates mitochondrial fission.

Results: After 8 weeks of feeding with high-fat diet, there were no changes in the levels of Drp1 in either slow- or fast-twitch muscles.

Conclusions: In conclusion, high-fat diet did not affect the protein level of Drp1 in the slow- or fast-twitch muscles.

Objective: To examine the effects of NADPH oxidase (NOX) and xanthine oxidase (XO) inhibition on the activation of AMPK signaling after exercise in skeletal muscle.

Methods: Adult male C57BL/6J mice were assigned to four weight-matched groups (n=8/group): 1) sedentary control (CON), 2) exercise (Ex), 3) exercise+NOX inhibitor (Ex+Apo), and 4) exercise+XO inhibitor (Ex+Allo). Animals in the Ex, Ex+Apo, and Ex+Allo groups were subjected to running on a treadmill at 15 m/min for 60 min. Animals in the Ex+Apo or Ex+Allo groups were intraperitoneally injected with a NOX inhibitor (apocynin, 20 mg/kg) or XO inhibitor (allopurinol, 20 mg/kg) 30 min before exercise. After exercise, the plasma levels of reactive oxygen metabolites (d-ROMs) were measured as oxidative stress marker, and the phosphorylation levels of AMPKα and ACC in the gastrocnemius muscle were determined by Western blot analysis.

Results: The d-ROMs level was significantly increased in the Ex group compared with the CON group, while the increase in d-ROMs was suppressed by NOX and XO inhibition. In addition, the phosphorylation levels of AMPKα at Thr172 and ACC at Ser79 in the Ex group was significantly increased compared with that in the CON group (p<0.05), whereas the phosphorylation levels in the Ex+Apo and Ex+Allo groups did not increase.

Conclusions: NOX and XO inhibition repressed the expected increase in oxidative stress following exercise and attenuated the activation of AMPK singling after exercise in skeletal muscle.

Background: Few studies have investigated the energy expenditure (EE) of resistance exercises using body weight with slow movement, the purpose of this study was to evaluate EE of resistance exercise using body weight with slow movement.

Methods: Eight young men aged 22-27 years performed 6 resistance exercises. The exercises consisted of Squat, Push-up, Lunge, Heel-raise, Hip-lift and Crunch. Both the concentric phase and eccentric phase were set to 3 seconds (6 seconds with one iteration), and the subjects adjusted the rhythm with the sound of a metronome. A total of 10 repetitions was set as 1 set (1 minute in total), rest between sets was 30 seconds, and a total of 3 sets were performed. After the end of the third set, the subject rested for 30 seconds, and carried out the next event, total time was 26 mins 30 seconds. For measurement of energy expenditure (EE), heart rate (HR), RPE and lactate (La) during resistance exercise, we used a face mask and expiratory gas analyzer, EE was calculated from Weir equation.

Result: Figure-1 shows mean EE while the subjects performed resistance exercise. With regard to the type of resistance exercise, EE of Squat, Push-up and Lunge, which is the multi-joint nature of the exercises and therefore the stimulation of large and multiple muscles, were higher than the other three exercises. Physiological responses were as follows, EE; 92.6±16.0 kcal, RER; 0.98±0.03, HR; 98.8±14.0 bpm, RPE; 13.5±2.3, La; 3.3±1.0 mM.

Conclusion: The EE observed in this study for resistance exercise using body weight with slow movement was 92.6±16.0 kcal/min in average.

Introduction: It is known that the increased intramyocellular lipid (IMCL) levels observed in obese subjects are closely associated with Insulin resistance in skeletal muscle. Interestingly, some reports suggested low intensity exercise (LIE) decreased IMCL and improved insulin resistance. On the other hand, a few reports showed vigorous intensity exercise (VIE) improved insulin resistance, although increased IMCL level. However, it is unknown whether exercises intensity is reflect to lipid alterations and insulin sensitivity (IS). The aim of this study was to clarify role of exercise intensity on changes in lipid composition and insulin resistance in skeletal muscle.

Methods: We recruited 20 Japanese men with moderate insulin resistance (HOMA-R > or=1.6). Subjects were randomly assigned to LIE (40% VO2 peak) group or VIE (70% VO2 peak) group. Each group performed LIE or VIE with ergometer for 5 consecutive days. Target energy expenditure of exercise was set at 300 kcal/day. Before and 3-day after completion of each exercise protocol, insulin resistance was evaluated by hyperinsulinemic euglycemic clamp and IMCL was measured by 1H-MRS. In addition, IMCL was also evaluated immediately after the exercise at day 5. Lipidomics in skeletal muscle were measured by hyperinsulinemic-euglycemic clamp and liquid chromatographymass spectrometry, respectively.

Results: As a result of exercise, IRI decreased in LIE group and body fat percentage and HDL-C decreased in VIE group (Table-1). Both exercise protocol similarly improved insulin resistance by ～20%. In both group, IMCL level was slightly decreased by 10～20% immediately after exercise at day 5. Although IMCL level was recovered to baseline value at 3-day after last bout of exercise in LIE group, IMCL level in VIE group increased twofold from baseline. When lipid composition change was compared before exercises and 3 days after exercise, in phosphatidylcholine (C32: 0, C36: 3), phosphatidylethanolamine (C36: 1, C36: 3) and lysophosphatidylethanolamine (C18: 1), it increased by 20% or more in LIE, although little change in VIE.

Conclusions: Exercise effects on insulin sensitivity and lipid composition in muscle vary with intensity.

Background: Ballistic training with projectile motions has proven to be more effective in improving power compared to the conventional resistance training without projectile motions. This is based on the fact that projectile motions minimize the deceleration of lifting required near the end of each concentric phase for the phase transition, allowing the trainees to exert greater velocity and power output. Recently, hyperventilation-induced respiratory alkalosis has been shown to attenuate performance decrement during repeated high power tasks, such as intermittent short pedaling sprints and heavy-loaded resistance training, via accelerated recovery from severe lactic acidosis. The resulting enhancement of power output during training with the aid of hyperventilation, particularly after fatigue, may increase the effectiveness of power training by incurring greater adaptive stimuli. However, the influence of hyperventilation on lifting velocity during repeated maximum ballistic training has not been studied to date.

Methods: Nine power-trained athletes (two females and seven males) performed maximum bench press throws and squat jumps at 40% 1 RM (12 reps×5 sets for both exercises) with (HV) and without hyperventilation (CON). Their 1 RM values were as follows: bench press=50.0～52.5 kg for females and 110.0～155.0 for males, squat=75.0～87.5 kg for females and 152.5～200.0 kg for males. The durations of inter-set recovery for bench press throws and squat jumps were respectively 3-min and 5-min. For the CON condition, each exercise set was preceded by spontaneous breathing. For the HV condition, subjects hyperventilated (V_E: 117～120 l/min, resp. rate: 53～56 breaths/min, TV_E : 2,212～2,250 ml) during the last 30-s of inter-set recovery before the 3rd, 4th and 5th sets to render P_ETCO₂ between 15～25 mmHg. Wireless electro-goniometers were attached about the elbow and the knee joints to calculate the peak and mean concentric joint angular velocities per repetition (V_peak and Vmean, respectively). Blood [La^-], pH and PCO₂ were examined to report physiological strains of the exercises, and to verify pH recovery and CO₂ excretion resulting from HV.

Results: HV intervention increased blood pH by 0.006～0.078 (p≤0.005) and lowered PCO₂ by 5.6～8.8 mmHg (p≤0.001). For bench press throws, the declines in V_peak and V_mean were similar between the two breathing conditions. For squat jumps, HV showed no effect on V_peak. The decline of V_mean with reps was, however, smaller for the HV condition. After the exercise, the blood [La^-] was greater (9.46±2.43 vs. 5.54±1.54 mM, p<0.001) and pH was lower (7.280±0.061 vs. 7.372±0.059, p<0.001) for squat jumps than bench press throws. The increase in blood [La^-] was not interacted by the breathing conditions.

Conclusion: Hyperventilation-induced alkalosis did not enhance peak and mean concentric velocities during repeated bench press throws, but demonstrated small ergogenic effects on the mean concentric velocity during squat jumps, which imposed greater physiological strains than bench press throws. Enhanced glycolytic energy supply, expected from implementing hyperventilation, was not evidenced from the blood [La^-] results.

Endogenous insulin secretion is suppressed during hyperinsulinemic euglycemic clamp, which is known as a feedback inhibition of insulin secretion (FI-IS) by insulin. Since FI-IS is impaired in obese subjects, inadequate FI-IS may partly contribute to enhanced insulin secretion seen in obesity with insulin resistance. However, significance of FI-IS in non-obese healthy subjects is unknown. To clarify the significance, we studied 49 non-obese healthy Japanese men. We evaluated steady state serum C-peptide (SSSC) and muscle insulin sensitivity (MIS) by hyperinsulinemic euglycemic clamp with tracer (insulin infusion rate = 20 mU/m² per min). We also measured intrahepatic lipid (IHL) by ¹H-MRS. Based on the median of SSSC, we divided the subjects into low FI-IS group and high FI-IS group and compared clinical parameters. While fasting C-peptide level was comparable between the groups, the SSSC was suppressed by 50% from baseline in the high FI-IS group (1.14±0.39 to 0.57±0.24 ng/ml, p<0.001), but less suppressed in the low FI-IS group (1.34±0.34 to 1.19±0.24 ng/ml, p=0.054). Although most of metabolic parameters such as fasting glucose, lipid levels and visceral fat volume were comparable between the groups, low FI-IS group showed IHL accumulation (3.0±4.2 vs. 0.6±0.2%, p=0.04) and impaired MIS (0.19±0.04 vs. 0.28±0.08 mg/kg FFM・min^-1・μU^-1・ml, p<0.001), compared with high FI-IS group. Consistently, we observed elevated AUC of insulin during 75 g-OGTT in low FI-IS group (6.6±3.0 vs. 3.9±2.0 μU・min/ml・10³, p=0.001), while AUC of glucose was comparable. In conclusion, even in healthy non-obese men, subjects with inadequate FI-IS were existed and those were characterized by impaired MIS and hyperinsulinemia during OGTT. These data suggested that impaired FI-IS may be early change to maintain metabolic status through enhancing insulin secretion in the face of moderate muscle insulin resistance in healthy non-obese men.

　It has been reported that 1-wk overfeeding impairs insulin sensitivity and elevates insulin level, and the latter is partly induced by impaired metabolic clearance rate of insulin (MCRI). Thus, MCRI is considered as a regulatory factor to maintain euglycemia during short term dietary change. However, the effect of low-carbohydrate/high-fat (LCHF) diet on MCRI has not been elucidated.

　To clarify the effect of 3-day LCHF diet, we studied 48 non-obese healthy men (BMI; 22.6±2.5 kg/m²). Each subject consumed a 3-day control diet, which was followed by a 3-day eucaloric LCHF diet (20% carbohydrate, 20% protein, 60% fat). After the completion of both diet protocols, we performed hyperinsulinemic euglycemic clamp (insulin infusion rate (IIR) =100 mU/m² per min) to evaluate glucose infusion rate (GIR) and MCRI, calculated as a ratio of IIR to steady state serum insulin (SS_SI). The 3-day LCHF diet increased MCRI (497.4±1.4 ml/min per m² to 540.1±85.0 ml/min per m², p<0.05); however, the individual changes were highly variable. To further investigate the role of MCRI, we divided the subject into high-responder (HR) and low-responder (LR) based on the median %change of MCRI by LCHF diet. At baseline, HR group showed higher GIR level compared with LR group (13.0±1.9 vs. 11.8±2.0 mg/kg FFM per min, p<0.05), while MCRI and SS_SI levels were comparable. After LCHF diet, MCRI was increased (481.9±58.8 to 582.5±90.8 ml/min per m², p<0.001) and SSSI was decreased (210.2±23.3 μU/ml to 175.1±23.5 μU/ml, p<0.001) in HR group, but those were not altered in LR group. In parallel with decreased SS_SI, GIR was decreased in HR group (from 13.0±1.9 to 11.7±2.4 mg/kg FFM per min, p=0.003) after LCHF diet, but not in LR group.

　In conclusion, MCRI was increased after 3-day LCHF diet; however, the effect was highly variable. The decreased GIR after LCHF diet in HR group may be partly due to decreased SSSI and contribute to maintain euglycemia during low-carbohydrate availability in insulin sensitive subjects.

Introduction: The onset of type 2 diabetes is influenced by genetic background. However, it is not well defined. The mitochondrial derived peptide mitochondrial open-reading-frame of the twelve s rRNA-c (MOTS-c) which comprises 16 amino acid residues, have been showed that it enhances muscular insulin sensitivity in mice. We have more recently reported that East Asian specific m.1382 A>C polymorphism accompanies amino acid replacement from Lys (K) to Gln (Q) at the 14th aminoacid residue of the MOTS-c (Fuku et al., Aging Cell, 2015). However, the relation between m.1382 A>C polymorphism and type 2 diabetes remain unknown. Therefore, we hypothesized that amino acid replacement (K14Q) of the MOTS-c by m.1382 A>C polymorphism affects the onset of type 2 diabetes because of changing insulin sensitivity on the skeletal muscle and/or liver in East Asian populations.

Aim: This study was conducted to clarify the relation between type 2 diabetes and m.1382 A>C polymorphism [MOTS-c (K14Q)] in Japanese individuals and to investigate the effect of MOTS-c amino acid replacement (K14Q) on glucose metabolism.

　Epidemiological study (Prevalence of type 2 diabetes in m.1382 A>C genotype of Japanese): This study examined 12,068 community-dwelling Japanese individuals (5,078 men and 6,990 women; aged 40-69 years). m.1382 A>C genotype was determined using Luminex methods. Physical activity of participants was measured using an accelerometer. Results showed that type 2 diabetes in men (11.0%) was more prevalent than women (4.6%). Because moderate to vigorous intensity physical activity (MVPA) alters type 2 diabetes in men, we combined analyses MVPA and m.1382 A>C genotype. In the lowest tertile of MVPA, subjects with C allele had a significantly higher prevalence of type 2 diabetes than those with A allele in men (C allele, 18%; A allele, 11%; P=0.02).

　Animal study (Effect of MOTS-c [K/Q14] on glucose tolerance test in mice): Eight-week old male CD1 mice were used for this experiment. We used two synthetic MOTS-c peptides: K14 (wild type) and Q14 (mutant type). For glucose tolerance tests, mice were treated with MOTS-c [K14] (0.5 mg/kg/day; IP), MOTS-c [Q14] (0.5 mg/kg/day; IP), or vehicle (equal volume; IP), daily for 21 days. Then mice were injected with D-glucose (1 g/kg; IP). Blood was sampled from the tail at 0, 15, 30, 45, 60, 90, and 120 min post-glucose injection. Glucose tolerance tests showed that MOTS-c [Q14] worse glucose clearance compared to MOTS-c [K14] (P=0.01).

Conclusion: Epidemiological study have revealed that m.1382 A>C polymorphism is associated with type 2 diabetes with lower MVPA in men. An animal model showed that MOTS-c amino acid replacement (K14Q) affects glucose tolerance in male mice. Taken together, these results suggest that MOTS-c amino acid replacement (K14Q) by m.1382 A>C polymorphism may influence prevalence of type 2 diabetes in human.

In this study, to evaluate cartilage and bone metabolism in athletes, the levels of type II collagen degradation marker CTX-II and synthesis marker CPII, and type I collagen degradation marker NTx were measured using urine samples of collegiate athletes belonging to various sports clubs (soccer, tennis, triathlon, squash, swimming, volleyball, kendo, judo, gymnastics, basketball, handball, baseball, long-distance, throwing-event, jumping, sprint and futsal) and compared with those of non-athlete controls (5～11 subjects in each group).

NTx levels were significantly increased in soccer, volleyball, basketball and handball players compared with non-athletes. Similarly, CTX-II levels were significantly increased in soccer, volleyball and handball players compared with non-athletes. In contrast, CPII levels were significantly increased in squash players and long-distance runners compared with non-athletes. Moreover, CTX-II/CPII ratios were increased in soccer, volleyball, basketball and handball players compared with non-athlete control, suggesting that type II collagen degradation is relatively increased compared with type II collagen synthesis in these players. Together these observations indicate that cartilage and bone metabolism (type II and type I collagen degradation) is enhanced in players of ball games associated with jumping action, such as soccer, volleyball, basketball and handball.

Cartilage and bone metabolism (type II collagen degradation) is increased by endurance exercise with intense joint loading. Interestingly, glucosamine-containing diet exhibits a chondroprotective action on osteoarthritis by inhibiting type II collagen degradation and improves the symptoms. Thus, in the present study, we evaluated the effect of glucosamine on cartilage metabolism in collegiate soccer players and professional rugby players with intense joint loading.

In soccer and rugby players, the urine level of type II collagen degradation maker CTX-II was significantly increased compared with non-athlete control, indicating that cartilage metabolism (type II collagen degradation) is increased in these athletes. In contrast, the urine level of type II collagen synthesis maker CPII was almost the same as in non-athletes. Based on these findings, the CTX-II/CPII ratios were higher in soccer and rugby players than non-athletes, suggesting that type II collagen degradation is relatively increased compared with type II collagen synthesis in these athletes. Importantly, the administration of glucosamine significantly decreased the CTX-II levels in soccer and rugby players; however, the CTX-II level returned to almost the pre-administration level after withdrawal of glucosamine administration. In contrast, the CPII level was not essentially changed during the test period. Based on these findings, the CTX-II/CPII ratios were reduced by glucosamine administration, and returned to the pre-administration level after withdrawal of glucosamine.

Together these observations suggest that glucosamine exhibits a chondroprotective action on endurance athletes, such as soccer and rugby players by preventing type II collagen degradation but maintaining type II collagen synthesis. However, the effect is transient and disappears after withdrawal of the administration.

Objective: We previously revealed that both the magnetic resonance imaging (MRI)-detected subchondral bone changes and synovial transforming growth factor (TGF)-β expression were associated with histological synovitis in end-stage knee osteoarthritis (OA) patients. However, it was unclear whether or not TGF-β signaling was activated in synovium and what OA-structural changes were associated with the activation of TGF-β signaling in the synovium in patients with end-stage knee OA.

Methods: Forty end-stage knee OA patients (female: 88%, mean age: 71.8 years, K/L grade 4) were enrolled. All participants underwent 3.0-Tesla MRI. The OA-structural changes were scored using the whole-organ MRI scoring (WORMS) method. Synovial samples were obtained from five regions of interest of the knee joint during total joint replacement surgery. The associations between WORMS and the synovial expression of TGF-β or phosphorylated (p)-Smad2/Smad2, which were semiquantitatively evaluated by immunohistochemistry, were examined.

Results: A multiple regression analysis revealed that among the MRI-detected OA changes, the subchondral bone attrition (SBA) and subchondral bone cyst (SBC) were associated with the synovial TGF-β expression (β=0.47, p<0.01) and pSmad2/Smad2 expression (β=0.42, p=0.02), respectively, in the synovium of end-stage knee OA patients. The subchondral bone changes, in which SBA and SBC were combined but bone marrow lesions were not, were associated with both the TGF-β (β=0.52, p<0.01) and the pSmad2/Smad2 (β=0.41, p=0.02) in synovium of end-stage knee OA patients.

Conclusion: TGF-β signaling is activated in the synovium and is associated with the subchondral bone changes in patients with end-stage knee OA.