Age-related differences in glenohumeral internal rotation deficit, humeral retrotorsion angle, and posterior shoulder tightness in baseball players.

BACKGROUND: Glenohumeral internal rotation deficit is generally recognized as a risk factor for throwing disability in baseball players. However, the pathology, timing of onset, role in the onset of humeral retrotorsion angle (HTA) and soft tissue extensibility (STE), and the relationship with age remain unclear. Therefore, the purpose of this cross-sectional study was to investigate age-related glenohumeral internal rotation deficit, HTA, and STE in Japanese baseball players and determine whether these factors correlate with throwing disability. METHODS: Participants were 172 male baseball players divided into a symptomatic group (n = 68) and an asymptomatic group (n = 104). The mean age at examination was 15.4 ± 3.2 (range, 8-22) years. Measurement items were range of motion of bilateral internal and external rotation at 90° abduction (2ndIR and 2ndER, respectively), bilateral HTA, and posterior shoulder muscle elasticity. Correlations of age, symptom, and dominance with these measurements were investigated, and significant bilateral differences in HTA and STE by age and symptom were analyzed. RESULTS: HTA and 2ndER of the dominant side were significantly greater than those of the nondominant side in those over the age of 13 years in both the asymptomatic and symptomatic groups. In contrast, 2ndIR of the dominant side was significantly smaller than that of the nondominant side in those over the age of 13 years in both the asymptomatic and symptomatic groups. The difference in HTA between the dominant and nondominant sides increased and then plateaued at 12° after the age of 16 years. STE was observed only in the symptomatic group, and the value of STE was significantly greater in players aged >16 years compared with that in players aged <12 years (P = .001). Muscle elasticity did not differ significantly between sides and showed no correlation with STE. CONCLUSIONS: The difference in HTA between the dominant and nondominant sides increased with age until 16 years old regardless of symptoms. STE in the dominant side was observed only in symptomatic baseball players after the age of 13 years and increased with age, plateauing around the age of 16 years. Posterior shoulder muscle elasticity was not indicated as a cause of STE.

Ankle osteoarthritis and its association with severe ankle injuries, ankle surgeries and health-related quality of life in recently retired professional male football and rugby players: a cross-sectional observational study.

OBJECTIVES: To determine (1) the prevalence of ankle osteoarthritis (OA) among former professional football and rugby players, (2) assess the association between ankle injuries or ankle surgeries with ankle OA, and (3) compare the mental and physical quality of life (QoL) between former professional football and rugby players with and without OA. METHODS: We conducted a questionnaire-based observational study with a cross-sectional design. Former professional football and rugby players were recruited by the Football Players Worldwide and the International Rugby Players. Information concerning ankle OA, sustained ankle injuries and ankle surgeries was gathered (medical record or most recent medical professional). Health-related QoL was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) physical and mental health scores. RESULTS: Overall, 553 former professional football (n=401) and rugby (n=152) players were enrolled in the study (response rate of 56%). Ankle OA prevalence among former professional football and rugby players was 9.2% and 4.6%, respectively. Football players were more likely to suffer from ankle OA following every ankle injury and/or surgery. Football and rugby players with ankle OA had similar PROMIS physical and mental health scores to the norm for the general population. CONCLUSION: Former professional football and rugby players had higher ankle OA prevalence than the general population (3.4%). Football players are more likely to suffer from ankle OA following every ankle injury and/or surgery. No clinically relevant difference was seen for physical or mental health-related QoL among football and rugby players. Preventive measures for ankle injuries are recommended.

Knee osteoarthritis in professional football is related to severe knee injury and knee surgery.

BACKGROUND: As a consequence of severe knee injuries, knee osteoarthritis (OA) seems prevalent in retired professional footballers. However, some epidemiological data remain missing, for instance whether knee OA is also prevalent in current professional footballers, whether knee OA is associated with knee injuries and surgeries, and whether knee OA leads to a lower level of functioning. Therefore, three research questions were answered: (i) what is the prevalence of knee osteoarthritis (OA) among current and retired professional footballers? (ii) is severe knee injury or knee surgery associated with knee OA among current and retired professional footballers? (iii) what are the consequences of knee OA on physical knee function among current and retired professional footballers? METHODS: An observational study based on a cross-sectional design by means of questionnaires was conducted. Participants were current and retired professional footballers recruited by the World Players' Union (FIFPro). Information about severe knee injury and knee OA was gathered (medical record or team doctor), while physical knee function was assessed through a validated scale. RESULTS: A total of 1360 participants (964 current and 396 retired professional footballers) were enrolled in the study (response rate of 54%). Prevalence of knee OA was 13% among current players and 28% among retired players (p < 0.01), being higher among older players. Current and retired professional footballers were nearly twice as likely to suffer from knee OA by every additional severe knee injury and by every additional knee surgery (risk ratio: 1.72-1.96; p < 0.01). Current and retired professional footballers with knee OA reported a lower level of physical knee function than current and retired players without OA (p < 0.01), their physical knee function being also lower than reference values (adult population, young athletic population and amateur footballers). CONCLUSION: The prevalence of knee OA was higher among retired than among current professional footballers and reached up to 40%, leading to negative consequences for their physical knee function. Current and retired professional footballers were nearly twice as likely to suffer from knee OA by every additional severe knee injury and by every additional knee surgery incurred during their career. Management of knee OA should be prioritized among professional footballers, especially to prevent the worsening of the condition during their retirement years.

Osteoarthritis is associated with symptoms of common mental disorders among former elite athletes.

PURPOSE: The primary aim was to establish the association between osteoarthritis (OA) and the occurrence and comorbidity of symptoms of common mental disorders (CMD: distress, anxiety/depression, sleep disturbance, adverse alcohol use) in a group of former elite athletes (rugby, football, ice hockey, Gaelic sports and cricket). A secondary aim was to explore this association in the subgroups of sports. METHODS: Cross-sectional analysis was performed on the baseline questionnaires from five prospective cohort studies conducted between April 2014 and January 2016 in former elite athletes of rugby, football, ice hockey, Gaelic sports and cricket. The presence of OA (diagnosed by a medical professional) was examined with a single question, and symptoms of CMD were evaluated through multiple validated questionnaires (4DSQ, GHQ-12, PROMIS, AUDIT-C). RESULTS: There was a significant association between OA and symptoms of distress (OR 1.7, 95 % CI 1.2-2.6), sleep disturbance (OR 1.6, 95 % CI 1.1-2.3), adverse alcohol use (OR 1.8, 95 % CI 1.2-2.6) and a comorbidity of symptoms of CMD (OR 1.5, 95 % CI 1.0-2.1) in former elite athletes. CONCLUSION: OA might be a risk factor for developing symptoms of CMD in former elite athletes. The clinical relevance of this study is that an interdisciplinary approach to the clinical care and support of former elite athletes after their careers is advocated as the interaction between the physical and mental health issues occurring on the long term is complex. Monitoring OA among former elite athletes should be empowered while strategies to prevent symptoms worsening should be developed and implemented. The self-awareness, prevention and care of mental health problems that might occur after a professional sports career should also be addressed. LEVEL OF EVIDENCE: Level III.

Are Level of Education and Employment Related to Symptoms of Common Mental Disorders in Current and Retired Professional Footballers?

BACKGROUND: Mental disorders have become a topic of increasing interest in research due to their serious consequences for quality of life and functioning. OBJECTIVES: The objective of this study was to explore the relationship of level of education, employment status and working hours with symptoms of common mental disorders (distress, anxiety/depression, sleep disturbance, adverse alcohol behaviour, smoking, adverse nutritional behaviour) among current and retired professional footballers. MATERIALS AND METHODS: Cross-sectional analyses were conducted on baseline questionnaires from an ongoing prospective cohort study among current and retired professional footballers. Based on validated scales, an electronic questionnaire was set up and distributed by players' unions in 11 countries across three continents. RESULTS: A total of 607 current professional footballers (mean age of 27 years) and 219 retired professional footballers (mean age of 35 years) were involved in the study. Among retired professional footballers, statistically significant negative correlations were found between employment status and symptoms of distress and anxiety/depression (P < 0.05), as well as between number of working hours and symptoms of anxiety/depression (P < 0.05). No other statistically significant associations were found among retired players. Among current professional footballers, level of education was not associated with symptoms of common mental disorders. CONCLUSIONS: Among retired professional footballers, employment status as well as a higher number of working hours was weakly correlated to symptoms of distress and anxiety/depression. Combining a football career with sustainable attention for educational and career planning might be important and of high priority.

Prevalence and determinants of symptoms related to mental disorders in retired male professional footballers.

BACKGROUND: The objective of this study was to determine the prevalence of symptoms related to mental disorders (distress, anxiety/depression, sleep disturbance, adverse alcohol behavior, adverse smoking behavior, adverse nutrition behavior) among retired professional footballers, and to explore their associations with stressors, i.e. determinants such as severe injury, surgery, life events and career dissatisfaction. METHODS: Cross-sectional analyses were conducted on baseline questionnaires from an ongoing prospective cohort study among retired male professional footballers. Based on validated questionnaires to assess both stressors and symptoms related to mental disorders, an electronic questionnaire was set up and distributed by players' unions in 11 countries across three continents. RESULTS: Prevalence of symptoms related to mental disorders among 219 retired professional footballers ranged from 11% for adverse smoking behavior and 18% for distress, to 35% for anxiety/depression and 65% for adverse nutrition behavior. Especially life events that occurred in the previous six months was positively associated with distress (OR=1.3; 95% CI: 1.0-1.6), anxiety/depression (OR=1.6; 95% CI: 1.2-2.1), sleeping disturbance (OR=1.3; 95% CI: 1.1-1.7) and adverse nutrition behavior (OR=1.4; 95% CI: 1.0-1.8). CONCLUSIONS: A high prevalence of symptoms related to mental disorders was found among retired professional footballers, confirming a previous study in a similar study population. Relationships were established between symptoms of mental disorders and severe injuries, recently occurred life events, and career dissatisfaction.

Sagittal Alignment of Spine and Spinal Cord for Upper Cervical Irreducible Atlantoaxial Kyphosis in Elderly Patients.

STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate clinical and radiographic outcome of posterior decompression and occipito-cervical/thoracic (OCT) fusion in patients with irreducible atlantoaxial kyphosis (IAK). SUMMARY OF BACKGROUND DATA: Posterior OCT fusion is an effective surgical procedure for treating IAK in the elderly. However, it is unclear whether correction can be obtained by the strong corrective force provided by implants, even in patients in whom reduction cannot be obtained preoperatively. There are no reports of improvement in patients in whom correction could not be achieved by a rigid system. METHODS: Twenty-five patients with IAK with mild vertical subluxation due to rheumatoid arthritis and 3 patients with IAK due to os odontoideum were treated with fossa magnum decompression, C1 laminectomy and OCT fusion. RESULTS: Mean follow-up period was 4.2 years. Preoperative and postoperative neurological findings revealed improvement by 1 or more grades in 18 of 28 (64.2%) patients. The parameters of spinal alignment, sagittal spinal cord alignment, and basilar invagination were evaluated on radiographs. No significant difference between preoperative and postoperative status was seen for the clivo-axial angle, occipito-upper cervical angle, atlantodental interval, or occipito-cervical 2 angle, whereas significant improvement was seen in the cervico-medullary and dorsal CM angles (both P<0.05). No significant postoperative change in the vertical direction was seen for any of the parameters. Width of the spinal cord at the C1 level was significantly increased postoperatively, with a significant expansion of the cerebral spinal fluid space at the same level (P<0.05). CONCLUSIONS: Posterior decompression with fusion for the treatment of IAK in the elderly did not produce significant change in spinal alignment, but did significantly improve spinal cord alignment and local spinal cord compression at the C1 level, achieving satisfactory clinical outcomes.

Are severe musculoskeletal injuries associated with symptoms of common mental disorders among male European professional footballers?

PURPOSE: To explore the associations of severe musculoskeletal injuries (joint and muscles) and surgeries with symptoms of common mental disorders (distress, anxiety/depression, sleeping disturbance, adverse alcohol behaviour , smoking, adverse nutrition behaviour) among male European professional footballers. METHODS: Cross-sectional analyses were conducted on electronic questionnaires completed by professional footballers recruited from the national players' unions of Finland, France, Norway, Spain or Sweden. The number of severe (time loss of more than 28 days) musculoskeletal injuries (total, joint, muscle) and surgeries during a professional football career was examined through four questions, while symptoms of common mental disorders were evaluated through validated scales. RESULTS: A total of 540 professional footballers (mean age of 27 years; 54 % playing in the highest leagues) participated in the study. Sixty-eight per cent of the participants had already incurred one or more severe joint injuries and 60 % one or more severe muscle injuries. Prevalence of symptoms of common mental disorders ranged from 3 % for smoking to 37 % for anxiety/depression and 58 % for adverse nutrition behaviour. The number of severe musculoskeletal injuries during a football career was positively correlated with distress, anxiety and sleeping disturbance, while the number of surgeries was correlated with adverse alcohol behaviour and smoking. Professional footballers who had sustained one or more severe musculoskeletal injuries during their career were two to nearly four times more likely to report symptoms of common mental disorders than professional footballers who had not suffered from severe musculoskeletal injuries. CONCLUSION: It can be concluded that the number of severe musculoskeletal injuries and surgeries during a career is positively correlated and associated with symptoms of common mental disorders among male European professional footballers. This study emphasises the importance of applying a multidisciplinary approach to the clinical care and support of professional footballers, especially when a player faces lengthy periods without training and competition as a consequence of recurrent severe joint or muscle injuries. LEVEL OF EVIDENCE: III.

Peroneal spastic flatfoot in adolescents with accessory talar facet impingement: a preliminary report.

This study analyzed imaging, arthroscopic findings, and treatment responses for peroneal spastic flatfoot (PSFF) caused by talocalcaneal impingement at the accessory anterolateral talar facet (AALTF) (accessory talar facet impingement) in 13 adolescents without histories of trauma and tarsal coalition. The AALTF was determined with computed tomography and MRI. Focal abutting bone marrow edema (FABME) on MRI around the AALTF was confirmed. In seven patients who underwent AALTF resection, subtalar arthroscopy was performed. All experienced alleviation PSFF after treatment; reduction in FABME was observed. AALTF resection alone is beneficial for PSFF caused by accessory talar facet impingement when peroneal spasms are restored by an injection of local anesthesia.

Symptoms of Common Mental Disorders and Adverse Health Behaviours in Male Professional Soccer Players.

To present time, scientific knowledge about symptoms of common mental disorders and adverse health behaviours among professional soccer players is lacking. Consequently, the aim of the study was to determine the prevalence of symptoms of common mental disorders (distress, anxiety/depression, sleep disturbance) and adverse health behaviours (adverse alcohol behaviour, smoking, adverse nutrition behaviour) among professional soccer players, and to explore their associations with potential stressors (severe injury, surgery, life events and career dissatisfaction). Cross-sectional analyses were conducted on baseline questionnaires from an ongoing prospective cohort study among male professional players. Using validated questionnaires to assess symptoms of common mental disorders and adverse health behaviours as well as stressors, an electronic questionnaire was set up and distributed by players' unions in 11 countries from three continents. Prevalence of symptoms of common mental disorders and adverse health behaviours among professional soccer players ranged from 4% for smoking and 9% for adverse alcohol behaviour to 38% for anxiety/depression and 58% for adverse nutrition behaviour. Significant associations were found for a higher number of severe injuries with distress, anxiety/depression, sleeping disturbance and adverse alcohol behaviour, an increased number of life events with distress, sleeping disturbance, adverse alcohol behaviour and smoking, as well as an elevated level of career dissatisfaction with distress, anxiety/depression and adverse nutrition behaviour. Statistically significant correlations (p<0.01) were found for severe injuries and career dissatisfaction with most symptoms of common mental disorders. High prevalence of symptoms of common mental disorders and adverse health behaviours was found among professional players, confirming a previous pilot-study in a similar study population.

Heat stress facilitates the regeneration of injured skeletal muscle in rats.

BACKGROUND: Skeletal muscle stem cells, so-called muscle satellite cells, are responsible for the repair and the regeneration of adult skeletal muscle tissues. Heat stress can facilitate the proliferation and the differentiation of myoblasts in vitro and can enhance their proliferative potential, which may stimulate the regrowth of atrophied skeletal muscle. The purpose of this study was to investigate the effect of heat stress on the regeneration of skeletal muscle injury induced by cardiotoxin. METHODS: Male Wistar rats, aged 7 weeks, were randomly divided into six groups: a nonheated control group that received a physiological saline injection, a group heat stressed before physiological saline injection, a group heat stressed after physiological saline injection, a group injected with cardiotoxin without heat stress, a group heat stressed before cardiotoxin injection, and a group heat stressed after cardiotoxin injection (25 in each group). To initiate muscle injury and regeneration, 0.5 ml of 10 microM cardiotoxin was injected into the left tibialis anterior muscle. Conscious rats in some groups were exposed to environmental heat stress (41 degrees C for 60 min) in a heat chamber 24 h before or immediately after cardiotoxin or physiological saline injection. The heating protocol in the present study causes an increase in the colonic temperature to 41 degrees C. The left tibialis anterior muscles were dissected 1, 3, 7, 14, and 28 days after injection of cardiotoxin or physiological saline. RESULTS: The wet weight and water content of muscles increased 1 day after cardiotoxin injection regardless of the application of heat stress, but normalized after 7-14 days. The muscle protein content in control rats had increased 7 days after heat stress. Although the muscle protein content decreased on cardiotoxin injection, heat stress caused a significant recovery in protein level. Expression of heat shock protein 72 (HSP72) and the number of Pax7-positive nuclei decreased after cardiotoxin injection but increased on the application of heat stress in both normal control and cardiotoxin-injected groups. CONCLUSIONS: Heat stress stimulated not only the proliferation of satellite cells but also protein synthesis during the regeneration of injured skeletal muscle. It is thus strongly suggested that the heating of injured skeletal muscle may facilitate recovery. There was no direct relationship between the level of HSP72 expression and muscle protein content, suggesting that HSP72 expression may not be the key signal for protein synthesis in the necrosis-regeneration process.

Transplantation of myocyte precursors derived from embryonic stem cells transfected with IGFII gene in a mouse model of muscle injury.

BACKGROUND: Reconstruction of skeletal muscle tissue is hampered by the lack of availability of functional substitution of the tissue. METHODS: Embryonic stem (ES) cells were transfected with the insulin-like growth factor (IGF) II gene and were selected with G418. The resultant cell clones were analyzed regarding their myogenic differentiation in vitro and in vivo. RESULTS: The cells expressed early and late myogenic differentiation markers, including myoD, myogenin, and dystrophin in vitro. They had phosphorylated Akt within the cells, suggesting their activation by the secreted IGFII. Transplantation of the cells to injured anterior tibial muscle of mice significantly improved their motor functions compared to injured mice transplanted with undifferentiated ES cells and injured mice given vehicle alone. The transfected cells adapted to the injured muscle, formed myofibers positive for dystrophin and negative for MyoD and myogenin. Trichrome staining and toluidine blue staining support myofiber formation in vivo. The enzymatic activity of acetylcholine esterase suggested the functional activity of the regenerated motor units. The evoked electromyogram of anterior tibial muscle transplanted with the transfected cells showed significantly higher potentials compared to that transplanted with undifferentiated ES cells and that injected with phosphate-buffered saline (control injury). Electron microscopic examination confirmed the myofiber formation in the cells in vivo. CONCLUSIONS: Transfection of IGFII gene into ES cells may be applicable for transplantation therapy of muscle damage due to injury and myopathies.

Introduction of the MASH1 gene into mouse embryonic stem cells leads to differentiation of motoneuron precursors lacking Nogo receptor expression that can be applicable for transplantation to spinal cord injury.

ES cells transfected with the MASH1 gene yielded purified spinal motoneuron precursors expressing HB9 and Islet1. The cells lacked the expression of Nogo receptor that was of great advantage for axon growth after transplantation to an injured spinal cord. After transplantation, mice with the complete transection of spinal cord exhibited excellent improvement of the motor functions. Electrophysiological assessment confirmed the quantitative recovery of motor-evoked potential in the transplanted spinal cord. In the grafted spinal cord, gliosis was inhibited and Nogo receptor expression was scarcely detected. The transplanted cells labeled with GFP showed extensive outgrowth of axons positive for neurofilament middle chain, connected to each other and expressed Synaptophysin, Lim1/2 and Islet1. Thus, the in vivo differentiation into mature spinal motoneurons and the reconstitution of neuronal pathways were suggested. The grafted cell population was purified for neurons and was free from teratoma development. These therapeutic strategies may contribute to a potent treatment for spinal cord injury in future.

Development and reliability of a standard rating system for outcome measurement of foot and ankle disorders I: development of standard rating system.

BACKGROUND: The aim of this study was to report the five scales comprising the rating system that the Japanese Society for Surgery of the Foot (JSSF) devised (JSSF standard rating system) and the newly offered interpretations and criteria for determinations of each assessment item. METHODS: We produced the new scales for the JSSF standard system by modifying the clinical rating systems established by the American Orthopaedic Foot and Ankle Society (AOFAS scales) and the Japanese Orthopaedic Association's foot rating scale (JOA scale). We also provided interpretations of each assessment item and the criteria of determinations in the new standard system. RESULTS: We improved the ambiguous expressions and content in the conventional standard rating systems so they would be easily understood by Japanese people. The result was five scales in total. Four were designed for use specifically for ankle-hindfoot, midfoot, hallux metatarsophalangeal-interphalangeal, and lesser metatarsophalangeal-ineterphalangeal sites; and the fifth was for the foot and ankle with rheumatoid arthritis. Furthermore, we described interpretations and criteria for determinations with regard to evaluation items in each scale. CONCLUSIONS: Conventionally, the AOFAS scales or the JOA scale have been separately applied depending on the sites or disorders concerned, but it was often difficult to decide on scores during practical evaluations because of differing expressions in different languages and also because of ambiguity in the interpretation of each evaluation item and in scoring standards as well. JSSF improved these scales and added definite interpretations of evaluation items as well as criteria for the rating (to be reported here in part I). Because these steps were expected to improve the reliability of outcomes assessed by each scale, we examined the reliability in scores of the newly developed scales, which are reported in part II (in this issue).

Development and reliability of a standard rating system for outcome measurement of foot and ankle disorders II: interclinician and intraclinician reliability and validity of the newly established standard rating scales and Japanese Orthopaedic Association rating scale.

BACKGROUND: This study evaluated the validity and inter- and intraclinician reliability of (1) the Japanese Society of Surgery of the Foot (JSSF) standard rating system for four sites [ankle-hindfoot (AH), midfoot (MF), hallux (HL), and lesser toe (LT)] and the rheumatoid arthritis (RA) foot and ankle scale and (2) the Japanese Orthopaedic Association's foot rating scale (JOA scale). METHODS: Clinicians from the same institute independently evaluated participating patients from their institute by two evaluations at a 1- to 4-week interval. Statistical evaluation was as follows. (1) The intraclass correlation coefficient (ICC) was calculated from data collected from at least two examinations of each patient by at least two evaluating clinicians (Data A). (2) Total scores for the two evaluations were determined from the distribution of differences in data between the two evaluations (Data B); each item was evaluated by determining Cohen's coefficient of agreement. (3) The relation between patient satisfaction and total score was investigated only for patients who underwent surgery (Data C). Spearman's rank correlation coefficient was obtained. RESULTS: Participants were 65 clinicians and 610 patients, including those with disorders of the AH (313), MF (47), HL (153), and LT (50) and those with RA (47). From Data A, the ICC was high for AH and HL by JSSF scales and for AH, MF, and LT by the JOA scale. From Data B, the coefficient showed high validity for both scales for AH, with almost no difference between the two scales; the validity for HL was higher with the JOA scale than with the JSSF scale. From Data C, correlations were significant between patient satisfaction and outcome for AH and HL by the JSSF scales and for AH, HL, and LT by the JOA scale. CONCLUSIONS: The validity of both scales was high. Clinical evaluation of the therapeutic results using these scales would be highly reliable.

Possible role of calcineurin in heating-related increase of rat muscle mass.

The purpose of this study was to investigate the contribution of calcineurin-related intracellular signal for heat-stress-associated muscle hypertrophy. Wistar strain male rats (7-week-old) were randomly divided into four groups: (1) control (CC, n=15), (2) control with the injection of cyclosporine A (CsA) (CA, n=15), (3) heat-stressed (HC, n=15), and (4) heat-stressed with the injection of CsA (HA, n=15). The heat-stress groups (HC and HA) were exposed to heat (41 degrees C for 60 min) in a controlled heat chamber without anesthesia. Soleus and extensor digitorum longus (EDL) muscles were dissected and weighed 1, 7, and 14 days after the exposure. Wet and dry weights of soleus were increased 7 days following heat exposure. The expressions of heat shock protein 72 (HSP72) and calcineurin in both muscles were also increased within 1 and 7 days following heat-stress, respectively. Administration of CsA, a specific inhibitor for calcineurin, depressed heat-stress-associated increase of muscle weight and calcineurin expression, especially in soleus. These observations suggest that a calcineurin-dependent signaling pathway may play an important role in the heat-stress-related skeletal muscular hypertrophy. Application of heat-stress to skeletal muscles may be a useful tool to gain muscular mass and force generation not only in athletes, but also in patients during rehabilitation.

Membrane-associated prostaglandin E synthase-1 is upregulated by proinflammatory cytokines in chondrocytes from patients with osteoarthritis.

Prostaglandin E synthase (PGES) including isoenzymes of membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES (cPGES) is the recently identified terminal enzyme of the arachidonic acid cascade. PGES converts prostaglandin (PG)H2 to PGE2 downstream of cyclooxygenase (COX). We investigated the expression of PGES isoenzyme in articular chondrocytes from patients with osteoarthritis (OA). Chondrocytes were treated with various cytokines and the expression of PGES isoenzyme mRNA was analyzed by the reverse transcription-polymerase chain reaction and Northern blotting, whereas Western blotting was performed for protein expression. The subcellular localization of mPGES-1 was determined by immunofluorescent microscopy. Conversion of arachidonic acid or PGH2 to PGE2 was measured by enzyme-linked immunosorbent assay. Finally, the expression of mPGES-1 protein in OA articular cartilage was assessed by immunohistochemistry. Expression of mPGES-1 mRNA in chondrocytes was significantly induced by interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha, whereas other cytokines, such as IL-4, IL-6, IL-8, IL-10, and interferon-gamma, had no effect. COX-2 was also induced under the same conditions, although its pattern of expression was different. Expression of cPGES, mPGES-2, and COX-1 mRNA was not affected by IL-1beta or TNF-alpha. The subcellular localization of mPGES-1 and COX-2 almost overlapped in the perinuclear region. In comparison with 6-keto-PGF1alpha and thromboxane B2, the production of PGE2 was greater after chondrocytes were stimulated by IL-1beta or TNF-alpha. Conversion of PGH2 to PGE2 (PGES activity) was significantly increased in the lysate from IL-1beta-stimulated chondrocytes and it was inhibited by MK-886, which has an inhibitory effect on mPGES-1 activity. Chondrocytes in articular cartilage from patients with OA showed positive immunostaining for mPGES-1. These results suggest that mPGES-1 might be important in the pathogenesis of OA. It might also be a potential new target for therapeutic strategies that specifically modulate PGE2 synthesis in patients with OA.

Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts.

BACKGROUND: Extracts of Tripterygium wilfordii Hook F (TWHF), a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis (RA). Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolide (a constituent of TWHF) could influence the proliferation of rheumatoid synovial fibroblasts (RSF) by induction of apoptosis. RESULTS: RSF were obtained from RA patients during surgery and were treated with triptolide under various conditions. The viability and proliferation of RSF were measured by the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay and by 5-bromo-2'-deoxyuridine incorporation, respectively. Apoptosis was identified by detection of DNA fragmentation using an enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). The role of caspases in apoptosis of RSF was analyzed by measuring caspase-3 activity. Activation of the peroxisome proliferator-activated receptor (PPAR) gamma was assessed by a luciferase reporter gene assay using RSF transfected with a plasmid containing the peroxisome proliferator response element. Triptolide decreased viability, inhibited proliferation, and induced apoptosis of RSF in a concentration-dependent manner at very low (nM) concentrations. Caspase-3 activity was increased by treatment with triptolide and was suppressed by caspase inhibitors. Although PPARgamma activation was induced by 15-deoxy-Delta12,14-prostaglandin J2, triptolide did not induce it under the same experimental conditions. An extract of TWHF also induced DNA fragmentation in RSF. CONCLUSION: The mechanism of action remains to be studied; however, triptolide may possibly have a disease-modifying effect in patients with RA.