Activities and Challenges of Sports Pharmacist: A Questionnaire Survey.

We conducted a questionnaire survey with sports pharmacists, who engage in anti-doping, to elucidate the activities and challenges they face in their daily work. A total of 218 responses were obtained with the cooperation of the four prefectural pharmacists' associations. We found that 46.8% of respondents had consultations for medication doping concerns once a year or less, while 17.0% reported these multiple times per year. 83.9% of respondents indicated that connections among sports pharmacists would be beneficial, whereas 41.3% had communication with sports pharmacists they were acquainted with. In free text responses, we found challenges experienced were a lack of practical experience, the necessity of increased skills, the lack of cooperation among sports pharmacists and between sports pharmacists and sports organizations, and low awareness of their presence. Regarding future plans, 93.6% indicated an intention to renew certification. 64.2% of respondents were interested in networking events with staff, such as coaches or trainers and 48.6% were interested in regular consultations at training venues. Our findings suggest that in order to expand the anti-doping activities of sports pharmacists, networking opportunities among sports pharmacists and platforms for collaboration with sports organizations should be considered.

Accelerated Return to Play for Professional Rugby Players After Facial Fractures.

BACKGROUND: Facial fractures may result in a significant time away from competition for professional rugby players. An understanding of the return-to-play times is an integral part of clinical decision making when treating professional athletes. A period of 8 to 12 weeks has been conventionally recommended for returning to collision sports after facial fractures. The conventional time to return to sports of 8 to 12 weeks is usually too long for professional players. However, the time of return to play after such facial fractures in elite athletes has not been well described. PURPOSE: To investigate the return to play after facial fractures in professional rugby players with an accelerated rehabilitation protocol. METHODS: Ten professional rugby players with facial fractures were identified and analyzed. The authors investigated the number of days required to return to training and full-contact play according to the trauma type. The authors also determined the presence or absence of refractures and sequelae. RESULTS: The average age of the patients was 26.9 years. Medial orbital wall fractures were the most represented pattern, followed by orbital floor fractures and zygomatic arch fractures. The players returned to jogging after 9.9 days, to sports-specific training after a mean of 10.8 days, and to full-contact training after 18.3 days. There were no cases of refractures and sequelae. CONCLUSION: Players were able to return to their regular rugby activities, earlier than the time commonly allowed to return to full activity.

Headless compression screw fixation of jones fractures: an outcomes study in Japanese athletes.

BACKGROUND: Internal fixation is advocated as the primary treatment for fifth metatarsal Jones fractures in athletes; however, screw insertion site discomfort and refracture can occur especially in competitive athletes. The ideal implant has not been determined. HYPOTHESIS: Headless compression screw fixation of proximal fifth metatarsal Jones fractures is an effective treatment approach especially in competitive athletes. STUDY DESIGN: Case series; Evidence level, 4. METHODS: We studied 60 athletes treated surgically with a headless compression screw for fifth metatarsal Jones fractures (mean age, 19 years). The mean follow-up time was 178 weeks. We evaluated the clinical and radiographic outcomes of headless compression screw fixation of Jones fractures. RESULTS: All athletes returned to full activity. The mean time to start running after surgery was 6.3 weeks (range, 3-12.7 weeks), and the mean time to full activity after surgery was 11.2 weeks (range, 6-25 weeks). One athlete suffered a delayed union, which healed uneventfully. One athlete suffered a nonunion and underwent reoperation for a screw exchange to an autogenous bone graft harvested from the iliac crest. No screw breakage was reported. No athlete suffered a refracture or discomfort in the screw insertion site. CONCLUSION: Headless compression screw fixation of fifth metatarsal Jones fractures provided excellent results, allowing athletes to return to full activity without both screw insertion site irritation and clinical refracture.

Effect of heat- and steam-generating sheet on daily activities of living in patients with osteoarthritis of the knee: randomized prospective study.

BACKGROUND: Thermotherapy is widely known to be effective for osteoarthritis of the knee (knee OA), but most treatment methods make use of dry heat. We developed a sheet that generates heat and steam simultaneously. In this prospective randomized study, we evaluated the effectiveness of this sheet. METHODS: Of 41 female patients with knee OA randomized to use the heat/steam-generating sheet or the dry heat-generating sheet, 37 patients (20 using the heat/steam-generating sheet and 17 using the dry heat-generating sheet) who used the sheets continuously for 4 weeks were studied. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Japan Orthopaedic Association (JOA) scores, which were applied at baseline and after 2 and 4 weeks of use. RESULTS: Significant improvement of the total WOMAC score was observed at 2 and 4 weeks (compared to baseline) in the heat/steam-generating sheet group, but no significant change was observed in the dry heat-generating sheet group. Among the JOA scores, the gait ability score was also improved significantly only in the heat/steam-generating sheet group. The effects were still seen 6 weeks after completion of treatment. CONCLUSIONS: The present study provided evidence that the heat/steam-generating sheet that we developed is effective for alleviating pain and is especially superior in regard to improving stiffness and gait impairment in patients with knee OA. Furthermore, the effect persists for at least 6 weeks after application.

Tumor necrosis factor-alpha inhibits chondrogenic differentiation of synovial fibroblasts through p38 mitogen activating protein kinase pathways.

We previously reported that synovial fibroblast-like cells (SFs) can be differentiated into chondrocytes through activin receptor-like kinase (ALK) 3 activation. The aim of this study was to clarify the effect and signaling pathways of tumor necrosis factor (TNF)-alpha on the chondrogenic differentiation of SFs. Primary SFs from patients with rheumatoid arthritis (RA) were treated with recombinant human bone morphogenetic protein-2 or transduced with a constitutively active mutant of the ALK3 gene (ALK3CA) with or without TNF-alpha, and then cultured in pellets. Expression of chondrocyte-specific genes was analyzed by real-time polymerase chain reaction or by histological analysis. Inhibitors of mitogen-activating protein kinase (MAPK) pathways or adenovirus vectors carrying a dominant-negative mutant of the IkappaB kinase 2 gene (AxIKK2DN) were used to analyze the signaling pathways of TNF-alpha. Expression of chondrocyte-specific genes was induced in SFs either by rhBMP-2 treatment or by ALK3CA transduction, which was strongly suppressed by TNF-alpha treatment. TNF-alpha markedly increased the p38 MAPK pathways in SFs, and inhibition of p38 MAPK activation partially restored the inhibitory effect of TNF-alpha on the chondrogenic differentiation of SFs. Combination therapy BMP-2 and anti-TNF-alpha agents especially targeting p38 MAPK might be a good approach to stimulating neochondrogenesis in the damaged joints in RA.

Tumor necrosis factor-α inhibits chondrogenic differentiation of synovial fibroblasts through p38 mitogen activating protein kinase pathways.

We previously reported that synovial fibroblast-like cells (SFs) can be differentiated into chondrocytes through activin receptor-like kinase (ALK) 3 activation. The aim of this study was to clarify the effect and signaling pathways of tumor necrosis factor (TNF)-α on the chondrogenic differentiation of SFs. Primary SFs from patients with rheumatoid arthritis (RA) were treated with recombinant human bone morphogenetic protein-2 or transduced with a constitutively active mutant of the ALK3 gene (ALK3CA) with or without TNF-α, and then cultured in pellets. Expression of chondrocyte-specific genes was analyzed by real-time polymerase chain reaction or by histological analysis. Inhibitors of mitogen-activating protein kinase (MAPK) pathways or adenovirus vectors carrying a dominant-negative mutant of the IκB kinase 2 gene (AxIKK2DN) were used to analyze the signaling pathways of TNF-α. Expression of chondrocyte-specific genes was induced in SFs either by rhBMP-2 treatment or by ALK3CA transduction, which was strongly suppressed by TNF-α treatment. TNF-α markedly increased the p38 MAPK pathways in SFs, and inhibition of p38 MAPK activation partially restored the inhibitory effect of TNF-α on the chondrogenic differentiation of SFs. Combination therapy BMP-2 and anti-TNF-α agents especially targeting p38 MAPK might be a good approach to stimulating neochondrogenesis in the damaged joints in RA.

Analysis of the risk factors regarding anterior cruciate ligament reconstruction using multiple-looped semitendinosus tendon.

The purpose of this study was to investigate the risk factors regarding anterior cruciate ligament (ACL) reconstruction using autogenous semitendinosus tendon by subjective evaluation of the patients. We studied 63 patients who had been followed for 18 months or longer after surgery. They comprised 31 men and 32 women aged 15-45 (mean, 25.5) years. The patients were divided into two groups by subjective scores. Subjective clinical evaluation was performed using 100 mm visual analogue scale (VAS). In the high score group (group H), the VAS score was 80 mm or higher, and in the low score group (group L), the score was less than 80 mm. Forty three patients were in group H and 20 patients were in group L. The parameters examined were age, gender, sports activity level, preoperative period, complicated meniscus injury, articular cartilage status, graft tendon size, joint stability, and knee extension muscle strength. There were 26 men and 17 women in group H, and 5 men and 15 women in group L. There were significantly more women in group L (p<0.01). The mean preoperative period after injury was 23+/-38 months in group H, and was 52+/-67 months in group L (p<0.05). The average side-to-side differences in anterior laxity were 1.3+/-1.0 mm in group H and 2.2+/-1.6 mm in group L (p<0.01). There were no significant differences in other parameters between the two groups. In this study the risk factors for poor subjective outcome following hamstring ACL surgery was female gender and prolonged delay from injury to operation.

[Relationship between gene transfer and cartilage tissue engineering].

Injury to the articular cartilage occurs under various pathological conditions such as trauma, inflammation and aging and is followed by osteoarthritic changes of the affected joints. Recently, some studies have revealed that enough chondrogenic proliferation was required using some factors such as TGF-beta and BMPs. We, also, have reported that synovial tissues include multipotent mesenchymal stem cells, which can differentiate into chondrocytes. These results suggest that not only are synovial cells a good therapeutic target of inflammatory joint diseases, but also can be utilized for tissue engineering of cartilage.

Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts.

The role of TGF-beta/bone morphogenetic protein signaling in the chondrogenic differentiation of human synovial fibroblasts (SFs) was examined with the adenovirus vector-mediated gene transduction system. Expression of constitutively active activin receptor-like kinase 3 (ALK3CA) induced chondrocyte-specific gene expression in SFs cultured in pellets or in SF pellets transplanted into nude mice, in which both the Smad and p38 pathways are essential. To analyze downstream cascades of ALK3 signaling, we utilized adenovirus vectors carrying either Smad1 to stimulate Smad pathways or constitutively active MKK6 (MKK6CA) to activate p38 pathways. Smad1 expression had a synergistic effect on ALK3CA, while activation of p38 MAP kinase pathways alone by transduction of MKK6CA accelerated terminal chondrocytic differentiation, leading to type X collagen expression and enhanced mineralization. Overexpression of Smad1 prevented MKK6CA-induced type X collagen expression and maintained type II collagen expression. In a mouse model of osteoarthritis, activated p38 expression as well as type X collagen staining was detected in osteochondrophytes and marginal synovial cells. These results suggest that SFs can be differentiated into chondrocytes via ALK3 activation and that stimulating Smad pathways and controlling p38 activation at the proper level can be a good therapeutic strategy for maintaining the healthy joint homeostasis and treating degenerative joint disorders.

Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim.

Osteoclasts (OCs) undergo rapid apoptosis without trophic factors, such as macrophage colony-stimulating factor (M-CSF). Their apoptosis was associated with a rapid and sustained increase in the pro-apoptotic BH3-only Bcl-2 family member Bim. This was caused by the reduced ubiquitylation and proteasomal degradation of Bim that is mediated by c-Cbl. Although the number of OCs was increased in the skeletal tissues of bim-/- mice, the mice exhibited mild osteosclerosis due to reduced bone resorption. OCs differentiated from bone marrow cells of bim-/- animals showed a marked prolongation of survival in the absence of M-CSF, compared with bim+/+ OCs, but the bone-resorbing activity of bim-/- OCs was significantly reduced. Overexpression of a degradation-resistant lysine-free Bim mutant in bim-/- cells abrogated the anti-apoptotic effect of M-CSF, while wild-type Bim did not. These results demonstrate that ubiquitylation-dependent regulation of Bim levels is critical for controlling apoptosis and activation of OCs.

Suppression of arthritic bone destruction by adenovirus-mediated dominant-negative Ras gene transfer to synoviocytes and osteoclasts.

OBJECTIVE: To determine the role of Ras-mediated signaling pathways in synovial cell activation and bone destruction in arthritic joints. METHODS: The E11 rheumatoid synovial cell line and primary synovial fibroblast-like cells (SFCs) from patients with rheumatoid arthritis (RA) were gene-transferred by replication-deficient adenovirus vector carrying the dominant-negative mutant of the ras gene (AxRasDN). The effects of RasDN overexpression on cellular proliferation, interleukin-1 (IL-1)-induced activation of mitogen-activated protein kinases (extracellular signal-regulated kinase [ERK], p38, c-Jun N-terminal kinase [JNK]), and IL-6 production by synovial cells were analyzed. The in vivo effects of Ras inhibition on synovial cell activation and arthritic bone destruction were analyzed by injection of AxRasDN into ankle joints of rats with adjuvant arthritis. RESULTS: AxRasDN markedly reduced the proliferation of RA SFCs. IL-1, a proinflammatory cytokine involved in RA pathology, induced activation of ERK, p38, and JNK in the cells. Adenovirus vector-mediated RasDN overexpression suppressed ERK activation, but not p38 or JNK activation, in SFCs. IL-6 is also an important proinflammatory cytokine, and RasDN inhibited IL-1-induced production of IL-6 by RA SFCs at both the transcriptional and protein levels. Injection of AxRasDN into ankle joints of rats with adjuvant arthritis ameliorated inflammation and suppressed bone destruction in the affected joints. CONCLUSION: Ras-mediated signaling pathways are involved in the activation of RA SFCs and the destruction of bone in arthritic joints, suggesting that inhibition of Ras signaling can be a novel approach for RA treatment that targets both synovial cell activation and bone destruction in the RA joint.