Febuxostat treatment attenuates oxidative stress and inflammation due to ischemia-reperfusion injury through the necrotic pathway in skin flap of animal model.

BACKGROUND: Ischemia-reperfusion (I/R) injury is a major contributor to skin flap necrosis, which is a serious complication of reconstructive surgery. The purpose of this study was to evaluate the protective effect of treatment with febuxostat, a selective xanthine oxidase inhibitor, on I/R injury in the skin flap of an animal (rat) model. METHODS: Superficial epigastric flaps were raised in Sprague-Dawley rats and subjected to ischemia for 3 h. Febuxostat at a dose of 10 mg/kg/day was administered to rats in drinking water from 1 week before the surgery (Feb group). Control animals received no drugs (Con group). The mean ratio of flap survival and contraction was evaluated and compared between animals with and without administration of febuxostat on day 5 after the surgery. In addition, infiltration by polymorphonuclear leukocytes and muscles of the panniculus carnosus in the flap were histologically evaluated using hematoxylin-eosin staining. Furthermore, xanthine oxidase activity, ATP levels, superoxide dismutase activity, and expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-α, and interleukin-1ß were quantitatively assessed in the skin flap 24 h after the surgery. RESULTS: In the Feb group, the survival and contraction rates at the 5 d timepoint post-surgery were significantly higher and lower than those in the Con group, respectively. Histological analysis showed significant reduction in polymorphonuclear leukocyte infiltration and muscle injury scores due to I/R injury in the Feb group. The expression of 8-OHdG was also significantly inhibited in animals administered febuxostat. Biochemical analysis showed a significant reduction in xanthine oxidase activity and significant increases in ATP levels and superoxide dismutase activity in the Feb group. Furthermore, the expression of interleukin-1ß was significantly lower in the Feb group than in the Con group. CONCLUSION: Febuxostat, which is clinically used for the treatment of hyperuricemia, was effective against necrosis of the skin flap via inhibition of oxidative stress and inflammation caused by I/R injury.

Pathological features of reinnervated skeletal muscles after crush injury of the sciatic nerve in ob/ob mice.

INTRODUCTION/AIMS: Obesity is a factor contributing to suboptimal improvement of motor function in peripheral nerve disorders. In this study we aimed to evaluate the skeletal muscles during denervation and reinnervation after nerve crush injury in leptin-deficient (ob/ob) mice. METHODS: Experiments were performed on the skeletal muscles of the hindlimbs in 20 male ob/ob mice and controls. Characteristics of the gastrocnemius muscles were evaluated by histological analysis, immunohistological analysis, and Sircol-collagen assay after measurement of body weight and wet weight of the skeletal muscles, and by walking track analysis. The sciatic nerve was denervated by crushing with smooth forceps and reinnervation was evaluated. RESULTS: Gastrocnemius wet weight was significantly lower in the ob/ob mice than in the control mice. A smaller cross-sectional area of type II fibers and increase of type I fiber grouping of the skeletal muscles was demonstrated in the ob/ob mice. After nerve injury, motor function recovery was equal between the groups but the cross-sectional area of type II fibers was significantly smaller in the ob/ob mice than in control mice at 4 weeks. The denervated muscles showed an increase in collagen deposition in the interstitial space; predominant in the ob/ob mice after nerve injury. DISCUSSION: The results of this study suggest that fibrosis in the skeletal muscle of obese patients after nerve injury is prominent, which may impair improvement of muscle function after treatment of peripheral nerve disorders.

Febuxostat reduces muscle wasting in tumor-bearing mice with LM8 osteosarcoma cells via inhibition of reactive oxygen species generation.

Cachexic condition due to malignant tumors has been a challenging problem. The aim of this study is to analyze effects of febuxostat on both in vitro and in vivo models of the wasting of skeletal muscles, due to LM8 osteosarcoma cells. C2C12 myotubes were incubated in the conditioned medium of LM8. Febuxostat was added at a concentration of 3 µM and 30 µM, and ROS, diameter of myotubes, and expression of atrogin-1 were analyzed. Furthermore, an in vivo study was performed by subcutaneous injection of LM8 on C3H mice. Febuxostat was administered in the drinking water at 5 µg/ml, and 25 µg/ml. In addition, tumor-bearing mice without febuxostat (group TB) and control mice (group C) were established. At 4 weeks, body weight, wet weights of the gastrocnemius muscles, XO activity, 8-OHdG, and expression of TNF-α and IL-6 were evaluated. ROS generation, atrophy of myotubes, and upregulation of atrogin-1 were clearly observed in C2C12 myotubes following incubation in the conditioned medium. These pathological conditions were significantly inhibited by febuxostat administration. Furthermore, mice in group TB showed significant loss of body weight and muscle weight in which XO activity, 8-OHdG, and expression of IL-6 were significantly increased compared to those in group C. Febuxostat administration not only significantly improved the body weight and muscleweight, but also reduced markers of oxidative stress and pro-inflammatory cytokines. Febuxostat did not show anti-tumor effects. Febuxostat, which is clinically used for treatment of hyperuricemia, is effective against the wasting of the skeletal muscles induced by LM8 osteosarcoma cells.

Endoscopic resection of scar tissues and bone graft with an intramedullary nail left in situ for distal femoral nonunion after nailing: A case report.

Femoral shaft nonunion after the intramedullary nailing has been successfully treated with advances in surgical technique. Nonetheless, the techniques cause morbidity to periosteum at the fracture site. We report the case of a 67-year-old man who underwent endoscopic surgery for refractory nonunion following the fracture of the distal femoral shaft, despite two fixations using an interlocking nail. In addition, the patient had uncontrolled diabetic mellitus. Endoscopy allowed us to acquire a clear view of the nonunion site, in which the resection of scar tissues and the packing of the cancellous bone were performed. At the final follow-up, bone healing was observed, and the patient was able to return to normal daily and social activity.

Arthroscopic ligamentoplasty for osteoarthritis of the thumb carpometacarpal joints: Clinical and radiological outcomes with a minimum 2-year follow-up.

BACKGROUND: We reported a new technique for arthroscopic ligamentoplasty for the thumb carpometacarpal osteoarthritis (CMC-OA) along with a minimum of 2 years of results. METHODS: Twenty-nine thumbs with CMC-OA in stages II and III according to the Eaton and Glickel classification, were treated by arthroscopic ligamentoplasty. The procedure included partial trapeziectomy followed by ligamentoplasty similar to the Thompson technique. We evaluated pain VAS; DASH; grip and pinch strength; thumb abduction range of motion, and radiographic examination preoperatively and every 3 months until 1 year after surgery, and every 6 months thereafter. The mean duration of the follow-up was 3.2 years with a range of 2.0-6.0 years. RESULTS: Pain, VAS, and DASH were significantly improved at 3 months after surgery than those preoperatively. Further, the strength of grip, tip, and key pinch significantly increased at 9, 9, and 12 months after surgery, respectively. Additionally, these improvements were maintained until the final follow-up. The range of motion tended to decrease in both palmar and radial abduction, although the differences were not significant. Radiographic examination after surgery showed that the ratio of trapezial space was significantly reduced because of surgical excision of the trapezium. However, there were no significant differences in the results between each follow-up time and the final follow-up. Moreover, the ratio of subluxation on the plain X-ray was significantly improved and maintained until the final follow-up. The parameters of clinical and radiographic outcomes, except motion, were significantly improved, even in patients with including those in stage III and with greater than 1/3 subluxation of the 1st metacarpal base on plain radiography. CONCLUSION: Arthroscopic ligamentoplasty was effective for pain relief and improvement of grip and pinch strength for the patients with symptomatic CMC-OA. LEVEL OF EVIDENCE: Therapeutic study/Level IV.