Pure nematic quantum critical point accompanied by a superconducting dome.

SignificanceThe notion of the quantum critical point (QCP) is at the core of modern condensed matter physics. Near a QCP of the symmetry-breaking order, associated quantum-mechanical fluctuations are intensified, which can lead to unconventional superconductivity. Indeed, dome-shaped superconducting phases are often observed near the magnetic QCPs, which supports the spin fluctuation-driven superconductivity. However, the fundamental question remains as to whether a nonmagnetic QCP of electronic nematic order characterized by spontaneous rotational symmetry breaking can promote superconductivity in real materials. Here, we provide an experimental demonstration that a pure nematic QCP exists near the center of a superconducting dome in nonmagnetic FeSe[Formula: see text] Tex. This result evidences that nematic fluctuations enhanced around the nematic QCP can boost superconductivity.

Novel electronic nematicity in heavily hole-doped iron pnictide superconductors.

Electronic nematicity, a correlated state that spontaneously breaks rotational symmetry, is observed in several layered quantum materials. In contrast to their liquid-crystal counterparts, the nematic director cannot usually point in an arbitrary direction (XY nematics), but is locked by the crystal to discrete directions (Ising nematics), resulting in strongly anisotropic fluctuations above the transition. Here, we report on the observation of nearly isotropic XY-nematic fluctuations, via elastoresistance measurements, in hole-doped Ba1-x Rb x Fe2As2 iron-based superconductors. While for [Formula: see text], the nematic director points along the in-plane diagonals of the tetragonal lattice, for [Formula: see text], it points along the horizontal and vertical axes. Remarkably, for intermediate doping, the susceptibilities of these two symmetry-irreducible nematic channels display comparable Curie-Weiss behavior, thus revealing a nearly XY-nematic state. This opens a route to assess this elusive electronic quantum liquid-crystalline state.

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.

Vastus lateralis myocutaneous flap for ischial skin wound following the treatment of epithelioid sarcoma using pazopanib.

Pazopanib, a targeted molecular drug, has been proposed as an effective treatment for soft tissue tumour and as a novel adjuvant therapy. There has been a paradoxical concern that wound healing could be inhibited by its anti-angiogenic properties, especially in reconstructive surgery. This paper reports on a 28-year-old woman who underwent flap surgery due to a skin and soft tissue injury after an effective treatment with pazopanib for refractory epithelioid sarcoma. The flap survived without any complication in off-periods of pazopanib for four weeks before and after the surgery, although it is only recommended that the washout periods of pazopanib commence at least seven days before scheduled surgery.

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.

Clinical outcome of latissimus dorsi reconstruction after wide resection of soft-tissue sarcoma.

BACKGROUND: We investigated the clinical outcomes of reconstruction using the latissimus dorsi (LD) flap after resection of soft-tissue sarcoma. MATERIALS AND METHODS: We analyzed 19 patients. Free LD flap was performed in 11 patients and pedicle flap in eight patients. The mean follow-up period after the surgery was 60 months. RESULTS: The mean age at diagnosis was 57 years. The mean tumor size was 9.8 cm. The median size of the LD flap was 140 × 100 mm. The mean surgical duration and bleeding were 510 min and 602 mL, respectively. Complications included partial skin and soft-tissue necrosis (n = 3) and wound dehiscence (n = 2). No additional free flap was not necessary for the closure of the defect due to the complications. The longer surgical duration was significantly associated with wound complications (P = 0.048). The 5-year survival rate was 80.7%, and the local recurrence-free survival rate was 89.2%. Two patients developed local recurrence, while 6 patients developed metastasis. None of the patients had any restrictions of daily life. CONCLUSION: The LD flap after surgical tumor resection in patients with soft-tissue sarcoma was useful for the coverage of soft tissue.

Minimally invasive surgery using intraoperative electron-beam radiotherapy for the treatment of soft tissue sarcoma of the extremities with tendon involvement.

BACKGROUND: When a soft tissue sarcoma (STS) is located at the distal part of an extremity and involves the tendon, a wide excision usually causes severe functional disability. We therefore developed a minimally invasive surgical technique using intraoperative electron-beam radiotherapy (IOERT) to reduce the incidence of post-operative functional disability in patients with peri-/intra-tendinous STS. We assessed the clinical outcomes of the novel minimally invasive surgery. METHODS: The study population included five patients who received treatment for distal extremity STSs. After elevating the tumor mass, including the tendon and nerve from the tumor bed with a wide margin, a lead board was inserted beneath the tumor mass to shield the normal tissue. IOERT (25-50 Gy) was then applied, and the tumor excised with care taken to maintain the continuity of the tendon. RESULTS: In a desmoid patient, local recurrence was observed outside the irradiated field. No cases of neuropathy or bone necrosis were observed. The mean limb function score was excellent in all patients. None of the high-grade sarcoma patients had local recurrence or distant metastasis. CONCLUSIONS: Although the current study is only a pilot study with a small number of patients, it shows that this minimally invasive procedure has the potential to become a standard treatment option for selected patients. TRIAL REGISTRATION: H17-250 (registered 2 November 2005) and H25-250 (modified from H17-250, registered 5 December 2013).

Pedicled flap transfer after chest wall malignant tumor resection and potential risk of postoperative respiratory problems for patients with low FEV1.0.

Introduction: Musculoskeletal transfer for chest wall tissue defects is a crucial method, and pedicled flaps around the chest wall are preferred in terms of location and simplicity of transfer. These require special care because of complications such as partial necrosis, fistula, wound dehiscence, infection, hematoma and restricted function of the arm or shoulder. However, studies of respiratory function are rare. In the present study, we investigated the complications including respiratory problems after wide resection for malignant chest wall tumors with musculoskeletal pedicle transfer. Methods: A total of 13 patients (15 operations) who underwent wide resection of primary, recurrent, or metastatic malignant chest wall tumors and musculoskeletal pedicle transfer for coverage of tissue defects were enrolled in the present study. A retrospective review of all patients was performed using data collected from hospital records and follow-up information. The complications of musculoskeletal transfer after chest wall wide resection, including respiratory problems, are evaluated. Results: Rib or sternal resection was performed in 12 operations, and only soft tissue resection was performed in 3 operations. Latissimus dorsi (LD) pedicle transfer was performed in 13 operations, and pectoralis major (PM) pedicle transfer was performed in 2 operations; basically, wounds were closed primarily. Surgical complications were observed following 5 of the 15 operations (33.3%). Respiratory complications were seen in 7 of the 15 operations (46.7%). Patients with respiratory complications showed significantly lower preoperative FEV1.0% values than those without respiratory complications (p = 0.0196). Skin resection area tended to be higher in the complication group than in the no complication group (p = 0.104). Discussion: Pedicled myocutaneous flap transfers such as LD, PM, and rectus abdominus can be used following multiple resections. After harvesting LD or PM, the wound can be closed primarily for an 8-10-cm skin defect in patients with normal respiratory function. However, for patients with low FEV1.0%, after primary closure of LD or PM transfer for wide soft tissue defects, attention should be paid to postoperative respiratory complications.

Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury on skeletal muscle in murine hindlimb.

BACKGROUND: Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle. The purposes of this study were 1) to assess the histological findings of gastrocnemius muscle (GC) and tibialis anterior muscle (TA) in I/R injury model mice, 2) to histologically analyze whether a single pretreatment of edaravone inhibits I/R injury to skeletal muscle in murine models and 3) to evaluate the effect of oxidative stress on these muscles. METHODS: C57BL6 mice were divided in two groups, with one group receiving 3 mg/kg intraperitoneal injections of edaravone (I/R + Ed group) and the other group receiving an identical amount of saline (I/R group) 30 minutes before ischemia. Edaravone (3-methy-1-pheny1-2-pyrazolin-5-one) is a potent and novel synthetic scavenger of free radicals. This drug inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway, in addition to having potent antioxidant effects against ischemia reperfusion. The duration of the ischemia was 1.5 hours, with reperfusion at either 24 or 72 hours (3 days). Specimens of gastrocnemius (GC) and anterior tibialis (TA) were removed for histological evaluation and biochemical analysis. RESULTS: This model of I/R injury was highly reproducible in histologic muscle damage. In the histologic damage score, the mean muscle fibers and inflammatory cell infiltration in the I/R + Ed group were significantly less than the corresponding values of observed in the I/R group. Thus, pretreatment with edaravone was observed to have a protective effect on muscle damage after a period of I/R in mice. In addition, the mean muscle injury score in the I/R + Ed group was also significantly less than the I/R group. In the I/R + Ed group, the mean malondialdehyde (MDA) level was lower than in the I/R group and western-blotting revealed that edaravone pretreatment decreased the level of inducible nitric oxide synthase (iNOS) expression. CONCLUSIONS: Edaravone was found to have a protective effect against I/R injury by directly inhibiting lipid peroxidation of the myocyte by free radicals in skeletal muscles and may also reduce the secondary edema and inflammatory infiltration incidence of oxidative stress on tissue.

Full-thickness chest wall resection for malignant chest wall tumors and postoperative problems.

Background: Chest wall malignant tumor (including primary and metastatic lesions) is rare, representing less than 5% of all thoracic malignancies. Local control of chest wall malignancies requires wide resection with tumor-free margins. These requirements increase the risk of thoracic cavity failure and subsequent pulmonary failure. The restoration strategy for chest wall defects comprises chest wall reconstruction and soft-tissue coverage. Various reconstruction methods have been used, but both evidence and guidelines for chest wall reconstruction remain lacking. The purposes of this study were to collate our institutional experience, evaluate the outcomes of full-thickness chest wall resection and reconstruction for patients with chest wall malignant tumor, and identify problems in current practice for chest wall reconstruction with a focus on local control, complications, pulmonary function and scoliosis. Methods: Participants comprised 30 patients with full-thickness chest wall malignant tumor who underwent chest wall resection and reconstruction between 1997 and 2021 in Mie University Hospital. All patients underwent chest wall resection of primary, recurrent or metastatic malignant tumors. A retrospective review was conducted for 32 operations. Results: Recurrence was observed after 5 operations. Total 5-year recurrence-free survival (RFS) rate was 79.3%. Diameter ≥5 cm was significantly associated with poor RFS. The postoperative complication rate was 18.8%. Flail chest was observed with resection of ≥3 ribs in anterior and lateral resections or with sternum resection without polyethylene methylmethacrylate reconstruction. Postoperative EFV1.0% did not show any significant decrease. Postoperative %VC decreased significantly with resection of ≥4 ribs or an area of >70 cm2. Postoperative scoliosis was observed in 8 of 28 patients. Posterior resection was associated with a high prevalence of scoliosis (88.9%). Conclusion: With chest wall reconstruction, risks of pulmonary impairment, flail chest and scoliosis were significantly increased. New strategies including indications for rigid reconstruction are needed to improve the outcomes of chest wall reconstruction.

Transfection of nuclear factor-kappaB decoy oligodeoxynucleotide protects against ischemia/reperfusion injury in a rat epigastric flap model.

BACKGROUND: Nuclear factor-kappaB (NF-κB) is considered to play an important role in the response to ischemia/reperfusion (I/R) injury in flap surgery. To inhibit NF-κB, synthetic double-stranded oligodeoxynucleotide (ODN) was used as a decoy. The present study aimed to evaluate the suppressive effects of NF-κB against I/R injury of experimental rat flap model. METHODS: An extended epigastric island flap was raised and ischemia was induced for 3 h. NF-κB decoy ODN (group D) or single-strand ODN (control; group S) was injected via the contralateral artery when the pedicle was clamped. Transfection efficiency was evaluated with fluorescein isothiocyanate (FITC)-labeled ODN. The effects of NF-κB decoy ODN were analyzed in groups D and S, and an untreated group (group N). RESULTS: FITC-labeled ODN was distributed over the entire flap. Mean survival rate of the flap was significantly higher in group D than in the other groups (group D: 57.9%; group S: 31.1%; group N 31.7%; p < 0.005). Injured muscle fibers, neutrophils and the expression of inducible nitric oxide synthase were significantly lower in group D. A real-time polymerase chain reaction also demonstrated a tendency for suppression of tumor necrosis factor-α, interleukin (IL)-1ß and IL-6. CONCLUSIONS: We show that NF-κB decoy ODN protected against flap necrosis as a result of I/R injury in rats. We also indicate that intra-arterial injection of naked NF-κB decoy ODN is effective for transfection into target organs. Therefore, transfection of NF-κB decoy ODN represents a novel therapeutic strategy for the treatment of flap surgery in I/R injury.

Expression and distribution pattern of aggrecanases and miR-140s in the thickened synovia of shoulder joints in rotator cuff tears: A retrospective observational study.

The rotator cuff (RC) is frequently torn at the enthesis composed of fibrocartilage. We aimed to histopathologically evaluate lining layers and assess the distribution of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, and microRNA (miR)-140s in the synovia of patients with RC tears. We recruited 51 patients who underwent arthroscopic surgical treatment for full-thickness rotator cuff tears, including 26 patients with < 3 cm tear size (group N) and 25 patients with ≥ 3 cm tear size (group W). Biopsied synovia were analyzed using histological and immunohistological techniques for the presence ADAMTS4 and ADAMTS5. The layers of the synovial lining were morphologically classified into 3 grades according to the synovitis score and staining levels of ADAMTSs. The glenohumeral synovia from 8 patients with recurrent shoulder dislocation (group C) were used as controls. Furthermore, in situ hybridization was performed to evaluate the presence of miR-140s in patients with massive tears and recurrent shoulder dislocation. The staining levels were evaluated and analyzed based on comparison between patient groups and correlation between ADAMTS5 and miR-140s. Histological analysis revealed significant differences between groups W and C. ADAMTS5 and ADAMTS4 were strongly expressed in the synovial lining of patients in group W, and this expression was significantly higher than that in groups C and N. In addition, expression of ADAMTS5 was inversely correlated with that of miR-140-3p. This study showed that synovia from group W had a significantly higher rate of severely thickened areas with strong expression of both aggrecanases. Furthermore, the area with weak expression of miR-140-3p showed strong ADAMTS5 expression.

Pedicled vastus lateralis musculofascial flap as a new technique for repairing rectourethral fistula after radical prostatectomy.

We present a case of successful operative management of an iatrogenic rectourethral fistula with a pedicled vastus lateralis musculofascial flap. The fistula was created during radical prostatectomy operation. During the operation, it was deemed possible to spare this patient from a diverting colostomy and primarily repair a rectal injury. Postoperatively, however, a rectourethral fistula occurred, which was confirmed on retrograde urethrogram. A first attempt failed to close the fistula utilizing the transanal rectal flap advancement technique. A novel technique was attempted using a pedicled vastus lateralis musculofascial flap. This is the first report to our knowledge of repairing a rectourethral fistula with a pedicled vastus lateralis musculofascial flap.

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.

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.

Arthroscopic resection of a loose body in the inextensible metacarpophalangeal joint of the middle finger complicated with osteoarthritis: A case report.

Arthroscopic surgery is a standard technique for removal of loose bodies in large joints. By contrast, there were a few reports of arthroscopic surgery for loose bodies in small joints. We herein report a case of a 70-year-old woman with an inextensible metacarpophalangeal joint in the right middle finger due to an intra-articular loose body that developed after osteoarthritis. Surgery proceeded under vertical traction using traction tower. Two portals were developed at dorsal aspect on the metacarpophalangeal joints. The loose body was removed under arthroscopy with a small incision of both skin and sagittal band, thereby resolving clinical symptoms, including pain and limitations to metacarpophalangeal joint motion.

Surgical Treatment for Delayed Ulnar Carpometacarpal Fracture-Dislocations.

Background Fracture and dislocations of the carpometacarpal (CMC) joints except the thumb are relatively rare. Herein, we report the case of a delayed fracture-dislocation of fourth and fifth carpometacarpal joints. Case Description The patient is a 41-year-old, right-handed male. To improve the complaints, such as decreased motion, reduced grip strength, and cosmetic appearance, surgical treatment surgically performed with resection of scar tissues and fixation using suture button at 11 weeks after injury. Movement began at 2 weeks after the surgery, which resulted in satisfactory appearance and good function of 92 and 101% of the motion of the unaffected side of the fifth CMC joint and grip strength, respectively. Literature Review Missed diagnosis can cause impairment of function including grip strength and range of motion. Nevertheless, a few previous studies reported that patients with delayed diagnosis did not need further treatment because of less functional loss and less improvement. Clinical Relevance The surgical treatment using the implant allowed early motion from 2 weeks after surgery which resulted in good motion of the ulnar CMC joints as well as increased hand grip.

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.

Are BMPs involved in normal nerve and following transection?: a pilot study.

Bone morphogenic proteins (BMPs) may have neurotrophic functions but there is limited evidence of these functions in the peripheral nervous system. We therefore investigated the expression of BMPs and BMP receptors (BMPRs) in normal and injured peripheral nerves. In 10 of 15 Sprague-Dawley rats, a 3-mm segment of sciatic nerve was resected at the trifurcation in the thigh. One day (n = 5) and 7 days (n = 5) after transection, proximal and distal stumps were removed and immunohistochemically analyzed for BMP-2, -7, BMPR-1A, -1B, and -2. The other five animals served as normal controls. In normal nerves, BMP-2 expression was localized at Ranvier's node, and BMP-7 and BMPR-1B were expressed in several axon-Schwann cell units, whereas other receptors were not expressed. After nerve transection, BMP-7 expression was upregulated at both proximal and distal stumps along with Schwann cell columns during Wallerian degeneration. BMPRs were also upregulated compared with the normal nerve. The upregulation in BMP expression after nerve transection suggests that BMPs may play a role in the healing response of the peripheral nerve.

Inhibitory effect of edaravone on systemic inflammation and local damage in skeletal muscles following long-term ischemia to murine hind limb.

PURPOSE: The purpose of this study was to evaluate local and systemic pathology in a murine model of ischemia-reperfusion (I/R) injury induced by long-term application of a tourniquet on the hind limbs and to assess the protective effects of edaravone, a potent systemic scavenger of free radicals, using this model. METHODS: Sixty C57BL6 mice were divided in two groups, with one group receiving a 3 mg/kg intraperitoneal injection of edaravone and the other group receiving an identical amount of saline 30 min before ischemia under deep anesthesia. The left thigh of each animal was constricted for 4 h with a 4.5-oz. orthodontic rubber band to induce ischemia; 4 h was the critical duration for skeletal muscles. After ischemia, specimens of skeletal muscles, both kidneys, and plasma were collected at 0, 2, 12, 24, 48, and 72 h. Injury to the skeletal muscles and vacuolar degeneration of the kidneys were histologically assessed. Additionally, apoptosis of skeletal muscle cells was assessed by analysis of caspase 3/7 activity and TUNEL staining. Plasma tumor necrosis factor (TNF)-α levels were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Skeletal muscles exhibited prominent injury of myofibers at 12 h after I/R injury, with clear upregulation of plasma TNF-α expression and histologic evidence of tubular dysfunction of the kidneys. Plasma TNF-α levels declined and histologic renal damage was ameliorated in edaravone-treated mice, but treatment did not protect skeletal muscle following ischemia for 4 h. Nonetheless, compared with group S, expression of the apoptosis marker caspase 3/7 was significantly inhibited in the skeletal hind limb muscles of Ed-group mice affected by reperfusion injury following ischemia for 4 h. CONCLUSION: The present study demonstrated that edaravone is a potentially useful drug for systemic or local treatment of reperfusion injury resulting from long-term ischemia.