Inhibitory Regulation of FOXO1 in PPARδ Expression Drives Mitochondrial Dysfunction and Insulin Resistance.

Forkhead box O1 (FOXO1) regulates muscle growth, but the metabolic role of FOXO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FOXO1 in skeletal muscle, we generated skeletal muscle-specific Foxo1 inducible knockout (mFOXO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFOXO1 iKO mice and assessed the correlation between FOXO1 and mitochondria-related protein in the skeletal muscle of patients with diabetes. Obese mFOXO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FOXO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle, and deletion of PPARδ abolished the beneficial effects of FOXO1 deficiency. FOXO1 protein levels were higher in the skeletal muscle of patients with diabetes and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FOXO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FOXO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ.

Does the proximal humeral bone quality influence alignment after reverse total shoulder arthroplasty with short humeral stems?

PURPOSE: When compared to standard-length humeral stem in reverse total shoulder arthroplasty (RTSA), short humeral stems in RTSA require good proximal humeral metaphyseal bone quality to gain proper and secure fixation during prosthetic implantation. Shorter humeral stems potentially carry more risk of misalignment than standard or long humeral stems. The hypothesis was that misalignment of the short humeral stems is influenced by regional bone quality. METHODS: RTSA with a short curved humeral stem with neck-shaft angle (NSA) default of 132.5° was reviewed. The study group included 35 cases at a mean age of 75.97 (± 6.23) years. Deltoid-tuberosity index (DTI) was measured to evaluate proximal humeral bone quality. The deltoid tuberosity index was measured at immediately above position of the upper end of the deltoid tuberosity. Stem alignment was given by the angle measured in degrees between the intramedullary humeral shaft axis and the axis of the humeral implant stem. RESULTS: The patient's mean DTI was 1.37 ± 0.16 (median, 1.32; range, 1.12-1.80). 22 patients had poor bone quality (DTI < 1.4), compared to 13 patients with acceptable bone quality (DTI > 1.4). After RTSA, ten humeral components (29%) were neutrally aligned, whereas 25 humeral components (71%) were misaligned. There was no correlation between misalignment and DTI (r = 0.117; p = 0.504). But there was a strong correlation between misalignment and the patient's own NSA (r = - 0.47; p = 0.004). The postoperative stem position and stem misalignment are not associated with functional outcomes (p > 0.05). CONCLUSION: The misalignment of the short curved humeral stem frequently occurs. Poor reginal humeral bone quality does not influence misalignment after RTSA with a short humeral stem. Postoperative stem alignment is associated with the patient's preoperative NSA and method of neck cut. The misalignment does not affect functional outcomes for midterm follow-up. Further long-term follow-up studies are needed to confirm its clinical relevance.

Does stress shielding after radial head arthroplasty affect functional outcomes?

BACKGROUND: Various complications related to the prosthesis, such as implant loosening and stress shielding phenomenon, could develop after prosthetic replacement of the radial head. Stress shielding is known to occur around rigidly fixed implants. The purpose of this study was to evaluate the clinical influence and causative factors of the stress shielding phenomenon after radial head arthroplasty (RHA). METHODS: Clinical records and radiographs of 56 patients with unreconstructable radial head fractures who received radial head replacement between 2009 and 2019 were reviewed. Exclusion criteria were infection, loosening, and follow-up of less than 24 months. After exclusion, 35 patients were enrolled. Patients were divided into two groups: an anatomical press-fit group (Anatomical Radial Head System; Acumed, Hillsboro, OR, USA) and a round bipolar cemented group (RHS; Tornier, Montbonnot Saint-Martin, France). Stress shielding around the prosthesis was assessed in the serial radiological examination. Clinical results were assessed using Mayo elbow performance score (MEPS), Quick Disabilities of the Arm, Shoulder, and Hand (q-DASH) score, range of motion (flexion-extension arc and pronation-supination arc), and visual analog scale score (VAS). Correlations between stress shielding phenomenon and demographic data and functional results were analyzed. RESULTS: At an average follow-up of 43.06 (± 14.6) months, 14 (40%) out of 35 fixed stems demonstrated stress shielding. Our results showed that the rate of stress shielding was significantly higher in cases with a bilateral ligament injury and in the anatomical press-fit group (p = 0.028 and p = 0.0091, respectively). However, stress shielding around prostheses did not affect the clinical results (p > 0.05). CONCLUSION: The stress shielding phenomenon around radial head prosthesis may vary according to prosthetic design and severity of ligament injuries. Stress shielding does not affect the mid-term outcomes in the treatment of acute fractures of the radial head. LEVEL OF EVIDENCE III: Retrospective Cohort Comparison; Treatment Study.

Flexion-extension-supination test compared to arthroscopic findings of biceps long head pathology: A physical examination that reflect anatomical evolution of human shoulder girdle.

The accuracy of physical examination for diagnosing lesions of the long head of the biceps tendon (LHBT) remains unsatisfactory. The purpose of this study was to describe a new diagnostic test, the Flexion-Extension-Supination (FES) test for diagnosing lesions of the long head of biceps tendon. A prospective study of 162 patients was performed to evaluate the diagnostic value of FES test. All the participants were evaluated on the basis of their clinical presentation, physical examination (FES test), radiologic findings and arthroscopic examination. Shoulder arthroscopy findings were used as the gold standard. To reduce the omission of the hidden lesion, LHBT was checked at the intra- and the extraarticular side via arthroscopic examination. Surgical findings related to biceps pathology were as follows: rotator cuff tears, 89.5% (145/162); subacromial impingement, 8.6% (14/162); and biceps tendinitis, 1.9% (3/162). The prevalence of biceps pathology was 77.2% (125/162) of all arthroscopic procedures. No significant differences for LHBT lesions were observed between the FES test and the arthroscopic findings (P = .850). The interrater reliability of the FES test was 0.747. After excluding inconclusive results between examiners, the sensitivity, specificity, positive predictive value, and negative predictive value of the FES test were 87.9%, 66.7%, 82.9%, and 63.2%, respectively. Positive and negative likelihood ratios were 2.67 and 0.18, respectively. The maneuvers of the FES test irritate intra- and extraarticular lesion of LHBT. The FES test is a reproducible and reliable test that can be used during physical examinations to evaluate patients with LHBT lesions.

Vertical Interfragmentary Doubled Suture for Displaced Patella Fractures: Sequential Compressive Tightening with Nice Knot.

In the treatment of displaced patella fractures, open reduction and internal fixation is essential for patellofemoral congruency and restoration of the knee extension mechanism. Various surgical techniques and materials can be used, and their clinical outcomes are favorable. However, soft-tissue and skin irritation, pain, and limited range of motion due to metallic hardware can occur, and removal of hardware such as screws and K-wire may be required after bony union. We present a vertical interfragmentary suture technique for patella fractures using sequential compressive tightening with the Nice knot. This knot-tying technique is low profile, provides stable fixation enough to hold displaced fractures, and does not require a secondary procedure for hardware removal.

Posteromedial Elbow Dislocations without Relevant Osseous Lesions: Clinical Characteristics, Soft-Tissue Injury Patterns, Treatments, and Outcomes.

BACKGROUND: Although simple posterolateral or posterior elbow dislocations are relatively common and usually stable after closed reduction, simple posteromedial dislocations are extremely rare and poorly characterized. We investigated the clinical characteristics, soft-tissue injury patterns, treatments, and outcomes of a series of posteromedial elbow dislocations without relevant osseous lesions. METHODS: We retrospectively reviewed 20 cases of simple posteromedial elbow dislocations without relevant osseous lesions that were treated at 7 fellowship training hospitals during a 10-year period. Soft-tissue injury patterns in 15 cases were investigated with use of magnetic resonance imaging. Clinical outcomes were evaluated after an average of 56.1 months (range, 24 to 93 months) with use of the Mayo Elbow Performance Score (MEPS) and the Quick-DASH (an abbreviated version of the Disabilities of the Arm, Shoulder and Hand [DASH]) score. Complications were also evaluated. RESULTS: On magnetic resonance imaging, significant tears of the lateral collateral ligament complex and common extensor group were observed in all cases. Seventeen cases (85%) required surgical treatment for acute instability. Fourteen cases underwent only lateral complex repair and 3 underwent repair of both the medial and lateral complexes. At the time of the latest follow-up, the mean MEPS and Quick-DASH scores were 85.8 ± 15.0 and 10.5 ± 16.3, respectively. Seventeen patients (85%) had a satisfactory clinical outcome. Complications following treatment included 4 patients with heterotopic ossification; 2 of these patients also experienced posttraumatic elbow stiffness, which was treated with arthrolysis at 8 and 18 months after the initial operation. CONCLUSIONS: Posteromedial elbow dislocations without relevant osseous lesions are associated with a more severe soft-tissue injury, especially to the lateral complex, resulting in a high rate of surgical treatment. With careful post-reduction evaluation, either operative or nonoperative treatment provided satisfactory clinical outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Distal clavicle fractures: A new classification system.

INTRODUCTION: Existing various classification systems for distal clavicle fractures have low interobserver and intraobserver reliability and provide limited information for treatment decision. The objective of this study was to determine interobserver and intraobserver reliability of the new classification system and the associated treatment choice for distal clavicle fractures. HYPOTHESIS: The new classification system has good reliability. METHODS: Eight observers including 4 experienced shoulder specialists and 4 orthopedic fellows independently reviewed routine plain radiographs of 74 patients with distal clavicle fractures. They were asked to determine the fracture type according to the new classification system and the treatment choice for each case through web-based survey. Images from each case were randomly presented to the observers in 2 rounds 4 weeks apart. Reliability was assessed on the basis of Fleiss κ values. RESULTS: Interobserver and intraobserver reliability of the classification system were moderate (κ=0.434) and substantial (κ=0.644), respectively. Interobserver and intraobserver reliability of the treatment choice were moderate (κ=0.593) and substantial (κ=0.698), respectively. There were no significant differences in the level of reliability between experienced shoulder specialists and orthopedic fellows for any κ values (all p>0.05). CONCLUSION: Our study demonstrated moderate interobserver and substantial intraobserver reliability of the new classification system and the associated treatment choice for distal clavicle fractures. We believe that our novel classification system will help physicians to choose treatment and implants. LEVEL OF EVIDENCE: III, Cohort study, Diagnosis study.

Supplementary Technique for Unstable Clavicle Shaft Fractures: Interfragmentary Wiring and Temporary Axial K-Wire Pinning.

BACKGROUND: Treatment of unstable clavicle fractures remains a challenge for orthopedic surgeons, but the evolution of treatment strategies has allowed for reliable results with minimal complications. Although several surgical options exist, open reduction with plating remains the treatment of choice for clavicle fractures. The purpose of this study is to determine an easy way to achieve successful preplating reduction while minimizing surrounding soft tissue damage during treatment of midshaft fractures of the clavicle. METHODS: A retrospective study included all consecutive adult patients operated on by a single surgeon for acute displaced clavicular midshaft fracture between January 2010 and October 2014. Hybrid technique with interfragmentary cerclage wiring, temporary axial K-wire pinning, or their combination was used in all patients. The demographic data and clinical outcomes, including operation time, union time, restoration of anatomy, shoulder functional score, and complications were evaluated. RESULTS: There were 54 male and 19 female patients, with an average age of 39.3 years (range, 18 to 77 years) for males and 58.3 years (range, 39 to 77 years) for females. They were followed up for 24 months (range, 12 to 44 months). All patients had reliable bone union after surgery using interfragmentary cerclage wiring and temporary axial K-wire fixation; fracture union was obtained at an average of 11.7 weeks (range, 8 to 21 weeks) postoperatively. Additionally, there was no postoperative loss of fracture reduction or plate loosening. At the final follow-up, all patients had regained excellent functional outcomes. CONCLUSIONS: The cognizant effort to achieve anatomic reduction without surrounding soft tissue insult before definitive plating allows excellent radiologic and functional outcomes. Interfragmentary cerclage wiring and temporary axial K-wire pinning can overcome difficulties associated with unstable clavicle fractures to allow proper fracture reduction. In this article, we introduce a concise technique for achieving the desired outcomes reliably and efficiently when treating unstable clavicle midshaft fractures.

Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B.

In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved.

Low Serum Vitamin D Is Not Correlated With the Severity of a Rotator Cuff Tear or Retear After Arthroscopic Repair.

BACKGROUND: Despite the essential role of vitamin D in muscle function, the prevalence of vitamin D deficiency has been reported to be very high. Recently, low vitamin D level was found to correlate with fatty degeneration of the rotator cuff tendon in humans and to negatively affect early healing at the rotator cuff repair site in an animal study. However, the effects of vitamin D level on severity of rotator cuff tear and healing after surgical repair have not been documented. PURPOSE: To evaluate (1) the prevalence of vitamin D deficiency among patients who underwent arthroscopic repair for a full-thickness rotator cuff tear, (2) the relationship of vitamin D level with severity of the rotator cuff tear, and (3) surgical outcomes after repair. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A consecutive series of 91 patients (age, 50-65 years) who underwent arthroscopic rotator cuff repair for full-thickness, small-sized to massive tears were evaluated. Preoperative serum vitamin D levels (25-hydroxyvitamin) were analyzed to detect correlations with the features of a preoperative rotator cuff tear as well as postoperative structural and functional outcomes. All patients were followed clinically for a minimum of 1 year. RESULTS: Preoperative vitamin D levels were deficient (<20 ng/mL) in 80 subjects (88%), insufficient (20-30 ng/mL) in 8 subjects (9%), and normal (>30 ng/mL) in 3 subjects (3%). No correlation was found between preoperative tear size (P = .23), extent of retraction (P = .60), degree of fatty infiltration of each cuff muscle (P > .50 each), or the global fatty infiltration index (P = .32). Similarly, no correlations were detected between vitamin D level and postoperative Sugaya type (P = .66) or any of the functional outcome scores (P > .50 each). CONCLUSION: Low serum vitamin D level was not related to tear size, extent of retraction, or the degree of fatty infiltration in cuff muscles. It also had no significant relationships with postoperative structural integrity and functional outcomes after arthroscopic repair. The results suggest that low serum vitamin D level is not a significant risk factor for the severity of rotator cuff tear or poor healing after repair.

TLR2 deficiency attenuates skeletal muscle atrophy in mice.

Oxidative stress and inflammation are associated with skeletal muscle atrophy. Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice. Immobilization for 2 weeks increased the expression of cytokine genes and the levels of carbonylated proteins and nitrotyrosine in the skeletal muscle, but these increases were lower in the TLR2 KO mice. Muscle weight loss and a reduction in treadmill running times induced by immobilization were also attenuated in TLR2 KO mice. Furthermore, immobilization increased the protein levels of forkhead box O 1/3, atrogin-1 and muscle ring finger 1 in the WT mice, which was attenuated in TLR2 KO mice. In addition, immobilization-associated increases in ubiquitinated protein levels were lower in the TLR2 KO mice. Immobilization increased the phosphorylation of Akt and p70S6K similarly in WT and KO mice. Furthermore, cardiotoxin injection into the skeletal muscle increased the protein levels of atrogin-1, interleukin-6, and nitrotyrosine and increased the levels of ubiquitinated proteins, although these levels were increased to a lesser extent in TLR2 KO mice. These results suggest that TLR2 is involved in skeletal muscle atrophy, and the inhibition of TLR2 offers a potential target for preventing skeletal muscle atrophy.

Treatment of thoracolumbar fracture.

The most common fractures of the spine are associated with the thoracolumbar junction. The goals of treatment of thoracolumbar fracture are leading to early mobilization and rehabilitation by restoring mechanical stability of fracture and inducing neurologic recovery, thereby enabling patients to return to the workplace. However, it is still debatable about the treatment methods. Neurologic injury should be identified by thorough physical examination for motor and sensory nerve system in order to determine the appropriate treatment. The mechanical stability of fracture also should be evaluated by plain radiographs and computed tomography. In some cases, magnetic resonance imaging is required to evaluate soft tissue injury involving neurologic structure or posterior ligament complex. Based on these physical examinations and imaging studies, fracture stability is evaluated and it is determined whether to use the conservative or operative treatment. The development of instruments have led to more interests on the operative treatment which saves mobile segments without fusion and on instrumentation through minimal invasive approach in recent years. It is still controversial for the use of these treatments because there have not been verified evidences yet. However, the morbidity of patients can be decreased and good clinical and radiologic outcomes can be achieved if the recent operative treatments are used carefully considering the fracture pattern and the injury severity.

Salmonella osteomyelitis of the femoral diaphysis in a healthy individual.

In reviewing the literature, we found few cases of Salmonella osteomyelitis of the femoral diaphysis in a healthy patient. Most are typically associated with sickle cell anemia or immunosuppressed patients. We report on the successful treatment of Salmonella osteomyelitis in the mid-diaphyseal region of the femur caused by Salmonella species in a healthy individual.

Reliability of the classification and treatment of dislocations of the acromioclavicular joint.

BACKGROUND: We evaluated interobserver and intraobserver reliability of the classification and treatment of acromioclavicular (AC) joint dislocations and assessed the impact of adding 3-dimensional computed tomography (3D CT) on the reliability of classification and treatment choice. METHODS: Ten surgeons independently reviewed plain radiographs and 3D CT in 28 cases with AC joint dislocation. Images from each case were randomly presented to the observers, with plain radiographs alone being presented first, followed by plain radiographs plus 3D CT 2 weeks later. Four weeks later, they repeated the same survey to evaluate intraobserver reliability. Reliability was assessed on the basis of Fleiss κ values. RESULTS: On the basis of plain radiographs alone, interobserver and intraobserver reliability of the Rockwood classification were fair (κ = .214) and moderate (κ = .474), respectively. Interobserver and intraobserver reliability of treatment were both fair (κ = .213 and .399, respectively). On the basis of a combination of plain radiographs and 3D CT, interobserver and intraobserver reliability of the Rockwood classification were slight (κ = .177) and moderate (κ = .565), respectively. Interobserver and intraobserver reliability of treatment were fair (κ = .253) and moderate (κ = .554), respectively. There were no significant differences in reliability between the two groups in terms of any κ values. CONCLUSION: This study suggests an overall lack of reliability of the Rockwood classification of AC joint dislocations and of decisions regarding their treatment. There is especially poor agreement between experienced shoulder surgeons. The addition of 3D CT did not improve reliability of classification and treatment of AC joint dislocations.

The association between meniscal subluxation and cartilage degeneration.

PURPOSE: The menisci play a critical protective role for the knee joint through shock absorption and load distribution. We hypothesized that cartilage degeneration will be abruptly progressed if meniscal subluxation exceeds a critical point. METHODS: Of 56 cases that showed medial meniscal subluxation without cartilage degeneration of ipsilateral medial femoral condyle (MFC) on initial MRI, from January 2005 to June 2007, meniscal subluxation index (MSI), the ratio of meniscal overhang to meniscal width in mid-coronal image of initial MRI, was measured. After 2 years, 40 cases were evaluated for cartilage degeneration of ipsilateral MFC on follow-up MRI. The relationship between medial MSI on initial MRI and cartilage degeneration of MFC on follow-up MRI was analyzed. Logistic regression analysis was conducted to find a critical point of meniscal subluxation related to cartilage degeneration. RESULTS: Abrupt progression of cartilage degeneration was observed from which MSI was 0.38. Logistic regression showed that if MSI was at the critical point, which was 0.38 in our study, then the probability of cartilage degeneration to grade 3 or 4 after 2 years was 44 %. If MSI was 0.4, then the probability was 50 %. If MSI was 0.6, then the probability was 99 %. CONCLUSIONS: The results suggest the existence of critical point from which the protective function of the meniscus appears to be significantly altered, and the degree of cartilage degeneration of ipsilateral femoral condyle corresponding to the amount of medial meniscal subluxation may be predictable.

Hemin, heme oxygenase-1 inducer, attenuates immobilization-induced skeletal muscle atrophy in mice.

AIMS: The present study examined the effect of the heme oxygenase (HO)-1 inducer hemin on skeletal muscle atrophy induced by single limb immobilization in mice. MAIN METHODS: Immobilization was conducted in the left hindlimb of C57BL/6 mice for 1 week and the right hindlimb was used as a control. Hemin (30 mg/kg) was administered intraperitoneally once a day during the immobilization period. Gastrocnemius muscles were used for analysis. Muscle weight was measured to quantify degree of atrophy, and exhaustion treadmill test was performed to assess muscle function. KEY FINDINGS: Immobilization increased HO-1 protein levels in skeletal muscle, which was further increased by hemin treatment. Immobilization induced weight loss and a functional reduction in skeletal muscle, which were attenuated by hemin treatment. Gene expression and protein levels of MuRF1 and atrogin-1 were increased by immobilization and hemin treatment attenuated the increment. The phosphorylation of mTOR and p70S6k was decreased by immobilization in skeletal muscle and hemin had no effect on mTOR and p70S6k phosphorylation. Gene expression of the antioxidants superoxide dismutase and glutathione peroxidase 1 in skeletal muscle was reduced by immobilization and hemin treatment recovered the reduction. Immobilization increased levels of carbonylated protein and nitrotyrosine in skeletal muscle, which was reversed by hemin treatment. Gene expression of inflammatory cytokines was increased by immobilization and was normalized as a result of hemin treatment. SIGNIFICANCE: These results suggest that hemin attenuates immobilization-induced skeletal muscle atrophy through the suppression of protein degradation via its anti-oxidant and anti-inflammatory properties.

Deficiency of inducible nitric oxide synthase attenuates immobilization-induced skeletal muscle atrophy in mice.

The present study examined the effects of inducible nitric oxide synthase (iNOS) deficiency on skeletal muscle atrophy in single leg-immobilized iNOS knockout (KO) and wild-type (WT) mice. The left leg was immobilized for 1 wk, and the right leg was used as the control. Muscle weight and contraction-stimulated glucose uptake were reduced by immobilization in WT mice, which was accompanied with increased iNOS expression in skeletal muscle. Deficiency of iNOS attenuated muscle weight loss and the reduction in contraction-stimulated glucose uptake by immobilization. Phosphorylation of Akt, mTOR, and p70S6K was reduced to a similar extent by immobilization in both WT and iNOS KO mice. Immobilization decreased FoxO1 phosphorylation and increased mRNA and protein levels of MuRF1 and atrogin-1 in WT mice, which were attenuated in iNOS KO mice. Aconitase and superoxide dismutase activities were reduced by immobilization in WT mice, and deficiency of iNOS normalized these enzyme activities. Increased nitrotyrosine and carbonylated protein levels by immobilization in WT mice were reversed in iNOS KO mice. Phosphorylation of ERK and p38 was increased by immobilization in WT mice, which was reduced in iNOS KO mice. Immobilization-induced muscle atrophy was also attenuated by an iNOS-specific inhibitor N(6)-(1-iminoethyl)-l-lysine, and this finding was accompanied by increased FoxO1 phosphorylation and reduced MuRF1 and atrogin-1 levels. These results suggest that deficiency of iNOS attenuates immobilization-induced skeletal muscle atrophy through reduced oxidative stress, and iNOS-induced oxidative stress may be required for immobilization-induced skeletal muscle atrophy.

Inhibition of Inducible Nitric Oxide Synthase Attenuates Monosodium Urate-induced Inflammation in Mice.

The present study elucidated the effect of the selective inducible nitric oxide synthase (iNOS) inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) on monosodium urate (MSU) crystal-induced inflammation and edema in mice feet. L-NIL (5 or 10 mg/kg/day) was administered intraperitoneally 4 h before injection of MSU (4 mg) into the soles of mice hindlimb feet. Twenty-four hours after MSU injection, foot thickness was increased by 160% and L-NIL pretreatment reduced food pad swelling in a dose dependent manner. Pretreatment of 10 mg/kg/day L-NIL significantly suppressed the foot pad swelling by MSU. Plasma level of nitric oxide (NO) metabolites and gene expression and protein level of iNOS in feet were increased by MSU, which was suppressed by L-NIL pretreatment. Similar pattern of change was observed in nitrotyrosine level. MSU increased the gene expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß and L-NIL pretreatment suppressed MSU-induced cytokines expression. The mRNA levels of superoxide dismutase and glutathione peroxidase1 were increased by MSU and L-NIL pretreatment normalized the gene expression. Phosphorylation of extracellular signal-regulated kinase 1/2 and p38 was increased by MSU, which was suppressed by L-NIL pretreatment. The mRNA levels of iNOS, TNF-α, and IL-1ß were increased by MSU in human dermal fibroblasts, C2C12 myoblasts, and human fetal osteoblasts in vitro, which was attenuated by L-NIL in a dose dependent manner. This study shows that L-NIL inhibits MSU-induced inflammation and edema in mice feet suggesting that iNOS might be involved in MSU-induced inflammation.

Simultaneous bilateral quadriceps tendon rupture in patient with chronic renal failure.

Simultaneous bilateral spontaneous rupture of the quadriceps tendon is a very rare condition and only a few cases have been reported in the literature. The etiology is not clear yet. But it occurs infrequently in patients with chronic metabolic disorders. A 30-year-old female patient with simultaneous bilateral spontaneous quadriceps tendon rupture visited our hospital. She had chronic renal failure and her parathyroid hormone level was elevated due to parathyroid adenoma. We report a surgical repair of both quadriceps tendons of a patient with chronic renal failure as well as management of hyperparathyroidism.