Peptidoglycan enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, focal adhesion kinase, Akt, and AP-1- dependent pathway.

Peptidoglycan (PGN), the major component of the cell wall of Gram-positive bacteria, activates the innate immune system of the host and induces the release of cytokines and chemokines. We investigated the signaling pathway involved in IL-6 production stimulated by PGN in rheumatoid arthritis synovial fibroblasts. PGN caused concentration- and time-dependent increases in IL-6 production. PGN-mediated IL-6 production was attenuated by TLR2 small interfering RNA and nucleotide-binding oligomerization domain 2 small interfering RNA. Pretreatment with PI3K inhibitor (Ly294002 and wortmannin), Akt inhibitor, and AP-1 inhibitor (tanshinone IIA) also inhibited the potentiating action of PGN. PGN increased the focal adhesion kinase (FAK), PI3K, and Akt phosphorylation. Stimulation of rheumatoid arthritis synovial fibroblast cells with PGN increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the IL-6 promoter. PGN mediated an increase in the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to AP-1 element was inhibited by Ly294002, Akt inhibitor, and FAK mutant. Our results suggest that PGN increased IL-6 production in human synovial fibroblasts via the TLR2 receptor/FAK/PI3K/Akt and AP-1 signaling pathway.

Thrombin-induced IL-6 production in human synovial fibroblasts is mediated by PAR1, phospholipase C, protein kinase C alpha, c-Src, NF-kappa B and p300 pathway.

Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA) in synovial tissues. We investigated the signaling pathway involved in IL-6 production caused by thrombin in synovial fibroblasts. Thrombin caused concentration- and time-dependent increases in IL-6 production. By using pharmacological inhibitors or activators or genetic inhibition by the protease activated receptor (PAR), siRNA revealed that the PAR1 receptor but not other PAR receptors is involved in thrombin-mediated up-regulation of IL-6. Thrombin-mediated IL-6 production was attenuated by thrombin inhibitor (PPACK), phospholipase C inhibitor (U73122), protein kinase C alpha inhibitor (Ro320432), Src inhibitor (PP2), NF-kappaB inhibitor (PDTC), I kappa B protease inhibitor (TPCK), or NF-kappaB inhibitor peptide. Stimulation of synovial fibroblasts with thrombin activated I kappa B kinase alpha/beta (IKK alpha/beta), I kappa B alpha phosphorylation, I kappa B alpha degradation, p65 phosphorylation at Ser(276), p65 and p50 translocation from the cytosol to the nucleus, and kappaB-luciferase activity. Thrombin-mediated an increase of IKK alpha/beta activity, kappaB-luciferase activity and p65 and p50 binding to the NF-kappaB element was inhibited by PPACK, U73122, Ro320432 and PP2. The binding of p65 and p50 to the NF-kappaB elements, as well as the recruitment of p300 and the enhancement of p50 acetylation on the IL-6 promoter was enhanced by thrombin. Our results suggest that thrombin increased IL-6 production in synovial fibroblasts via the PAR1 receptor/PI-PLC/PKC alpha/c-Src/NF-kappaB and p300 signaling pathway.

Transpedicular partial corpectomy without anterior vertebral reconstruction in thoracic spinal metastases.

STUDY DESIGN: We retrospectively reviewed surgical results of posterolateral transpedicular partial corpectomy without anterior vertebral reconstruction in 23 consecutive patients with symptomatic metastatic spinal cord compression at thoracic spine. OBJECTIVE: To evaluate postoperative outcomes and survival rates of patients undergoing transpedicular partial corpectomy without anterior vertebral reconstruction. SUMMARY OF BACKGROUND DATA: The need for anterior reconstruction after radical resection of vertebral body tumors has been emphasized by several authors. However, the stability of thoracic spine is substantially increased by the rib cage. The role of reconstruction may be not necessary in thoracic spine when partial corpectomy is performed. METHODS: From November 2001 to November 2006, 23 patients with symptomatic metastatic spinal cord compression at thoracic spine underwent palliative surgery using a transpedicular partial corpectomy without anterior vertebral reconstruction. The indication for surgery was neurologic progression due to spinal cord compression. RESULTS: Patients ranged in age from 20 to 88 years (mean, 57.0 years). Neurologic improvement by at least one Frankel grade was noted in 19 of 23 cases (82.6%). Overall, 73.9% of patients (17 of 23) could walk after surgery. There was no intraoperative mortality. Median survival time was 11.3 months. There was no implant failure. CONCLUSION: The results of this study suggest that the stability of implants can be maintained up to 55.8 months without anterior vertebral reconstruction in thoracic spine.

Local metastases along the tract of needle: a rare complication of vertebroplasty in treating spinal metastases.

STUDY DESIGN: Needle tract seeding after biopsy has been reported by many authors. Since the procedure of needle insertion in vertebroplasty is the same as in biopsy, tumor metastasis along the tract of the needle in vertebroplasty should be possible. OBJECTIVE: We report local metastases along the needle tract as a rare complication of percutaneous vertebroplasty in treating spinal metastases in a lung cancer patient. SUMMARY OF BACKGROUND DATA: The true incidence of tumor implantation along the needle tract may be underestimated as many patients die before the metastases become clinically significant. METHODS: A 76-year-old man diagnosed with adenocarcinoma of lung underwent percutaneous vertebroplasty at L1 and L3 vertebral levels due to painful spinal metastases. His condition worsened 3 months later, however, with recurrent back pain and weakness of both legs. RESULTS: MRI of lumbar spine performed post-percutaneous vertebroplasty revealed new contrast-enhanced lesions at the posterior aspect of L1 vertebral body with extension to the adjacent anterior epidural space of L1 and posterior epidural space along T12 to L3 levels with compression of the adjacent dural sac and additional paraspinal involvement. CONCLUSION: To our knowledge, local metastasis after vertebroplasty in treating spinal metastases has not been reported in the literature. However, this may be a potential complication of vertebroplasty in treating spinal metastases as improvement in cancer treatments occurs with subsequent longer survival times.

Surgical results of metastatic spinal cord compression secondary to non-small cell lung cancer.

STUDY DESIGN: The results for 37 surgical interventions in 31 consecutive patients with non-small cell lung cancer (NSCLC) with symptomatic spinal cord compression were reviewed retrospectively. OBJECTIVES: To evaluate postoperative outcomes and survival rates of NSCLC patients surgically treated for symptomatic spinal metastasis. SUMMARY OF BACKGROUND DATA: For patients with spinal cord compression secondary to lung cancer, the prognosis is usually poor. However, with the development of new chemotherapeutic drugs and targeted therapeutic agents, the survival rate may be better. METHODS: From November 2000 to March 2005, 31 patients with symptomatic metastatic spinal cord compression secondary to NSCLC underwent palliative surgery using a posterolateral transpedicular approach (PTA) or combined posterior and anterior procedures. The indication for surgery was neurologic progression due to spinal cord compression. RESULTS: The patients ranged in age from 20 to 81 years (mean, 61.4 years). Twenty-eight patients (90%) underwent PTA, and 3 patients had combined posterior and anterior procedures. Neurologic improvement by at least one Frankel grade was noted in 25 of 31 cases (80%). Overall, 74% of patients (23 of 31) were able to walk after surgery. There was no case of intraoperative mortality, but two deaths occurred in the postoperative period. Median survival time was 8.8 months. CONCLUSIONS: Even though lung cancer is considered an aggressive tumor, it is justifiable to aggressively treat patients with symptomatic spinal cord compression. Surgery by PTA can lead to good results in these patients.

Stromal cell-derived factor-1 induces matrix metalloprotease-13 expression in human chondrocytes.

The production of chemokine stromal cell-derived factor (SDF)-1 is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinase (MMP)-13 may contribute to the breakdown of articular cartilage during arthritis. Here, we found that SDF-1alpha increased the secretion of MMP-13 in cultured human chondrocytes, as shown by reverse transcriptase-polymerase chain reaction, Western blot, and zymographic analysis. SDF-1alpha also increased the surface expression of CXCR4 receptor in human chondrocytes. CXCR4-neutralizing antibody, CXCR4-specific inhibitor [1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane (AMD3100)], or small interfering RNA against CXCR4 inhibited the SDF-1alpha-induced increase of MMP-13 expression. The transcriptional regulation of MMP-13 by SDF-1alpha was mediated by phosphorylation of extracellular signal-regulated kinases (ERK) and activation of the activator protein (AP)-1 components of c-Fos and c-Jun. The binding of c-Fos and c-Jun to the activator protein (AP-1) element on the MMP-13 promoter and the increase in luciferase activity was enhanced by SDF-1alpha. Cotransfection with dominant-negative mutant of ERK2 or c-Fos and c-Jun antisense oligonucleotide inhibited the potentiating action of SDF-1alpha on MMP-13 promoter activity. Taken together, our results provide evidence that SDF-1alpha acts through CXCR4 to activate ERK and the downstream transcription factors (c-Fos and c-Jun), resulting in the activation of AP-1 on the MMP-13 promoter and contributing cartilage destruction during arthritis.

Intradural cement leakage: a devastatingly rare complication of vertebroplasty.

STUDY DESIGN: The aim of this case report is to examine the devastating complication that may follow vertebroplasty. OBJECTIVES: To report 1 case of intradural cement leakage caused by percutaneous vertebroplasty with polymethyl methacrylate. SUMMARY OF BACKGROUND DATA: Cement leakage is not a rare complication of vertebroplasty. But intradural cement leakage is rare. We herein report a rare but devastating complication of vertebroplasty. METHODS: A 90-year-old woman with a T12 and L1 osteoporotic compression fracture underwent percutaneous vertebroplasty using polymethyl methacrylate at local hospital. A literature search was performed to assess complications of vertebroplasty. RESULTS: She was transferred to our hospital due to abdominal pain. Physical examination revealed distended abdomen with local tenderness and weakness of both legs (muscle power: Grade 2). Plain radiograph of abdomen showed ileus and intradural cement leakage. Conservative treatment with nasogastric decompression was done, and her abdominal pain subsided 1 week later. CONCLUSIONS: Percutaneous vertebroplasty with polymethyl methacrylate is relatively safe, but it still should be proceeded under careful safeguard. The needle tip should not cross the medial border of the pedicle on the anteroposterior view before it has crossed the posterior cortex of the vertebral body on the lateral view. Good quality of image monitoring and clear visualization of cement should be helpful to prevent complications.

Superficial radial nerve compression caused by a parosteal lipoma of proximal radius: a case report.

The superficial radial nerve might be compressed or injured at various anatomical sites along its course in the forearm. Most of the superficial radial nerve neuropathy are caused by pathological lesions such as trauma, a mass or tight band at the distal third of the forearm. Wartenberg's syndrome is the most common cause of sensory radial entrapment at the distal forearm. Compression of superficial radial nerve occurring at the proximal third of forearm is unusual. We present a rare case of superficial radial nerve compression due to a parosteal lipoma of proximal radius. Results of complete physical and radiological examinations are also presented. Surgical intervention of the tumour mass was performed for nerve decompression. The patient reported total relief of the neurological symptom post-operatively. This rare case demonstrates the unique characteristics of parosteal lipoma with unusual superficial radial nerve neuropathy at the proximal radius. This report reminds us that there is the possibility of superficial nerve compression caused by tumour mass over the proximal third of forearm.

Displacement of the distal radioulnar joint of clinically symptom-free patients.

There are three methods for evaluation of dislocation of the distal radioulnar joint using computed tomography: the radioulnar line method, the epicenter method, and the congruity method. However, some patients who are clinically symptom-free have abnormal findings from computed tomography of the distal radioulnar joint according to the aforementioned criteria. In addition, these methods are qualitative, not quantitative definitions. Forty patients were included in this study. Computed tomography scans of the wrists were done. The variation of displacement of the distal radioulnar joint was measured. By the epicenter method, the 95% confidence interval (mean +/- 1.96 standard error) was from 0.0026 to 0.1114 in supination and from -0.1171 to 0.0446 in pronation. By the radioulnar line method, the 95% confidence interval was from 0.0026 to 0.0479 in supination and from -0.0065 to 0.0745 in pronation. By the modified radioulnar line method, the 95% confidence interval was from 0.1778 to 0.2752 in supination and from 0.0990 to 0.2310 in pronation. There was a wide range of the displacement of the distal radioulnar joint in patients with clinically normal wrists. The results can be regarded as reference points for normal variation of the distal radioulnar joint. This can help to differentiate the causes of internal derangement of the wrist.

Spinal epidural lipomatosis with thoracic osteoporotic compression fracture causing paraplegia.

Spinal epidural lipomatosis (SEL) frequently occurs as a result of long-term steroid administration for various disorders, and patients often present with osteoporosis. Acute paraplegia in patients with extensive thoracic SEL is rare. We report a case of acute paraplegia caused by osteoporotic compression fracture with extensive thoracic SEL in a 44-year-old man with rheumatoid arthritis who had received steroid therapy for 4 years. He presented initially with abdominal distension and weakness of lower limbs, and a sudden onset of paraplegia with complete motor and sensory loss below the T6 level ensued. Plain radiographs showed an osteoporotic compression fracture of the T6 vertebra. Magnetic resonance imaging showed osteoporotic compression fractures of the T5 and T6 vertebrae and SEL from T2 to T10 vertebrae. Decompressive laminectomy with epidural fat debulking was performed, and the pathology was confirmed as epidural lipomatosis. His neurological condition showed no improvement below the T6 level 3 months after surgery. Osteoporotic compression fracture is a risk factor for acute paraplegia in patients with thoracic SEL and decompressive surgery should be performed without delay.

Isolated supra-acetabular insufficiency fracture: a case report.

In the absence of trauma, fracture of the acetabulum is a rare injury, and an isolated insufficiency fracture in the supra-acetabular region is extremely rare. We describe a 59-year-old postmenopausal woman with systemic lupus erythematosus (SLE) who developed a fracture in the roof of the acetabulum with underlying corticosteroid-induced bony insufficiency. Faint medullary sclerosis over the roof of the acetabulum was observed on plain roentgenograms. Diagnosis was made using magnetic resonance imaging. Irregular linear low signal intensity lines were observed on T1-weighted, T2-weighted, proton density, and contrast enhanced images, and these represented the fracture. The fracture healed with conservative management. Insufficiency fracture in this location should be suspected in an osteopenic woman with spontaneous hip pain.

Clinical features and outcome of crush syndrome caused by the Chi-Chi earthquake.

BACKGROUND AND PURPOSE: Few reports exist concerning the peak serum concentration of creatine kinase (CK) and the severity of crush syndrome, and the efficacy of fasciotomy in crush syndrome patients remains controversial. This study aimed to analyze and assess the clinical features, treatment, and outcome of patients with crush syndrome sustained in the Chi-Chi earthquake in September 21, 1999. METHODS: Pertinent data were collected from major hospitals in central Taiwan via questionnaire. Patients with a peak serum CK concentration of more than 1,000 U/L within 2 weeks following the earthquake were included in the study. Eight hospitals responded and a total of 95 patients were included for the analysis. RESULTS: Forty-four patients (46.3%) with acute renal failure were found to have a serum creatinine level of more than 159 mumol/L (1.8 mg/dL) or daily urine output of less than 400 mL. Thirty patients (31.6%) required hemodialysis, which completely restored renal function. The incidence of acute oliguria, acute renal failure, and the need for hemodialysis were significantly increased if the peak CK concentration was more than 50,000 U/L (p < 0.01). Thirty-five patients underwent fasciotomy to treat compartment syndrome caused by crush syndrome. Among these, 31 patients (88.6%) had a peak CK concentration higher than 10,000 U/L. The incidence of acute renal failure (p < 0.01) and the need for hemodialysis (p < 0.01) were significantly higher in the fasciotomy group than in the non-fasciotomy group. Eight patients developed superficial infection and 16 developed deep infections after fasciotomy. Six patients underwent amputations and one patient died of sepsis due to uncontrolled infection of the fasciotomy wound. CONCLUSION: CK concentration is a good indicator of the occurrence of acute renal failure and the need for dialysis. The high infection rate and amputation rate after fasciotomy may be due to inadequate debridement. Fasciotomy in crush syndrome patients with high serum CK concentrations should be deliberated.