Tunicamycin decreases the probability of single-channel openings for N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors.

In whole-cell patches from cultured rat hippocampal neurons, tunicamycin (0.1-30 microM), an inhibitor of protein N-glycosylation, depressed currents through N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor channels in a concentration-dependent manner. Tunicamycin shifted the agonist concentration-response curve for each receptor type to the right. In an outside-out patch-clamp configuration, tunicamycin reduced the number of single-channel opening events in parallel with prolonged mean shut time, without affecting the slope conductance for both the receptors. These tunicamycin effects were obtained with acute treatment, suggesting an action independent of any blockage of N-glycosylation. Tunicamycin, thus, may modify the agonist binding affinity of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, thereby causing a decrease in the probability of single-channel openings leading to the depression of whole-cell membrane currents.

Modulation of P2X receptors via adrenergic pathways in rat dorsal root ganglion neurons after sciatic nerve injury.

The present study examined noradrenaline-induced modulation of ATP-evoked currents in dorsal root ganglion (DRG) neurons after sciatic nerve injury (transection). ATP (10 microM) generated fast/mixed type of whole-cell membrane currents, possibly as mediated via P2X(3)/P2X(3)-like receptors, and slow type of the currents, possibly as mediated via P2X(2/3) receptors, in acutely dissociated L4/5 DRG neurons, without significant difference between sham and injury group. For sham group, noradrenaline (10 microM) enhanced fast/mixed type of ATP-evoked currents in ipsilateral DRG neurons, that is not inhibited by H-7, a broad inhibitor of protein kinases, but otherwise it had no effect on slow type of the currents. For injury group, noradrenaline (10 microM) significantly potentiated slow type of ATP-evoked currents in ipsilateral DRG neurons, that is abolished by H-7 or GF109203X, a selective inhibitor of protein kinase C (PKC), while it depressed fast/mixed type of the currents. In the analysis of real-time reverse transcription-polymerase chain reaction, an increase in the mRNAs for alpha(1b), alpha(2a), alpha(2d), and beta(2) adrenergic receptors was found with the ipsilateral DRGs after sciatic nerve injury. Collectively, the results of the present study suggest that noradrenaline potentiates P2X(2/3) receptor currents by activating PKC via alpha(1) adrenergic receptors linked to G(q) protein, perhaps dominantly alpha(1b) adrenergic receptors, in DRG neurons after sciatic nerve injury. This may account for a nociceptive pathway in response to noradrenergic sprouting after peripheral nerve injury.

Tunicamycin inhibits NMDA and AMPA receptor responses independently of N-glycosylation.

In a whole-cell patch-clamp configuration, currents through N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels were monitored in cultured rat hippocampal neurons, and those currents were depressed to 25 and 28% of basal levels, respectively, by 3-min treatment with tunicamycin (10 microM), an inhibitor of protein N-glycosylation. Tunicamycin (10 microM) reduced amplitude of population spikes elicited in the dentate gyrus of rat hippocampal slices, reaching 78% of basal levels 60 min after the beginning of treatment, and long-term potentiation (LTP) of the perforant path was never induced in the presence of tunicamycin. Tunicamycin, thus, appears to serve as a modulator for NMDA and AMPA receptors, regardless of N-glycosylation, thereby inhibiting neurotransmission and LTP in the dentate gyrus.

Distinction between well-differentiated liposarcoma and intramuscular lipoma by power Doppler ultrasonography.

BACKGROUND: This study evaluates the feasibility of ultrasonography in the distinction between well-differentiated liposarcoma (WDLS) and intramuscular lipoma (IL). MATERIALS AND METHODS: Three WDLSs and 9 ILs were included. Gray scale images were assessed for echogenicity, textural pattern and margins. Power Doppler ultrasonography was used to assess the number of detectable flow velocity signals in a 3 x 3 cm area. Furthermore, the ratio of the area occupied by colour flow signals relative to the selected area was determined. RESULTS: Gray scale images showed no differences between WDLSs and ILs. However, power Doppler showed more than 2 flow velocity signals in all WDLSs, whereas only 11% of the ILs had 2 signals. In all WDLSs, colour flow signals occupied more than 30% of the selected area. In contrast, ILs were characterized by a low color-dot ratio. Histologically, increased vascularity was found close to malignant cell invasions. CONCLUSION: Power Doppler ultrasonography is feasible to evaluate increased vascularity and thus differentiate WDLSs from ILs.

Usefulness of ultrasonography for early recurrent myositis ossificans.

Myositis ossificans is a benign heterotopic ossifying condition of soft tissues. The lesion may cause persistent functional impairment of adjacent joints. Surgical intervention is often needed to regain normal function, even though a high recurrence rate is reported. In the present case, we found that recurrent myositis ossificans could not be demonstrated by radiography during the early stage. However, ultrasonography proved to be an excellent tool for detecting early recurrence of myositis ossificans and for distinguishing the condition from extraosseous sarcomas.

Successful reimplantation of total femoral prosthesis after deep infection.

A 16-year-old boy developed a deep infection with methicillin-resistant Staphylococcus aureus 6 months after total femoral replacement including knee and hip joints. The deep infection was eradicated by the use of débridement with continuous irrigation and removal of all prosthetic components followed by insertion of an antibiotic-impregnated cement spacer. Six weeks later, the total femoral prosthesis could be successfully reimplanted with both acetabular and tibial components. Two and half years later, the patient remained free of infection. Débridement with continuous irrigation and an antibiotic-impregnated cement spacer can be a feasible technique for the treatment of deep infection after large prosthetic replacement. Furthermore, reimplantation should be performed after a short waiting period. Such treatment should be considered before deciding on amputation.

Sonographic appearance of fibrous nodules in patellar clunk syndrome: a case report.

Patellar clunk syndrome is a rare complication causing pain after total knee arthroplasty. However, it is important to differentiate it from the other causes of patellofemoral pain. In this article, we apply ultrasonography for the first time to demonstrate the suprapatellar fibrous tissue causing this condition. A 50-year-old woman with rheumatoid arthritis had left total knee arthroplasty. The patient had excellent results until 2 years after surgery, when she complained of anterior knee pain. On physical examination, a patellar "catch" and "pop" were noted from 45 degrees flexion to full extension. Roentgenograms showed a radiolucent line at the upper pole of the patella and no subluxation of the patella on skyline view. Sagittal and transverse gray-scale sonographic images revealed an echogenic area attached to the quadriceps tendon. Corresponding color Doppler sonographic images showed marked vascularity in this echogenic area. The patient was treated with removal of the suprapatellar tissue and a patellar component revision. Intraoperatively, the suprapatellar tissue, which measured 4 x 4 x 2 cm, entered the notch area of the femoral component on flexion and caused the patellar "pop" on knee extension. Pain relief was obtained immediately after the operation when smooth gliding motion of the patella was restored.

Evaluation of an interference screw for tendon reattachment to small bones.

OBJECTIVES: To compare the strength of interference screw fixation of the tendon to suture button fixation and staple fixation methods. DESIGN: Biomechanical study. METHODS: The femurs and flexor digitorum tendon of twelve rabbits were used. The tendon was attached to the medial condyle of the femur using one of the following three surgical procedures: (a) interference screw fixation: tendon-junction screw was used as an interference screw, (b) suture button fixation: the tendon was inserted through a hole and attached with a button on the opposite side, and (c) staple fixation: the tendon was attached using two staples. Strengths of the attached tendons were then measured using a universal testing machine. RESULTS: The ultimate failure load of interference screw fixation was 62.8 +/- 9.0 N, whereas that of suture button fixation was 13.9 +/- 3.8 N and staple fixation was 23.9 +/- 2.6 N. CONCLUSION: Interference screw fixation provides significant initial fixation strength (p < 0.05).

Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation.

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic joint changes. Interleukin (IL)-18 is a potent inducer of prostaglandin (PG) E2 in vitro. We determined the relation between IL-18 and PGE2 in synovial fluid (SF) of human OA, and discussed the role of IL-18 in the pathogenesis of OA and also its therapeutic consequences. SF was collected from 30 patients with knee OA. The concentrations of IL-18 and other cytokines including IL-1beta, tumor necrosis factor (TNF)-alpha, IL-6, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of PGE2 was also assessed by inhibitory ELISA. The average value of IL-18 was 248 +/- 310 pg/mL. The average value of PGE2 was 93 +/- 103 pg/mL. There was a relatively strong correlation between IL-18 and PGE2 (r = 0.78, p = 0.0001). In contrast, IL-1beta was undetectable (cutoff point of 20 pg/mL), except for one case. TNF-alpha was also undetectable (cutoff point of 20 pg/mL), except for two cases. The average value of IL-6 was 1,310 +/- 2,623 pg/mL (n = 17), whereas IL-8 was 5,208 +/- 6,031 pg/mL (n = 5). Furthermore, IL-6 and IL-8 correlated with IL-18 (r = 0.69, p = 0.0024 and r = 0.87, p = 0.0527, respectively). Our results suggest that IL-18 could play a major role in vivo in inducing the production of PGE2, which in turn can cause cartilage degradation in OA pathogenesis. Thus, targeting this cytokine appears to be an important therapeutic approach in OA.

Successful limb salvage of pathological fracture of the distal tibia caused by cancer metastasis.

Pathological fractures of the distal tibia as a result of cancer metastases are rare. In particular, the management of intraarticular fractures of the distal tibia has not been established. In this article, we present a case of pathological intraarticular fracture with an extensive bone defect of the distal tibia that was successfully treated by limb salvage with a locked intramedullary nail and pirarubicin-impregnated methylmethacrylate. A 52-year-old patient with duodenal cancer presented with a painful swelling in the left crus. The condition was diagnosed as an impending pathological fracture of the tibia because of cancer metastasis. During radiation therapy, an actual pathological fracture of the distal tibia occurred due to an accident. Limb-salvage surgery was performed by removing the metastatic lesion, followed by using a locked intramedullary nail. Three distal and seven proximal locking screws were inserted into the tarsal bones and the remaining tibia. About 10 cm of bone defect was reconstructed by pirarubicin-impregnated methylmethacrylate. Consequently, good stability was achieved. One month later the patient could walk without any aid. Postoperative functional score was 77% according to the Musculoskeletal Tumor Society criteria. There was no recurrence; however, the patient died of lung metastases 4 months after the limb-salvage surgery.