Terumasa Ikeda

Effects of sodium hyaluronic acid on fibrinolytic factors in the synovial fluid (in vivo)

Abstract Twelve patients with osteoarthritis of the knee were administrated hyaluronic acid (HA), and measured for fibrinolytic factors on synovial fluids. It was observed that urokinase-type plasminogen activator (u-PA) activity is enhanced 3 h after administration of HA, and that the activity gradually decreased from the 2nd to the 4th week on the patients whose clinical parameters showed improvement. Antigen of u-PA and PA inhibitor-1 (PAI-1) were increased 3 h after the administration of HA in the cases that improved. However, u-PA antigen gradually decreased from the 2nd to the 4th week similarly to u-PA activity. On the other hand PAI-1 antigen was increased from the 2nd to the 4th week in the improved cases. These results demonstrate that the decrease of fibrinolytic activity in synovial fluid is associated with the improvement of osteoarthritis by treatment with HA.

Radiologic analysis of pedicle marker for the cervical spine

PURPOSE To elucidate the usefulness of the pedicle marker (PM) for more accurate insertion of cervical pedicle screws (CPSs). METHODS Artificial bone study. Fifty pedicles of five artificial bone specimens were examined. PMs were inserted in five different positions (confirmed by computed tomography (CT)); (1) insertion angle correct, insertion point too medial, (2) both insertion angle and insertion point correct, (3) insertion angle correct, insertion point too lateral, (4) insertion point correct, insertion angle too big, and (5) insertion point correct, insertion angle too small. Oblique radiographs were taken to assess the relationships between the pedicle and the PM as IN and OUT. Clinical series. A total of 228 CPSs were inserted in 59 consecutive patients using either CT cutout technique or navigation. During surgery, PMs were inserted, and the locations were confirmed on oblique fluoroscopic views in CT cutout technique and intraoperative CT in navigation. Intraoperative misplaced PM and postoperative misplaced CPS were assessed. RESULTS Artificial bone study. Evaluation found 67% of Types 1 and 100% of Type 5 seemed to be IN on the oblique views at 10, 20, and 30° because the pedicle and PM overlapped. All cases of Type 2 were IN at any angles. Almost all Types 3 and 4 were OUT at any angle. Clinical series. The route was modified under the recognition of misplaced PM during surgery in 3.7% (all Type 4) of CT cutout and 4.2% (four Type 4 and one Type 5) of navigation. One CPS was malpositioned (0.9%, Type 1) in CT cutout and none in navigation by postoperative CT. CONCLUSIONS By applying PM, lateral displacement is easier to recognize in fluoroscopy. Medial misplacement should be aware because the PM and the rim of the pedicle overlap. Even after launching navigation, PM helped to indicate the wrong route before inserting the CPS during surgery.

An algorithmic strategy of surgical intervention for cervical degenerative kyphosis

PURPOSE Correction surgery for cervical degenerative kyphosis (CDK) may carry a greater risk of causing neural complications such as spinal cord injury and C5 nerve palsy because spinal canal stenosis, osteoarthritis of the facet, and consequent foraminal stenosis may coexist with CDK. We have produced an algorithmic strategy of surgical intervention for CDK, and report the outcome. METHODS Thirty-one patients who underwent correction surgery for CDK, with a kyphotic angle of 20° or more (from 20 to 74) were involved. An algorithmic surgical strategy is shown. Clinical and radiological outcomes were examined amongst the groups. RESULTS Recovery rate of the JOA score was a mean of 44%. Preoperative kyphotic angle and correction angle were; 24.4°and 26.5°in P, 38.4°and 41.1°in AP, and 42.0°and 46.9°in PAP respectively. No spinal cord injury was found. Five cases of C5 nerve palsy occurred in P, and one in AP. Four cases of C5 palsy occurred in seven patients in PAP, although prophylactic foraminotomy was performed. All C5 palsy patients recovered fully at follow-up. CONCLUSIONS This study showed that our algorithmic surgical strategy for CDK is acceptable because we obtained good outcomes, and no catastrophic complications occurred. Although we did not intend to obtain excessive postoperative lordosis, we still had several incidence of C5 nerve palsy. We have to be aware of this incidence in PAP, which required a massive range of realignment. The incidence occurred even after we performed prophylactic foraminotomy, however, this procedure may lessen the severity of C5 palsy because those were all transient.

LOX-1 deficient mice show resistance to zymosan-induced arthritis

Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX- 1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KO mice with ZIA or the salineinjected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.

Effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density in patients with ophthalmologic disease treated with glucocorticoid

Abstract Objectives. Glucocorticoid (GC) is usually used for the treatment of systemic inflammatory diseases. We performed the prospective study to clarify the effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density (BMD) in 90 patients treated with GC for ophthalmologic diseases without systemic disorders for 12 months. Methods. BMD was measured with dual-energy X-ray absorptiometry. Serum bone-specific alkaline phosphatase (BAP) and urinary Type I collagen cross-linked N-telopeptide (NTx) were measured as bone metabolic indices. Results. BMD values in the alendronate group were significantly higher than those in the alfacalcidol group during 12 months. Alendronate significantly reduced urinary NTX levels from the baseline during 12 months, although alfacalcidol did not affect them. Serum BAP levels in the alendronate group were significantly lower than those in the alfacalcidol group during 9 months. The effects of alendronate on BMD and NTx in male patients seemed to be somewhat potent compared with those in female patients. Conclusions. Alendronate is effective to prevent BMD loss and bone resorption induced by GC treatment in patients with ophthalmic diseases without systemic disorders. There might be sex differences in the potency of alendronate effects.

Effects of Sodium Hyaluronic Acid on Fibrinolytic Factors in Humans with Arthropathies

High molecular weight (90- to 100-kDa) plasminogen activator (PA) urokinase-type/inhibitor-1 ([u-PA/PAI-1] complex) and 55-kDa u-PA were identified in synovial fluid collected from 12 osteoarthritis (OA) patients given hyaluronic acid (HA) into the knee joint. HA administration led to an increase in levels of u-PA and PAI-1 antigen as well as increases in the u-PA:PAI-1 ratio. In inhibition of their symptoms, the fibrinolytic activity was progressively suppressed. The u-PA content was higher at the weight-bearing site in OA and rheumatoid arthritis (RA) patients compared to cartilage tissue from controls. The PAI-1 content was higher in osteophyte-forming sites and in RA, compared to controls. Weight-bearing sites in OA patients expressed a high u-PA mRNA level but a low PAI-1 mRNA level. Osteophyte-forming sites in OA patients expressed a low u-PA mRNA level but a high PAI-1 mRNA level. The levels of u-PA and PAI-1 antigen increased in cartilage tissues exposed to mechanical stress. In contrast, the release of u-PA and PAI-1 antigens from specimens was suppressed with HA. At the weight-bearing site, the levels of matrix metalloproteinase (MMP) were high and levels of TIMP (tissue inhibitor of metalloproteinase) mRNA expression were low. In osteophyte-formed sites, the levels of TIMP were high and the levels of MMP mRNA expression low. These findings suggest that regulation of fibrinolysis may play a important role in the matrix of articular cartilage with arthropathy.