Toru Suguro

Inflammatory cytokines in the herniated disc of the lumbar spine.

Study Design Tissues in the area of herniated lumbar discs were examined for inflammatory cytokines to elucidate the causes of sciatic pain in lumbar disc herniation. Objectives To determine the role of inflammatory cytokines in the stimulation of sciatic pain in lumbar disc herniation. Summary of Background Data It is postulated that in addition to mechanical compression of lumbar nerve roots and sensory root ganglia by herniated discs, there is a chemical stimulus to the production of sciatic leg pain. The exact mechanisms of chemical stimulation are not clearly defined. Methods During surgery, cases of lumbar disc herniation in 77 patients were classified macroscopically into protrusion, extrusion, and sequestration types. Tissues adjacent to nerve roots at the herniation were excised and analyzed biochemically and immunohistochemically for the presence of inflammatory cytokines and for the production of these cytokines and prostaglandin E2 in vitro. Results The homogenates of samples were analyzed for interleukin-1α, interleukin-1β, interleukin-6, tumor necrosis factor-α, and granulocyte-macrophage colony stimulating factor, which were detectable. Most of the cytokine-producing cells were histiocytes, fibroblasts, or endothelial cells in extrusion and sequestration types, and chondrocytes in protrusion type. The secretion of these cytokines and prostaglandin E2 was decreased by the addition of betamethasone. The prostaglandin E2 production was dramatically enhanced by additional interleukin-1α, but decreased by the addition of tumor necrosis factor-α. Conclusion The results demonstrate that at the site of lumbar disc herniation, inflammatory cytokines such as interleukin-1α are produced, which increases prostaglandin E2 production. Further studies are required to elucidate the role of inflammatory cytokines in causing sciatic pain.

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

Adiponectin stimulates prostaglandin E2 production in rheumatoid arthritis synovial fibroblasts

OBJECTIVE Adipokines may influence inflammatory and/or immune responses. This study was undertaken to examine whether adiponectin affects the production of prostaglandin E(2) (PGE(2)) by rheumatoid arthritis synovial fibroblasts (RASFs). METHODS Synovial tissue was obtained from patients with RA who were undergoing joint replacement surgery. Fibroblast-like cells from the third or fourth passage were used as RASFs. Expression of adiponectin receptor messenger RNA (mRNA) and protein was detected. PGE(2) (converted from arachidonic acid) was measured by enzyme-linked immunosorbent assay (ELISA). Expression of mRNA and protein for cyclooxygenase 2 (COX-2) and membrane-associated PGE synthase 1 (mPGES-1), key enzymes involved in PGE(2) synthesis, was detected in RASFs. The effects of RNA interference (RNAi) targeting the adiponectin receptor genes and the receptor signal inhibitors were examined. The influence of adiponectin on NF-kappaB activation in RASFs was measured with an ELISA kit. RESULTS Adiponectin receptors were detected in RASFs. Adiponectin increased both COX-2 and mPGES-1 mRNA and protein expression by RASFs in a time- and concentration-dependent manner. PGE(2) production by RASFs was also increased by the addition of adiponectin, and this increase was inhibited by RNAi for the adiponectin receptor gene, or coincubation with the receptor signal inhibitors. Enhancement of NF-kappaB activation by adiponectin as well as by interleukin-1beta was observed in RASFs. CONCLUSION Our findings indicate that adiponectin induces COX-2 and mPGES-1 expression, resulting in the enhancement of PGE(2) production by RASFs. Thus, adiponectin may play a role in the pathogenesis of synovitis in RA patients.

Analysis of the kinematics of total knee prostheses with a medial pivot design.

Analysis of the kinematics of the FINE Total Knee System (Nakashima Medical, Okayama, Japan) revealed that the medial condyle is fixed and the lateral condyle shows lateral posterior movement and tibial internal rotation. Analysis of the kinematics of the ADVANCE Total Knee System (Wright Medical Technology, Arlington, Tenn) revealed that the medial condyle is fixed and the lateral condyle shows anterior movement in the early stage, changing thereafter to posterior movement. With regard to rotation, initial external rotation subsequently changes to internal rotation. Analysis of the kinematics of the ADVANTIM Total Knee System (Wright Medical Technology) revealed that the bicondyle shows posterior movement, subsequently changing to anterior and posterior movements. Thus, unlike the FINE or ADVANCE Total Knee Systems, the ADVANTIM Total Knee System shows internal rotation.

Perioperative complications in elective surgery in patients with rheumatoid arthritis treated with biologics.

We retrospectively investigated the influence of biological agents on delayed wound healing and the occurrence of postoperative surgical site infection (SSI) in patients after surgery for rheumatoid arthritis. The patients were divided into two groups—those with and without treatment with biological agents (276 and 278 joints, respectively)—and adverse events (delay in wound healing and SSI) were investigated. Wound healing was delayed in 11.4% of total knee arthroplasty (TKA) operations, 16.7% of total ankle arthroplasty operations, and 9.7% of foot surgeries in the treatment group, and in 5.5% of TKA operations, 12.5% of total elbow arthroplasty operations, and 5.7% of foot surgeries in the non-treatment group. The difference in the incidence of delayed wound healing between the two groups was not statistically significant. In the treatment group, postoperative superficial and deep infection developed in one and two joints, respectively. In the non-treatment group, superficial infection developed in one joint. There was no statistically significant difference between the two groups. These findings suggest that the use of biological agents may not affect the incidence of postoperative adverse events related to wound healing and SSI.

Recent trends in orthopedic surgery performed in Japan for rheumatoid arthritis

The aim of this report was to review the use of orthopedic surgeries performed to manage rheumatoid arthritis (RA). Our review of studies published in English indicates that there has been a decrease in RA-associated surgeries in Western countries. Improvements in medical treatment may partly explain the reduction in numbers of orthopedic joint surgeries, which also suggests a worldwide trend toward improved long-term outcomes. However, the results of our multicenter study in Japan indicate that the number of RA-associated operations has not decreased, and that the numbers of operations performed annually have been relatively stable from 1998 to 2008. Although there definitely has been a decline in the numbers of synovectomy surgeries, the numbers of operations on the upper limbs and foot arthroplasties have increased. With the trend toward milder disease because of improved medical treatment, we speculate that RA patients may want and need better function for the activities of daily living. The combination of medical treatment and surgical intervention is thought to improve outcomes in RA patients who will develop joint destruction. Additional studies, including analyses of RA databases containing long-term data on a variety of surgical interventions, are needed.

Antimicrobial prophylaxis for spinal surgery

BackgroundThe concept of antimicrobial prophylaxis (AMP) did not exist in Japan until recently. Therefore, postoperative administration of antimicrobial drugs has long been practiced under the pretext of prophylaxis against surgical site infection (SSI). In recent years, however, the concept of AMP and prophylactic countermeasures against SSI, based on evidence of the effectiveness of AMP, has gradually spread in Japan. From 2000 onward, we have undertaken prophylactic countermeasures against SSI in patients undergoing spinal surgery referring to the Guideline for Prevention of Surgical Site Infection published by the Centers for Disease Control and Prevention in 1999. The purpose of this study was to investigate the type of AMP that would be appropriate for spinal surgery and the manner in which it should be used.MethodsThe subjects were 1415 patients who underwent spinal surgery at our department from January 1990 to March 2008. The patients were classified into four groups according to the method of AMP administration: group 1, AMP was employed for 7 days, only postoperatively; group 2, initial AMP dosing was administered at the time of anesthesia induction, followed by administration of AMP for 5 days, including the day of the operation; group 3, initial AMP dosing was administered at the time of anesthesia induction, and AMP was administered for 3 days, including the day of the operation; group 4, the initial dosing was administered at the time of anesthesia induction, and AMP was administered for 2 days, including the day of the operation. The frequency of SSI was assessed in the four groups.ResultsThe frequencies of SSI in groups 1—4 were 2.6% (14/539), 0.9% (5/536), 0% (0/257), and 0% (0/83), respectively. Thus, the frequency of SSI decreased as the duration of the AMP administration period decreased.ConclusionsAs a result of thorough implementation of preventive measures against perioperative occurrence of infections, which included additional preoperative and intraoperative administration of AMP, the incidence of SSI could be decreased despite shortening the duration of AMP administration to 2 days.

Effect of cage geometry on sagittal alignment after posterior lumbar interbody fusion for degenerative disc disease.

Purpose. To compare the sagittal alignment of the lumbar spine after one-segment posterior lumbar interbody fusion (PLIF) using the horizontal cylinder (HC) or open box (OB) type cage. Methods. 66 patients underwent instrumented one-segment PLIF with bone grafting for lower lumbar degenerative disease. HC-type cages were used in 33 men and 13 women aged 20 to 73 (mean, 47) years between September 2001 and July 2004. OB-type cages with a 3° lordotic angle were used in 9 men and 11 women aged 25 to 70 (mean, 53) years between July 2004 and September 2006. Pre- and post-operative lumbar lordosis and intervertebral body angles in the fused and upper adjacent levels in the 2 groups were compared. Results. There was no significant difference between the 2 groups with regard to changes in the lumbar lordosis and intervertebral body angle in the fused and upper adjacent levels. In both groups, the upper adjacent intervertebral body angle increased significantly by about 2°. Conclusion. Lumbar alignment was similar after the use of the HC- or OB-type cages. This may be due to the surgical procedure and insufficient cage lordotic angle.

Chondrocyte distribution and cartilage regeneration in silk fibroin sponge

Chondrocytes distribution and cartilage formation in three types of fibroin sponges with different average pore sizes (40-80, 80-120 and 100-140 μm) was measured. The image processing was performed combining two methods to identify cells automatically: extraction of local maximum luminance and multi-threshold analysis. The results showed that initial accumulation of chondrocytes localized at surface area at 3 h in the small and medium-pore groups, however, the difference in the cell distributions become equivalent until 24 h after seeding. Cartilaginous tissue was well formed in each group at 21 days, and that in the smaller pore group tend to distribute at the surface area. Spherical tissues were located at the subsurface (200-600 μm below the surface) of the sponge in the medium- and large-pore groups at 21 days. Local cell aggregation was observed at 24 h at the same depth of the fibroin sponge as the spherical tissues observed at 21 days. These results suggest that the initial cell condensation process till 24 h after seeding play an important role in cartilage tissue formation.

Irradiation up-regulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells.

We have previously demonstrated irradiation‐induced up‐regulation of CD80 expression in A20‐HL B lymphoma cells by inducing expression of tumour necrosis factor‐α (TNF‐α) and CD154. In the present study, we investigated whether irradiation also up‐regulates CD80 expression in mouse spleen B cells. Because freshly prepared spleen B cells are highly sensitive to irradiation, we employed spleen B cells stimulated with lipopolysaccharide (LPS‐B cells). X‐irradiation (8 Gy) followed by incubation (9–12 hr) highly and selectively up‐regulated CD80 expression in LPS‐B cells, whereas the same treatment slightly increased expression of CD54 and did not affect expression of CD86, major histocompatibility complex class II, CD11a or surface immunoglobulin M. The irradiation‐induced up‐regulation of CD80 expression resulted in enhanced APC function of LPS‐B cells. Up‐regulation of CD80 expression on LPS‐B cells was accompanied by an increase in CD80 mRNA accumulation and nuclear factor (NF)‐κB activation. Activation of NF‐κB was shown to be critical for up‐regulation of CD80 expression as pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF‐κB, severely decreased the observed up‐regulation. X‐irradiation of LPS‐B cells induced expression of TNF‐α but not CD154. However, anti‐TNF‐α monoclonal antibody (mAb) with anti‐CD154 mAb did not inhibit X‐irradiation‐induced up‐regulation of CD80 expression in LPS‐B cells, whereas these mAbs almost completely inhibited this up‐regulation in A20‐HL cells and bone marrow‐derived dendritic cells (DCs). In contrast, a thiol antioxidant, N‐acetyl‐l‐cysteine, completely blocked X‐irradiation‐induced up‐regulation of CD80 expression in LPS‐B cells, but not in A20‐HL cells or in DCs. Based on these findings, we concluded that X‐irradiation up‐regulates CD80 expression not only in A20‐HL cells and DCs but also in LPS‐B cells, and that this up‐regulation in LPS‐B cells via NF‐κB activation is dependent on the generation of reactive oxygen species, while that in A20‐HL cells and DCs is not.