Safety and effectiveness of Rixubis in patients with hemophilia B:a real-world, prospective, postmarketing surveillance study in South Korea

Background@#Rixubis (recombinant factor IX, nonacog gamma) is indicated for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis in hemophilia B patients. This real-world, postmarketing surveillance study aimed to evaluate the safety and effectiveness of Rixubis in adult and pediatric hemophilia B patients in South Korea. @*Methods@#This prospective, observational, multicenter study (clinicaltrials.gov identifier: NCT029 22231) was conducted in hemophilia B patients between April 2015 and April 2019, who were observed for up to 6 months after the initiation of Rixubis treatment. Safety was evaluated based on the number and severity of adverse events (AEs) and serious AEs (SAEs). Hemostatic effectiveness was assessed by physicians and patients by using a four-point scale and rated as excellent, good, fair, or no response based on treatment type. @*Results@#In all, 58 patients were enrolled from four centers by seven physicians during the study period. The safety and effectiveness analysis sets included 57 and 54 patients, respectively. Overall, 11 AEs were reported in eight patients (14.0%), of which three were SAEs and occurred in three patients (5.3%). All 11 AEs were reported as unexpected and mild in severity, with no anaphylactic reaction, and 10 AEs (90.9%) resolved. The majority of AEs (10) were unrelated to Rixubis. Of the 142 hemostatic effectiveness assessments, 123 (86.6%) were reported as good or excellent. @*Conclusion@#Rixubis demonstrated an acceptable safety and effectiveness profile in the treatment of bleeding, perioperative management, and prophylaxis in hemophilia B patients in a real-world setting in South Korea.

Safety and effectiveness of Rixubis in patients with hemophilia B:a real-world, prospective, postmarketing surveillance study in South Korea

Background@#Rixubis (recombinant factor IX, nonacog gamma) is indicated for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis in hemophilia B patients. This real-world, postmarketing surveillance study aimed to evaluate the safety and effectiveness of Rixubis in adult and pediatric hemophilia B patients in South Korea. @*Methods@#This prospective, observational, multicenter study (clinicaltrials.gov identifier: NCT029 22231) was conducted in hemophilia B patients between April 2015 and April 2019, who were observed for up to 6 months after the initiation of Rixubis treatment. Safety was evaluated based on the number and severity of adverse events (AEs) and serious AEs (SAEs). Hemostatic effectiveness was assessed by physicians and patients by using a four-point scale and rated as excellent, good, fair, or no response based on treatment type. @*Results@#In all, 58 patients were enrolled from four centers by seven physicians during the study period. The safety and effectiveness analysis sets included 57 and 54 patients, respectively. Overall, 11 AEs were reported in eight patients (14.0%), of which three were SAEs and occurred in three patients (5.3%). All 11 AEs were reported as unexpected and mild in severity, with no anaphylactic reaction, and 10 AEs (90.9%) resolved. The majority of AEs (10) were unrelated to Rixubis. Of the 142 hemostatic effectiveness assessments, 123 (86.6%) were reported as good or excellent. @*Conclusion@#Rixubis demonstrated an acceptable safety and effectiveness profile in the treatment of bleeding, perioperative management, and prophylaxis in hemophilia B patients in a real-world setting in South Korea.

Ultrasound-Guided Greater Occipital Nerve Block for Primary Headache: Comparison of Two Techniques by Anatomical Injection Site

OBJECTIVE: Greater occipital nerve block (GONB) is a widely accepted treatment of primary headaches. Two ultrasound (US)-guided blockade techniques exist: 1) the classical distal nerve block technique performed medial to the occipital artery at the superior nuchal line, and 2) the new proximal nerve block technique performed at the obliquus capitis inferior muscle at the level of C2. Our study aim was to perform a head-to-head comparative study of these two US-guided techniques.METHOD: Forty-nine patients with primary headache treated in our university hospital were recruited. Patients were randomized into two groups of the classical nerve block and the new proximal nerve block techniques. The headache questionnaire was made to assess the intensity of the pain of headache attacks, number of days they experience headache, duration of headache, and amount of pain medication they consumed.RESULTS: In both groups, a decrease in the severity and frequency of the headache was observed. There was no measurable difference in outcome between the two groups.CONCLUSION: Our study showed that the classic and new proximal techniques are equally effective in decreasing the headache severity and frequency.

Correlations Between Values of Articulation Tests and Language Tests for Children With Articulation Disorder in Korea

OBJECTIVE: To evaluate correlations between values of articulation tests and language tests for children with articulation disorder in Korea. METHODS: Data of outpatients with chief complaint of an articulation problem were retrospectively collected. Patients who underwent Urimal Test of Articulation and Phonation (U-TAP) with Assessment of Phonology and Articulation for Children (APAC), Preschool Receptive-Expressive Language Scale (PRES), or Receptive and Expressive Vocabulary Test (REVT) simultaneously were identified. Patients whose word-level percentages of correct consonants in U-TAP (UTAP_wC) were more than 2 standard deviations below the mean as diagnostic criteria for articulation disorder were selected. Those whose receptive language age (P_RLA), expressive language age (P_ELA), or combined language age (P_CLA) in PRES was delayed more than 24 months compared to their chronological age in months as diagnostic criteria for language disorder were excluded. RESULTS: Thirty-three children aged 3–6 years were enrolled retrospectively. PRES and U-TAP showed significant correlations for most of value relationships. PRES and APAC showed significant correlations for all value relationships except for receptive language age. All values of REVT were significantly correlated with all values from U-TAP, but not with any value from APAC. Articulation tests U-TAP and APAC showed significant correlations between percentages of correct consonants. Language tests PRES and REVT showed significant correlations for all value relationships. CONCLUSION: This study suggests that articulation abilities and language abilities might be correlated in children with articulation disorder.

Radiating Pain and Postural Balance with Pulsed Radiofrequency Treatment in Patients with Lumbosacral Radiculopathy

OBJECTIVE: To investigate the effect of pulsed radiofrequency (PRF) treatment on pain and balance in patients with lumbosacral radiculopathy.METHOD: This study included twenty-five patients who were diagnosed with chronic lumbosacral radiculopathy. They underwent PRF treatment in prone position under the fluoroscopic guidance. The effect of PRF was measured by the visual analog score (VAS). Patient ability to balance was evaluated by using the Tetra-ataxiometric posturography (Tetrax).RESULTS: After PRF all patients showed improvement in pain as measured by VAS (p < 0.001) and none of the patients reported any side effects. The posturographic balance, which was evaluated by Tetrax showed no significant decline after PRF treatment. The weight distribution index (WDI) with eyes open before treatment was 5.43 ± 2.88 and after treatment was 5.37 ± 2.65 (p=0.917). The mean stability index (SI) with eyes open before treatment was 16.52 ± 6.05 and after treatment was 16.61 ± 4.85 (p=0.906). The mean WDI with eyes closed before treatment was 5.66 ± 2.81 and after treatment was 5.16 ± 2.70 (p=0.470). Finally, the mean SI with eyes closed before was 25.88 ± 9.88 and after treatment was 25.99 ± 12.30 (p=0.962).CONCLUSION: The results suggest that PRF has an effect on pain in patients with chronic lumbosacral radiculopathy. The patients did not experience adverse effects, such as hypoesthesia, dysesthesia and decreased proprioception after PRF, and there were no significant declines in balance.

The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints

This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 mug ml-1) or IL-1beta (0.1 ng ml-1) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1beta. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1beta-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1beta. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1beta in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.

New Paradigm of Total Hip Arthroplasty in Asia in 21st Century / 대한고관절학회지

No abstract available.

Surgery in patients with congenital factor VII deficiency: A single center experience / 대한혈액학회지

BACKGROUND: Congenital factor VII (FVII) deficiency is a rare hemorrhagic disorder that can cause excessive bleeding during and after surgery in affected patients. The recombinant form of activated factor VII (rFVIIa, NovoSeven(R) from Novo Nordisk, Bagsvaerd, Denmark), which was developed as a second-generation bypassing agent, has recently been used in the management of bleeding for patients with congenital FVII deficiency. METHODS: We reviewed the results of 8 surgical procedures in 5 patients with congenital FVII deficiency at the Kyung Hee University Hospital, Gangdong, Seoul, Korea, between January 2008 and June 2010. We administrated rFVIIa preoperatively in six patients and postoperatively in five patients. RESULTS: Between January 2008 and June 2010 at our center, 8 operations were performed successfully and no complications were observed in the 5 patients with congenital FVII deficiency. The median level of FVII activity was 2% (range, 0.6-7%). Four orthopedic procedures, 1 tonsillectomy, and 3 dental extractions were performed. The median duration of hospitalization was 8.5 days (range, 0-15 days). rFVIIa was administered at all procedures, except the dental extraction that was performed using only antifibrinolytic agents without any replacement. No bleeding or thrombogenic complications were observed in any case. CONCLUSION: Patients with congenital FVII deficiency who require surgery can be treated efficiently and safely with rFVIIa or antifibrinolytic agents. rFVIIa was well tolerated and maintained effective hemostasis and showed good clinical outcome after the major surgery.

Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve beta-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients.

Synergy between adiponectin and interleukin-1beta on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1beta regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1beta, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1beta to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1beta each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1beta did not synergistically support the degradation of IkappaB-alpha or the nuclear translocation of NF-kappaB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-kappaB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1beta may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.

Revision Total Hip Arthroplasty Using Acetabular Reinforcement Ring: Midterm Follow-up Result

PURPOSE: To evaluate the clinical and radiographic outcomes of the revision total hip arthroplasty using the acetabular reinforcement ring. MATERIALS AND METHODS: Thirty-six acetabular revisions were performed in 36 patients with use of the reinforcement ring and structural or morselized allograft, between 1997 and 2005, in thirty-six patients. According to the AAOS classification, thirty-four cases of acetabular defects were Ttype III, and two were Ttype IV. Mean follow-up period after surgery was 7.2 years. RESULTS: The mean Harris hip score was 92.3, which was significantly increased compared with the preoperative score. (p<0.001). There were five failures: a case of aseptic loosening of Muller ring, two cases of infection (5.4%) and two cases of hip dislocation (5.4%). Graft incorporation and bone remodeling occurred successfully in all hips, but in the case of aseptic loosening in which the ring fixation had been inadequate at the time of surgery. The success rate was 91.7% with a mean follow-up of 7.2 years, if the cases of revision or loosening of the component were classified into failure cases. CONCLUSION: Patients treated with acetabular revision with three kinds of reinforcement ring had reconstitution of periacetabular bone stock as well as good clinical and radiographic results. For the good results, the secure implant fixation during the surgery should be confirmed and we should completely understand the characters of the each kinds of reinforcement rings.

Isolated Polyethylene Liner Exchange in a Revision Total Hip Arthroplasty

PURPOSE: To analyze the results of isolated exchange of polyethylene (PE) liners for treatment of wear and osteolysis around a well-fixed Harris-Galante (HG) cementless acetabular cup. MATERIALS AND METHODS: Thirty-three PE liner changes were performed without the removal of stably ingrown implants (33 hips of 32 patients). They were able to be followed for a mean period of 92 months. Clinically, the Harris hip score (HHS), pain evaluation, and complications were evaluated. Radiologically, the annual wear rate and the size of the osteolytic lesions were measured before the operation and the latest follow-up. The bone graft incorporation scale and the development of new osleolytic lesions were checked during the final follow-up. RESULTS: HHS improved to 89.3 at last follow-up. The size of the osteolysis was significantly reduced postoperatively. Bone graft incorporation scales were Grade I in 9 and Grade II in 14 cases. New osteolytic lesions have not developed at latest follow-up. As a complication, one case of dissociation of a liner and a periprosthetic fracture were noted. Annual wear rates during the same period were significantly reduced. There was no sign of alteration in stability of the PE liner. CONCLUSION: Exchange of a PE liner without removal of stable implants can be a good option for the treatment of wear and osteolysis around a stable cementless THA implant, even if the system has a weak locking mechanism, such as the HG cup. In these cases, under certain states with a higher risk of early failure in the locking mechanism, it would be better to select other revision procedures such as cup revision or cemented polyethylene liner fixation.

Hip Resurfacing Arthroplasty in Patients with Rheumatoid Arthritis

OBJECTIVE: This study analyzed the midterm results of hip resurfacing arthroplasty in patients with rheumatoid arthritis. METHODS: Between October of 2003 and September of 2008, 13 consecutive hips that were treated with hip resurfacing arthroplasty due to rheumatoid arthritis were analyzed. The average follow up period was 48.6 months and the mean age at the time of operation was 35.9 years old. The mean BMI at the operation was 23.2 kg/m2. The implanted prostheses were the Conserve Plus system in five hips, the Birmingham hip resurfacing system in four hips and the Durom system in four hips. The results were clinically evaluated with the Harris hip score, the UCLA activity score, hip or thigh pain, the limb length discrepancy and the range of motion. As radiological evaluation, we observed the patterns of bone remodeling and complications such as femoral neck fracture, loosening and osteolysis. RESULTS: The average Harris hip score improved from 62.2 to 98.9 at the final visit. The range of motion improved to 0degrees in flexion contracture, 118.1degrees in further flexion, 22.7degrees in internal rotation, 40.4degrees in external rotation, 28.8degrees in adduction and 38.1degrees in abduction, respectively. No patient complained of a limb length discrepancy and hip or thigh pain. Radiographically, impingement between the acetabular component and the femoral neck was observed in one case. However, radiographic findings such as osteolysis, radiolucency, wear and loosening were not observed. CONCLUSION: The midterm results of hip resurfacing arthroplasty in patients with rheumatoid arthritis were excellent. But long-term studies are needed to determine the survivorship and to evaluate the osteoporotic change, the metal ion level and their influence after hip resurfacing arthroplasty.

Revision Total Hip Arthroplasty Using a Fully Porous-Coated Long Stem: a Minimum 5 Years Follow up

PURPOSE: We wanted to evaluate the mid-term results of revision total hip arthroplasty using a fully porous-coated long stem. MATERIALS AND METHODS: A retrospective series of 20 hips in 19 patients who underwent stem revision with a fully porous-coated long stem were evaluated at a mean follow-up of 64.6 months. The causes of revision were aseptic loosening, periprosthetic fracture and infected arthroplasty. Four kinds of implants had previously been used and an additional bone graft procedure had been done in 17 cases. The Harris hip scores, thigh pain, limping and ROM were reported. Radiological changes of the radiolucent signs, subsidence, loosening and the stress shielding signs were evaluated. RESULTS: The Harris hip score improved from an average of 56.5 to 91.9 and the ROMs were satisfactory. The only case with persistent thigh pain showed stable bony ingrowth. No signs of subsidence or loosening of the stem was found in all the cases. There were 2 cases of periprosthetic fracture. None of the patients experienced re-revision surgery. CONCLUSION: The mid-term results of revision hip arthroplasty using a fully porous coated long stem have demonstrated that it provides a reliable initial fixation with a propensity for stable longevity. It is relatively easy for the techniques, and there is the opportunity to restore the bone stock by bone-grafting procedures with diaphyseal fixation and bypassing a bone defect. Yet alternative techniques may be required for the femur with extensive diaphyseal bone loss. There are some concerns about the technique and the possibility of making a crack in the femur during the operation, which will cause thigh pain at the follow-up. So, only by employing great caution when performing this technique can successful results be guaranteed.

Treatment of Infected Hip Arthroplasty with Antibiotic-Loaded Cement Spacers

PURPOSE: This study evaluated the effect of antibiotic-loaded cement spacers on the treatment of infected hip arthroplasty. MATERIALS AND METHODS: Twenty-one patients, twenty-one cases that experienced infection after total hip arthroplasty, were treated with two-stage arthroplasty using antibiotic-loaded cement spacers between July 1995 and March 2005. The average age was 56.3 years (range, 36~84 years). The follow-up period was 7.2 years (range, 3~11.4 years). The period from the first operation to diagnosis of infection was 28 months (range, 1~49 months). Preoperative culture, Tc 99m scan or Gallium scan, intraoperative culture and biopsy were performed for the evaluation of infection. We postoperatively evaluated clinical and radiological outcomes, blood analysis including serologic study, complete blood cell count, differential count, erythrocyte sedimentation rate and C-reactive protein. RESULTS: Of a total of 21cases, acetabular cup, femoral head and femoral stem were substituted in 10 cases (48%). Acetabular cup and femoral head were substituted in 11 cases (52%). Revision arthroplasty was performed in 19 cases, on average 11.9 months (range 2~31 months) after insertion of antibiotic-loaded cement spacers. Infection recurred in 1 case. In 18 cases, excluding the reinfected one, the average Harris hip score, 46.8 points (range, 35~72 points) preoperatively, improved to 89.5 points (range, 78~100 points) at last follow-up in the revision group. In 2 cases in which revision total hip arthroplasty was not performed, the Harris hip score was 53 points (range, 36~70 points) preoperatively, and 86 points (range,72~100 points) at last follow-up. CONCLUSION: The use of antibiotic-loaded cement spacers in two-stage arthroplasty is an effective method for management of infection, preserving joint function until performing revision arthroplasty. Preservation of the femoral stem should be considered in cases in which were fixed firmly and in cases which show no evidence of the spreading of infection to the distal part of the stem on Tc 99m scan or Gallium scan performed preoperatively.

Cementless Total Hip Arthroplasty with Medial Wall Osteotomy for the Sequelae of Septic Arthritis of the Hip

BACKGROUND: We performed a retrospective study to evaluate the results of acetabular circumferential medial wall osteotomy, a procedure designed to provide secure fixation of a cementless hemispherical acetabular cup for the sequelae of septic arthritis of the hip. METHODS: We assessed 38 total hip arthroplasties (THAs) with circumferential acetabular medial wall osteotomies performed on patients with sequelae of septic arthritis of the hip between 1993 and 2000, who were followed up for > or = 3 years. The average follow-up period was 8.3 years (range, 3 to 12 years). The indication for this technique was poor acetabular cup coverage of < or = 70% on preoperative templating. In all cases, cementless hemispherical acetabular cups were fixed to the true acetabulum. Additional procedures included soft tissue release in 16 hips and femoral derotational and shortening osteotomies in 12 hips. We evaluated both clinical and radiological results. RESULTS: The Harris hip scores improved from 57 points preoperatively to 91 points postoperatively. Radiological analysis revealed no aseptic loosening or radiolucent lines around the acetabular cup. Stable bony fixation of the acetabular cup in the true acetabulum was seen in all cases. Acetabular osteolysis was demonstrated in 12 hips. Revision surgery was performed in 6 hips, but there were no complications related to acetabular circumferential medial wall osteotomy. CONCLUSIONS: Circumferential acetabular medial wall osteotomy can provide appropriate positioning and sufficient coverage of the acetabular cup and thus preserve the medial wall thickness in cementless THA without the need for additional bone grafting for the sequelae of septic arthritis of the hip.

Revision Total Hip Arthroplasty with S-ROM Modular System

PURPOSE: To evaluate the clinical and radiological outcomes after revision total hip arthroplasty using the S-ROM modular system. MATERIALS AND METHODS: Twenty-three consecutive patients (24 hips) who underwent femoral stem revision with the S-ROM modular system were followed for more than two years. The average follow-up period was 44 months (range, 24~72 months), and the average age at the time of the revision was 48 years (range, 30~68 years). Underlying causes for revisions included 23 cases of aseptic loosening and 1 case of septic loosening. Femoral bone defects according to the Paprosky system were classified as type II in 12 hips, type III in 8, and type IV in 4. The clinical and radiographic results were evaluated. RESULTS: At the time of latest follow-up, there was no femoral stem loosening, osteolysis, radiolucency, or rerevision. Although 3 cases of Paprosky classification type IV showed subsidence, stable fibrous fixation was achieved in these hips. Complications included 1 intraoperative femoral shaft crack and 1 postoperative deep infection. CONCLUSION: We can achieve stable initial fixation using the S-ROM modular system with proximal press fitting sleeve and fluted stem.

The Effect of Repeated Intraarticular Bleeding in the Synovium and Articular Cartilage: An Animal Model / 대한정형외과학회잡지

PURPOSE: We designed this study to demonstrate the pathophysiology of hemophilic arthropathy (HA) by creating an animal model for determining the effect of repeated intraarticular bleeding in the synovium and articular cartilage. MATERIALS AND METHODS: 20 normal male New Zealand white rabbits were used for this study. We injected 1 ml of autologous blood from the ear vein of the rabbits into the right knee joint three timeds a week for 18 weeks, and we injected 1 ml of normal saline into the left knee joint three times a week for 18 weeks as a control group. We examined the pathologic changes by microscopy and plain X-ray, and we determined the mRNA expression of proinflammatory cytokines in the synovium of the HA by performing real time RT-PCR at the 11th week and 18th week after starting blood-injection. We also examined the GAG and the PGE2 production in cultured chondrocytes that were extracted from the HA knees. RESULTS: At the 11th week, after blood injection there were no remarkable gross changes in the HA knees and the control knee joints. At the 18th weeks, the experimental knee joints (HA knees) showed grossly swelling and degenerative changes by X-ray. The infiltration of inflammatory cells and the synovial proliferation in the HA knee joints were compared with that in the control knee joints by microscopic examination. The expressions of the mRNA of TNF-alpha, IL-1, MMP-1 and MMP-3 in the HA synovium were increased, as determined by real time RT- PCR, as compared with that in the control knee. In the cultured chondrocytes, the GAG production was decreased and the PGE2 was increased, but the MMP-1 and MMP-3 were not changed, as determined by ELISA. CONCLUSION: Our results showed that the GAG production of chondrocytes of the HA knees was decreased and there was increased PGE2, so that the cartilage degeneration by intra-articular bleeding was caused by the decreased metabolism of chondrocytes rather than by increased catabolism of the chondrocytes. We suggest that HA was associated with synovitis and cartilage degeneration, but decreased cartilage metabolism was the major mechanism of HA.

Coptis chinensis Extract Inhibits the Production of Inflammatory Mediators and Delayed Type Hypersensitivity in Mice

BACKGROUND: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. METHODS: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 (PGE(2)), interleukin (IL)-2 and IFN-gamma were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. RESULTS: The CCE at 100 microgram/ml significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-gamma) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. CONCLUSION: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.

Coptis chinensis Extract Inhibits the Production of Inflammatory Mediators and Delayed Type Hypersensitivity in Mice

BACKGROUND: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. METHODS: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 (PGE(2)), interleukin (IL)-2 and IFN-gamma were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. RESULTS: The CCE at 100 microgram/ml significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-gamma) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. CONCLUSION: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.