[Show abstract][Hide abstract] ABSTRACT: 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 μg ml(-1)) or IL-1β (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-1β. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1β-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1β. 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-1β in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.
[Show abstract][Hide abstract] ABSTRACT: Osteopontin (OPN) is known to be significantly involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to evaluate if the serum concentration of OPN in patients with RA before and after therapeutic treatments was correlated to disease activity and response to therapy. Blood samples from 40 patients with RA were collected at baseline and six months after starting treatment with disease-modifying antirheumatic drugs (DMARDs) and/or tumor necrosis factor (TNF)-α blockers. Serum levels of OPN were measured by ELISA. At baseline, the serum OPN level in RA patients was significantly higher than that of the healthy group. The OPN level at baseline in RA patients with severe disease activity as evaluated by DAS28 was slightly higher than that of those with moderate disease activity. The serum OPN level in RA patients was not significantly correlated with the DAS28 level. The serum OPN level in both responders and non-responders after therapy was significantly decreased regardless of responsiveness to therapy. Also, the OPN level at baseline did not affect the responsiveness to therapeutic treatments. In conclusion, serum OPN level was not correlated with disease activity or responsiveness of RA patients to therapeutic treatments.
[Show abstract][Hide abstract] ABSTRACT: Type 1 myotonic dystrophy (DM1) is an autosomal-dominant inherited disorder with a multisystem involvement, caused by an abnormal expansion of the CTG sequence of the dystrophic myotonia protein kinase (DMPK) gene. DM1 is a variable multisystem disorder with muscular and nonmuscular abnormalities. Increasingly, endocrine abnormalities, such as gonadal, pancreatic, and adrenal dysfunction are being reported. But, Electrolytes imbalance is a very rare condition in patients with DM1 yet. Herein we present a 42-yr-old Korean male of DM1 with abnormally elevated serum sodium and potassium. The patient had minimum volume of maximally concentrated urine without water loss. It was only cured by normal saline hydration. The cause of hypernatremia was considered by primary hypodipsia. Hyperkalemic conditions such as renal failure, pseudohyperkalemia, cortisol deficiency and hyperkalemic periodic paralysis were excluded. Further endocrine evaluation suggested selective hyperreninemic hypoaldosteronism as a cause of hyperkalemia.
Journal of Korean medical science 07/2013; 28(7):1111-3. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated whether taurine chloramine (TauCl), which is -endogenously produced by immune cells such as macrophages that infiltrate adipose tissue, affects the differentiation of preadipocytes into adipocytes or modulates the expression of adipokines in adipocytes. To study the physiological effects of TauCl on human adipocyte differentiation and adipokine expression, preadipocytes were cultured under differentiation conditions for 14 days in the presence or the absence of TauCl. Differentiated adipocytes were also treated with TauCl in the presence or the absence of IL-1β (1 ng/ml) for 7 days. The culture supernatants were analyzed for adipokines such as adiponectin, leptin, IL-6, and IL-8. At concentrations of 400-600 μM, TauCl significantly inhibited the differentiation of human preadipocytes into adipocytes in a dose-dependent manner. It did not induce the dedifferentiation of adipocytes or inhibit fat accumulation in adipocytes. Expression of major transcription factors of adipogenesis and adipocyte marker genes was decreased after treatment with TauCl, in agreement with its inhibition of -differentiation. These results suggest that TauCl may inhibit the differentiation of -preadipocytes into adipocytes. Thus, TauCl or more stable derivatives of TauCl could potentially be a safe drug therapy for obesity-related diseases.
Advances in experimental medicine and biology 01/2013; 775:247-57. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily involving the spine and sacroiliac joint and rarely the kidneys. This study aimed to define the clinical and histological features and biology of renal disease in AS. We reviewed the medical records of 681 patients diagnosed with AS from November 2008 to November 2009. Baseline characteristics and laboratory and urinalysis results were reviewed. We identified patients with proteinuria or hematuria and analyzed their risk factors. After providing informed consent, 6 patients underwent a renal biopsy to determine the cause of proteinuria or hematuria. Of the 681 enrolled patients, 547 were men and 134 were women; 81 % were HLA B27 positive, and 8 % had abnormal urinalysis findings (proteinuria, 5.9 %; hematuria, 2.8 %; both, 0.7 %). Incidences of peripheral arthritis and uveitis were 29 % and 18.6 %, respectively. Immunoglobulin (Ig)A and uric acid levels were significantly different between patients with and without proteinuria. Erythrocyte sedimentation rate (ESR), total cholesterol, creatinine, and C-reactive protein (CRP) levels were not statistically significantly different between the 2 groups nor were there any significant differences in IgA, uric acid, ESR, total cholesterol, creatinine, and CRP levels between patients with and without hematuria. Six patients who had >1 g/day proteinuria underwent a renal biopsy; 2 were diagnosed with IgA nephropathy, 1 with amyloidosis, and 3 with non-specific glomerulonephropathy. In the amyloidosis patient, severe proteinuria was the dominant feature. For patients with renal amyloidosis and other forms of glomerulonephritis who initially had normal creatinine levels, tumor necrosis factor (TNF)-alpha blocker therapy resolved proteinuria, but this was not the case for patients with initial renal insufficiency. Renal involvement is not a rare complication of AS, and prognoses differ depending on kidney pathology. Serum levels of uric acid and IgA may predict renal involvement in AS. In cases where abnormal urine sediment is identified, renal biopsy is required to determine prognosis and decide the treatment protocol. Baseline serum creatinine level is important for predicting treatment response.
Rheumatology International 12/2012; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVES.: Ultrasound-guided cervical periradicular steroid injection (US-CPSI) is an attractive alternate to conventional C-arm guided transforaminal epidural injection for treatment of cervical radicular pain. We compared the technical differences and clinical outcomes between these two techniques. METHODS.: Following ultrasound-guided needle placement, the extent of contrast media spread and the degree of tissue penetration were monitored by real-time fluoroscopy at the time of cervical periradicular injection in 59 patients. The spread pattern was judged to be medial foramen (medial bisector of foramen), lateral foramen (lateral bisector of foramen), or extraforaminal. The degree of tissue penetration was classified into periradicular, pararadicular, and intramuscular based on the penetration characteristics. Ultrasonographic images were categorized into crescent, perineuronal protruding, and intramuscular types. These groups were then correlated with clinical outcomes. RESULTS.: The actual distance between the ultrasound-guided needle position and fluoroscopic target point was 1.9 and 2.3 cm in the oblique and anteroposterior view, respectively. Despite a difference in ultrasound and fluoroscopic end points, contrast dye spread was found to reach lateral foramen in 53%, medial foramen in 34%, and extraforaminal in 13% of the subjects. Analysis of postprocedural pain reduction (PPPR) showed significantly the better outcomes in periradicular and pararadicular penetration, medial and lateral, and crescent and perineural protruding type without subgroup differences than intramuscular penetration, extraforaminal spread, and ultrasonographic images of intramuscular type (P < 0.001). Analysis of clinical overall outcome showed favorable outcome in the groups with better results of PPPR. CONCLUSION.: Our preliminary data suggest that the technique of UP-CPSI can provide an adequate local spread pattern, tissue penetration for treatment of cervical radicular pain.
[Show abstract][Hide abstract] ABSTRACT: IntroductionWhiplash-associated disorder (WAD) is a general after-effect of motor vehicle collisions or sporting accidents. Acupuncture is a common intervention for pain conditions such as musculoskeletal disease. We conducted a pilot trial to determine the efficacy and safety of acupuncture for patients with WAD.MethodologyForty participants were randomly allocated to an acupuncture group or a waiting-list group. The acupuncture group received acupuncture treatment three times per week for 2 weeks.Symptoms were evaluated before random allocation and after 2 weeks. The primary outcome measure was pain intensity. Secondary outcome measures were the SF-36, cervical range of motion (ROM), Self-Rating Depression Scale (SDS), and the Cornell Medical Index (CMI).ResultsThe results demonstrated that the change in visual analogue scale (VAS) in the acupuncture group was −1.85 [−2.67 to −1.02], compared to −0.40 in the waiting-list group [95% CI: −1.18 to 0.38] (p = 0.001). VAS significantly improved from 4.59 [3.67–5.48] at baseline to 2.74 [2.08–3.37] at the endpoint (p < 0.001) in the acupuncture group. No significant changes in secondary outcomes such as SF-36, Cervical ROM, SDS and CMI within either group were observed, and the scores from baseline revealed no significant differences between the groups. There were no reports of serious adverse events related to acupuncture treatment.Conclusions
Acupuncture treatment was associated with a significant alleviation of pain. This pilot study provided preliminary data on the efficacy and safety of acupuncture treatment for WAD. A full-scale randomized controlled trial is required to provide firm evidence of the effectiveness of this intervention.
European Journal of Integrative Medicine 06/2012; 4(2):e151–e158. · 0.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, 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 E(2) (PGE(2)), 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-1β 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-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB 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-1β 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.
Experimental and Molecular Medicine 05/2012; 44(7):440-7. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to determine the early cardiac valvular changes in young male ankylosing spondylitis (AS) patients.
A total of 70 AS patients on treatment without clinical cardiac symptoms were divided into group I (< 10 years, n = 50) and group II (≥ 10 years, n = 20) depending on their disease duration after first diagnosis. Twenty-five healthy volunteers were selected as control subjects. All the subjects underwent transthoracic and transesophageal echocardiography, electrocardiography, and rheumatologic evaluation for AS patients.
The thickness of both the aortic and mitral valve was more increased in AS patients than in controls. Aortic valve thickness over 1.3 mm could predict AS with a sensitivity of 73% and specificity of 76%. The prevalence of aortic valve thickening was higher in the AS group compared to the controls. The prevalence of aortic and mitral regurgitation was very low and there was no difference between the controls and the patients. The aortic valve thickening was related to longer disease duration, high blood pressure, disease activity and inflammatory markers.
Thickening of the aortic and mitral valve was observed without regurgitation in male AS patients early in the course of their disease without clinical cardiac manifestations. This subclinical change of aorto-mitral valve in early AS should be considered and followed up to determine its prognostic implication and evolution.
Journal of cardiovascular ultrasound 03/2012; 20(1):30-6.
[Show abstract][Hide abstract] ABSTRACT: Diabetes mellitus (DM) is a chronic metabolic disease and is associated with vascular complications. However, the association of musculoskeletal manifestations and DM is not clear. We investigated musculoskeletal manifestations in the diabetic animal model Otsuka Long-Evans Tokushima Fatty (OLETF) rat. OLETF rats and control LETO (Long-Evans Tokushima Otsuka) rats at two different ages (44 and 95 weeks) were used. Knee joints and ankles with interphalangeal joints were removed, dissected, stained with hematoxylin and eosin (H&E), periodic acid-Schiff, methenamine silver, and Masson-trichrome staining and examined under light microscopy. Mild degenerative changes with focal edema and mild fibrosis were noted in OLETF rats (at 95 weeks of age) and in age-matched LETO rats, particularly in the interphalangeal joints. Necrosis, phagocytosis of necrotic fibers, regeneration, mononuclear inflammatory cell infiltration, granulation tissue, calcification and cartilage erosion were not observed in either the aged diabetic or the non-diabetic group. We found no prominent musculoskeletal manifestations in the OLETF rats. The reasons may be due to the low prevalence rate of these anomalies, or the life span of rats may be too short to express these alterations. More studies are needed to elucidate the pathophysiological mechanisms by demonstrating the musculoskeletal manifestations histologically.
Molecular Medicine Reports 12/2011; 5(3):779-82. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) national database, as well as to provide an overview of the RA patients who are currently registered in KORONA.
The KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database.
A total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010.
KORONA is the first nationwide Korean RA-specific cohort and it will provide valuable "real-world" information for Korean RA patients.
Seminars in arthritis and rheumatism 12/2011; 41(6):745-51. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To further understand the expression regulation of MMP-1 and MMP-13 under physiological and pathological conditions, we investigated the combined effects of hypoxia and pro-inflammatory stimuli on the expression of MMP-1 and MMP-13 in rheumatoid synovial fibroblasts.
Synovial fibroblasts were cultured under either hypoxic or normoxic conditions in the presence of IL-1β stimulation. The culture supernatant was analysed for secreted levels of VEGF, MMP-1 and MMP-13. Their gene expression was quantified with real-time and semi-quantitative PCR. Another group of cells was transfected with small-interfering RNA (siRNA) specific for hypoxia-inducible factor-1 α (HIF-1α). The protein levels of HIF-1α were detected by western blot analysis.
In response to 10 ng/ml of IL-1β under normoxia, the levels of MMP-1 and MMP-13 increased compared with the levels observed under hypoxia. IL-1β stimulation under hypoxia induced a 2-fold increase in the level of MMP-1 and a 2-fold decrease in the level of MMP-13 compared with cells cultured under normoxia. A similar pattern of differential expression for MMP-1 and MMP-13 was observed with 1 and 5 ng/ml IL-1β, but not at 0.1 ng/ml. The differential expression of MMPs under the combined effect of IL-1β and hypoxia was significantly attenuated by silencing HIF-1α with siRNA.
Hypoxia in arthritic joints may differentially affect the IL-1β-stimulated expression of MMP-1 and MMP-13 in rheumatoid synovial fibroblasts. This effect is dependent on HIF-1α expression. This hypoxia-mediated differential effect should be taken into consideration when testing the efficiency of therapies that target HIF-1α.
[Show abstract][Hide abstract] ABSTRACT: Peripheral nerves in different body locations display different echotextures on ultrasound imaging, and knowledge of peripheral nerve echotexture is helpful for locating target nerves. However, the degree of echogenicity is often difficult to characterize. We aimed to define objectively the degree of echogenicity of peripheral nerves using grayscale measurements and compare nerve echotexture with matched histologic samples.
Ultrasound images of peripheral nerves in 12 body locations were obtained in 20 healthy subjects using linear 8- to 12-MHz and curved 3- to 5-MHZ transducers. Corresponding nerve segments from 2 cadavers were imaged in vitro before they were sectioned for histologic examination. Nerve echogenicity was assessed by an objective grayscale (G) and a subjective echogenicity index (SEI) determined by experienced evaluators. The results of G and SEI in selected peripheral nerves were compared and correlated with histologic morphometry.
There is a close correlation between SEI and G (P < 0.05). Mixed echogenicity was seen in 30% of the peripheral nerves; 25.4% were predominantly hypoechogenic, and 44.5% hyperechogenic. Nerves in the neck and upper arm are more frequently hypoechoic, whereas those in the leg are more frequently hyperechoic. Histologically, differences in echogenicity are dependent on fascicle diameter and on nerve fascicular pattern, that is, differing ratios of fascicle number to total nerve area.
This study suggests that grayscales can be used to objectively determine echogenicity and shows that grayscale measurements match well with subjective visual grading. Histologic analysis showed that both ratio of total fascicular area to whole nerve area and fascicular pattern are important determinants of echogenicity.
Regional anesthesia and pain medicine 06/2011; 36(4):382-6. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was performed to provide evidence, albeit indirectly, as to which matrix metalloproteinases (MMPs), among the gelatinases MMP-2 and MMP-9 and the collagenases MMP-1 and MMP-13, play a more proactive role in the angiogenic process in arthritic joint. Joint fluid was collected from 33 patients with rhuematoid arthritis (RA) and osteoarthritis (OA), and protein (MMPs and vascular endothelial growth factor (VEGF)) levels were measured by ELISA, and the association of MMPs with VEGF was evaluated in joint fluid of patients with RA or OA. The levels of collagenases (total MMP-1 and total MMP-13) and gelatinases (total MMP-2 and total MMP-9) in RA joint fluid were significantly higher than those in OA fluid. Total MMP-9 levels were significantly associated with VEGF levels in RA fluids, but not in OA fluid, while total MMP-13 levels were strongly associated with VEGF levels in both RA and OA fluid. However, total MMP-2 and total MMP-1 levels were not associated with VEGF levels in either RA or OA joint fluid. Our results indirectly suggest that in RA and OA, MMP-9 and MMP-13 may play a more important role in angiogenesis than MMP-2 and MMP-1.
Rheumatology International 04/2011; 31(4):543-7. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pressure-controlled manometric discography is used by clinicians to evaluate discogenic pain. However, some would improve diagnostic accuracy. The goal of this study was to investigate potential confounding factors that might affect discographic results. Pressure differences depending on different speed of injection, lengths of connecting tubing and locations of sensors were evaluated using an in vitro model system.
Two sets of automated discography devices were arranged to record post-syringeal pressure pressures (PSPs) and intradiscal pressures (IDPs) in an "air chamber disk model" representing intradiscal pressure. PSPs and IDPs were measured simultaneously while varying injection speeds, and using intrasyringeal and extrasyringeal pressure sensors and contrast medium-filled tubing of different lengths. All pressure/volume curves were collected and viewed dynamically, and stored for further analysis.
At injection speed of 0.1 cc/second, the mean pressure difference (mean ΔP) between PSP and IDP was 38.1 psi. As injection speed was reduced, mean ΔP was proportionally decreased. Mean ΔP was 5.3 psi at injection speed of 0.01 cc/second and 0.7 psi at 0.005 cc/second. Mean ΔP values were significantly higher when pressures were recorded using intrasyringeal sensor: at injection speed of 0.1 cc/second, PSP and IDP values were 82.9 and 30.1 psi, respectively, compared with 50.6 and 12.5 psi measured by extrasyringeal sensor. Mean ΔP due to increased length of tubing was not significant.
Discography can be better performed with low speed injection (≤0.01 cc/second), using an extrasyringeal sensor. Difference of length of connecting tubings did not cause significant pressure differences. These data suggest that automated discography is a helpful adjunct to improve diagnostic accuracy, due to extrasyringeal location of pressure sensor and greater control of injection speed.
Pain Medicine 11/2010; 12(1):36-44. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor (TNF)-alpha is a pro-inflammatory cytokine that plays an important role in the pathogenesis of a variety of autoimmune diseases. TNF-alpha inhibitors have been shown to offer clinical benefits in the treatment of autoimmune and inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis (AS), and Crohn's disease. Occasionally, these agents have been associated with infectious complications because of their immunosuppressive activity. Globally, several cases of infections associated with TNF-alpha inhibitors have been reported. However, Aspergillus infection associated with etanercept is very rare. We report a case of chronic necrotizing pulmonary aspergillosis in a 51-year-old man with AS that developed after treatment with etanercept.
International Journal of Rheumatic Diseases 08/2010; 13(3):e16-9. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of adiponectin in the pathogenesis of arthritis is still controversial. This study was performed to examine whether adiponectin is involved in joint inflammation and destruction in rheumatoid arthritis (RA) in relation to the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs).
Synovial cells from RA patients were treated with adiponectin or interleukin (IL)-1beta for 24 hours. The culture supernatant was collected and analyzed for the levels of IL-6, IL-8, prostaglandin E2 (PGE2), VEGF, and MMPs by enzyme-linked immunosorbent assay. The levels of adiponectin, VEGF, MMP-1, and MMP-13 in the joint fluids from 30 RA or osteoarthritis (OA) patients were also measured.
Adiponectin at the concentration of 10 microg/mL stimulated the production of IL-6, IL-8, and PGE2 in RA fibroblast-like synoviocytes (FLSs), although the level of these was much lower than with 1 ng/mL IL-1beta. However, adiponectin stimulated the production of VEGF, MMP-1, and MMP-13 at the same level as IL-1beta. In addition, the level of adiponectin and MMP-1 in the joint fluid of RA patients was significantly higher than in OA patients. Adiponectin was positively correlated with VEGF in RA patients but not in OA patients, while the level of MMPs in joint fluid was not correlated with adiponectin in either RA or OA patients.
Adiponectin may play a significant role in the pathogenesis of RA by stimulating the production of VEGF and MMPs in FLSs, leading to joint inflammation and destruction, respectively.
Arthritis research & therapy 11/2009; 11(6):R161. · 4.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor (TNF) is a central regulator of chronic inflammatory diseases and plays a major role in the host immune system against tuberculosis (TB). TNF antagonists, infliximab and etanercept are effective in treating chronic inflammatory diseases by inhibiting TNF, but increase the risk of TB as a result of immunosuppression. Previous studies have shown that the risk of TB is greater in patients who received infliximab than in those who received etanercept and several hypotheses on the action mechanisms of the two agents have been presented in order to explain this difference in the risk of TB. As the clinical use of TNF antagonists increase, the incidence rate of TB may increase. Therefore, it is necessary that clinicians considering the use of TNF antagonists pay much attention to the prevention and control of TB and understand the mechanisms of action of the TNF antagonists. This case shows that etanercept treatment can be safely administered during the treatment of TB. In the future, additional studies will be needed to determine the safety of etanercept and the optimal time for the administration of etanercept during the TB treatment.
Rheumatology International 02/2009; 29(11):1377-80. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mizoribine is a disease-modifying anti-rheumatic drug (DMARD) that is used in the treatment of rheumatoid arthritis. However, clinical use of the drug is restricted to a few Asian countries due to a lack of comprehensive evidence on its effectiveness. The inhibitory effect of the drug on human osteoclastogenesis was investigated in the hopes of providing some clear evidence. Mizoribine was found to inhibit in vitro osteoclastogenesis in a dose-dependent manner. In addition, the size of the pit area was closely related to the number of osteoclasts in a bone resorption assay. However, mizoribine did not affect the phosphorylation of MAP kinase (p38, JNK, ERK), the degradation of IkappaBalpha, or receptor activator of NF-kappaB ligand (RANKL) expression in fibroblast-like synoviocytes stimulated with IL-1beta. These results suggested that mizoribine may partially suppress osteoclastogenesis, leading to progressive bone erosion by inhibiting the growth or the signaling pathway of precursor cells to form osteoclasts rather than fibroblast-like synoviocytes.
European journal of pharmacology 02/2009; 605(1-3):46-8. · 2.59 Impact Factor