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Objectives: This study aims to investigate the role of cluster of differentiation 14 (CD14) expressed monocytes and soluble CD14-mediated pathway in the synovial inflammation of knee osteoarthritis (OA). Patients and methods: Between May 2012 and July 2013, a total of 35 patients with knee OA (9 males, 26 females; mean age: 66.3±8.8 years; range, 52 to 79 years) were included in this cross-sectional study. Synovial fluid was obtained from knee joints of 35 OA patients. The CD14+ monocytes from synovial fluid mononuclear cells (SFMCs) were isolated using the MACS. The fibroblast-like synoviocytes (FLSs) isolated from knee joint tissue were incubated with recombinant CD14 and lipopolysaccharide (LPS) for 24 h. Cytokine profiling was performed with the Luminex® Performance Assay or magnetic bead panel kit. The expression of CD14 and CD16 was analyzed by immunohistochemistry and flow cytometry. Results: The concentration of sCD14 in synovial fluid was correlated with the interleukin-6 (IL-6) level (n=35) (ρ=0.654, p<0.001). The culture supernatants of CD14+ monocytes isolated from SFMC (n=15) showed a correlation between sCD14 and IL-6 (ρ=0.784, p=0.001), along with complement component 3 (ρ=0.756, p=0.010), IL-1b (ρ=0.652, p=0.012), and tumor necrosis factor-alpha (ρ=0.806, p=0.001). Following recombinant CD14 and LPS treatment, OA FLS synergistically enhanced the secretion of IL-6, IL-8, and matrix metalloproteinase 3 (n=3, p<0.05). In five paired-samples from identical patients, the proportions of CD14+ monocytes were significantly elevated in recurred synovial fluid compared to those in initial synovial fluid (p=0.043). When monocyte subsets were analyzed in SFMC (n=26), CD14+CD16+ monocytes were abundant (p=0.019) and had higher toll-like receptor 4 expression than CD14+CD16- (p<0.001). Conclusion: Our study results suggest that CD14+ monocytes and the sCD14-mediated pathway play an important role in OA aggravation through inflammatory cytokine secretion. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to examine the possible associations of mitochondrial single nucleotide polymorphisms (SNPs) and Behcet's disease (BD) in a larger patient group. Patients and methods: Whole blood or buffy coat was collected from 98 BD patients (31 males, 67 females; mean age 48±2.8 years; range 20 to 60 years) from four university hospitals located in the Chung-Cheong district of the Republic of Korea, and 196 age- and sex-matched healthy controls (HCs) (62 males, 134 females; mean age46.91±12.90 years; range 20 to 68 years) from Konyang University Hospital. Twenty targeted mitochondrial deoxyribonucleic acids (DNAs) were genotyped and compared using the revised Cambridge Reference Sequence. Chi square and Fisher's exact tests were used to analyze association of mitochondrial DNA SNPs with BD susceptibility and its clinical characteristics. Results: There were no differences for m.248A>G, m.304C>A, m.709G>A, m.3010G>A, m.3970C>T, m.4883C>T, m.5178C>A, m.6392T>C, m.6962G>A, m.10310G>A, m.10609T>C, m.12406G>A, m.12882C>T, m.13928G>C, m, 14668C>T, m.16129G>A, and m16304T> between patient and HC groups. However, m.16182A>C and m.16183A>C were more frequently observed in the patient group than the HC group (22 [22.4%] vs. 24 [12.2%], p=0.061 and 32 [32.7%] vs. 42 [21.4%], p=0.092) but without statistical significance. m.4883C>T and m.5178C>A were associated with posterior location of oral ulcers (p=0.025 for each) and m.16l83A>C was associated with deep oral ulcers (p=0.001), while m, 16189T>C was associated with deep oral ulcers and thrombosis (p=0.042,0.048, respectively). Conclusion: m.16182A>C and m.16l83A>C may be associated with BD in the Korean population. [ABSTRACT FROM AUTHOR]

Interleukin-7 (IL-7), which is required for the development and survival of T cells in the thymus and periphery, plays a role in joint destruction. However, it remains unclear how IL-7 affects osteoclast formation. Thus, we investigated the mechanism by which IL-7 induced osteoclast formation through IL-7 receptor α (IL-7Rα) in osteoclast precursors. We cultured peripheral blood mononuclear cells or synovial fluid mononuclear cells with IL-7 in the presence or absence of an appropriate inhibitor to analyze osteoclast formation. We also constructed IL-7Rα-expressing RAW264.7 cells to uncover the mechanism(s) by which IL-7 induced osteoclast formation differed from that of receptor activator of nuclear factor κB ligand (RANKL). We found that IL-7 induced osteoclast formation of human monocytes from peripheral blood or synovial fluid in a RANKLindependent and a signal transducer and activator of transcription 5 (STAT5)-dependent manner. IL-7-induced osteoclasts had unique characteristics, such as small, multinucleated tartrate-resistant acid phosphatase positive cells and no alterations even when RANKL was added after IL-7 pretreatment. RAW264.7 cells, if overexpressing IL-7Rα, also were able to differentiate into osteoclasts by IL-7 through a STAT5 signaling pathway. Furthermore, IL-7-induced osteoclast formation was repressed by inhibitors of the IL-7R signaling molecules Janus kinase and STAT5. Our findings demonstrate that IL-7 is a truly osteoclastogenic factor, which may induce osteoclast formation via activation of STAT5, independent of RANKL. We also suggest the possibility that an IL-7R pathway blocker could alleviate joint damage by inhibiting osteoclast formation, especially in inflammatory conditions. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to evaluate the long-term effect of anti-platelet treatment on the radiological progression of collagen-induced arthritis in rats. Methods: Female Lewis rats with collagen-induced arthritis were divided into three experimental groups: saline, aspirin monotherapy (n = 12), and aspirin-clopidogrel dual therapy (n = 12). Drugs were administered daily and continued up to 70 days after the induction of arthritis. The clinical arthritis index (weight, morphology score, and paw thickness) and radiological scores were evaluated. Results: The clinical arthritis index peaked on day 20, while the radiological scores peaked on day 35. No intergroup difference was observed in the clinical arthritis index throughout the experiment. The aspirin-clopidogrel dual therapy group had a significantly higher mean radiological score than the other groups (p = 0.045) on day 35. Further treatments resulted in significantly improved radiological findings in the aspirin monotherapy and aspirin-clopidogrel dual therapy groups on day 70 but no significant improvement in the saline group. Conclusion: Anti-platelet agent treatment improved radiological findings on day 70. These observations emphasize the importance of a future long-term study of the effects of anti-platelet agent treatment on arthritis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with systemic sclerosis (SSc). Early detection and prompt treatment of PAH associated with SSc (SSc-PAH) result in better prognosis. We conducted echocardiographic study to presume the prevalence of PAH in Korean adult SSc patients and to diagnose SSc-PAH in their early stages with right heart catheterization (RHC). METHODS: We performed free of charge echocardiographic study including 37 adult SSc patients at the Chungnam National University Hospital. The possibility of PAH is determined by the estimation of pulmonary arterial pressure by peak tricuspid regurgitation velocity of > 3.0 m/s. Patients with possible PAH were recommended to undergo RHC to confirm the diagnosis. RESULTS: In 37 patients, 8 patients were suspected with PAH. Among them, 6 patients agreed to be examined with RHC, and 4 were confirmed with PAH. The prevalence of possible PAH was 21.6% (8 of 37 patients), and that of confirmed PAH was 10.8% (4 of 37 patients). Four patients who were confirmed with SSc-PAH through RHC have been treated with specific pulmonary vasodilators and maintained stable. CONCLUSION: Eight patients (21.6%) were possible PAH and 4 (10.8%) were diagnosed as SSc-PAH by RHC after the echocardiographic screening study of 37 adult SSc patients. [ABSTRACT FROM AUTHOR]

Background Pelubiprofen is a prodrug of 2-arylpropionic acid with relatively selective effects on cyclooxygenase-2 activity. The aim of this study was to compare the efficacy and safety profiles of pelubiprofen with those of celecoxib in patients with rheumatoid arthritis. Methods This was a 6-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, non-inferiority clinical trial. The primary end point was non-inferiority of pain decrease from baseline to week-6 as determined using a 100 mm pain visual analog scale (VAS). Pelubiprofen was considered non-inferior to celecoxib if the lower limit of the 97.5% confidence interval for treatment difference [(pain reduction in pelubiprofen group) - (pain reduction in celecoxib group)] was more than -10 mm. The secondary end points were as follows: non-inferiority of (1) reduction of Korean health assessment questionnaire (KHAQ) score; (2) decreased duration of morning stiffness; and (3) decrease in the frequency and total dose of rescue drugs after 6 weeks of treatment. Results Seventy-seven patients in the pelubiprofen group and 68 patients in the celecoxib group started the study medication. Pelubiprofen was non-inferior to celecoxib with regard to reduction in VAS pain severity (difference, mean ± SD 5.0 ± 20.1; 97.5% CI, -2.3 to ∞). Pelubiprofen was also non-inferior to celecoxib in terms of the secondary end points, such as, decrease in KHAQ score (0.0 ± 0.5, 97.5% CI -0.2 to ∞), decrease in duration of morning stiffness (median 0.0 minute in both groups), and decrease in the frequency (0.7 ± 3.5, 97.5% CI -0.6 to ∞) and total amount (0.7 ± 3.6, 97.5% CI -0.6 to ∞) of rescue medication uses during the 6 week study period. Safety analysis revealed 31.2% patients in the pelubiprofen group and 20.6% patients in the celecoxib group experienced an adverse drug reaction (ADR). The frequency of gastrointestinal ADRs was 20.8 % and 8.8%, respectively. Conclusions Pelubiprofen was found to be as effective as celecoxib at pain reduction and for relieving stiffness in RA patients. However, more patients in the pelubiprofen group experienced ADR and the frequency of gastrointestinal ADRs was higher in the pelubiprofen group. [ABSTRACT FROM AUTHOR]

Objectives To identify non-major histocompatibility complex susceptible genes that might contribute to Behçet's disease (BD). Methods We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated. Results We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01x10-8 in a minor allele dominant model; rs11769828, allele based p=1.60x10-6). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70x10-6) in GIMAP4; rs10266069 (OR=1.32, p=2.67x10-4) and rs10256482 (OR=1.27, p=5.27x10-4) in GIMAP2; and rs2286900 (OR=1.61, p=3.53x10-5) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis. Conclusions These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD. [ABSTRACT FROM AUTHOR]

Vasculitides are characterized by vessel wall inflammation of unknown etiology. We report two cases of eosinophilic vasculitis and hypereosinophilia with thrombosis. They have been treated with a high-dose glucocorticoid and anticoagulation. These cases emphasize that thrombosis should be anticipated in patients with eosinophilic vasculitis. [ABSTRACT FROM AUTHOR]

Avian prolactin (PRL) secretion is regulated by vasoactive intestinal peptide (VIP) neurons residing in the infundibular nuclear complex (INF) of the hypothalamus. This VIPergic activity is modulated by stimulatory dopaminergic inputs. Dynorphin, serotonin (5-HT), dopamine (DA) and VIP all appear to stimulate PRL secretion along a hypothalamic pathway, expressing κ opioid, serotonergic, dopaminergic and VIPergic receptors in succession, with the VIPergic system as the final mediator. Electrical stimulation (ES) within the turkey hypothalamus at the level of the medial preoptic area (POA), the ventromedial hypothalamic nucleus (VMN), the INF or the median eminence (ME) results in the release of PRL. When the selective D[sub 1] DA receptor antagonist SCH-23390 HCl was infused intraventricularly at the rate of 10 nmol/min, ES in the POA or VMN was unable to increase PRL levels, while ES in the INF and ME did increase PRL to the same level as that of controls. These results were interpreted to suggest that the D[sub 1] DA receptors involved in PRL release lie caudally to the VMN and dorsally to the INF. Bilateral microinjections (50 ng) of the D[sub 1] DA receptor agonist SKF-38393 HCl into the POA or VMN failed to produce any increase in PRL, while similar microinjections in the INF increased PRL significantly within 15 min. Bilateral microinjections of the D[sub 1] DA antagonist (50 ng) into the INF blocked the rise in PRL associated with ES in the POA. Bilateral microinjections of a D[sub 2] DA antagonist (50 ng) into the INF failed to block PRL secretion induced by ES in the POA. Tract tracing, using double-label immunocytochemistry, revealed the presence of a monosynaptic dopaminergic pathway projecting from the POA to the INF. These data imply that the only hypothalamic D[sub 1] DA receptors involved in the regulation of avian PRL secretion are those residing within the INF in the same region as the VIP neurons known to be involved in PRL secretion.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Marfan syndrome (MS) is a dominantly inherited connective tissue disorder characterized by arachnodactyly, tall stature, the presence of aortic aneurysm, and lens dislocation. Takayasu's arteritis (TA) is a chronic vasculitis that primarily affects the aorta and its branches. The authors report the first case of TA in a patient with MS. The simultaneous presence of TA and MS could be a coincidence, however; the pathogenesis of TA might be linked with autoimmunity induced by abnormal extracellular matrix protein derived from the genetic mutations in MS. [ABSTRACT FROM AUTHOR]