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Scalable and economical methods for the production of optically pure amino acids, both natural and unnatural, are essential for their use as synthetic building blocks. Currently, enzymatic dynamic kinetic resolution (DKR) underpins some of the most effective processes. Here we report the development of enantioselective extraction coupled with racemization (EECR) for the chirality conversion of underivatized amino acids. In this process, the catalytic racemization of amino acids in a basic aqueous solution is coupled with the selective extraction of one enantiomer into an organic layer. Back-extraction from the organic layer to an acidic aqueous solution then completes the deracemization of the amino acid. The automation of the EECR process in a recycling flow reactor is also demonstrated. Continuous EECR is made possible by the sterically hindered chiral ketone extractant 5, which prevents the coextraction of the copper racemization catalyst because of its nonplanar geometry. Furthermore, the extractant 5 unexpectedly forms imines with amino acids faster and with greater enantioselectivity than less bulky derivatives, even though 5 cannot participate in intramolecular resonance-assisted hydrogen bonding. These features may allow EECR to challenge the preponderance of enzymatic DKR in the production of enantiomerically enriched amino acids. Dynamic kinetic resolution is a common approach for the preparation of optically pure amino acids using enzymes. Here the authors report an alternative method based on enantioselective extraction coupled with racemization, in which a bulky extractant affords hydrophobic extractable imines with amino acids rapidly, reversibly and enantioselectively. [ABSTRACT FROM AUTHOR]

The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is a cytoplasmic multimolecular complex that generates interleukin (IL)-1β and is considered a main pathogenic mechanism for uric acid-induced inflammation. Whether toll-like receptor 9 (TLR9) is responsible for uric acid-induced NLRP3 inflammasome activation remains unclear. Thus, the aim of this study was to identify the role of TLR9 in NLRP3 inflammasome activation through monosodium urate (MSU) crystal-induced mitochondrial DNA. RAW 264.7 cells treated with MSU crystals, CpG oligonucleotides (ODNs), or a combination of both were used to assess nuclear factor (NF)-κB signaling, NLRP3 inflammasome components such as NLRP3, ASC, and caspase-1, and IL-1β. Real-time polymerase chain reaction (RT-PCR), Western blotting, DNA fragmentation assay, mitochondrial DNA copy number assay, and immunofluorescence were used in the in vitro study. RAW 264.7 cells treated with CpG-ODN stimulated the activation of NF-κB signaling, the NLRP3 inflammasome components NLRP3, ASC, and caspase-1, and IL-1β gene and protein expression. DNA fragmentation assay showed that MSU crystals induced cellular apoptosis. Fragmented DNA prompted by MSU crystals induced TLR9 expression. RAW 264.7 cells treated with CpG-ODN or MSU crystals and both increased expression of mitochondrial DNA relative to nuclear DNA. CpG-ODN and MSU crystals augmented the activation of NLRP3 inflammasome components and IL-1β expression, which was significantly suppressed in RAW 264.7 cells transfected with TLR9 siRNA. This study suggests that TLR9 activated by MSU crystal-mediated mitochondrial DNA contributes to the activation of NLRP3 inflammasomes and IL-1β production. [ABSTRACT FROM AUTHOR]

This paper deals with the current Blockchain adopted in the various types of trading markets supporting smart contracts that process text-based transaction information only when exchanging cryptocurrencies. Even though the Blockchain itself is decentralized, services can still be provided through a centralized system in order to provide adequate services to the users. It also allows the Autochain to apply Blockchain technology to existing businesses conducted under the Fourth Industrial Revolution to realize higher productivity or competitiveness and improve profitability to a remarkable extent. The Autochain is adaptable to all Blockchain technologies, companies, or research works around the world to overcome the limitations of the existing Blockchain technology. It creates the Blockchain-platform ecology chain and ecosystem, making our lives more convenient while revolutionizing every industry. In addition, it automates all Blockchain-based systems and offers a base for constructing a system wherein everyone can easily provide, operate, and maintain Blockchain services. This paper discusses a number of Blockchain-related technologies and presents a decentralized Application (dApp) exclusively designed for mobile use, taking house rental service as an example. It also presents the existing Blockchain and the Blockchain database storage method and proposes the dApp based on it. [ABSTRACT FROM AUTHOR]

There is an ongoing debate regarding the relationship between uric acid and osteoarthritis (OA). Therefore, we sought to clarify this association using data from the Seventh Korea National Health and Nutrition Examination Survey (KNHANES VII-1) 2016 in the Korean population. A total of 5842 subjects over 19 years old were analyzed from the KNHANES VII-1 2016 data, which was conducted by the Korean Centers for Disease Control and Prevention. All of the statistical analyses were performed on the basis of a sampling weight that represents the entire Korean population. The data were described as case numbers with weighted percentages (%), and means with standard errors (SE). The association between OA and the serum uric acid level was statistically analyzed using univariate and multivariate logistic regression methods. A total of 669 subjects (8.6%) had OA, of which 557 were female (14.0%), and 112 male (3.0%). OA was more frequent in female than male subjects (n = 557, 82.6% in women) (p < 0.001). The serum uric acid level was significantly higher in subjects without OA than those with OA (p < 0.001). Subgroup analysis in female subjects demonstrated that the serum uric acid level in OA was much higher than those without OA [4.48 (SE 0.05) vs. 4.34 (SE 0.02), p = 0.013]. In contrast, there was no such difference in male subjects. However, the statistical significance in women was lost after adjusting for covariates (OR 0.888, 95% CI 0.785-1.005, p = 0.060). The serum uric acid level was not significantly associated with OA in the Korean population, although there was a trend toward such a relationship in female subjects. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the relationships among the risk factors for and components of metabolic syndrome (MetS) and health-related quality of life (HRQOL) in a hypothesized causal model using structural equation modeling (SEM) in patients with systemic lupus erythematosus (SLE).Methods: Of the 505 SLE patients enrolled in the Korean Lupus Network (KORNET registry), 244 had sufficient data to assess the components of MetS at enrollment. Education level, monthly income, corticosteroid dose, Systemic Lupus Erythematosus Disease Activity Index, Physicians' Global Assessment, Beck Depression Inventory, MetS components, and the Short Form-36 at the time of cohort entry were determined. SEM was used to test the causal relationship based on the Analysis of Moment Structure.Results: The average age of the 244 patients was 40.7 ± 11.8 years. The SEM results supported the good fit of the model (χ 2 = 71.629, p = 0.078, RMSEA 0.034, CFI 0.972). The final model showed a direct negative effect of higher socioeconomic status and a positive indirect effect of higher disease activity on MetS, the latter through corticosteroid dose. MetS did not directly impact HRQOL but had an indirect negative impact on it, through depression.Conclusions: In our causal model, MetS risk factors were related to MetS components. The latter had a negative indirect impact on HRQOL, through depression. Clinicians should consider socioeconomic status and medication and seek to modify disease activity, MetS, and depression to improve the HRQOL of SLE patients. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate the prevalence and incidence of gout in Korea and predict the future prevalence and incidence of gout. Data were collected from the national health claims database. Patients who had at least one claim for gout between 2007 and 2015 were included in the study. The prevalence of gout from 2007 to 2015 and the incidence of gout from 2009 to 2015 were determined. We estimated sex- and age-specific prevalence and incidence of gout during the period. The prevalence and incidence of gout were predicted using time series analysis. The prevalence of gout (95% CI) increased from 3.49 (3.48-3.51) per 1000 persons in 2007 to 7.58 (7.55-7.60) per 1000 persons in 2015. The incidence of gout (95% CI) was 1.52 (1.51-1.53) in 2009 and rose to 1.94 (1.93-1.95) per 1000 persons in 2015. The prevalence and incidence of gout were higher in men than in women. The older population had a higher prevalence and incidence than the younger population. The increase in prevalence was higher in the older population than the younger population, whereas the increase in incidence was higher in the younger population than the older population. The predicted prevalence and incidence of gout (95% CI) in 2025 were 16.59 (15.85-17.34) per 1000 persons and 3.81 (3.14-4.47) per 1000 persons. The prevalence and incidence of gout increased in Korea between 2007 and 2015. Men and the older population had a higher prevalence and incidence of gout compared to women and the younger population. However, the incidence of gout in the younger population has increased rapidly in recent years. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the role of thioredoxin-interacting protein (TXNIP) and its interaction with antioxidants in the activation of the fructose-induced NOD-like receptor protein 3 (NLRP3) inflammasome in human macrophages. The study was performed with U937 and THP-1 macrophage cell lines. Total reactive oxygen species (ROS) were measured by flow cytometry. Interleukin-1β (IL-1β), IL-18, NLRP3, TXNIP, and caspase-1 protein expression was detected using western blotting. Quantitative real-time polymerase chain reaction was used to detect IL-1β, IL-18, and caspase-1 gene expression. Intracellular shuttling of TXNIP was assessed by immunofluorescent staining with MitoTracker Red. Increased production of ROS and expression of IL-1β, IL-18, and caspase-1 genes and proteins were observed in U937 and THP-1 cells incubated with fructose and were effectively inhibited by quercetin and ascorbic acid. Intracellular shuttling of TXNIP from the nucleus into the mitochondria was detected under stimulation with fructose, which was also attenuated by antioxidants quercetin and ascorbic acid but not butylated hydroxyanisole. Treatment of macrophages with fructose promoted the association between TXNIP and NLRP3 in the cytosol, sequentially resulting in the activation of the NLRP3 inflammasome. This study revealed that intracellular TXNIP protein is a critical regulator of activation of the fructose-induced NLRP3 inflammasome, which can be effectively blocked by the antioxidants quercetin and ascorbic acid. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical effectiveness of two treatment strategies for active rheumatoid arthritis (RA) refractory to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs): starting TNF inhibitors (TNFIs) or changing csDMARDs. Methods: We used two nationwide Korean RA registries for patient selection. TNFI users were selected from the BIOPSY, which is an inception cohort of RA patients starting biologic DMARDs. As a control group, we selected RA patients with moderate or high disease activity from the KORONA database whose treatment was changed to other csDMARDs. After comparing baseline characteristics between the two groups in either unmatched or propensity score matched cohorts, we compared potential differences in the 1-year remission rate as a primary outcome and changes in HAQ-DI and EQ-5D scores as secondary outcomes. Results: A total of 356 TNFI starters and 586 csDMARD changers were identified from each registry as unmatched cohorts, and 294 patients were included in the propensity score matched cohort. In the intention-to-treat analysis, TNFI starters had higher 1-year remission rates than csDMARD changers in both unmatched (19.1 vs. 18.4%, p < 0.01) and matched cohorts (19.7 vs. 15.0%, p < 0.01). In per protocol analysis, TNFI starters had much higher remission rates in unmatched (37.2 vs. 28.0%, p = 0.04) and matched cohorts (35.4 vs. 19.1%, p = 0.04). However, in matched cohorts, no significant differences were observed between two groups in HAQ-DI and EQ-5D scores. Conclusions: We compared the clinical effectiveness of the two treatment strategies for active RA refractory to csDMARDs. TNFI starters showed higher 1-year remission rates than csDMARD changers. [ABSTRACT FROM AUTHOR]

Despite improved quality of care for rheumatoid arthritis (RA) patients, many still experience treatment failure with a biologic agent and eventually switch to another biologic agent. We investigated patterns of biologic treatment and reasons for switching biologics in patients with RA. Patients with RA who had started on a biologic agent or had switched to another biologic agent were identified from the prospective observational Korean nationwide Biologics (KOBIO) registry. The KOBIO registry contained 1184 patients with RA at the time of initiation or switching of biologic agents. Patients were categorized according to the chronological order of the introduction of biologic agents, and reasons for switching biologics were also evaluated. Of the 1184 patients with RA, 801 started with their first biologic agent, 228 were first-time switchers, and 89 were second-time or more switchers. Second-time or more switchers had lower rheumatoid factor and anti-CCP positivity, and higher disease activity scores at the time of enrollment than the other groups. Among these patients, tocilizumab was the most commonly prescribed biologic agent, followed by adalimumab and etanercept. The most common reason for switching biologics was inefficacy, followed by adverse events, including infusion reactions, infections, and skin eruptions. Furthermore, the proportion of inefficacy, as a reason for switching, was significantly higher with respect to switching between biologics with different mechanisms of action than between biologics with similar mechanisms. In this registry, we showed diverse prescribing patterns and differing baseline profiles based on the chronological order of biologic agents. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the characteristics of Andersson lesions using whole spine magnetic resonance imaging (MRI) compared with plain radiography in ankylosing spondylitis (AS). A total of 62 patients with AS who had undergone whole spine MRI and plain radiography were retrospectively enrolled in this study. We compared the number of discovertebral units (DVUs) with Andersson lesions with clinical and radiographic indices such as erythrocyte sediment rate (ESR), C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Fifty-three patients (85.5 %) by whole spine MRI and 23 patients (37.1 %) by plain radiography had at least one Andersson lesion. We found 129 DVUs with Andersson lesions (11.1 %) by MRI and 35 DVUs by plain radiography over all the spine levels. Andersson lesions by MRI were most commonly detected at the lower thoracic spine (from T7-8 to T12-L1). Among the 151 total Andersson lesions by whole spine MRI, 41 were identified as central disc type, 26 as anterior peripheral disc type, 44 as posterior peripheral disc type, and 40 as diffuse disc type. However, the number of Andersson lesions did not correlate with ESR, CRP, BASDAI, BASFI, or mSASSS ( p > 0.05 for all). Our study indicates that the presence of Andersson lesions in patients with AS is clearly underestimated. MRI is a superior technique for detecting early Andersson lesions compared with plain radiography. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the role of p62-dependent mitochondrial apoptosis in the initiation of monosodium urate (MSU) crystal-induced inflammation in macrophages. The induction of mitochondrial apoptosis in RAW 264.7 murine macrophages by MSU crystals was measured using western blotting and quantitative real-time polymerase chain reaction for Bax, caspase-3, caspase-9, or PARP1, and by flow cytometric analysis. Immunoprecipitation and western blotting was applied to detect ubiquitination of p62, TRAF6, and caspase-9. Mitochondrial apoptosis, reactive oxygen species (ROS) generation, and cell proliferation were assessed in cells transfected with p62 small interfering RNA (siRNA). Treatment of RAW 264.7 cells with MSU crystals induced activation of Bax, caspase-3, caspase-9, and PARP1 at the early phase, in addition to enhancing IL-1β expression, but these findings were attenuated at the late phase. MSU crystals induced ubiquitination of p62, followed by ubiquitination of TRAF6 and caspase-9, which were significantly reversed by ascorbic acid. RAW 264.7 cells transfected with p62 siRNA showed attenuated expression of Bax, caspase-3, caspase-9, and PARP1, decreased ROS and IL-1β production, and increased cell proliferation, compared to controls. The antioxidant ascorbic acid inhibited p62, caspase-9, and IL-1β expression increased by MSU crystals. p62 may be a crucial mediator for the mitochondrial apoptosis pathway in MSU crystal-induced inflammation, which is linked to the acute inflammatory response during the early phase of gout. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome is an autoimmune disease that primarily affects exocrine glands. Renal involvement of Sjögren's syndrome may lead to tubulointerstitial disease, whereas secondary glomerulopathies such as anti-neutrophil cytoplasmic antibody (ANCA)-related pauci-immune crescentic glomerulonephritis are rarely observed. In addition, crescent glomerulonephritis that is simultaneously positive for both myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA has never been reported in Sjögren's syndrome. Here, we report a case of pauci-immune crescentic glomerulonephritis exhibiting positivity for both MPO- and PR3-ANCAs in a patient with primary Sjögren's syndrome. A 71-year-old female was hospitalized for cough, blood-tinged sputum, and dyspnea two weeks after diagnosis with Sjögren's syndrome. On admission, serum anti-nuclear antibody, anti-Ro/SS-A antibody, MPO-ANCA, and PR3-ANCA were all positive, and serum blood urea nitrogen and creatinine (Cr) levels were 42.7 and 2.9 mg/dL, respectively. On the seventh day of hospitalization, the patient's serum Cr level was 5.7 mg/dL, indicating rapidly progressive glomerulonephritis. Renal biopsy resulted in the diagnosis of ANCA-related pauci-immune crescentic glomerulonephritis, for which intravenous methylprednisolone (7 mg/kg/day) was administered for three consecutive days, followed by combination therapy with oral prednisolone (1 mg/kg/day) and intravenous cyclophosphamide (500 mg/m). The patient was positive in the Schirmer's I test, and a salivary gland biopsy showed sialadenitis with lympho-plasmacytic infiltrations. On day 28 of hospitalization, the patient was discharged after amelioration of respiratory symptoms and azotemia. At 6 months after discharge, the patient continued to receive appropriate daily medications and was negative for both MPO- and PR3-ANCAs, with a slight elevation in serum Cr levels. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify serum and urine biomarkers that correlate with disease activity in female patients with systemic lupus erythematosus (SLE). Methods: Serum and urine levels of interferon γ-induced protein-10 (IP-10), TNF-like weak inducer of apoptosis (TWEAK), and monocyte chemotactic protein-1 (MCP-1) of 70 patients with SLE and 61 healthy controls were measured with enzyme-linked immunosorbent assays. Results: The serum and urine levels of TWEAK, IP-10, and MCP-1 in both high and low SLE disease activity index (SLEDAI) groups of SLE patients were markedly higher compared with those of healthy controls. Moreover, the serum TWEAK level was positively correlated with the serum IP and serum MCP-1 levels ( p < 0.001 for both). The serum TWEAK levels, SLEDAI scores, and urine protein/creatinine levels were significantly different between the SLE group with non-renal involvement and with renal involvement ( p = 0.034, p < 0.001, and p < 0.001, respectively). The serum TWEAK level was a crucial determinant for a high SLEDAI score and renal involvement ( p = 0.044 and p = 0.046, respectively). Conclusion: Serum TWEAK might be a serologic biomarker candidate that reflects disease activity and renal involvement in patients with SLE. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether body mass index (BMI) is associated with clinical response to biologics in patients with rheumatoid arthritis (RA). We enrolled 68 patients with RA who were treated with biological disease-modifying antirheumatic drugs (bDMARDs). Biologics included abatacept, tocilizumab, and tumor necrosis factor-α (TNF-α) blockers (etanercept and adalimumab). Baseline BMI (kg/m) was classified as normal (BMI < 23.0), overweight (23.0 ≤ BMI < 25.0), or obese (BMI ≥ 25.0). Improvement of disease activity score 28 (DAS28) and achievement of the European League Against Rheumatism (EULAR) remission and responses between baseline and 24 weeks were our measures of clinical improvement. Mean baseline BMI before treatment with bDMARDs in patients with RA was 22.2 (SD 3.6). DAS28-ESR and DAS28-CRP were significantly reduced from baseline after 24 weeks of treatment with bDMARDs ( p < 0.001 of both). ∆DAS28-ESR and ∆DAS28-CRP were not found among patients with normal, overweight, or obese BMI ( p = 0.133 and p = 0.255, respectively) nor were EULAR responses or EULAR remission ( p = 0.540 and p = 0.957, respectively). Logistic regression analysis showed no relationship of BMI with EULAR clinical responses ( p = 0.093 for good response and p = 0.878 for EULAR remission). This study reveals that BMI is not a predictive factor of clinical response to bDMARDs in patients with RA. [ABSTRACT FROM AUTHOR]

The aim of this study was to estimate the mapping model for EuroQol-5D (EQ-5D) utility values using the health assessment questionnaire disability index (HAQ-DI), pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) in a large, nationwide cohort of rheumatoid arthritis (RA) patients in Korea. The KORean Observational study Network for Arthritis (KORONA) registry data on 3557 patients with RA were used. Data were randomly divided into a modeling set (80 % of the data) and a validation set (20 % of the data). The ordinary least squares (OLS), Tobit, and two-part model methods were employed to construct a model to map to the EQ-5D index. Using a combination of HAQ-DI, pain VAS, and DAS28, four model versions were examined. To evaluate the predictive accuracy of the models, the root-mean-square error (RMSE) and mean absolute error (MAE) were calculated using the validation dataset. A model that included HAQ-DI, pain VAS, and DAS28 produced the highest adjusted R as well as the lowest Akaike information criterion, RMSE, and MAE, regardless of the statistical methods used in modeling set. The mapping equation of the OLS method is given as EQ-5D = 0.95−0.21 × HAQ-DI−0.24 × pain VAS/100-0.01 × DAS28 (adjusted R = 57.6 %, RMSE = 0.1654 and MAE = 0.1222). Also in the validation set, the RMSE and MAE were shown to be the smallest. The model with HAQ-DI, pain VAS, and DAS28 showed the best performance, and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured. [ABSTRACT FROM AUTHOR]

This study investigated the effect of rebamipide on activation of the NLRP3 inflammasome and generation of reactive oxygen species (ROS) in monosodium urate (MSU) crystal-induced interleukin-1β (IL-1β) production. Human monocyte cell line THP-1 and human umbilical venous endothelial cells (HUVECs) were used to assess the inflammatory response to MSU crystals. NADP/NADPH activity assays were used as a marker of ROS generation. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate levels of IL-1β, caspase-1, NLRP3, associated speck-like protein (ASC), nuclear factor-κB (NF-κB), p65, IκBα, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Experimental pharmaceuticals included rebamipide, colchicine, dexamethasone, and ascorbic acid. In THP-1 cells, treatment with MSU crystals increased NADP/NADPH ratios and IL-1β expression, and both of these responses were potently inhibited by addition of rebamipide. Rebamipide also attenuated enhanced expression of caspase-1 gene by MSU crystals ( p < 0.05). Western blotting demonstrated that MSU crystals stimulated caspase-1 but not NLRP3 and ASC activation. Similarly, MSU crystals activated the NF-κB pathway, which in turn was blocked by rebamipide. Stimulation of HUVECs with MSU crystals increased expression of VCAM-1 and ICAM-1, which were markedly inhibited by both rebamipide and dexamethasone. This study demonstrated that rebamipide inhibits IL-1β activation through suppression of ROS-mediated NF-κB signaling pathways and caspase-1 activation in MSU crystal-induced inflammation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the characteristic magnetic resonance imaging (MRI) findings in neuropsychiatric systemic lupus erythematosus (NPSLE) and to investigate the association between MRI findings and neuropsychiatric manifestations in SLE. Brain MRIs with a diagnosis of SLE from 2002 to 2013 from three tertiary university hospitals were screened. All clinical manifestations evaluated by brain MRI were retrospectively reviewed. If the clinical manifestations were compatible with the 1999 NPSLE American College of Rheumatology (ACR) nomenclature and case definitions, the brain MRIs were assessed for the presence of white matter hyperintensities, gray matter hyperintensities, parenchymal defects, atrophy, enhancement, and abnormalities in diffusion-weighted images (DWI). The number, size, and location of each lesion were evaluated. The neuropsychiatric manifestation of each brain MRI was classified according to the 1999 ACR NPSLE case definitions. The associations between MRI findings and NPSLE manifestations were examined. In total, 219 brain MRIs with a diagnosis of SLE were screened, and 133 brain MRIs met the inclusion criteria for NPSLE. The most common MRI abnormality was white matter hyperintensities, which were observed in 76 MRIs (57.1 %). Gray matter hyperintensities were observed in 41 MRIs (30.8 %). Parenchymal defects were found in 31 MRIs (23.3 %), and atrophy was detected in 20 MRIs (15.0 %). Patients who had seizures were more associated with gray matter hyperintensities than patients with other neuropsychiatric manifestations. Patients with cerebrovascular disease were more associated with gray matter hyperintensity, parenchymal defects, and abnormal DWI than patients with other neuropsychiatric manifestations. In addition to white matter hyperintensities, which were previously known as SLE findings, we also noted the presence of gray matter hyperintensities, parenchymal defects, and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizures. [ABSTRACT FROM AUTHOR]

Caffeine, a commonly consumed food constituent, is known to exert beneficial physiological effects in humans. There is a lack of comprehensive population data for the effects of caffeine intake on urate metabolism. Therefore, the aim of this study was to determine whether coffee, tea, and caffeine intake influences serum uric acid and the risk of hyperuricemia in the Korean Multi-Rural Communities Cohort. We enrolled 9,400 participants in this study. An assessment of various dietary intake amounts of substances such as coffee and tea was performed using a food frequency questionnaire. The content of caffeine was calculated from coffee (74 mg/cup) and tea (15 mg/cup) intake information from the past year. Multivariate logistic regression models, multiple linear regression models, and analysis of covariance were applied to identify any association of dietary intake with serum uric acid levels or the risk of hyperuricemia. No trends for coffee, tea, or caffeine intake were found according to each quintile with serum uric acid in males, although there were weak, marginally significant trends between the content of coffee and caffeine intake and serum uric acid level in females ( p = 0.07 for both). Tea intake in males and caffeine intake in females were significantly different between non-hyperuricemia and hyperuricemia ( p = 0.04 and p = 0.04, respectively). In addition, a significant association of serum uric acid level with tea intake in males ( β = 0.0006, p = 0.02) and with tea intake and caffeine intake in females ( β = 0.0003, p = 0.04 and β = 0.0006, p = 0.02, respectively) was observed. There was no effect of coffee, tea, or caffeine intake on the risk of hyperuricemia in either males or females. This study suggests that caffeine consumption might have an effect on serum uric acid in females. However, coffee, tea, and caffeine intake amounts were not associated with the risk of hyperuricemia. [ABSTRACT FROM AUTHOR]

The aim of this study is to clarify the effect of oxidative stress on monosodium urate (MSU)-mediated apoptosis of renal cells. Quantitative real-time polymerase chain reaction and immunoblotting for Bcl-2, caspase-9, caspase-3, iNOS, cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-18, TNF receptor-associated factor-6 (TRAF-6), and mitogen-activated protein kinases were performed on human embryonic kidney 293 (HEK293) cells, which were stimulated by MSU crystals. Fluorescence-activated cell sorting was performed using annexin V for assessment of apoptosis. Reactive oxygen species (ROS) were measured. IL-1β siRNA was used for blocking IL-1β expression. MSU crystals promoted ROS, iNOS, and COX-2 expression and also increased TRAF-6 and IL-1β expression in HEK293 cells, which was inhibited by an antioxidant ascorbic acid. Caspase-dependent renal cell apoptosis was induced through attenuation of Bcl-2 and enhanced caspase-3 and caspase-9 expression by MSU crystals, which was significantly reversed by ascorbic acid and transfection of IL-1β siRNA to HEK293 cells. Ascorbic acid inhibited phosphorylation of extracellular signal-regulated kinase and Jun N-terminal protein kinase stimulated by MSU crystals. ROS accumulation and iNOS and COX-2 mRNA expression by MSU crystals was also suppressed by transfection with IL-1β siRNA. Oxidative stress generated by MSU crystals promotes renal apoptosis through the mitochondrial caspase-dependent apoptosis pathway. [ABSTRACT FROM AUTHOR]

To evaluate the performance of Routine Assessment of Patient Index Data 3 (RAPID3) with the disease activity score 28 (DAS28) and the clinical/simplified disease activity index (CDAI/SDAI) in a Korean population with rheumatoid arthritis (RA). Four hundred patients with RA were consecutively enrolled. All patients completed disease activity indices such as RAPID3, DAS28, SDAI, and CDAI. The kappa and/or weighted coefficients were used to assess agreement between RAPID3 and other disease activity indices. ANOVA, Mantel-Haenszel chi-square test, and Spearman's partial correlation analysis were used for analyses. RAPID3 scores were significantly correlated with DAS28 ( r = 0.62), SDAI ( r = 0.74), and CDAI ( r = 0.75; p < 0.0001 for all indices) and other activity measures including swollen/tender joint counts, erythrocyte sediment rate, and C-reactive protein. The weighted kappa coefficients of RAPID3 with DAS28, SDAI, and CDAI among the four disease activity categories were 0.33, 0.34, and 0.33, respectively. Kappa coefficients for RAPID3 in two disease activity categories increased more than four categories ( κ = 0.40-0.42) indicating fair agreement. More than 86 % of patients with high-to-moderate disease activity in DAS28, CDAI, and SDAI had high-to-moderate disease activity using RAPID3 criteria. However, approximately 50 % of patients with remission-to-low disease activity in DAS28, CDAI, and SDAI showed remission-to-low disease activity in RAPID3. This study confirms RAPID3 as an informative disease activity index with equivalent values in DAS28, CDAI, and SDAI. RAPID3 reveals differential agreement in patients with lower disease activity. [ABSTRACT FROM AUTHOR]

The debate regarding the influence of body mass index (BMI) on clinical disease activity in rheumatoid arthritis (RA) remains unsolved. This study investigates whether BMI is associated with disease activity composites and clinical parameters in Korean patients with RA. A total of 568 patients with RA were consecutively enrolled in this study. BMI and disease activity composites including the Disease Activity Score 28 (DAS28) and the Clinical/Simplified Disease Activity Index (CDAI/SDAI) were assessed. Statistical analyses were performed using Chi-square, one-way ANOVA, and multivariate regression analyses. Remission of RA disease activity was defined as ≤2.6 in a DAS28 score. The mean BMI was 22.3 kg/m (SD 3.1). About 60.6 % ( n = 344) of enrolled patients fell into the underweight and normal BMI categories. Swollen joint count was significantly different among the four BMI categories ( p = 0.038). Multivariate regression analysis showed a negative correlation of BMI and erythrocyte sediment rate (ESR) in all patients ( β= − 0.011, p = 0.049) and also found that other disease activity indices were not found to be associated with BMI. In patients with remission, lower BMI was associated with higher physician global estimate ( β= − 0.446, p = 0.030). The negative association between BMI and ESR in the non-remission group was noted ( β= − 0.016, p = 0.019). This study revealed lack association between BMI and disease activity composites of RA, although only ESR was found to be associated with BMI in RA patients. [ABSTRACT FROM AUTHOR]

To analyze the association of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) with non-remission and with disease activity measures in rheumatoid arthritis (RA). Cross-sectional study of consecutive RA patients. Non-remission was defined as a disease activity score (DAS28) ≥2.6 at study enrollment. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were additionally measured. Serum titers of RF and anti-CCP were transformed into incremental levels (100/units) and log-transformed levels. Analysis of association with non-remission was done with logistic regression models, with and without adjustment for age, sex, disease duration, and corticoid use. Multiple regression models, raw and similarly adjusted, were used to measure the association of RF and anti-CCP with the disease activity measures. A total of 385 patients were included, of whom 286 (74 %) were not in remission. Log-transformed RF level was associated with an increased risk of non-remission after adjustment (OR = 1.32, 95 % CI 1.04-1.67). This association was especially evident in patients with less than 10 years of disease duration (OR = 1.51, 95 % CI 1.15-1.99) and in those using steroids (OR = 2.06, 95 % CI 1.22-3.48). Serum RF titers and log-transformed RF levels showed a small but significant association with DAS28 score (adjusted beta coefficients 0.002 and 0.18, respectively; both p ≤ 0.01), but neither with SDAI or CDAI nor with anti-CCP antibody. : Log-transformed RF levels might be associated with non-remission in RA, especially in patients with short disease duration or on steroids. [ABSTRACT FROM AUTHOR]

Interleukin-15 (IL-15) is a pleotrophic cytokine that is involved in the pathogenesis of diverse inflammatory rheumatic diseases. The aims of this study were to compare serum IL-15 levels and expression of its receptor (IL-15Rα) in Behçet's disease (BD) with those in other rheumatic diseases and to identify the relationship between serum IL-15 levels and various clinical parameters in BD. One hundred fifty-eight subjects consisting of 40 BD, 38 systemic lupus erythematosus (SLE), 40 rheumatoid arthritis (RA), and 40 healthy controls were enrolled. Serum IL-15 levels were measured using an enzyme-linked immunosorbent assay. The proportion of IL-15Rα expression on each leukocyte subset was measured by flow cytometry. Erythrocyte sediment rate (ESR) and C-reactive protein (CRP) were measured for each enrolled subject. The clinical activity index of BD was assessed for BD patients. Serum IL-15 levels in BD patients are significantly higher than those of healthy controls, SLE, and RA patients ( p < 0.001, p < 0.001, and p < 0.001, respectively). Serum IL-15 levels in BD were closely related to ESR ( r = 0.405, p = 0.027), but not to CRP or the clinical activity index of BD ( p > 0.05 for both). Additionally, there was no difference in serum IL-15 levels between active and inactive disease states in BD ( p > 0.05). The proportion of IL-15Rα expression on total leukocytes was much lower for all rheumatic diseases, including BD, than in healthy controls ( p < 0.01 for SLE, p < 0.01 for RA, and p < 0.05 for BD). IL-15 and IL-15Rα system may be involved in the inflammatory process and pathogenesis of BD. [ABSTRACT FROM AUTHOR]

Small ubiquitin-like modifier 4 (SUMO4) is involved in a range of autoimmune diseases and is known to downregulate the transcription activity of nuclear factor kappa B (NF-κB). Our objective was to investigate the association of a certain polymorphism (C438T) of the SUMO4 gene with Behçet's disease (BD) in terms of its incidence and clinical features in Korean patients. We consecutively enrolled 83 patients with BD and 120 healthy controls. Genomic DNA was extracted from whole-blood samples. We identified a single nucleotide change (C438T) in the SUMO4 gene using an amplification refractory mutation system (ARMS) technique. To validate the ARMS technique, we compared its results to the results of direct sequencing in 20 subjects. HLA-B51 status was determined by polymerase chain reaction sequence-specific primers. The presence of papulopustular lesions ( P = 0.006) and vascular involvement ( P = 0.045) was significantly different between C438T genotypes in HLA-B51-positive patients with BD. There were no differences in allelic or genotypic frequencies of the SUMO4 C438T polymorphism between patients with BD and controls ( P = 0.567 and P = 0.818, respectively). The difference in papulopustular skin lesions between CC and CT + TT genotypes in HLA-B51-positive patients with BD was also statistically significant ( P = 0.002, OR = 23.40, 95% CI: 2.33-235.54). The C438T polymorphism in the SUMO4 gene is associated with significantly increased risk of papulopustular skin lesions in HLA-B51-positive patients. [ABSTRACT FROM AUTHOR]

SLC22A12 gene, encoding urate transport 1, has been known to be responsible to urate metabolism. This study sought to determine the association between the novel G109T polymorphism in SLC22A12 with serum uric acid and the development of metabolic syndrome in Korean male subjects. A total of 132 healthy male subjects were enrolled in this study. Metabolic syndrome was determined using the modified guidelines for metabolic syndrome proposed by the National Cholesterol Education Program's Third Adult Treatment Panel. Genotyping for the SLC22A12 gene was assessed using denaturing high-performance liquid chromatography analysis. Serum uric acid and fractional excretion of uric acid (FEUA) from blood and urine samples were measured. Frequencies of the 109GG, 109GT, and 109TT genotypes were 57.6, 38.6, and 3.8%, respectively. Serum uric acid levels and FEUAs were significantly different among the three genotypes of the G109T polymorphism ( P = 0.035 and P = 0.033, respectively). In addition, subjects of genotypes with the T allele had lower uric acid levels and higher FEUAs compared to those with the 109GG genotype ( P = 0.007 and P = 0.031, respectively). The G109T polymorphism of the SLC22A12 gene has no association with metabolic syndrome. However, a number of metabolic syndrome components were related to serum uric acid level ( r = 0.285, P = 0.001) and also significantly different between genotype with and without T allele ( P = 0.008). The novel G109T polymorphism of the SLC22A12 gene is related to serum uric acid level, but not to the development of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether promoter -2518 single nucleotide polymorphism (SNP) of the monocyte chemoattractant protein-1 ( MCP-1) gene contributes to susceptibility and clinical features or severity in Behçet's disease (BD) patients. Methods: One hundred and thirty-two BD patients and 113 healthy subjects, matched by sex and age, were enrolled. Promoter -2518 polymorphism of the MCP-1 gene was analyzed using automated sequencing. Clinical severity in BD patients was classified into mild, moderate, and severe features and assessed by total severity scores. Clinical features and severity was also compared according to genotypes using either the chi-squared or Fisher's exact test and Mann-Whitney test, as indicated. Results: There were no significant differences in alleles (G allele vs. A allele, p = 0.845) and genotypes with -2518 SNP (GG vs. GA vs. AA, p = 0.916) between BD patients and controls. No clinical features were associated with genotypes with -2518 polymorphism of MCP-1. However, the frequency of either GA or AA genotype in patients with moderate lesions and moderate to severe lesions was significantly increased compared with that in patients with the GG genotype ( p = 0.044 and p = 0.038, respectively). Total severity scores in the AA genotype were higher than those in the GG and GA genotypes ( p = 0.039 and p = 0.003, respectively). Moreover, patients with either the GA or AA genotype had higher scores than those with the GG genotype ( p = 0.041). Conclusions: This study demonstrated that genotypes with A allele with -2518 polymorphism of the MCP-1 gene might have increased risk of severity of clinical features, but not susceptibility to BD. [ABSTRACT FROM AUTHOR]

We investigated associations between the methylenetetrahydrofolate reductase (MTHFR) polymorphisms C677T and A1298C and methotrexate (MTX)-related toxicities in Korean patients with rheumatoid arthritis (RA) taking MTX. One hundred sixty-seven patients with RA were enrolled in a cross-sectional study and genotyped for the single-nucleotide polymorphisms C677T and A1298C in MTHFR. Alleles, genotypes, and haplotypes of the C677T and A1298C polymorphisms were not associated with specific MTX toxicities. However, among RA patients with the 1298CC genotype, the proportion who experienced at least one toxicity was significantly greater than the proportion of patients with 1298AA who did ( P = 0.043). In addition, the proportion of patients with the 677C/1298A haplotype who experienced toxicity was greater than the proportion of those with 677C/1298C who did ( P = 0.032, odds ratio = 2.085, 95% confidence interval 1.058-4.106). In this study, MTHFR polymorphisms were associated with MTX toxicities in Korean patients with RA. Further study for association of MTHFR polymorphisms with MTX toxicities should be needed in larger RA population. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that individuals with fibromyalgia (FM) have impairments in general cognitive functions. However, few studies have explored the possibility of dissociation between verbal and visuospatial memory impairments in FM. Therefore, the purpose of this study was to investigate the asymmetrical impairment of cognitive functions between verbal and visuospatial memory and between short-term and long-term memory. Neuropsychological assessments were carried out on 23 female patients with FM and 24 healthy female controls. Verbal memory abilities were assessed using the Korean version of the Rey auditory verbal learning test (KAVLT) and digit span task, and visuospatial memory abilities were assessed using the Korean version of the Rey complex figure test (KCFT) and spatial span task. The analysis of covariance was used to assess group differences in performance on cognitive tests after controlling for depression. The two groups did not significantly differ in terms of age, years of education, or in their estimated verbal and performance IQ, but FM patients reported more severe depressive symptoms than did controls on the Beck depression inventory. Significant group differences were found in immediate and delayed recall on the KCFT ( F = 6.49, p = 0.014 and F = 6.96, p = 0.011, respectively), whereas no difference was found in immediate and delayed recall on the KAVLT. In terms of short-term memory, neither the digit span task nor spatial span task showed any difference between groups, regardless of whether repetition was forward or backward. These findings suggest that spatial memory abilities may be more impaired than verbal memory abilities in patients with FM. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to identify the inhibitory effect of rebamipide on tumor necrosis factor-α (TNF-α)-induced interleukin-8 (IL-8) production and nuclear factor-κB (NF-κB) activation in human umbilical vein endothelial cells (HUVECs). Methods: After stimulation with TNF-α, HUVECs were treated with rebamipide in a dose-dependent manner. The viability of HUVECs was assessed using methylthiazol tetrazolium assay after 24 h incubation with rebamipide. TNF-α-induced IL-8 expression was determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (RT-PCR). TNF-α-induced IκB-α phosphorylation and translocation of NF-κB p65 subunit into nucleus in endothelial cells were assessed using immunoblot analysis. Results: We found that rebamipide decreased the expression of IL-8 in the dose-dependent manner under the treatment with TNF-α 10 ng/ml. TNF-α-induced degradation of IκB-α at 15 min was maximally observed and rebamipide (2 mM) inhibited TNF-α-induced phosphorylation of IκB-α in the cytoplasm of endothelial cells by western blot analysis. Rebamipide also suppressed TNF-α-stimulated NF-κB p65 nuclear translocation. Conclusion: Rebamipide suppresses TNF-α-induced IL-8 production through (1) inhibition of IκB-α phosphorylation in the cytoplasm and (2) blockage of NF-κB p65 protein transport into the nucleus. We suggest that the anti-inflammatory effect of rebamipide is related to the down-regulation of IL-8 expression that is important in endothelial inflammation. [ABSTRACT FROM AUTHOR]

IL-17 is a novel cytokine that is characterized by an ability to induce several types of cells to secrete proinflammatory cytokines in various inflammatory diseases. This study analyzed the influence of IL-17F gene polymorphisms on disease susceptibility and clinical features. Ninety-nine Behçet’s disease (BD) patients and 114 controls were genotyped to analyze three single nucleotide polymorphisms (SNPs) including A126G, G155A, and A161G of the IL-17F gene using automated sequencing. We compared the frequencies of IL-17F alleles, genotypes, and haplotypes in patients with BD and controls using the chi-square or Fisher’s exact test. Significant differences in the frequencies of allele and genotype in A126G SNP of IL-17 gene were found between BD patients and controls ( P < 0.001 and P < 0.001, respectively). None of three IL-17F SNPs were associated with diverse clinical features in BD. The frequency of haplotype AA did not differ between patients with BD and controls ( P = 0.985). The haplotypes, AG, and GG, have positive and inverse association with BD susceptibility ( P < 0.001 and P < 0.001, respectively). These findings suggest that IL-17 gene SNPs may influence the susceptibility of BD. [ABSTRACT FROM AUTHOR]