• 한국약용작물학회지
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• 제28권6호
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• pp.471-480
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• 2020

Background: The roots of Cirsium japonicum var. ussuriense (RCJ) have been used as traditional medicine in Korea for hematuria and hematemesis. These extracts exert anti-oxidative and anti-inflammatory effects by scavenging for free radical and regulating the inflammatory response. However, the effect of RCJ on rheumatoid arthritis (RA) has not been elucidated. Thus, we evaluated the water extract of RCJ (WRCJ) using type II collagen-induced RA models. Methods and Results: RA was induced by immunization with type II collagen. All experimental materials were orally administered daily for three weeks. The positive control group was administered with 0.2 mg/kg methotrexate (n = 7), while the experimental group was administered with WRCJ (100 or 500 mg/kg, n = 7). Serum levels of TNF-alpha, Interleukin 6 (IL-6), and type II collagen IgG (CII) were measured using ELISA. Administration of 500 mg/kg WRCJ decreased the levels of TNF-alpha, IL-6, and CII. Moreover, WRCJ treatment diminished swelling of hind legs and infiltration of inflammatory cells in RA models' synovial membrane. Conclusions: These results indicate that WRCJ could improve RA, reduce inflammatory indicators and synovial inflammation. However, further experiments are required to determine how WRCJ can influence the signal transduction pathway in RA.

• IMMUNE NETWORK
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• 제22권1호
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• pp.8.1-8.20
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• 2022

Rheumatoid arthritis (RA) is a representative autoimmune disease that is primarily characterized by persistent inflammation and progressive destruction of synovial joints. RA has a complex and heterogeneous pathophysiology, involving interactions among various immune and joint stromal cells and a diverse network of cytokines and intracellular signaling pathways. With improved understanding of RA, over the past decades, therapeutic strategies have become considerably advanced and now included targeted molecular therapies, such as tumor necrosis factor inhibitors, IL-6 blockers, B-cell depletion agents, as well as inhibitors of T-cell co-stimulation and Janus kinases. However, a considerable proportion of RA patients experience refractory disease and interrupted treatment owing to the associated risk of developing serious infections and cancers. In contrast, although IL-1β, IL-17A, and p38α play significant roles in RA pathogenesis, several drugs targeting these factors have not been approved because of their low efficacy and severe adverse effects. In this review, we provide an overview of the working mechanism, advantages, and limitations of the currently available targeted drugs for RA. Additionally, we suggest potential mechanistic causes for clinically approved and failed drugs. Thus, this review provides perspectives on approaches for basic and translational studies that hold promise for identifying future next-generation therapeutics for RA.

• Safety and Health at Work
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• 제11권2호
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• pp.136-142
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• 2020

Background: Rheumatoid arthritis (RA) is an autoimmune disease with systemic inflammatory arthritis. This meta-analysis was conducted to examine the association between occupational exposure to silica and the risk of developing RA among different workers. Methods: In this meta-analysis, we searched relevant published studies using major electronic databases including Scopus, PubMed, ISI Web of Science, and Google Scholar search engine up to October 2019, and the references of retrieved articles were also checked for further possible sources. A random-effects model was used to account for heterogeneity among the results of the studies using the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The Q-statistic and I² tests were calculated to assess heterogeneity between the studies. Results: The pooled calculation of OR indicated a significant association between occupational exposure to silica and risk of developing RA among different workers (OR = 2.59, 95% CI = 1.73 to 3.45). In addition, the pooled estimates of OR in smokers were statistically significant (OR = 2.49, 95% CI = 1.13 to 3.86). Conclusions: The findings of the present study reveal that occupational exposure to silica may be associated with increased risk of developing RA.

• Journal of Oral Medicine and Pain
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• 제41권4호
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• pp.169-179
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• 2016

Purpose: This study is designed to analyse etiology and bone pattern at the first visit using cone-beam computed tomography (CBCT) and to evaluate the treatment outcome of conservative treatment in temporomandibular disorder (TMD) patients with rheumatoid arthritis (RA). Methods: One hundred condyles in 50 subjects with RA were chosen among the patients who presented to the Department of Oral Medicine of Pusan National University Dental Hospital, diagnosed as TMD. Condylar bone changes were classified by normal, erosive bony change, proliferative bony change and combined group (erosive bony change+proliferative bony change). They were treated conservatively with physical therapy, medication, behavioral therapy and/or occlusal stabilizing splint therapy. After 3 months on average, patients were re-evaluated with regards to subjective symptoms and the clinical findings were investigated. Results: TMD patients with RA have behavioral contributing factors such as parafunctional habit. The results that analyse bone pattern at the first visit using CBCT proliferative bony changes group (32.6%) were more common than erosive bony changes group (15.2%). In comparison between unilateral and bilateral bony change in temporomandibular joint, the ratio showed no significant differences. After 3 months of conservative treatments, pain, noise, limitation of motion (LOM) were markedly improved regardless of occlusal splint therapy. However only LOM was significantly improved through occlusal splint therapy during 3 months. Conclusions: TMD patients with RA had similar behavioral contributing factors and characteristics of CBCT images shown in general TMD patients and also similar response to conservative treatment so it is difficult to differentiate. Therefore when TMD patients show symptoms corresponding to clinical diagnostic criteria of RA at the first visit, serological testing should be conducted and through this, early diagnosis and treatment of RA should be initiated.

• 동의생리병리학회지
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• 제25권6호
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• pp.1000-1007
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• 2011

This study was conducted to determine the analgesic effect of onion and acanthopanax senticosus mixture extract using the rheumatoid arthritis rat model. Rheumatoid arthritis model was made by the intradermal injection of type II collagen emulsified. Rats were divided into four groups: (1) Sham group(n=5), (2) Control group(administered DW 3 $m{\ell}$/1 day after RA induced, n=7), (3) Experimental group I(administered Onion extractor 600 mg/3 $m{\ell}$/1 day after RA induced, n=7). (4) Experimental group III(administered Onion and Acanthopanax senticosus mixture extractor 600 mg/3 $m{\ell}$/1 day after RA induced, n=7). After that, we examined the arthritic index, paw edema, pain threshold at 1st, 14th, 28th days. And also we examined histopathologic study(safranin-O green), immunohistochamical stain(COX-2) of knee joint at 28th days. Arthritic index, paw edema and pain threshold test were decrease in experimental group I, II than control group. Especially group II was most significantly inhibit effect than the other groups at 28th days. On the histopathologic view, all experimental groups were relieved and reproduced the erosion of arthritic site compared with control group. All experimental groups were COX-2 positive cells in the immunohistological stain of the knee joint were significantly decreased compared with control group. Especially group II was most significantly decreased than the other groups at 28th days. Onion and Acanthopanax senticosus mixture extractor can be used for curing rheumatoid arthritis. Anti-inflammatory effects may be somewhat better in combination of Onion and Acanthopanax senticosus.

• The Journal of Korean Physical Therapy
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• 제21권2호
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• pp.103-108
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• 2009

Purpose: Electrical stimulation is one of several treatments recommended for RA patients. Electrical stimulation of RA patients, reduces pain, or facilitates joint motion prior to exercises. However, there is still limited evidence on the efficacy of electrical stimulation and thus any conclusions drawn about this method remain controversial. Recently, Microcurrent Electrical Neuromuscular Stimulation (MENS) has received significant attention as a potential method of electrical stimulation. In this study, we investigated the effect of microcurrent treatment in rheumatoid arthritis rat. Methods: Subjects were allocated either to the control group or experimental group, which was subject to microcurrent stimulation. Interleukin-1 expression in the metatarsophlangeal joint and the oedema index in the ankle were used for classification and subsequent evaluation of pathology. Subjects were assessed at 1, 7 and 14 days after inducing rheumatoid arthritis through adjuvant injection. Thirty-six subjects, 18 in each group, were used in this study. Statistical analysis was performed by calculating the differences between the two groups and between each interval assessment. Categorical variables were compared between the two groups with the paired-T test. The one-way ANOVA test was performed to assess changes in ordinal variables. Results: Baseline characteristics were similar in both groups. Statistically significant differences were found between the two groups. The biological marker of pro-inflammatory cytokine and oedema index were decreased in response to this treatment. Conclusion: These data show that treatment of rheumatoid arthritis with a microcurrent stimulation device reduced the oedema index and pro-inflammatory cytokine IL-1.

• 근관절건강학회지
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• 제7권1호
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• pp.89-101
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• 2000

This study was carried out to compare the bone mineral density and risk factors of osteoporosis between normal and rheumatoid arthritis in postmenopausal women. Sixty-eight postmenopausal patients with rheumatoid arthritis(RA) were compared with 124 postmenopausal normal women. Data were collected from october, 1998 to April, 1999 at Dong-a university hospital in Pusan. From all subjects, individual characteristics such as age, body weight, height, age of menarche, duration of menopause, gravity, parity, and breast feeding period and factors of life style such as milk consumption, exercise, alcohol intake, cigarette smoking, coffee consumption were identified as influencing factors of osteoporosis by questionnaire. From RA patients, health assessment score, Ritchie articular index, erythrocyte sedimentation rate, C-reactive protein and steroid dosage were measured by rheumatologist on measuring bone mineral density. Bone mineral density was measured at the Lumbar spine, femoral neck, femur Ward's triangle, and femur trochanter using dual x-ray absorptiometry. The data was analyzed by using a frequency, t-test, Chi-square, ANCOVA with SPSS PC program. The results could be summarized as follows : 1) There was a significant difference in age and breast feeding period between RA patients and normal women. 2) RA patients took less calcium in the past and practiced less regular exercise in past and present than normal women. 3) There was no difference in lumbar bone mineral density between RA patients and normal women. 4) There was a significant difference in femur Ward's triangle and femur trochanter between RA patients and normal women after adjustment for age and breast feeding period. 5) The prevalence of osteoporosis of all subjects was the highest in femur Ward's triangle. In summary, our findings suggest that the bone mineral densities of femur Ward's triangle and trochanter in postmenopausal women with RA is significantly lower than normal women. Also the exercise participation rate of postmenopausal women with RA is lower than normal women. For the further study, we recommend to develop exercise program that improve the bone mineral density in femur Ward's triangle and trochanter and to test the effect of that exercise program.

• 근관절건강학회지
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• 제8권2호
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• pp.250-261
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• 2001

Alternative therapy for rheumatoid arthritis has become worldwide phenomenon this decade without scientific validation. This study was undertaken to explore the prevalence, patterns of use, and perceived efficacy of alternative therapies by patients attending a rheumatology clinic. We conducted a crossectional survey of 142 RA patients with structured questionnaire at outpatient rheumatic clinic from July to August in 2001. Results of this study were summarized as follows : 1. 85.9% of subjects were woman. Mean age was 49.97years, duration of rheumatoid arthritis was 5.6years. Mean pain score was 5.29cm. 2. 74.6% of subjects perceived rheumatoid arthritis as a controllable disease. 31% of patients combined medical treatments with alternative therapies. 58.5% of patients perceived that combining medical treatments with alternative therapies is the most effective strategy in controlling disease. 3. 77.5% had used more than one alternative therapy since the diagnosis was made. The major reason of discontinuation of use was no effect for the treatment of their disease. 4. 34.5% were currently using an alternative therapies and 50.9% were going to use alternative therapies in future. 5. 42.7% reported that alternative therapies was effective and only 3.6% reported side effects. 6. The perceived effect score was 3.14cm in general expecially the physiological score 2.91cm, psychological score 4.16cm. In conclusion, our results demonstrate a high use of alternative therapies by rheumatoid arthritis patients. And the perceived effect score of physiological aspect was not higher than one of psychological aspect. Therefore it should be considered in education program for the use of alternative therapies.

• IMMUNE NETWORK
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• 제3권2호
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• pp.89-95
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• 2003

Background: Unusually high amounts of N region addition and CDR3 length diversity were found in immunoglobulin (Ig) light chain Vk and Jk joins in patients with rheumatoid arthritis (RA). We sought to determine whether this finding is due to excessive activity of the enzyme responsible for N region addition (terminal deoxynucleotidyl transferase [TdT]) in B lineage cells in bone marrow or from positive antigenic selection of B cells with long CDR3 lengths. Methods: We used FACS to isolate $IgM^+/IgD^+$ B cells (predominantly naive) and $IgM^-/IgD^-$ B cells (predominantly class-switched) B cells from peripheral blood of a patient with RA known to have enrichment for long Vk CDR3s and from that of two normal controls. RT-PCR of VkIII transcripts was performed, followed by sequencing of individual cDNA clones. We analyzed the CDR3 lengths and N region additions in 97 clones. Results: There was enrichment for long CDR3 lengths (11 or 12 amino acids) in both $IgM^+/IgD^+$ and $IgM^-/IgD^-$ B cells in RA compared to B cell subsets in the normal controls. The $IgM^+/IgD^+$ B cell subset in RA was markedly enriched for N region addition and was similar to that seen in the $IgM^-/IgD^-$ subset. Conclusion: These data suggest that enrichment for N region addition and long CDR3 lengths in RA may result from unusually high or prolonged activity of TdT in bone marrow.

• IMMUNE NETWORK
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• 제13권6호
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• pp.240-248
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• 2013

In this study, we compared the immune cell populations in rheumatoid arthritis (RA) synovial fluid, which shows lymphoid tissue-like structure, with those in tonsils, which are normal secondary lymphoid tissues. Firstly, we found that $CD4^-CD11b^+$ macrophages were the major population in RA synovial fluid and that B cells were the major population in tonsils. In addition, synovial fluid from patients with osteoarthritis, which is a degenerative joint disease, contained $CD4^+CD11b^+$monocytes as the major immune cell population. Secondly, we categorized three groups based on the proportion of macrophages found in RA synovial fluid: (1) the macrophage-high group, which contained more than 80% macrophages; (2) the macrophage-intermediate group, which contained between 40% and 80% macrophages; and (3) the macrophage-low group, which contained less than 40% macrophages. In the macrophage-low group, more lymphoid tissue inducer (LTi)-like cells were detected, and the expression of OX40L and TRANCE in these cells was higher than that in the other groups. In addition, in this group, the suppressive function of regulatory T cells was downregulated. Finally, CXCL13 expression was higher in RA synovial fluid than in tonsils, but CCL21 expression was comparable in synovial fluid from all groups and in tonsils. These data demonstrate that increased lymphocyte infiltration in RA synovial fluid is correlated with an increase in LTi-like cells and the elevation of the chemokine expression.