• 대한수의학회지
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• 제46권4호
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• pp.395-398
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• 2006

A 2-month-old female Shih-tzu dog was referred because of lameness, exercise intolerance, depression, elbow and stifle joint swelling. Physical examination, complete blood counts, serum-chemistry, radiography, synovial fluid analysis, antinuclear antibody test, and rheumatoid factor measurement were initiated. On radiography, soft tissue swelling of elbow and stifle joints without erosiveness were founded. The results of synovial fluid analysis revealed severe neutrophilic pleocytosis (nondegenerative), decreased viscosity, increased turbidity, positive on mucin-clot test, and negative on bacterial culture. The results of rheumatoid factor measurement and antinuclear antibody test were negative and below 1 : 40, respectively. Based on all tests, we diagnosed this case as juvenile onset type I immune-mediated polyarthritis. Azathioprine (1 mg/kg body weight, per os q 24 h, for 4 weeks) was then administered and clinical signs improved gradually. Four weeks after azathioprine administration, clinical signs were disappeared. This report describes the clinical findings, imaging characteristics, synovial fluid findings, and other laboratory results of type I immune-mediated polyarthritis and successful management with azathioprine therapy.

• International Journal of Oral Biology
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• 제45권1호
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• pp.15-24
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• 2020

The fruit of Chaenomeles sinensis (Thouin) Koehne (Chaenomelis Fructus) known as "Mo-Gua" in Korea has been commonly used in traditional medicine to treat inflammatory diseases, such as sore throat. However, its effect on bone metabolism has not been elucidated yet. Here, we examined the effect of Chaenomelis Fructus ethanol extract (CF-E) on receptor activator of nuclear factor (NF)-κB ligand (RANKL)-mediated osteoclast differentiation and formation. CF-E considerably inhibited osteoclast differentiation and tartrate-resistant acid phosphatase-positive multinuclear cell formation from bone marrow-derived macrophages and osteoclast precursor cells in a dose-dependent manner. In addition, the formation of actin rings and resorption pits were significantly suppressed in CF-E-treated osteoclasts as compared with the findings in non-treated control cells. Consistent with these phenotypic inhibitory results, the expressions of osteoclast differentiation marker genes (Acp5, Atp6v0d2, Oscar, CtsK, and Tm7sf4) and Nfatc1, a pivotal transcription factor for osteoclastogenesis, were markedly decreased by CF-E treatment. The inhibitory effect of CF-E on RANKL-induced osteoclastogenesis was associated with the suppression of NFATc1 expression, not by regulation of mitogen-activated protein kinases and NF-κB activation but by the inactivation of phospholipase C gamma 1 and 2. These results indicate that CF-E has an inhibitory effect on osteoclast differentiation and formation, and they suggest the possibility of CF-E as a traditional therapeutic agent against bone-resorptive diseases, such as osteoporosis, rheumatoid arthritis, and periodontitis.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.405-413
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• 2020

Fibroblast-like synoviocytes (FLS) play a crucial role in initiating rheumatoid arthritis. B-cell activating factor (BAFF) plays a role in FLS survival as well as in B cell maturation and maintenance. Here, we investigated whether tumor necrosis factor (TNF)-α-induced BAFF expression controls FLS migration and whether BAFF expression in FLS could be regulated by KR33426 which is the inhibitor of BAFF binding to BAFF receptors (BAFF-R) by using MH7A synovial cells transfected with the SV40 T antigen. More TNF-α-treated cells migrated compared to the control. TNF-α increased BAFF expression in FLS, significantly. FLS migration was inhibited by the transfection with BAFF-siRNA. KR33426 also inhibited BAFF expression increased by TNF-α treatment in FLS as judged by western blotting, PCR, and transcriptional activity assay. Kinases including JNK, p38 and Erk were activated by TNF-α treatment. While JNK and p38 were inhibited by KR33426 treatment, no changes in Erk were observed. Transcription factors including p65, c-Fos, CREB and SP1 were enhanced by TNF-α treatment. Among them, c-Fos was inhibited by KR33426 treatment. Small interference(si)-RNA of c-fos decreased BAFF transcriptional activity. FLS migration induced by TNF-α was inhibited by the transfection with BAFF-siRNA. KR33426 increased Twist, Snail, Cadherin-11 and N-Cadherin. In contrast, KR33426 decreased E-cadherin and TNF-α-enhanced CCL2. Taken together, our results demonstrate that synovial cell migration via CCL2 expression could be regulated by BAFF expression which is decreased by KR33426 and c-Fos-siRNA. It suggests for the first time that the role of BAFF-siRNA on FLS migration might be matched in the effect of KR33426 on BAFF expression.

• Clinical and Experimental Pediatrics
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• 제49권4호
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• pp.424-430
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• 2006

목 적 : JRA는 소아에서 가장 흔한 결체 조직 질환 중의 하나이고 장, 단기적인 신체장애를 유발하는 중요한 원인이 된다. 저자들은 JRA 환아들의 질병 양상과 경과를 알아보기 위하여 본 연구를 시행하였다. 방 법 : 1990년 8월부터 2004년 11월까지 서울아산병원 소아과를 내원한 59명의 JRA 환아를 대상으로 하였다. 성별, 연령, 유형, 침범 관절, 관절 외 소견, 검사 및 방사선 소견, 치료, 경과 등에 대하여 후향적으로 고찰하였다. 결 과 : 소수 관절형은 32.2%, 다수 관절형은 30.5%, 전신형은 37.3%였다. 남녀비는 1.7 : 1이었으며 평균 발병 연령은 $9.3{\pm}3.7$(1.3-15.9)세이었다. 가장 흔히 침범된 관절은 무릎과 발목, 팔목이었다. 관절 외 소견을 살펴보면 발열, 발진, 근육통, 림프절 비대 등이 있었다. 검사 소견을 살펴보면 백혈구증가증, 빈혈, 혈소판증가증, ESR 상승, CRP 상승 등의 소견을 보였다. 류마토이드 인자, 항핵항체 양성률은 각각 5.3%, 18.0%이었다. 비스테로이드성 소염제(NSAID)가 가장 많이 투여되었으며, 메토트렉세이트 또는 스테로이드를 함께 투여했던 경우가 27.1%였다. 88.1%의 환아에서 장애 후유증 없이 완치되었으며 한 명의 환아에서만 기능성 상태 IV의 장애가 있었다. 폐침범이 동반되었던 한 명의 환아가 사망하였다. 결 론 : 본 연구에서는 균등한 유형별 분포, 남아에서 호발하는 양상, 늦은 발병 연령, 낮은 홍채모양체염 발병률, 그리고 낮은 ANA 양성률을 보였는데 이러한 소견들은 한국에서의 JRA의 소견이며 서양에서의 보고와는 상이한 결과들이다. JRA가 민족과 지역에 따라서 서로 다른 발병양상을 보인다는 점을 시사한다고 생각된다. 앞으로 더 많은 수의 환자들을 대상으로 하는 다기관 협동 연구 및 역학조사가 필요할 것으로 생각된다.

• Journal of Korean Medical Science
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• 제33권52호
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• pp.346.1-346.11
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• 2018

Background: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. Methods: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) ($2.6{\leq}DAS28$ < 3.2). Results: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (-0.38 vs. -0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). Conclusion: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.

• Journal of Microbiology and Biotechnology
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• 제9권1호
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• pp.106-112
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• 1999

The therapeutic potential of phosphodiesterase 4(PDE4) inhibitors in inflammatory diseases including some autoimmune diseases has been explored recently with some hopeful results. These PDE4 inhibitors are thought to show their anti-inflammatory effect by down-regulating tumor necrosis factor-a (TNF-$\alpha$) production in lymphocytes and macrophages. A high concentration of TNF-$\alpha$has been found in rheumatoid arthritis (RA) synovium and reducing TNF-$\alpha$using biological agents was proven to be an effective RA treatment. To test the possibility of using PDE4 inhibitors for RA treatment, the effects of a newly synthesized PDE4 inhibitor, DWP205505, on TNF-$\alpha$ and IL-10 production was tested in cells isolated from normal peripheral blood and rheumatoid arthritis synovial fluid. Cytokine production was assayed at the protein level by sandwich enzyme-linked immunosorbent assay (ELISA) and at the mRNA expression level by semi-quantitative RT-PCR. Another PDE4 inhibitor, RP73401, was used for comparison. DWP205505 and RP73401 had no harmful effect on cell viability up to 10 $\mu$M concentration during the 24 h culture period. DWP205505 as well as RP73401 significantly reduced TNF-$\alpha$ secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (pBMC) and synovial fluid mononuclear cells (SFMC). The effect of DWP205505 or RP73401 treatment on the mRNA expression of TNF-$\alpha$ was also studied in LPS-stimulated PBMC and SFMC. TNF-$\alpha$ mRNA expression was increased by LPS stimulation and both of the PDE4 inhibitors suppressed TNF-$\alpha$ mRNA expression. For interleukin-l0 (IL-l0), a little different results were obtained from PBMC and SFMC; IL-l0 secretion was unaffected by LPS stimulation and only minimally affected by both of the PDE4 inhibitors in PBMC. In unstimulated SFMC, DWP205505 and RP73401 slightly enhanced IL-10 secretion, while they reduced IL-l0 secretion from LPS-stimulated SFMC where IL-l0 secretion was a lot higher than unstimulated SFMC. These results suggest that the newly synthesized PDE4 inhibitor DWP205505 may have anti-rheumatoid arthritis activity.

• Journal of Acupuncture Research
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• 제24권6호
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• pp.1-14
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• 2007

Backgrounds : Rheumatoid Arthritis(RA) is known as the chronic inflammatory diseasethat induces persistent inflammation in the joint cavity. The destruction of cartilage occurs as the result of bones destoyed by pannus, several influential cytokines induced by the synovial capsulitis, varieties of proteinases, $O_2$ radicals, and the secondary degenerative changes of articular cartilage. The type 2 collagen-induced arthritis model is used in recent experimental research on rheumatoid arthritis. Cervus elaphus sibiricus (Nockyong) has the effect of relieving pain by nourishing the muscles, joints, and bones. It is also known to be efficacious in promoting and enhancing the immune system. The objective of this study was to investigate the effect of Cervus elaphus sibiricus herbal acupuncture to inhibit the generation of proinflammatory enzyme on type 2 collagen-induced arthritis. I investigated the inhibition of mRNA transcription of MIF(macrophage migration inhibitory factor), $TNF-{\alpha}$(Tumor necrosis $factor-{\alpha}$) and MMP-9 (matrix metalloproteinase-9) of Cervus elaphus sibiricus herbal acupuncture using an in vitro test. Also investigated was the inhibition of differentiation of Th 1 cells and activation of cytokines(MIF, $TNF-{\alpha}$, IL-6, MMP-9), which are known to cause initial RA ,and are also related to the morphology of the synovial membranes of the joint capsule, by an in vivo test, using CIA(collagen induced arthritis) model mice. Materials & methods : The laboratory animals used in this experiment were 4 week-old DBA female mice, weighing approximately 20 grams, and adjusted to the laboratory environment. The experiment was divided into the normal group(NOR)-no treated group, control group(CON)-CIA induced group, and sample group(SAM)-Cervus elaphus sibiricus herbal acupuncture treated group. RA was induced in the mice via injection of $50{\mu}{\ell}$ C II mixed CFA. The Cervus elaphus sibiricus herbal acupuncture solution was applied on $GB_{35}$(陽陵泉) for 26 days from the 3rd day of RA inducement. The concentration of the solution was determined via a MTT assay. To research the effect on the expression of MIF, $TNF-{\alpha}$ and MMP-9 mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. C II induced RA knee joint's histo-chemical synovial membrane was observed using a specimen model via the Hematoxilin and Eosin dying technique. Results : The expression of mRNA of RA-related cytokines such as MIF, $TNF-{\alpha}$, and MMP-9 dosedependently decreased in the cell from the synovial membranes of the joint, which is treated with Cervus elaphus sibiricus herbal acupuncture solution. In mice treated with Cervus elaphus sibiricusherbal acupuncture, the damage of synovial membranes of the joint was lessened, and differentiation of Th 1 cells was suppressed. The activation of RA-related cytokines such as MIF was suppressed, and the generation of $TNF-{\alpha}$ and MMP-9 showed a statistically significant decreas. Conclusions : It is speculated that Cervus elaphus sibiricus herbal acupuncture has the therapeutic effect of palliating the damage of the tissue impaired by RA by inhibition of the initial RA progression and by regulating excessive differentiation of Th 1 cell as it suppresses the generation of RA-related cytokines during the highest stage of RA by acting on pro-inflammatory enzymes.

• 한국약용작물학회지
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• 제15권4호
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• pp.271-275
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• 2007

Naturally occurring substances are important biomedical resources with low toxicity and ethnopharmacology-based efficacy. Four out of 45 extracts (Celastrus orbiculatus, Cercis chinensis, Stephanadra incisa, and Weigela subsessilis) prepared from the bark of Korea Forest plants exhibited more than 50% of inhibition on $TNF-{\alpha}$ production in lipopolysaccharide (LPS)-activated RAW264.7 cells at $100\;{\mu}g/m{\ell}$. In particular, potential inhibitory components of 4 extracts showed more than 50% inhibition seemed to be concentrated in methylene chloride (MC) fraction from C. orbiculatus, in ethyl acetate (EtOAc) fraction from C. chinensis and in hexane (Hx) fraction from S. incisa, whereas inhibitory activities of W. subssilis were broadly seen in non-polar solvent fractions such as Hx, MC and EtOAc. Therefore, our results suggest that extracts from C. orbiculatus, C. chinensis, S. incisa and W. subsessilis may be developed as a therapeutic remedy against $TNF-{\alpha}-mediated$ diseases such as rheumatoid arthritis or further fractionated to isolate active components having $antiTNF-{\alpha}$ inhibitory activity.

• Journal of Chest Surgery
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• 제25권4호
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• pp.412-417
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• 1992

Pulmonary artery aneurysm is Behcet`s disease is rare and can be fatal due to rupture. We experienced a case of pulmonary artery aneurysm in Behcet`s disease. The patient was 21 year old woman who was adimitted with three month history of dyspnea, fever and cough. On examination, she had aphthous ulcer in the mouth and erythema nodosum on the left popletial fossa and forearm, but didn`t have any lesion at eyes and genitalia. The latex fixation test for rheumatoid factor, VDRL test for syphillis, antinuclear antibody and LE cell test were all negatives. The third and fourth components of complement in the serum, serum immunoglobulin concentrations[IgG, IgM, IgA] were within normal range. The chest radiography revealed a 5x6cm sized radiopaque mass density in the left hilar region. Two months later, the mass was enlarged to 6x7cm. The IV-DSA showed a single aneurysm at the proximal part of left lower lobe artery with lingular segment artery and no distal perfusion by thombotic obstruction. The steroid therapy was done for a month, but symptoms not improved. We performed resection of lingular segment and lower lobe including the aneurysm. The microscopic findings of the operative specimen were intimal hyperplasia and fragmentation of the internal elastic fibers. She was improved without remarkable event, except infection of the operative wound.

• Journal of Acupuncture Research
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• 제19권5호
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• pp.176-188
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• 2002

Objective : Sono-acupoint (SA) therapy is a new therapeutic technique that combined with acupuncture points, herbal medicine and ultrasound therapy. This study was carried out to investigate the analgesic and anti-inflammatory effects of sono-acupoint therapy. Methods : We performed the tail-flick test with normal rats to examine the tail-flick latency (TFL), and the Freund's adjuvant-induced arthritis rat model to examine the edema, skin temperature and serum concentration of c-reactive protein and rheumatoid factor (RF). Herbal SA (HSA) treatment was performed at bilateral Zusanli (ST36) with the hanbang-gel made of several selected herbal drugs in Sprague-Dawley rats (male, $250{\pm}30g$). General SA (GSA) treatment was performed at bilateral Zusanli (ST36) with the gel used in ultrasound therapy. In arthritis rat model, Freund's adjuvant (50mg/ml) was injected in dorsal part of right foot, and these treatments were performed after 15 days. Results : TFL was lengthened after SA treatments. Skin temperature and RF concentration that were the evidence of arthritis in rats were decreased by HSA treatment (P < 0.05). Conclusion : These results indicate that HSA has the analgesic and anti-inflammatory effects in rats, and further developments will produce the advance of this new therapeutic skill.