• The Korean journal of internal medicine
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• 제33권6호
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• pp.1224-1233
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• 2018

Background/Aims: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. Methods: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. Results: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ${\geq}1.2$ (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. Conclusions: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.

• Journal of Periodontal and Implant Science
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• 제48권6호
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• pp.347-359
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• 2018

Purpose: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. Methods: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. Results: The RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020). Conclusions: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.

• Journal of Acupuncture Research
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• 제19권1호
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• pp.135-146
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• 2002

Background and Purpose : This study shows the clinical effects on treatment with Rheumatoid arthritis using Aqua-acupuncture such as Ursi Fel Bovis Calculus and Cathami Flos that are known for which have anti-inflammatory and analgesic effects. Objective and Methods : This study has been carried out Aqua-acupuncture treatment such as Cathami Flos and Ursi Fel Bovis Calculus twice or three times a week with patients diagnosed as rheumatoid arthritis on 7 criteria of US Rheumatism Academy. Results : 1. If you see the sexual distribution, it shows the rates of male and female 1: 1.83. Age distribution shows as age ascend it shows high. 2. If you see the duration distribution, it shows chronic tendency in order of more than 6 months(63.3%), 2 to 5 months, and I month. 3. If you see the invaded distribution, it shows chronic tendency in order of hand(37 cases), wrist joint(34 cases), knee joint(32 cases), ankle joint(21 cases), elbow joint(16 cases), shoulder joint(14 cases), feet(14 cases), hip joint(9 cases), low back(6 cases), neck(4 cases). 4. Seeing the mean post-therapeutic index among groups on RA factor level distinction, it shows that 0-18(normal range) scored 89.0, 19-50 scored 94.8, 51-80 scored 101.2, 81-100 scored 97.3, 101-140 scored 102.4, above 141 scored 97.5. 5. Seeing the mean post-therapeutic index among groups on CRP level distinction, it shows that 0-0.4(normal range) scored 100, 0.5-1.0 scored 48.6, 1.1-2.0 scored 34.9, 2.1-3.0 scored 35.7, 3.1-4.0 scored 37.1, 4.1-5.0 scored 53.8, above 5.0 scored 70.4. 6. Seeing the mean post-therapeutic index among groups on ESR level distinction, it shows that 0-20(normal range) scored 48.6, 21-40 scored 57.5, 41-60 scored 59.2, 61-80 scored 59.2, above 81 scored 66.0. 7. If you see the satisfactory assesment after Aqua-acupuncture treatment such as Cathami Flos and Ursi Fel Bovis Calculus, Excellent is 11 cases, Good is 14 cases, and Moderate 5 cases. Conclusion : It will be better effects, if herbal medicine, moxibustion, and acupuncture are used together with Cathami Flos and Ursi Fel Bovis Calculus on rheumatoid arthritis as chronic inflammatory disease.

• BMB Reports
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• 제43권8호
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• pp.513-523
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• 2010

Cytokines that bind to and signal through the gp130 co-receptor subunit include interleukin (IL)-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and ciliary neutrophic factor (CNTF). Apart from contributing to inflammation, gp130 signalling cytokines also function in the maintenance of bone homeostasis. Expression of each of these cytokines and their ligand-specific receptors is observed in bone and joint cells, and bone-active hormones and inflammatory cytokines regulate their expression. gp130 signalling cytokines have been shown to regulate the differentiation and activity of osteoblasts, osteoclasts and chondrocytes. Furthermore, cytokine and receptor specific gene-knockout mouse models have identified distinct roles for each of these cytokines in regulating bone resorption, bone formation and bone growth. This review will discuss the current models of paracrine and endocrine actions of gp130-signalling cytokines in bone remodelling and growth, as well as their impact in pathologic bone remodelling evident in periodontal disease, rheumatoid arthritis, spondylarthropathies and osteoarthritis.

• Food Science and Biotechnology
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• 제18권4호
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• pp.923-927
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• 2009

This study is to investigate the anti-inflammatory effects of the ethylacetate extract of Rehmannia glutinosa (RGEAE). The anti-inflammatory activities using nitric oxide (NO), cytokine, and chemokine production in lipopolysaccharide (LPS)-induced RAW 264.7 cells were checked. Results indicated that RGEAE suppressed the NO, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner. Inhibition of NO formation was due to a decrease in inducible NOS (iNOS) expression. It was also found that the anti-inflammatory activities of RGEAE resulted from its inhibitory role on the nuclear factor $(NF)-{\kappa}B$ activation and reactive oxygen species (ROS) production. Therefore, it is suggested that RGEAE has potential as a therapeutic material to attenuate the inflammatory disease such as rheumatoid arthritis.

• BMB Reports
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• 제41권4호
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• pp.278-286
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• 2008

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been approved for use to treat patients with colorectal, lung, renal and liver cancers. These drugs have opened a novel field of cancer therapy, i.e. anti-angiogenesis therapy. However, as yet they cannot completely cure patients, and cancer cells could become resistant to these drugs. Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy.

• IMMUNE NETWORK
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• 제14권3호
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• pp.123-127
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• 2014

Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-${\alpha}(TNF{\alpha})$ and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.173.1-173.1
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• 2003

One of attractive target for Rheumatoid Arthritis (RA) therapy is the cytokine, tumor necrosis factor-alpha (TNF-$\alpha$), which has been shown to be overproduced in the joint of RA patients. The clinical success of anti- TNFR biologics has validated TNF-$\alpha$ as a drug discovery target. Thus, inhibiting of formation of TNF-$\alpha$ has been emerged to an intriguing approach for RA therapy. TNF-$\alpha$ is processed from its membrane bound precursor by the metalloprotease TNF-$\alpha$ converting enzyme (TACE), Here, biological evaluation, mode of action of natural TACE inhibitor, Gelastatin hydroxamate, are addressed. (omitted)

• 대한통합의학회지
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• 제11권2호
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• pp.119-128
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• 2023

Purpose : The fruit of Actinidia polygama has been used in oriental medicine for the treatment of gout, rheumatoid arthritis, and inflammation. Though A. polygama exhibited anti-inflammatory activity in RAW 264.7 cells and carrageenan-induced rat paw edema, the exact mechanism for anti-inflammation was not evaluated yet. In this study, the anti-inflammatory mechanisms of A. polygama ethanol extract (APEE) in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Methods : WST-1 assay was applied to analyze the cytotoxic effect of APEE in RAW 264.7 cells. The productions of nitric oxide (NO) and prostaglandin (PG) E₂ were analyzed by the Griess reaction and enzyme immunoassay (EIA) assay, respectively. In addition, protein expressions for inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured by Western blot analysis. The activated status of an inflammatory transcription factor, NF-κ B, and its upstream signaling molecules, mitogen-activated protein kinases (MAPKs), was also evaluated by Western blot analysis. Results : As a result, APEE treatment did not exhibit any cytotoxicity until the concentration of 200 ㎍/㎖. APEE treatment significantly inhibited NO and PGE₂ productions as well as their enzymes, iNOS and COX-2 in a dose-dependent manner. The inflammatory transcription factor, NF-κ B, was also attenuated by APEE treatment. In addition, the phosphorylated status of MAPKs such as extracellular regulated kinase (ERK), c-jun NH2 kinase (JNK), and p38, were significantly diminished by APEE treatment in LPS stimulated RAW 264.7 cells. Conclusion : Consequently, APEE treatment significantly attenuated the production of inflammatory mediators and their enzyme expressions in LPS-stimulated RAW 264.7 cells. The inflammatory transcription factor, NF-κ B, and upstream signaling molecules, MAPKs, were also significantly attenuated by APEE treatment in LPS-activated RAW 264.7 cells. These results indicate that APEE might be a candidate to be utilized as a promising candidate for the treatment of inflammatory disorders.

• Tuberculosis and Respiratory Diseases
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• 제42권6호
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• pp.878-887
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• 1995

연구배경: 류마티스 관절염 환자에서 폐침범의 빈도는 10~50%로 보고되어 있고 사망의 주요원인으로 알려져 있다. 따라서 최근에 면역학 및 방사선학의 발달과 더불어 폐침범의 조기진단에 대한 관심이 증가되고 있다. 방법: 1990년 3월부터 1995년 7월까지 본원에 입원한 환자중 임상소견과 흉부 고해상도 컴퓨터 단층 촬영상 폐침범 소견을 보였던 29명의 환자와 임상적 소견 및 검사소견상 폐침범이 없었던 연령 범위가 같은 18명의 환자에서 면역학적 지표와 폐기능 검사소견을 비교하여 비침습적 검사를 이용한 폐침범의 조기 진단에 유용한 지료플 찾고자 하였다. 결과: 1) 남녀의 비는 폐침범군의 경우 1 : 1.07이었고 대조군의 경우 18명 모두 여자이었으며 그중 흡연력은 폐침범군에서 31%(9/29)였으며 대조군은 없었다. 2) 류마티스 인자는 폐침범군의 경우 96.5%(28/29)에서 양성이였으며 대조군의 경우 100%(18/18)에서 양성이었다(p=0.12). 3) 항핵주변인자는 폐침범군의 경우 86.9%(20/23, 평균치: 2.0)에서 양성이었고 대조군의 경우 50%(8/16, 평균치: 1.1)에서 양성으로 유의한 차이가 있었다.(p=0.04). 4) 항핵항체는 폐침범군의 경우 60.7%(17/28)에서 양성이었고 대조군의 경우 72.2%(13/18)에서 양성이었다.(p=0.33). 5) Cryoglobulin은 폐침범군의 경우 72%(18/25)에서 양성이었고 대조군의 경우 56.2%(9/16)에서 양성으로 유의한 차이가 있었다(p=0.02). 6) 골 미란은 폐침범군의 경우 61.5%(16/26)에서 양성이었으며 대조군의 경우 77.7%(14/18)에서 양성이었다(p=0.8). 7) 폐기능 검사상 폐포량으로 교정된 폐확산능치와 페잔기량은 폐침범군의 경우평균값이 각각 1.07mmol/min/KPa(predicted value: 64.2%)와 1.32L(70%)이었고 대조군은 1.44mmol/min/KPa(78.1%)와 3.75L(86.6%)으로 유의한 차이가 있었다(p=0.003, p=0.004). 총폐용적과 최대자발성호흡량은 폐침범군의 평균값이 각각 3.98L(102.9%)와 70.63L/min(101.6%)이었고 대조군은 4.0L(87.4%)와 74.59L/min(100.9%)이었디(p=0.51, p=0.42). 결론: 결론적으로 류마티스 관절염 환자에서 폐침범을 진단하는데 있어서 혈청학적 검사중 항핵주변인자와 cryoglobulin, 폐기능 검사상 폐잔기량과 폐확산능의 측정은 유효한 지표로 사용될 수 있겠다.