• The Korean journal of internal medicine
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• v.33 no.6
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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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• v.48 no.6
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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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• v.19 no.1
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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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• v.43 no.8
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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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• v.18 no.4
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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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• v.41 no.4
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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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• v.14 no.3
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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.

• Proceedings of the PSK Conference
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• 2003.10b
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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)

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.2
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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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• v.42 no.6
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• pp.878-887
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• 1995

Background: It is reported that frequency of pulmonary involvement in the patients with rheumatoid arthritis reaches 10 to 50% and pulmonary involvement is a principal cause of death. As immunology and radiology has developed, interest for the early diagnosis of pulmonary involvement is increasing. Method: Among the patients at Hanyang University Hospital from March, 1990 to July, 1995, we compared the 29 patients having pulmonary involvement with the 18 patients controls in clinical and chest high resolution computed tomography(HRCT) findings by immunological markers and findings of pulmonary function test. We sought useful markers for early diagnosis of pulmonary involvement with noninvasive investigations. Results: The ratio of males to females was 14 : 15 in the group of pulmonary involvement, and all of the 18 patients were females in the control group. Smoking history was 31%(9/29) in the former group and none in the latter group. Rheumatoid factor(RF) was positive in 95.5%(28/29) of the pulmonary involvement group and in 100%(18/18) of the control group(p=0.12). Antiperinuclear factor(APF) showed a significant difference: 86.9%(20/23, average value: 2.0) was positive in the pulmonary involvement group and 50%(8/16, average value: 1.1) in the control group(p=0.04). Antinuclear antibody(ANA) was positive in 60.7%(17/28) of the pulmonary involvement group and in 72.2%(13/18) of the control group(p=0.33). Cryoglobulin also showed a significant difference: 72%(18/25) in the pulmonary involvement group was positive and 56.2%(9/16) in the control group was positive(p=0.02). Bony erosion was positive in 61.5%(16/26) of the pulmonary involvement group and in 77.7%(14/18) of the control group(p=0.8). On the pulmonary function test, the average value of alveolar volume corrected diffusion capacity and residual volume in the pulmonary involvement group and in the control group were 1.07mmol/rnin/KPa(predicted value: 64.2%), 1.32L(predicted value: 70%) and 1.44mmol/min/KPa, 3.75L(predicted value: 86.6%), respectively(p=0.003, p=0.004), showing a significant difference. Conclusion: APF or cryoglobulin on the serological test, the measurement of residual volume and alveolar volume corrected diffusion capacity may be used as effective markers in the diagnosis of pulmonary involvement of the patients with rheumatoid arthritis.