• Journal of Preventive Medicine and Public Health
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• v.32 no.3
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• pp.343-346
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• 1999

Objectives : In Korea, pharmacists can dispense medicines without doctor's prescription. This causes the high proportion of pharmaceutical expenditures. The study shows the prescribing behaviors of practicing pharmacists with the simulated patient of arthritis. We select the arthritis as a subject of simulation, because the arthritis is one of the major health problems and the abuse of cortico-steroids is usual in treatment of arthritis patients. Methods : Twenty drug stores among the 320 drug stores in a district, Seoul, Korea were randomly selected. One of the researchers visited the drug stores and received the medicines from the pharmacists after explaining standardized scenario of arthritis. The simulated patient recorded the practice behaviors of pharmacists. Results: The mean number of prescribed drugs are four and half. Among the twenty pharmacists, the nineteen prescribed non-steroidal anti-inflammatory drugs and the seven(35%) prescribed the cortico-steroids. The antacids were prescribed by the fourteen(70%) pharmacists. The five(25%) pharmacists only recommended the simulated patients to visit the medical doctors, and the three(15%) performed physical examination to the simulated patients. The three pharmacists(15%) asked the past history of the drug adverse effects and no pharmacist explained the adverse effects of prescribed medicines. Conclusions : The research shows that the cortico-steroids are frequently prescribed and the pharmacists commonly do not give the explanations of the prescribed medicines to the arthritis patients.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.4
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• pp.33-49
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• 2010

Objectives : This study was designed to elucidate the anti-pathogenetic and curative effects of Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) on Type II collagen-induced arthritis(CIA) in mice. Methods : In experiment, twenty four mices were divided into non-treated normal group(n=6), bovine type II collagen-induced control group(n=6), collagen immunized and treated two group medicated with extract of GCP(concentration of extraction: 200 mg/kg n=6, 400 mg/kg n=6) for 4 weeks after collagen immunization, Various experimental such as arthritis, incidence, index, total cell number of spleen, total cell number of peripheral lymph node(PLN), paw joint total cell number, analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice, effects of inflammatory gene expression in spleen, PLN and paw joint of CIA mice, production of cytokine(IFN-${\gamma}$, IL-4, TNF-${\alpha}$, IL-6), analysis of rheumatoid factor(anti-collagen lgG, lgM level in serum) and histopathological study on the paw joint. The arthritis index, incidence were measured a week over 4 weeks after second boosting. Total cell number of spleen, peripheral lymph node, paw joint were measure after performed experiment over 7 weeks. Concentration of cytokine and rheumatoid factor in serum were measured after experiment finished. Histopathological study on the paw joint was measured after 40 days medicated with extract of GCP. Results : 1. Incidence of arthritis and index of arthritis were significantly decreased in treated group with 400 mg/kg. 2. Total cell number of spleen, PLN and paw joint were significantly decreased in treated group. 3. Analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice were significantly controled compare with control group. 4. Effects of inflammatory gene expression in spleen, PLN and paw joint of CIA induced mice were significantly controled compare with control group. 5. IFN-${\gamma}$, IL-6, TNF-${\alpha}$, concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. But IL-4 was significantly increased. 6. lgM and lgG concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. 7. Histopathologically, suppurative and destructive lesion of synovial membrane, articular cartilage and subchondral bony tissue in treated group were alleviated compare with those of control group. Conclusions : Based on the results described above, it might be consider that Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) has antiarthritic and analgesic effects and also inhibitory effects on the progression of collagen-induced arthritis mice.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.73-90
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• 2006

Objectives : The effects of water extract of deer antler herbal-acupunture solution(DHS), prepared from the pilose antler of Cervus korea TEMMINCK var. mantchuricus Swinhoe (Nokyong), a traditional immunosuppressive and immune-activating Korean herbal- acupuncture, on collagen-induced arthritis(CIA:RA model) in mice was studied. Destruction of cartilage and bone are hallmarks of human rheumatoid arthritis, and controlling these erosive processes is the most challenging objective in the treatment of RA. Methods : We investigated the tissue protective effects of deer antler treatment using established murine collagen-induced arthritis(CIA) as a model. Potential synergy of low dosages of anti-inflammatory glucocorticosteroids and deer antler was also evaluated. Results : Treatment of established murine CIA with deer antler herbal-acupunture solution(DHS) $(10-50{\mu}g/day)$ suppressed disease activity and protected against cartilage and bone destruction. Although $10-50{\mu}g/day$ DHS had only a moderate effect on the inflammatory component of the disease activity, it strongly reduced cartilage pathology, as determined by histological examination. Serum cartilage oligomeric matrix protein(COMP) levels were significantly reduced, confirming decreased cartilage involvement. Histological analysis showed that bone destruction was prevented. DHS administration increased serum IL-1Ra levels and reduced anticollagen type II antibody levels. Treatment with low-dose $DHS(1{\mu}g/day)$ was ineffective in suppressing disease score, serum COMP or joint destruction. Synergistic suppression of both arthritis oseverity and COMP levels was noted when low-dose DHS was combined with prednisolone(0.05mg/kg/day), however, which in itself was not effective. Conclusion : DHS was shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption. These results indicated that the DAS is not only highly stable and applicable to clinical uses in bone resorption, but also it will be served as a potent anti-inflammatory and anti-arthritic agents for treatment of human RA.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.97-114
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• 2011

Objectives : The object of this study is to observe the favorable anti arthritic effects of Sowhalrack-dan($Xi\check{a}ohu\acute{o}lu\grave{o}-d\bar{a}n$)(SWRD), which has been traditionally used in Korean medicine to treat rheumatoid arthritis on Freund's complete adjuvant(FCA) induced arthritic Wistar rats. Methods : Rheumatoid arthritis was induced by intradermal injection of FCA(10 mg in 1 ml paraffin oil 0.1 ml/rats). Each of 8 rats showing regular ankle circumferences per group were selected in 14 days after FCA treatment to confirm the induction of rheumatoid arthritis. 300, 150 or 75 mg/kg of SWRD was orally administered once a day for 14 days from 14 days after FCA treatments. Dexamethasone was intraperitoneally administered 15 mg/kg, once a day for 14 days from 14 days after FCA treatments. Rats were sacrificed after 14 days of continuous oral treatment of SWRD or intraperitoneal administration of dexamethasone, and changes were observed; the body weight, knee circumferences, gross arthritis score, inflammatory tissue $prostaglandin(PG)E_2$ levels and cartilage collagen, glucosaminoglycans compositions - chondroitin sulphate, heparin sulphate and hyaluronic acid in the present study. Results : As results of FCA treatment, classic rheumatoid arthritis featuring dramatical decreases on the body weights, cartilage collagen contents and bone glucosaminoglycans - chondroitin sulphate, heparin sulphate and hyaluronic acid contents. Also, it increases the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels. However, these changes from FCA induced rheumatoid arthritis were clearly reduced due to the dexamethasone and both two different dosages of SWRD, 300 and 150 mg/kg in the present study. Although FCA induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg compared to SWRD 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats. Conclusions : The results obtained in this study suggest that over 150 mg/kg of SWRD showed favorable anti-arthritic effects on the FCA induced arthritis mediated by suppression of $PGE_2$. However, detailed mechanism studies are needed with the screening of the biological active compounds in SWRD. Although FCA induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg compared to SWRD 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats, in the present study.

• Korean Journal of Medicinal Crop Science
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• v.28 no.6
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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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• v.13 no.6
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• pp.257-263
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• 2013

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

• Journal of Dental Rehabilitation and Applied Science
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• v.29 no.2
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• pp.203-207
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• 2013

Psoriatic arthritis is a chronic inflammatory form of arthritis that is associated with psoriasis. A 54-yr-old male with chronic psoriatic temporomandibular joint arthritis and myofascial pain was treated using methotrexate and a myofascial pain protocol. Jaw pain improved after 3 weeks, however, tenderness to palpation of muscles remained. Comprehensive evaluation and multidisciplinary clinical treatment is required for the treatment of patients with psoriatic temporomandibular joint arthritis.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.1-15
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• 2018

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin $(IL)-1{\beta}$ and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.165-176
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• 2003

The present study was carried out to examine the effects of Kami-hwal-hyeol-tang(KHHT) on the immune responses of synoviocyte cells prepared from the rheumatoid arthritis patients, and also on the collagen-mediated arthritis in mouse model. Several experiments were performed in vitro and in vivo to analyse the immunomodulatory effects of KHHT, and the major findings are summarized below: 1. KHHT did not show the cytotoxicity against mLFCs and hFLSs. 2. KHHT inhibited gene expression of IL-1β, IL-6, TNF-α, COX-2, NOS and GM-CSF in hFLSs. Furthermore, KHHT-treated hFLSs showed reduced production of pro-inflammatory cytokines such as IL-1β and IL-6 compared to the control cells. 3. KHHT treatment of hFLSs inhibited the binding activity of NF-kB and AP-1 to their consensus DNA sequences. 4. KHHT treatment(400 ㎍/㎖) of hFLSs significantly inhibited hFLSs proliferations compared to the control cells. 5. KHHT significantly reduced the production of ROS in hFLSs compared to the control cells. The present data show that KHHT plays an important role for the regulation of AP-1 and NF-kB gene expression. Also, it was found that KHHT has anti-arthritis effect. Further studies of KHHT in relation to RA therapeutics may provide important information to develop drugs to treat this disease.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.172-183
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• 2020

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.