• 한방재활의학과학회지
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• 제19권2호
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• pp.125-156
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• 2009

Objectives : To research the trend of studies related to rheumatoid arthritis and to indicate the hereafter direction for its study in oriental medicine and its treatment. Methods : I reviewed 75 domestic oriental medical journals, and 50 medical journals about rheumatoid arthritis published after 2004, and comparative analysis was made. And these theses were classified by college, year, field of study, subject. Results : The following are the results of this study. 1. Classified by oriental medical college, Dae-jeon college published the most theses, followed by Dong-guk, Kyung-hee, Se-myung and Dong-shin college. Han-yang college published the most theses among college of medicine. 2. Classified by type of thesis, experimental theses(70 pieces, 94%) showed higher rate than that of clinical theses(4 pieces, 5%) in oriental medical studies. However, in medical studies, clinical theses(34 pieces, 68%) showed higher rate than that of experimental theses(15 pieces, 30%). 3. Analyzed by subject, the most dealt subject in oriental medicine was herb medication, followed by herbal acupuncture, single herb, electroacupuncture, sasang & gene, acupuncture & moxibustion, complex accordingly. The most dealt subject in medical clinical journals was standards of diagnosis & prognosis, followed by medication, gene analysis, pathogenesis, clinical pattern, operative treatment and complication accordingly. 4. In theses related to herb medication, most of the subject was to evaluate anti-inflammatory and immunoregulatory effects of herb medication with geopungseup, jibitong, hwalhyeolgeoer function. The tendency of experimental methods was focusing on understanding anti-inflammatory and immunoregulatory mechanisms through molecular biologic methods by analyzing cytokine and gene. 5. Most of theses related to herbal acupuncture were experimental studies verifying ant-inflammatory and immnoregulatory effects through methods observing change of cytokine and immunoregulatory factors. Regarding remedies for herbal acupuncture, Ulmus davidiana Planch was most preferred, followed by bee venom. 6. In theses related to single herb, Boik-yak was most prefered, followed by Geopungseup-yak and Hwalhyeolgeoer-yak. Regarding methods of research, there were tendency of shifting from methods verifying travail, anti-inflammatory and anti-pyretic effects through a test of behavior, morphometry, serology and temperature measurement of the rectum and the skin into verifying anti-inflammatory and immunoregulatory effects through observing inflammatory cytokine in the joint and cells of spleen. 7. In theses related to electroacupuncture, ST36 and adjuvant were most preferred as acupoints and induced factor. The tendency of experimental methods was turning from verifying mechanism of travail effect to analyzing inflammation and pain inducing factors. 8. Diverse medical clinical studies were published. Subjects such as diagnosis and prognosis, medication, gene analysis, clinical pattern, operational treatment, complication and pathogenesis were published. Especially, studies about standards of early diagnosis, and research on possible parallel medications with methotrexate were actively inquired. 9. Most of theses related to medical experimental studies was about mediators and receptors related to inflammatory induction and osteoclasia mechanism. Also, it was presented blockage of them can be effective on rheumatoid arthritis. Conclusions : The oriental medicine studies have merit in its diversity of treatment, but it clinical studies is lacking compared to experimental studies. Also, more diversity of subjects is necessary. Therefore, complementary measures are needed. Hereafter, oriental medicine research about rheumatoid arthritis needs more clinical research verifying the effectiveness and safety in clinical field. Also, we require oriental medical standard of diagnosis and researches on pathological generation which would make early checkup and prognosis possible.

• IMMUNE NETWORK
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• 제3권2호
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• pp.136-144
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• 2003

Oral administration of antigen has long been considered as a promising alternative for the treatment of chronic autoimmune diseases including rheumatoid arthritis (RA), and oral application of type II collagen (CII) has been proven to improve pathogenic symptoms in RA patients without problematic side effects. To further current understandings about the immune suppression mechanisms mediated by orally administered antigens, we examined the changes in IgG subtypes, T-cell proliferative response, and proportion of interleukin (IL)-10 producing Th subsets in a time course study of collagen induced arthritis (CIA) animal models. We found that joint inflammation in CIA mouse peaked at 5 weeks after first immunization with CII, which was significantly subdued in mice pre-treated by repeated oral administration of CII. Orally tolerized mice also showed increase in their serum level of IgG1, while the level of IgG2a was decreased. T-cell proliferation upon CII stimulation was also suppressed in lymph nodes of mice given oral administration of CII compared to non-tolerized controls. When cultured in vitro in the presence of CII, T-cells isolated from orally tolerized mice presented higher proportion of $CD4^+IL-10^+$ subsets compared to non-tolerized controls. Interestingly, such increase in IL-10 producing cells were obvious first in Peyer's patch, then by 5 weeks after immunization, in mesenteric lymph node and spleen instead. This result indicates that a particular subset of T-cells with immune suppressive functions might have migrated from the original contact site with CII to inflamed joints via peripheral blood after 5 weeks post immunization.

• Korean Journal of Acupuncture
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• 제24권4호
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• pp.111-129
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Coicis Semen Herbal-acupuncture solution (CS-HAS) at the Joksamni (ST36) on the collagen-induced arthritis in the DBA/1J mouse. The author performed several experiments to analyze the effects of CS-HAS on arthritis; change of the weight; the spleen size and adhesion rate; serum cytokine levels; serum antibody levels; changes of immunocyte counts; the histological changes of joint. Results : In the Coicis Semen Herbal-acupuncture (CS-HA), arthritis index, the incidence of arthritis, and the degree of joint edema were decreased. In CS-HA, there was no weight loss. The size of the spleen, adhesion rate, and the edema and transformation of joint were lowered. In CS-HA, the levels of IL-1${\beta}$, IL-6, TNF-${\alpha}$, IFN-${\gamma}$, IgG, IgM, and anti-collagen II in serum and the levels of IFN-${\gamma}$, IL-4, IL-10 in spleen were significantly decreased. In CS-HA, the expression ratios of $CD45^+$ to $CD3e^+$ and $CD8^+$ to $CD4^+$ were decreased. Also, the overall $CD4^+/CD8^+$ cell ratio was lowered in spleen. Ratios of the $CD4^+/CD25^+$, $CD45^+/CD69^+$ cells were decreased in lymph nodes. In addition, ratios of the $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$ cells were also decreased in synovium. In the histological study, the cartilage destruction and synovial cell proliferation, and collagen fiber destruction were decreased with CS-HA treated group. Conclusions : From the results mentioned above, it is suggested that CS-HA at the ST36 has several significant effects on the collagen-induced arthritis.

• Journal of Ginseng Research
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• 제33권2호
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• pp.149-154
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• 2009

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and progressive cartilage and bone erosion. Korean red ginseng (KRG) has been shown to have an anti-inflammatory effect by inhibiting the secretion of inflammatory cytokines like $TNF-{\alpha}$, IL-1, -6, and -8, and $IPN-{\gamma}$. In this study, whether KRG extract has an inhibitory effect on the collagen-inducible development of arthritis in DBA/1J mice was investigated. To induce arthritis, type II collagen emulsified in Complete Freund's Adjuvant was intradermally injected into the base of the tails of mice. Three weeks after the initial injection, a booster injection of type II collagen emulsified in Incomplete Freund's Adjuvant was administered. The oral administration of KRG extract for 8${\sim}$10 weeks at the dose of 300 mg/kg (three days a week) inhibited the development of arthritis in the experimental group, compared to the control group which was given saline. While the administration of KRG extract three times a week demonstrated both preventive and inhibitory effects, the administration of KRG extract once a week had little inhibitory effect. In other studies, the regimen of KRG administration has been shown to decrease the plasma level of inflammatory cytokines like IL-8 and TNF-${\alpha}$, but the plasma levels of these cytokines were not decreased in the present study. The results of the present study suggest that KRG has preventive and inhibitory effects on collagen-induced arthritis.

• 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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• 제18권1호
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• pp.100-112
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• 2001

Objective : The purpose of this study is to investigate the immunological effect of Ramulus Cinnamomum aqua-acupuncture on the cellular immune response in mice with LPS induced arthritis. Methods : All the BALB/C mice used in this study were bred and maintaned in our pathogen-free mouse colony and were 6wk of age at the start of the experiment. The experimental model of arthritis was induced by injeciton of 300${\mu}g$/kg LPS in mice knee joint. Ramulus Cinnamomum aqua-acupuncture was injected into Yangnungchon(Gb34) of mice 2daily for 14days. Immunohistochemical analysis was carried out to assess CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 expression in common iliac lymph nodes and synovial menbrane after stimulation with Ramulus Cinnamomum. Electron microscopy was carried out to assess change of synovial membrane. Ramulus Cinnamomum aqua-acupuncture stimulation group was compared to control group and non stimutated with aqua-acupuncture. Resutts : At day 14 post arthritis onset, Immunohistological studies using monoclonal antibodies showed that Ramulus Cinnamomum aqua-acupuncture goup had decreased expression of CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 at common illiac lymph nodes and synovial membrane compared with control group. Conclusions : Ramulus Cinnamomum aqua-acupuncture stimulation inhibited the development of cellular immunity to LPS-induced arthritis in mice. Thus, aqua-acupuncture stimulation may have preventive effects on autoimmune inflammatory joint diseases. The effects of AA on immune function and disease activity in patients with RA warrant further investigation.

• Journal of Acupuncture Research
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• 제27권5호
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• pp.25-34
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• 2010

Objectives : The purpose of this study is to investigate that effect of Angelica gigas NAKAI pharmacopuncture(AGN-Ph) by concentration at $ST_{36}$(足三里) and $BL_{23}$(腎兪) in Freund's adjuvant rats. Methods : The experimental model of arthritis was induced by injection of Freund's adjuvant into Sprague Dawley(SD) rats. After arthritis was induced, AGN-Ph was injected by concentration at $ST_{36}$ and $BL_{23}$ of rats every other day for 6 times. Thereafter, edema rate, body weight, IFN-${\gamma}$, TNF-${\alpha}$, hematologic assay were measured. Results : The results were as follows, 1. After 3 times AGN-Ph treatment, the mean of edema rate was significantly decreased in AGN-Ph group 3 than control group. And after 6 times AGN-Ph treatment, the mean of edema rate was significantly decreased in AGN-Ph group 1, 2, 3 than control group. 2. The mean of body weight was significantly increased in AGN-Ph group 1, 3 than control group and saline group. 3. The mean of IFN-${\gamma}$ was significantly increased in AGN-Ph group 3 than control group. 4. The mean of TNF-${\alpha}$ was significantly increased in saline group than control group. But the mean of TNF-${\alpha}$ in AGN-Ph group 2, 3 showed no significance compared with control group's. 5. In hematologic assay, levels of WBC, RBC, Hemoglobin, Hematocrit showed no significance in all groups. Conclusions : These results are suggest that the Angelica gigas NAKAI pharmacopuncture(AGN-Ph) at $ST_{36}$ and $BL_{23}$ has a suppressing inflammation effect on Freund's adjuvant arthritis in rats.

• Journal of Acupuncture Research
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• 제20권2호
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• pp.77-84
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• 2003

Objective : In order to study the effects of bee venom(BV) on the pain, edema, and acute inflammatory reactant of rheumatoid arthritis(RA) patients. Methods : Patients with RA who met the ACR(American College of Rheumatology) 1987 revised criteria for the diagnosis of RA were treated with the BV therapy twice a week for 3 months. Tender joint counts, swollen joint counts, Visual analog scale(VAS), morning in stiffness, ESR, C-reactive protein(CRP) were analyzed before and after BV therapy. Results : The results as follows: 1. Tender joint counts in patients after BV therapy were significantly lower than those before BV therapy($9.0{\pm}7.9$ vs $15{\pm}11.4$, p=0.002). 2. Swollen joint counts of the patients after BV therapy were significantly lower than those before BV therapy ($5.0{\pm}6.1$ vs $1.5{\pm}2.3$, p=0.001). 3. VAS in patients after BV therapy was significantly lower than before BV therapy($60.8{\pm}17.6$ vs $38.0{\pm}15.9$, p=0.000). 4. Duration of morning stiffness in patients after BV therapy was significantly reduced compared with that before BV therapy($119.1{\pm}112.6min$ vs $59.0{\pm}89.7min$, p=0.009). 5. ESR and CRP were not significantly changed before and after BV therapy, suggesting BV itself could make inflammatory reaction as well as therapeutic effect. Conclusions: BV therapy improved tender joint counts, swollen joint counts and duration of morning stiffness in this study, and further study is needed in log-term effect of BV therapy.

• The Korean journal of internal medicine
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• 제33권6호
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• pp.1241-1251
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• 2018

Background/Aims: To estimate the level of agreement and positivity rates of latent tuberculosis infection (LTBI) tests prior to the use of tumor necrosis factor (TNF) inhibitors in relation to underlying rheumatic diseases and endemic tuberculosis levels. Methods: The Ovid-Medline, Embase, and Cochrane Libraries were searched for articles before October 2013 involving LTBI screening in rheumatic patients, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis. Results: In pooled analyses, 5,224 rheumatic patients had undergone both a tuberculin skin test (TST) and an interferon-gamma release assay (IGRA) before TNF inhibitors use. The positivity of TST, QuantiFERON-TB Gold In Tube (QFT-GIT), and T-SPOT.TB (T-SPOT) tests were estimated to be 29%, 17%, and 18%, respectively. The agreement percentage between the TST and QFT-GIT, and between the TST and T-SPOT were 73% and 75%. Populations from low-to-moderate endemic TB presented with slightly less agreement (71% between TST and QFT-GIT, and 74% between TST and T-SPOT) than patients from high endemic countries (73% between TST and QFT-GIT, and 81% between TST and T-SPOT). By underlying disease stratification, a lower level of agreement between TST and QFT-GIT was found among AS (64%) than among JIA (77%) and RA patients (73%). Conclusions: We reaffirm the current evidence for accuracy of LTBI test done by TST and IGRA among rheumatic patients is inconsistent. Our stratified analysis suggests different screening strategies might be needed in clinical settings considering the endemic status in the patient's country of origin and the precise nature of underlying diseases.

• Journal of Acupuncture Research
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• 제18권1호
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• pp.157-169
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• 2001

Objective : The purpose of this study is to investigate the effects on WBC counts and each differential of neutrophils, lymphocytes, monocytes in whole blood sample of each experimental Aqua-acupuncture treated mice groups PCortex Ulmi Pumilae(CU), Ramulus Cinnamomum(RC), Radix Achyranthes(RA), Apitoxin(BV), Calculus Bovis Fel Ursi Moschus compound(BUM). Materials & Method : All the BALB/c mice used in this study were bred and maintained in our pathogen-free mouse facility and were 6 weeks of age at the start of the experiment. The experimental model of arthritis was induced by injecting 300${\mu}g$/kg LPS to all mice knee joint. The each of Aqua-acupuncture(Cortex Ulmi Pumilae, Ramulus Cinnamomum, Radix Achyranthes, Apitoxin, Calculus Bovis Fel Ursi Moschus compound) was injected into GB34(陽陵泉) of mice groups every other day for 6 times. And the WBC counts and each differential of neutrophils, lymphocytes, monocytes were measured at the 3rd, 7th and 14th day after LPS injection. Results : 1. The WBC counts were significantly decreased compared with the control(CON) group in every Aqua-acupuncture groups at all days. And at the 14th day, BV & BUM groups were more significantly decreased than RA group. 2. The Neutrophil's ratio was significantty increased compared with the CON group in CU & RC groups at the 3rd day and RC group was more significant than CU group. But at the 7th and 14th day, every Aqua-acupuncture groups were significantly increased compared with the CON group and at the 7th day, RC group was more significant than RA, BV & BUM groups and at the 14th day, RC, BV & BUM groups were more significant than RA group. 3. The Lymphocyte's ratio was significantly decreased compared with the CON group in RC group at the 3rd day. At the 7th day, CU, RC & BV groups were significantly decreased compared with the CON group. At the 14th day, every Aqua-acupuncture groups were significantly decreased compared with the CON group and RC group was more significant than RA group, 4. The Monocyte's ratio was significantly decreased compared with the CON group in every Aqua-acupuncture groups at the 7th day. At the 14th day, BV & BUM groups were significantly decreased compared with the CON group. Conclusion : According to the above results, it was concluded that CU & RC groups were more effective at the early period of this experiment, and at the latter period, BV & BUM groups were more effective than others. RA group was less effctive than others.