Results: 1. In the AlPR-HA group, the incidence of arthritis and arthritis index were significantly decreased. 2. In the AlPR-HA group, the levels of $IL-6,\;IFN-{\gamma},\;TNF-{\alpha},\;IL-1{\beta},\;IgG,\;IgM,\;Anti-collagen\;II$ in serum of the CIA mouse were significantly decreased. 3. In the AlPR-HA group, the levels of $IFN-{\gamma:,\;IFN-{\gamma}\;/IL-4$ in spleen cell culture of the CIA mouse were significantly decreased. 4. In the Hematoxylin and eosin stain, the cartilage destruction and synovial cell proliferation were decreased in the AIPR-HA group. 5. In the Masson's trichrome stain, the collagen fiber expressions were similar with that of the Normal group. 6. In the AlPR-HA group, the expression ratio of $CD3e^+$ to $CD19^+$ cell and $CD4^+$ to $CD8^+$ cell were similarly maintained as Normal group in the CIA mouse lymph nodes. 7. In the AlPR-HA group, $CD3e^+/CD69^+$ cells in the CIA mouse joint and $CD11a^+/CD19^+$ cells and $CD11b^+/Gr-1^+$ cells in the CIA mouse lymph nodes were significantly decreased. 8. In the AIPR-HA group, $CD4^+/CD25^+$ cells were significantly decreased in the CIA mouse spleen cell and were similarly maintained as Normal group in the CIA mouse lymph nodes. Conclusions: These results suggest that AlPR-HA at 51'36 has an effect to control synovial cell proliferation and cartilage destruction in rheumatoid arthritis.
Objectives : This study was carried out to know the effects of Gwanjul8-bang(here in after reffered to GJ8) on the inhibition of arthritis induced by collagen on DBA/1J mice. Methods : For this purpose, GJ8 was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, hepatotoxicity, arthritis index, value of immunocyte in draining lymph node(DLN) and paw joint, cytokine in serum were measured in vivo. Results : 1. The arthritis index was decreased significantly. 2. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was a significant decrease in paw joint. 3. In lymph nodes, $CD19^+$, $CD3^+$, $CD4^+/CD25^+$ cells increased significantly, and $B220^+/CD23^+$ cells decreased significantly. 4. In joints, $CD3^+$, $CD4^+$, $CD11b^+/Gr-1^+$ cells decreased significantly. 5. The levels of $TNF-{\alpha}$, IL-6, IL-17, MCP-1 and vascular endothelial growth factor(VEGF) in serum was significantly decreased compared with control. 6. Anti-collagen II in serum was significantly decreased compared with control. 7. The degree of arthritis induced damage of joint of GJ8 group is slight compared with control group in histopathologic observation(hematoxylin & eosin(H&E), Masson-Trichrome(MT) staining). Conclusions : Comparison of the results for this study showed that GJ8 had immunomodulatory effects. So we expect that GJ8 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore there seems to be many clinical research needed in the future.
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.
Objectives : Lonicerae japonicae Flos(LJF) has been reported to exhibit anti-oxidant, anti-inflammatory, anti-viral, anti-rheumatoid properties. However, it is still largely unknown whether LJF inhibits the ultraviolet(UV)B-induced oxidative damage in human HaCaT keratinocytes. Therefore in this paper, we investigated the anti-oxidative capacity and protective effect of LJF against UVB-induced oxidative demage in human HaCaT keratinocytes. Methods : To evaluate the anti-oxidative activity of LJF extracts, we measured total phenolic contents, total flavonoid contents, antioxidant capacity, and superoxide scavenging activity. To give an oxidative stress to HaCaT cells, UVB was irradiated with $200mJ/cm^2$ to HaCaT cells. To detect the protective effect of LJF against UVB, we measured cell viability, DNA fragmentation and reactive oxygen species (ROS) production. In addition, we performed high-performance liquid chromatography (HPLC) analysis to find a major component of LJF. Results : LJF contained phenolic and flavonoid contents, and showed the anti-oxidant and superoxide scavenging activity. The UVB-induced oxidative conditions led to the cell death, DNA fragmentation and reactive oxygen species (ROS) production. However, pretreatment with LJF reduced oxidative conditions, including inhibition of cell death, DNA fragmentation and ROS production. In addition, we found out chlorogenic acid as major component of LJF. Conclusions : These results could suggest that LJF contained anti-oxidative contents and exhibited protective effects against UVB on human HaCaT keratinocytes. And the effective compound of LJF which could show protective activities against UVB is chlorogenic acid. Thus, LJF and chlorogenic acid would be useful for the development of drug or cosmetics treating skin troubles.
This study was conducted to determine whether CD4 T cell responses to citrullinated fibrinogen occur in patients with rheumatoid arthritis (RA), especially in HLA-DR4-positive subjects. Whole peripheral blood mononuclear cells (PBMCs) of RA patients and control subjects were stimulated with citrullinated fibrinogen peptides, and T-cell production of proliferation and proinflammatory cytokines, such as interferon-${\gamma}$(IFN-${\gamma}$) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, $Fib-{\alpha}$ R84Cit, identified as a DRB1*0401-restricted T cell epitope in HLA-DR4 transgenic mice, and the degree of T cell activation was examined similarly. No proliferative responses to the citrullinated fibrinogen peptides were observed in whole PBMCs or CD4 T cells from RA patients. Furthermore, no increased production of IFN-${\gamma}$ or IL-17A was found in whole PBMCs or CD4 T cells stimulated with the citrullinated fibrinogen peptides, although these cells responded to recall antigen, a mixture of tetanus toxoid, purified protein derivative (PPD) from Mycobacterium tuberculosis, and Candida albicans. The results of this study indicate that anti-citrulline immunity in RA patients may be mediated by fibrinogen because there is no evidence of CD4 T cell-mediated immune responses to citrullinated fibrinogen peptides.
The purposes of this study were to test the negative association between schizophrenia and rheumatoid arthritis(RA) and to clarify the role of prolactin and estrogen as protective factors in this association. The author compared the prevalence rate of RA between 561 patients with schizophrenia and 222 patients with mood disorder. For investigating the role of estrogen and prolactin, the author checked the plasma prolactin and estradiol level in 80 patients with paranoid schizophrenia and 77 patients with RA. The results were as follows. 1) Epidemiological data The prevalence rate of RA in the schizophrenic group was 0/561 and that of RA in the mood disorder group was 2/222. To compare these results between two groups, the author applied the Binomial test using the average prevalence rate of RA(0.8%) in the general population as a reference rate. The prevalence rate of RA in the schizophrenic group was significantly lower than that of RA in the general population. However, the prevalence rate of RA in the mood disorder group was not significantly different to that of RA in the general population. 2) Comparison of plasma prolactin and estradiol level between two groups The plasma level of prolactin in the schizophrenic group was significantly higher than that of prolactin in the RA group(p=0.000). However, the plasma level of estradiol in the schizophrenic group was significantly lower than that of estradiol in the RA group(p=0.017). These results were not consistent across gender. To contrast with the results in the female group, which were consistent with the results in the total subjects, for the male group, the plasma levels of prolactin and estradiol in the schizophrenic group were significantly higher than those of prolactin and estradiol in the RA group. These results support the results of previous studies which confirm the negative association between schizophrenia and RA. These results also suggest that the elevation of plasma prolactin level in the patients with schizophrenia has a antirheumatic effect while the elevation of plasma estradiol level in the patients with RA has a anti-schizophrenic effect, and that these effects act as a possible mechanism in the negative association between two disorders. However, these results suggest that this association is specific to female patients.
Context: Interest exits in whether TNF-alpha antagonists increase the risk of breast cancer and total malignancies in patients with rheumatoid arthritis (RA). Objectives: To analyze the risk of malignancies, especially breast cancer, in patients with RA enrolled in randomized control trials (RCTs). Methods: A systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safety of at least one dose of the five TNF-${\alpha}$ antagonists with placebo or methotrexate (MTX) (or TNF-${\alpha}$ antagonists plus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references into document management software EndNote${\times}6$. Two independent reviewers selected studies and extracted the data about study design, patients' characteristics and the type, number of all malignancies. Results: 28 RCTs from 34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during the double-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, there was no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were also no significant trend for increased risk of total malignancies on anti-TNF-${\alpha}$ therapy administered at approved doses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two models, modified intention to treat model analysis led to higher estimation than per protocol model analysis. Conclusions: This study did not find a significantly increased risk of breast cancer and total malignancies in adults RA patients treated with TNF-${\alpha}$ antagonists at approved doses. However, it cannot be ignored that more patients developed malignancies with TNF-${\alpha}$ antagonists therapy compared with patients with placebo or MTX, in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed, and both mITT and PP analyses should be used in such safety analyses.
Leflunomide는 최근에 개발된 항류마티스 약물로서 기존의 약물과 작용기전이 다르면서 효과가 우수하여 활동성 류마티스관절염에 널리 사용되고 있다. 알려진 부작용에는 간독성과 피부독성, 조혈기능부전, 위장관계 증상등이 있는데, 시판후 조사에서는 호흡기계 부작용도 드물지만 경한 정도에서 치명적인 경우까지 모두 보고 되었다. 세계 각 처에서의 시판후 조사에 의하면 호흡기계 부작용으로 사망한 경우가 있어서 심각한 폐독성의 가능성을 시사한다. 우리나라에서는 leflunomide로 인한 호흡기계 부작용에 대한 보고가 없었다. 저자들은 leflunomide에 의한 간질성 폐렴 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다.
Essential hypertension is a typical chronic disease requiring adequate and continuous management. And many studies supported that self-care was the essential factor to promote the wellbeing. The purpose of this study is to identify and understand the behavior patterns of self-care in hypertensives. As a research method, 35 Q-statements were collected through Individual interviews and review of the related literatures. 21 subjects were interviewed and the data were analyzed by the PC QUANL program with principal component analysis. There were 6 different self-care types classified as follows 1) Type 1 was the self-oriented control type, monitoring the blood pressure and taking the low salt diet. But they didn't take the anti -hypertensive drug and visit the health agency regularly. 2) Type 2 was the stress-control type. Their main activities were meditation to relieve the stress and communication with family. 3) Type 3 was called daily-life control type. This type tried to make their mind comfort and think positively. They also preferred walking and exercise regularly. 4) Type 4 was the medical-oriented control type, taking the anti-hypertensive drug, visiting the medical personnel and following the medical regimens. 5) Type 5 was the medication-oriented type. They only took the anti -hypertensive drug regularly and didn't any other self-care like as monitoring the blood pressure, taking the low salt diet and exercise. 6) Type 6 was called non-medication control type. This type had no medication, but tried to visit the health agency and health personnel. From the above results, it can be concluded that the self-care types were very various and self-care education have to provide individually according to the characteristics of self-care type. Another repeated study can be recommended to improve the nursing intervention the self-care behavior in chronic patient like as diabetics or rheumatoid arthritis.
Kim, Kyoung-Soo;Choi, Hyun-Mi;Yang, Hyung-In;Yoo, Myung-Chul
Biomolecules & Therapeutics
/
제20권1호
/
pp.50-56
/
2012
WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, $PGE_2$, and MMP-13 in IL-$1{\beta}$-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of $PGE_2$, NO, IL-$1{\beta}$, and TNF-${\alpha}$ were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and $PGE_2$ was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. I${\kappa}B$B signaling pathways were inhibited by WIN-34B, and the migration of NF-${\kappa}B$ into the nucleus was inhibited, which is consistent with the degradation of $I{\kappa}B-{\alpha}$. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators.
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