• Archives of Pharmacal Research
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• 제29권12호
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• pp.1147-1153
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• 2006

Mizoribine (MZR) has been shown to possess immunosuppressive activity that selectively inhibits the proliferation of lymphocytes by interfering with inosine monophosphate dehydrogenase. The efficacy of MZR is not only in patients who have had renal transplantation, but also in patients with rheumatoid arthritis (RA), lupus nephritis, and primary nephritic syndrome. Because the exact mechanism of its immunosuppressive action is not clear, the object of this study was to examine the ability of MZR to regulate the antigen presenting cells (APCs), dendritic cells (DCs). In this work, we tested whether MZR ($1{\sim}10\;{\mu}g/mL$) could inhibit the cross-presentation of DCs. DC2.4 cells ($H-2K^{b}$) or bone marrow-derived DCs (BM-DCs) generated from BM cells of C57BL/6 mouse ($H-2K^{b}$) were cultured in the presence of MZR with OVA-microspheres, and the amount of OVA peptide-class I MHC complexes was measured by a T cell hybridoma, B3Z, that recognizes OVA (257-264 : SIINFEKL)-$H-2K^{b}$ complex and expresses-galactosidase. MZR profoundly inhibited the expression of SIINFEKL-$H-2K^{b}$ complexes. This inhibitory activity of MZR appeared to affect the phagocytic activity of DCs. MZR also decreased IL-2 production when we examined the effects of MZR on $CD4^{+}$ T cells. These results provide an understanding of the mechanism of immunosuppressive activity of MZR on the inhibition of MHC-restricted antigen presentation and phagocytic activity in relation to their actions on APCs.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.485-490
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• 1999

The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated buy a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate the in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at $70^{\circ}C$ for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.

• Journal of muscle and joint health
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• 제2권1호
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• pp.17-40
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• 1995

Rheumatoid arthritis is the one of the chronic diseases, one of its major symptoms is a chronic pain. Despite developing medical treatment and surgical techniques, it is suggested that to control the pain is the goal of the treatment. But pain is an inner experience and even those closest to the patient cannot truly observe its progress or share in its suffering. The National Academy of Sciences Institute of Medicine's report on Pain and Disability concluded that there is no objective measure of pain-(exactly) no pain thermometer-nor can there ever be one, because the experience of pain is inseparable from personal perception and social influence such as culture. To explore chronic pain experience is to understand the process and property of the patient's perception of pain through the response to pain, the coping with pain, and the adaptation to pain. Therefore a qualitative study was conducted in order to gain an understanding of pain experience of patients with RA in korea. I used naturalistic inquiry as a research methodology, which had 5 axioms, the first is that realities are multiple, constructed, and holistic, the second is that knower and known are interactive, inseparable, the third is only time and context bound working hypotheses(idiographic statements) are possible, the forth is all entities are in a state of mutual simultaneous shaping, so that it is impossible to distinguish causes from effects and the last is that inquiry is value-bound. Purposive sampling was conducted as a sampling. 20 subjects who experienced pain over 10 years, lived in middle-sized city and big city in Korea, and 17 women and 3 men. The subject's age was from 32 to 62 (average 48.8), all were married, living with their spouse and children, except two-one divorced and the other widow before they became ill. I collected data using In depth structured interview. I had interviews two or three times with each subject, and the interviews were conducted at each subject's home. Each interview lasted about two hours an average. A recording was taken with the consent of the subject. I used inductive data analysis-such as unitizing and categorizing. unitizing is a process of coding, whereby raw data are systematically transformed and aggregated into units. Categorizing is a process wherby previously unitized data are organized into categories that provide descriptive or inferential information about the context or setting from which the units were derived. This process is used constant comparative method. The pain controlling process is composed of behavior of pain control. The behaviors of pain control are rearranging of ADL, hiddening role conflict, balancing treatment, and changing social relation. Rearranging of ADL includes diet management, sleep management, and the adjustment of daily life activities. The subjects try to rearrange their daily activities by modified style of motions, rearranging time span & range of activities, using auxillary facilities, and getting help in order to keep on the pace of daily life. Hiddening role conflict means to reduce conflicts between sick role and their role as a family member. In this process, the subjects use two modes, one is to control the pain complaints, and the other is to internalize the value which is to stay home is good for caring her children and being a good mother. To control pain complaints is done by 'enduring', 'understanding' the other family members, or making them undersood in order to reduce pain. Balancing treatment is composed of two aspects. One is to keep the pain within the endurable level, the other is to keep in touch with medical personnel in order to get the information of treatment and emotional support. Changing social relation is made by information seeking and sharing, formation of mutual support relation, and finally simplification of social relationships. The subjects simplify their social relationships by refraining from relations with someone who makes them physically and psychologically strained. In particular the subjects are apt to avoid contact with in-laws, and the change of relation to in-laws results in lessening the family boundary. In the course of this process, they confront the crisis of family confict result in family dissolution. This crisis is related to the threat of self-existence. Findings from this study contribute to understanding the chronic pain experience. To advance this study, we should compare this result with other cases in different cultural contexts. I think to interpret these results, korean cultural background should be considered. Especially the different family concept, more broader family members and kinship network, and the traditional medical knowledge influences patients' behavior.

• IMMUNE NETWORK
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• 제3권1호
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• pp.69-77
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• 2003

Background: Celecoxib, a COX-2 specific inhibitor, has recently been used for the treatment of rheumatoid arthritis. However, the molecular and cellular mechanisms of celecoxib against RA inflammation remain to be defined. To elucidate the action mechanism of celecoxib on inflammatory cells, we investigated the effect of celecoxib on the production of two important mediators of inflammation, nitric oxide and PGE2 Methods: RAW 264.7 cells stimulated with LPS were preincubated with various concentrations of celecoxib (from $10^{-8}$ to $10^{-5}$ M) and $10{\mu}M$ hydrocortisone, respectively. The production of NO and PGE2, the end products of iNOS and COX-2 genes, were estimated in culture supernatants by Greiss method and EIA, respectively. The expression of iNOS gene, COX-2 gene, $NF-{\kappa}B$, and $I-{\kappa}B$ were determined by RT-PCR and western blot analysis. Results: Celecoxib and hydrocortisone inhibited the production of NO and PGE2 in dose dependent manner, when RAW 264.7 cells were stimulated with LPS. The expression of iNOS was also down-regulated by celecoxib and hydrocortisone. Interestingly, COX-2 gene differentially expressed according to the dose of celecoxib, a decrease with lower dose ($10^{-8}$ M) but an increase with higher dose ($10^{-5}$ M). $NF-{\kappa}B$ binding activity was decreased by lower dose of celecoxib, whereas was not affected by higher dose of it. The expression of $I-{\kappa}B$ was suppressed by higher dose of celecoxib. Conclusion: The celecoxib strongly suppressed the production of NO and PGE2 in LPS-stimulated RAW264.7 cells. The decrease of NO seems to be linked to the inhibition of iNOS by celecoxib. The lower and higher dose of celecoxib differentially regulated the COX-2 expression and $NF-{\kappa}B$ activity.

• IMMUNE NETWORK
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• 제14권1호
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• pp.21-29
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• 2014

Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• 제27권6호
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• pp.782-788
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• 2013

Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae), colloquially known "Gujulcho" in Korea, has been used in traditional medicine for the treatment of various diseases, including cough, common cold, bladder-related disorders, gastroenteric disorders, hypertension, and inflammatory diseases, such as pneumonia, bronchitis, pharyngitis, and rheumatoid arthritis (RA) However, the effect of Chrysanthemum zawadskii var. latilobum on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of Chrysanthemum zawadskii var. latilobum extract (CZE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. CZE were not cytotoxic up to 100 ${\mu}g/ml$ concentration in the MCF-7 cell line. CZE decreased MMP-9 expression. TPA substantially increased NF-${\kappa}B$ DNA binding activity. Pre-treatment with CZE inhibited TPA-stimulated NF-${\kappa}B$ binding activity and NF-${\kappa}B$ related protein expression. To identify invasion ability of MCF-7 cells decreased by CZE, we used martrigel invasion assay. As a result, it is significantly decreased cell invasion. These results indicate that CZE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. Chrysanthemum zawadskii var. latilobum may have potential value in restricting breast cancer metastasis.

• Journal of Korean Neurosurgical Society
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• 제42권4호
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• pp.311-316
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• 2007

Objective : The objective of this study is to investigate the safety, surgical efficacy, and advantages of a polyaxial screw-rod system for posterior occipitocervicothoracic arthrodesis. Methods : Charts and radiographs of 32 patients who underwent posterior cervical fixation between October 2004 and February 2006 were retrospectively reviewed. Posterior cervical polyaxial screw-rod fixation was applied on the cervical spine and/or upper thoracic spine. The surgical indication was fracture or dislocation in 18, C1-2 ligamentous injury with trauma in 5, atlantoaxial instability by rheumatoid arthritis (RA) or diffuse idiopathic skeletal hyperostosis (DISH) in 4, cervical spondylosis with myelopathy in 4, and spinal metastatic tumor in 1. The patients were followed up and evaluated based on their clinical status and radiographs at 1, 3, 6 months and 1 year after surgery. Results : A total of 189 screws were implanted in 32 patients. Fixation was carried out over an average of 3.3 spinal segment (range, 2 to 7). The mean follow-up interval was 20.2 months. This system allowed for screw placement in the occiput, C1 lateral mass, C2 pars, C3-7 lateral masses, as well as the lower cervical and upper thoracic pedicles. Satisfactory bony fusion and reduction were achieved and confirmed in postoperative flexion-extension lateral radiographs and computed tomography (CT) scans in all cases. Revision surgery was required in two cases due to deep wound infection. One case needed a skin graft due to necrotic change. There was one case of kyphotic change due to adjacent segmental degeneration. There were no other complications, such as cord or vertebral artery injury, cerebrospinal fluid leak, screw malposition or back-out, or implant failure, and there were no cases of postoperative radiculopathy due to foraminal stenosis. Conclusion : Posterior cervical stabilization with a polyaxial screw-rod system is a safe and reliable technique that appears to offer several advantages over existing methods. Further biomechanical testings and clinical experiences are needed in order to determine the true benefits of this procedure.

• Journal of the Korea Institute of Information and Communication Engineering
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• 제14권5호
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• pp.1209-1216
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• 2010

It has increased that peripheral disturbance(blood flow, nerve, Raynaud's phenomenon) and finger rheumatoid arthritis which is caused by the diabetic complications. To improve these pain issues, we proposed new method for the Finger Disease Therapy(FDT). In this paper, we manufactured solenoid cylindrical coil which was only for the FDT using a variable micro-electromagnetic. Also, we designed the Finger Disease Therapy System(FDTS) which could select three stimulation modes(N_pulse, S_pulse, N/S_pulse) and frequency(0.25hz, 0.5hz, 1hz). We used a Teslameter to measure magnetic flux inner solenoid, and measured magnetic flux as distance(0 ~ 3cm) inner solenoid with stimulation modes and frequency. In the results, magnetic flux was the highest in center of solenoid(0cm) for all stimulation modes. Also, the highest magnetic flux was measured as N_pulse(294.3mT), S_pulse(293.8mT) in 1Hz and N/S_pulse (275.4mT) in 0.25Hz, respectively. Therefore, we developed the FDTS using various pattern and intensity for finger diseases therapy, and checked therapy clinic application possibility of the FDTS as measuring magnetic flux inner solenoid.

• The Journal of Dong Guk Oriental Medicine
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• 제7권2호
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• pp.107-120
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• 1999

Synovial joint of BALB/C mice were injeced with Lipopolysaccharide(LPS) were observed to investigate the morphological changes of synovial capsule caused by rheumatoid arthritis(RA). The RA on female Balb/c mice were induced by LPS injection, as dose of $300{\mu}{\ell}/kg$, into synovial cavity of knee joint. And then these specimen were fixed in 10% neutral buffered formalin and were decalcificated in EDTA solution for 4 weeks. The hyperplasia of synovium were appeared in synovial membrane. The filopodia of phagocytic like synoviocyte(type I synoviocyte) projected into synovial cavity and the number of fibroblast like synoviocyte(type II synoviocyte) with well-developed endoplasmic reticulum were increased in synovium. In fibrous membrane, the fibrosis induced by synthesis of collagen fiber were enlarged to all fibrous membrane, and the number of fibroblast were increased. A great number of inflammation component cell as lymphocyte and neutrophil leukocyte were infiltrated around capillary and the degranulate typed mast cell were increased. As results indicated that the hyperplasia of synovium induced by LPS, subsequently to cause the fibrosis, infiltration of imflammation component cell, and increase of degranulated type mast cell as same as symptoms of RA.

• Natural Product Sciences
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• 제8권1호
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• pp.1-15
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• 2002

An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.