Quality Indicators for Evaluating the Health Care of Patients with Rheumatoid Arthritis: a Korean Expert Consensus.

BACKGROUND: There is increasing interest in the quality of health care and considerable efforts are being made to improve it. Rheumatoid arthritis (RA) is a disease that can result in favorable outcomes when appropriate diagnosis and treatment are provided. However, several studies have shown that RA is often managed inappropriately. Therefore, the Korean College of Rheumatology aimed to develop quality indicators (QIs) to evaluate and improve the health care of patients with RA. METHODS: Preliminary QIs were derived based on the existing guidelines and QIs for RA. The final QIs were determined through two separate consensus meetings of experts. The consensus was achieved through a panel of experts who voted using the modified Delphi method. RESULTS: Fourteen final QIs were selected among 70 preliminary QIs. These included early referral to and regular follow-up with a rheumatologist, radiographs of the hands and feet, early initiation and maintenance of disease-modifying anti-rheumatic drug (DMARD) therapy, periodic assessment of disease activity, screening for drug safety and comorbidities, including viral hepatitis and tuberculosis before biologic DMARD therapy, periodic laboratory testing, supplementation with folic acid, assessment of the risk for cervical spine instability before general anesthesia, patient education, and specialized nurse. CONCLUSION: These QIs can be used to assess and improve the quality of health care for patients with RA.

Factors Associated with the Use of Complementary and Alternative Medicine for Korean Patients with Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is often painful and debilitating. Patients with RA are increasingly receiving complementary and alternative medicine (CAM). We aimed to identify the patient characteristics and disease-specific factors associated with Korean patients with RA who decide to start treatment with CAM. METHODS: Among the total 5371 patients with RA in the KORean Observational study Network for Arthritis (KORONA), 2175 patients who had no experience with CAM were included in our study. In our study, we assessed the frequency of new incident CAM use, its patterns, and the predictive factors of new CAM use. RESULTS: Of the 2175 patients, 229 patients (10.5%) newly started receiving CAM within a year of enrolling in the cohort. Of those who started treatment with CAM, 17.0% received only herbal medicine, 54.6% only acupuncture treatments (7.0% used a combination of both), and 21.4% "Other" (e.g., physical therapy and placental extract injections). Women (OR 1.89, 95% CI 1.13-3.14) and patients with depression (OR 3.52, 95% CI 1.65-7.50) were significantly more likely to be treated with CAM. Regarding household types, patients who lived in an extended family (OR 1.78, 95% CI 1.08-2.95) or as part of a couple (OR 1.55, 95% CI 1.07-2.24) were more likely to be treated with CAM than patients living in a nuclear family. CONCLUSION: Our study found, within a year, an incidence rate of 10.5% for new CAM use among patients with no previous experience with CAM. Sex, depression, and household type were significantly associated with new CAM use.

Increased expression of endocan in arthritic synovial tissues: effects of adiponectin on the expression of endocan in fibroblast-like synoviocytes.

This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, was increased in rheumatoid arthritic tissues. In addition, the involvement of adiponectin in the regulation of endocan expression in arthritic joints was examined. Arthritic synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) were immunostained with antibodies to endocan and vascular endothelial growth factor (VEGF). Subsequently, synovial cells and human umbilical vein endothelial cells were cultured and stimulated with interleukin-1 ß (IL-1ß) or adiponectin. The mRNA and protein levels of endocan were evaluated by polymerase chain reaction and ELISA, respectively. Endocan expression was markedly increased in the inflammatory sites of RA synovial tissues. In OA tissues, endocan expression was higher in tissues displaying moderate and severe inflammation than in those with mild inflammation. In vitro expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1ß stimulation. Adiponectin was a more potent stimulant of endocan than IL-1ß at their respective physiological concentrations in synovial cells. Endocan silencing by small interfering RNA transfection of synovial cells decreased in vitro cell migration and invasion. In conclusion, adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints.

Anti-inflammatory effects of methanol extract of Patrinia scabiosaefolia in mice with ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Patrinia scabiosaefolia Fisch is used in folk medicines to treat intestinal abscesses, acute appendicitis, and dysentery in Asia. Although recent reports indicate that Patrinia scabiosaefolia has sedative and anti-tumor effects, its effects on ulcerative colitis have not been previously explored. AIM OF THE STUDY: To determine the effects and the mode of action of the methanol extract of the roots of Patrinia scabiosaefolia (PME) on a model of colitis in mice induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: We induced colitis using DSS in 5-week-ICR mice over 7 days and estimated disease activity index (DAI), which took into account body weight, stool consistency, gross bleeding, and tissue myeloperoxidase (MPO) accumulation. Colon lengths and spleen weights were measured. Histological changes were observed by H&E staining. Pro-inflammatory mediators, namely, nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), were determined using Griess assays, immunoassays, and by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), respectively. RESULTS: PME significantly attenuated DSS-induced DAI scores and tissue MPO accumulation, which implied that it suppressed weight loss, diarrhea, gross bleeding, and the infiltrations of immune cells. PME administration also effectively and dose-dependently prevented shortening of colon length and enlargement of spleen size. Histological examinations indicated that PME suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, PME inhibited the abnormal secretions and mRNA expressions of pro-inflammatory cytokines, such as, TNF-α, IL-1ß, and IL-6. CONCLUSION: These results suggest that PME has an anti-inflammatory effect at colorectal sites that is due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may have therapeutic value in the setting of inflammatory bowel disease (IBD).

Assessment of prescribed herbal medicine on liver function in Korea: a prospective observational study.

OBJECTIVE: The aim of this study was to investigate the influence of herbal medicine (HM) prescribed by doctors of Korean medicine (KMD) on liver function in Korea. DESIGN AND INTERVENTIONS: For this multicenter, prospective, observational study, we enrolled patients who wished to take HM prescribed by KMD for various medical purposes in Korea. One hundred and twenty-two (122) patients took HM for an average of 20.6 +/- 8.4 (mean +/- standard deviation) days, and completed questionnaires. OUTCOME MEASURES: Liver function tests (LFTs) were performed before (first test) and after each HM treatment (second test). For LFT, aspartate aminotransferase, alanine aminotransferase, total bilirubin (t-Bil), direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase were measured. RESULTS: There were no significant changes in LFT data between the first and second tests, except in the t-Bil level. However, all data of total bilirubin level in second test were within normal range, except only one patient. Multivariate analysis did not identify any herb that significantly increased t-Bil; hence no hepatotoxic herb was found. Twenty-one (21) of the 122 patients were abnormal on first testing, and 10 at the second testing. Of the patients taking herbs, 4 changed from normal to abnormal and 15 from abnormal to normal (p = 0.019). CONCLUSION: The current study showed that ingestion of HM prescribed by KMD did not increase the frequency of abnormal LFTs, at least in the short term.

Suppressive effects of nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by Citrus reticulata extract in RAW 264.7 macrophage cells.

Immature peels of Citrus reticulata extract (CR) are widely used as traditional herbal medicine in Korea. We studied its effects on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 macrophage cells. NO production was assessed by nitrite assay and iNOS expression was identified by reverse transcription-polymerase chain reaction (RT-PCR), Real-time PCR and Western blot. The promoter activity of iNOS gene was also determined by luciferase reporter gene assay using 5'-flanking region of murine iNOS gene. Activation of nuclear factor kappa B (NF-kappaB) was determined by electrophoretic mobility shift assay (EMSA). CR (20, 50, and 100 microg/ml) significantly inhibited the lipopolysaccharide (LPS)-induced NO production (P<0.01; 9.2+/-1.5, 4.8+/-0.6, and 3.3+/-0.4 microM), iNOS protein (38.1+/-3.8, 32.3+/-5.8, and 36.8+/-4.5%) and mRNA expression (34.2+/-4.1, 13.1+/-5.8, and 20.8+/-1.2%) in RAW 264.7 macrophage cells. CR (20, 50, and 100 microg/ml) also reduced the iNOS promoter activity (68.7+/-3.9, 50.6+/-5.6, and 45.9+/-3.9%) in piNOS-LUC-transfected cells. In addition, CR (20, 50, and 100 microg/ml) significantly inhibited the activity of NF-kappaB DNA binding activity in LPS-induced macrophage cells (P<0.05; 51.8+/-4.1, 32.7+/-5.5, and 35.7+/-2.9%). These results suggest that CR may suppress LPS-stimulated NO production by inhibiting of NF-kappaB.

Antiinflammatory effects of a combined herbal preparation (RAH13) of Phellodendron amurense and Coptis chinensis in animal models of inflammation.

In an attempt to develop an antiinflammatory herbal remedy that is as potent as current synthetic medicines, the cortex of Phellodendron amurense Rupr (Rutaceae) and the rhizomes of Coptis chinensis Franch (Ranunculaceae) were combined in a 2:1 ratio. This ratio was chosen based on in vitro experiments and traditional Asian medicine prescriptions. The combined ethanol extract, named RAH13, was evaluated for antiinflammatory properties using animal models of acute inflammation such as the croton oil-induced ear edema test and an acetic acid-induced capillary permeability test. Models of chronic inflammation were also tested using the cotton pellet test and a delayed-type hypersensitivity (DTH) test. Oral administration of RAH13 at a dose of 200 mg/kg showed in vivo antiinflammatory activity as potent as the effects associated with 100 mg/mL of celecoxib or 1 mg/kg of dexamethasone. These effects were seen in both acute and chronic inflammation models, suggesting that RAH13 may be effective in controlling some inflammation-related diseases.

Silkworm (Bombyx mori L.) reduces vasopressin expression in the hypothalamus of streptozotocin-induced diabetic mice.

BACKGROUND: Hyperglycemia plays an important role in the development and progression of diabetic neuropathy, with which the expression of vasopressin is associated. This study was designed to investigate the effect of silkworm on the expression of vasopressin, a hormone synthesized in hypothalamic area, in the paraventricular (PVN) and supraoptic nucleus (SON) of hypothalamus in streptozotocin (STZ)-induced diabetic mice. METHODS: Vasopressin-positive neurons in the PVN and SON of STZ-induced diabetic mice were identified by immunohistochemistry. Blood glucose levels were measured by One Touch Basic glucose measurement system. Intraperitoneal glucose tolerance (IPGT) tests were performed on overnight fasted mice. RESULTS: STZ-induced diabetic mice fed with 0.4% silkworm group resulted in significantly decreased expression of vasopressin-positive neurons (107.8 +/- 5.4 in PVN and 140.8 +/- 8.5 in SON, p<0.05). In addition, blood glucose levels increased significantly in STZ-induced diabetic group (p<0.05). In contrast, STZ-induced mice fed with 0.4% silkworm group showed significantly decreased blood glucose level (p<0.05. CONCLUSION: These observations may provide a scientific foundation for the increasingly used silkworm powder as an adjunct in the treatment of diabetes mellitus, especially diabetic neuropathy.

Panax ginseng increases hypoxia-induced down-regulated cellular response related genes in human neuroblastoma cells, SK-N-MC.

BACKGROUND: Many studies have suggested that hypoxia plays a crucial role in the pathogenesis of various neurological disorders. To determine protective effect of Panax ginseng (PG) on hypoxia (0.1% O(2))-induced cell death in human neuroblastoma cells SK-N-MC, we profiled the gene expression among hypoxia, PG-treated hypoxia and normoxia groups. METHODS: To determine protective effect on hypoxia-induced cytotoxicity of PG, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We compared the gene expression profiles among hypoxia, PG-treated hypoxia (100 mug/ml, 6 hours) and normoxia groups using 8K human cDNA microarray analysis. Additionally, in order to identify differentially expressed genes between hypoxia and PG-treated hypoxia groups, hierarchical clustering of genes was also performed. RESULTS: MTT assay showed that PG protected hypoxia-induced cell death. In cDNA microarray analysis, hypoxia remarkably down-regulated IGF-II mRNA-binding protein 3 (IMP-3), integrin alpha 2 (ITGA2), syndecan binding protein (SDCBP), insulin-like growth factor binding protein 3 (IGBP3) and M-phase phosphoprotein 10 (MPHOSPH10), belonging to category of cellular physiologic response (global M<-3.5). In cluster analysis, 1428 genes exhibited differential expression levels between hypoxia and PG-treated hypoxia groups. Of them, the expressions of 11 genes were increased more than two-fold by PG treatment compared to those in hypoxia group. Particularly, of 11 genes, the expression levels of cellular physiologic response related genes such as MPHOSPH10, IMP-3 and SDCBP, which markedly down-regulated by hypoxia, are increased more than four-fold by PG treatment, compared to hypoxia group. CONCLUSION: In summary, hypoxia induced down-regulation of cellular physiologic response related genes in human neuroblastoma cells, SK-N-MC, and PG ameliorated the hypoxia-induced down-regulation of such genes. These results indicate possible usage of PG in hypoxia-induced neuronal injury including ischemia, trauma and degenerative diseases.

Ganoderma lucidum extract stimulates glucose uptake in L6 rat skeletal muscle cells.

The effect of Ganoderma lucidum extract on glucose uptake was studied in L6 rat skeletal muscle cells. G. lucidum extract increased glucose uptake about 2-fold compared to control. The extract stimulated the activity of phosphatidylinositol (PI) 3-kinase which is a major regulatory molecule in the glucose uptake pathway. About 7-fold increased activity of a PI 3-kinase was observed after treatment with G. lucidum extract, whereas PI 3-kinase inhibitor, LY294002, blocked the G. lucidum extract-stimulated PI 3-kinase activity in L6 skeletal muscle cells. Protein kinase B, a downstream mediator of PI 3-kinase, was also activated by G. lucidum extract. We then assessed the activity of AMP-activated protein kinase (AMPK), another regulatory molecule in the glucose uptake pathway. G. lucidum extract increased the phosphorylation level of both AMPK alpha1 and alpha2. Activity of p38 MAPK, a downstream mediator of AMPK, was also increased by G. lucidum extract. Taken together, these results suggest that G. lucidum extract may stimulate glucose uptake, through both PI 3-kinase and AMPK in L6 skeletal muscle cells thereby contributing to glucose homeostasis.

Anti-inflammatory effects of an ethanolic extract from Clematis mandshurica Rupr.

Clematis mandshurica Rupr (Ranunculaceae) roots are used in traditional Korean medicine to treat inflammation-related diseases. Therefore, we undertook to investigate their inhibitory effect on inflammation under non-cytotoxic conditions. The ethanolic extract of Clematis mandshurica at 100 microg/ml was found to significantly block the production of the pro-inflammatory mediators, nitric oxide (NO) and prostaglandin E(2) (PGE(2)), in lipopolysaccharide (LPS)/interferon(IFN)-gamma-stimulated mouse peritoneal macrophages, by up to 77% and 59%, respectively. In addition, it significantly inhibited cell proliferation and cytokine production (interleukin (IL)-2 and IFN-gamma) in splenocytes stimulated with Con A (concanavalin A; 5 microg/ml). Furthermore, when splenocytes from extract fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and the production of IL-2 and IFN-gamma were significantly inhibited. In addition, the extract reduced in vivo inflammation in oxazolone-induced delayed type hypersensitivity (DTH) model mice. Taken together, these data suggest that Clematis mandshurica is able to ameliorate inflammatory disease by exerting an anti-inflammatory effect in cases of proinflammatory and cell-mediated inflammation.

The inhibitory effects of aqueous extract of Magnolia officinalis on human mesangial cell proliferation by regulation of platelet-derived growth factor-BB and transforming growth factor-beta1 expression.

Mesangial cell (MC) proliferation, mediated by platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-beta1, and cyclin-dependent kinases (CDK), is the common feature of glomerulosclerosis. Magnolia officinalis, stem bark of Machilus thunbergii S., has multiple pharmacological effects. In this study, we investigated the influence of aqueous extract of Magnolia officinalis on MC proliferation, DNA synthesis, and expression of PDGF-BB, TGF-beta1, CDK1, CDK2, and CDK4 in fetal bovine serum (FBS)-activated human MC. Magnolia officinalis inhibited the MC proliferation, DNA synthesis, and the expression of PDGF-BB, CDK1, and CDK2 gene and CDK1, CDK2, and TGF-beta1 protein. These results suggest that the inhibitory effect of Magnolia officinalis on MC proliferation may be mediated by regulation of PDGF-BB and TGF-beta1expressions and by modulation of CDK1 and CDK2 expression.