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  • articleNo Access

    In Silico Investigation Targeting the IL-6/JAK-1/TNF-α Pathway in Rheumatoid arthritis: Matricaria chamomilla L. Compounds

    Chamomile, emphasized as an herbal remedy with healing potential for human health, is used in traditional medicine. In this study, the potential of compounds derived from Matricaria chamomilla L. against IL-6, JAK-1 and TNF-α target proteins associated with rheumatoid arthritis (RA) was compared with known inhibitors. The drug-likeness and ADME/T properties of these compounds were investigated using online tools, and molecular docking and molecular dynamics simulations of the selected structures were examined. IL-6, JAK-1 and TNF-α formed stable complexes with apigenin, quercetin and galaxolide, respectively, demonstrating that these compounds exhibit potential inhibitory activity against RA.

  • articleNo Access

    Anti-inflammatory Effect of Bee Venom on Type II Collagen-Induced Arthritis

    Bee venom (BV) has been used to relieve pain and reduce inflammation in traditional Oriental medicine, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). We previously reported that the BV injection into a traditional acupuncture point (Zusanli) reduced arthritis-associated edema and nociceptive responses in Freund's adjuvant-induced arthritis in rats (Kwon et al., 2001). This study was designed to evaluate the anti-inflammatory and anti-cytokine effect of BV on a murine type-II collagen-induced arthritis (CIA) model. Male mice were immunized by spontaneous injection of 100 μg of an emulsion of bovine type-II collagen and complete Freund's adjuvant (CFA), with a booster injection after 2 weeks. In the experimental group, 0.1 ml BV was injected at acupuncture point (Zusanli) near both knees twice a week for a total of 5 times. In the control group, normal saline was injected at the same frequencies. These injections began 5 weeks after the first collagen injection. Starting the 3rd week after the first collagen injection, we examined limb swelling and severity of arthritis twice a week. At 8 weeks, mice were sacrificed and synovial tissue was examined with the light microscope and serum cytokines (IL-1β and TNF-α) were measured by ELISA.

    The incidence of arthritis, the mean arthritis index and the number of arthritic limbs were significantly lower in the treatment compared to the control group (63% versus 75%, 3.4% versus 8.5%, 23% versus 75%, respectively). Among the serum proinflammatory cytokines, the production of TNF-α in the BV group was suppressed compared to the control group (59+/-4.5 versus 99.5+/-6.5, p<0.05), but IL-1β was not suppressed. The examination of the histopathology of the joints of murine CIA showed decreased inflammation signs and less lymphocyte infiltration after BV acupuncture therapy. Acupuncture therapy with BV suppressed the development of arthritis and caused inhibition of the immune responses in type-II collagen-induced arthritis.

  • articleNo Access

    Symptom Combinations Assessed in Traditional Chinese Medicine and Its Predictive Role in ACR20 Efficacy Response in Rheumatoid Arthritis

    The predictive roles of symptom combination traditionally evaluated in traditional Chinese medicine (TCM) in the treatment of rheumatoid arthritis (RA) were explored. Three hundred and ninety six patients were randomly divided into 197 subjects receiving Western medicine therapy (WM) and 199 subjects receiving TCM therapy (TCM). A complete physical examination and 18 clinical manifestations typically assessed in TCM were recorded before the randomization. The ACR responses were used for efficacy evaluation. ACR20 and 50 responses with WM treatment were higher than in the TCM group. The 18 symptoms in RA could be clustered into 4 symptom combinations with factor analysis, which represent joint symptoms, cold pattern, deficiency pattern and hot pattern in TCM respectively. TCM would be more effective in patients with weak-symptom combination 3 (deficiency pattern in TCM), and WM would be more effective in patients with symptom combination 2 (cold pattern in TCM). Symptom combinations judged with TCM may have influence on the efficacy of therapy in the treatment of RA.

  • articleNo Access

    The Anti-Arthritic Effects of Synthetic Melittin on the Complete Freund's Adjuvant-Induced Rheumatoid Arthritis Model in Rats

    Bee venom (BV) has been used for millennia in Chinese traditional medicine to treat rheumatoid arthritis (RA). However, its components and mechanism remain unclear, which has hampered its development and application for the treatment of RA. In this study, we examined the anti-arthritis effects of melittin, which composes nearly 50% of the dry weight of whole BV, on the complete Freund's adjuvant-induced (CFA-induced) RA model in rats. The RA animal models were treated with solutions of BV, melittin, and saline by injection into a specific acupoint (Zusanli). The BV and melittin treatments statistically diminished the thickness of the arthroses in the injected side of the paw, compared to the saline treatment. Melittin therapy also significantly reduced arthritis-induced nociceptive behaviors, as assessed by the thermal hyperalgesia test. In addition, CFA-induced Fos expression in the superficial layer of the lumbar spinal cord was significantly suppressed by the BV and melittin treatments, compared to the saline treatment. These results indicate that melittin is an effective anti-arthritis component of whole bee venom, making it a promising candidate as an anti-arthritis drug.

  • articleNo Access

    The New Use of an Ancient Remedy: A Double-Blinded Randomized Study on the Treatment of Rheumatoid Arthritis

    Rheumatoid arthritis (RA) is the most common chronic inflammatory disease with unknown causes and unknown cures in Western medicine. This double-blinded study aimed to investigate the efficacy and safety of a widely used traditional Chinese medicine (Paeoniflorin (PAE) plus cervus and cucumis polypeptide injection (CCPI) using disease-modifying antirheumatic drugs (DMARD) as a control (methotrexate (MTX) plus leflunomide (LEF)). Patients were randomly assigned to one of the three groups: PAE + CCPI, MTX + LEF, and MTX + LEF + CCPI. The primary end point was the American College of Rheumatology 20% improvement response criteria (ACR20). The secondary end point was that of adverse effect frequencies and the speed of onset action. Our results showed that more patients in the CCPI-containing groups responded to the ACR20 during early treatment. After six months, ACR20 showed no significant difference among the three treatments. The maximum improvement in the two DMARD groups was significantly higher than that in the PAE + CCPI group (p < 0.01). CCPI made the onset action of the DMARD therapy 4.6 times faster. PAE + CCPI had significantly lower adverse event incidences than the two DMARD groups. These results indicate that PAE + CCPI appear to be a more acceptable alternative to DMARDs when patients cannot use DMARDs. CCPI appears to be a beneficial add-on to DMARDs that makes the onset of action faster, especially when patients need to relieve RA symptoms as soon as possible. Although not as effective as DMARDs, PAE appears to be a safer option to substitute DMARDs for long-term RA treatment when DMARD toxicity is an issue.

  • articleNo Access

    Bauhinia championii Extraction Treatment of Collagen-Induced Arthritis via Downregulation of the Expression of TLR4, MyD88 and NF-κB

    Rheumatoid arthritis (RA) has emerged as an important worldwide public health problem. Due to the lack of efficacy and major side effects related to many Western medical treatments, traditional Chinese medicine or herbal medicine is very often used to treat this disease. In the present study, we evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) in a rat model of RA induced by type-II collagen. Wistar rats with type-II collagen-induced arthritis (CIA) were given either 125 or 500 mg/kg of BCBE for RA. Paw swelling and weight were measured, and pathological joint sections of CIA rats were observed using the hematoxylin and eosin (HE) staining method. Protein and mRNA expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor κB (NF-κB) were determined by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis in synovial tissue. During therapeutic treatment, BCBE significantly suppressed paw swelling, increased weight loss and ameliorated pathological joint changes. The protein and mRNA expressions of TLR4, MyD88 and NF-κB were downregulated in the CIA model when treated with BCBE. In conclusion, these results suggest that the treatment of RA with BCBE confers anti-RA activity and has therapeutic potential in this CIA model.

  • articleNo Access

    Dioscin, a Steroidal Saponin Isolated from Dioscorea nipponica, Attenuates Collagen-Induced Arthritis by Inhibiting Th17 Cell Response

    Dioscin, a steroidal saponin isolated from Dioscorea nipponica Makino, has previously been shown to possess antiarthritic effects. However, the underlying mechanism is still elusive. Herein, we investigated the therapeutic effects of dioscin on collagen-induced arthritis (CIA) in DBA/1 mice and related mechanism. Cytokine production in CII-specific immune responses were measured by enzyme-linked immunosorbent assay (ELISA); Th17 cell-related gene expression, including IL-17A, RORγτ and IL-23p19, were detected by qPCR analysis; Surface marker, T regulatory (Treg) cells and intracellular cytokines (IL-17A and IFN-γ) were evaluated by flow cytometry. We performed Th17 cell differentiation assay in vitro. Results showed that, in vivo, dioscin treatment significantly reduced the severity of CIA, which was accompanied by decreased Th17 response, but not Th1 and Treg response; dioscin-treated mice also showed lower percentage of CD11b+ Gr-1+ neutrophils; In vitro, dioscin treatment suppressed the differentiation of naive CD4+ T cells into Th17 cell and decreased IL-17A production. Collectively, our results indicate that dioscin exerts antiarthritic effects by inhibiting Th17 cell immune response.

  • articleNo Access

    Curcumin-Pretreated Adipose-Derived Stem Cells Enhance the Neuroprotective Ability to Repair Rheumatoid Arthritis-Induced Damage in the Rat Brain

    Neurodegenerative diseases have become increasingly prevalent in the aged population. Rheumatoid arthritis (RA) is an autoimmune disease that causes systemic inflammation, damaging the neurons. However, only a few treatment options can reduce RA-induced neurodegeneration. This study aimed to evaluate whether adipose-derived stem cells (ADSCs) pretreated with curcumin could ameliorate RA-induced neurodegenerative illness in an RA rat model. Wistar rats were randomly classified into the following four groups: control, RA, RA + ADSC (1 × 106 cells per rat), and RA + curcumin-pretreated ADSC (1 × 106 cells per rat). After treatment for two months, the effects were specifically evaluated in the brains collected from the rats. Our results demonstrated that the transplantation of curcumin-pretreated ADSCs substantially reduced inflammation and apoptosis in the cortices of RA rats compared to those of other groups. Thus, the combination of ADSCs and curcumin exerts a synergistic effect in enhancing neuronal protection in RA rats. In the future, this combination therapeutic strategy can potentially be used as a novel treatment method to reduce RA-induced neurodegenerative disorders.

  • articleOpen Access

    Deer Velvet Antler Extracts Exert Anti-Inflammatory and Anti-Arthritic Effects on Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Distinct Mouse Arthritis

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint deformity and disability. Deer velvet antler (DA), a traditional Chinese medicine, has been used to treat various types of arthritis for several thousands of years, but the underlying mechanisms are unknown. Herein, we investigated the anti-arthritic and anti-inflammatory effects of DA in vitro and in vivo. The ethyl acetate layer of DA ethanol extract (DA-EE-EA) was used to treat tumor necrosis factor (TNF)-α-stimulated fibroblast-like synoviocyte MH7A cells, collagen-induced arthritis DBA/1 mice, and SKG mice with zymosan-induced arthritis. DA-EE-EA reduced nitric oxide production, prostaglandin E2 levels, and levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and IL-8 in MH7A cells. DA-EE-EA also downregulated the phosphorylation of mitogen-activated protein kinase p38 and c-Jun N-terminal kinase and the translocation of nuclear factor kappa B p65. Intraperitoneal injection of DA-EE-EA for 3 weeks substantially reduced clinical arthritis scores in vivo models. Pathohistological images of the hind paws showed that DA-EE-EA reduced immune cell infiltration, synovial hyperplasia, and cartilage damage. The levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, IL-1β, IL-6, IL-8, IL-17A, and interferon-gamma, decreased in the hind paw homogenates of DA-EE-EA-treated mice. We also identified several potential components, such as hexadecanamide, oleamide, erucamide, and lysophosphatidylcholines, that might contribute to the anti-inflammatory effects of DA-EE-EA. In conclusion, DA-EE-EA has the potential to treat RA by regulating inflammatory responses. However, the individual components of DA-EE-EA and the underlying anti-inflammatory mechanisms need further investigation in future studies.

  • articleNo Access

    Umbelliferone Inhibits Migration, Invasion and Inflammation of Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Relieves Adjuvant-Induced Arthritis in Rats by Blockade of Wnt/β-Catenin Signaling Pathway

    Umbelliferone (UMB), a natural coumarin compound, has been reported to possess anti-rheumatic effects on rheumatoid arthritis (RA) experimental models, but its potential role of UMB in regulating migration, invasion and inflammation of RA fibroblast-like synoviocytes (FLS) remain unclear. Herein, MTT assay was performed to confirm the non-cytotoxic concentrations (10, 20, and 40μM) and the treatment time (24h) of UMB on TNF-α-stimulated RA FLS (MH7A cells) in vitro. Results of wound-healing, transwell and phalloidin staining assays revealed that UMB inhibited TNF-α-induced migration, invasion and F-actin cytoskeletal reorganization in MH7A. Results of ELISA, western blot and gelatin zymography indicated that UMB decreased the productions of pro-inflammatory factors, including IL-1β, IL-6, IL-8, MMP-2 and MMP-9, and inhibited MMP-2 activity in TNF-α-stimulated MH7A cells. In vivo, UMB (25mg/kg and 50mg/kg) relieved the joint damage and synovial inflammation in rats with adjuvant-induced arthritis (AIA). Mechanistically, UMB could suppress Wnt/β-catenin signaling both in TNF-α-induced MH7A cells and in AIA rat synovium, evidenced by decreasing Wnt1 protein level, activating GSK-3β kinase by blocking GSK-3β (Ser9) phosphorylation, and reducing the protein level and nuclear translocation of β-catenin. Importantly, combined use of lithium chloride (a Wnt/β-catenin signaling agonist) eliminated the inhibitory effects of UMB on migration, invasion and inflammation in vitro and the anti-arthritic effects of UMB in vivo. We concluded that UMB inhibited TNF-α-induced migration, invasion and inflammation of RA FLS and attenuated the severity of rat AIA through its ability to block Wnt/β-catenin signaling pathway.

  • articleNo Access

    Analytical study of heat transfer rate of peristaltic flow in asymmetric channel with laser and magnetic effects: Remedy for autoimmune disease

    This paper addresses a hybrid nanoflow of Casson fluid. The theoretical formulation is derived by considering spherical and, as well as, platelet shape nanoparticles. Electro-osmotic flow (EOF) through an asymmetric channel endures the simultaneous effects of Joule heating, viscous dissipation and magnetic fields. Lubrication effects have also been taken into account to subdue the skin friction. Moreover, the contribution of thermal slip boundary conditions and laser radiation articulately devises a theoretical remedy for rheumatoid arthritis. Detailed parametric reveals the promising results for the application of spherical shape nanoparticles to curb autoimmune diseases.

  • articleNo Access

    MAINTAINING WRIST FUNCTION IN SEVERE RHEUMATOID ARTHRITIS: A CASE STUDY OF REVISION SWANSON WRIST ARTHROPLASTY STAGED VIA A WRIST FUSION IN RHEUMATOID ARTHRITIS

    Hand Surgery01 Dec 2002

    We present a case of revision Swanson wrist arthroplasty staged via a wrist fusion in a patient with rheumatoid arthritis. Due to extensive bone loss in the rheumatoid patient, it may not be possible initially to revise a wrist arthroplasty; however after fusion with a bone graft to regain bone stock we have demonstrated that this is possible. It may even be possible to convert such a fusion to a total wrist arthroplasty.

  • articleNo Access

    MODIFIED MATCHED ULNAR RESECTION FOR ARTHROSIS OF DISTAL RADIOULNAR JOINT IN RHEUMATOID ARTHRITIS

    Hand Surgery01 Jan 2006

    The pain of distal radioulnar arthrosis in rheumatoid patients is often due to disease largely confined to the radioulnar rather than the ulnocarpal articulation. This is a retrospective study of 14 patients (14 wrists) who underwent selective shaving of the radial articulation of the ulnar head leaving the ulnocarpal articulation intact. The ulnar head is reduced to the circumference of its shaft and a dorsal retinacular flap is interposed between it and the distal radius. Average age of the patients and follow-up were 63.5 years and 31 months, respectively. All patients had rheumatoid arthritis. Pain improved in 14 out of 15 wrists. Overall results were 67% good to excellent and 33% fair based on the modified Mayo's wrist score. This novel procedure for DRUJ arthrosis produces predictable pain relief in low demand rheumatoid patient.

  • articleNo Access

    THE EFFECTIVENESS OF RA WRIST FUSION USING BETA-TCP WITHOUT AUTOGENOUS ILIAC BONE GRAFTING: A REPORT OF FOUR CASES

    Hand Surgery01 Jan 2006

    Wrist arthrodesis is indicated for the rheumatoid hand especially in cases with severe destruction of the carpal bones. In the arthrodesis procedure for the rheumatoid wrist, autogenous iliac bone grafting is required in most cases. However, autogenous iliac bone graft necessitates the additional surgical intervention, and can be associated with the problem of inadequate bony quality or quantity. It is thought that use of the artificial bone substitute in the procedure can lessen the surgical morbidity while supplying the consistent material without shortage of graft quantity. We have performed arthrodesis of the rheumatoid wrist using beta-TCP for four patients. Clinical results of these patients were satisfactory both in pain relief and functional improvement with complete bony healing. Therefore, this procedure seems to be an effective option for the rheumatoid wrist with severe destructive changes.

  • articleNo Access

    REVISION METACARPOPHALANGEAL JOINT REPLACEMENT 30 YEARS AFTER PRIMARY SWANSON FLEXIBLE SILICONE IMPLANT ARTHROPLASTY IN A RHEUMATOID PATIENT: A CASE REPORT

    Hand Surgery01 Jan 2009

    We report a case of a patient with rheumatoid arthritis undergoing revision surgery 30 years after primary metacarpophalangeal joint arthroplasty using a Swanson implant. Removal and replacement of the implant were successfully performed, and the patient was satisfied with the revision surgery.

  • articleNo Access

    RADIOSCAPHOLUNATE ARTHRODESIS — A PROSPECTIVE STUDY

    Hand Surgery01 Jan 2009

    The purpose of this prospective study was to evaluate pain levels, range of motion, patient activity and satisfaction after radioscapholunate (RSL) arthrodesis. This was in association with distal scaphoid excision and complete resection of the triquetrum. The non-union rate for radioscapholunate arthrodesis was examined and the results compared with previous studies.

    Twenty-three patients (14 males and nine females) with an average age of 47 (range 26–73) years underwent RSL fusion for post-traumatic osteoarthritis, rheumatoid arthritis and Kienböck's disease of the lunate with a mean follow-up of 32 (range 13–70) months. The absolute prerequisite for any of these groups of patients was a functional midcarpal joint which was assessed pre-operatively with radiographs and intra-operatively prior to RSL fusion.

    The average flexion to extension motion changed from 66° to 57°. The ulnoradial range of motion also increased to 43° from a pre-operative value of 22°. The patients visual analogue pain scores reduced from an average of 64 to 28 (p = 0.01). Nineteen patients had no restriction in activity and all but one was satisfied with the outcome. All patients remained in full time employment with ten returning to some form of sport.

    RSL fusion with excision of the distal pole of the scaphoid and the entire triquetrum led to minimal reduction in the flexion-extension arc of motion and an increase in the ulnoradial arc. There was also good pain relief and maintenance of a patient's function. Memory staples are also an effective method of securing fusion in the wrist obtaining similar results to that seen in forefoot surgery.

  • articleNo Access

    EXTENSOR TENDON RUPTURE IN RHEUMATOID ARTHRITIS: A SURVEY OF PATIENTS BETWEEN 2005 AND 2010 AT FIVE KOREAN HOSPITALS

    Hand Surgery01 Jan 2012

    Background. Recent medical advancements in the treatment of rheumatoid arthritis (RA) can prevent joint damage and tendon involvement. The authors evaluated patterns of extensor tendon ruptures in RA patients that presented to hand surgeons over a recent five-year period.

    Methods. Medical records and radiographs were retrospectively reviewed, and telephone interviews were conducted with 38 patients that had experienced extensor tendon ruptures in a rheumatoid hand during the study period and were operated on at one of five tertiary referral hospitals in South Korea. Patterns of tendon ruptures were compared in patients that did or did not receive medical treatment.

    Results. Twenty-nine of the 38 patients (76%) had tendon ruptures in more than two digits. When multiple digits were involved, mean duration between first and latest rupture was 2.9 months. When patients treated with medications by rheumatologists (24 patients) were compared with those not treated (14 patients), no significant differences were found for; number of ruptured tendons, time from first to last rupture, disease duration, or radiographic RA severity.

    Conclusions. RA patients who once experienced a tendon rupture are still at risk of sequential tendon ruptures despite recent advancement of medical treatment. Education of the risks of sequential tendon ruptures and timely consultation to hand surgeons continue to be necessary in RA patients.

  • articleNo Access

    SHORT TO MEDIUM RESULTS USING THE REMOTION TOTAL WRIST REPLACEMENT FOR RHEUMATOID ARTHRITIS

    Hand Surgery01 Jan 2013

    We present the clinical outcome of patients who underwent RE-MOTION Total Wrist Replacement (TWR) for the treatment of Rheumatoid arthritis involving the wrist.

    Ten patients were available for follow-up, ranging from one to five years after index surgery. Two patients required surgical intervention for wound breakdown, including one patient who required a radial forearm flap for skin coverage. No patients required revision surgery or conversion to fusion. Patients who did not have complications gained statistically significant pain relief and improvement in mean overall flexion.

    In this small case series with short to medium results patients reported an improvement in terms of flexion and pain. Despite this, the question of efficacy of TWR compared to fusion in the long term remains unanswered due to the high rate of complications.

  • articleNo Access

    EXTENSOR TENDON DISLOCATION AFTER END-TO-SIDE TRANSFER IN A RHEUMATOID PATIENT

    Hand Surgery01 Jan 2014

    We report a case of extensor tendon dislocation at the metacarpophalangeal joint of the middle finger in which it appeared that an ulnar translation force created by an end-to-side transfer contributed to the dislocation. We recommend alterations in technique or alternative method of extensor tendon reconstruction to avoid this complication if unfavorable factors for end-to-side transfer exist.

  • articleNo Access

    TOTAL PROXIMAL INTERPHALANGEAL JOINT ARTHROPLASTY FOR OSTEOARTHRITIS VERSUS RHEUMATOID ARTHRITIS — A SYSTEMATIC REVIEW

    Hand Surgery01 Jan 2015

    Osteoarthritis (OA) and rheumatoid arthritis (RA) of the proximal interphalangeal joints (PIPJ) can be treated with arthroplasty, although the complicated anatomy of the joint makes surgery challenging. Controversy exists regarding outcomes in relation to disease aetiology. This study aims to compare functional outcomes and re-operation rates in these two conditions. The electronic databases MEDLINE, EMBASE, Cochrane database and Google scholar were searched in accordance with PRISMA. The study quality was assessed using the Methodological Index for Non-Randomised Studies (MINOR). A total of 16 studies were reviewed including 506 cases in the OA and 542 in the RA group. Five studies assessed function and patient satisfaction, demonstrating a non-significant improvement in the OA group. Five studies reported re-operation rate; three showing it to be lower in the OA group and two reporting similar rates. This review suggests that those undergoing PIPJ arthroplasty for OA may have a better functional outcome and lower re-operation rate.