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ID PMID Title PublicationDate abstract
25101488 Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis. 2014 Sep 25 High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.
24662560 Nonvasculitic autoimmune meningoencephalitis after rituximab: the potential downside of de 2014 Apr Nonvasculitic autoimmune meningoencephalitis (NAIM) is a rare condition describing a syndrome of steroid-responsive encephalopathy in patients with similar clinical and pathologic features. It can be associated with autoimmune diseases, such as Sjogren's syndrome and autoimmune thyroiditis. Brain biopsies usually show inflammatory cells without evidence of vasculitis. In this article, we present a patient who developed NAIM after receiving rituximab, a B-cell-depleting therapy for rheumatoid arthritis. The brain biopsy showed a lack of B lymphocytes in the brain tissue, and the patient responded well to intravenous immunoglobulins. We further discuss the role of B lymphocytes and specific regulatory B lymphocytes in suppressing autoimmunity in the brain and propose that the depletion of regulatory B cells may contribute to the pathogenesis of NAIM. This case illustrates a potential side effect of rituximab and demonstrates the importance of regulatory B cells in maintaining the immune response.
24680620 Therapeutic effects of standardized Vitex negundo seeds extract on complete Freund's adjuv 2014 May 15 The seeds of Vitex negundo L. (Verbenaceae) have been commonly used as a folk remedy for the treatment of rheumatism and joint inflammation in Traditional Chinese Medicine. This study aimed to evaluate the anti-arthritic activity of the extract of V. negundo seeds (EVNS) using Freund's complete adjuvant (CFA) induced arthritis (AA) in rat model. As a result, EVNS, with abundant phenylnaphthalene-type lignans, significantly inhibited the paw edema, decreased the arthritis score and spleen index, and reversed the weight loss of CFA-injected rats. Histopathological studies showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of EVNS-treated animals. The remarkable decrement of serum inflammatory factors (TNF-α, IL-1β and IL-6) were observed in EVNS-treated rats, whereas, IL-10, an anti-inflammatory cytokine, was found to be significantly increased by EVNS. The expressions of COX-2 and 5-LOX in PBMC were also inhibited by administration of EVNS. Our results demonstrated that V. negundo seeds possessed potential therapeutic effect on adjuvant induced arthritis in rats by decreasing the levels of TNF-α, IL-1β and IL-6 and increasing that of IL-10 in serum as well as down-regulating the levels of COX-2 and 5-LOX, and therefore may be an effective cure for the treatment of human rheumatoid arthritis.
24061286 Auto-antibodies to vascular endothelial cadherin in humans: association with autoimmune di 2013 Nov To identify patients with autoimmune diseases who are at high risk of developing vascular cell dysfunction, early biomarkers must be identified. This study was designed to detect and characterize circulating autoantibodies to VE-cadherin (AAVEs) in patients with early-stage autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) was developed to capture autoantibodies, using a recombinant human VE-cadherin fragment covering the extracellular domains as a target antigen. AAVEs specificity for the target antigen was confirmed by western blotting. Basal AAVEs levels were determined for healthy donors (n=75). Sera from patients (n=100) with various autoimmune diseases, including rheumatoid arthritis (n=23), systemic lupus erythematosus (SLE, n=31), systemic sclerosis (n=30), and Behçet's disease (BD, n=16) were also tested. Levels of AAVEs were significantly higher in rheumatoid arthritis (P<0.0001), SLE (P<0.05), and BD (P<0.05) populations than in healthy subjects. Purified immunoglobulin G (IgG) from a BD patient with exceptionally high AAVEs levels recognized the EC1-4 fragment in western blots. Further characterization of the epitopes recognized by AAVEs showed that BD patients had antibodies specific for the EC3 and EC4 domains, whereas SLE patients preferentially recognized the EC1 fragment. This suggests that distinct epitopes of human VE-cadherin might be recognized in different immune diseases. Purified IgG from BD patients was found to induce endothelial cell retraction, redistribution of VE-cadherin, and cause the formation of numerous intercellular gaps. Altogether, these data demonstrate a potential pathogenic effect of AAVEs isolated from patients with dysimmune disease. This is the first description of AAVEs in humans. Because regions EC1 and EC3-4 have been shown to be involved in homophilic VE-cadherin interactions, AAVEs produced in the course of dysimmune diseases might be specific biomarkers for endothelial injury, which is part of the early pathogenicity of these diseases.
23571448 Regulation of neutrophil apoptosis differs after in vivo transmigration to skin chambers a 2013 Short-lived neutrophils are major players in inflammation, arriving early to infected and/or injured tissues. After performed duty, neutrophils are programmed to die by apoptosis and are thereafter rapidly cleared by other phagocytes. In vitro, modulation of the apoptotic process has been thoroughly investigated in neutrophils isolated from peripheral blood, but less is known about the regulation of this process in neutrophils derived from extravascular tissues. We recently demonstrated that neutrophils having transmigrated in vivo, obtained from experimental skin chambers of healthy human subjects, are resistant to the death-delaying signals induced by a range of antiapoptotic stimuli. In the current study, we show that skin chamber neutrophils spontaneously secrete high levels of antiapoptotic interleukin (IL)-1β which delays neutrophil apoptosis. Contrary to skin chamber fluid, synovial fluid from patients with rheumatic arthritis contained only moderate levels of IL-1β, and neutrophils taken from this site were fully responsive to antiapoptotic stimulation during in vitro culture. Our data demonstrate that resistance to antiapoptotic stimulation is not a general feature of tissue neutrophils and imply that autocrine IL-1β signaling could be an important factor in determining how life and death of neutrophils is regulated in inflamed tissues.
24661783 Utilization and adherence patterns of subcutaneously administered anti-tumor necrosis fact 2014 May BACKGROUND: Adherence to therapy is a key requirement underlying achievement of clinical outcomes in randomized controlled drug registration trials. In postmarketing studies, comparison of adherence among therapies can become more complicated when drug dosing and administration schedules differ or when methods used to measure adherence are not consistently applied. OBJECTIVE: The objective of this exploratory study was to investigate a broad range of utilization and adherence outcomes associated with subcutaneous biologic treatments for rheumatoid arthritis (RA). METHODS: Adult patients (aged ≥18 years) exhibiting ≥2 claims with an RA diagnosis (code 714.x), at least 24 months of continuous medical and pharmacy eligibility, and 30-day supplies of adalimumab, etanercept, or golimumab were selected from the Optum Insight Clinformatics database. Adherence and utilization measures were calculated and compared across treatment groups. RESULTS: A total of 1532 adalimumab, 2099 etanercept, and 261 golimumab patients met inclusion criteria. Compared with both adalimumab and etanercept patients, golimumab patients were significantly more likely to have a medication possession ratio of ≥0.80 (82% vs 71% vs 62%; P < 0.001) and significantly less likely to have ≥4 late medication refills (6.9% vs 17.7% vs 26.1%; P < 0.001 for all). Etanercept patients had significantly greater refill intervals (37.7 vs 34.9 and 35.1 days) and had the lowest proportion of adherent fills (70% vs 77% and 75%) compared with both golimumab and adalimumab patients (P < 0.001 for all). Bivariate effects were reproduced in multivariate models that controlled for treatment duration. CONCLUSIONS: A number of statistically significant medication adherence differences were observed among golimumab, adalimumab, and etanercept patients in treatment for RA. Overall, golimumab patients appeared to be the most adherent group. Findings may be partially attributable to golimumab patients' likely increased disease severity, their prior experience with biologic medication, or golimumab's once-monthly dosing schedule, which requires fewer administrations than both adalimumab and etanercept.
24876668 Amyloidosis, inflammation, and oxidative stress in the heart of an alkaptonuric patient. 2014 BACKGROUND: Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. RESULTS: Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. CONCLUSIONS: SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.
22395477 Clinical and radiographic evaluation of total hip arthroplasties using porous tantalum mod 2013 Jan OBJECTIVES: Porous tantalum is a biomaterial newly applied for artificial joints. We present here 5-years follow-up report of a multicenter clinical trial of total hip arthroplasties (THA) with porous tantalum modular acetabular component (modular PTC). METHODS: Study participants received 82 hips in 79 cases, with 61.2 months follow-up on average. Age at operation was 60.9 years. Clinical results were evaluated using Merle d'Aubigne Postel score. Presence of implant loosening, periacetabular radiolucency, osteolysis, and gap filling were examined for radiographic results. RESULTS: Merle d'Aubigne Postel score improved from 10.0 to 16.4 points. All PTC were radiographically stable, with no evidence of progressive radiolucencies. Average polyethylene wear rate was 0.004 mm/year, with no periacetabular osteolysis. Fifteen hips (18.3%) showed a gap >1 mm; however, all showed bone filling within 12 months. PTC with oversized reaming was significantly less likely to have a gap. No implant failure was noted related to modularity. Resulting survival rate of modular PTC was 100% at 5 years. CONCLUSIONS: Modular PTC showed excellent results at 5-years of follow-up. Some hips showed periacetabular gaps, which were filled with bone within 1 year. Further follow-up was needed to determine long-term efficacy.
23549103 Immune suppression in cynomolgus monkeys by XPro9523: an improved CTLA4-Ig fusion with enh 2013 May The CTLA4-Ig fusion proteins abatacept and belatacept are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplant, respectively. Given that both biologics are typically administered chronically by infusion, a need exists for a next-generation CTLA4-Ig with more convenient dosing. We used structure-based protein engineering to optimize the affinity of existing CTLA4-Ig therapeutics for the ligands CD80 and CD86, and for the neonatal Fc receptor, FcRn. From a rationally designed library, we identified four substitutions that enhanced binding to human CD80 and CD86. Coupled with two IgG1 Fc substitutions that enhanced binding to human FcRn, these changes comprise the novel CTLA4-Ig fusion protein, XPro9523. Compared with abatacept, XPro9523 demonstrated 5.9-fold, 23-fold, and 12-fold increased binding to CD80, CD86, and FcRn, respectively; compared with belatacept, CD80, CD86, and FcRn binding increased 1.5-fold, 7.7-fold, and 11-fold, respectively. XPro9523 and belatacept suppressed human T cell proliferation and IL-2 production more potently than abatacept. XPro9523 also suppressed inflammation in the mouse collagen-induced arthritis model. In cynomolgus monkeys, XPro9523 saturated CD80 and CD86 more effectively than abatacept and belatacept, potently inhibited IgM and IgG immunization responses, and demonstrated longer half-life. Pharmacokinetic modeling of its increased potency and persistence suggests that, in humans, XPro9523 may demonstrate superior efficacy and dosing convenience compared with abatacept and belatacept.
23843680 Mechanisms of chronic state of inflammation as mediators that link obese adipose tissue an 2013 The metabolic syndrome is a cluster of cardiometabolic alterations that include the presence of arterial hypertension, insulin resistance, dyslipidemia, and abdominal obesity. Obesity is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of proinflammatory signalling pathways resulting in the induction of several biological markers of inflammation. Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Adiponectin can either act directly on macrophages to shift polarization and/or prime human monocytes into alternative M2-macrophages with anti-inflammatory properties. Meanwhile, the chronic inflammation in adipose tissue is regulated by a series of transcription factors, mainly PPARs and C/EBPs, that in conjunction regulate the expression of hundreds of proteins that participate in the metabolism and storage of lipids and, as such, the secretion by adipocytes. Therefore, the management of the metabolic syndrome requires the development of new therapeutic strategies aimed to alter the main genetic pathways involved in the regulation of adipose tissue metabolism.
24453414 The role of TL1A and DR3 in autoimmune and inflammatory diseases. 2013 TNF-like ligand 1A (TL1A), which binds its cognate receptor DR3 and the decoy receptor DcR3, is an identified member of the TNF superfamily. TL1A exerts pleiotropic effects on cell proliferation, activation, and differentiation of immune cells, including helper T cells and regulatory T cells. TL1A and its two receptors expression is increased in both serum and inflamed tissues in autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Polymorphisms of the TNFSF15 gene that encodes TL1A are associated with the pathogenesis of irritable bowel syndrome, leprosy, and autoimmune diseases, including IBD, AS, and primary biliary cirrhosis (PBC). In mice, blocking of TL1A-DR3 interaction by either antagonistic antibodies or deletion of the DR3 gene attenuates the severity of multiple autoimmune diseases, whereas sustained TL1A expression on T cells or dendritic cells induces IL-13-dependent small intestinal inflammation. This suggests that modulation of TL1A-DR3 interaction may be a potential therapeutic target in several autoimmune diseases, including IBD, RA, AS, and PBC.
24492951 Swertiamarin ameliorates inflammation and osteoclastogenesis intermediates in IL-1β induc 2014 Jun OBJECTIVE AND DESIGN: Rheumatoid arthritis is a chronic inflammatory and autoimmune disease that leads to aggressive joint cartilage and bone destruction. Swertiamarin is a secoiridoid glycoside found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in the Indian system of traditional medicine. In the present study, the potential of swertiamarin was evaluated in IL-1β induced fibroblast-like synoviocytes (FLS). METHODS: The FLS were isolated from Freund's Complete Adjuvant induced arthritic (AA) rats and cultured with IL-1β. The normal FLS and AA-FLS were cultured and used for subsequent experiment in fibroblastic morphology form. The efficacy of swertiamarin (10-50 μg/ml) was evaluated on mRNA and protein expression levels of inflammatory and osteoclastogenesis mediators. The efficacy was also evaluated on p38 MAPKα levels with time course studies (2, 4, 6, 8 and 12 h). RESULTS: IL-1β induced cell proliferation (149.46 ± 13.73 %) and NO production (162.03 ± 11.03%) in AA-FLS; treatment with swertiamarin controlled proliferation (82.77 ± 4.22%) and NO production (82.06 ± 3.91% at 50 μg/ml) in a dose-dependent manner. It also significantly (P < 0.05) modulated the expression of apoptotic marker (caspase 3), proinflammation mediators (TNFα, IL-6, PGE2, COX-2, iNOS, MMPs) and osteoclastogenic mediator (RANKL) at both the mRNA and protein levels. Treatment with swertiamarin inhibited the levels of p38 MAPKα in a dose-dependent manner and also significantly (P < 0.05) attenuated the release of the same in time dependent mode. CONCLUSION: These findings suggest that treatment with swertiamarin attenuated IL-1β induced FLS, and it revealed anti-inflammatory potential by attenuating aggressive FLS.
24261755 Retreatment efficacy and safety of tocilizumab in patients with rheumatoid arthritis in re 2014 Jan OBJECTIVES: To evaluate the safety and efficacy of retreatment with tocilizumab (TCZ) in patients who had participated in the DREAM study (Drug free remission/low disease activity after cessation of tocilizumab [Actemar] monotherapy study) and had experienced loss of efficacy. METHODS: Patients were retreated with TCZ or other disease modifying antirheumatic drugs (DMARDs). Disease activity was measured using the 28-joint disease activity score (DAS28) for 12 weeks. RESULTS: A total of 164 eligible patients, including 161 who experienced loss of efficacy within 52 weeks of the DREAM study, resumed treatment: 157 with TCZ and 7 with DMARDs and/or infliximab. Of TCZ-treated patients, 88.5 % (139 patients) achieved DAS28 <2.6 within 12 weeks, whereas among patients treated with DMARDs and/or infliximab only 14.3 % (1 patient) achieved DAS28 <2.6. Adverse events were observed in 70 TCZ-treated patients (44.0 %), but no serious infusion reactions were observed. CONCLUSIONS: Retreatment with TCZ was well-tolerated and effective in patients who had responded to the preceding TCZ monotherapy but had experienced loss of efficacy after cessation of TCZ.
24750968 [Tibio-talo-calcaneal arthrodesis with the retrograde intramedullary nail MEDIN]. 2013 PURPOSE OF THE STUDY: When the talus and the talocalcaneal joint are both affected, their fusion is the method of treatment. Ankle arthrodesis is carried out using various osteosynthetic materials such as external fixators, screws and plates. One of the options is retrograde nailing. Tibio-talo-calcaneal arthrodesis is frequently indicated in patients with rheumatoid arthritis (RA) in whom both the talus and the subtalar joint are often affected. MATERIAL AND METHODS: A retrograde nail for tibio-talo-calcaneal arthrodesis was developed at our department in cooperation with MEDIN Company. This is a titanium double-curved nail, with the distal part bent at 8 degrees ventrally and 10 degrees laterally. It is inserted from the transfibular approach. RESULTS: Sixty-two patients, 35 women and 27 men, were treated at our department from 2005. Since one patient had bilateral surgery, 63 ankles were included. The indications for arthrodesis involved rheumatoid arthritis in 42, post-traumatic arthritis in 10, failed ankle arthrodesis in two and failed total ankle arthroplasty in five ankles; tibial stress fractures close above the ankle in two RA patients, one patient with dermatomyositis and one with lupus erythematodes. The average age at the time of surgery was 64.2 years (range, 30 to 80). The average follow-up was 4.5 years (range, 1 to 9 years), Satisfaction with the treatment outcome and willingness to undergo surgery on the other side were reported by 82% of the patients. The AOFAS score improved from 35 to 74 points. Three (4.8%) patients complained of painful feet due to the fact that exact correction of the calcaneus was not achieved and the heel after arthrodesis remained in a slightly varus position. Of them, two had a failed total ankle arthroplasty. Post-operative complications included early infection managed by antibiotic treatment and early surgical revision with irrigation.in two (3.2%) RA patients, who were undergoing biological therapy. Late infection developed at 2 to 3 years after surgery in three (4.3%) patients (two had RA). The infection was managed by revision surgery with nail removal and irrigation. All patients healed well. Necrosis of the talus and development of a pseudoarthrosis were recorded in four (6.4%) patients, who subsequently underwent nail removal and repeat fusion using an external fixator. DISCUSSION: Retrograde nailing for tibio-talo-calcaneal arthrodesis is used by many authors. Its complication rate is comparable with the other methods of arthrodesis. CONCLUSIONS: The use of tibio-talo-calcaneal arthrodesis aims at a painless and stable joint. Arthrodesis of the talus and the subtalar joint using a retrograde nail is an effective surgical treatment of the joints affected. It is especially recommended for RA patients who have severe deviations. Retrograde nailing provides a stable osteosynthesis which does not require plaster cast immobilisation. The double-curved nail allows for its insertion in the solid part of the calcaneus and helps avoiding injury to the neurovascular bundle.
23677140 Do tibiofemoral contact point and posterior condylar offset influence outcome and range of 2014 Mar PURPOSE: The posterior condylar offset (PCO) and the tibiofemoral contact point (CP) have been reported as important factors that can influence range of motion and clinical outcome after total knee arthroplasty. A mobile-bearing knee implant with an anterior posterior gliding insert would in theory be more sensitive for changes in PCO and CP. For this reason, we analysed the PCO and CP and the relation with outcome and range of motion in 132 patients from a prospectively documented cohort in this type of implant. METHODS: The prosthesis used was a posterior cruciate retaining AP gliding mobile-bearing total knee replacement (SAL II Sulzer Medica, Switzerland). In 132 knees, the pre- and postoperative PCO and postoperative CP were evaluated. Measurements were made on X-rays of the knee taken in approximately 90° of flexion and with less than 3-mm rotation of the femur condyles. The outcome parameters, range of motion (ROM) and the knee society score (KSS), for each knee were determined preoperatively and at 5-year follow-up. RESULTS: The mean KSS improved from 91 to 161 at 5-year follow-up (p < 0.001) and the mean ROM from 102 to 108 (p < 0.05). The mean PCO difference (postoperative PCO-preoperative PCO) was--0.05 mm (SD 2.15). The CP was on average 53.9% (SD 5.5%). ROM was different between the 3 PCO groups (p = 0.05): patients with 3 or more mm decrease in PCO had the best postoperative ROM (p = 0.047). There was no statistical difference between the postoperative ROM between patients with a stable PCO and those with an increased PCO. There was no correlation between the difference in PCO and the difference in ROM; R Pearson = -0.056. There was no difference in postoperative ROM or postoperative total KSS between CP <60% and CP >60%: p = 0.22, p = 0.99, for ROM and KSS, respectively. Scatter plots showed uniform clouds of values: increase or decrease in PCO and CP had no significant influence on ROM or KSS. CONCLUSION: The hypotheses that a stable PCO and a more natural CP increase postoperative ROM and improve clinical outcome could not be confirmed. On the contrary, a decreased PCO seemed to improve knee flexion. Furthermore, a relationship between PCO and CP could not be found. LEVEL OF EVIDENCE: Prospective cohort study, Level II.
24062058 Inhibition of P2X4 suppresses joint inflammation and damage in collagen-induced arthritis. 2014 Feb Recent data have shown that the purinergic receptor P2X4 plays key roles in inflammatory responses. We evaluated whether P2X4 inhibition could affect the development of arthritis and autoimmunity in collagen-induced arthritis (CIA) model. P2X4 antisense oligonucleotide (asODN) was injected intravenously via tail vein into the CIA mice to selectively inhibit P2X4 expression daily for 14 days. P2X4 asODN treatment reduced the clinical score of CIA in mice. P2X4 asODN also decreased the levels of serum IL-1β, TNF-α, IL-6, and IL-17. P2X4 asODN treatment significantly inhibited synovial inflammation and joint destruction. P2X4 asODN treatment also suppressed the NLR family, pyrin domain containing 1 (NLRP1) inflammasome activation in CIA mice and synovial cells of human rheumatoid arthritis. These data show that P2X4 asODN confers a therapeutic benefit on CIA. Inhibition of the NLRP1 inflammasome signaling pathway is the underlying mechanism of action.
25351421 Role of cysteine‑rich angiogenic inducer 61 in fibroblast‑like synovial cell prolifera 2015 Feb Cysteine‑rich angiogenic inducer 61 (Cyr61) is a novel molecule that has been shown to be increased in the synovial tissues of patients with rheumatoid arthritis (RA). The present study was conducted in order to investigate the role of Cyr61 in the pathogenesis of RA. A human genome‑wide gene assay was used to screen gene expression in synovial tissues obtained from four patients with RA and three patients with osteoarthritis (OA). To examine the role of Cyr61 in the phenotype of RA‑fibroblast‑like synovial (FLS) cells, Cyr61 expression in RA‑FLS cells was knocked down using small interfering RNA (siRNA). Normal FLS cells transduced with lentiviral vectors encoding Cyr61 cDNA were used to further explore the effects of this molecule on FLS cell apoptosis, proliferation and invasion. The study found that the Cyr61 gene was highly expressed in the synovial cells from patients with RA compared with those from patients with OA. Downregulation of Cyr61 by siRNA led to impaired cell proliferation and invasion. Furthermore, it decreased the levels of matrix metalloproteinase (MMP)‑3 and MMP‑13, and induced apoptosis in RA‑FLS cells. Conversely, overexpression of Cyr61 in normal FLS cells led to opposite effects. In conclusion, these results indicate that Cyr61 is capable of promoting RA‑FLS cell proliferation and invasion via the suppression of apoptosis and the regulation of MMP expression. Therefore, Cyr61 may be a good target molecule for the treatment and prevention of RA.
24327007 Manipulation for stiffness following total knee arthroplasty: when and how often to do it? 2014 Oct Stiffness following total knee arthroplasty is a disabling complication. One of the management options of stiffness includes manipulation under anaesthesia, but no real consensus exist on appropriate timing of intervention, and the timing and results of the manipulation under anaesthesia (MUA) are under debate in the literature. Our aim was to determine the efficacy of single and multiple manipulations under anaesthesia following total knee arthroplasty and to determine the most appropriate timing for manipulation. We retrospectively reviewed 86 patients who underwent manipulation for stiffness following primary total knee replacement with at least 1-year follow-up. Range of motion before surgery, at the time of the MUA, immediately after MUA and at 6 weeks and 1 year post-MUA were recorded. At the end of 1 year post-manipulation, manipulations performed at less than 20 weeks, following primary total knee arthroplasty, showed 31° of flexion gain as compared to only 1.5° of flexion gain when manipulation was undertaken after 20 weeks. Of the 86 patients, 21 had multiple manipulations with no significant difference in flexion gain after the second manipulation. Patients on warfarin (26%) had an increased incidence of stiffness and poor flexion gain. This study showed that better results were achieved when manipulation was performed at less than 20 weeks (particularly between 12 and 14 weeks) from primary surgery with no added benefit from re-manipulations.
23814243 Total knee replacement with retention of both cruciate ligaments: a 22-year follow-up stud 2013 Jul We report on the long-term results of 163 bicruciate-retaining Hermes 2C total knee replacements in 130 patients at a mean follow-up of 22.4 years (20.3 to 23.5). Even when the anterior cruciate ligament had a partially degenerative appearance it was preserved as long as the knee had a normal anterior drawer and Lachman's test pre-operatively. The description and surgical technique of this minimally constrained prosthesis were published in 1983 and the ten-year clinical results in 1999. A total of 12% of the knees (20 of 163) in this study were revised because of wear of the polyethylene tibial insert. Excellent stability was achieved and the incidence of aseptic component loosening was 4.3% (seven of 163). The survival rate using revision for any reason as the endpoint was 82% (95% confidence interval 76.2 to 88.0). Although this series included a relatively small number of replacements, it demonstrated that the anterior cruciate ligament, even when partially degenerated at the time of TKR, remained functional and provided adequate stability at a long-term follow-up.
24160450 Expression of iron-related proteins in the duodenum is up-regulated in patients with chron 2014 Mar 28 Mechanisms responsible for derangements in Fe homeostasis in chronic inflammatory conditions are not entirely clear. The aim of the present study was to test the hypothesis that inflammation affects the expression of Fe-related proteins in the duodenum and monocytes of patients with chronic inflammatory disorders, thus contributing to dysregulated Fe homeostasis. Duodenal mucosal samples and peripheral blood monocytes obtained from patients with chronic inflammatory disorders, namely ulcerative colitis (UC), Crohn's disease (CD) and rheumatoid arthritis, were used for gene and protein expression studies. Hb levels were significantly lower and serum C-reactive protein levels were significantly higher in patients in the disease groups. The gene expression of several Fe-related proteins in the duodenum was significantly up-regulated in patients with UC and CD. In patients with UC, the protein expression of divalent metal transporter 1 and ferroportin, which are involved in the absorption of dietary non-haem Fe, was also found to be significantly higher in the duodenal mucosa. The gene expression of the duodenal proteins of interest correlated positively with one another and negatively with Hb. In patients with UC, the gene expression of Fe-related proteins in monocytes was found to be unaffected. In a separate group of patients with UC, serum hepcidin levels were found to be significantly lower than those in the control group. In conclusion, the expression of Fe-related proteins was up-regulated in the duodenum of patients with chronic inflammatory conditions in the present study. The effects appeared to be secondary to anaemia and the consequent erythropoietic drive.