Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
20523983 | PET assessment of disease activity in children with juvenile idiopathic arthritis. | 2010 Nov | BACKGROUND: The degree of 18-fluorodeoxyglucose (FDG) uptake is previously reported to correlate with physical examination and laboratory tests for evaluating disease activity in patients with rheumatoid arthritis. The clinical validity of (18)F-FDG positron emission tomography (PET) has not been evaluated in juvenile idiopathic arthritis (JIA). OBJECTIVE: To assess the relationship between (18)F-FDG PET uptake and disease activity in children with JIA. MATERIALS AND METHODS: A total of 560 joints in 28 children (mean age, 5.4 years; range, 1-16 years) with JIA who had undergone whole-body (18)F-FDG PET before treatment were retrospectively assessed clinically, biochemically and radiographically. PET images were assessed independently by two readers. We investigated the relationships between the degree of synovial (18)F-FDG uptake and radiographic and clinical symptoms and laboratory findings. RESULTS: Joint tenderness and swelling had a positive association with abnormal (18)F-FDG uptake in the joint [odds ratio (OR) 5.37, 7.12, respectively]. The standardized uptake value (SUV) max correlated with the neutrophil count, plasma C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and matrix metalloproteinase (MMP) 3. Joint erosion (OR, 6.17), soft-tissue swelling (OR, 3.77), major joints involvement (OR, 3.50), tenderness (OR, 5.22), and CRP concentration in plasma (OR, 1.81) were positively associated with SUVmax. CONCLUSION: The degree of (18)F-FDG uptake may be associated with the severity of synovitis in children with JIA. | |
21109519 | Development and preliminary validation of a paediatric-targeted MRI scoring system for the | 2011 Mar | OBJECTIVES: To develop and validate a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis (JIA). To compare the paediatric MRI score with the adult-designed. Outcome Measures in Rheumatology Clinical Trials-Rheumatoid Arthritis MRI Score (RAMRIS), whose suitability for assessing growing joints was tested. METHODS: In 66 patients with JIA the clinically more affected wrist was studied. Thirty-nine patients had a 1-year MRI follow-up. Two readers independently assigned the paediatric score and the RAMRIS to all studies. Validation procedures included analysis of reliability, construct validity and responsiveness to change. A reduced version of the bone erosion score was also developed and tested. RESULTS: The paediatric score showed an excellent reproducibility (interclass correlation coefficient >0.9). The interobserver agreement of RAMRIS was moderate for bone erosions and excellent for bone marrow oedema (BMO). The paediatric score and RAMRIS provided similar results for construct validity. The responsiveness to change of the paediatric score was moderate for synovitis and bone erosion, and poor for BMO and did not improve when RAMRIS was applied. The reduced version of the bone erosion was valuable for the assessment of joint damage, and provided time-saving advantages. CONCLUSION: The results demonstrate that the paediatric MRI score is a reliable and valid method for assessing disease activity and damage in JIA. Unexpectedly, the RAMRIS provides acceptable suitability for use in the paediatric age group. Further work, especially in a longitudinal setting, is required before defining the most suitable MRI scale for assessing growing joints. | |
20526808 | Expression of Mycobacterium leprae HSP65 in tobacco and its effectiveness as an oral treat | 2011 Apr | Transgenic plants are able to express molecules with antigenic properties. In recent years, this has led the pharmaceutical industry to use plants as alternative systems for the production of recombinant proteins. Plant-produced recombinant proteins can have important applications in therapeutics, such as in the treatment of rheumatoid arthritis (RA). In this study, the mycobacterial HSP65 protein expressed in tobacco plants was found to be effective as a treatment for adjuvant-induced arthritis (AIA). We cloned the hsp65 gene from Mycobacterium leprae into plasmid pCAMBIA 2301 under the control of the double 35S promoter from cauliflower mosaic virus. Agrobacterium tumefaciens bearing the pChsp65 plasmid was used to transform tobacco plants. Incorporation of the hsp65 gene was confirmed by PCR, reverse transcription-PCR, histochemistry, and western blot analyses in several transgenic lines of tobacco plants. Oral treatment of AIA rats with the HSP65 protein allowed them to recover body weight and joint inflammation was reduced. Our results suggest a synergistic effect between the HSP65 expressed protein and metabolites presents in tobacco plants. | |
19177262 | Lack of association between beta 2-adrenergic receptor polymorphisms and juvenile idiopath | 2009 Mar | OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune arthropathy. Beta 2-adrenergic receptors are a link between the sympathetic nervous system and the immune system. Associations between variants in the gene encoding the beta 2-adrenergic receptor (ADRB2) and autoimmune disorders such as rheumatoid arthritis (RA) have been demonstrated. We aimed to investigate ADRB2 variants for association with JIA. METHODS: Genotypes and haplotypes of two ADRB2 variants (G16R and Q27E) were determined in 348 children with JIA and 448 healthy controls by direct molecular haplotyping using melting-curve analysis of a fluorescently labelled loci-spanning probe. Case-control analysis was performed to investigate whether ADRB2 variants were associated with JIA. RESULTS: No association was found between JIA and alleles, genotypes, or haplotypes of ADRB2. Specifically, the haplotype that demonstrated a strong association with RA (R16/Q27) was not associated with JIA. None of the variants demonstrated association after stratification by JIA subtypes or gender. CONCLUSIONS: Our results indicate that ADRB2 variants are not associated with JIA or any of the major JIA subtypes. These observations suggest that, although they share several clinical and pathological features, JIA and RA have unique genetic associations. | |
19700744 | Sjögren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice. | 2009 Sep | Thrombospondin-1 (TSP-1) is a major activator of latent transforming growth factor-beta in vitro as well as in vivo. Mice deficient in TSP-1, despite appearing normal at birth, develop a chronic form of ocular surface disease that is marked by increased apoptosis and deterioration in the lacrimal gland, associated dysfunction, and development of inflammatory infiltrates that result in abnormal tears. The increase in CD4(+) T cells in the inflammatory infiltrates of the lacrimal gland, and the presence of anti-Sjögren's syndrome antigen A and anti-Sjögren's syndrome antigen B antibodies in the serum resemble autoimmune Sjögren's syndrome. These mice develop an ocular surface disorder dry eye that includes disruption of the corneal epithelial layer, corneal edema, and a significant decline in conjuctival goblet cells. Externally, several mice develop dry crusty eyes that eventually close. The inflammatory CD4(+) T cells detected in the lacrimal gland, as well as those in the periphery of older TSP-1 null mice, secrete interleukin-17A, a cytokine associated with chronic inflammatory diseases. Antigen-presenting cells, derived from TSP-1 null, but not from wild-type mice, activate T cells to promote the Th17 response. Together, these results indicate that TSP-1 deficiency results in a spontaneous form of chronic dry eye and aberrant histopathology associated with Sjögren's syndrome. | |
21078710 | A randomized controlled trial of the cost-effectiveness of ultrasound-guided intraarticula | 2011 Feb | OBJECTIVE: We studied whether sonographic needle guidance affected the outcomes of intraarticular (IA) injection for inflammatory arthritis. METHODS: Joints with inflammatory arthritis (n = 244; 76% rheumatoid arthritis, 3% small joints, 51% intermediate, and 46% large) were randomized to injection by conventional palpation-guided anatomic injection (120 joints) or sonographic image-guided injection enhanced with a 1-handed reciprocating procedure device mechanical syringe (124 joints). A 1-needle, 2-syringe technique was used. After IA placement and synovial space dilation were confirmed by sonography, a syringe exchange was performed, and triamcinolone acetonide was injected with the second syringe through the indwelling IA needle. Baseline pain, procedural pain, pain at outcome (2 weeks and 6 months), responders, therapeutic duration, reinjection rates, total cost, and cost per responder were determined. RESULTS: Relative to conventional palpation-guided methods, sonographic guidance for injection of inflammatory arthritis resulted in an 81% reduction in injection pain (p < 0.001), 35% reduction in pain scores at outcome (p < 0.02), 38% increase in the responder rate (p < 0.003), 34% reduction in the non-responder rate (p < 0.003), 32% increase in therapeutic duration (p = 0.01), 8% reduction ($7) in cost/patient/year, and a 33% ($64) reduction in cost/responder/year for a hospital outpatient (p < 0.001). CONCLUSION: Sonographic needle guidance improves the performance, clinical outcomes, and cost-effectiveness of IA injections for inflammatory arthritis. (Clinical Trial Identifier NCT00651625). | |
21794748 | [Use and application in clinical practice of the CASPAR criteria]. | 2010 Mar | Several classification criteria for psoriatic arthritis have been proposed in the literature but it is still unclear which one of them best represents the diseases' ample spectrum. None of these classification criteria have been universally accepted. New classification criteria (CASPAR) have been recently published. Their application is simple, fast and easy to perform. In addition, they show two important qualities. One is that they allow for the diagnosis of psoriatic arthritis even when there is no skin disease present at the moment of diagnosis. The other is is that it enables us to classify a patient as having psoriatic arthritis in spite of a positive rheumatoid factor. The CASPAR criteria have a sensitivity of 91.4% and a specificity of 98.7%. It seems, in contrast, that it is not as high for recent-onset psoriatic arthritis. Therefore establishing the definition of inflammatory arthritis becomes paramount. | |
21120997 | Matrix metalloproteinase 8 deficiency in mice exacerbates inflammatory arthritis through d | 2010 Dec | OBJECTIVE: Neutrophil accumulation is balanced by both cell infiltration and cell clearance, the controls of which are pivotal in the pathogenesis of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Of the neutrophil-specific proteases, matrix metalloproteinase 8 (MMP-8; also known as neutrophil collagenase or collagenase 2) is traditionally viewed as being crucial for collagen degradation and hence cell migration and infiltration. This study was undertaken to examine the role of MMP-8 in a murine model of spontaneous RA. METHODS: MMP-8(-/-) mice were backcrossed onto the Fas-defective MRL/lpr background, a mouse strain characterized by systemic autoimmunity including spontaneous autoimmune arthritis. Arthritis was induced with Freund's complete adjuvant and clinical disease and histologic parameters were assessed. RESULTS: MMP-8(-/-) mice had earlier and more severe joint inflammation than their MMP-8(+/+) counterparts, coupled with a massive accumulation of neutrophils in synovial tissue, an unexpected result considering the commonly held view that MMP-8 has important extracellular matrix-degradative functions. Protease and protease inhibitor analysis of MMP-8(-/-) mouse neutrophils by CLIP-CHIP microarray revealed very little additional change in protease levels except for low expression of the apoptosis initiator caspase 11. This was confirmed at the protein level in unstimulated, lipopolysaccharide-treated, and interferon-γ-treated MMP-8(-/-) mouse neutrophils. Downstream of caspase 11, the activity of the apoptosis executioner caspase 3 was consequently reduced in MMP-8(-/-) mouse neutrophils, translating to reduced neutrophil apoptosis and cell accumulation compared with wild-type mouse cells. CONCLUSION: Our findings indicate that MMP-8 is not essential for neutrophil migration in arthritis and likely other autoimmune diseases. Rather, MMP-8 is important for normal rates of neutrophil apoptosis and hence regulates cell clearance. Because MMP-8 deficiency leads to an exaggerated accumulation of neutrophil infiltrates due to delayed apoptosis and concurrent pathologic changes associated with dramatically increased neutrophil infiltration, MMP-8 is antiinflammatory and therefore a drug antitarget in the treatment of arthritis. | |
20936538 | Attenuation of arthritis in rodents by a novel orally-available inhibitor of sphingosine k | 2011 Apr | Pro-inflammatory cytokines like TNF-α activate sphingosine kinase (SK). Therefore, inhibition of SK is a potential molecular target for the treatment of rheumatoid arthritis. AIMS: The primary goal of this study was to assess the efficacy of ABC249640 (a selective SK-2 inhibitor) in two models of rodent arthritis. A secondary goal was to evaluate the pharmacological profile of ABC294640, when given in combination with methotrexate. METHODS: The efficacy of ABC294640 was determined by paw diameter/volume measurements, histological evaluations, and micro-CT analyses. RESULTS: ABC294640 attenuated both collagen-induced arthritis in mice, as well as adjuvant-induced arthritis in rats. With the adjuvant arthritis model, the prophylactic efficacy profile of ABC294640 was similar to indomethacin. Of note, ABC294640 reduced the bone and cartilage degradation, associated with adjuvant-induced arthritis. Rats treated with a suboptimal dose of MTX (50 μg/kg/day) in combination with ABC249640 (100 mg/kg/day) had better anti-arthritis effects in the adjuvant model, than treatment with either agent alone. CONCLUSION: Our results suggest that ABC249640 is an orally available drug candidate with a good pre-clinical efficacy profile for the prevention and/or treatment of RA. | |
19914365 | Anti-inflammatory effect of Sanshuibaihu decoction may be associated with nuclear factor-k | 2010 Feb 3 | Sanshuibaihu decoction (SSBH) is an anti-arthritic Chinese herbal formula which has been used in the treatment of rheumatoid arthritis (RA) for many years. We herein aimed to confirm its anti-arthritic effect and explore the potential mechanism of action on collagen-induced arthritis (CIA) in rats. CIA was induced by immunizing 50 female Wistar rats with bovine type II collagen. 13 days following the immunization rats with CIA were treated with SSBH (50mg/kg), leflunomide (LEF) (10mg/kg) and physiological saline for 30 days, and rats without CIA were left untreated. After the treatment, paw edema was obviously improved in SSBH-treated rats, with the significant difference of arthritis score (F=6.032, P=0.006) observed between the three treated groups. In pathological observation, SSBH-treated rats showed a significant improvement of inflammatory infiltration, synovial hyperplasia, cartilage and bone destruction and joint fusion. After the treatment of SSBH, radiological score of knee (t=11.504, P=0.000) and ankle joints (t=9.250, P=0.000) was decreased significantly. In situ hybridization on joint tissue section indicated only slight synovial hyperblastosis and expression of NF-kappaB in SSBH-treated rats. Image analysis indicated a significant difference of means of integrated optical density (MIOD) (F=3.956, P=0.040) and means of stained area (MSA) (F=3.867, P=0.032) of NF-kappaB between the three treated groups. MIOD and MSA of SSBH-treated group were significantly lower vs control. Enzyme linked immunosorbent assay (ELISA) showed a significant difference (F=10.167, P=0.000) of the amount of p-p38 MAPKalpha in the three treated groups. The detected amount of p-p38 MAPKalpha in SSBH-treated group was significantly lower vs control. These results show SSBH has an inhibiting effect on CIA, which may be associated with NF-kappaB and p38 MAPKalpha. | |
19735175 | Dietary vitamin E and quercetin modulate inflammatory responses of collagen-induced arthri | 2009 Aug | Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints. This study investigated whether or not a diet deficient in vitamin E is a possible risk factor in the development of RA and evaluated the efficacy of antioxidant supplementation. Male DBA/1J mice were maintained on either a control diet (C) or a vitamin E-depleted (-VE) diet for 4 weeks before arthritis induction. The mice in the control group were subdivided into the control group (C/C), the 0.05% alpha-tocopherol-supplemented group (C/+VE), and the 0.5% quercetin-supplemented group (C/+Q). The vitamin E-depleted group was subdivided into the -VE group (-VE/-VE), the 0.05% alpha-tocopherol-supplemented group (-VE/+VE), and the 0.5% quercetin-supplemented group (-VE/+Q) (in total, six groups, 27 mice per group). The mice were maintained on the experimental diets for 9 weeks. Study results indicate that the -VE/-VE group showed higher joint tissue tumor necrosis factor-alpha and interleukin-1beta mRNA expressions, whereas alpha-tocopherol or quercetin supplementation reduced tissue cytokine mRNA levels to values comparable to those of the C/C group. The mice fed the -VE/-VE diet exhibited higher levels of circulating macrophage chemoattractant protein 1, nitric oxide, and prostaglandin E(2) compared to those in other groups. Supplementation with alpha-tocopherol or quercetin in mice fed -VE diet decreased these markers similar to those of the mice in the C/C group. No supplementation effect was observed, however, in the mice fed with the control diet prior to RA induction. These results suggest that dietary deficiency of vitamin E increases inflammatory responses and that antioxidants successfully suppress the inflammatory responses. However, significant clinical improvement may require longer observation. | |
21417026 | [The identification and advances of regulatory B cells]. | 2009 Oct | B cells are typically characterized by their ability to regulate the immune responses through presenting antigens and producing antibodies. However, a novel B cell subset, named regulatory B cells (Bregs), has been identified. As Tregs, the Bregs are capable of performing both pathogenic and regulatory functions by production of suppressive cytokines, such as IL-10 or TGF-beta1, or by interaction with pathogen T cells or other immune cells. Recent studies indicate that the Bregs play a critical role in the development and resolution of multiple chronic diseases, including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalomyelitis. The identification and the clarification of action mechanisms of the Bregs will greatly contribute to understanding the mechanisms of immune tolerance comprehensively and deeply, and to develop the rational therapeutic strategies for arthritis, diabetes, multiple sclerosis, infectious diseases and cancer, etc. In this review, we summarized the recent insights of identification, characterizations, development, and regulation mechanisms of Bregs and these cells' contribution to the pathogenesis of inflammatory diseases. | |
20425532 | Use of rituximab in the antiphospholipid syndrome. | 2010 Feb | B cells are promising targets for treatment in autoimmune diseases. Rituximab, a chimeric anti-CD20 monoclonal antibody that depletes B cells, is approved for use in rheumatoid arthritis and is often used to treat refractory autoimmune thrombocytopenia. There is increasing interest in using rituximab in other autoimmune diseases, including the antiphospholipid syndrome. We reviewed the published clinical experience of rituximab use in patients with the antiphospholipid syndrome. Data are limited to case reports and small case series. In 19 of 21 reported cases, rituximab appeared to have a beneficial clinical effect. Antiphospholipid antibodies levels were significantly decreased in ten of 12 cases. Controlled clinical trials are needed to determine if rituximab is effective in the antiphospholipid syndrome. | |
18555649 | Managing skin necrosis and prosthesis subluxation after total knee arthroplasty. | 2009 Feb | Skin necrosis and prosthetic subluxation are dreaded complications after total knee arthroplasty. It can result in deep infection with subsequent failure of prosthesis. The incidence of infection in patients with rheumatoid arthritis who undergo knee arthroplasty is high when compared to patients with primary osteoarthritis. The gastrocnemius muscle flap has been described for cover of proximal tibia and tendon loss because of malignancy and has been used as a bridge graft in trauma patients with patellar tendon loss. We describe a patient with total knee arthroplasty with anterior knee skin necrosis and prosthesis subluxation because of attenuation and loss of continuity of patellar tendon. This was managed by using gastrocnemius bridge grafting. Here, the gastrocnemius bridge graft was used as a soft tissue cover as well as a dynamic anterior stabilizer for the prosthesis. | |
19601788 | Progress towards the identification of new aggrecanase inhibitors. | 2009 | Degenerative diseases are still a challenging issue in clinical therapy; even though in several cases it is possible to treat symptoms, drugs able to block disease progression are lacking at present. Osteoarthritis (OA) and Rheumatoid Arthritis (RA) are degenerative diseases leading to serious cartilage destruction, affecting joint functions and giving rise to restricted movement, pain and chronic disability. Current clinical treatment for arthritis is confined to Non Steroidal Anti-Inflammatory Drugs (NSAIDs), which are effective in treating symptoms but fail to block the progression of the disease. Matrix Metalloproteases (MMPs) inhibitors have been clinically studied as possible drugs for cartilage degradation prevention. However, their clinical use has been limited by severe side-effects. Aggrecan, which plays a fundamental role in maintaining the structural and mechanical properties of cartilage, has recently been found to be specifically cleaved by "aggrecanases". Aggrecanases are multidomain zinc metalloproteases, different from MMPs, which cleave the aggrecan within the interglobular domain (IGD). Aggrecan breakdown at this site has been found to be crucial for cartilage degradation. These new findings re-addressed the interest of the research for new arthritis therapeutic agents focusing on aggrecanases rather than on MMPs. This review is meant to provide a critical appraisal of the ongoing developments of Zn-chelating and non chelating aggrecanase inhibitors, with a particular emphasis on the related structure-activity relationships (SARs), in the light of the protein structural information recently made available. | |
20461114 | Arterial distensibility in chronic inflammatory rheumatic disorders. | 2010 Feb 23 | The pulse wave velocity (PWV), as an indicator of arterial distensibility, may play an important role in the stratification of patients based on the cardiovascular risk. PWV inversely correlates with arterial distensibility and relative arterial compliance. Decreased arterial distensibility alters arterial blood pressure and flow dynamics, and disturbes coronary perfusion. Systemic immune and inflammatory diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased morbidity and mortality, predominantly due to adverse cardiovascular events. Systemic inflammation in these disorders may alter arterial compliance and arterial distensibility and, through this effect, lead to accelerated atherosclerosis. We have demonstrated an increase in the carotid-femoral (aortic) PWV that is a technique in which large artery elasticity is assessed from analysis of the peripheral arterial waveform, in patients with chronic inflammatory conditions such as RA, SLE, familial Mediterranean fever (FMF), Wegener's granulomatosis (WG), sarcoidosis, psoriasis and psoriatic arthritis except Behçet's disease (BD). In this review, the issue of arterial stiffness in RA, SLE, as well as WG, psoriasis, FMF, BD, sarcoidosis, systemic sclerosis (SS) and Takayasu's arteritis (TA) is overviewed. | |
20074447 | Assessment instruments for patients with fibromyalgia: properties, applications and interp | 2009 Sep | A comprehensive assessment of the multiple symptom domains associated with fibromyalgia (FM) and the impact of FM on multidimensional aspects of function should form a routine part of the care of FM patients. Clinical trials and long-term clinical registries have used various outcome measures, but the key domains include pain, fatigue, disturbed sleep, physical functioning, emotional functioning, patient global ratings of satisfaction, and their health-related quality of life (HRQL). A number of measures have been ''borrowed'' from the fields of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and adapted to FM, and others are being developed specifically for FM. However, despite the burgeoning theoretical literature and the proliferation of instruments for measuring various health status domains, no unified approach has been developed and there is little agreement concerning the meaning of the results. There is, therefore, still a need for further consensus and the development of a core set of measures and response criteria, more refined measuring instruments, standardised assessor training, cross-cultural adaptations of health status questionnaires, electronic data capture, and the introduction of standardised quantitative measurements into routine clinical care. This article discusses the advantages and limitations of a selection of both newly developed and well-established and validated distress screening instruments that underlines the continuing challenge of assessing FM. | |
21234398 | Immunomodulation of Autoimmune Arthritis by Herbal CAM. | 2011 | Rheumatoid arthritis (RA) is a debilitating autoimmune disease of global prevalence. The disease is characterized by synovial inflammation leading to cartilage and bone damage. Most of the conventional drugs used for the treatment of RA have severe adverse reactions and are quite expensive. Over the years, increasing proportion of patients with RA and other immune disorders are resorting to complementary and alternative medicine (CAM) for their health needs. Natural plant products comprise one of the most popular CAM for inflammatory and immune disorders. These herbal CAM belong to diverse traditional systems of medicine, including traditional Chinese medicine, Kampo, and Ayurvedic medicine. In this paper, we have outlined the major immunological pathways involved in the induction and regulation of autoimmune arthritis and described various herbal CAM that can effectively modulate these immune pathways. Most of the information about the mechanisms of action of herbal products in the experimental models of RA is relevant to arthritis patients as well. The study of immunological pathways coupled with the emerging application of genomics and proteomics in CAM research is likely to provide novel insights into the mechanisms of action of different CAM modalities. | |
20392262 | Functions of nuclear factor kappaB in bone. | 2010 Mar | Nuclear factor kappaB (NF-kappaB) is a set of multifunctional transcription factors that regulate expression of genes involved in numerous normal cellular activities. They also are activated in many inflammatory and neoplastic conditions in which their expression may be stimulated by proinflammatory cytokines. NF-kappaB, in turn, regulates the expression of cytokines and so can mediate autocrine self-amplifying cycles of cytokine release and NF-kappaB activation, leading to maintenance of inflammatory reactions beyond the initial stimulus, as seen in rheumatoid arthritis and asthma. Since discovery of the requirement of NF-kappaB for basal and cytokine-induced osteoclast formation in the mid-1990s, much has been learned about the role of NF-kappaB in bone. NF-kappaB has roles in skeletal development, endochondral ossification, osteoclast and osteoblast functions, and common bone diseases. NF-kappaB inhibitors have been developed, but none have made it to clinical trials for the treatment of common bone diseases. Here we review the roles for NF-kappaB in bone and in common bone diseases. | |
20101428 | Local effects of intra-articular corticosteroids. | 2010 Apr | Intra-articular corticosteroid injection (IACI) is a very popular procedure. In this review, we wanted to review all that had been published about local effects of IACIs. English literature search was made through PubMed using the terms intra-articular and local effect. Effects on subjective, functional, structural, cellular, humoral, molecular, and imaging aspects were included. Also, all local adverse effects were documented. The main beneficial effect of IACI is pain relief. The duration of this effect is variable and depends on underlying disease, type of disease, amount of structural damage, type of IACI, dose of IACI, presence of joint effusion, level of inflammatory mediators, emptiness of joint effusion, availability of imaging, and others. At large, inflammatory problems had higher rate of favorable response in terms of pain and function. IACI at the knee joint in juvenile idiopathic arthritis patients resulted in remission for >6 months in >80% of the patients with a mean duration of approximately 1.2 years, while in the osteoarthritic knee there was a pain relief for 3 weeks only and in rheumatoid arthritis (RA) knee for 8 weeks. There was no joint space loss at the knee joint following multiple IACI in osteoarthritis and also no increase in cartilage or bone erosions in RA following a single IACI. IACI guide imaging is important in achieving better results in particular joints. Joint infection rate is very low. Other adverse effects included intra-articular and periarticular calcifications, cutaneous atrophy, cutaneous depigmentation, avascular necrosis, rapid destruction of the femoral head, acute synovitis, Charcot's arthropathy, tendinopathy, Nicolau's syndrome, and joint dislocation. IACI is associated with a wide range of local effects. Subjective and functional favorable response is prominent mainly in juvenile idiopathic arthritis patients. Adverse effects are either rare or insignificant. |