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ID PMID Title PublicationDate abstract
19004048 Inhibition of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 re 2008 Dec OBJECTIVE: To investigate whether the blockade of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) has any therapeutic effects on rheumatoid arthritis. METHODS: A functional blocking monoclonal antibody for SHPS-1 (anti-SHPS-1 mAb) was administered at various doses to collagen-induced arthritis (CIA) mice, and severity of the arthritis was evaluated by clinical and histological scores of the limbs. To clarify the mechanisms of action of the antibody, the serum concentration of anti-type II collagen antibody was measured in those mice, and in vitro experiments were conducted to determine the effects of the antibody on the induction of osteoclasts and the release of cytokines from mouse spleen cells. RESULTS: Compared with mice given control IgG, the administration of anti-SHPS-1 mAb significantly reduced the severity of inflammation and destruction of bone and cartilage in CIA mice. This therapeutic effect was observed even when the antibody treatment was started after the onset of arthritis. The appearance of anti-type II collagen antibody in CIA mice was not altered by the antibody treatment. In in vitro experiments, the anti-SHPS-1 mAb significantly inhibited osteoclastogenesis of bone marrow cells, and significantly reduced the release of interleukin 1beta (IL-1beta), IL-2, IL-12, interferon-gamma, and tumor necrosis factor-alpha, but not that of IL-4 or IL-10, from the spleen cells after stimulation with concanavalin A. CONCLUSION: Administration of a monoclonal antibody for SHPS-1 reduced the severity of arthritis in CIA mice. Regulation of biological functions of SHPS-1 may be a novel and potent strategy to treat patients with rheumatoid arthritis.
16382308 Pannus resolution after occipitocervical fusion in a non-rheumatoid atlanto-axial instabil 2006 Mar Periodontoid pseudotumor or pannus is considered to be an inflammatory mass most frequently associated with rheumatoid arthritis. Transoral resection of the pannus has been the treatment of choice for patients with associated myelopathy, followed in many instances by posterior stabilization. However, some authors have reported resolution of pannus associated with rheumatoid arthritis and other forms of chronic atlanto-axial instability only after posterior stabilization. We report a case of a 69-year-old man who presented with a rapidly progressing myelopathy due to a retro-odontoid mass produced by chronic atlanto-axial instability associated with an occipital assimilation of C1 and tight posterior fossa. An urgent posterior fossa craniectomy followed by occipitocervical fixation was performed. After surgery, the patient's clinical condition improved and 1 year after surgery was asymptomatic, walked without any help and had normal strength. Control MR showed complete resolution of the retro-odontoid pannus.
17151007 Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory 2007 May BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disease of unknown aetiology characterised by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. AIM: To propose a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions. METHODS: DBA/1J mice with collagen-induced arthritis were treated with cortistatin after the onset of disease, and the clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of various inflammatory mediators (cytokines and chemokines) in joints and serum. T helper cell type 1 (Th1)-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies. RESULTS: Cortistatin treatment significantly reduced the severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction in the two deleterious components of the disease-that is, the Th1-driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as interleukin 10 and transforming growth factor beta1. Cortistatin exerted its effects on synovial cells through both somatostatin and ghrelin receptors, showing a higher effect than both peptides protecting against experimental arthritis. CONCLUSION: This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.
18177597 Psoriatic arthritis epidemiology. 2007 Dec Recent studies have added to our knowledge of the epidemiology of psoriatic arthritis (PsA) across various populations. Absence of a standard case definition and the relative rarity of PsA may have contributed to the paucity of available data to date. Reported prevalence estimates appear to vary more than incidence estimates. Prevalence estimates may vary as a result of differences in genetic factors, exposure to environmental factors, and study methods. Although prevalence data among different subgroups and extrapolation from clinical and laboratory data allow some inferences about the role of various potential risk factors for PsA, only one study has investigated them specifically. Overall, quality of life in PsA appears similar to that in rheumatoid arthritis, whereas available data on the mortality impact of PsA are conflicting, preventing a unified conclusion. This review summarizes recent data on PsA epidemiology.
17345531 [Non-infective inflammations of the vertebral spine]. 2007 Jan Non-infective inflammations of the vertebral spine can be caused by seronegative spondylarthropathies or rheumatoid arthritis, respectively. Seronegative spondylarthropathies include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel diseases and undifferentiated arthritis. This review discusses etiology and pathogenesis, epidemiology, clinical features, diagnosis and differential diagnoses of these chronic inflammatory diseases with a special focus on vertebral involvement.
16569257 Magnetic resonance imaging in psoriatic arthritis: a review of the literature. 2006 Psoriatic arthritis is a diverse condition that may be characterized by peripheral inflammatory arthritis, axial involvement, dactylitis and enthesitis. Magnetic resonance imaging (MRI) allows visualization of soft tissue, articular and entheseal lesions, and provides a unique picture of the disease process that cannot be gained using other imaging modalities. This review focuses on the literature on MRI in psoriatic arthritis published from 1996 to July 2005. The MRI features discussed include synovitis, tendonitis, dactylitis, bone oedema, bone erosions, soft tissue oedema, spondylitis/sacroiliitis and subclinical arthropathy. Comparisons have been drawn with the more extensive literature describing the MRI features of rheumatoid arthritis and ankylosing spondylitis.
18930069 Mechanical hyperalgesia is attenuated by local administration of octreotide in pristane-in 2008 Nov 21 AIMS: The Dark-Agouti (DA) rat is very susceptible to pristane-induced arthritis (PIA) and represents a suitable model for rheumatoid arthritis. In the present study, we examined the pain sensitivity and the effect of local administration of octreotide (OCT) on mechanical hyperalgesia in PIA DA rats. MAIN METHODS: Arthritis was induced by intradermal injection of pristane (300 microl). The mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were used to evaluate the pain sensitivity. In addition, we recorded the discharge firings in the tibial nerve sensory C-fibers innervating the inflamed toe joints of arthritic DA rats. KEY FINDINGS: Two weeks after injection of pristane, all DA rats developed severe arthritis. This symptom was associated with a decreased MWT (78.50+/-5.68 mN before pristane injection, 19.50+/-6.27 mN on day 14 after pristane injection), indicating a mechanical hyperalgesia in PIA. In contrast, HWL was comparable before and after pristane injection (10.25+/-0.70 s before injection; 9.45+/-1.23 s on day 14 after injection). Local injection of OCT markedly increased MWT and relieved the hyperalgesia in PIA. In addition, OCT significantly decreased the discharge rate of afferent C units evoked by both non-noxious and noxious joint movements. SIGNIFICANCE: Taken together, the results demonstrate that mechanical hyperalgesia, but not thermal hyperalgesia is associated with PIA and that the mechanical hyperalgesia and the discharge of afferent C units are attenuated by local administration of OCT. These observations provide evidence for a novel therapeutic strategy for pain control in rheumatoid arthritis.
18641245 Radiographic evaluation of arthritis: inflammatory conditions. 2008 Aug In the presence of joint space narrowing, it is important to differentiate inflammatory from degenerative conditions. Joint inflammation is characterized by bone erosions, osteopenia, soft-tissue swelling, and uniform joint space loss. Inflammation of a single joint should raise concern for infection. Multiple joint inflammation in a proximal distribution in the hands or feet without bone proliferation suggests rheumatoid arthritis. Multiple joint inflammation in a distal distribution in the hands or feet with bone proliferation suggests a seronegative spondyloarthropathy, such as psoriatic arthritis, reactive arthritis, or ankylosing spondylitis.
16738903 Psoriasis onset during infliximab treatment: description of two cases. 2006 Oct The authors describe two patients with no personal or family history of psoriasis who developed psoriatic lesions during infliximab treatment: a woman affected by seronegative rheumatoid arthritis and a man affected by ankylosing spondylitis.
18190474 Pneumococcal septic arthritis as the initial presentation of multiple myeloma. 2008 Feb Septic arthritis induced by Streptococcus pneumoniae is an uncommon manifestation of pneumococcal infection. Pneumococcus has been identified as the inciting pathogen in only 6% of cases of septic arthritis in recent retrospective studies (Ross et al., 2003). Approximately 50% of patients with pneumococcal septic arthritis have a preceding or concurrent extra-articular focus of infection. The septic joint evolves from hematogenous seeding of the highly vascular synovial membrane by bacteria. Polyarticular disease occurs in only approximately 36% of patients. Most pneumococcal septic arthritis occurs with coexistant joint disease, prosthesis, alcoholism, HIV infection, or rheumatoid arthritis (Baraboutis & Skoutelis, 2004; Raad & Peacock, 2004). We report a case of polyarticular septic arthritis as the first manifestation of an underlying disease. Our literature review discloses that this is the first reported case of multiple myeloma initially presenting as pneumococcal septic arthritis in the USA and the third internationally (Cuesta et al., 1992; Renou et al., 2007).
18056694 Juvenile onset central nervous system folate deficiency and rheumatoid arthritis. 2008 Jan Isolated cerebral folate deficiency was detected in a 13-year-old girl with cognitive and motor difficulties and juvenile rheumatoid arthritis. Her serum contains autoantibodies that block membrane-bound folate receptors that are on the choroid plexus and diminish the uptake of folate into the spinal fluid. Whereas her serum folate exceeded 21 ng/mL, her spinal fluid contained 3.2 ng/mL of 5-methyltetrahydrofolate as a consequence of the autoantibodies diminishing the uptake of this folate.
17902637 Estrogen receptor dependent inhibitors of NF-kappaB transcriptional activation-1 synthesis 2007 Nov 1 Pathway selective ligands of the estrogen receptor inhibit transcriptional activation of proinflammatory genes mediated by NF-kappaB. Substituted 2-cyanopropanoic acid derivatives were developed leading to the discovery of WAY-204688, an orally active, pathway selective, estrogen receptor dependent anti-inflammatory agent. This propanamide was shown to be orally active in preclinical models of inflammatory diseases, such as rheumatoid arthritis, without the proliferative effect associated with traditional estrogens.
16778596 Comparison of health-related quality of life between heterozygous women with Fabry disease 2006 Jun PURPOSE: Fabry disease is an X-linked lysosomal disorder due to mutations in the GLA gene. Manifestations of the disease are documented in hemizygous males. Recent studies have indicated that women with GLA mutations may report symptoms. The impact on their health-related quality of life is unclear. This study compares the quality of life of obligate heterozygotes to a historical healthy control population and to populations with multiple sclerosis and rheumatoid arthritis. METHODS: The RAND-36 and Fabry-disease specific questions were administered to study participants. Study subjects were obligate heterozygotes for mutations in GLA. Mean scores in each of the subscales from the RAND-36 were compared between study subjects and previously published data from the Women's Health Initiative and studies on multiple sclerosis and rheumatoid arthritis. RESULTS: Comparisons between 202 study participants and the Women's Health Initiative indicated that all eight subscale scores of the RAND-36 were significantly lower for women with Fabry disease (P < 0.0001). The mean scores of the study participants more closely resembled the mean scores of the participants in the multiple sclerosis and rheumatoid arthritis studies. CONCLUSION: Study participants reported clinically important effects on health-related quality of life. It is critical to develop management protocols for this population.
27726708 NICE U-turn for life-saving drugs. 2007 Jul 1 Thousands of people with rheumatoid arthritis have been given new hope by the National Institute for Health and Clinical Excellence (NICE) which has granted an appeal overturning its decision to limit access to life-changing 'anti-TNF' drugs.
23489074 A future perspective on the development of chemokine receptor CXCR4 antagonists. 2008 Oct BACKGROUND: In the postgenome era, G-protein-coupled receptor families have been recognized as significant drug targets in medicinal chemistry. A specific chemokine receptor, CXCR4, has multiple critical functions in normal physiologies including embryonic development of the cardiovascular, hemopoietic and central nervous systems, and underlies problematic pathologies such as HIV infection, cancer metastasis, leukemia progression and rheumatoid arthritis. METHODS AND RESULTS: A tetradecamer peptide, T140, derived from the horseshoe crab, and its biologically stable derivative, 4F-benzoyl-TN14003, were found to be powerful CXCR4 antagonists that block HIV entry to cells. These peptides have also shown remarkable inhibitory activity against cancer metastasis and progression in a variety of cancers. Slow release administration of 4F-benzoyl-TN14003, for example, was found to significantly reduce pulmonary metastasis of breast cancer cells in severe combined immunodeficient mice. This peptide also shows inhibitory effects against melanoma metastasis and Epstein-Barr virus-associated lymphoproliferation in mice, suppresses the delayed-type hypersensitivity response induced by sheep red blood cells and reduced collagen-induced arthritis in both mouse models of arthritis. CONCLUSION: T140 analogues have the potential to become promising agents for chemotherapy of AIDS, cancer and rheumatoid arthritis. This review summarizes the development of low molecular weight CXCR4 antagonists based on pharmacophore identification in T140 analogues and also provides an opinion on the future of the development of CXCR4 antagonists.
28925826 Tumor necrosis factor-α inhibits chondrogenic differentiation of synovial fibroblasts thr 2008 Aug We previously reported that synovial fibroblast-like cells (SFs) can be differentiated into chondrocytes through activin receptor-like kinase (ALK) 3 activation. The aim of this study was to clarify the effect and signaling pathways of tumor necrosis factor (TNF)-α on the chondrogenic differentiation of SFs. Primary SFs from patients with rheumatoid arthritis (RA) were treated with recombinant human bone morphogenetic protein-2 or transduced with a constitutively active mutant of the ALK3 gene (ALK3(CA)) with or without TNF-α, and then cultured in pellets. Expression of chondrocyte-specific genes was analyzed by real-time polymerase chain reaction or by histological analysis. Inhibitors of mitogen-activating protein kinase (MAPK) pathways or adenovirus vectors carrying a dominant-negative mutant of the IκB kinase 2 gene (AxIKK2(DN)) were used to analyze the signaling pathways of TNF-α. Expression of chondrocyte-specific genes was induced in SFs either by rhBMP-2 treatment or by ALK3(CA) transduction, which was strongly suppressed by TNF-α treatment. TNF-α markedly increased the p38 MAPK pathways in SFs, and inhibition of p38 MAPK activation partially restored the inhibitory effect of TNF-α on the chondrogenic differentiation of SFs. Combination therapy BMP-2 and anti-TNF-α agents especially targeting p38 MAPK might be a good approach to stimulating neochondrogenesis in the damaged joints in RA.
23424348 Emerging therapies offer new methods for treating rheumatoid arthritis. 2006 Apr The approvals of abatacept and rituximab have invigorated the already competitive market for biologic RA treatments. The new generation of RA therapies now reaching the market presents opportunities for patients - and challenges for payers.
16568212 WITHDRAWN: Validation of the Tunisian version of the rheumatoid arthritis quality of life 2006 Jul 13 Ahead of Print article withdrawn by publisher
16892138 [Effect of multiple amino acid substitutions of collagen II 263-272 on collagen-induced ar 2006 Aug 18 OBJECTIVE: To evaluate the effect of multiple amino acid substitutions of C II 263-272 peptide on collagen-induced arthritis, and explore a therapeutic strategy of rheumatoid arthritis. METHODS: A panel of altered C II 263-272 peptides was synthesized with substitutions of TCR-contact residues of C II 263-272 with alanine. The competitive inhibition of APL to wild type C II 263-272 was analyzed by 3H incorporation assay. CIA model was induced by intradermal injection of bovine CII. Altered CII peptide was injected subcutaneously in different doses (1, 10, 100 microg, respectively, twice per week) after onset of CIA. The arthritis index, radiologic and histologic scores were recorded to evaluate the severity change of arthritis. Serum levels of IFN-gamma were examined by ELISA. RESULTS: Competitive inhibition to wild type C II 263-272 of the altered C II 263-272 peptides (APL1, APL2, APL3) was found in PBMC from RA patients. Among them, APL3 with substitution of residues 267(Q), 270(K) and 271(G) to A showed the most significant effect and thus was used in the treatment of CIA rats. We observed significantly reduced arthritis scores in CIA rats treated with 100 microg/dose of APL as compared with rats treated with PBS and peptide control. The mean radiographic and histologic scores was also markedly lower in APL-treated CIA rats than in PBS or peptide control-treated rats. On day 35 after immunization, the serum level of IFN-gamma in rats was examined and a significantly low level of serum IFN-gamma was found in APL-treated rats. CONCLUSION: C II 263-272 peptide with TCR-contact residues substitutions inhibited joint destruction in CIA rats and down-regulated IFN-gamma production, suggesting that altered CII peptide might be potentially therapeutic in rheumatoid arthritis.
18362310 Oral manifestations of Sjögren's syndrome. 2008 Apr Sjögren's syndrome is a common autoimmune rheumatic disease. The most common symptoms of Sjögren's syndrome are extreme tiredness, along with dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia). Saliva plays an essential role in numerous functions of the mouth. Xerostomia can be caused by medications, chronic diseases like Sjögren's syndrome, and medical treatments, such as radiation therapy and bone marrow transplant. Xerostomia can eventually lead to difficulty in swallowing, severe and progressive tooth decay, or oral infections. Despite having excellent oral hygiene, individuals with Sjögren's syndrome have elevated levels of dental caries, along with the loss of many teeth, early in the disease. Sjögren's syndrome alters the protein profile and brings about a change in the composition of saliva. There is an increase in the levels of lactoferrin, beta(2)-microglobulin, sodium, lysozyme C, and cystatin C, and a decrease in salivary amylase and carbonic anhydrase. Up to 90% of individuals with Sjögren's syndrome have antibodies targeting the Ro 60 and La autoantigens. Natural aging, regardless of Sjögren's syndrome, is also another factor that brings about a significant change in the composition of saliva. The most prevailing cause of xerostomia in elderly persons is the use of anticholinergic medications. Currently, there is no cure for Sjögren's syndrome, and treatment is mainly palliative.