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ID PMID Title PublicationDate abstract
19734733 Liver abnormalities in adult onset Still's disease: a retrospective study of 77 Chinese pa 2009 Sep OBJECTIVE: Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology, characterized by high fever, transient cutaneous rash, arthralgia/arthritis, and leukocytosis. Liver involvement in AOSD has been described, but few reports have described it in depth. The present study analyzed clinical and laboratory features in a series of Chinese AOSD patients. METHODS: Data of 77 patients with AOSD (fulfilling Yamaguchi's diagnostic criteria) were retrospectively reviewed and compared with other series. RESULTS: The characteristics of our patients are similar to those reported in the literature. Hepatomegaly occurred in 11.7% of the cases; abnormal liver enzymes in 62.3% mild cytolysis (level of transaminases <2 N) (23.4%), moderate cytolysis (between 2 and 5 N) (23.4%), severe cytolysis (>5 N) (15.6%), and increase in the level of alkaline phosphatase (32.9%), gamma-glutamyltransferase (48.1%), lactic dehydrogenase (69.0%). Complete recovery occurred in all patients, except for 1 who died of severe liver failure and complications. CONCLUSION: AOSD is a systemic disease, and the present study reemphasizes the high frequency of liver involvement. Although it was slight to moderate in most cases, severe cytolytic hepatitis has been described. Treatment for AOSD patients with liver involvement aimed mainly at AOSD itself and most of the patients with liver involvement got complete remission with systemic corticosteroid therapy.
19614726 Xerostomia in Sjögren's syndrome and lupus erythematosus: a comparative histological and 2010 Apr BACKGROUND: Xerostomia is a symptom that can be triggered by chronic diseases such as Sjögren's syndrome (SS) and lupus erythematosus (LE). Many authors regard most cases of salivary hypofunction in LE to secondary SS. Others believe that salivary changes in patients with LE might reflect a multisystem presentation of the disease. The present study compared histopathological and direct immunofluorescence (DIF) alterations in salivary glands of patients with xerostomia and diagnosis of LE or SS. METHODS: Twenty-eight salivary gland biopsies from patients with xerostomia and diagnosed with LE or SS were submitted to histopathological and DIF exams. RESULTS: From the 28 patients, 16 had SS and 12 had LE. In SS, a moderate to intense sialadenitis was detected, with infiltration and destruction of excretory salivary ducts. In LE, mild/moderate sialadenitis with thickening and hyalinization of the ductal basement membrane was observed. DIF revealed that 50% of SS patients presented intercellular ductal IgA deposits, whereas 58% of LE patients showed deposits of IgG in the ductal basement membrane. CONCLUSIONS: Alterations in salivary glands of LE patients may be a specific manifestation of the disease (lupus sialadenitis), reflecting its multisystemic presentation, instead of an association of secondary SS and LE.
18930990 Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjög 2009 Oct OBJECTIVES: To compare the prevalence and pattern of neuropsychiatric (NP) syndromes observed in systemic lupus erythematosus (SLE) to patients with Primary Sjögren syndrome (PSS) using the American College of Rheumatology (ACR) criteria for the 19 NP syndromes seen in SLE. METHODS: A population-based study was conducted including 68 patients with SLE (mean (SD) age 43.8 (13.6) years) and 72 with PSS (age 57.8 (13.0) years). Specialists in internal medicine, neurology and neuropsychology performed standardised examinations. Cerebral MRI scans and neurophysiological studies were performed in all patients. RESULTS: Similar prevalences in SLE and PSS were observed for headaches (87% vs 78%, p = 0.165), cognitive dysfunction (46% vs 50%, p = 0.273), mood disorders (26% vs 33%, p = 0.376), anxiety disorders (12% vs 4%, p = 0.095), cranial neuropathy (1% vs 4%, p = 0.339) and seizure disorders (7% vs 3%, p = 0.208). Cerebrovascular disease was more common in SLE than PSS (12% vs 3%, p = 0.049); but mononeuropathy (0% vs 8%, p = 0.015) and polyneuropathy (18% vs 56%, p<0.001) were less common in SLE than PSS. Other syndromes were rare or absent in both patient groups. CONCLUSIONS: Headache, cognitive dysfunction and mood disorders are common in both diseases, but otherwise there are distinct differences in NP involvement, with cerebrovascular diseases more prevalent in SLE and neuropathies more common in PSS. This indicates that some NP disease mechanisms are shared while others differ between the two diseases.
20652270 Renal thrombotic microangiopathies/thrombotic thrombocytopenic purpura in a patient with p 2013 Jan Thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP) is a rare but potentially lethal condition requiring rapid recognition, diagnosis, and initiation of therapy. We experienced a case of a 61-year-old woman with primary Sjögren's syndrome (pSS) complicated with severe renal TMA/TTP following IgM monoclonal gammopathy of undetermined significance (MGUS). She was admitted to our hospital for further evaluation of hypergammaglobulinema, acute renal failure, and severe thrombocytopenia. She had been diagnosed with pSS 13 years prior to admission. Histological examination of her kidney revealed fibrin thrombi in the glomeruli and arterioles, a finding that is consistent with TMA/TTP. The patient was subsequently treated with plasma exchange, which resulted in a successful outcome without any complications. This rare case suggests that it is important to make a therapeutic decision based on appropriate and prompt pathological diagnosis.
20355334 Effect of yeast superoxide dismutase treatment on some mediators of inflammation during ad 2010 Jan * Author for correspondence and reprint requests Z. Naturforsch. 65c, 141-147 (2010); received June 17/July 21, 2009 The superoxide radical (O2-), hydrogen peroxide (H2O2) and nitric oxide (NO) are pleiotropic inflammatory mediators which play an important role in inflammatory joint diseases. They are overproduced during rheumatoid arthritis and its experimental model - adjuvant-induced arthritis in rodents--and may be detected both systemically and intra-articularly. Their secretion is up-regulated by proinflammatory cytokines such as IFN-gamma, IL-12, IL-6 and TNF-alpha, and they are responsible for the destruction of joint tissue. In this work, the effect of superoxide dismutase (SOD) from a thermotolerant yeast strain, Kluyveromyces marxianus, on the production of proinflammatory cytokines, reactive oxygen and nitrogen species was studied. Mice received three intraperitoneal injections of yeast SOD at a dose of 10 mg/ kg body weight (30,000 U/kg) on consecutive days starting on the day after arthritic induction. On days 3, 8 and 14 post induction peritoneal macrophages were isolated and both spontaneous and stimulated production of reactive oxygen and nitrogen metabolites were measured. Early in arthritic development yeast SOD treatment did not influence the O2- production, but on day 14 both spontaneous and PMA-induced secretion were dramatically reduced. Spontaneous H2O2 release was inhibited on day 14, while PMA-stimulated production was decreased from the beginning of the arthritic development. Yeast SOD treatment effectively suppressed the spontaneous and recombinant mouse IFN-gamma + LPS induced release of NO as well. Serum levels of proinflammatory cytokines, IL-12, IFN-gamma, IL-6 and TNF-alpha, were also significantly reduced. The obtained results show some of the mechanisms of action of SOD in reducing the severity of arthritic inflammation. Besides direct inhibition of joint tissue destruction exogenous SOD substantially limits the existing positive feedback between secretion of reactive oxygen species and inflammatory cytokine production.
19030778 Comparison of anti-rheumatic effects of local RNAi-based therapy in collagen induced arthr 2009 RNA interference (RNAi) provides a powerful means of sequence-specific gene silencing. Several studies show that RNAi may provide promising strategies to treat human diseases by suppressing disease responsible genes in vivo. In locomotor diseases, the progression of collagen-induced arthritis (CIA) is suppressed by tumor necrosis factor-alpha (TNF-alpha)-specific small interfering RNA (siRNA) delivered into the joint. The aim of this study, is to compare the effects of intraarticularly administered siRNAs targeting TNF-alpha, interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and receptor activator of NF-kappaB ligand (RANKL) on CIA in rats. We confirmed that the silencing effects of siRNA duplexes specific for rat TNF-alpha, IL-1beta, IL-6 and RANKL in vitro. Each siRNA was also delivered into the knee joint of CIA rats by the in vivo electroporation method 7, 10, 13 and 16 days after immunization with collagen. Local delivery of TNF-alpha or IL-1beta-specific siRNA ameliorated CIA in rats effectively at the gross morphological, radiographical and histological evaluations. Our results suggested that TNF-alpha and IL-1beta were the cytokines to be targeted in the joint for the treatment of rheumatoid arthritis. The in vivo siRNA transfection method may be useful for selection of target molecules to be silenced for treatment of joint diseases.
20716449 Regulatory effect of vasoactive intestinal peptide on the balance of Treg and Th17 in coll 2010 Vasoactive intestinal peptide (VIP) is a well-known anti-inflammatory neuropeptide. The capacity of VIP can be exhibited through inhibiting inflammatory responses, shifting the Th1/Th2 balance in favor of anti-inflammatory Th2 immunity and inducing regulatory T cells (Tregs) with suppressive activity. In addition to pro-inflammatory Th1 response, Th17 are also believed to play important roles in the pathogenesis of rheumatoid arthritis (RA). In this study, we used collagen-induced arthritis (CIA) model in Wistar rats to investigate the role of VIP in the balance of CD4(+) CD25(+) Tregs and Th17 on RA. Data presented here showed that administration of VIP decreased incidence and severity of CIA. Disease suppression was associated with the upregulation of CD4(+) CD25(+) Tregs, downregulation of Th17- and Th1-type response and influence on the RANK/RANKL/OPG system. The results provide novel evidence that the therapeutic effects of VIP on CIA rats were associated with the balance of CD4(+) CD25(+) Tregs and Th17.
21188452 Therapeutic effect of D1-like dopamine receptor antagonist on collagen-induced arthritis o 2011 Jun Dopamine activates D1-like and D2-like receptors (D1R and D2R). While D1R antagonists have ameliorated the severity of disease in some experimental autoimmune models of mice by promoting interferon (IFN)-γ and inhibiting interleukin (IL)-17 production by T cells, dopamine effects in the immune system are reportedly diverse. To investigate the impact of D1R blockade on an animal model of rheumatoid arthritis (RA), DBA/1 mice with collagen-induced arthritis (CIA) were treated with a selective D1R antagonist, SCH23390, after the primary immunization. This treatment suppressed the severity of the CIA. Nevertheless, serum levels of antibodies to type II collagen were not affected by the treatment. Th1/Th17 differentiation of splenic T cells in the treated animals was not biased. In vitro, when bone marrow-derived macrophages were stimulated in the presence of the D1R antagonist SCH23390, alteration of inflammatory cytokine expression was not observed, but their in vitro differentiation to osteoclasts was inhibited. Co-administration of a selective D1R agonist, A68930, abrogated the in vivo anti-arthritic effect and the in vitro suppression of osteoclastogenesis by the D1R antagonist. Our results argue that D1R blockade is potentially a new approach to the treatment of RA. Its effect could be partly attributable to the inhibition of osteoclastogenesis.
20517889 Exercise prevents the effects of experimental arthritis on the metabolism and function of 2010 Jun Active lymphocytes (LY) and macrophages (MPhi) are involved in the pathophysiology of rheumatoid arthritis (RA). Due to its anti-inflammatory effect, physical exercise may be beneficial in RA by acting on the immune system (IS). Thus, female Wistar rats with type II collagen-induced arthritis (CIA) were submitted to swimming training (6 weeks, 5 days/week, 60 min/day) and some biochemical and immune parameters, such as the metabolism of glucose and glutamine and function of LY and MPhi, were evaluated. In addition, plasma levels of some hormones and of interleukin-2 (IL-2) were also determined. Results demonstrate that CIA increased lymphocyte proliferation (1.9- and 1.7-fold, respectively, in response to concanavalin A (ConA) and lipopolysaccharide (LPS)), as well as macrophage H(2)O(2) production (1.6-fold), in comparison to control. Exercise training prevented the activation of immune cells, induced by CIA, and established a pattern of substrate utilization similar to that described as normal for these cells. Exercise also promoted an elevation of plasma levels of corticosterone (22.2%), progesterone (1.7-fold) and IL-2 (2.6-fold). Our data suggest that chronic exercise is able to counterbalance the effects of CIA on cells of the IS, reinforcing the proposal that the benefits of exercise may not be restricted to aerobic capacity and/or strength improvement.
21794746 [Diagnosing early spondyloarthritis in Spain: the ESPeranza program]. 2010 Mar Spondyloarthropathies are a group of diseases with an important social and health-care impact. Their prevalence is not low, affecting around 1,9% of the general population and represents around 13% of patients of the Spanish Rheumatology departments, according to the National Spondyloarthropathy Validation Study. On the other hand, it is estimated that ankylosing spondylitis, the paradigmatic disease in the group, leads to a mean yearly loss of work of 62 days per patient, leading 20% of patients to change professions and another 20% to a situation of permanent incapacity. However, up to this moment it has not received the same degree of attention as other rheumatic diseases, such as rheumatoid arthritis or osteoporosis.
19507500 [Genetics of autoimmune and collagen diseases]. 2009 Jun Most of autoimmune and collagen diseases such as rheumatoid arthritis and systemic lupus erythematosus are multifactorial diseases, where both genetic and environmental factors are involved in their pathogenesis. Recent progress in the genetic study of disease has enabled us to perform genome-wide scanning of disease susceptibility genes and brought us a new picture of disease mechanism. We herein review the recent findings of genetic studies on autoimmune and collagen diseases. Some of disease-susceptibility genes like PTPN22 and CTLA4 are shared in common among different diseases, while other genes contribute to a specific disease, suggesting combination of genetic predispositions may determine an individual's pathophysiology.
20038877 Intravenous administration of antineoplastic drugs: review of basics and what's new in 200 2009 Sep Today, newer treatment regimens combine chemotherapy with targeted therapy, based on an improved understanding of cancer pathophysiology. New diagnostic testing with microarray technology is helping to identify mutational sequences in patient tumors, so individualized treatment of cancer will occur during our lifetime. The administration of IV antineoplastic drugs continues to be an important role of infusion nurses. In addition, this therapy has also found a niche in the treatment of nonmalignant conditions such as rheumatoid arthritis. This article reviews the fundamentals of administration of IV antineoplastic drugs and current issues and trends.
21686950 Lymphoproliferative disorder due to sulphasalazine. 2009 We present the case of a 57-year-old man who had been on sulphasalazine for 20 years for seropositive non-erosive rheumatoid arthritis and developed a lymphoproliferative disorder, which resolved completely on cessation of sulphasalazine. This is the first report of lymphoproliferative disorder secondary to sulphasalazine. Lymphoproliferative disorders are well recognised with methotrexate and cyclosporine, and recognition of this disorder is critical due to the fact that a number of patients' symptoms will resolve completely with discontinuation of the drug and will not need further treatment. This case report discusses the literature on lymphoproliferative disorders as well as differential diagnoses like drug rash with eosinophilia and systemic symptoms (DRESS) syndrome.
19337742 [Cellular therapy in autoimmune disease]. 2009 Jun In addition to natural thymus-derived regulatory T-cells (Tregs), peripherally-induced Tregs are of central importance in immune homeostasis. Homotypic interactions between activated effector T-cells and resting memory T-cells induced the generation of IL-10 and IFNgamma producing Tregs in vitro. This mechanism in Treg development allows new insights into T-cell vaccination, which has been employed in pilot trials of multiple sclerosis and rheumatoid arthritis with promising results.
20506183 Attenuation of pain and inflammation in adjuvant-induced arthritis by the proteasome inhib 2010 Jul OBJECTIVE: In rheumatoid arthritis (RA), pain and joint destruction are initiated and propagated by the production of proinflammatory mediators. Synthesis of these mediators is regulated by the transcription factor NF-kappaB, which is controlled by the ubiquitin proteasome system (UPS). The present study explored the effects of the proteasome inhibitor MG132 on inflammation, pain, joint destruction, and expression of sensory neuropeptides as markers of neuronal response in a rat model of arthritis. METHODS: Arthritis was induced in rats by injection of heat-killed Mycobacterium butyricum. Arthritis severity was scored, and nociception was evaluated by mechanical pressure applied to the hind paw. Joint destruction was assessed by radiologic and histologic analyses. NF-kappaB DNA-binding activity was analyzed by electromobility shift assay, and changes in the expression of the p50 NF-kappaB subunit and the proinflammatory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) were detected by immunohistochemistry. RESULTS: Arthritic rats treated with MG132 demonstrated a marked reduction in inflammation, pain, and joint destruction. The elevated DNA-binding activity of the NF-kappaB/p50 homodimer and p50, as well as the neuronal expression of SP and CGRP, observed in the ankle joints of arthritic rats were normalized after treatment with MG132. CONCLUSION: In arthritic rats, inhibition of proteasome reduced the severity of arthritis and reversed the pain behavior associated with joint inflammation. These effects may be mediated through the inhibition of NF-kappaB activation and may possibly involve the peripheral nervous system. New generations of nontoxic proteasome inhibitors may represent a novel pharmacotherapy for RA.
20157785 Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute and chroni 2010 Jun The present study was undertaken to assess the activity/anti-inflammatory potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea, turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally, significantly inhibited the castor oil-induced diarrhoea and turpentine oil-induced exudative joint oedema in a dose-dependent manner. Significant inhibitory effect of L. usitatissimum fixed oil was observed in formaldehyde-induced proliferative global oedematous arthritis when given intraperitoneally, with significant checking of the serum glutamic oxaloacetic acid transaminase and serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil showed a significant dose-dependent protective effect against CFA-induced arthritis as well. Secondary lesions produced by CFA due to a delayed hypersensitivity reaction were also reduced in a significant manner. Anti-inflammatory activity of L. usitatissimum fixed oil can be attributed to the presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3) having dual inhibitory effect on arachidonate metabolism resulting in suppressed production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished vascular permeability. These observations suggest possible therapeutic potential of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid arthritis.
21199477 Therapeutic effects of astragalus polysaccharides on inflammation and synovial apoptosis i 2010 Oct BACKGROUND: Rheumatoid arthritis (RA), an autoimmune disease, is characterized by pronounced inflammation and cell accumulation within affected joints. Beneficial effects of active ingredients of the astragalus root (Radix astrogali) in treatment of immunological diseases have been previously observed, but the mechanisms are not well understood. This study aims to evaluate therapeutic effects and the mechanisms of astragalus polysaccharides (APS) on adjuvant-induced arthritis (AA) in rats. METHODS: Effects of treatment of AA rats with increasing doses of APS, Tripterygium glycosides (positive control) and saline (negative control) on swelling, arthritic index, synovial cell accumulation, serum concentrations of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), synovial apoptosis and immunostaining for Bcl-2 and Bax were determined. RESULTS: APS treatment reduced cell accumulation, swelling and arthritic index of the joints and serum concentrations of TNF-α and IL1-β in a dose-dependent manner in AA rats. Synovial cell apoptosis was elevated in response to APS treatment and accompanied by increased staining for pro-apoptotic Bax protein and decreased staining for anti-apoptotic Bcl-2 protein. CONCLUSIONS: APS treatment reduced multiple indices of arthritis in rats with AA. Results support further investigation of therapeutic effects of APS in treatment of RA and other autoimmune diseases.
20920569 Evaluation of the disease modifying activity of Colchicum luteum Baker in experimental art 2011 Jan 27 ETHNOPHARMACOLOGICAL RELEVANCE: Colchicum luteum (CL) has been traditionally used in the Unani system of medicine as a chief ingredient of many polyherbal formulations for the treatment of joint pain and rheumatoid arthritis (RA). AIM OF THE STUDY: To evaluate the antiarthritic activity of CL hydroalcoholic extract (CLHE) in formaldehyde and complete Freund's adjuvant (CFA) induced arthritis. MATERIALS AND METHODS: Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. Joint swelling was measured on days 8, 9 and 10 in formaldehyde induced arthritis and days 3, 7, 14 and 21 in CFA induced arthritis. In order to evaluate the effect of CLHE on disease progression, serum TNF-α level and synovial expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was determined in CFA induced arthritis. RESULTS: CLHE produced a significant and dose dependent inhibition of joint swelling during the entire duration of the study in both, formaldehyde and CFA induced arthritis. Serum TNF-α level was also reduced significantly in a dose dependent manner in all the CLHE treated groups. The expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was also found to be less in the CLHE treated group as compared to control. CONCLUSION: We believe that the antiarthritic activity of CLHE was due to its modulatory effect on the expression of proinflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of CL in the treatment of RA and other inflammatory joint disorders.
20459298 Etanercept treatment patterns in managed-care patients with psoriasis or psoriatic arthrit 2010 OBJECTIVE: To evaluate the actual dosing of etanercept in US commercially insured patients with psoriatic disease, to estimate treatment cost. METHODS: This study evaluated medical and pharmacy claims in a US commercial claims database from November 1, 2003 through June 30, 2008. Biologic-naïve patients diagnosed with psoriasis, psoriatic arthritis, or both, who filled prescriptions for etanercept and were enrolled for ≥ 6 months before the first claim and 1 year after, were included. Patients with rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis during the study period were excluded. RESULTS: Among 2,359 patients, diagnoses included psoriasis (n = 1,810), psoriatic arthritis (n = 212), and both diseases (n = 337). Psoriasis patients used a mean 98% (standard deviation [SD] 28%) and psoriatic arthritis patients used 107% (SD 31%) of label-recommended etanercept doses. CONCLUSIONS: Overall, patients with psoriatic disease used 98-104% of the expected etanercept dose, depending on whether the expected dose for patients with both diagnoses was the psoriasis or psoriatic arthritis dose. This study does not evaluate effectiveness or clinicians' intent and may not be representative of other populations. Nevertheless, average usage was as expected for all cohorts, providing a basis for cost estimation.
19535169 [Can tumor necrosis factor inhibitors induce sclero-uveitis?]. 2009 Sep We report three cases of female patients who presented a first episode of unilateral scleritis or acute anterior uveitis while they were treated for 12-16 months by TNF inhibitor: etanercept (Enbrel((R))) 25mg twice weekly for rheumatologic diseases (rheumatoid arthritis or ankylosing spondylitis). Ocular inflammation was resistant to the usual treatment. Some cases of scleritis and uveitis are known to be drug-induced. TNF inhibitors seem to be part of them. Ocular inflammation is usually the first episode. It appears generally in the first year of the treatment by TNF inhibitors and resists to usual treatment. The general disease is usually well stabilized. In our cases, inflammation decreased only when the etanercept was discontinued.