Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18955216 Regulation of Cellular Metabolism and Cytokines by the Medicinal Herb Feverfew in the Huma 2009 Mar The herb feverfew is a folk remedy for various symptoms including inflammation. Inflammation has recently been implicated in the genesis of many diseases including cancers, atherosclerosis and rheumatoid arthritis. The mechanisms of action of feverfew in the human body are largely unknown. To determine the cellular targets of feverfew extracts, we have utilized oligo microarrays to study the gene expression profiles elicited by feverfew extracts in human monocytic THP-1 cells. We have identified 400 genes that are consistently regulated by feverfew extracts. Most of the genes are involved in cellular metabolism. However, the genes undergoing the highest degree of change by feverfew treatment are involved in other pathways including chemokine function, water homeostasis and heme-mediated signaling. Our results also suggest that feverfew extracts effectively reduce Lipopolysaccharides (LPS)-mediated TNF-alpha and CCL2 (MCP-1) releases by THP-1 cells. We hypothesize that feverfew components mediate metabolism, cell migration and cytokine production in human monocytes/macrophages.
18494155 [The liver and methotrexate]. 2008 Feb Methotrexate is proposed for the treatment of inflammatory disorders such as rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of methotrexate has been investigated and prolonged treatment can induce liver fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with liver fibrosis in patients treated with this drug. Therefore, liver fibrosis associated with methotrexate could be due to associated factors instead of methotrexate itself. Recommendations to monitor and diagnose methotrexate induced liver damage vary depending on the disease. Frequent evaluation of liver fibrosis with liver biopsy is recommended during therapy, especially in patients treated for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for the assessment of liver fibrosis associated with methotrexate and hence, need further evaluation.
18425565 Osteoclast cell fusion: mechanisms and molecules. 2008 Osteoclasts are bone-resorbing multinuclear polykaryon that are essential for bone remodeling and are formed through cell fusion of mononuclear macrophage/monocyte-lineage hematopoietic precursors. In arthritic joints, a large number of activated osteoclasts can be detected, which are suggested to be causative of bone erosion in rheumatoid arthritis. It has been fully established that osteoclastogenesis is critically regulated by several key essential factors, such as M-CSF and RANKL. However, regarding their most characteristic property, i.e., cell fusion to form giant polykaryons, there are still miscellaneous questions to be clarified, although several molecules have been shown to be critically involved in this process. Here we review the latest knowledge about osteoclastogenic cell fusion and novel concepts underlying the characteristic phenomenon. Because cell fusion is a genuine property of mature osteoclasts, modulating this process will become a promising therapeutic tool for bone resorptive disorders in the future.
18399589 Cement fixation of the femoral component in older patients. 2008 Polymethylmethacrylate cement fixation of the femoral component in total hip arthroplasty is still a reasonable option in a select group of patients. Cement fixation is indicated in sedentary patients older than 75 years, certain older patients with rheumatoid arthritis, and patients with femoral neck fractures or conversion surgery. Hips with severe osteopenia or a "stove-pipe" femur (Dorr type C) may also be considered for cement fixation. The cemented femoral component should be fabricated of a cobalt-chromium alloy with a modern geometry and offset. Third-generation cementing techniques should be used to obtain a grade A or B cement mantle. Antibiotic cement may be used in patients at higher risk for infection. The 10-year results of cemented femoral components in these patient populations are excellent.
18207065 Antiphospholipid antibody syndrome and autoimmune diseases. 2008 Feb The arbitrary division between antiphospholipid antibody syndrome and secondary antiphospholipid antibody syndrome has not proven useful. Antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome often occur as epiphenomena in many autoimmune diseases. They are very common in systemic lupus erythematosus. Antiphospholipid antibody syndrome is a significant comorbidity in lupus but is uncommon in Sjögren's syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitis. Evidence is growing that antiphospholipid antibodies may have a pathogenic role in pulmonary hypertension and accelerated atherosclerosis of autoimmune diseases.
18194823 Leflunomide as adjuvant treatment of dermatomyositis. 2008 Mar We report 3 cases of recalcitrant dermatomyositis that responded to the addition of daily leflunomide, a novel immunomodulatory drug that is currently used to treat rheumatoid arthritis. In our patients, leflunomide proved both safe and effective as adjuvant therapy in treating dermatomyositis.
19195158 Laughter education and the psycho-physical effects: introduction of smile-sun method. 2007 Dec With the aim of reducing cases of bully and suicide, 34 core laughter producers and 179 laughter producers were educated using Smile-Sun Messages in Aomori Prefecture. The purpose of this paper is to explore the key to spontaneous laughter for further application to healthcare settings. METHOD: Andragogy is the backbone idea. The author modified as seven tools such as sharing the objective, learning by heart, concentration, focusing on points, repetition, humor and evaluation. The contents of Smile-Sun Messages are as follows: 1. I love myself, 2. I love to make you happy, 3. I sympathize, 4. "Let's think of it this way", 5. Talk in P-N-P, 6. "I" message with eye-contact and love and 7. Thanks for all. There is no curriculum on how to laugh. RESULTS: Participants gained self confidence by having their good points praised by others. Their depression decreased. Spontaneous laughter arose from participants. They all improved physically in terms of appearance, posture and attitude. There are some reports of better fingering in piano playing in 2 ladies, pain relief in a patient with cancer and improved walking without using a stick for 2 ladies with rheumatoid arthritis and a limp due to an unknown cause. CONCLUSION: Spontaneous laughter can be drawn when self-confidence is recognized. With Smile-Sun Messages in hospitals and healing environments, spontaneous laughter can be drawn from patients which will decrease their depression and help them recover rapidly from their illness.
17854745 Hyperprolactinemia and autoimmune diseases. 2007 Sep The autoimmune diseases are more common in females. The sex hormones have an important role in this gender bias, mainly estrogen and prolactin (PRL) which modulate the immune response. PRL is secreted from the pituitary gland and other organs and cells mainly the lymphocytes. PRL has an immunostimulatory effect and promotes autoimmunity: PRL impairs the negative selection of autoreactive B lymphocytes occurring during B cell maturation into fully functional B cells. PRL has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens and enhances the production of immunoglobulins and autoantibodies. Hyperprolactinemia (HPRL) is observed in multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE) rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT) and multiple sclerosis (MS). There is no consistent correlation between PRL levels and disease activity. Murine models and small studies in SLE patients suggest some role of dopamine agonists in the therapy of those diseases. The genetic factor may have a role in humans as in animal models. The PRL isoform has an important effect on the bioactivity on prolactin receptors (PRL-Rs).
17163538 A syndrome of immunodeficiency, autoimmunity, and spondylometaphyseal dysplasia. 2007 Jan 1 We treated a 5-year-old boy, in our hospital in south India, who had a history of recurrent respiratory infections, tuberculosis, and severe varicella infection. He was short in build and a radiological examination revealed evidence of spondylometaphyseal dysplasia. Investigation of the immune system was suggestive of compromised cellular immunity. Immunofluorescence and immunoblot assay for antibodies detected underlying multiple disorders such as systemic lupus erythematosus (SLE), autoimmune thrombocytopenia, and juvenile rheumatoid arthritis (JRA). Roifman et al. described a similar syndrome in 2000 and 2003, which was characterized by spondylometaphyseal dyplasia, combined immunodeficiency, and autoimmunity and called it Roifman-Costa syndrome (OMIM 607944). Hence a diagnosis of Roifman-Costa syndrome was made. Ours shall be the first report of such a condition from the Indian subcontinent and hence the communication.
17122157 Tissue inhibitors of metalloproteinases (TIMPs): their biological functions and involvemen 2006 Dec Several families of enzymes are responsible for the degradation of extracellular matrix (ECM) proteins during the remodeling of tissues. An important family of such enzymes is that of the matrix metalloproteinases (MMPs). To control MMP-mediated ECM breakdown, tissue inhibitors of metalloproteinases (TIMPs) are able to inhibit MMP activity. A disturbed balance of MMPs and TIMPs is found in various pathologic conditions, such as cancer, rheumatoid arthritis, and periodontitis. The role of MMPs in pathology has been extensively described in the literature. The main focus of this review lies in the biological functions of TIMPs and their occurrence in disease, especially in the head and neck area. Their biological functions and their role in diseases like oral cancers and periodontitis, and in the development of cleft palate, will be discussed. Finally, the diagnostic and therapeutical opportunities of TIMPs will be evaluated.
16932466 Drug insight: Immunomodulatory effects of statins--potential benefits for renal patients? 2006 Jul Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase, an enzyme crucial to cholesterol synthesis. Drugs of this class reduce the risk of coronary heart disease and stroke, in large part through lipid modulation. Emerging evidence indicates that statins have additional modes of action. These actions, which encompass modification of endothelial function, plaque stability, thrombus formation and inflammatory pathways, are widely referred to as 'pleiotropic effects'. These pleiotropic effects indicate that the therapeutic potential of statins might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders or conditions such as transplantation, multiple sclerosis, rheumatoid arthritis and chronic kidney disease. Experimental and clinical data provide evidence to support these broader applications of statins; however, more large-scale trials are needed to clarify the therapeutic benefit.
16889230 Advances in cathepsin S inhibitor design. 2006 Jul Cathepsin S is expressed in antigen-presenting cells and plays a role in invariant chain processing and major histocompatibility complex class II (MHCII) antigen presentation leading to CD4+ T-cell activation. An oral cathepsin S inhibitor that blocks MHCII antigen presentation could result in a T-cell-selective immunosuppressant agent with improved safety over the current standard of care for the treatment of rheumatoid arthritis, psoriasis, multiple sclerosis and other autoimmune-based inflammatory diseases. This review focuses on advances in cathepsin S inhibitor utility and design since January of 2004.
21136668 Proteomic analysis of autoantigens associated with systemic lupus erythematosus: Anti-aldo 2007 Feb To screen for autoantibodies associated with systemic lupus erythematosus (SLE), we used proteomic approaches combining 2-D PAGE and Western blot analysis, followed by protein identification by LC-MS/MS analysis, resulting in the identification of aldolase A as a novel autoantigen in SLE. ELISA showed the prevalence of anti-aldolase A antibodies to be 29.3% in SLE, 8.2% in rheumatoid arthritis, 18.1% in polymyositis and absent in healthy controls. Furthermore, 43.4% of SLE patients suffering from nephritis showed anti-aldolase A autoantibodies, which was significantly higher than the prevalence for those without nephritis (11.1%). In lupus nephritis, there are few reliable diagnostic methods, other than urinalysis. Therefore, these results indicate that autoantibodies against aldolase A may serve as an alternative clinical biomarker of SLE associated with nephritis.
17588554 Restorative and synergistic efficacy of Kalpaamruthaa, a modified Siddha preparation, on a 2007 Jul 20 BACKGROUND: Rheumatoid arthritis (RA) is a prevalent and debilitating disease that affects the joints. Infiltration of blood-derived cells in the affected joints upon activation generate reactive oxygen/nitrogen species, resulting in an oxidative stress. One approach to counteract this oxidative stress is the use of antioxidants as therapeutic agents. OBJECTIVES: Kalpaamruthaa (KA), a modified indigenous Siddha preparation constituting Semecarpus anacardium nut milk extract (SA), Emblica officinalis (EO) and honey was evaluated for its synergistic antioxidant potential in adjuvant induced arthritic rats than sole SA treatment. MATERIALS AND METHODS: Levels/activities of reactive oxygen species (ROS)/reactive nitrogen species (RNS), myeloperoxidase, lipid peroxide and enzymic and non-enzymic antioxidants were determined in control, arthritis induced, SA and KA treated (150 mg/kg b.wt.) animals. RESULTS AND CONCLUSION: The levels/activities of ROS/RNS, myeloperoxidase and lipid peroxide were increased significantly (p<0.05) and the activities of enzymic and non-enzymic antioxidants were in turn decreased in arthritic rats, whereas these changes were reverted to near normal levels upon SA and KA treatment. KA showed an enhanced antioxidant potential than sole treatment of SA in adjuvant induced arthritic rats. KA via enhancing the antioxidant status in adjuvant induced arthritic rats than sole SA treatment proves to be an important therapeutic modality in the management of RA and thereby instituting the role of oxidative stress in the clinical manifestation of the disease RA. The profound antioxidant efficacy of KA than SA alone might be due to the synergistic action of the polyphenols such as flavonoids, tannins and other compounds such as vitamin C and hydroxycinnamates present in KA.
17709823 Molecular imaging: integration of molecular imaging into the musculoskeletal imaging pract 2007 Sep Chronic musculoskeletal diseases such as arthritis, malignancy, and chronic injury and/or inflammation, all of which may produce chronic musculoskeletal pain, often pose challenges for current clinical imaging methods. The ability to distinguish an acute flare from chronic changes in rheumatoid arthritis, to survey early articular cartilage breakdown, to distinguish sarcomatous recurrence from posttherapeutic inflammation, and to directly identify generators of chronic pain are a few examples of current diagnostic limitations. There is hope that a growing field known as molecular imaging will provide solutions to these diagnostic puzzles. These techniques aim to depict, noninvasively, specific abnormal cellular, molecular, and physiologic events associated with these and other diseases. For example, the presence and mobilization of specific cell populations can be monitored with molecular imaging. Cellular metabolism, stress, and apoptosis can also be followed. Furthermore, disease-specific molecules can be targeted, and particular gene-related events can be assayed in living subjects. Relatively recent molecular and cellular imaging protocols confirm important advances in imaging technology, engineering, chemistry, molecular biology, and genetics that have coalesced into a multidisciplinary and multimodality effort. Molecular probes are currently being developed not only for radionuclide-based techniques but also for magnetic resonance (MR) imaging, MR spectroscopy, ultrasonography, and the emerging field of optical imaging. Furthermore, molecular imaging is facilitating the development of molecular therapies and gene therapy, because molecular imaging makes it possible to noninvasively track and monitor targeted molecular therapies. Implementation of molecular imaging procedures will be essential to a clinical imaging practice. With this in mind, the goal of the following discussion is to promote a better understanding of how such procedures may help address specific musculoskeletal issues, both now and in the years ahead.
16842160 Regulation of angiogenesis by the kallikrein-kinin system. 2006 High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease. This proteolytic event results in a nonapeptide, bradykinin (BK), and a kinin-free derivative of HK, namely HKa. BK promotes angiogenesis by upregulation of bFGF through the B1 receptor or by stimulation of VEGF formation via the B2 receptor. Kininogen-deficient rats show diminished angiogenesis when neovascularization is stimulated. The formation of HKa results in exposure of domain 5 (D5). HKa or D5 inhibit endothelial cell migration and proliferation, both of which are needed for angiogenesis. In the chicken chorioallantoic membrane assay when neovascularization is stimulated by bFGF or VEGF, HKa or D5 inhibit angiogenesis. Monoclonal antibody C11C1, which prevents binding of HK to endothelial cells, also limits its conversion to BK thus downregulating angiogenesis. In vivo, mAb C11C1 inhibits tumor angiogenesis in mice as well as in experimental inflammatory arthritis and inflammatory bowel disease in Lewis rats. In vitro HKa or D5 inhibits endothelial cell adhesion to vitronectin and fibrinogen, resulting in anokis and apoptosis. The HKa receptor, uPAR, forms a signaling complex containing the integrin alphavbeta3 or alpha5beta1, caveolin, Src kinase Yes, focal adhesion kinase and paxcillin. HKa physically disrupts the complex by interfering with the binding of vitronectin to uPAR. Both mAb C11C1 and D5 have potential applications for controlling unwanted angiogenesis in inflammation and cancer.
18755518 Targeting the PIAS1 SUMO ligase pathway to control inflammation. 2008 Oct Protein sumoylation is a post-translational-modification event, in which small ubiquitin-like modifier (SUMO) is covalently attached to protein substrates by a three-step process. Sumoylation has been suggested to regulate multiple cellular processes, including inflammation. Inflammation is initiated in response to pathogenic infections, but uncontrolled inflammatory responses can lead to the development of inflammatory disorders such as rheumatoid arthritis. Recent studies indicate that proinflammatory stimuli, such as tumor necrosis factor alpha and lipopolysaccharide, can activate PIAS1 [protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1)] SUMO E3 ligase through a SUMO-dependent, inhibitor of kappaB kinase alpha (IKKalpha)-mediated phosphorylation event. Activated PIAS1 is then recruited to inflammatory gene promoters to repress transcription. These findings support a hypothesis that therapies targeting the PIAS1 SUMO ligase pathway might be developed for the treatment of inflammatory disorders such as rheumatoid arthritis and atherosclerosis.
22461216 The role of osteoprotegerin (OPG) and estrogen receptor (ER-α) gene polymorphisms in rheu 2007 May Objective. Osteoclast activation at the cartilage pannus junction is an essential step in the destruction of bone matrix in patients affected by rheumatoid arthritis (RA). Receptor activator of NFkappaB ligand (RANK-L) is responsible for osteoclast differentiation and activation. Osteoprotegerin (OPG) is an alternative, high-affinity soluble receptor for RANK-L which significantly inhibits osteoclastogenesis. Estrogens and the specific receptors α and β (ER-α and ER-α) are known to play an important role in the pathophysiology of osteoarthritis (OA). Scope of the present study is to investigate the role of ER-α and OPG gene polymorphisms in a group of women affected by RA.Materials and Methods. 139 consecutive RA patients (115 females and 34 males; median age 65.8 years) were selected. Bone mineral density (BMD) was measured by dual energy x-ray absorptinometry at the lumbar spine (LS-BMD) and femoral neck (FN-BMD) and the presence of bone erosions was evaluated by conventional X-ray. ER-α gene polymorphisms were determined by PvuII and XbaI restriction endonuclease digestion of polymerase chain reaction (PCR) products. By convention, the presence of the endonuclease restriction site was indicated with lowercase (p and x) letters while the absence of the restriction site was indicated with uppercase letters (P and X). OPG gene polymorphism was determined by RsaI restriction endonuclease digestion of PCR products and the presence and absence of restriction fragment was identified as TT and CC respectively.Results. Pearson's χ(2)analysis for the ER-α gene polymorphism showed a prevalence of Pp genotype (58%) (p=0.04) and Xx (54%) (p=0.04) in the total population, without differences between males and females. We did not observed any significant differences between ER-α genotypes and LS-BMD. However subjects with xx or pp genotype had a lower LS-BMD in comparison with the opposite genotype.For OPG gene polymorphism, non significant differences in the distribution of the genotypes were observed between males and females. In addition, we did not observed significant differences on LS-BMD between the genotypes.Finally, we observed that patients with ER-α pp genotype was significant more represented in patients with hand erosions (p = 0.05). No significant correlation was observed for ER-α XbaI genotype, however a trend characterized by a correlation between xx and hand erosions was observed (p = 0.13). For OPG gene polymorphism, we found a statistical correlation between C allele of OPG and hands bone erosions (p = 0.02).Conclusion. We found a significant association between ER-α and OPG gene polymorphisms and the presence of bone erosions in RA patients. These preliminary data suggest a role of ER-α and OPG gene polymorphisms in bone turnover and disease progression.
16586042 Tacrolimus and cyclosporine A inhibit human osteoclast formation via targeting the calcine 2007 Feb In the present study, we aimed to determine whether tacrolimus (FK506) and cyclosporine A act directly on human osteoclast precursors obtained from patients with rheumatoid arthritis (RA) and influence monocyte-osteoclast differentiation induced by receptor activator of NF-kappaB ligand (RANKL) in vitro, the stage at which differentiation was affected and the manner in which tacrolimus or cyclosporine A affected the osteoclast signaling pathway. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and cultured in the presence of RANKL and macrophage-colony stimulating factor (M-CSF). Tacrolimus or cyclosporine A was added to these cultures to determine the effect on the osteoclast differentiation. Osteoclast formation was determined by assessing the number of tartrate resistant acid phosphatase (TRAP) staining cells and measuring the extent of lacunar resorption. The expression of osteoclast transcription factors, such as TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells c1 (NFATc1), c-Fos, c-Jun, microphthalmia transcription factor (MITF) and PU.1 in mononuclear cells (MNCs) was assayed by quantitative reverse transcription-polymerase chain reaction. Addition of tacrolimus or cyclosporine A resulted in a decrease in the number of TRAP-positive multinucleated cells (TRAP+ MNCs) and a decrease in the extent of lacunar resorption pit formation as compared to the control cultures; thus, human monocyte-osteoclast differentiation was more effectively inhibited at the late stage and addition of tacrolimus or cyclosporine A resulted in a decrease in the mRNA expression of NFATc1, c-Jun, and MITF at the late stage. Our results suggest that tacrolimus or cyclosporine A acts directly on human osteoclast precursors in RA patients and exerts their immunosuppressive effects on human monocyte-osteoclast formation via targeting both the calcineurin-dependent NFAT pathway and activation pathway for c-Jun or MITF.
18598385 High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheuma 2008 High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 can serve as an alarmin to activate the innate system and mediate a wide range of physiological and pathological responses. To function as an alarmin, HMGB1 translocates from the nucleus of the cell to the extra-cellular milieu, a process that can take place with cell activation as well as cell death. HMGB1 can interact with receptors that include RAGE (receptor for advanced glycation endproducts) as well as Toll-like receptor-2 (TLR-2) and TLR-4 and function in a synergistic fashion with other proinflammatory mediators to induce responses. As shown in studies on patients as well as animal models, HMGB1 can play an important role in the pathogenesis of rheumatic disease, including rheumatoid arthritis, systemic lupus erythematosus, and polymyositis among others. New approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling.