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ID PMID Title PublicationDate abstract
21069274 [What has been confirmed in the treatment of inflammatory bowel disease?]. 2010 Dec The therapy of inflammatory bowel diseases is currently guided by clinical variables. An escalation of immunosuppressive therapy is required in case of treatment failure. However, clinical remission does not necessarily imply mucosal healing. In parallel to the treatment of rheumatoid arthritis a novel concept is emerging suggesting that an early anti-inflammatory treatment can reduce structural changes in inflammatory bowel diseases. The studies supporting this novel therapeutic strategy that mucosal healing might build the future therapeutic goal will be discussed. In order to adjust the therapy, risk factors indicating a complicated disease course will be identified, resulting in the development of an individual disease course. The benefit of these strategies will be discussed together with therapy-associated complications.
20963555 Adiponectin action from head to toe. 2010 Feb Adiponectin, the most abundant protein secreted by white adipose tissue, is known for its involvement in obesity-related disorders such as insulin resistance, type 2 diabetes mellitus and atherosclerosis. Moreover, modulation of the circulating adiponectin concentration is observed in pathologies that are more or less obesity-related, such as cancer and rheumatoid arthritis. The wide distribution of adiponectin receptors in various organs and tissues suggests that adiponectin has pleiotropic effects on numerous physiological processes. Besides its well-known insulin-sensitizing, anti-inflammatory and antiatherosclerotic properties, accumulating evidence suggests that adiponectin may also have anticancer properties and be cardioprotective. A beneficial effect of adiponectin on female reproductive function was also suggested. Since adiponectin has numerous beneficial biological functions, its use as a therapeutic agent has been suggested. However, the use of adiponectin or its receptors as therapeutic targets is complicated by the presence of different adiponectin oligomeric isoforms and production sites, by multiple receptors with differing affinities for adiponectin isoforms, and by cell-type-specific effects in different tissues. In this review, we discuss the known and potential roles of adiponectin in various tissues and pathologies. The therapeutic promise of administration of adiponectin and the use of its circulating levels as a diagnostic biomarker are further discussed based on the latest experimental studies.
20536425 CCR1 antagonists: what have we learned from clinical trials. 2010 The identification of chemokines and their receptors as potent mediators of leukocyte infiltration raised interest in the potential role of these proteins on disease pathogenesis. This is exemplified by the chemokine receptor, CCR1, which has been shown to be up-regulated in a number of human diseases, the implications of which have been suggested by animal models where inhibition of CCR1 or its ligands have shown beneficial effects. These data support the possibility that a CCR1 antagonist will provide therapeutic benefit to patients with inflammatory diseases. Over the last several years, several of these antagonists entered clinical trials, including CP-481,715 (Pfizer) and MLN3897 (Millennium) for rheumatoid arthritis, BX471 (Berlex / Scherring AG) for multiple sclerosis, and AZD-4818 (Astra-Zeneca) for COPD. This review will describe the evidence that supported the role of CCR1 in these diseases, the results from clinical trials, and provide perspectives on what has been learned from these trials for potential application / consideration to other studies with chemokine receptor antagonists.
20337545 The management of rheumatic diseases in pregnancy. 2010 Mar Pregnancy can create a challenge for physicians caring for women with rheumatic diseases. For many women with rheumatoid arthritis (RA), pregnancy can provide a reprieve from long-term joint pain and inflammation, but others will not experience remission and will continue to need medication. Systemic lupus erythematosus (SLE) may remain quiet in some women, but in others may become more aggressive during pregnancy, putting both mother and foetus at risk. Women with limited scleroderma can do remarkably well, but scleroderma renal crises can be difficult to manage. A third of pregnancies in women with antiphospholipid syndrome (APS) may be refractory to our best therapy. In general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes.
20145961 Inorganic polyphosphate differentiates human mesenchymal stem cells into osteoblastic cell 2010 Jul The existence of inorganic polyphosphates [poly(P)] in human cells has been demonstrated. In osteoblasts, it is suggested that the concentration of cellular poly(P) is relatively high. In this study, we examined whether poly(P) accelerates the differentiation of human mesenchymal stem cells (hMSCs) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) into osteoblastic cells. Alkaline phosphatase (ALP) activity was induced by poly(P) in hMSCs from both OA and RA. In Alizarin Red S and osteocalcin EIA, there was a significant difference between the control and poly(P) group. In real-time PCR, there was a significant difference in ALP, collagen type 1A, osteocalcin, and bone sialoprotein between the control and poly(P) group. Our findings suggest that poly(P) have the potent role of differentiating hMSCs into osteoblastic cells at the early and later stages of osteoblastic differentiation.
20090527 The genetics of scleroderma (systemic sclerosis). 2010 Mar PURPOSE OF REVIEW: To determine the advances made in the genetics of scleroderma in candidate gene association studies. RECENT FINDINGS: Over the past 18 months, a number of candidate gene studies using large case-control series in scleroderma have been reported. The studies have identified multiple genes involved in immune regulation including BANK1, C8orf13-BLK, IL-23R, IRF5, STAT4, TBX21, and TNFSF4 as susceptibility genes for the development of SSc. Furthermore, gene-gene interaction studies suggest that IRF5, STAT4, and BANK1 as well as TBX21 and STAT4 interact with regard to scleroderma susceptibility. Many of the genetic variants associated with SSc susceptibility are shared among other autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. SUMMARY: Candidate gene association studies have substantially advanced our understanding of the pathogenesis of SSc and demonstrate that SSc is a polygenic, autoimmune disease.
20085454 A human CXCL13-induced actin polymerization assay measured by fluorescence plate reader. 2010 Feb The chemokine receptor CXCR5 is predominantly expressed on mature B cells and follicular T-helper cells. CXCR5 and its ligand CXCL13 participate in ectopic germinal center formation at the inflammatory sites of multiple immune diseases such as rheumatoid arthritis, multiple sclerosis, and Sjogren's syndrome. Therefore, disrupting CXCL13-induced chemotaxis may be a fruitful approach for developing therapeutics in treating these diseases. Cells undergo cytoskeletal rearrangement prior to chemotaxis, and therefore actin polymerization can be used as a surrogate readout more proximal to chemokine receptor activation than chemotaxis. Conventionally, actin polymerization is measured by fluorescence microscopy or flow cytometry, which are either of low throughput or in need of special instruments. We developed a 96-well actin polymerization assay that can process 1,000 to 1,500 samples a day. This assay uses a standard laboratory fluorescence microplate reader as the detection instrument and was optimized for various experimental conditions such as cell density, actin filament staining reagent, staining buffer, and cell culture conditions. We demonstrate that this actin polymerization assay in 96-well format exhibits the expected pharmacology for human CXCR5 and is suitable as a primary functional assay to screen neutralizing scFv in crude bacterial peri-preps and a secondary assay for small compound collections.
20083235 Autoimmune diseases: Solution of the environmental, immunological and genetic components w 2010 Jun Autoimmune diseases have environmental and genetic components. These are the microbial trigger, the immunity system component and the genetic component. Here we describe these components and how they interact. Known microbial triggers are Streptococcus pyogenes for rheumatic carditis, Proteus mirabilis for rheumatoid arthritis and Klebsiella pneumoniae for ankylosing spondylitis. The immunity system component has been clarified by realisation that no autoimmune disease is caused by loss of suppressor T cells. This leaves Burnet's forbidden clones, clearly seen in Graves' disease, as the immunological defect. With wide scope for clonal diversification by somatic gene mutations, to prevent frequent autoimmunity the immunity system is policed by the histocompatibility system. This dictates the immune response repertoire by deleting complementary clones (H Gene Theory). We show molecular evidence of how specific histocompatibility antigens can predispose to an autoimmune disease by influencing choice of the microbial antigen to which the immunity system reacts. Because of the unlucky random element in the somatic mutations involved in their development, forbidden clones are unlikely to reappear in new immune repertoires developing after immune ablation and autologous bone marrow cell reconstitution, as observed clinically. Isolation of autoantigens and their attachment to cytotoxic moieties could provide specific immunotherapy for autoimmune diseases. Kaplans's discovery that xenografts can be accepted without rejection after immune ablation followed by autologous and xenogeneic bone marrow inoculation, could enable widespread use of pig grafts for humans.
20018054 Predictive modeling in case-control single-nucleotide polymorphism studies in the presence 2009 Dec 15 In this paper, we apply the gradient-boosting machine predictive model to the rheumatoid arthritis data for predicting the case-control status. QQ-plot suggests severe population stratification. In univariate genome-wide association studies, a correction factor for ethnicity confounding can be derived. Here we propose a novel strategy to deal with population stratification in the context of multivariate predictive modeling. We address the problem by clustering the subjects on the axes of genetic variations, and building a predictive model separately in each cluster. This allows us to control ethnicity without explicitly including it in the model, which could marginalize the genetic signal we are trying to discover. Clustering not only leads to more similar ethnicity groups but also, as our results show, increases the accuracy of our model when compared to the non-clustered approach. The highest accuracy is achieved with the model adjusted for population stratification, when the genetic axes of variation are included among the set of predictors, although this may be misleading given the confounding effects.
20000302 Evening primrose oil. 2009 Dec 15 Evening primrose oil (Oenothera biennis) is a commonly used alternative therapy and a rich source of omega-6 essential fatty acids. It is best known for its use in the treatment of systemic diseases marked by chronic inflammation, such as atopic dermatitis and rheumatoid arthritis. It is often used for several women's health conditions, including breast pain (mastalgia), menopausal and premenstrual symptoms, cervical ripening, and labor induction or augmentation. However, there is insufficient evidence to make a reliable assessment of its effectiveness for most clinical indications. The current evidence suggests that oral evening primrose oil does not provide clinically significant improvement in persons with atopic dermatitis, and that it is also likely ineffective for the treatment of cyclical mastalgia and premenstrual syndrome. However, most trials to date have significant methodologic flaws and must be considered preliminary. The use of evening primrose oil during pregnancy is not supported in the literature and should be avoided. Evening primrose oil is generally well tolerated, with reported minor adverse effects, including gastrointestinal upset and headaches. Optimal dosing standards and treatment regimens await clarification in adequately powered clinical trials.
19900982 Bilateral retinal vasculitis in a patient with systemic lupus erythematosus and its remiss 2010 Mar Severe retinal vasculitis is a rare, but potentially blinding, complication of patients with systemic lupus erythematosus (SLE). We describe here the first reported case of treating severe bilateral SLE-associated retinal vasculitis with the anti-CD20 monoclonal antibody rituximab, a drug which has established its role in rheumatoid arthritis and has shown promise in case series for the treatment of severe SLE that is unresponsive to other therapies. This case suggests that rituximab-induced B-cell depletion may provide an important new therapeutic option for refractory cases of this devastating ocular complication.
19361810 Epstein-Barr virus and multiple sclerosis. 2009 Nov 15 Epstein-Barr virus (EBV) is a human DNA herpesvirus infecting more than 90% of the world's population. EBV is the etiological agent of infectious mononucleosis (Pfeiffer's disease). Furthermore, diverse malignancies such as Burkitt and Hodgkin lymphoma have been associated with EBV. More recently, a possible role for EBV has been suggested in chronic inflammatory/autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus as well as in multiple sclerosis (MS). MS is currently regarded as a disease with multifactorial etiology, EBV being one possible factor in MS manifestation: Infectious mononucleosis has been shown to increase the risk of developing MS later in life. EBV seroprevalence rates are higher in MS as compared to controls, in adult as well as in pediatric MS patients. Moreover, EBV antibody titres and EBV specific T-cells are increased in MS patients as compared to healthy individuals. Recently, CNS B-cells of MS patients have been reported to harbour EBV. However, there is still controversy whether EBV could be a causative agent as opposed to an innocent bystander in the pathogenesis of MS. This review summarizes current knowledge on the association of EBV and MS including a critical discussion of equivocal findings.
19052836 Diagnosis delay in patients with ankylosing spondylitis: factors and outcomes--an Indian p 2009 Mar This study focuses on the causes and consequences of delay in diagnosis of ankylosing spondylitis (AS). Seventy consecutive patients presenting at a rheumatology clinic in India were studied. Mean (+/-S.D) delay in diagnosis was 6.9 (+/-5.2) years. The main cause of delay was incorrect diagnosis as non-specific back pain (19/54, 35.1%), degenerative disc disease (14/54, 25.9%), rheumatoid arthritis (11/54, 20.37%), and tuberculosis of spine (9/54, 16.6%) in that order, for which the patient received prolonged treatment. Absence of extra-articular manifestations and juvenile age also significantly correlated with diagnostic delay. Delay in diagnosis resulted in significantly worse disease activity index (BASDAI), functional index (BASFI), and damage index (BASMI). Most incorrect initial diagnoses were made by orthopedicians (75.9%), followed by general physician (50%), and rheumatologist (12%). Continuing medical education workshops with a focus on clinical diagnosis of inflammatory back pain may help in early diagnosis of AS.
19781951 Synthesis and evaluation of benzo[b]thiophene derivatives as inhibitors of alkaline phosph 2009 Oct 15 Presence of basic calcium phosphate in knee joints of osteoarthritis patients could be prevented by inhibiting tissue non-specific alkaline phosphatase (TNAP) activity. Levamisole or the L stereoisomer of tetramisole (a known TNAP inhibitor) has been used as a treatment for curing rheumatoid arthritis but its therapeutical use is limited due to side effects. We report the synthesis and the TNAP inhibition property of benzo[b]thiophene derivatives, among which benzothiopheno-tetramisole and benzothiopheno-2,3-dehydrotetramisole, which could be involved in a drug therapy for osteoarthritis. Two water soluble racemic benzothiopheno-tetramisole and -2,3-dehydrotetramisole with apparent inhibition constants K(i)=85+/-6 microM and 135+/-3 microM (n=3) comparable to that of enantiomeric levamisole 93+/-4 microM were found. Several novel derivatives showed more pronounced inhibition properties towards intestinal alkaline phosphatase than TNAP.
19693642 Drug treatment-induced downregulation of antiphospholipid antibodies in PAPS. 2009 Nov Although low-dose methotrexate (MTX) has been used to treat several autoimmune diseases like lupus erythematosus, rheumatoid arthritis, etc., it has not yet been used to treat patients with primary antiphospholipid syndrome (PAPS). Parallel to clinical follow-up of female patient with a severe form of PAPS, antiphospholipid antibodies (aPL), blood coagulation, and hematological parameters in the peripheral blood have been monitored. MTX improved ulcers, livedo reticularis, decreased aPL titers, increased platelet counts, and improved blood coagulation parameters (e.g., factor VIII) and was well tolerated. Low-dose MTX was safe and effective in the presented case with PAPS. The clinical benefit may be due to the downregulation of increased aPL titers and amelioration of disturbed coagulation parameters.
19630828 Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the card 2009 Jul While inflammation is a crucial component of atherothrombosis and patients with elevated inflammatory biomarkers such as high sensitivity C-reactive protein (hsCRP) are at increased vascular risk, it remains unknown whether inhibition of inflammation per se will lower vascular event rates. The recently completed JUPITER (N Engl J Med 2008, 359, 2195) trial demonstrates that statins reduce myocardial infarction, stroke, and all-cause mortality among healthy individuals with low cholesterol and elevated hsCRP. However, a direct test of the inflammatory hypothesis of atherothrombosis requires an agent that inhibits inflammation without impacting other components of the atherothrombotic process, and has an acceptable safety profile for a trial setting. On this basis, the cardiovascular inflammation reduction trial (CIRT) proposes to allocate 7000 stable coronary artery disease patients with persistent elevations of hsCRP to placebo or very-low-dose-methotrexate (VLDM, 10 mg weekly), a proven anti-inflammatory regimen that reduces TNFalpha, IL-6, and CRP levels and is in wide use among rheumatoid arthritis patients. If successful, CIRT would both confirm the inflammatory hypothesis of atherothrombosis and open novel approaches to the treatment and prevention of cardiovascular disorders.
19434074 Type 17 T helper cells-origins, features and possible roles in rheumatic disease. 2009 Jun Type 17 T helper (TH17) cells are a population of CD4+ effector T cells that are distinct from TH1 and TH2 cells owing to their ability to produce interleukin (IL)-17. Although TH1 and TH2 cells are similar in mice and humans, TH17 cells differ in several ways. The differentiation of mouse TH17 cells requires transforming growth factor beta and IL-6, whereas human naive T cells can develop into TH17 cells in the presence of IL-1beta and IL-23 alone, transforming growth factor beta having an indirect role in their development via the selective inhibition of TH1 cell expansion. in both mice and humans, a late developmental plasticity of TH17 cells towards the TH1 lineage has been shown. Mainly based on mouse gene knockout studies, TH17 lymphocytes have been found to have a pathogenic role in several autoimmune disorders; however, whether human autoimmune disorders, including rheumatoid arthritis (RA) and psoriasis, are prevalently TH1-mediated or TH17-mediated, is still unclear. research suggests that both TH1 and TH17 cells are involved in RA pathogenesis, raising the possibility that interventions that target both the IL-23-IL-17 (TH17) and the IL-12-interferon gamma (TH1) axes might be successful future therapeutic approaches for RA.
20492890 [Psoriasiform skin reactions during treatment with etanercept]. 2010 May Anti-TNFs have a wide spectrum of skin lesions, psoriasis being found among them paradoxically. A 42-year old woman with a history of rheumatoid arthritis since 19 years of age was referred to the Dermatology service due to pustular psoriasis on both soles during treatment with etanercept. Due to her incapacity to walk and the pain reported by the patient, etanercept was replaced with adalimumab with clinical improvement and total disappearance of the lesions at six weeks of switching the anti-TNF. Tumor necrosis factor inhibitors are drugs that act in T cell mediated diseases. The appearance of psoriasiform rashes is more frequent than reported in the literature. They appear in all the indications and with all the anti-TNFs. Adalimumab is the most frequent. Three types of reactions are produced, the pustular one being the most frequent. It predominates in women and may appear chronologically at any time during the treatment. Regarding the treatment, it is recommendable to continue with the anti-TNFs.
20459111 Synthesis and characterization of gold at gold(i)-thiomalate core at shell nanoparticles. 2010 Jun 22 In this paper, the synthesis of gold at gold(I)-thiolate core at shell nanoparticles is described for the first time. The chemical nature and structure of these nanoparticles were characterized by a multi-technique approach. The prepared particles consist of gold metallic cores, about 1 nm in size, surrounded by stable gold(I)-thiomalate shells (Au at Au(I)-TM). These nanoparticles could be useful in medicine due to the interesting properties that gold(I)-thiomalate has against rheumatoid arthritis. Furthermore, the described results give new insights in the synthesis and characterization of metallic and core at shell nanoparticles.
20358579 MicroRNAs and their role in gynecological tumors. 2011 Nov There have been only few events in the history of molecular biology that could be compared to the discovery of microRNAs and their role in cell physiology and pathology. MicroRNAs are small, single-stranded, noncoding RNAs composed of 19-25 nucleotides (∼22 nt), which have been proven to regulate gene expression at the posttranscriptional level. The regulatory function of microRNAs was demonstrated in normal and diseased conditions. In particular, it has been linked to cell cycle regulation, cell proliferation and differentiation, inflammatory response, and apoptosis. Altered expression profiles of microRNA have been observed in many pathologies, including diabetes, rheumatoid arthritis, and several cancers. To date, more than 700 human microRNAs have been identified and in silico-based analyses estimate at least 500 more to be identified. The purpose of this review is to present the current perspective on microRNAs structure and biogenesis as well as their contribution to the etiopathogenesis of gynecological tumors. We discuss results of the recent publications that indicate possibilities of microRNAs use as novel markers for tumors screening, early diagnosis, and treatment monitoring. The possible utilization of microRNAs as prognostic factors and specific therapy targets is also reviewed.