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ID PMID Title PublicationDate abstract
21283596 Proteomics in rheumatology: the dawn of a new era. 2010 Dec 8 Most rheumatic autoimmune diseases are complex in terms of their genetic origins and underlying pathogenic processes. Non-hypothesis-driven scanning platforms are adding novel insights to our understanding of these multifactorial diseases. This review summarizes the handful of recent proteomic studies that have been executed using samples from patients with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, osteoarthritis, or Sjogren's syndrome. The candidate biomarkers that have been uncovered in the reviewed studies have potential applications in diagnosis, prognosis, and theranostics. Though we are at the infancy of the proteomics era in rheumatology, the limited number of molecules uncovered thus far already hold promise. Ongoing research in proteomics holds tremendous potential for shaping how rheumatic diseases are diagnosed, prognosticated, and managed clinically over the coming years.
20030190 [Research progress in neuropsychopharmacology updated for the post-genomic era]. 2009 Nov Neuropsychopharmacological research in the post genomic (genomic sequence) era has been developing rapidly through the use of novel techniques including DNA chips. We have applied these techniques to investigate the anti-tumor effect of NSAIDs, isolate novel genes specifically expressed in rheumatoid arthritis, and analyze gene expression profiles in mesenchymal stem cells. Recently, we have developed a novel system of quantitative PCR for detection of BDNF mRNA isoforms. By using this system, we identified the exon-specific mode of expression in acute and chronic pain. In addition, we have made gene expression profiles of KO mice of beta2 subunits in acetylcholine receptors.
19370838 [Biologics--the new horizon for medical therapy]. 2009 Mar 1 Biologics include a wide range of medications that are produced by means of biological processes involving recombinant DNA technology. Approximately one in four of the recently approved new therapeuticals belongs to this group. Biologics have added major therapeutic options for the treatment of many diseases with an especially profound impact on rheumatoid arthritis, chronic inflammatory bowel disease, psoriasis, multiple sclerosis and a great array of malignancies. Many more targets are already screened in clinical research. Despite their clinical promises, monoclonal antibodies are raising concern about the potential adverse effects of long-term use. Costs are dramatically higher than for conventional medications, raising severe pharmacoeconomic concerns.
19283719 Diseases that may benefit from manipulating the Th17 pathway. 2009 Mar The discovery of IL-17 and of the Th17 pathway has been a step in the classification of human diseases. Th17 targeting appears rather straightforward in diseases associated with inflammation and matrix destruction, such as rheumatoid arthritis, psoriasis, and Crohn's disease. In other conditions where IL-17 is expressed and Th17 activated, it is unclear whether this is a primary or secondary event, making the use of Th17 inhibitors less obvious.
21686441 Diabetes mellitus type I associated with dermatomyositis: an extraordinary rare case with 2009 Insulin dependent diabetes mellitus (IDDM) is considered to be an autoimmune disease. IDDM is associated with other autoimmune diseases such as rheumatoid arthritis, autoimmune thyroid disease, multiple sclerosis, ankylosing spondylitis, psoriasis and systemic lupus erythematosus. Dermatomyositis (DM) is a disease of autoimmune aetiology involving skin and skeletal muscles damaged by an inflammatory process dominated by lymphatic infiltration. The association of IDDM with DM is extraordinarily rare. To our best knowledge, to date only two reports-one of them referring to a patient in childhood-have been published worldwide. DM and IDDM affect children and young adults. Herein, a case of DM in association with IDDM in a 28-year-old man is presented.
20471669 Unfavorably altered fibrin clot properties in patients with active rheumatoid arthritis. 2010 Jul OBJECTIVE: Altered fibrin clot properties have been reported in cardiovascular diseases (CVD) and inflammatory states. Given increased prevalence of CVD in patients with rheumatoid arthritis (RA), we investigated whether fibrin characteristics are also altered in RA patients. PATIENTS AND METHODS: We studied 46 consecutive RA patients versus 50 controls matched for age and gender. Ex vivo plasma clot permeability, turbidity, tissue-type plasminogen activator (tPA)-induced fibrinolysis, and scanning electron microscopy (SEM) images of clots were evaluated. RESULTS: Patients with RA had lower clot permeability, faster clot formation, higher maximum clot absorbency indicating thicker fibrin fibers, maximum clot mass and prolonged fibrinolysis time than controls. Maximum rates of clot lysis were similar in both groups. SEM images showed formation of dense clots with many projections on fibrin fibers. Clot permeability inversely correlated with fibrinogen, tPA, plasminogen activator inhibitor-1 (PAI-1), CRP, platelet count, disease activity score (DAS28) and a marker of oxidative stress, 8-iso-prostaglandin F2alpha (r from -0.44 to -0.79; all, p<0.0001). Similar positive associations were found for clot lysis time (r 0.44 to 0.69; all, p<0.01). Multiple regression analysis showed that fibrinogen was the only independent predictor of clot permeability (R2=0.87, p<0.0001) and lysis time (R2=0.80, p<0.003) in RA. Maximum D-dimer levels released from clots, maximum clot turbidity and the time of clot formation were predicted by PAI-1 (all, p<0.05). CONCLUSION: We showed unfavorably altered plasma fibrin clot structure and function in RA, which might contribute to an increased risk of thrombotic events in this disease.
20423309 Clinical uses of melatonin: evaluation of human trials. 2010 During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date. The efficacy of melatonin has been assessed as a treatment of ocular diseases, blood diseases, gastrointestinal tract diseases, cardiovascular diseases, diabetes, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome, infectious diseases, neurological diseases, sleep disturbances, aging and depression. Melatonin has been also used as a complementary treatment in anaesthesia, hemodialysis, in vitro fertilization and neonatal care. The conclusion of the current review is that the use of melatonin as an adjuvant therapy seems to be well funded for macular degeneration, glaucoma, protection of the gastric mucosa, irritable bowel syndrome, arterial hypertension, diabetes, side effects of chemotherapy and radiation in cancer patients or hemodialysis in patients with renal insufficiency and, especially, for sleep disorders of circadian etiology (jet lag, delayed sleep phase syndrome, sleep deterioration associated with aging, etc.) as well as in those related with neurological degenerative diseases (Alzheimer, etc.,) or Smith-Magenis syndrome. The utility of melatonin in anesthetic procedures has been also confirmed. More clinical studies are required to clarify whether, as the preliminary data suggest, melatonin is useful for treatment of fibromyalgia, chronic fatigue syndrome, infectious diseases, neoplasias or neonatal care. Preliminary data regarding the utility of melatonin in the treatment of ulcerative colitis, Crohn's disease, rheumatoid arthritis are either ambiguous or negative. Although in a few cases melatonin seems to aggravate some conditions, the vast majority of studies document the very low toxicity of melatonin over a wide range of doses.
20018080 Effects of covariates and interactions on a genome-wide association analysis of rheumatoid 2009 Dec 15 While genetic and environmental factors and their interactions influence susceptibility to rheumatoid arthritis (RA), causative genetic variants have not been identified. The purpose of the present study was to assess the effects of covariates and genotype x sex interactions on the genome-wide association analysis (GWAA) of RA using Genetic Analysis Workshop 16 Problem 1 data and a logistic regression approach as implemented in PLINK. After accounting for the effects of population stratification, effects of covariates and genotype x sex interactions on the GWAA of RA were assessed by conducting association and interaction analyses. We found significant allelic associations, covariate, and genotype x sex interaction effects on RA. Several top single-nucleotide polymorphisms (SNPs) (~22 SNPs) showed significant associations with strong p-values (p < 1 x 10-4 - p < 1 x 10-24). Only three SNPs on chromosomes 4, 13, and 20 were significant after Bonferroni correction, and none of these three SNPs showed significant genotype x sex interactions. Of the 30 top SNPs with significant (p < 1 x 10-4 - p < 1 x 10-6) interactions, ~23 SNPs showed additive interactions and ~5 SNPs showed only dominance interactions. Those SNPs showing significant associations in the regular logistic regression failed to show significant interactions. In contrast, the SNPs that showed significant interactions failed to show significant associations in models that did not incorporate interactions. It is important to consider interactions of genotype x sex in addition to associations in a GWAA of RA. Furthermore, the association between SNPs and RA susceptibility varies significantly between men and women.
19066899 Prevalence of rheumatic diseases and disability in China. 2009 Mar The objective of this study was to provide a single source for the best available estimates of the national prevalence of common rheumatic disorders and rheumatic disability by reviewing the epidemiological surveys conducted in China. Relevant publications were retrieved by search engines in both the English and the Chinese language web sites. Only community-based surveys conducted in China were included. A pooled prevalence with 95% confidence interval was calculated. Forty-one surveys met the inclusion criteria. Prevalence of rheumatic pain varied from 11.6 to 46.4%, with significantly higher rate in northern China in comparison to the southern part. Prevalence of rheumatic disability, however, did not increase with higher latitude. Limitation to daily life and work was 1-2 and 3-6%, of general population, respectively. The pooled prevalence of rheumatoid arthritis, ankylosing spondylitis, and undifferentiated spondylarthropathy is 0.37, 0.22 and 0.57%, respectively. The estimated prevalence is 37.7/100,000 for systemic lupus erythematosus, and 0.45% for primary Sjögren's syndrome. In the past decade, prevalence of gout and hyperuricemia was 0.22-0.43 and 12.1-25.2%, respectively. In elderly Chinese age >or=60, prevalence of symptomatic cervical OA, lumbar OA, knee OA and hand OA was 14.5, 24.0, 19.4, and 5.0%, respectively. Symptomatic hip OA was rare. Rheumatoid arthritis and gout are less frequent in Chinese than in Caucasians. The prevalence of ankylosing spondylitis, systemic lupus erythematosus and primary Sjögren's syndrome is comparable to that in Caucasians. In comparison to the whites, the Chinese population has a higher prevalence of knee OA, a lower prevalence of hand OA, and a much lower prevalence of hip OA.
20059240 Quantitative three-dimensional photoacoustic tomography of the finger joints: an in vivo s 2009 Nov We present for the first time in vivo full three-dimensional (3-D) photoacoustic tomography (PAT) of the distal interphalangeal joint in a human subject. Both absorbed energy density and absorption coefficient images of the joint are quantitatively obtained using our finite-element-based photoacoustic image reconstruction algorithm coupled with the photon diffusion equation. The results show that major anatomical features in the joint along with the side arteries can be imaged with a 1-MHz transducer in a spherical scanning geometry. In addition, the cartilages associated with the joint can be quantitatively differentiated from the phalanx. This in vivo study suggests that the 3-D PAT method described has the potential to be used for early diagnosis of joint diseases such as osteoarthritis and rheumatoid arthritis.
21694922 Advances in the management of gout: critical appraisal of febuxostat in the control of hyp 2010 Gout recently passed rheumatoid arthritis to become the most common inflammatory arthritis in the United States (US). However, epidemiologic studies indicate that the quality of gout management is suboptimal owing to both patient and physician issues. Only three options for urate-lowering therapy are currently available in the US: allopurinol, probenecid, and recently, febuxostat. Probenecid is generally safe except for the occurrence of urolithiasis, but is only effective for the subset of patients with better kidney function. Allopurinol use is limited due to its side effects, potential toxicity of uncertain magnitude in patients with renal disease, and failure to achieve targeted serum urate levels. In part this failure may be due to the necessity for it to be titrated for optimal therapeutic effect. Febuxostat is a new medication that may offer several advantages and can be given as an alternative to allopurinol. We review the basic biology and clinical performance of febuxostat, and consider the potential utility of this agent in comparison to the older, better-established gout therapeutics.
19725489 Acupuncture for pain. 2009 Sep 1 Acupuncture is increasingly used as an alternative or complementary therapy for the treatment of pain. It is well tolerated, with a low risk of serious adverse effects. Traditional and modern acupuncture techniques may result in reported improvement in pain patterns. Research on acupuncture has had a number of limitations, including: incomplete understanding of the physiologic effects of acupuncture; ineffective blinding of participants; unclear adequacy of acupuncture "dose;" difficulty in identification of suitable sham or placebo treatments; and the use of standardized treatment regimens rather than the individualized approach that characterizes most acupuncture practice. Controlled trials have been published regarding acupuncture for lumbar, shoulder, and neck pain; headache; arthritis; fibromyalgia; temporomandibular joint pain; and other pain syndromes. Enough data are available for some conditions to allow systematic evaluations or meta-analyses. Based on published evidence, acupuncture is most likely to benefit patients with low back pain, neck pain, chronic idiopathic or tension headache, migraine, and knee osteoarthritis. Promising but less definitive data exist for shoulder pain, fibromyalgia, temporomandibular joint pain, and postoperative pain. Acupuncture has not been proven to improve pain from rheumatoid arthritis. For other pain conditions, there is not enough evidence to draw conclusions.
21159208 Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis develop 2010 Dec 16 BACKGROUND: Collagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis. METHODS: Female B10.Q-ncf1*/*mice were sham-operated or ovariectomized, and CIA was induced. 22 days later, when 30% of the mice had developed arthritis, treatment with raloxifene, estradiol or vehicle was started, and the clinical disease was evaluated continuously. Treatment was continued until day 56 after immunization. At termination of the experiment (day 73), bone mineral density (BMD) was analyzed, paws were collected for histological examination, and sera were analyzed for markers of cartilage turnover and pro-inflammatory cytokines. RESULTS: Raloxifene and estradiol treatment, as well as endogenous estrogen, decreased the frequency of arthritis, prevented joint destruction and countered generalized osteoporosis. These effects were associated with lower serum levels of the pro-inflammatory cytokine IL-6. CONCLUSIONS: This is the first study to show that raloxifene and estradiol can ameliorate established erosive arthritis and inflammation-triggered osteoporosis in this chronic arthritis model. We propose that treatment with raloxifene could be a beneficial addition to the treatment of postmenopausal RA.
20802320 The association of keratoconus with immune disorders. 2010 Nov PURPOSE: To evaluate the association between keratoconus (KC) and immune disorders (IDs). METHODS: A retrospective observational case-control study of all the members in the Central District of Clalit Health Services in Israel who were diagnosed to have KC (years 2000-2007; n = 426) and 1704 age- and gender-matched controls. We calculated the prevalence of the following IDs: rheumatoid arthritis, ulcerative colitis, arthropathy, amyloidosis, systemic lupus erythematosus, celiac disease, multiple sclerosis, myasthenia gravis, polymyalgia rheumatica, idiopathic thrombocytopenic purpura, Crohn disease, Hashimoto thyroiditis, autoimmune hepatitis, irritable bowel syndrome, asthma, and environmental allergy. The odds ratio (OR) of having IDs among patients with KC was compared with controls. RESULTS: The association between KC and the following IDs was statistically significant: rheumatoid arthritis [OR = 8.1; 95% (confidence interval) CI: 1.5-44.2], ulcerative colitis (OR = 12.1; CI: 1.3-116), autoimmune chronic active hepatitis (OR = 6; CI: 1.01-36), Hashimoto thyroiditis (OR = 2.0; CI: 1.2-3.3), arthropathy (OR = 1.4; CI: 1.1-1.8), asthma (OR = 2.1; CI: 1.4-3.2), environmental allergy (OR = 1.3; CI: 1.02-1.75), and irritable bowel syndrome (OR = 5; CI: 2.1-12.1). Two autoimmune diseases, multiple sclerosis (OR = 2; CI: 0.2-22) and Crohn disease (OR = 1.6; CI: 0.3-8.3), were more prevalent among patients with KC but did not reach statistical significance. CONCLUSION: Some strong associations between KC and several immune conditions of autoimmune diseases and allergic IDs may point to the role of the immune system in the pathogenesis of KC.
19604259 Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in B cell-d 2009 Aug B cell-directed therapies are promising treatments for autoimmune disorders. Besides targeting CD20, newer B cell-directed therapies are in development that target other B cell surface molecules and differentiation factors. An increasing number of B cell-directed therapies are in development for the treatment of autoimmune disorders. Like rituximab, which is approved as a treatment for rheumatoid arthritis (RA), many of these newer agents deplete B cells or target pathways essential for B cell development and function; however, many questions remain about their optimal use in the clinic and about the role of B cells in disease pathogenesis. Other therapies besides rituximab that target CD20 are the furthest along in development. Besides targeting CD20, the newer B cell-directed therapies target CD22, CD19, CD40-CD40L, B cell activating factor belonging to the TNF family (BAFF) and A proliferation-inducing ligand (APRIL). Rituximab is being tested in an ever-increasing number of autoimmune disorders and clinical studies of rituximab combined with other biological therapies are being pursued for the treatment of rheumatoid arthritis (RA). B cell-directed therapies are being tested in clinical trials for a variety of autoimmune disorders including RA, systemic lupus erythematosus (SLE), Sjögren's syndrome, vasculitis, multiple sclerosis (MS), Graves' disease, idiopathic thrombocytopenia (ITP), the inflammatory myopathies (dermatomyositis and polymyositis) and the blistering skin diseases pemphigus and bullous pemphigoid. Despite the plethora of clinical studies related to B cell-directed therapies and wealth of new information from these trials, much still remains to be discovered about the pathophysiological role of B cells in autoimmune disorders.
19295413 Experience of mycophenolate mofetil in 10 patients with autoimmune-related interstitial lu 2009 May BACKGROUND: Interstitial lung disease (ILD) is a frequent manifestation of connective tissue disease (CTD), especially systemic sclerosis (SSc), polymyositis-dermatomyositis, and rheumatoid arthritis. ILD related to CTDs heralds a poor prognosis and is associated with high mortality and 60% of patients have evidence of ILD. Cyclophosphamide (CYC) is extensively used in SSc ILD with moderate initial response but a poor long-term outcome, and is associated with significant toxicity. RESULTS: Mycophenolate mofetil (MMF) was administered to 10 patients with autoimmune-related ILD: 4 with SSc, 3 with rheumatoid arthritis, 2 with polymyositis, and 1 with systemic lupus erythematosus and Sjögren syndrome. Five patients received remote CYC infusion. Ten patients had improvement in alveolitis, symptoms (cough, dyspnea, and chest discomfort), perceived quality of life and activity levels. Four of 5 patients discontinued oxygen. Two of 8 repeat high-resolution computed tomography improved, 6 stabilized, none worsened. Pulmonary function testing in 1 of 9 patients showed worsening, 3 with improvement and 5 stabilized. Serial echocardiograms revealed no new pulmonary arterial hypertension and no worsening of preexisting pulmonary arterial hypertension. Very importantly, averaged prednisone dose decreased from 58 to 1.4 mg without worsening. CONCLUSION: MMF is safe, well tolerated, and allows reduction or discontinuation of prednisone without worsening of symptoms or objective progression of disease. MMF is less toxic and its targeted antifibrotic properties make it a potentially more effective agent than CYC that may supplant it as a first-line agent or provide sensible post-CYC maintenance or synergistic strategy in the treatment of CTD-ILD.
21187837 Carnosine inhibits degradation of hyaluronan induced by free radical processes in vitro an 2010 OBJECTIVE: New ways of supplementary or combinatory therapy of rheumatoid arthritis (RA) are of great importance. The aim is to find an additive to classical RA therapy with natural molecules without side effects possessing anti-inflammatory and anti-oxidative properties. In this study we investigated the anti-oxidative and anti-inflammatory properties of the endogenous natural compound carnosine (CARN) in vitro and in vivo. Moreover, we tested also the inhibitory properties of the drug methotrexate (MTX) on dynamic viscosity of hyaluronan (HA) solutions in the same manner. METHODS: For in vitro testing of the inhibitory properties of CARN against degradation of HA solutions, we used the model of degradation of hyaluronan (HA) induced by free radicals. Both substances, CARN and MTX, were compared to glutathione (GSH). Rotational viscometry was used in evaluation of protective properties of compounds studied. The ability of CARN to restore the redox imbalance occurring in adjuvant arthritis (AA) of rats was also tested. We monitored the effect of CARN on hind paw volume (HPV) and on the levels of protein carbonyls, and thiobarbituric acid reacting substances (TBARS) in AA. RESULTS: In the reaction system with the prevalence of •OH and/or peroxy-type radicals, CARN in 200 μmol/L concentration tested was shown to exert a protective action on HA degradation. MTX was less effective than CARN in preventing HA degradation. Its ability to protect HA against radical degradation was evident only at the highest concentration of 400 μmol/L. In AA, carnosine significantly reduced TBARS and protein carbonyls in plasma, and also decreased the HPV of animals most effectively on the day 14. CONCLUSIONS: CARN proved its inhibitory properties against degradation of HA solutions at experimental conditions in vitro and showed its beneficial efficiency in vivo. Moreover, it reduced also HPV, the clinical marker of inflammation in AA.
20062603 Poststaphylococcal coagulase negative reactive arthritis: a case report. 2009 Dec 18 We report a case of a 49-year-old patient who developed poststaphylococcal coagulase negative reactive arthritis. The woman presented with constitutional symptoms, arthritis, urinary infection and conjunctivitis. The blood culture was positive for the staphylococcal coagulase negative infection. Erythrocyte sedimentation rate and C-reactive protein were elevated, whereas the rheumatoid factor was negative. Radiographic findings confirmed diagnosis of pleuropneumonia, and one year later of chronic asymmetric sacroileitis. Physicians should be aware of possible reactive arthritis after staphylococcal coagulase negative bacteremia.
19250226 Introduction: arthritis and myositis. 2009 Feb In this chapter background medical information pertinent to the use of MRI and/or ultrasound in various musculoskeletal conditions is presented. Appreciation of the genetic, biochemical, histological, and immunological features of rheumatic diseases will be of benefit to the technician responsible for performing and interpreting these types of interrogations. For example, recognizing that cartilage disorder predates bone findings in osteoarthritis will help identify early versus late degenerative findings. Similarly, understanding the fibrovascular nature of rheumatoid pannus will help guide the use of more sophisticated ultrasound techniques such as power Doppler.
20528612 Emerging drugs for psoriatic arthritis. 2010 Sep IMPORTANCE OF THE FIELD: The socioeconomic burden of psoriatic arthritis (PsA) is considerable and not different from that of rheumatoid arthritis. Current treatment options do not always allow reaching the therapeutic objectives consisting of the remission of symptoms and prevention of the appearance of damage in the early stage of PsA or the blocking of PsA progression in the established cases. AREAS COVERED IN THIS REVIEW: After reviewing the current treatment choices, we examine the new drugs in clinical Phase II and III trials for PsA up to January 2010. Information was mainly obtained from the network of international clinical trial registries. WHAT THE READER WILL GAIN: The current management of PsA includes NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-alpha blocking agents. These last drugs are more effective than traditional DMARDs on symptoms/signs of inflammation, quality of life and function and can inhibit the progression of the structural joint damage. Recent advancement in the knowledge of the immunopathogenesis of PsA has permitted the development of novel drugs including new TNF-alpha blockers, IL-1, -6, -12, -23 and -17 inhibitors, co-stimulator modulation inhibitors, B-cell depleting agents, small molecules and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand inhibitors. TAKE HOME MESSAGE: The currently available anti-TNF-alpha blocking agents have revolutionized the management of PsA. However, there is a need for more effective and safer drugs.