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ID PMID Title PublicationDate abstract
18628282 Thymic function in juvenile idiopathic arthritis. 2009 Jun OBJECTIVE: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined. METHODS: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alphaTREC/SigmabetaTREC ratio. Lastly, regulatory T cells (T(Reg)) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset. RESULTS: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD. CONCLUSIONS: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA" suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.
16482643 Preliminary validation of clinical remission criteria using the OMERACT filter for select 2006 Apr OBJECTIVE: To begin the validation process of the preliminary criteria for inactive disease (ID), clinical remission on medication (CRM), and clinical remission off medication (CR) in children with select forms of juvenile idiopathic arthritis (JIA). METHODS: We used the OMERACT filter paradigm to estimate the validity of the criteria within each of the filter's 3 components: truth, discrimination, and feasibility, in 5 categories of JIA: systemic arthritis, persistent and extended oligoarthritis, and rheumatoid factor-positive and negative polyarthritis. Data sources for determining validity estimates included a Delphi questionnaire survey sent to 246 pediatric rheumatologists in 34 countries, a consensus conference attended by 20 senior pediatric rheumatologists representing 9 countries, a retrospective chart review of 437 patients with JIA from 3 tertiary care clinics who had been followed between 4 and 22 years, and the literature. RESULTS: Truth component: face and content validity. These aspects of validity were largely established via the Delphi questionnaire exercise and the consensus conference. Using an 80% consensus level, participants felt that a set of non-redundant variables could effectively differentiate the clinical states of ID, CRM, and CR. Criterion validity could not be irrefutably established because no gold standard for inactive disease exists for JIA. As an alternative, published investigations of remission in JIA were used to estimate concurrent and convergent validity, as surrogates for criterion validity and as indicators of overall construct validity. Correlational analyses revealed the new criteria to have good construct validity. Discrimination component: the criteria demonstrated moderate to high levels of classification, prognosis, and responsiveness (sensitivity to change) using data from the chart review. Patients who were able to attain CR remained disease-free for substantially longer periods than did those who attained only ID or CRM. Responsiveness was evidenced by the ability of the criteria to allow movement of most patients between the disease states, consistent with what is known of the course of the disease. Feasibility component: Results of the Delphi and consensus conference produced a set of criteria that are easily, quickly, and inexpensively completed in the physician's office, and present minimal or no risk to the patient. CONCLUSION: The preliminary criteria demonstrated moderate to excellent validity characteristics in some, but not all components of the OMERACT filter. Prospective validation studies are under way.
18669081 [The dry eye syndrome in children with juvenile idiopatic arthritis]. 2008 PURPOSE: The aim of the study was to evaluate the dry eye syndrome in children with juvenile idiopathic arthritis (JIA), and its relation to the immunological markers of the JIA (antynuclear antybodies ANA and rheumatoid factor RF). MATERIAL AND METHODS: The study included 62 children with JIA. The age of patients during the first ophthalmic examination ranged from 9 to 18 years (62 children). A control group consisted of 49 healthy children. The time of observation was 18 months during which the children and adolescents were subjected to complex ophthalmic examinations (including a history of eye discomfort and Schirmer and BUT tests), in the intervals of 9 months. The diagnosis towards dry eye syndrome was made (including a history of eye discomfort and Schirmer and BUT tests). RESULTS: The majority of children with JIA complained of discomfort in the eyes. The difference appeared to be statistically significant between the group of children with JIA and the control group in the range of 5 features. The results of Schirmer test were found to be inadequate in 7 children (13%) and of BUT test in 9 children (15%). In total, inadequate results of Schirmer and/or BUT tests and a high score of discomfort evaluation were detected in 11 patients (17.7%). CONCLUSIONS: 1. The dry eye syndrome may occur in the course of JIA in children without any distinct clinical signs, resulting in subjective symptoms and decreasing the quality of life. 2. No correlation between immunological markers of the JIA and ocular changes was observed.
18793632 BAFF-targeting therapy, a promising strategy for treating autoimmune diseases. 2008 Nov 12 Since B cell activating factor belonging to tumor necrosis factor (TNF) family (BAFF) has been identified as a critical factor for B cell maturation and survival, convincing evidence indicates that deregulation of BAFF is involved in pathogenesis of B cell related autoimmune diseases. Blockade of BAFF activity significantly improves the symptoms of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis both in animal models and clinical trials. Therefore, BAFF-targeting therapy is a promising approach to treat B cell related autoimmune diseases.
17589405 Postoperative evaluation of plasma interleukin-6 concentration in patients after total hip 2006 Oct 31 Background. The aim of this study was to examine the circulating IL-6 in patients after orthopedic surgery, and the correlation between IL-6, body temperature and the level of postoperative pain. Material and methods. We studied 27 patients undergoing orthopedic hip arthroplasty, including 14 with osteoarthritis and 13 with rheumatoid arthritis. The local medical ethics committee approved the study, and all patients signed informed consent upon being enrolled. All patients received spinal anesthesia. Samples were collected just before and at 24, 48, and 72 hours after surgery; at the same time, body temperature and reported pain were monitored. Results. Plasma IL-6 levels showed a decrease after surgery. This suggests some influence of plasma cytokines on the possible beneficial effects of regional anesthesia on the clinical course after surgery. The level of IL-6 was associated with body temperature and pain in patients after operation. Conclusions. The plasma concentration of IL-6 is a significant factor affecting body temperature and pain after surgery in patients who have undergone hip arthroplasty.
18728714 Cannabinoids in the management of difficult to treat pain. 2008 Feb This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol((R))) and nabilone (Cesamet((R))) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex((R)), a cannabis derived oromucosal spray containing equal proportions of THC (partial CB(1) receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB(1) receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.
18697494 [Ruptured pseudoaneurysm of the renal artery associated with segmental arterial mediolysis 2008 Jul We present a 71-year-old woman with spontaneous perinephric hematoma due to a rupture of pseudoaneurysm of the right renal artery on the fourth day after radical cystectomy and bilateral ureterocutaneostomy for bladder cancer. This patient received steroid therapy for chronic rheumatoid arthritis for several years. The digital subtraction angiography of the right renal artery showed two pseudoaneurysms in the anterior inferior segmental branch and the posterior inferior segmental branch. Transarterial coil embolization of the right renal artery proximally and distally to the two aneurysms was performed without complications. Moreover, the additional angiography showed typical string-of-beads appearance and small aneurysms in abdominal visceral arteries, suggesting segmental arterial mediolysis (SAM) as a possible etiology. Differential diagnoses of SAM are discussed.
18454584 Omega-3 fatty acids: proven benefit or just a "fish story"? 2008 Mar The potential health benefit of omega-3 fatty acids has been the focus of much research in the past decade. While the typical diet in the United States has a much greater ratio of omega-6 fatty acids compared with omega-3 fatty acids, research is showing that shifting this ratio-by increased consumption of fatty fish or fish oil supplements-may provide significant health benefits. Reductions in cardiovascular risk, depression, and rheumatoid arthritis symptoms have been correlated with omega-3 fatty acid intake, and there is increased interest in the use of omega-3 fatty acid supplementation for other psychiatric illnesses and prevention of Alzheimer's disease.
21794545 [Common genetic factors in autoimmunity]. 2008 Mar Autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) among others, are characterized by a complex etiology in which the combination of several genetic and environmental factors leads to an altered immune response. Several lines of evidence, such as the presence of chromosomal regions associated with several AIDs and the existence of similar gene expression patterns in autoimmune disorders, suggest that different AIDs share common genetic factors. The identification of common genetic factors associated with autoimmunity is of great relevance, since it will allow a better understanding of disease pathogenesis and could help for the development of molecular diagnosis tools and new therapeutic targets. In the past few years, a great progress has been made in the knowledge of the common genetic factors associated with autoimmunity. The PTPN22 gene, an important regulator of T cell response, has been identified as a relevant genetic marker for AIDs. This gene is implicated in the susceptibility to autoimmune disorders such as, RA, SLE, and type 1 diabetes (T1D). In the case of RA the association with the PTPN22 gene is the most replicated after association with HLA genes. In addition, genes implicated in the altered balance between cytokines, such as MIF and IRF5, have been identified as genetic factors predisposing to AIDs.
18239324 Pulmonary sequestration with elevated serum level of progastrin-releasing peptide. 2008 A 74-year-old woman with rheumatoid arthritis was referred for a mass incidentally noted on chest radiograph. Chest CT scan showed cystic lesions in the right lower lobe. The lesion was evaluated as bronchiectasis, and she was followed up. Three years after the initial presentation, the appearance of the lesion had changed significantly and an elevated air-fluid level in the cystic structures was shown on chest CT scan. The preoperative serum progastrin-releasing peptide (proGRP) level was elevated (108.0 pg/ml; normal: <50 pg/ml). Histopathological specimen obtained by standard lower lobectomy confirmed that the lesion was an intralobar pulmonary sequestration. In the resected lobe, there was no malignant finding, but there were neuroendocrine tumorlet cells, which were positive for proGRP. One month after the resection, the serum proGRP level returned to normal. No pulmonary sequestration with high levels of proGRP has been reported, and this is the first case with elevated serum levels of proGRP.
29593453 Short Term Hyperthermia Prevents Activation of Proinflammatory Genes in Type B Synoviocyte 2007 Dec The aim of this study was to investigate the effect and mechanisms of short term hyperthermia on a series of proinflammatory genes in type-B-synoviocytes (fibroblast like synoviocytes - FLS). In vitro experiments demonstrate that exposure of FLS to elevated temperatures for the duration of 30 minutes prevents activation of a series of genes with proinflammatory properties. Exposure to hyperthermia reduces IL-1f3 induced PGE2 release, suppresses activation of the adhesion molecules VCAM-1, ICAM-1, the cytokines TNFa, IL-1a, IL-1p, IL-8 as well as COX-2 protein synthesis. Real time RT-PCR showed that hyperthermia altered gene expression at the transcriptional level. As to the mechanism of inhibition, EMSA experiments demonstrated that exposure of FLS to hyperthermia prevents IL-1f3 induced NF-κB translocation and subsequent DNA binding. Many mechanisms have been shown to be involved in hyperthermia mediated effects on NF-κB-DNA interactions. We demonstrated by Western blot experiments that in FLS, hyperthermia prevents the phosphorylation and subsequent degradation of IκBCC, therefore retaining the NF-κB complex in the cytoplasm. Such data might, at least in part, explain and provide a rationale for treating inflammation e.g. associated with rheumatoid arthritis by balneological means.
18021711 [Multiple talents of the chemokine receptor-CXCR4]. 2007 Nov CXCR4 is a clinically relevant chemokine receptor that has first gained attention as one of the cofactors for HIV entry into target cells. Moreover, the receptor is involved in cancer cell migration to distant metastatic sites and immune effector recruitment in inflammatory diseases such as asthma and rheumatoid arthritis. Unfortunately, pharmacologic intervention is complicated by the vital function of CXCR4 in the organism. The most prominent of these functions is its role in stem cell homing. The CXCR4 chemokine ligand, produced by bone marrow stromal cells, leads both to migration of hematopoietic stem cells towards this niche and their retention in this compartment. As models of G-protein coupled receptor (GPCR) activation evolve, it becomes clear that multiple factors modulate the functional outcome of ligand binding to a receptor. Modulation of GPCR activity, for example by allosteric ligands, may permit more subtle therapeutic approaches adapted to long term treatment. In addition, GPCR signalling can be altered by hetero-oligomerization of GPCRs. In this perspective, it might be possible to achieve modulation of GPCR signalling by also targeting the oligomerization partner of a given receptor. This approach is described using the example of strategies that aim at the optimization of stem cell homing in the context of cord blood-derived hematopoietic stem cell transplantation.
17110139 Glutamate receptors and pain. 2006 Oct Pain is an important survival and protection mechanism for animals. However, chronic/persistent pain may be differentiated from normal physiological pain in that it confers no obvious advantage. An accumulating body of pharmacological, electrophysiological, and behavioral evidence is emerging in support of the notion that glutamate receptors play a crucial role in pain pathways and that modulation of glutamate receptors may have potential for therapeutic utility in several categories of persistent pain, including neuropathic pain resulting from injury and/or disease of central (e.g., spinal cord injury) or peripheral nerves (e.g., diabetic neuropathy, radiculopathy) and inflammatory or joint-related pain (e.g., rheumatoid arthritis, osteoarthritis). This review focuses on the role of glutamate receptors, including both ionotropic (AMPA, NMDA and kainate) and metabotropic (mGlu1-8) receptors in persistent pain states with particular emphasis on their expression patterns in nociceptive pathways and their potential as targets for pharmacological intervention strategies.
16918413 Leukocyte adhesion: a suitable target for anti-inflammatory drugs. 2006 Inflammatory responses in all tissue compartments require the emigration of leukocytes from the microvasculature through endothelial cells into the respective microenvironment. Adhesion to endothelial cells is the most crucial step in order to facilitate selective and effective capture of leukocytes. The sequence of adhesions events, e.g. rolling, tethering, and firm adhesion are tightly regulated by a variety of molecules expressed by endothelial cells and leukocytes either constitutively or after induction by mainly inflammatory mediators. In diseases with a prominent inflammatory response such as psoriasis, rheumatoid arthritis, or Crohn's disease, interference with leukocyte adhesion and/or emigration may be of substantial clinical effect. A number of therapeutic approaches by using monoclonal antibodies, designed molecules, and other modulators of adhesion molecule expression have been investigated in clinical trials. This review aims to give an overview about the current knowledge of targeting adhesion molecules as a therapeutic strategy to treat inflammatory diseases.
16710576 Autoimmune diseases and vitamin D receptor Apa-I polymorphism are associated with vitiligo 2006 Vitiligo has been associated with the host's genetic profile, metabolic abnormality and immunostatus. The purpose of this study was to investigate the association of vitiligo with autoimmune diseases for 31 out of 39 subjects with vitiligo and their first-degree relatives living in a small Caucasian inbred rural community. They were compared with healthy individuals. A 2.28% prevalence of vitiligo was calculated and the presence of consanguine marriages (72.3%) was noted for this community. Our results indicate an increased prevalence of thyroidopathies, diabetes mellitus and rheumatoid arthritis in families with vitiligo. We also show that the Apa-I polymorphism of the vitamin D receptor gene is associated with vitiligo. This is the first study of its kind performed in Romania suggesting that the vitamin D receptor gene might play a role in the aetiopathogenesis of skin depigmentation.
16209908 A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol a 2006 This study examines the current knowledge of physiological and clinical effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) and presents a rationale for their combination in pharmaceutical preparations. Cannabinoid and vanilloid receptor effects as well as non-receptor mechanisms are explored, such as the capability of THC and CBD to act as anti-inflammatory substances independent of cyclo-oxygenase (COX) inhibition. CBD is demonstrated to antagonise some undesirable effects of THC including intoxication, sedation and tachycardia, while contributing analgesic, anti-emetic, and anti-carcinogenic properties in its own right. In modern clinical trials, this has permitted the administration of higher doses of THC, providing evidence for clinical efficacy and safety for cannabis based extracts in treatment of spasticity, central pain and lower urinary tract symptoms in multiple sclerosis, as well as sleep disturbances, peripheral neuropathic pain, brachial plexus avulsion symptoms, rheumatoid arthritis and intractable cancer pain. Prospects for future application of whole cannabis extracts in neuroprotection, drug dependency, and neoplastic disorders are further examined. The hypothesis that the combination of THC and CBD increases clinical efficacy while reducing adverse events is supported.
19469306 [Metalloproteinases: therapeutic target in atherosclerosis]. 2008 May Matrix metalloproteinases are a family of enzymes which collectively can cleave all components of the extracellular matrix. In physiological situations, the expression of matrix metalloproteinases is very low. The increase of their expression leads to several diseases as atherosclerosis, restenosis, rheumatoid arthritis and cancers. In atherosclerosis, metalloproteinases are implicated in the rupture of the atheromatous plaque and contribute to acute vascular accident. Consequently, several studies hypothesized that the inhibition of matrix metalloproteinases activity could reduce the volume of the atheromatous plaque and prevent its destabilisation and therefore could be useful in the treatment of atherosclerosis. However, clinical results have so far been inconclusive because matrix metalloproteinases inhibitors are not very specific. The development of selective inhibitors and gene transfer approaches may better suit the treatment of atherosclerosis.
19081854 The role of nuclear factor-kappaB in the development of autoimmune diseases: a link betwee 2008 Although autoimmune diseases are relatively common, mechanisms that lead to their development remain largely unknown. Nuclear factor-kappaB (NF-kappaB), as a key transcription factor involved in the regulation of immune responses and apoptosis, appears to be a good candidate for studies on the pathogenesis of autoimmunity. This review presents how perturbations of the NF-kappaB signaling pathway may contribute to self-tolerance failure, initiation of autoimmune inflammatory response as well as its persistent maintenance and therefore to the development of common autoimmune diseases including rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, thyroid autoimmune diseases, systemic lupus erythematosus as well as inflammatory bowel diseases and psoriasis. A special emphasis is put on the genetic variations in the NF-kappaB related genes and their possible association with susceptibility to autoimmune diseases, as well as on the therapeutic potential of the NF-kappaB targeted strategies in the treatment of autoimmunity.
19023530 Pulse steroid therapy. 2008 Oct Intravenous supra-pharmacological doses of corticosteroids are used in various inflammatory and autoimmune conditions because they are cumulatively less toxic than sustained steroid treatment at lower quantitative dosage. Their action is supposed to be mediated through non-genomic actions within the cell. Common indications for use in children include steroid resistant and steroid dependent nephrotic syndrome, rapidly progressive glomerulonephritis, systemic vasculitis, systemic lupus erythematosus, acute renal allograft rejection, juvenile rheumatoid arthritis, juvenile dermatomyositis, pemphigus, optic neuritis, multiple sclerosis and acute disseminated encephalomyelitis. Methylprednisolone and dexamethasone show similar efficacy in most conditions. Therapy is associated with significant side effects including worsening of hypertension, infections, dyselectrolytemia and behavioral effects. Adequate monitoring is essential during usage.
18700174 Human parvovirus B19 infection and autoimmunity. 2008 Dec Human parvovirus B19 infection is responsible for a wide range of human diseases ranging from mild erythema infectiosum in immunocompetent children to fetal loss in primary infected pregnant women and aplastic anemia or lethal cytopenias in adult immunocompromised patients. Since persistent viral infection is responsible for an autoimmune response and clinical symptoms can mimic autoimmune inflammatory disorders, parvovirus B19 is the object of intense efforts to clarify whether it is also able to trigger autoimmune diseases. Indeed the virus has been implicated as the causative or the precipitating agent of several autoimmune disorders including rheumatoid arthritis, systemic lupus, antiphospholipid syndrome, systemic sclerosis and vasculitides. Molecular mimicry between host and viral proteins seems to be the main mechanism involved in the induction of autoimmunity. By means of a random peptide library approach, we have identified a peptide that shares homology with parvovirus VP1 protein and with human cytokeratin. Moreover the VP peptide shares similarity with the transcription factor GATA1 that plays an essential role in megakaryopoiesis and in erythropoiesis. These new data sustain the role played by molecular mimicry in the induction of cross-reactive (auto)antibodies by parvovirus B19 infection.