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ID PMID Title PublicationDate abstract
18514052 [Amyloidosis AA]. 2008 Jul Amyloidosis remains one of the three major types of multisystemic amyloidosis, with immunoglobulinic (AL) and hereditary varieties. Recently, however, its incidence has been decreasing in Western countries. Inflammatory disorders are currently the major causes of amyloid-associated (AA) amyloidosis; first of all it is rheumatoid arthritis, then ankylosing spondylarthropathy and auto-inflammatory syndromes. Some tumours may lead to amyloidosis, including Castleman's disease. Complete surgery can result in regression of amyloid. It is not exactly known why some patients develop a progressive amyloidosis, whereas others do not. A permanent acute phase response, ideally evaluated with serial measurement of serum protein SAA, the precursor of the AA protein deposited in tissues, seems to be a prerequisite to the development of inflammatory (AA) amyloidosis. Genetic factors have however been recently emphasized. Nephropathy is the main clinical manifestation of amyloidosis. Serial search for proteinuria and serum creatinine measurement remain quite useful for detecting the first sign of renal impairment during chronic inflammatory disorders. A thorough diagnosis of AA amyloidosis deserves to gather whole clinical and pathological data, including immunohistochemistry. Some pitfalls exist and another type of amyloidosis should not be misdiagnosed as the AA variety. Ultimate renal failure and gut involvement with denutrition account for the persistent poor prognosis of AA amyloidosis. Current treatment aim at decreasing the inflammatory response; drugs targeting other steps of amyloid deposition are currently developed.
18241178 Tumour necrosis factor alpha inhibitors: screening for tuberculosis infection in inflammat 2008 Feb 4 Tumour necrosis factor (TNF) alpha inhibitors such as infliximab are becoming more widely used for the treatment of selected patients with Crohn's disease, rheumatoid arthritis, and other inflammatory disorders. TNFalpha inhibitors increase the risk of serious infections, including tuberculosis. Screening for and treatment of latent tuberculosis infection before infliximab therapy reduces the risk of developing active tuberculosis. New blood tests that measure interferon gamma production are an alternative to traditional tuberculin skin testing and offer some significant advantages over skin testing for screening of latent tuberculosis infection.
17409707 [Metabolism of non-steroidal anti-inflammatory drugs by peroxidase: implication for gastro 2007 Apr Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammatory diseases including rheumatoid arthritis and gout. The anti-inflammatory action of NSAIDs is due to the inhibition of prostaglandin synthesis by preventing cyclooxygenase (COX) activity of prostaglandin H synthase (PGS). However, administration of NSAIDs causes gastrointestinal mucosal lesions and a decrease of granulocytes as side effects. PGS catalyzes two distinct enzyme reactions: (1) bis-dioxygenation of arachidonic acid catalyzed by COX activity of PGS to form PGG(2); and (2) reduction of the hydroperoxide group in PGG(2) by PGS hydroperoxidase. Most NSAID are oxidized by peroxidases to produce NSAID radicals that damage biological components such as lipids and enzymes. Indomethacin, phenylbutazone, and piroxicam are more toxic under aerobic conditions than anaerobic conditions during the interaction with peroxidase. We discuss the contribution of peroxidases in the formation of gastrointestinal mucosal lesions induced by NSAIDs.
17334042 [Annexin-1: 2nd messanger of the anti-inflammatory actions of glucocorticoids]. 2006 Oct Glucocorticoids have important immunosupressive properties, being used as anti-inflammatory therapeutic agents in a wide range of inflammatory and auto-immune pathologies. One of the best studied mechanisms by which glucocorticoids exert most of their anti-inflammatory actions involves the induction of the synthesis and the secretion of the mediator and effector protein annexin 1 (ANXA1). Here we review the molecular and cellular pathways involved on the glucocorticoid-induced synthesis and secretion of ANXA1 in a variety of cell types. Since its discovery as an anti-phospholipase A2 protein, ANXA1 has come a long way to encompass a wide range of cellular effects, the most relevant ones being those that directly modulate the inflammatory response. The results presented in this review open the way to further pharmacological studies which will allow the identification of the role of ANXA1 in inflamatory pathologies, namely rheumatoid arthritis.
17302210 A case of orbital abscess following porous orbital implant infection. 2006 Dec PURPOSE: We present a case of orbital abscess following porous orbital implant infection in a 73-year-old woman with rheumatoid arthritis. METHODS: Just one month after a seemingly uncomplicated enucleation and porous polyethylene (Medpor) orbital implant surgery, implant exposure developed with profuse pus discharge. The patient was unresponsive to implant removal and MRI confirmed the presence of an orbital pus pocket. Despite extirpation of the four rectus muscles, inflammatory granulation debridement and abscess drainage, another new pus pocket developed. RESULTS: After partial orbital exenteration, the wound finally healed well without any additional abscess formation. CONCLUSIONS: A patient who has risk factors for delayed wound healing must be examined thoroughly and extreme care such as exenteration must be taken if there is persistent infection.
17168521 Histone citrullination by protein arginine deiminase: is arginine methylation a green ligh 2006 Aug 22 Protein citrullination, a once-obscure post-translational modification (PTM) of peptidylarginine, has recently become an area of significant interest because of its suspected role in human disease states, including rheumatoid arthritis and multiple sclerosis, and also because of its newfound role in gene regulation. One protein isozyme responsible for this modification, protein arginine deiminase 4 (PAD4), has also been proposed to "reverse" epigenetic histone modifications made by the protein arginine methyltransferases. Here, we review the in vivo and in vitro studies of transcriptional regulation by PAD4, evaluate conflicting evidence for its ability to use methylated peptidylarginine as a substrate, and highlight promising areas of future work. Understanding the interplay of multiple arginine PTMs is an emerging area of importance in health and disease and is a topic best addressed by novel tools in proteomics and chemical biology.
17154080 [Susceptibility genes for the development of autoimmune thyroid disease]. 2006 Dec Autoimmune thyroid disease (AITD) is caused by an immune response to self thyroid antigens. Twin studies and familial aggregation indicated that AITD is a complex disease with genetic factors and major histocompatibility complex is the most clearly established genetic factor. We confirmed the association of the co-receptor CTLA4 with AITD. We have identified the association of the SNP in the Fc receptor-like 3 with several autoimmune diseases, including AITD, SLE and rheumatoid arthritis, which SNP affected the level of autoantibody production. Furthermore, we have identified ZFAT as a susceptibility gene in 8q24 for AITD by whole-genome linkage analysis and further SNP-based dense mapping. The associated SNP in ZFAT affected the antisense transcript of ZFAT, which in turn affected the ZFAT expression.
17073677 Functional genome and proteome analyses of cutaneous autoimmune diseases. 2006 The use of functional genomics and proteomics technologies has dramatically increased through recent years with a special emphasis on cancer biology. However, a series of more recent reports has also addressed inflammatory diseases. These included studies on different autoimmune diseases, such as rheumatoid arthritis, lupus erythematosus, and systemic sclerosis. Gene and protein expression profiles from these studies have emphasized the role of cytokines, chemokines, and apoptosis-related molecules for the pathogenesis of autoimmune diseases. Much less is known about gene and protein patterns of these diseases in dermatology. Here we provide an overview on current knowledge about genomics and proteomics analyses of cutaneous autoimmune diseases. These diseases include psoriasis, lupus erythematosus, systemic sclerosis, vitiligo, and alopecia areata. The presented findings not only provide deeper insights into the pathogenesis of each individual disease but also show overlapping gene patterns suggestive for common pathogenic mechanisms. However, many open questions remain to be resolved since data about local gene expression pattern in affected tissues are still scarce.
16989586 RANK ligand inhibition with denosumab for the management of osteoporosis. 2006 Oct Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine member of the tumour necrosis factor family that is the principal final mediator of osteoclastic bone resorption. It plays a major role in the pathogenesis of postmenopausal osteoporosis, as well bone loss associated with rheumatoid arthritis, metastatic cancer, multiple myeloma, aromatase inhibitor therapy and androgen deprivation therapy. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL. By inhibiting the action of RANKL, denosumab reduces the differentiation, activity and survival of osteoclasts, thereby slowing the rate of bone resorption. Denosumab has been shown to increase bone mineral density (BMD) and reduce bone turnover in postmenopausal women with low BMD. Denosumab is a potential treatment for osteoporosis and other skeletal disorders.
16919890 Why does chloroquine impair renal function?: chloroquine may modulate the renal tubular re 2007 Chloroquine is one of the antimalaria drugs, also used to treat rheumatoid arthritis and systemic lupus erythematosus (SLE). Although well tolerated in most individuals, it was suggested that chloroquine can exert a profound influence on renal function, especially in individuals with compromised body fluid status. However, epidemiological studies are still lacking. The renal actions of chloroquine are further exacerbated by co-administration of other commonly used drugs such as paracetamol. The following discussion will focus on the evidence that chloroquine is a stimulator of nitric oxide (NO), which mediates many of its renal actions (diuresis, natriuresis and an increase in both glomerular filtration rate (GFR) and plasma vasopressin). Chloroquine appears to modulate the renal tubular response to vasopressin either by directly inhibiting cAMP generation or indirectly via NO.
16918401 Emerging peptide therapeutics for inflammatory diseases. 2006 Aug Steroids are the best known anti-inflammatory drugs and have been in use for more than 50 years. Their chronic use however was limited by safety concerns. Non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors although devoid of steroid side effects often possess gastrointestinal side effects. In addition recent data suggest that chronic use of some Cox inhibitors is associated with cardiovascular risk. Currently biologics represent the best option for many inflammatory diseases where TNFalpha is the main culprit. These include rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease and psoriasis. A wealth of information is now available on the role of different cytokines and adhesion molecules in the origin and progression of inflammatory diseases. With the success of protein therapeutics such as Etanercept (Enbrel), which binds TNFalpha and inhibits its activity, research has been focused on developing small peptides that can interfere with cytokines or specific cell surface molecules and inhibit the inflammatory reactions. Here we review these peptides that are in discovery and development phases and their potential in the treatment of inflammatory diseases.
16855137 Hypoglycemia, an old tool for new findings in the adrenomedullary hormonal system in patie 2006 Jun Over the past decades, research in patients with rheumatic disorders showed enormous progress in detecting various perturbations of the neuroendocrine system including those affecting autonomic nervous function. There is, however, a substantial lack of data on adrenomedullary hormonal system (AMHS) function in those patients. Insulin-induced hypoglycemia (IIH) represents a metabolic stressor, which elicits a counterregulatory stress response not only of the hypothalamic-pituitary axis but also of the AMHS. Therefore, in addition to traditional testing of hypothalamic-pituitary function, IIH can be used as a well-controlled functional test of the AMHS. Our recent studies showed, for the first time, attenuated epinephrine and norepinephrine responses to IIH in premenopausal females with rheumatoid arthritis (RA) and systemic sclerosis (SSc). These findings are suggestive of downregulation, or possibly defects, of the AMHS in those patients. This article reviews mechanism of the AMHS activation during IIH and demonstrates applications of the test in neuroendocrine-immune research.
18835000 Immunosuppressive pregnane glycosides from Periploca sepium and Periploca forrestii. 2008 Nov Nine pregnane glycosides containing peroxy functions in their sugar moieties (1-5 and 11-14), five oligosaccharides (6-10), six pregnane glycosides (15-20), and five cardiac glycosides (21-25) were isolated from the root barks of Periploca sepium Bge. (Asclepiadaceae) and the roots of Periploca forrestii Schltr. (Asclepiadaceae), two traditional Chinese medicines used for the treatment of rheumatoid arthritis. Among them, 1-8 are hitherto unknown. Their structures were characterized on the basis of spectroscopic analyses. In pharmacological testing, compounds 1-5 and 11-14 were found to exhibit inhibitory activity against the proliferation of T lymphocyte in vitro with IC50 values ranging from 0.29microM to 1.97microM, while the other components showed no significant inhibitory activity.
24422733 Major malformations after first trimester exposure to aspirin and NSAIDs. 2008 Sep The use of aspirin and other NSAIDs during the first trimester of pregnancy is widespread, despite inconclusive evidence regarding the possible risks for the baby. We present an overview of the current evidence relating to the associations between aspirin or NSAID use during the first trimester of pregnancy and the risk of congenital malformations. We systematically searched Medline, Embase, the Cochrane Library and the reference lists of all relevant articles from 1966 to March 2008 that examined the association between aspirin and NSAID use during the first trimester of pregnancy and the risk of congenital malformations in humans. We analyzed 30 studies that met the predefined inclusion criteria: 22 case-control studies, seven cohort studies and one randomized, controlled trial. There are not enough human data available to assess the effect of high-dose aspirin and NSAIDs in pregnant women, such as those used in the treatment of rheumatoid arthritis, osteoarthritis and pain relief. This review suggests that the exposure to aspirin or NSAIDs during the first trimester of pregnancy is associated with an increased risk of gastroschisis (aspirin), cardiac malformations (NSAIDs) and orofacial malformations (naproxen).
18355596 Distraction osteogenesis for temporomandibular joint reconstruction. 2008 Apr PURPOSE: This clinical study evaluated the use of transport distraction osteogenesis in reconstruction of the ramus-condyle unit (RCU) of the temporomandibular joint (TMJ). PATIENTS AND METHODS: Thirteen TMJ reconstructions were carried out in 12 patients. Diagnoses included tumors, trauma, ankylosis, and degenerative joint disease. The follow-up period has ranged from 7 to 59 months. RESULTS: Successful distraction was carried out in all cases, with development of solid regenerate bone and an effective new articulation. There were no complications. A good functional level was achieved in all cases. One patient with bilateral rheumatoid arthritis has experienced ongoing degenerative changes in the reconstructed condyles, with reappearance of an anterior open bite. The occlusion has remained stable in all other cases. CONCLUSIONS: Distraction osteogenesis is a promising treatment option in reconstruction of the RCU of the TMJ.
18281865 Musculoskeletal syndromes associated with malignancy (excluding hypertrophic osteoarthropa 2008 Jan PURPOSE OF REVIEW: To examine recent data about the association between rheumatic disorders and cancer. This article focuses on paraneoplastic rheumatic disorders, which usually precede by a short period of time the diagnosis of malignancy, and on malignant transformation, which occurs late in the course of rheumatic disorders. Evidence of causality between malignancies and rheumatic disorders was reviewed based on statistical indicators (standardized incidence ratios and odds ratios) and by applying Bradford Hill's criteria of causality. RECENT FINDINGS: Firm epidemiological evidence was found attesting that dermatomyositis and polymyostis may present as paraneoplastic syndromes. Several other musculoskeletal disorders may be present akin to paraneoplastic syndrome, based on clinicians' impressions, but with scarce epidemiological evidence supporting a causal determinism. In contrast, robust evidence has accumulated on the role of longstanding rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis as premalignant conditions. Evidence that systemic lupus erythematosus may evolve into lymphoma is equivocal. SUMMARY: The link between malignancies and rheumatic disorders may impact on clinical practice. First, paraneoplastic rheumatic syndromes can provide the clinician with hints for earlier diagnosis of occult cancer. Second, the risk of malignant transformation during the course of rheumatic disorders may motivate the search for strategies aimed at prevention.
18270862 Hepatitis B virus (HBV) and autoimmune disease. 2008 Feb The etiology and pathogenesis of autoimmune diseases have long been an enigmatic subject that have involved genetic and environmental factors. Recent intriguing data has contributed to the mechanisms involved, including the relationship of infectious agents and loss of tolerance. This loss of tolerance is illustrated by the data on the immune response to Hepatitis B virus such as the molecular mimicry between HBV antigens and self proteins, the generation of immune complexes between HBV antigens and antibodies, and apoptosis/tissue damage resulting in the exposure of intracellular antigens to the immune system. In this paper, we review the current database related to HBV infection and a variety of autoimmune conditions, including autoimmune hepatitis, systemic lupus erythematosus, aplastic anemia, antiphospholipid syndrome, polyarteritis nodosa, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, thyroid disease and uveitis.
18064949 Ocular manifestations of antiphospholipid (Hughes)' syndrome--minor features? 2007 The ocular manifestations are described in autoimmune disease, being most common associated with systemic lupus erythematosus, scleroderma, rheumatoid arthritis, insulin-dependent diabetes mellitus, and dermatomyositis. Nonetheless, the antiphospholipid syndrome is a relatively newly recognized autoimmune disorder. Ocular conditions in which to consider antiphospholipid syndrome include amaurosis fugax, transient ischemic attack, retinal haemorrhages and cotton wool spots, central retinal vein and artery occlusion, anterior ischemic optic neuropathy, ophthalmic and cilioretinal artery occlusions. Ocular features due to antiphospholipid antibodies - induced thrombosis should be treated with anticoagulant drugs. In opposition, for the treatment of ocular features due to immunological mechanisms such as vasculitis, immunosuppressants seem to be more suitable. The aim of this article is to underline the mainly ocular features of Hughes' syndrome and for the most part attention should be paid to the patients with central retinal vascular occlusion with no cause but most likely caused by lupus anticoagulant.
17959451 Comparison of two and three-dimensional optical tomographic image reconstructions of human 2006 We have developed an images reconstruction algorithm to recover spatial distribution of optical properties in human finger joints for early diagnosis and monitoring of rheumatoid arthritis (RA). An optimization method iteratively employs a light propagation and scattering coefficients distribution for near-infrared (NIR) light inside the joint tissue. We developed the differences in cross-sectional images obtained by using the reconstruction algorithms with 2-dimensional and 3-dimensional light propagation models. In particular we examined how these different approaches affect the discrimination between healthy and RA joints.
18027204 Role of Txk, a member of the Tec family of tyrosine kinases, in immune-inflammatory diseas 2007 Sep Txk/Rlk, a member of the Tec family of tyrosine kinases, is an important signaling mediator. We previously reported that human Txk is expressed in Th1/Th0 cells, and Txk translocates from cytoplasm into nuclei upon activation. Txk regulates specifically interferon-gamma gene transcription. Txk, poly(ADP-ribose) polymerase 1, and elongation factor 1alpha make a complex to bind to interferon-gamma gene promoter region-53/-39 (Txk responsive element) to exert positive effects on transcription as a Th1 cell-associated transcription factor. Txk expression is enhanced in rheumatoid arthritis and Behçet's disease, where Th1 dominant immunity occurs. In bronchial asthma and atopic dermatitis, typical Th2 diseases, Txk expression is reduced. Modulation of Txk expression by gene transfer or similar modality may lead to the correction of aberrant immunity and, consequently, disease treatment.