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

ID PMID Title PublicationDate abstract
17091377 Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial appl 2007 Jan Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. It has a high molecular mass, usually in the order of millions of Daltons, and interesting viscoelastic properties influenced by its polymeric and polyelectrolyte characteristics. HA is present in almost all biological fluids and tissues. In clinical medicine, it is used as a diagnostic marker for many diseases including cancer, rheumatoid arthritis and liver pathologies, as well as for supplementation of impaired synovial fluid in arthritic patients by means of intra-articular injections. It is also used in certain ophthalmological and otological surgeries and cosmetic regeneration and reconstruction of soft tissue. Herein we present an overview of the occurrence and physiological properties of HA, as well as of the recent advances in production biotechnology and preparation of the HA-based materials for medical application.
16932709 Prospects for disease modification in osteoarthritis. 2006 Jun Osteoarthritis (OA) can be a progressive, disabling disease, leading to diminished quality of life, and, for over 500,000 individuals annually in the US, total joint replacement. The etiology of OA will vary among individuals, with potential roles for systemic factors (such as genetics and obesity) as well as for local biomechanical factors (such as muscle weakness, joint laxity and traumatic injury). Joint deterioration occurs over extended periods of time, and the diverse molecular mechanisms that mediate pathogenic events of early, mid and late disease are not yet fully understood. The success of biologic therapies in the treatment of rheumatoid arthritis has demonstrated that the blockade of a single dominant cytokine or regulatory molecule can prevent cartilage destruction in a complex disease, and has raised expectations that mechanism-based treatments could also be developed for patients with OA. In this review, we will address the biological mechanisms that mediate structural damage in OA and examine current targets that are candidates for disease modification. The challenges to drug development and the obstacles to disease modification strategies will also be addressed.
16920579 The human genome and gene expression profiling. 2006 The mapping and sequencing of the human genome has generated a large resource for answering questions about human disease. This achievement is akin in scientific importance to developing the periodic table of elements. Plastic surgery has always been at the frontier medical research. This resource will help us to improve our understanding on the many unknown physiological and pathogical conditions we deal with daily, such as wound healing keloid scar formation, Dupuytren's disease, rheumatoid arthritis, vascular malformation and carcinogenesis. We are primed in obtaining both disease and normal tissues to use this resource and applying it to clinical use. This review is about the human genome, the basis of gene expression profiling and how it will affect our clinical and research practices in the future and for those embarking on the use of this new technology as a research tool, we provide a brief insight on its limitations and pitfalls.
16827231 [Method for determining leukocytic lipid-releasing capacity in the diagnosis of mechanisms 2006 May The authors have studied the mechanism responsible for neutrophilic accumulation and release of protein-lipid complexes in patients with atherosclerosis and the clinical value of this reaction. They present the results of experimental studies and clinical observations in the groups of patients with ischemic stroke, coronary heart disease, bronchial asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis. Whether the process of neutrophilic and release of protein-lipid can be in vitro modulated in a 3-day culture has been demonstrated. The high diagnostic value of the method for determining the lipid-releasing capacity of leukocytes is shown. Some proteins involving in the formation of pathogenic protein-lipid complexes are identified. There is evidence for the use of new differential criteria for visceral diseases originating from atherosclerosis.
16434856 Histology of two rice bodies isolated from the stifle of an adult draught horse stallion. 2006 Mar In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia.
16283973 Nonlipid-lowering effects of statins. 2005 Dec Statins have been shown to effectively reduce cardiovascular events in patients with hypercholesterolemia, diabetes, and coronary disease, and after an acute coronary syndrome in several large-scale clinical trials. Interestingly, numerous studies have suggested that statins exert potentially important effects independent of lipid lowering (ie, improve endothelial function, reduce oxidant stress), and have direct anti-inflammatory, antithrombotic, and plaque-stabilizing effects. These beneficial effects may contribute to cardiovascular protection by statin therapy beyond low-density lipoprotein (LDL) cholesterol lowering. Therefore, it remains unclear at present to what extent the beneficial cardiovascular effects of statin treatment are dependent on LDL cholesterol lowering (ie, whether the same effect would be achieved by other modes of lipid lowering). Consequently, statins should be used as a first-line therapy for lipid lowering. Importantly, the observation of LDL cholesterol-independent effects of statins has stimulated clinical studies testing a wider use of statin treatment for diseases that are not thought to be related to increased LDL cholesterol levels, such as in patients with chronic heart failure (in particular dilated cardiomyopathy) and even in inflammatory diseases such as rheumatoid arthritis and multiple sclerosis.
15989010 [Unwanted reactions to modifying antirheumatic drugs]. 2005 AIM: To specify causes of discontinuation of the disease-modifying antirheumatic drugs (DMAD) used in rheumatoid arthritis (RA) by the results of special questionnaire survey. MATERIAL AND METHODS: The study included 298 RA patients treated in the Institute of Rheumatology (34 males and 264 females aged 18-82, mean age 54.6%, duration of the disease 1 to 38 years, mean 10.7 years) who responded to questioning. RESULTS: The following DMAD were used: metotrexate (n = 137), sulfasalasine (n = 49), aminoquinoline drugs (n = 33), chlorbutin (n = 19), azathioprin (n = 13), tauredon (n = 11), cyclophosphamide (n = 5). The drugs were discontinued due to unwanted effects in 50, 10, 46, 9, 4, 3, 3 (methotrexate, sulfasalasin, aminoquinolines, chlorbutin, azathioprin, Ag salts, cyclophosphamide, respectively). Cyclophosphamide and chlorbutin appeared most toxic, while sulfasalasine and aminoquinolines were found least effective. CONCLUSION: DMAD discontinuation rate ranges from 12.1% (aminoquinolines) to 60% (cyclophosphamide), mean 31.1%.
15963445 Striatal deformities of the hand and foot in Parkinson's disease. 2005 Jul Striatal deformities of the hand and foot are abnormal postures that are common in patients with advanced Parkinson's disease (PD); they can present in the early stages of PD and in other parkinsonian disorders. Over a century ago, Charcot and Purves-Stewart recognised these deformities, which cause substantial functional disability and discomfort. The term striatal is used because pathology in the neostriatum (putamen and caudate) has been suggested to cause the deformities, but the pathogenesis is unknown. Misdiagnosis of the deformities is common-particularly when they occur early and in the absence of cardinal parkinsonian signs, such as tremor, bradykinesia, and rigidity-because the hand deformities are similar to those in rheumatoid arthritis, equinovarus foot deformity typically suggests an orthopaedic problem, and toe extension may be thought to be the Babinski sign of upper-motor-neuron syndromes. Here we review the background and clinical features of these deformities to highlight these commonly unrecognised and poorly understood parkinsonian signs.
15645271 Bilateral patellar tendon rupture without predisposing systemic disease or steroid use: a 2005 Mar Simultaneous bilateral patella tendon ruptures are very rare injuries of the knee extensor complex often associated with systemic disorders such as lupus erythematosus or rheumatoid arthritis. We describe the case of a 34-year-old man without concomitant systemic disease or steroid use and provide the most comprehensive review of the German and English literature. Furthermore, we discuss the predisposing factors and causal mechanisms as well as current diagnostic procedures and treatment options. In the literature review, only a few patients without systemic disorder or steroid medication present with potential predisposing factors that may be responsible for degenerative changes of the patella tendon, weakening its stability. In addition, in most of these cases, it remains difficult to explain the bilateral and simultaneous nature of this injury.
21783692 Subacute toxicity of celecoxib on thyroid and testis of rats: Hormonal and histopathologic 2006 Jul Celecoxib is an effective agent in the treatment of signs and symptoms of inflammation, rheumatoid arthritis and osteoarthritis. The purpose of this study is to assess the effects of two different doses of celecoxib on some hormones and endocrine glands of male rats. In this study, the doses of 10 and 50mg/kg/day of celecoxib were given to male rats orally for 28 days. At the end of the study, serum total triiodothyronine (T(3)), total thyroxine (T(4)), thyroid stimulating hormone (TSH), testosterone and luteinizing hormone (LH) levels of rats were analyzed by radioimmunoassay technique using RIA kits. Thyroid and testis tissues of male rats were examined histopathologically. While there was no a change in serum T(3), T(4) and LH levels of celecoxib-treated rats, there were differences in serum TSH and testosterone levels of rats treated with 50mg/kg/day celecoxib for 28 days compared with those of control rats. In histopathological examinations, celecoxib-related changes were found in thyroid glands of the rats.
20704876 Crypticity of self antigenic determinants is the cornerstone of a theory of autoimmunity. 2005 Aug Extract: The immune system is designed to keep in check, to kill, and to clear from the body any invading disease-causing microbial agents such as bacteria and viruses. This immunity against foreign pathogens is mediated primarily through T lymphocytes and antibodies. Furthermore, there are in-built regulatory mechanisms that monitor the activity of these immune effector components. However, under certain constellations of genetic predisposition and environmental triggers, the same immune system can turn against the host and cause damage to the body's own ("self") cells and tissues (autoimmunity). Diseases like multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and thyroiditis represent a spectrum of autoimmune diseases caused by a dysregulated immune system. Although the autoimmune nature of many of these disorders is clear, their precise etiology is far from evident. Both the genetic composition of an individual [represented, for example, by the major histocompatibility complex (MHC), which in humans is termed HLA (human leukocyte antigens)] and environmental influences (e.g., microbial agents, stress, etc.) are believed to be the major factors that determine outcome of an immune response against self components.
15807195 Statins: immunomodulators for autoimmune rheumatic disease? 2005 Inhibitors of 3-hydroxy-3-methylgluttaryl coenzyme A (HMG-CoA) reductase, or statins, are used extensively to reduced elevated lipid levels and reduce cardiovascular risk. However, accumulated evidence suggests that stains not only act by lowering cholesterol levels, but also exert pleiotropic effects on many essential cellular functions including cell proliferation, differentiation, and survival and participate in the regulation of cell shape and motility. Thus cardiovascular benefit is provided by lowering raised cholesterol levels and by modulation of the inflammatory component of this disease. Such an anti-inflammatory effect may also benefit patients with autoimmune rheumatic disease. This overview assesses the evidence for using statins in patients with rheumatoid arthritis and systemic lupus erythematosus (SLE).
15737895 Iron requirements in erythropoietin therapy. 2005 Jun When erythropoietin (epoetins or darbepoetin) is used to treat the anemias of chronic renal failure, cancer chemotherapy, inflammatory bowel diseases, HIV infection and rheumatoid arthritis, functional iron deficiency rapidly ensues unless individuals are iron-overloaded from prior transfusions. Therefore, iron therapy is essential when using erythropoietin to maximize erythropoiesis by avoiding absolute and functional iron deficiency. Body iron stores (800-1200 mg) are best maintained by providing this much iron intravenously in a year, or more if blood loss is significant (in hemodialysis patients this can be 1-3 g). There is no ideal method for monitoring iron therapy, but serum ferritin and transferrin iron saturation are the most common tests. Iron deficiency is also detected by measuring the percentage of hypochromic red blood cells, content of hemoglobin in reticulocytes, soluble transferrin receptor levels, and free erythrocyte protoporphyrin values, but iron overload is not monitored by these tests. Iron gluconate and iron sucrose are the safest intravenous medications.
15706375 A survey on the uses of acupuncture by a group of UK dentists. 2005 Feb 12 A small number of fully trained Chinese doctors practise Traditional Chinese Medicine (TCM) in western cities. Use of these services by British citizens is extremely limited, mostly due to lack of any knowledge on the effectiveness of acupuncture or exposure to complementary medicine in this country. Common situations where British patients seek the help of TCM are when medical therapy has failed; in relapsing chronic diseases like asthma, rheumatoid arthritis; and in pain management (mostly headache, migraine and back pain). Patients often appreciate that only limited interventions are available for treatment of these conditions in western medicine. At least one in 10 UK specialist physicians are actively involved in complementary and alternative medicine treatments.(1) A large number of westerners offer acupuncture therapy but lack basic medical training. It is likely that people are reluctant to use these services largely because of hygiene and safety reasons. Moreover, it has been demonstrated that the serious side effects reported are five times more frequent when treatments are provided by non-medically trained therapists compared with professionally registered health care providers.(2).
15639052 Developments in glucocorticoid therapy. 2005 Feb Recent evidence for a disease-modifying potential of low-dose glucocorticoids (GCs) in the treatment of rheumatoid arthritis has renewed the debate on the risk benefit ratio with this therapy. Two recent developments are described that might have a positive influence on these risk benefit ratios. One is the improvement in new GC compounds--designer GCs, alterations in bioactivity, and alterations in formulations. The other is a better understanding and management of the toxicity of GCs.
16700833 A mutilating arthropathy, "rhupus hands" associated with multiple synovial cysts in a pati 2006 Jun "Rhupus hands" is a phrase coined to describe one of the deforming arthropathies associated with systemic lupus erythematosus (SLE), because the clinical features are indistinguishable from those of rheumatoid arthritis. Herein, we report a case of rhupus hands with multiple synovial cysts arising in a 60-year-old woman with SLE.
20477603 Interleukin-18 treatment options for inflammatory diseases. 2005 Nov Several autoimmune diseases are believed to be mediated, in part, by interleukin (IL)-18. Many are those with associated elevated interferon-gamma levels, such as systemic lupus erythematosus, macrophage activation syndrome, rheumatoid arthritis, Crohn's disease, psoriasis, as well as graft-versus-host disease. Clinical and animal studies also support the concept that IL-18 is a key player in atherosclerosis, acute renal ischemia and hepatitis. IL-18 is a member of the IL-1 family; IL-1beta and IL-18 are closely related, and both require the intracellular cysteine protease caspase-1 for biologic activity. The IL-18 binding protein, a naturally occurring, specific inhibitor of IL-18, neutralizes IL-18 activities and is likely to be safe in patients. Other options for reducing IL-18 activities are inhibitors of capsase-1, human monoclonal antibodies to IL-18, soluble IL-18 receptors and anti-IL-18 receptor monoclonal antibodies.
16218477 T cells and cytokines in atherogenesis. 2005 Recent findings suggest that inflammation plays a key role in atherosclerosis from the earliest stage of lesion initiation, to the ultimate complication of thrombosis. In patients who died because of acute coronary syndromes (ACS), coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion. The rupture-related inflammatory cells are activated, indicating ongoing inflammation. ACS patients are also characterized by activated circulating lymphocytes, monocytes and neutrophils, and by increased concentrations of proinflammatory cytokines and of the highly sensitive acute phase reactant C-reactive protein. Interestingly, an unusual subset of T cells, CD4+ CD28null T cells, involved in vascular complication of rheumatoid arthritis because of their functional profile predisposing for vascular injury, are expanded in the peripheral blood and infiltrate the coronary lesions of ACS patients. The presence of activated T lymphocytes implies antigenic stimulation, but the nature of such antigen(s) remains to be investigated. Several autoantigens expressed in the atherosclerotic plaque, including oxidized LDL and heat shock proteins, and infectious agents are able to elicit an immune response. The inflammatory component is not localized to the 'culprit' plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium.
18648641 Radon treatment controversy. 2006 Aug 19 In spite of long traditions, treatments utilizing radon-rich air or water have not been unequivocally embraced by modern medicine. The objective of this work is to examine factors that contribute to this continuing controversy. While the exact mechanism of radon's effect on human body is not completely understood, recent advances in radiobiology offer new insights into biochemical processes occurring at low-level exposures to ionizing radiation. Medical evidence and patients' testimonials regarding effectiveness of radon spa treatments of various ailments, most notably rheumatoid arthritis are accumulating worldwide. They challenge the premise of the Linear-No-Threshold (LNT) theory that the dose-effect response is the same per unit dose regardless of the total dose. Historically, such inference overshadowed scientific inquiries into the low-dose region and lead to a popular belief that no amount of radiation can be good. Fortunately, the LNT theory, which lacks any scientific basis, did not remain unchallenged. As the reviewed literature suggests, a paradigm shift, reflected in the consideration of hormetic effects at low-doses, is gaining momentum in the scientific community worldwide. The impetus comes from significant evidence of adaptive and stimulatory effects of low-levels of radiation on human immune system.
17050376 MT1-MMP: a key regulator of cell migration in tissue. 2006 Oct Controlled cell migration is a fundamental and critical event in many physiological processes. However once control is lost, cell migration facilitates disease progression such as seen in cancer metastasis, atherosclerosis, and rheumatoid arthritis. One of the critical proteinases involved in cell migration is membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14). MT1-MMP degrades extracellular matrix to make a path for cells to migrate, sheds cell surface molecules to give migratory signals, and activates ERK (extracellular signal-regulated protein kinase) enhancing cell migration. For MT1-MMP to promote cell migration, it needs to act in co-ordination with other cell migration machinery. Understanding such regulatory links may provide insights into the development of novel disease therapies.