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ID PMID Title PublicationDate abstract
16842224 Antioxidants and inflammatory disease: synthetic and natural antioxidants with anti-inflam 2006 Jul Oxidants play a significant role in the pathogenesis of a number of disorders such as inflammation, rheumatoid arthritis, asthma, psoriasis and contact dermatitis leading to oxidative stress. Oxidative stress may be defined as an imbalance between cellular production of reactive oxygen species (ROS) and antioxidant defense mechanisms. ROS (e.g., superoxide radical, peroxynitryl, hydroxyl radical and hydrogen peroxide) are constantly produced as a result of metabolic reactions in living systems. The aim of this review is to describe recent developments in the study of antioxidants and their role in preventing the formation of ROS. The processes associated with inflammatory responses are complex and often involve ROS. There are many mediators, which initiate and amplify the inflammatory response such as histamine, serotonin, pro-inflammatory cytokines (interleukin-1B (IL-1b) and tumor necrosis factor (TNF-alpha), inflammatory cells (leukotrienes, macrophages), metabolic products of arachidonic acid (thomboxane A(2), prostaglandins and leukotrienes). The first part of this review focuses on the role of ROS in inflammation. The second part concerns synthetic antioxidants with antiinflammatory activity, and the third part addresses naturally occurring antioxidants with antiinflammatory activity.
16829986 Biologics targeted at TNF: design, production and challenges. 2006 Apr Several biotech-derived drugs aimed at Tumor Necrosis Factor (TNF) have been licensed in the last years, profoundly changing the therapy of several autoimmune diseases based on inflammation, affecting the life of patients and bringing to the market attention the growth potentials of biologics directed at cytokines. The proof of principles that led to the design of these compounds dates back from the nineties, when the involvement of TNF in rheumatoid arthritis was proved by the ability of specific anti-TNF proteins to modulate the inflammatory response in animal models. Monoclonal antibodies aimed at neutralizing the excess TNF were developed with therapeutic purposes, and a chimeric and a full human antibody are now approved for several clinical indications. The design of soluble receptors able to bind and neutralize human TNF paralleled the development of antibodies as therapeutics, and the clinical success of these drugs was achieved by the clever design of a novel recombinant dimeric protein, consisting of the extracellular portion of human TNF receptor linked to the constant portion of a human immunoglobulin. All approved biologics designed to bind and neutralize TNF were obtained through the power of biotechnological methods: the development of these important biopharmaceutical products, their means of production and the challenges they face will be analyzed here in details.
16803617 The Autoimmune Disease Database: a dynamically compiled literature-derived database. 2006 Jun 27 BACKGROUND: Autoimmune diseases are disorders caused by an immune response directed against the body's own organs, tissues and cells. In practice more than 80 clinically distinct diseases, among them systemic lupus erythematosus and rheumatoid arthritis, are classified as autoimmune diseases. Although their etiology is unclear these diseases share certain similarities at the molecular level i.e. susceptibility regions on the chromosomes or the involvement of common genes. To gain an overview of these related diseases it is not feasible to do a literary review but it requires methods of automated analyses of the more than 500,000 Medline documents related to autoimmune disorders. RESULTS: In this paper we present the first version of the Autoimmune Disease Database which to our knowledge is the first comprehensive literature-based database covering all known or suspected autoimmune diseases. This dynamically compiled database allows researchers to link autoimmune diseases to the candidate genes or proteins through the use of named entity recognition which identifies genes/proteins in the corresponding Medline abstracts. The Autoimmune Disease Database covers 103 autoimmune disease concepts. This list was expanded to include synonyms and spelling variants yielding a list of over 1,200 disease names. The current version of the database provides links to 541,690 abstracts and over 5,000 unique genes/proteins. CONCLUSION: The Autoimmune Disease Database provides the researcher with a tool to navigate potential gene-disease relationships in Medline abstracts in the context of autoimmune diseases.
16678704 Giant-cell temporal arteritis in a 17-year-old male. 2006 May Temporal arteritis, particularly in its classic form, is exceedingly rare in individuals <50 years old. We report the youngest case of biopsy-proven giant cell temporal arteritis. A 17-year-old male presented with a progressively expanding and pulsatile but otherwise asymptomatic mass in his forehead. The patient's medical history was significant for uveitis since the age of 3, and severe allergic rhinitis, mild asthma, and juvenile rheumatoid arthritis as a young adolescent. Admission laboratory values included a mildly elevated erythrocyte sedimentation rate and C-reactive protein level. A computed tomography evaluation demonstrated aneurysmal degeneration of the frontal branch of the right superficial temporal artery and confirmed no other cerebrovascular changes. Histologically, the aneurysmal arterial segment demonstrated subacute temporal arteritis. The arterial wall had a primarily lymphoplasmacytic infiltrate with rare giant cells and focally marked medial destruction. Additionally, severely obstructive intimal hyperplasia with chronic adventitial and periadvential dense fibrosis was noted. The diagnosis of classic giant cell temporal arteritis was established from the biopsy result. Postoperatively, the patient was treated with prednisone for 3 months. Three years after surgery, the patient remains well and reports no recurrence of temporal artery disease.
16567355 The ICF comprehensively covers the spectrum of health problems encountered by health profe 2006 Oct OBJECTIVES: The objective of this study was to investigate, whether the International Classification of Functioning, Disablity and Health (ICF) comprehensively covers the spectrum of health problems encountered by medical doctors and physiotherapists in patients with musculoskeletal conditions. METHODS: A worldwide e-mail survey with questionnaires that requested lists of relevant areas in the ICF components-body functions, body structures, activities and participation, and environmental factors-in patients with rheumatoid arthritis, osteoarthritis, low back pain and osteoporosis was conducted. The suitability of linking the named concepts to the ICF as well as the precision of the linking was characterized by assigning the concepts to six groups. RESULTS: All concepts that were named by the experts could be linked to the ICF, with the exception of personal factors. Between 32% (environmental factors) and 51% (activities and participation) of the named concepts were linked to an ICF category with an identical meaning and the same grade of precision. All other named concepts were linked to ICF categories with a lower level of precision, or encompassed more than one ICF category, or were linked to an ICF category with a related, but not identical meaning. CONCLUSIONS: The ICF covers comprehensively the spectrum of problems encountered in patients with musculoskeletal conditions by clinical experts throughout the world. This strengthens the validity of the ICF in the view of the users and will encourage the use of ICF-based applications such as the ICF checklist and the now-developed ICF Core Sets.
16513409 High-mobility group box 1 (HMGB1) protein: friend and foe. 2006 Jun HMGB1 was originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be "passively released" into the extracellular milieu by necrotic and damaged somatic cells. Extracellular HMGB1 represents an optimal "necrotic marker" selected by the innate immune system to recognize tissue damage and initiate reparative responses. HMGB1 in the extracellular milieu promotes maturation of myeloid and plasmacytoid dendritic cells, and induces myocardial regeneration after infarction. However, extracellular HMGB1 also acts as a potent pro-inflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders. A growing number of studies indicate that HMGB1 is a successful therapeutic target in experimental models of ischemia/reperfusion, acute respiratory distress syndrome, rheumatoid arthritis, sepsis, and cancer. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses while preventing its pathological potential. This article focus on the immuno-regulatory role of HMGB1 and its contribution to infectious and inflammatory disorders.
16504830 Newer therapeutic approaches to the vasculitides: biologic agents. 2006 Feb Biologic therapies have emerged as important treatments in chronic inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, and are now garnering more attention in the vasculitides. These agents, including tumor necrosis factor-alpha inhibitors, B-cell-depleting agents, interferon-alpha, and some antiviral treatments, target specific components of the immune system and may have lower side effect risk profiles than the conventional immunosuppressives and cytotoxic agents. This article addresses the encouraging data and the possible pitfalls of these new therapeutic options, thus far evaluated mostly by case reports, small series, and open-label trials. Confirming the efficacy of existing and newer therapies will require further clinical investigation through randomized placebo-controlled studies to identify the proper doses and treatment schedules and single out those drugs that may expose patients to dangers that outweigh the potential benefits.
16480261 Dual binding mode of a novel series of DHODH inhibitors. 2006 Feb 23 Human dihydroorotate dehydrogenase (DHODH) represents an important target for the treatment of hyperproliferative and inflammatory diseases. In the cell DHODH catalyzes the rate-limiting step of the de novo pyrimidine biosynthesis. DHODH inhibition results in beneficial immunosuppressant and antiproliferative effects in diseases such as rheumatoid arthritis. Here, we present high-resolution X-ray structures of human DHODH in complex with a novel class of low molecular weight compounds that inhibit the enzyme in the nanomolar range. Some compounds showed an interesting dual binding mode within the same cocrystal strongly depending on the nature of chemical substitution. Measured in vitro activity data correlated with the prevailing mode of binding and explained the observed structure-activity relationship. Additionally, the X-ray data confirmed the competitive nature of the inhibitors toward the putative ubiquinone binding site and will guide structure-based design and synthesis of molecules with higher activity.
16448842 The SHAP-hyaluronan complex in serum from patients with chronic liver diseases caused by h 2006 Mar Our previous study suggested that the serum-derived hyaluronan associated protein (SHAP)-hyaluronan (HA) complex in the sera of patients with rheumatoid arthritis is useful as a marker that directly correlates with the degree of inflammation. Here, we have investigated the serum levels of the SHAP-HA complex in patients at various clinical stages of chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) caused by infection with the hepatitis C or hepatitis B virus. Both serum levels of the SHAP-HA complex and HA in those patients were significantly higher than those of the controls and increased in the order of CH
16406714 Unresponsiveness of C-reactive protein in the non-infectious inflammation of systemic lupu 2006 Jun C-reactive protein (CRP) response is abnormal to a non-infectious inflammation in systemic lupus erythematosus (SLE). We evaluated the role of cytokines in this CRP unresponsiveness. The sera of 138 SLE patients and 71 rheumatoid arthritis patients were collected prospectively. SLE with infection had higher WBC count, ESR, CRP and C4 levels than those without infection. IL-6, IL-10 and IFN-gamma levels were higher in SLE with infection than SLE without infection. In SLE with infection, the CRP was correlated with the IL-6 (r = 0.77, P < 0.001) but not correlated with IL-10 and IFN-gamma. These data suggest that IL-6 may have a role in the unresponsiveness of CRP to a non-infectious inflammation of SLE.
16367941 Expression of OX40 (CD134) on CD4+ T-cells from patients with myasthenia gravis. 2006 Jan Myasthenia gravis (MG) is commonly regarded as the prototype of an antibody-mediated, organ-specific autoimmune disease. Antibodies against the acetylcholine receptor (AChR) on the muscle endplate trigger its typical clinical manifestations of weakness and fatiguability. T-B cell interactions are thought to play a crucial role in the pathogenesis of MG. OX40 (CD134), a costimulatory molecule that is expressed on activated CD4+ T-cells, might contribute to the development or pathogenesis of immune-mediated diseases such as rheumatoid arthritis and graft-versus-host disease. In the present study, we investigated the expression of OX40 on CD4+ T-cells from patients with MG and healthy individuals. Results from 36 MG patients and 28 healthy controls revealed that more freshly isolated CD4+ T-cells from MG patients expressed OX40 than cells from healthy individuals. High levels of antibodies against the AChR, thymic hyperplasia and onset at an early age were associated with elevated expression of OX40. Upon activation by various concentrations of anti-CD3 antibodies, CD4+ T-cells from MG patients showed a tendency toward higher levels of OX40 expression than cells from healthy individuals. Given the role of OX40 in the immune system, we conclude that OX40 might contribute to the development of MG.
16286433 Searching bibliographic databases for literature on chronic disease and work participation 2006 Jan BACKGROUND: The work participation of people with chronic diseases is a growing concern within the field of occupational medicine. Information on this topic is dispersed across a variety of data sources, making it difficult for health professionals to find relevant studies for literature reviews and guidelines. AIM: The goal of this project was to identify bibliographic databases and search terms that could be most useful for retrieving relevant studies on this topic. METHODS: Five broad questions regarding work participation and chronic disease were formulated, focusing on angina pectoris, depression, diabetes mellitus, hearing impairment and rheumatoid arthritis. A search strategy for retrieving information on these questions was developed and run in five bibliographic databases: Medline, EMBASE, PsycINFO, Cinahl and OSHROM. Relevant publications were selected from the search results. The utility of the selected databases and search terms was evaluated by analysing the number of relevant publications that were retrieved. RESULTS: The number of relevant publications retrieved from each database varied. Most (84%) of the relevant publications that were retrieved from each database were unique to that source. For each database, specific search terms for the concept of 'work' were useful for retrieving relevant publications. CONCLUSION: Medline, EMBASE and PsycINFO are useful databases for quick searches. Useful search terms for the concept of 'work' are work capacity, work disability, vocational rehabilitation, occupational health, sick leave, absenteeism, return to work, retirement, employment status and work status. For comprehensive searches, we recommend additional searches in Cinahl and OSHROM, adapting the search terms to specific databases.
18190689 Rapidly destructive osteoarthritis of the hip joint: a case series. 2008 Jan 11 BACKGROUND: Rapidly destructive arthrosis of the hip is a rare and incompletely understood disorder with scarce literature about variations in natural history within a population. METHODS: A series of cases from North Wales with rapid progressive joint destruction and extensive subchondral bone loss in the femoral head and acetabulum are presented. Radiographic findings mimicked those of other disorders such as septic arthritis, rheumatoid and seronegative arthritis, primary osteonecrosis with secondary osteoarthritis, or neuropathic osteoarthropathy, but none of the patients had clinical, pathologic, or laboratory evidence of these entities. RESULTS: Rapid progression of hip pain and disability was a consistent clinical feature. The average duration of symptoms was 1.4 years. Radiographs obtained at various intervals before surgery (average 14 months) in 18 patients documented rapid hip destruction, involvement being unilateral in 13 cases. All patients underwent total hip arthroplasty, and osteoarthritis was confirmed at pathologic examination. CONCLUSION: The authors postulate that these cases represent an uncommon subset of osteoarthritis and regular review, both clinically and radiologically, are required to assess speed of progression and prevent rapid loss of bone stock without the surgeon being aware. These cases are unsuitable for being placed on long waiting list due to technical difficulties in delayed surgery and compromised outcome following surgery.
16377621 The role of human HtrA1 in arthritic disease. 2006 Mar 10 Human HtrA1 belongs to a widely conserved family of serine proteases involved in various aspects of protein quality control and cell fate. Although HtrA1 has been implicated in the pathology of several diseases, its precise biological functions remain to be established. Through identification of potential HtrA1 targets, studies presented herein propose that within the context of arthritis pathology HtrA1 contributes to cartilage degradation. Elevated synovial HtrA1 levels were detected in fluids obtained from rheumatoid and osteoarthritis patients, with synovial fibroblasts identified as a major source of secreted HtrA1. Mass spectrometry analysis of potential HtrA1 substrates within synovial fluids identified fibronectin as a candidate target, and treatment of fibronectin with recombinant HtrA1 led to the generation of fibronectin-degradation products that may be involved in cartilage catabolism. Consistently, treatment of synovial fibroblasts with HtrA1 or HtrA1-generated fibronectin fragments resulted in the specific induction of matrix metalloprotease 1 and matrix metalloprotease 3 expression, suggesting that HtrA1 contributes to the destruction of extracellular matrix through both direct and indirect mechanisms.
17364081 Seronegative spondyloarthropathy--studies from the Asia Pacific region. 2007 Feb Recent therapeutic advances, in particular the use of anti-tumour necrosis factor (anti-TNF) agents, have revived interest in the seronegative spondyloarthropathies (SpA), a group of arthritides characterised by axial skeletal involvement and the absence of rheumatoid factor. The purpose of this article is to review the studies that have been done in the Asia Pacific region, as a broad understanding of the scope and severity of this group of diseases would enable rheumatologists and physicians in this part of the world to better manage their patients. The majority of genetic studies have focused on the associations of HLA-B27 with ankylosing spondylitis (AS) and SpA, while a few studies examined the associations of the CARD, IL-1, LMP2, TAP and TGF with AS. There are a handful of studies on the immunological responses to bacteria and cytokine levels in AS. The onset and clinical features of SpA have been reported from most countries in the region, but no data on patient outcomes, using current measurement tools such as the Bath Ankylosing Spondylitis Disease Activity index (BASDAI), is available. Validation of these instruments of measurement as well as classification criteria in different ethnic populations is necessary where no prior data exist. Future studies will likely be focused on better clinical characterisation of patient cohorts, particularly with regard to the use of currently used measurement tools for disease activity and spinal function and mobility, and the identification of the need for biologic therapy in each country.
18570753 HCV infection: pathogenesis, clinical manifestations and therapy. 2008 Jan Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2-3%. It is believed that about 170 million people are currently infected (about 3% of the world's population), and a further 3-4 million are infected each year. HCV is the main reason for liver transplantation in the developed world, and the main cause of liver-related morbidity and mortality in a number of countries, including Italy. It is not only a frequent cause of chronic liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma, but is also involved in the pathogenesis of various autoimmune and rheumatic disorders (arthritis, vasculitis, sicca syndrome, porphyria cutanea tarda, lichen planus, nephropathies, thyroid diseases, and lung fibrosis), as well as in the development of B-cell lymphoproliferative diseases. Furthermore, patients suffering from C hepatitis tend to produce rheumatoid factor, cryoglobulins and a large series of autoantibodies (ANA, anti-SSA/SSB, SAM, ATG, aCL). The use of glucocorticoids or immuno-suppressant agents in HCV infected individuals, which are needed to treat autoimmune and rheumatic disorders, leads to a risk of worsening the clinical outcome of HCV. Under these conditions, the viral infection often needs to be treated with antiviral agents, mainly pegylated interferon combined with ribavirin. However, cyclosporine A seems to be safe and effective in patients with autoimmune disease (AD) and concomitant chronic HCV infection as is documented by the reduction in viremia and transaminases, particularly in patients with high baseline levels. Finally, HCV is the main trigger of mixed cryoglobulinemia. An attempt at viral eradication is therefore indicated in most patients, and is particularly effective in the case of mild or moderate manifestations. In severe cases, rituximab is an apparently safe and effective alternative to conventional immunosuppression and, specifically, it controls B-cell proliferation.
23675042 Antibodies against M. Bovis 65 KDa Heat Shock Protein and Its P180-188 Epitope in Sera of 2007 Sep We screened the levels of antibodies to M. bovis hsp65 and the 180-188 epitope by using ELISA in a cohort of 72 juvenile idiopathic arthritis (JIA) patients and 38 healthy controls. We analysed an association between antibody levels and rheumatoid factor, antinuclear antibodies, human leukocyte antigen B27 and the severity and the duration of the disease. The majority of anti-hsp65 antibodies in a cohort of JIA patients were of the IgG isotype (54.2%) with IgM (13.9%) antibodies increased to a lesser degree. IgG antibodies to M. bovis hsp65 (P<0.001) and the 180-188 epitope (P<0.001) were significantly increased in all of three disease onset types when compared with healthy controls. The highest levels of IgG antibodies to M. bovis hsp65 and its P180-188 epitope were observed in oligoarthritis and in patients with no X-ray changes and functional limitation, while the lowest antibody levels were detected in patients with the most severe stage of articular damage. When antibody levels to M. bovis hsp65 and the 180-188 epitope were examined within patient and control populations, significantly higher levels of IgG and IgM antibodies to M. bovis hsp65 were observed in both JIA (P<0.001) and healthy control (P<0.001) cohorts. These findings may suggest that the high levels of IgG antibodies to M. bovis hsp65 and its P180-188 epitope would reflect the least serious cases of JIA. Since IgM antibodies to M. bovis hsp65 and P180-188 M. bovis hsp65 epitope exceeded the control level in a few patients with JIA we believe they are not of concern.
16866652 Scleroderma in South Australia: further epidemiological observations supporting a stochast 2006 Aug The aim of this study was to determine the incidence, prevalence, survival and selective demographic characteristics of scleroderma occurring in South Australia over the 10-year period 1993-2002. Analysis of the database of the South Australian Scleroderma Register: a population-based register established in 1993. Patients with scleroderma resident in South Australia (n = 353 at 2002) were ascertained from multiple sources and clinical and demographic data were obtained from mailed questionnaire and from review of computerized hospital databases, case notes or referring letters. Time-space cluster analysis was carried out according to the Knox method. Control data were obtained from the Australian Bureau of Statistics census. The mean prevalence was 21.4 per 10(5) (95% confidence interval 20.2-22.6) and the mean cumulative incidence of 1.5 per 10(5) (95% confidence interval 1.32-1.73) with no significant change in incidence over the study period (P = 0.13). Cumulative survival improved over the study period, with patients with diffuse disease having significantly reduced survival (as compared with limited disease, P < 0.001). The proportion with diffuse disease ( approximately 22%) remained steady. There was a small but significant predisposition in patients with a continental European birthplace (P < 0.001). A family history of scleroderma was noted in 1.6% with lambda1 (familial risk) of 14.3 (95% confidence interval 5.9-34.5). However, a family history of systemic autoimmunity (especially rheumatoid arthritis) was more common (6%). No socioeconomic stratification, temporal clustering nor spatio-temporal clustering was observed either at time of initial symptom or at 10 years before disease onset. Scleroderma occurs relatively infrequently in South Australia with no significant change in incidence observed over the 10-year study period. However, cumulative survival has improved. Identified risk factors include family history of scleroderma (risk approximately 14-fold), female sex (risk approximately 5-fold) and European birthplace (risk approximately 2.5-fold); however, the majority of the disease variance appears unexplained. A stochastic explanation based on genetic instability is favoured to explain this paradox.
17675728 An approach to the diagnosis of neutrophilic dermatoses: A histopathological perspective. 2007 Jul Neutrophilic dermatoses comprises of non-infective dermatoses which are histopathologically characterized by neutrophil predominant infiltrate and clinically, respond promptly to corticsteroids. Conditions primarily with vasculitis though neutrophilic are excluded from this group. In this article we intend to briefly outline the approach to diagnose these conditions with histological perspective. The ambiguity regarding few recent dermatosis viz, rheumatoid neutrophilic dermatosis, bowel associated-dermatosis-arthritis syndrome etc. with regard to their inclusion in this group has also been highlighted.
17536534 Hemiarthroplasty of the distal ulna with an eccentric prosthesis. 2007 Mar Replacement arthroplasty of the ulnar head is indicated primarily for stiffness and pain as a consequence of rheumatoid, degenerative, and posttraumatic arthritis of the distal radioulnar joint. It is also successfully used in the setting of previous failed excisional arthroplasty of the distal ulna. A distal ulnar hemiarthroplasty, which anatomically recreates the native ulnar head by employing an eccentric design, is discussed. The surgical technique includes a dorsal approach and careful repair of the soft tissue stabilizers.