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ID PMID Title PublicationDate abstract
18180578 [Biochemical markers in cartilage injury and repair]. 2007 Articular cartilage is a highly specialized tissue composed of chondrocytes which regulate the metabolism of extracellular matrix molecules responsible for maintaining cartilage function. Chondrocytes and synoviocytes are metabolically highly active cells and respond to various factors such as hormones, cytokines, growth factors, and mechanical stresses. Under normal physiological conditions, degradation and synthesis of extracellular matrix molecules are maintained in a state of balance. Any disruption of this balance results in degenerative cartilage diseases such as osteoarthritis and rheumatoid arthritis. Currently, diagnoses of both diseases are based on the assessment of a combination of clinical symptoms and radiological findings. However, degenerative changes in the articular cartilage occurs long before radiological changes are observed. Therefore, new laboratory tools are required to detect cartilage degradation in the early phase of the disease, to show the progression of cartilage destruction, and to assess response to treatment. In recent years, there has been an increase in the use of some biochemical markers derived from bone and cartilage for the diagnosis and follow-up of cartilage diseases. In this paper, the utility of these markers for early diagnosis and follow-up of cartilage injury is discussed in the light of the current literature.
18353448 New endogenous CXC chemokine ligands as potential targets in lung emphysema. 2008 Apr Chronic respiratory inflammation is caused by a sustained influx of macrophages and neutrophils, which leads to tissue remodeling and collagen breakdown. Recently, we have identified collagen-breakdown products that can activate and attract inflammatory cells via the CXC (two cysteines with an inverting amino acid)1 and CXC2 receptors (CXCR1 and CXCR2). By using a technique called 'inverted hydropathy', small peptides were synthesized that interact specifically with the responsible collagen-breakdown products and inactivate them. After inactivation, the collagen-breakdown products are no longer able to bind to their receptors. These neutralizing peptides inhibited neutrophil influx, heart hypertrophy and lung emphysema in animal models, and they are likely to be useful in other diseases that are characterized by a chronic inflammation, such as rheumatoid arthritis and inflammatory bowel diseases, where neutrophils are potential target cells. In this opinion article we will present a new hypothesis through which the chronicity and remodeling of tissue of several inflammatory diseases could be explained.
18226895 Probing the structural and topological requirements for CCR2 antagonism: holographic QSAR 2008 Feb 15 CCR2 is the major family of chemokine receptors which involve in the pathophysiology of the acute or chronic inflammatory conditions such as rheumatoid arthritis, atherosclerosis, asthma, obesity, and type-2 diabetes. Herein, we report the results of HQSAR model, developed for CCR2 antagonistic activity of indolopiperidine derivatives. The best HQSAR model with r(2)=0.916, q(2)=0.562 with atom count=4-7 was used to predict the activity of the test set molecules. The predicted values are in good agreement with experimental results and show the potential of the model for untested compounds. Analysis of molecular fragments throws light on essential structural and topological features of indolopiperidine derivatives for antagonist activity. The analysis shows that the presence of tertiary hydrogen bond acceptor groups is important for CCR2 antagonism. Fragments containing benzene ring substituted with one or more chlorine atoms show the positive effect of electron withdrawing group for favorable activity.
18222646 Will hematopoietic stem cell transplantation cure human autoimmune diseases? 2008 May Hematopoietic stem cell transplantation is becoming an accepted therapy for severe autoimmune diseases, and over 1,000 patients have been transplanted worldwide. Diseases include neurological (multiple sclerosis, others), rheumatological (systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis), haematological (aplastic anemia, single line immune mediated cytopenias) and others. The aim of this article is not to review the copious specific literature, but to analyze whether the up to now existing evidence satisfies the requirements of cure. Prospective randomized trials have been launched by the European Group of Blood and Marrow Transplantation (EBMT). Autologous transplantation, by far the most widely utilized because of its safety, has been shown to possess a powerful disease-arresting effect, but whether the attendant immune reconstitution ("re-education") will finally lead to cure is not demonstrated. The experience with allogeneic transplantation is too limited to draw even tentative conclusions. A Graft-versus-Autoimmunity effect has been ascertained both experimentally and clinically, but cure of autoimmunity by this procedure has not been demonstrated. Unexpected relapses in spite of full donor chimerism have been published. Further experience and studies are necessary.
18044201 [Occupation and carpal tunnel syndrome]. 2007 Nov Carpal tunnel syndrome (CTS), compression of the median nerve at the carpal tunnel of the wrist, is the most common of all entrapment syndromes. Diabetes, Rheumatoid arthritis, hypothyroidism and pregnancy are known to cause CTS. And certain occupations were been reported the risk factor of CTS. We report two patients with occupationally induced CTS, and discuss the relation between the development of CTS and occupation with reference to previous papers. Occupations that appear to promote CTS were classified in to three groups: jobs entailing the use of vibratory tools, assembly work and food processing and packing. These occupations involved repeated flexion and extension of the wrist. The prevalence of CTS was related to not only repetitive work but also forceful work involving the wrist. Both occupational and non-occupational factors (gender, age, body mass index, thyroid function and diabetes mellitus) were considered risk factors for CTS. The prevalence of CTS in Visual Display Terminal (VDT) workers was not high compared to that in control groups. If the cause of CTS is considered to be due to an occupational factor, the patient would be eligible workmen's compensation, and should be suspended from work as soon as possible. It has been reported that assembly line workers showed resolution of symptoms and normal nerve conduction studies after 2 years of a reduced work schedule. Treatment for CTS should begin early. When these workers return to work, the environment and the condition of work should be improved to prevent recurrence.
17763056 Influence of polymers on the bioavailability of microencapsulated celecoxib. 2007 Nov Celecoxib, a selective COX-2 inhibitor, primarily used in treatment of osteoarthritis, rheumatoid arthritis and acute pain was encapsulated in microparticles composed of various polyesters, polymethacrylates or cellulose derivatives used alone or blended. The influence of polymers on microparticle mean diameter, encapsulation efficiency and in vitro and in vivo celecoxib release was investigated. Microparticles were in the size range 11-37 microm. Encapsulation efficiency was optimal due to poor aqueous solubility of celecoxib. Considering in vitro release, microparticles could be divided into drug delivery systems with fast and slow release profiles. Microparticles prepared with poly-epsilon-caprolactone, Eudragit RS and low viscosity ethylcellulose, together with physical mixture of celecoxib with lactose and Celebrex, were tested in vivo. Relative bioavailability of celecoxib was below 20% in all cases and was probably the consequence of a slow in vivo release of celecoxib from microparticles or low wettability in the case of Celebrex and physical mixture.
17646822 [Tibial diaphysis fractures below a total knee prosthesis]. 2007 Jun The fractures of the tibial diaphysis below a total knee prosthesis are a surgical challenge and intra medullary nailing seems impossible. For the SOFCOT 2005 symposium on peri prosthetic fractures we reviewed our files: six cases were found and analysed. These fractures are rare: 5 cases from the symposium (out of 96 periprosthetic fractures at the knee) are reported plus a more recent one. They were observed in elderly (over 70) women except two cases of rheumatoid arthritis. All the patients were osteoporotic either due to aging or to a long duration corticosteroid treatment. All happened after minor trauma (fall from height). The fractures were classified as SOFCOT C1: letter C means diaphyseal below the prosthetic keel or stem, number 1 means: a well-fixed implant. Intra medullary nailing became the preferred treatment over time. A good analysis of the preoperative lateral radiograph of the knee shows if there is room enough for the nail between the prosthetic keel and the anterior tibial tuberosity, the nail remaining outside the synovium. Bone healed as usually for this type of fracture without impairment of knee or ankle function. However the patients became more dependent. In some instances, an unusual type of fracture may need an unusual treatment.
17643940 Hyperhomocysteinemia, inflammation and autoimmunity. 2007 Aug Hyperhomocysteinemia is independently associated with the development of coronary, cerebral and peripheral vascular disease and deep-vein thrombosis in the general population. The evidence that cardiovascular involvement is particularly frequent and advanced in patients affected with several autoimmune diseases (AD), in which hyperhomocysteinemia represent a common finding, led to an intensive investigation on homocysteine (Hcy) as a putative risk factor for the development of cardiovascular disease in such subjects. Indeed, recent data intriguingly expanded the spectrum of the possible pathogenetic implications for hyperhomocysteinemia in the course of AD. In fact, a bi-directional link seems to connect Hcy and the immuno-inflammatory activation characterizing AD, in which immuno-inflammatory activation may contribute to Hcy increase, and Hcy, in its turn, may act as a pro-inflammatory and immuno-stimulating molecule putatively cooperating to the injury of the disease-specific target organs, at least in rheumatoid arthritis and inflammatory bowel disease. Moreover, Hcy may be also a trigger of autoimmune reactions through its capability to bind and structurally modify specific proteins, then resulting in neoantigens formation potentially relevant either in the onset of specific AD and in the progression of the associated cardiovascular damage. More investigation is necessary to fully define the clinical relevance of such phenomena.
17635793 The role of microparticles in inflammation and thrombosis. 2007 Aug Microparticles (MP) are small membrane-bound vesicles that circulate in the peripheral blood and play active roles in thrombosis, inflammation and vascular reactivity. While MP can be released from nearly every cell type, most investigation has focused on MP of platelet, leucocyte and endothelial cell origin. Cells can release MP during activation or death. Flow cytometry is the usual method to quantify MP; the small size of these structures and lack of standardization in methodology complicate measurement. As MP contain surface and cytoplasmic contents of the parent cells and bear phosphatidylserine, antibodies to specific cell surface markers and annexin V can be used for identification. Through various mechanisms, MP participate in haemostasis and have procoagulant potential in disease. MP contribute to inflammation via their influence on cell-cell interactions and cytokine release, and MP also function in mediating vascular tone. In several disease states characterized by inflammation and vascular dysfunction, MP subpopulations are elevated, correlate with clinical events, and may have important roles in pathogenesis. In the rheumatic conditions such as rheumatoid arthritis and systemic lupus erythematosus, MP are potentially important markers of disease activity and have an increasingly recognized role in immunopathogenesis. It is clear that MP play an important role in atherosclerosis, and study of these structures may provide insight into the link between chronic inflammatory conditions and accelerated atherosclerosis. As biomarkers, MP allow access to usually inaccessible tissues such as the endothelium. Further research will hopefully lead to interventions targeting MP release and function.
17618635 Affinity-based methodologies and ligands for antibody purification: advances and perspecti 2007 Aug 10 Many successful, recent therapies for life-threatening diseases such as cancer and rheumatoid arthritis are based on the recognition between native or genetically engineered antibodies and cell-surface receptors. Although naturally produced by the immune system, the need for antibodies with unique specificities and designed for single application, has encouraged the search for novel antibody purification strategies. The availability of these products to the end-consumer is strictly related to manufacture costs, particularly those attributed to downstream processing. Over the last decades, academia and industry have developed different types of interactions and separation techniques for antibody purification, affinity-based strategies being the most common and efficient methodologies. The affinity ligands utilized range from biological to synthetic designed molecules with enhanced resistance and stability. Despite the successes achieved, the purification "paradigm" still moves interests and efforts in the continuous demand for improved separation performances. This review will focus on recent advances and perspectives in antibody purification by affinity interactions using different techniques, with particular emphasis on affinity chromatography.
17582219 The roles of synoviolin in crosstalk between endoplasmic reticulum stress-induced apoptosi 2007 Jun 1 Endopalsmic reticulum (ER) is specialized organelle to maintain the integrity of secreted and membranous proteins. ER also senses so-called "ER stress", which is a result of various internal and external stresses, and triggers apoptosis when the diverse attempts to accommodate with the stress are in fail. The impairment these ER functions has been implicated in several human diseases, in which aberrant ER stress induced apoptosis is observed. We discuss about another disease model related with ER mediated apoptosis based on the recent studies about Synoviolin, an E3 ubiquitin ligase inherently utilized for ER associated degradation (ERAD). In addition to its canonical role in ERAD, Synoviolin targets tumor suppressor gene p53 for proteasomal degradation, suggesting the crosstalk between ERAD and p53 mediated apoptotic pathway under ER stress. Together with the anti-apoptotic property of Synoviolin previously elucidated by both in vitro and in vivo analyses, its new function in p53 regulation may provide a new insight into the pathomechanism of proliferative diseases such as cancer or rheumatoid arthritis.
17464345 Novel irreversible caspase-1 inhibitor attenuates the maturation of intracellular interleu 2007 Feb Caspase-1, the most efficient enzyme in processing the proinflammatory cytokines interleukin 1beta and interleukin 18 in humans, is associated with inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and some neuronal diseases. We previously reported that isoquinoline-1,3,4-trione and its derivatives are novel caspase-3 inhibitors that could attenuate apoptosis in vitro and in vivo. Here we report a novel derivative of isoquinoline-1,3,4-trione that is highly potent in inhibiting caspase-1 activity in an irreversible and slow-binding manner, thus inhibiting cellular caspase-1 activity and the maturation of interleukin 1beta in U-937 cells.
17457680 Angiogenesis and chronic inflammation: cause or consequence? 2007 Evidence has been gathered regarding the association between angiogenesis and inflammation in pathological situations. These two phenomena have long been coupled together in many chronic inflammatory disorders with distinct etiopathogenic origin, including psoriasis, rheumatoid arthritis, Crohn's disease, diabetes, and cancer. Lately, this concept has further been substantiated by the finding that several previously established non-inflammatory disorders, such as osteoarthritis and obesity, display both inflammation and angiogenesis in an exacerbated manner. In addition, the interplay between inflammatory cells, endothelial cells and fibroblasts in chronic inflammation sites, together with the fact that inflammation and angiogenesis can actually be triggered by the same molecular events, further strengthen this association. Therefore, elucidating the underlying cellular and molecular mechanisms that gather together the two processes is mandatory in order to understand their synergistic effect, and to develop new therapeutic approaches for the management of these disorders that cause a great deal of discomfort, disability, and in some cases death.
17086602 Cost-effectiveness of biologic agents for treatment of autoimmune disorders: structured re 2006 Nov OBJECTIVE: Four new biologic treatments have been approved for several autoimmune disorders. Economic evaluations have been used to model their cost-effectiveness. METHODS: We conducted a structured literature review in Embase and PubMed to identify all relevant cost-effectiveness models investigating one or more of these 4 drugs in autoimmune disorders. RESULTS: Fifteen full economic evaluations were identified [13 for rheumatoid arthritis (RA), 2 for Crohn's disease (CD), and 1 for ankylosing spondylitis (AS)]. While several studies found adalimumab, etanercept, and infliximab to be cost-effective (using a threshold around $50,000/quality-adjusted life-year) for treatment of severe RA, not all studies concurred, and there was significant variation in the range of cost-effectiveness ratios reported. Neither study in CD found treatment with infliximab to be cost-effective. Only one study was identified in AS: treatment with infliximab was found to be cost-effective. CONCLUSION: Modeling treatment strategies in chronic relapsing diseases such as RA, CD, and AS presents particular challenges, as reflected in the variation in cost-effectiveness results reported. A reference case for economic evaluations, such as that suggested by the OMERACT (Outcome Measures in Rheumatology) Health Economics Working Group will facilitate comparison and interpretation of results.
17040588 Etanercept, a tumour necrosis factor alpha receptor antagonist, and methotrexate in acute 2006 Dec Patients with autoimmune inner-ear disease (AIED) are treated with high doses of steroids in the short term when suffering an acute hearing loss. As a consequence, substances such as methotrexate have been employed in the role of steroid-sparing agents. Additionally, it is known that tumour necrosis factor alpha (TNFalpha) is an important mediator of the inflammatory process, inhibition of which may be of benefit in AIED. This case report illustrates the use of a TNFalpha inhibitor in combination with methotrexate, which is known to be an effective combination in rheumatoid arthritis but has yet to be described for sensorineural hearing loss. We conclude that progressive AIED may respond well to TNFalpha inhibition, whilst more difficult cases, such as this example, could benefit from combining such therapy with methotrexate.
17038280 Thromboembolic disease after foot and ankle surgery. 2006 Sep BACKGROUND: The incidence and potential life-threatening complications of thromboembolic disease after major orthopaedic surgery has been extensively studied. However, there are two studies pertaining to the incidence of thromboembolic disease after foot and ankle surgery, the findings of which suggest that the incidence is too low to justify routine thromboprophylaxis. METHODS: This is a retrospective study identifying the incidence of thromboembolic disease after foot and ankle surgery in the practices of two foot and ankle specialists. The purpose of the study was to evaluate the risk factors for the development of thromboembolic disease and to examine the issue of routine thromboprophylaxis. Six hundred and two patients were included in this study. RESULTS: There was a 4% incidence (24 patients) of postoperative thromboembolic complications. Risk factors identified for postoperative thromboembolic disease were a history of rheumatoid arthritis, a recent history of air travel, previous deep vein thrombosis or pulmonary embolism, and limb immobilization. CONCLUSIONS: The incidence of thromboembolic disease after foot and ankle surgery could be higher than that previously reported particularly if a patient has certain risk factors. Prospective randomized clinical trials are needed to establish the true incidence of thromboembolic disease after foot and ankle surgery and to define the indications for routine thromboprophylaxis.
16972399 What has ageing to do with periodontal health and disease? 2006 Aug Periodontitis is a multi-factorial disease and in most cases also a disease with a chronic progression. Exposure to factors which contribute to periodontitis occurs over a long period, so that at the time of diagnosis it may be difficult to identify and evaluate what co-factors have contributed to its development. These include exposure to bacteria and viruses, inflammation, genetic factors, health behaviours and a variety of social factors, socio-economic status, behavioural and nutritional habits, the ability to cope with stress and the ability of the immune system to fight infections. Many patients in their 50s also experience other conditions such as heart disease, diabetes mellitus, or rheumatoid arthritis and recent reports on the associations and potential biological mechanisms by which periodontitis can be linked to other systemic diseases suggest that the patient with periodontitis is a challenged individual. Neither individuals nor their oral health care providers are currently prepared for the challenges in oral health care as the expectation of successful ageing with remaining and aesthetically functional teeth is increasing. The scientific evidence is, however, growing, and while the opportunities to prepare for successful ageing exist they must be included in the educational process of both current and future oral health care providers and their patients.
16872476 Lichenoid and granulomatous dermatitis associated with atypical mycobacterium infections. 2006 Jul BACKGROUND: Lichenoid and granulomatous dermatitis defines a distinctive pattern of cutaneous inflammation that may be part of the morphologic spectrum of idiopathic lichenoid reactions such as lichen planus and as well may be seen with lichenoid drug reactions, endogenous T-cell dyscrasias and as a feature of certain systemic diseases especially Crohn's disease and rheumatoid arthritis. RESULTS: We encountered three cases of lichenoid and granulomatous dermatitis in which the basis was one of primary cutaneous Mycobacterium infection. In all three cases acid fast stains revealed pathogenic organisms and as well cultures were positive for Mycobacterium kansasii in one case and Mycobacterium marinum in another. Other features included a prominent perineural and periadnexal lymphocytic infiltrate. CONCLUSIONS: The differential diagnosis of lichenoid and granulomatous dermatitis should also encompass primary cutaneous Mycobacterium infection in addition to the other more characteristic entities associated wtih this distinctive reaction pattern. Infection with Mycobacterium induces a TH1 dominant response which would hence produce an infiltrate.
16760752 Safety issues with biological therapies for inflammatory bowel disease. 2006 Jul PURPOSE OF REVIEW: The purpose of this review is to summarize recent evidence describing specific complications associated with the use of biological therapy derived from controlled trials and from post-marketing surveillance. RECENT FINDINGS: Biological therapies, particularly anti-tumour necrosis factor antibodies, are increasingly used in patients with Crohn's disease and ulcerative colitis. Some adverse events, such as serious infections, are a consequence of the immunomodulatory effect of biological agents, while other complications, such as the induction of autoimmune phenomena, neurotoxicity and the development of an immune response to engineered proteins, are class or molecule-specific. Although the immunopathogenesis of these side effects is often a matter of debate, they have been observed not only in inflammatory bowel disease, but also in other immune disorders such as rheumatoid arthritis and psoriasis. SUMMARY: The benefits of biological agents clearly outweigh the risks. Nevertheless, they are associated with specific toxicity, and this requires the attention of the clinician.
16393950 A case for regulatory B cells. 2006 Jan 15 B cells are typically characterized by their ability to produce Abs, including autoantibodies. However, B cells possess additional immune functions, including the production of cytokines and the ability to function as a secondary APC. As with T cells, the B cell population contains functionally distinct subsets capable of performing both pathogenic and regulatory functions. Recent studies indicate that regulatory B cells develop in several murine models of chronic inflammation, including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalomyelitis. The regulatory function may be directly accomplished by the production of regulatory cytokines IL-10 and TGF-beta and/or by the ability of B cells to interact with pathogenic T cells to dampen harmful immune responses. In this review, we make a case for the existence of regulatory B cells and discuss the possible developmental pathways and functional mechanisms of these B cells.