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ID PMID Title PublicationDate abstract
17062028 Treatment of inflammatory dermatoses by tumour necrosis factor antagonists. 2006 Nov BACKGROUND: The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches, based on an incomplete knowledge of the immune pathogenesis, are mostly unavailable. The currently applied treatments can in fact lead to remission of the disease; however, under certain circumstances undesirable side-effects must be expected. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the application of TNF-alpha inhibitors represents a novel, more specific, and effective therapeutic option for distinct chronic inflammatory diseases. PATIENTS AND METHODS: The current status of the therapeutic effect of TNF-alpha blockers is discussed based on our own observations and a review of the current literature. Also discussed are potential undesirable side-effects and possible contraindications of this therapy. RESULTS AND CONCLUSIONS: Based on recent findings, the use of TNF-alpha blockers seems to be promising in the treatment of therapy-resistant inflammatory dermatoses. At present, guidelines for indications and contraindications of anti-TNF-alpha treatment of inflammatory skin disorders are rare. Such guidelines are necessary to improve the efficacy of anticytokine treatment and the reduction of side-effects.
16970913 Antioxidant properties of bucillamine: possible mode of action. 2006 Oct 27 The antioxidant properties of Bucillamine (BUC), a di-thiol compound used for treatment of rheumatoid arthritis (RA) and its possible mode of action, were investigated. BUC exhibits potent antioxidant activity similar to those of trolox and ascorbic acid. It reduces the stable free radical diphenyl-2-picrylhydrazyl (DPPH) with IC(50) of 18.5+/-0.1 micromol, its relative antioxidant activity by the ferric reducing ability (FRAP) is 2.07+/-0.01 mM and by the trolox equivalent antioxidant capacity (TEAC), 1.46+/-0.05 mM. However, its superoxide and apparent hydroxyl radical scavenging activities are low (IC(50) at millimolar concentrations). We found that BUC is a strong iron (II) and copper (II) chelator. This finding is very important since these metal ions are significantly higher in RA patients and may be involved in oxidative stress-induced damage. Our study suggests that BUC is a potent antioxidant which exerts its beneficial therapeutic activities in RA patients by metal chelation rather than by scavenging free radical species.
16938258 [Vascular development in inflammatory bowel disease]. 2006 Aug There are 4 major concepts in vascular development: vasculogenesis (formation of blood vessels from angioblasts), angiogenesis (formation of vascular sprouts from preexisting vessels), arteriogenesis (thickening and development of vessels) and lymphangiogenesis (formation of lymphatic vessels). In the last decade, these concepts, especially angiogenesis and lymphangiogenesis, have acquired major importance due to their role in tumoral growth and metastatic dissemination. Moreover, the activity of various diseases that involve chronic inflammation, such as asthma, psoriasis and rheumatoid arthritis, has been associated with vascular development. Several growth factors and cytokines are involved in this process and consequently investigation into these elements, both in peripheral blood and their expression in affected tissues, could elucidate the role of vascular development in diseases whose pathogenesis involves chronic inflammation, such as inflammatory bowel disease. The presence of distinct molecules involved in vascular development processes, such as vascular endothelial growth factor (VEGF), basic fibroblastic growth factor and placental growth factor, among others, has been studied in both ulcerative colitis and Crohn's disease, although not extensively. It has been suggested that the phenomena of vasculogenesis, angiogenesis and lymphangiogenesis play a critical, although not exclusive, role in the inflammation that characterizes inflammatory bowel disease. In general, the results obtained to date suggest that new vascular formation is involved in the pathogenesis of these diseases.
16918457 The cannabinergic system as a target for anti-inflammatory therapies. 2006 Habitual cannabis use has been shown to affect the human immune system, and recent advances in endocannabinoid research provide a basis for understanding these immunomodulatory effects. Cell-based experiments or in vivo animal testing suggest that regulation of the endocannabinoid circuitry can impact almost every major function associated with the immune system. These studies were assisted by the development of numerous novel molecules that exert their biological effects through the endocannabinoid system. Several of these compounds were tested for their effects on immune function, and the results suggest therapeutic opportunities for a variety of inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, atherosclerosis, allergic asthma, and autoimmune diabetes through modulation of the endocannabinoid system.
16906083 Intraoperative contamination influences wound discharge and periprosthetic infection. 2006 Nov Intraoperative bacterial contamination increases risk for postoperative wound-healing problems and periprosthetic infection, but to what extent remains unclear. We asked whether bacterial contamination of the instruments and bone during primary prosthesis insertion was associated with prolonged wound discharge and subsequent periprosthetic infection. During 100 total hip arthroplasties, four intraoperative cultures were taken from the instruments and two portions of removed bone. Postoperatively, the duration of wound discharge was monitored, with Day 5 as the cut-off point. All patients were followed for 2 years to determine whether periprosthetic infection occurred. Bacterial contamination occurred in 36 operative procedures (36%). We found an association between intraoperative contamination and prolonged wound discharge, with a relative risk of 2.5. The culturing of removed bone had a positive predictive value of 81% to 90%. Other factors associated with prolonged wound discharge were rheumatoid arthritis (relative risk, 6.4), use of cement (relative risk, 1.6), and increased blood loss (relative risk, 1.5).
16713722 MRI and non-cartilaginous structures in knee osteoarthritis. 2006 Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy.
19180261 Certolizumab pegol in Crohn's disease. 2008 Nov Certolizumab pegol is a humanized Fab' fragment monoclonal antibody to tumor necrosis factor alpha (TNF-alpha). PEGylation increases its half-life, and it is administered subcutaneously to treat immune-mediated inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Certolizumab pegol improves quality of life and reduces clinical disease activity. Inflammatory markers such as C-reactive protein (CRP) also decrease after administration of certolizumab pegol. The dose for induction of remission is 400 mg subcutaneously at weeks 0, 2 and 4. The dose for maintenance of remission is 400 mg sc given every four weeks. The safety profile is comparable with other anti-TNF agents, and the major adverse events are related to infections. This article reviews the published data regarding the efficacy and safety of certolizumab pegol.
19412418 The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. 2007 Nov The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves' disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves' disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.
16863659 Targeting BAFF: immunomodulation for autoimmune diseases and lymphomas. 2006 Dec In an effort to develop more effective treatments for inflammatory diseases, immunologists have targeted numerous molecular pathways, but with limited success. Notable exceptions are anti-TNF agents, which have proved efficacious in a proportion of rheumatoid arthritis (RA) patients. Another TNF family member, termed BAFF ("B cell-activating factor belonging to the TNF family"), plays a central role in autoimmune diseases, as well as in B cell maturation, survival, and T cell activation. Agents that block BAFF have proven to be highly effective in the treatment of certain autoimmune conditions in mice. In addition, phase II data in human clinical trials for RA appear very promising. BAFF is also a survival factor for certain B cell lymphomas. Despite the relatively recent identification of BAFF, this molecule has provided considerable new insight into B cell homeostasis and immune function, and represents an important new molecular target for treatment of autoimmune diseases and lymphomas.
16855172 Adipose tissue has anti-inflammatory properties: focus on IL-1 receptor antagonist (IL-1Ra 2006 Jun The formation of adipose tissue could result from abnormal metabolic processes and, at the local level, from chronic inflammatory processes such as those occurring in the synovial cavity in rheumatoid arthritis or osteoarthritis, or the peritoneal cavity in various inflammatory processes of the digestive system. Adipocytes are said to produce many hormones and proinflammatory mediators. So far, however, little attention has been paid to cytokine inhibitory molecules. Based on our observation of high levels of serum interleukin receptor antagonist (IL-1Ra) in obese patients contrasting with decreased levels after gastric bypass surgery, we found white adipose tissue (WAT) in the human system to be the main source of IL-1Ra. IL-10 was also present in WAT. Furthermore, we found that interferon-beta (IFN)-beta was the principal cytokine inducing IL-1Ra in various WAT, such as that present in the synovium. We suggest that in addition to other functions adipose tissue may give rise to a host-defense mechanism against local inflammation and that fibrotic tissue in the vicinity may further induce IL-1Ra in adipocytes via the production of IFN-beta.
16838644 [Prospects of treatment using interferon for bone diseases]. 2006 Jul Osteoblasts and osteoclasts produce a variety of cytokines to maintain bone homeostasis. One of the most important cytokines, receptor activator of nuclear factor-IkappaB ligand (RANKL), is essential for osteoclastogenesis. Recently, it was shown that activated T cells promote osteoclastogenesis through RANKL expression and also negatively affect osteoclastogenesis through interferon (IFN)-gamma production. Additionally, it was revealed that IFN-beta was involved in osteoclast regulation by signaling cross-talk with RANKL and that it contributed to the maintenance of normal bone mass. These studies indicate that there are complex regulatory interactions between bone-remodeling cells and immune cells, which depend on the balance between RANKL and IFN. Thus, the interaction between T cells and bone cells could be physiologically critical for the maintenance of normal bone metabolism, and IFN might be an attractive cytokine for use in therapy for bone disease in pathological bone resorptive conditions such as rheumatoid arthritis, osteoporosis, osteomyelitis and bone metastasis of cancers.
16827241 [Optimization of a method for determination of complement activity from 50% hemolysis of s 2006 May The method for determination of compliment activity from 50% hemolysis of sensitized blood cells (CH5) was modified in accordance with the recommendations of the International Clinical Chemistry Association, which could reduce the consumption of reagents, enhance the accuracy and reproducibility of results. The activity of CH50 was calculated for each serum sample by regression analysis, by graphically reflecting the results and by assessing the quality of each performance. The sigma-deviation method was used to calculate the normal CH50 ranges (55-160 conventional units) whose values were in compliance with the international standards. A series of experiments were made to assess the reproducibility of results. To evaluate the diagnostic informative value, the authors analyzed serum samples from 119 persons: 49 apparently healthy individuals, 74 patients with allergic diseases that are generally unattended by hypocomplementemia (Group 1) and 76 with disease the risk of which is increased in the presence of complement system defect (Group 2). Group 1 patients were those who had bronchial asthma or utricaria; Group 2 patients were those who had systemic lupus erythematosus, scleroderma, rheumatoid arthritis, chronic glomerulonephritis, acute glomerulonephritis, chronic furunculosis, chronic tonsillitis, or necrotic vasculitis. In Group 1, the value of CH50 was similar to that in the group of donors (108.0 +/- 3.1 and 105.1 +/- 3.8, respectively; p = 0.565), but it significantly differed from its mean value (91.6 +/- 5.1) in Group 2 (p = 0.00724). The difference in CH50 was also significant in the group of donors and Group 2 (p = 0.0349).
16806940 Pyrexia following total knee replacement. 2006 Aug This study aims to determine the incidence and factors associated with pyrexia following total knee replacement (TKR). We performed a retrospective analysis of the temperature charts and histories of patients who underwent 170 TKRs. There was a statistically significant increase in mean temperature from pre-operation to post-operation, and this increase remained significant through to 5 days post surgery (p<0.0001). Sixty-two (36.5%) patients were pyrexial (>or=38 degrees C) at some point. Fourteen patients developed a clinical infection, but only four of these were pyrexial. There was no association between pyrexia and infection, allogenic blood transfusion, haemoglobin loss, use of urinary catheter, rheumatoid arthritis, anaesthetic type, and previous pyrexia following TKR. Pyrexia as a diagnostic test for the development of infection had a sensitivity of 0.286 (95% CI=0.084-0.581), specificity of 0.628 (95% CI=0.548-0.704) and positive predictive value of 0.065 (95% CI=0.018-0.157). Pyrexia in the first 5 days following TKR is usually a normal physiological response and should not cause undue concern about the presence of infection.
16736418 SAA1 alpha/alpha alleles in amyloidosis. 2006 Mar BACKGROUND: Amyloidosis, mainly AA type, is one of the common diseases in nephrology clinics in Turkey. AA type amyloidosis is a complication of various chronic infections or inflammatory diseases such as familial Mediterranean fever (FMF), rheumatoid arthritis (RA), tuberculosis and bronchiectasis. A controversy exists in the literature regarding the relationship between SAA1 genotypes and AA type amyloidosis. This study aimed to investigate SAA1 gene polymorphism in different patient groups: 1) amyloidosis, 2) FMF and 3) healthy controls. METHODS: Eighty-two patients from the three groups were included in the study: 1) amyloidosis, 2) FMF without amyloidosis, and 3) healthy controls. SAA1 genotypes were studied by the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The homozygous alpha/alpha genotype is the most common SAA1 genotype among patient groups with amyloidosis, and the alpha/alpha genotype frequency is significantly higher than in healthy controls (68 vs. 38%, p<0.05). CONCLUSIONS: The SAA1 alpha/alpha genotype is a risk factor for AA type amyloidosis in Caucasoid populations and more studies are needed to investigate why the gamma/gamma genotype is associated with AA type amyloidosis in Japan.
16724943 Anti-oxidant gene therapy by NF kappa B decoy oligodeoxynucleotide. 2006 Apr Oxidative stress to cardiovascular cells induced by an interaction of multiple cytokines and adhesion molecules has been postulated to be responsible for cardiovascular disease. Since nuclear factor-kappaB (NFkappaB) also plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes, we utilized oligodeoxynucleotides (ODNs) as "decoy" cis-elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation. Indeed, transfection of NFkappaB decoy ODNs into coronary artery effectively prevented transactivation of essential cytokine and adhesion molecule protein expression, and thereby protected the myocardium from infarction. Transfection of NFkappaB decoy ODNs into balloon-injured carotid artery or porcine coronary artery markedly reduced neointimal formation. Thus, a clinical trial using NFkappaB decoy ODNs to treat restenosis was started in 2002. Recently, the therapeutic target utilizing NFkappaB decoy has been expanded to glomerulonephritis, rheumatoid arthritis, atopic dermatitis and osteoporosis. Moreover, the clinical trials to treat RA patients were initiated in 2003 and a Phase I/IIa human clinical trial using NFkappaB decoy ODNs to treat atopic dermatitis was initiated in December 2001. Topical application of NFkappaB decoy ODNs exhibited marked therapeutic effects on the facial skin condition of patients with atopic dermatitis. The covalently modified ODNs were developed by enzymatically ligating two identical molecules, thereby preventing their degradation by exonucleases. Indeed, the modified decoy ODNs possess increased nuclease resistance and are transported more efficiently into cells. Although there are still unresolved issues, decoy ODN drugs should become a reality.
16515469 Screening methods for antioxidants-a review. 2006 Mar Various environmental, physical and chemical stresses on cells may induce either an overproduction of ROS (Reactive Oxygen Species) or a deficiency of antioxidant enzymes. ROS are responsible for various cellular anomalies like protein damage, deactivation of enzymes, alteration of DNA and lipid peroxidation which in turn leads to pathological conditions like carcinogenesis, reperfusion injury, rheumatoid arthritis, diabetes etc. The regular intake of antioxidants seems to limit or prevent the dangerous effects caused by ROS. Thus, to maintain cellular health, it is important to have a specific and effective antioxidant that scavenges multiple types of free radicals so that it can be used in multiple diseases. Different in vitro and in vivo test systems are available in the literature to assess the free radical scavenging activity of various compounds. Based on the efficiency of free radical scavenging, the compounds are classified into strong, moderate and weak antioxidants. The following review explains the brief procedure and the principle behind various methods available in the literature, which can be used to determine the scavenging of different types of free radicals.
16467313 Factor structure of the child health questionnaire-parent form in pediatric populations. 2006 Mar OBJECTIVE: To conduct separate exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) of the Child Health Questionnaire-Parent Form 50 (CHQ-PF-50) with a sample of children and adolescents with chronic conditions and physically healthy children seen in a pediatric setting. METHOD: Parents of 329 children with chronic conditions including cancer, epilepsy, recurrent headache, inflammatory bowel disease (IBD), juvenile rheumatoid arthritis (JRA), sickle cell disease (SCD), and recurrent sleep disturbance and 332 physically healthy children completed CHQ-PF-50. RESULTS: The EFA yielded a 27-item measure with seven factors for children with chronic conditions and a 28-item measure with eight factors for physically healthy children. Structural equation modeling procedures were used to conduct a second order CFA, which yielded the secondary factors of physical health and psychosocial health. A CFA yielded an excellent fit to the data for each group, but the models were different for each group. CONCLUSIONS: CFA-derived models of the CHQ-PF-50 demonstrated construct validity for measuring the latent constructs of physical and psychosocial health in children and adolescents with chronic conditions and physically healthy children and adolescents. However, somewhat different factor solutions emerged for each group, suggesting that the specific domains assessed by the CHQ-PF-50 were not equivalent across groups. Findings have implications for applications of the CHQ-PF-50.
16449368 Current provision of rheumatology education for undergraduate nursing, occupational therap 2006 Jul OBJECTIVES: Rheumatological conditions are common and all health professionals (HPs) therefore need sufficient knowledge and skills to manage patients safely and effectively. The aim of this study was to examine current undergraduate education in rheumatology for HPs in the UK. METHODS: A questionnaire was sent to curriculum organizers and clinical placement officers for all undergraduate courses in adult nursing, occupational therapy (OT) and physiotherapy (PT) in the UK to ascertain the nature and amount of rheumatology theory and clinical exposure provided. RESULTS: Of the 47 adult nursing, 26 OT and 30 PT undergraduate courses surveyed, 85-90% responded. Overall, rheumatology teaching is 5-10 h over 3 yr. Nursing students receive moderate/in-depth teaching on rheumatoid arthritis (RA) in only 52% of courses (OT 91%, PT 96%) and on osteoarthritis (OA) in 63% (OT 91%, PT 92%). Clinical experience of RA is probably/definitely available in only 56% of nursing courses (OT 72%, PT 88%), with similar results in OA. Overall, nursing students receive the least rheumatology exposure, particularly in psychosocial issues and symptom management, while PT students receive the most. OT students have limited opportunities for clinical exposure to psychosocial and joint protection issues. Use of local rheumatology clinical HP experts is variable (18-93%) and cross-disciplinary exposure is limited (0-36%). Many educators consider their rheumatology training to be insufficient (nursing 50%, PT 42%, OT 24%). CONCLUSIONS: Rheumatology training for undergraduate HPs is limited in key areas and often fails to take advantage of local clinical expertise, with nursing students particularly restricted. Clinical HP experts should consider novel methods of addressing these shortfalls within the limited curriculum time available.
16397778 An unusual patient with kidney stones composed of 1-methyluric acid. 2006 Feb An unusual case with kidney stones composed mainly of 1-methyluric acid is described. The patient, a Caucasian male of Celtic descent, reportedly drank at least eight cups of coffee per day and had a long history of rheumatoid arthritis, gouty attacks and renal colics--the latter attributed to nephrocalcinosis and analgesic nephropathy. He was treated with allopurinol. At 54 years, a bilateral nephrolithotomy was performed. Stone samples were analysed by thermogravimetry and infrared spectroscopy and reported to be 12-25% calcium oxalate, the remainder being organic uric acid-like material. Analysis of the extracts by HPLC confirmed that the organic material contained 67% of 1-methyluric acid and 33% of uric acid. Possible mechanisms leading to the precipitation of 1-methyluric acid from urine are discussed. We conclude that the high caffeine intake resulted in extremely elevated urinary concentrations of 1-methyluric acid favouring the formation of 1-methyluric acid stones.
16370952 Toxicity of infliximab in the course of treatment of Crohn's disease. 2006 Jan Infliximab is a monoclonal antibody directed against the pro-inflammatory mediator TNF-alpha, which was approved in the US in 1998 for treatment-resistant Crohn's disease. Since that time, the indications have dramatically expanded to include rheumatoid arthritis, ankylosing spondylitis, psoriasis and most recently, active ulcerative colitis. Although the safety profile in the initial studies was quite favourable, subsequent studies have shown that a small percentage of patients reported severe side effects, including pneumonia, tuberculosis, lymphoma, drug-induced lupus and hepatotoxicity. Although these complications are rare, it is important to properly screen patients for predisposing conditions before beginning treatment. Furthermore, concurrent use of other immunosuppresive agents, such as 6-mercaptopurine, may reduce the incidence of less serious side effects, such as arthralgias, myopathies and other antibody-associated diseases. Since its approval, infliximab has revolutionised the treatment of Crohn's disease and has shown benefit in a variety of other inflammatory conditions, but significant toxicities can occur that necessitate thorough screening protocols and periodic clinical evaluation.