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ID PMID Title PublicationDate abstract
17907197 Evidence for a different anatomic basis for joint disease localization in polymyalgia rheu 2007 Oct OBJECTIVE: The anatomic basis for joint disease localization in polymyalgia rheumatica (PMR) is poorly understood. This study used contrast-enhanced and fat suppression magnetic resonance imaging (MRI) to evaluate the relationship between synovial and extracapsular inflammation in PMR and early rheumatoid arthritis (RA). METHODS: Ten patients with new-onset PMR and 10 patients with early RA underwent dynamic contrast-enhanced MRI and conventional MRI of affected metacarpophalangeal (MCP) joints. Synovitis and tenosynovitis were calculated based on the number of enhancing voxels, initial rate of enhancement, and maximal enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone edema were scored according to the OMERACT (Outcome Measures in Rheumatology Clinical Trials) scoring system in both groups. The degree of extracapsular Gd-DTPA enhancement was assessed in both conditions using semiquantitative scoring. RESULTS: No significant differences were seen in the volume of synovitis (P = 0.294), degree of flexor tenosynovitis (P = 0.532), periarticular erosions (P = 0.579), or degree of bone edema (P = 0.143) between RA and PMR joints. However, despite comparable degrees of synovitis, the proportion of MCP joints showing extracapsular enhancement was higher in the PMR group (100%) than in the RA group (50%) (P = 0.030). One PMR patient, but none of the RA patients, had bone edema at the capsular insertion. CONCLUSION: Despite degrees of synovitis and tenosynovitis comparable with those in RA, PMR-related hand disease is associated with prominent extracapsular changes, suggesting that inflammation in these tissues is more prominent than joint synovitis, which is common in both conditions. This suggests that the anatomic basis for joint disease localization differs between RA and PMR.
18302096 [Whipple's disease with segmental lesions in the proximal small intestine]. 2008 Mar HISTORY AND ADMISSION FINDINGS: A 67-year-old man with anemia was referred to our hospital. He had suffered from rheumatoid arthritis for ten years. Two months before admission he had been an inpatient at another hospital because of heart failure. He presented with edema, slightly elevated temperature and effusion in the right knee. INVESTIGATIONS: Laboratory findings revealed a chronic inflammation and an anemia of iron malabsorption. Duodenal histology showed PAS-positive macrophages typical for Whipple's disease. Tropheryma whippelii-DNA was found by polymerase chain reaction (PCR) in synovial and cerebrospinal fluid and broncho-alveolar lavage. TREATMENT AND COURSE: Antibiotic therapy was initiated, the antirheumatic medication terminated and iron was administered intravenously. The outcome was satisfactory. CONCLUSIONS: Rare systemic diseases should be considered in patients presenting with symptoms involving several organs. Whipple's disease can be cured only by adequate antibiotic therapy. The use of PCR facilitates the correct diagnosis.
17164993 The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fus 2006 Osteoclasts are bone-resorbing cells that play a critical role for bone destruction in rheumatoid arthritis. It is well known that osteoclasts form multinuclear cells by cell-cell fusion of mononuclear osteoclasts; however, what molecules are required for osteoclast cell-cell fusion, and the role of multinucleation remain uncharacterized. We identified the dendritic cell-specific transmembrane protein DC-STAMP, a putative seven transmembrane protein, and generated DC-STAMP-deficient mice. The cell fusion of osteoclasts was completely abrogated in DC-STAMP-deficient mice, while the transcription factors required for osteoclast differentiation or osteoclast maturation markers were induced as wild type osteoclasts. Interestingly, bone-resorbing activity was reduced in DC-STAMP-deficient osteoclasts compared with wild-type osteoclasts, and DC-STAMP-deficient mice showed osteopetrosis. Thus, we identified DC-STAMP as an essential molecule for osteoclast cell-cell fusion, and found that multinuclear osteoclasts have a higher bone-resorbing activity than mononuclear osteoclastic cells seen in DC-STAMP-deficient mice.
17078590 [What is the frequency of cardiovascular risk factors and co-morbidity in patients with rh 2006 Sep Analysis of national data from the health ministry programme of reduction of the cardiovascular risks (2002-2005) shows a high frequency of cardiovascular disease and cardiovascular risk factors in the general population. It is of interest to analyse these data in relation to the practice of rheumatology. In addition, the frequency of cardiovascular pathologies is higher in patients with rheumatoid arthritis and spondylarthropothy. These notions are also very important since these two populations are often treated with non-steroidal anti-inflammatory drugs for a long duration. General knowledge shown in this article concerning the cardiovascular risk factors and co-morbidities in the patients with rheumatic pathologies allows, within the context of a therapeutic decisional strategy in rheumatology, a better estimation of the individual benefit/risk ratio of each prescription and more particularly that of non-steroidal anti-inflammatory drugs.
18467862 Effects of a tetramethoxyhydroxyflavone p7f on the expression of inflammatory mediators in 2008 Apr The inhibitory effects of 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (labeled as p7F) were elucidated on the productions of proinflammatory cytokines as well as inflammatory mediators in human synovial fibroblasts and macrophage cells. p7F inhibited IL-1beta or TNF-alpha induced expressions of inflammatory mediators (ICAM-1, COX-2, and iNOS). p7F also inhibited LPS-induced productions of nitric oxide and prostaglandin E2 in RAW 264.7 cells. In order to investigate whether p7F would inhibit IL-1 signaling, p7F was added to the D10S Th2 cell line (which is responsive to only IL-1beta and thus proliferates), revealing that p7F inhibited IL-1beta-induced proliferation of D10S Th2 cells in a doseresponse manner. A flow cytometric analysis revealed that p7F reduced the intracellular level of free radical oxygen species in RAW 264.7 cells treated with hydrogen peroxide. p7F inhibited IkappaB degradation and NF-kappaB activation in macrophage cells treated with LPS, supporting that p7F could inhibit signaling mediated via toll-like receptor. Taken together, p7F has inhibitory effects on LPS-induced productions of inflammatory mediators on human synovial fibroblasts and macrophage cells and thus has the potential to be an antiinflammatory agent for inhibiting inflammatory responses.
18821648 Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR 2008 Oct 15 OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.
18793005 Population-level influence of rheumatoid arthritis on mortality and recent trends: a multi 2008 Oct OBJECTIVE: We studied the population-level influence of rheumatoid arthritis (RA) on the mortality of the French population and the pattern of associated causes between 1970 and 2002, using death certificates. METHODS: All French death certificates (n=17,806,923) between 1970 and 2002 were analyzed. Mortality rates related to RA were studied using Poisson regression, and associated causes of death were estimated using the method of observed/expected pairs. Modifications of the International Classification of Diseases and coding methods were considered. RESULTS: RA was mentioned in 0.22% of death certificates. The age-adjusted mortality rates declined during the initial period, but increased in the early 1990s, this trend being driven by the rise in mortality in older groups. The mean age at death was lower for RA-associated deaths than for the general population. Patterns of associated causes of death were identified: there was an increase of the associations with injury, poisoning, external causes, and immunosuppressive toxicities; and a decrease of the associations with endocrine diseases, decubitus ulcers, and glucocorticoid toxicities. CONCLUSION: RA has a significant impact on mortality in the French population, with a trend toward an increase of associated mortality rates in the older population groups starting in the 1990s.
18565254 Anti-TNF-alpha therapy modulates resistin in patients with rheumatoid arthritis. 2008 Mar OBJECTIVE: Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study, we investigated whether anti-TNF-alpha antagonist-monoclonal antibody-infliximab administration alters circulating levels of resistin, a proinflammatory adipokine. We further assessed associations of circulating resistin concentrations with CRP and ESR levels, platelet counts and metabolic syndrome and demographic characteristics in RA patients on periodical treatment with infliximab. METHODS: We investigated 33 patients with RA on periodical treatment with infliximab. Serum resistin levels were determined immediately prior to and after infliximab infusion. RESULTS: Upon infliximab administration, mean (SD) serum resistin concentrations (ng/ml) decreased from 21.9 (9.9) to 17.4 (8.9) (p=0.005). Also, a significant association between the mean ESR (r=0.405; p=0.03) and CRP (r=0.571; p=0.0005) from disease diagnosis and ESR (r=0.486; p=0.004), CRP (r=0.599; p=0.0005) and platelet count (r=0.559; p=0.0007) at the time of the study and baseline resistin levels was found. CONCLUSION: The present study shows that anti-TNF-alpha therapy results in a rapid reduction of serum resistin levels in patients with RA. It also confirms a close association between laboratory markers of inflammation, particularly CRP and resistin levels. These observations support a potential role of resistin in the inflammatory cascade in RA.
17662659 Syk kinase as a treatment target for therapy in autoimmune diseases. 2007 Sep Spleen tyrosine kinase (Syk) associates with a variety of immunoreceptors in myeloid and lymphoid cells. Syk initiates intracellular signaling once the receptor is engaged by its ligand. Blocking Syk may prove beneficial in interrupting the propagation of the abnormal immune response in both autoimmune and allergic diseases.
17962428 Modeling and simulation of abatacept exposure and interleukin-6 response in support of rec 2007 Nov Abatacept is a recombinant soluble fusion protein that inhibits the CD80/CD86:CD28 costimulatory signal required for T cell activation and has demonstrated efficacy in the treatment of rheumatoid arthritis. The objectives of this analysis were to provide support for a body weight-tiered dosing regimen approximating 10 mg/kg by (1) quantifying the effect of body weight on exposure and (2) characterizing the relationship between exposure and serum interleukin (IL)-6 concentration. The abatacept exposure and exposure-response models were developed with 2148 abatacept serum concentrations (from 388 subjects) and 1894 IL-6 serum concentrations (from 799 subjects), respectively, followed by simulation with these models to address the above objectives. Abatacept exposure was characterized by a linear 2-compartmental model, in which clearance was linearly related to body weight. The IL-6 response was characterized by an indirect-response model, in which the IL-6 production rate increased with baseline C-reactive protein levels. Model-based simulations demonstrated that body weight-tiered dosing was desirable to ensure consistent steady-state abatacept trough concentrations across a range of body weights; doses approximating 10 mg/kg (500, 750, 1000 mg for subjects weighing <60, 60-100, and >100 kg, respectively) provided consistent exposure across the body weight groups. In addition, doses >10 mg/kg did not result in further increases in IL-6 suppression. These modeling and simulation results indicate that the body weight-tiered abatacept therapeutic doses approximating 10 mg/kg will ensure consistent abatacept exposure and optimal IL-6 suppression.
17444592 Influence of nonclassical cardiovascular risk factors on the accuracy of predicting subcli 2007 May OBJECTIVE: To determine whether nontraditional risk factors increase the accuracy of predicting the presence of carotid artery plaque based on traditional cardiovascular risk factors only in patients with rheumatoid arthritis (RA). METHODS: We identified risk factors that were independently associated with ultrasonographically located plaque. In predicting carotid artery plaque, the area under the curve (AUC) of the receiver-operating characteristic (ROC) curve for the combination of traditional and nontraditional risk factors was compared to the AUC of the ROC curve for traditional risk factors and nontraditional risk factors considered separately in 91 patients with RA. RESULTS: Thirty-one (34%) patients had carotid artery plaque. The 3 traditional risk factors of age > 55 years, hypertension, and ever-smoking, and the 3 nontraditional risk factors of a disease duration > 8 years, polymorphonuclear cell count > 4.5 x 10(6)/l, and hypothyroidism were each independently associated with the presence of plaque (odds ratios 2.08-8.78; p = 0.001-0.02). The percentage of patients with plaque was 0, 10%, 50%, and 83% in patients with 0-1, 2, 3, and 4-6 of these risk factors, respectively. In predicting plaque, the AUC of the ROC curve for the combination of traditional and nontraditional risk factors (0.90 +/- 0.03) was greater than that for either traditional (0.80 +/- 0.05; p = 0.006) or nontraditional (0.80 +/- 0.04; p = 0.005) risk factors considered separately. CONCLUSION: The combination of disease duration, polymorphonuclear cell counts, and thyroid status increased the accuracy of predicting subclinical atheroma in patients with RA. We believe that our findings merit external validation.
17697449 Etoricoxib versus naproxen in patients with rheumatoid arthritis: a prospective, randomize 2007 Sep BACKGROUND: Etoricoxib is a cyclooxygenase-2 (COX-2) selective inhibitor effective in the treatment of rheumatoid arthritis. An initial 12-week treatment study found that etoricoxib (90 mg once daily) was more effective than naproxen (500 mg twice daily) or placebo in treating rheumatoid arthritis. The present two-part extension of that study was performed to monitor tolerability and examine long-term efficacy of etoricoxib 90 mg or 120 mg compared with naproxen. METHODS: Patients completing the initial 12-week study and those discontinuing due to lack of efficacy, were eligible for the Extension Study Part I (12-52 weeks) and assigned (2:1:2 ratio) to receive etoricoxib (90 mg or 120 mg daily) or naproxen (500 mg twice daily); these patients remained on the same therapy for Extension Study Part II (52-121 weeks). Primary outcome measures included investigator and patient assessment of disease activity, and tender and swollen joint counts. RESULTS: Of 816 patients enrolled in the initial 12-week trial, 717 continued into the Extension Study Part I; 505 patients completed and 390 entered the Extension Study Part II, with 283 patients completing 121 weeks. Patients receiving etoricoxib (90 mg) or naproxen throughout the study experienced sustained efficacy in all outcomes, as did patients transitioning to etoricoxib (120 mg) following the initial 12-week trial. Patients transitioning from placebo to etoricoxib (90 mg) experienced rapid, sustained improvements in all outcome measures. CONCLUSION: In conclusion, etoricoxib provided sustained efficacy throughout the 121-week study, with efficacy comparable to naproxen.
17204310 Patients with rheumatoid arthritis undergoing surgery: how should we deal with antirheumat 2007 Apr OBJECTIVES: To review published data on the perioperative management of antirheumatic treatment and perioperative outcome in patients with rheumatoid arthritis (RA). METHODS: The review is based on a MEDLINE (PubMed) search of the English-language literature from 1965 to 2005, using the index keywords "rheumatoid arthritis" and "surgery". As co-indexing terms the different disease-modifying antirheumatic drugs (DMARDs) as well as nonsteroidal anti-inflammatory drugs (NSAIDs) and "glucocorticoids" were used. In addition, citations from retrieved articles were scanned for additional references. Furthermore, because the number of published articles is so limited, relevant abstracts presented at congresses were included in the analysis. RESULTS: Continuation of methotrexate (MTX) appears to be safe in the perioperative period. Only a limited number of studies address the use of leflunomide and the results are conflicting. Because of the very long drug half-life, its discontinuation would need to be of long duration and is probably not necessary. Data on hydroxychloroquine do not show increased risks of infection. Regarding sulfasalazine, there are no studies from which definite answers could be drawn on whether it should be withheld perioperatively. Preliminary data show that the risk of infections during treatment with TNF-blocking agents may be lower than initially expected. The only available recommendation (Club Rhumatismes et Inflammation, CRI) suggests discontinuing the drugs before surgery for several weeks, depending on the risk of infection and the drug used. They should not be restarted until wound healing is complete. To avoid the antiplatelet effect during surgery, NSAIDs other than aspirin should be withheld for a duration of 4 to 5 times the drug half-life. Patients with chronic glucocorticoid therapy and suppressed hypothalamic-pituitary-adrenal (HPA) axis need perioperative supplementation. CONCLUSIONS: While continuation of MTX likely is safe, data on other DMARDs are sparse. In particular, more data on the perioperative use of the biologic agents are needed.
17328050 Up-regulation of metastasis-promoting S100A4 (Mts-1) in rheumatoid arthritis: putative inv 2007 Mar OBJECTIVE: To examine the involvement of the metastasis-inducing protein S100A4 (Mts-1) in the pathogenesis of rheumatoid arthritis (RA). METHODS: Synovial tissue, synovial fluid, and plasma were obtained from RA and osteoarthritis (OA) patients who were undergoing joint surgery. Immunohistochemical and immunofluorescence analyses and enzyme-linked immunosorbent assays were used to determine the locations and concentrations of S100A4. The conformational structure of S100A4 in plasma and synovial fluid was determined after fractionation by size-exclusion chromatography, protein separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blot analysis. Expression of various S100 proteins in RA synovium was determined by immunofluorescence and double-staining using specific anti-S100 antibodies. RESULTS: We found an up-regulation of S100A4 in cells infiltrating RA synovial tissue. Most cell types identified by cell-specific markers (fibroblasts, immune cells, and vascular cells) contributed to the production of S100A4 in RA synovial tissue. The pattern of S100A4 expression differed significantly from that of the proinflammatory proteins S100A9 and S100A12, which were restricted to phagocytes and granulocytes. The up-regulation of S100A4 in RA synovial tissue was consistent with the high concentrations of the protein in RA versus OA plasma (mean 1,100 versus 211 ng/ml) and synovial fluid (mean 1,980 versus 247 ng/ml). Moreover, we found that S100A4 in RA plasma and synovial fluid was present in bioactive multimeric (M-S100A4) conformations, whereas in OA, the majority of extracellular S100A4 was detected as the less active dimeric form. Consistent with our observations in tumor models, extracellular S100A4 stabilized the p53 tumor suppressor in RA synovial fibroblast-like cells and affected the regulation of p53 target genes, including Bcl-2, p21(WAF), and Hdm-2, as well as matrix metalloproteinases. CONCLUSION: Overexpression of S100A4 in RA synovial tissue and its release as M-S100A4 can influence p53 function and modulate the expression of several genes that are potentially implicated in the disease process. Thus, S100A4 might play an important role in the pathogenesis of RA and might represent a new target for the treatment of RA.
18514017 Rheumatoid polyarthritis caused by a defect in DNA degradation. 2008 Jun Macrophages phagocytose cells that die during programmed cell death and the nuclei that are expelled from erythroid precursor cells during erythropoiesis; subsequently, the ingested DNA is degraded in their lysosomes. A defect in this lysosomal DNA degradation activates the macrophages to produce cytokines such as IFNbeta and TNFalpha in a Toll-like receptor (TLR)-independent manner. IFNbeta thus produced in the mouse fetus induces the apoptosis of erythroid and lymphoid precursor cells, and kills the embryos. On the other hand, when the capacity for lysosomal DNA degradation is knocked out after birth, TNFalpha production increases in adulthood, causing chronic polyarthritis that resembles human rheumatoid arthritis. Here, I summarize recent findings on inflammatory diseases induced by such defects in DNA degradation.
19032829 Anti-glucose-6-phosphate isomerase, anti-cyclic citrullinated peptide antibodies and HLA-D 2008 Sep OBJECTIVE: Our goal was to evaluate the associations of antibodies (Abs) to glucose-6-phosphate isomerase (GPI) with Abs to cyclic citrullinated peptide (CCP) and HLA-DRB1 genotypes in Japanese patients with early rheumatoid arthritis (RA). METHODS: One hundred and eight patients with early RA (85 female, 23 male) who visited our clinic within 1 year of symptom onset were examined for anti-GPI and anti-CCP Ab levels, and HLA-DRB1 genotype. Anti-GPI and anti-CCP Ab levels, and HLA-DRB1 genotypes were also determined in 63 controls and 265 healthy controls, respectively. RESULTS: Of the 108 patients with early RA and the 63 controls, 20 (18.5%) and 3 (4.8%) were anti-GPI Ab-positive, respectively. Of the 20 patients with anti-GPI Abs, 17 (85%) were positive for anti-CCP Abs. HLA-DRB1*0405 and shared epitope (SE) carrier frequencies were significantly increased not only in anti-GPI Ab-positive patients (p=0.00057, odds ratio [OR] 4.6, 95% CI 1.8-11.8; p=0.0011, OR 5.0, 95% CI 1.7-14.0), but also in anti-GPI Ab-negative patients (p=0.0017, OR 2.2, 95% CI 1.3-3.7; p=0.00011, OR 2.6, 95% CI 1.6-4.3), when compared with controls. In addition, the carrier frequency of HLA-DRB1*1201 was significantly increased in anti-GPI Ab-positive patients compared with controls (p=0.0056, OR 4.3, 95% CI 1.4-13.2). CONCLUSIONS: The majority of anti-GPI Ab-positive RA patients constitute a subset of HLA-DRB1* SE-associated, anti-CCP Ab-positive RA patients.
17202177 Down-regulation of leucocyte immunoglobulin-like receptor expression in the synovium of rh 2007 May OBJECTIVES: To compare the expression of leucocyte immunoglobulin-like receptors (LILRs) also known as ILTs and LIRs in rheumatoid arthritis (RA) synovial membrane before and after treatment with disease-modifying anti-rheumatic drugs (DMARDs) and investigate regulation of LILR-expression and function in vitro. METHODS: A study was performed on serial synovial biopsies obtained from 10 RA patients before and after treatment with DMARDs. Expression of the activating LILRA2 (ILT1 or LIR-7) and inhibitory LILRB2 (ILT4 or LIR-2) and LILRB3 (ILT5 or LIR-3) was evaluated by immunohistochemical staining, and quantified by a validated scoring system. Peripheral blood mononuclear cells and in vitro derived macrophages were used to determine effects of DMARDs on expression and function of LILRs. RESULTS: Abundant expression of LILRB2, B3 and A2 was found in synovial tissue of all patients before treatment. Number of inflammatory cells expressing both inhibitory and activating LILRs dramatically decreased in patients who responded to treatment, but remained high in those who did not. However, treatment of macrophages with DMARDs in vitro did not down-regulate LILR expression. On the other hand, reduction in LILR expression in RA synovia was associated with decreased inflammatory infiltrates in those who responded to treatment. Cross-linking of LILRA2 on macrophages caused substantial production of tumour necrosis factor (TNF-alpha) in a dose- and time-dependent manner that was strongly inhibited by dexamethasone. CONCLUSIONS: We show that expression of LILRs in RA synovium was significantly reduced only in patients who responded to treatment. However, clinical responses may not be due to direct effects of DMARDs on LILR expression but due to partial inhibition of LIRA2-mediated TNF-alpha production by steroids leading to suppression of inflammation.
17666446 The dual inhibitor of lipoxygenase and cyclooxygenase ML3000 decreases the expression of C 2008 Apr OBJECTIVE: To find previously unknown properties of ML3000, a competitive inhibitor of the cyclooxygenase and the lipoxygenase (LO) pathway. METHODS: Gene expression of ML3000 treated and untreated rheumatoid arthritis synovial fibroblasts were measured with Affymetrix gene arrays. Downregulation of chemokine (C-X-C motif) ligands CXCL9, CXCL10 and CXCL11 was verified with Real-time polymerase chain reaction, CXCL10 protein levels were determined with ELISA. Rheumatoid arthritis synovial fibroblasts were treated with the cyclooxygenase inhibitor naproxen, the 5-LO inhibitor BWA4C and the 5-lipoxygenase-activating protein (FLAP) inhibitor MK886, and consecutive changes in CXCL10 protein levels measured. 5-LO expression was determined by polymerase chain reaction and Western blot. RESULTS: In synovial fibroblasts and monocyte-derived macrophages ML3000 inhibited the tumour necrosis factor induced expression of CXCL9, CXCL10 and CXCL11, which are all ligands of the chemokine receptor CXCR3. No effect was observed in monocytes. Whereas inhibition of the cyclooxygenase pathway or the FLAP protein showed no effect, blockade of 5-LO significantly downregulated CXCL10 protein levels. 5-LO mRNA was detected in monocytes and in monocyte-derived macrophages. All tested cell types expressed 5-LO protein. CONCLUSIONS: ML3000 effectively downregulates CXCR3 ligands. This study confirms that a thorough analysis of the impact of a drug on its target cells cannot only reveal unexpected properties of a substance, but also helps to understand the underlying molecular mechanisms. Accordingly, our data provide the basis for further clinical studies testing the application of ML3000 in diseases such as rheumatoid arthritis or multiple sclerosis.
16547691 A modified Hohmann method for hallux valgus and telescoping osteotomy for lesser toe defor 2007 Jan To preserve the function of metatarsophalangeal joints and to ensure forefoot stability in patients with rheumatoid arthritis (RA), we performed a modified Hohmann method for hallux valgus (HV) and telescoping osteotomy of lesser toe deformities instead of fusion of HV or resection of all metatarsal heads. From October 1995 through March 2001, 47 RA patients (90 feet) with severe HV and forefoot deformities were examined. The indication for the procedure in all the patients was disabling foot pain secondary to intractable plantar callosities below the lesser metatarsal heads, painful HV deformities, and the severe deviation of the sesamoid complex diagnosed by the basis of X-ray images. The HV and intermetatarsal (M1M2 and M1M5) angles and sesamoid complex were measured on the preoperative and postoperative roentgenograms. According to the results of a questionnaire survey, the patients were divided into three groups using the visual analogue scale; group 1: satisfied, group 2: fair and or no pain, group 3: dissatisfied. HV and M1M2 angles significantly improved compared between pre- and postoperative or preoperative and the follow-up periods. Out of the 47 patients, 78.9% were satisfied with the results of the operation and 8.9% were dissatisfied. Of these patients, 12.2% reported fair results. There were several complications, such as painful callosity, which was recurrent in seven feet, and delayed wound healing was observed in two out of 90 feet. A modified Hohmann method and abductor hallucis correction are effective in relieving pain and ensuring the bony union of the great toe in spite of severe osteoporosis.
17207386 Activity of N-acetyl-beta-hexosaminidase and its isoenzymes in serum and synovial fluid fr 2006 Nov OBJECTIVE: To evaluate the activity of N-acetyl-Beta-hexosaminidase (HEX) and its isoenzymes in the serum and synovial fluid of healthy volunteers and patients with an injury to the anterior cruciate ligament and/or meniscus (ACL) osteoarthritis (OA), juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA). METHODS: The activity of HEX and its isoenzymes was determined according to Zwierz et al. method. Protein content was determined by the biuret method. RESULTS: The specific activity of HEX and its isoenzymes in the serum of patients with JIA showed a tendency to increase in comparison to the reference group. The specific activity of total HEX in the serum of RA patients was significantly increased in comparison to control. Our results show, that specific activity of HEX in synovial fluid, in the reference group 4.2 +/- 0.21 microkat/kg protein (0.25 unit/mg protein), is similar to activity in normal temporomandibular joint fluid (0.3 unit/mg protein). Therefore, we included this group in our research. In patients with OA and ACL injuries, HEX and its isoenzymes showed a tendency to increase in the specific activity in synovial fluid. The specific activity of HEX and its isoenzymes in the synovial fluid of patients with RA and JIA was significantly elevated in comparison to the control and the remaining groups. CONCLUSION: In the synovial fluid of patients with JIA and RA, the specific activity of HEX and its isoenzymes significantly increased in comparison to control and patients with diseases of a non-inflammatory etiology (OA and ACL). In the synovial fluid of control and diseased groups, HEX constituted a higher percent of total proteins than in serum.