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ID PMID Title PublicationDate abstract
15743490 Do the pleiotropic effects of statins in the vasculature predict a role in inflammatory di 2005 Pleiotropic effects are now described for the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (or statins) that might have utility in the context of chronic inflammatory autoimmune disease. Here we discuss the pharmacology and established uses of statins and in this context describe potential anti-inflammatory and immune-modulatory effects. An extensive in vitro data set defines roles for statins in modifying endothelial function, particularly with respect to adhesion molecule expression and apoptosis. Broader effects on leukocyte function have now emerged including altered adhesion molecule expression, cytokine and chemokine release and modulation of development of adaptive immune responses via altered MHC class II upregulation. In vivo data in several inflammatory models, including collagen-induced inflammatory arthritis and experimental autoimmune encephalomyelitis, suggest that such effects might have immune-modulatory potential. Finally, a recent clinical trial has demonstrated immunomodulatory effects for statins in patients with rheumatoid arthritis. Together with their known vasculoprotective effects, this growing body of evidence provides compelling support for longer-term trials of statin therapy in human disease such as rheumatoid arthritis.
16052599 Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. 2005 Aug Administration of anti-tumor necrosis factor (anti-TNF) agents is beneficial in a variety of chronic inflammatory conditions, including psoriasis. We describe 5 patients in whom psoriasiform skin lesions developed 6-9 months after the initiation of anti-TNF therapy for longstanding, seropositive rheumatoid arthritis (etanercept or adalimumab), typical ankylosing spondylitis (infliximab), and Adamantiades-Behçet's disease (infliximab). In all 5 patients, the underlying disease had responded well to anti-TNF therapy. Four patients developed a striking pustular eruption on the palms and/or soles accompanied by plaque-type psoriasis at other skin sites, while 1 patient developed thick erythematous scaly plaques localized to the scalp. In 3 patients there was nail involvement with onycholysis, yellow discoloration, and subungual keratosis. Histologic findings from skin biopsies were consistent with psoriasis. None of these patients had a personal or family history of psoriasis. In all patients, skin lesions subsided either with topical treatment alone, or after discontinuation of the responsible anti-TNF agent. The interpretation of this paradoxical side effect of anti-TNF therapy remains unclear but may relate to altered immunity induced by the inhibition of TNF activity in predisposed individuals.
15894165 Pathophysiological roles of G-protein-coupled receptor kinases. 2005 Aug G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated form of G-protein-coupled receptors (GPCRs) to effect receptor phosphorylation and to initiate profound impairment of receptor signalling, or desensitization. GPCRs form the largest family of cell surface receptors known and defects in GRK function have the potential consequence to affect GPCR-stimulated biological responses in many pathological situations. This review focuses on the physiological role of GRKs revealed by genetically modified animals but also develops the involvement of GRKs in human diseases as, Oguchi disease, heart failure, hypertension or rhumatoid arthritis. Furthermore, the regulation of GRK levels in opiate addiction, cancers, psychiatric diseases, cystic fibrosis and cardiac diseases is discussed. Both transgenic mice and human pathologies have demonstrated the importance of GRKs in the signalling pathways of rhodopsin, beta-adrenergic and dopamine-1 receptors. The modulation of GRK activity in animal models of cardiac diseases can be effective to restore cardiac function in heart failure and opens a novel therapeutic strategy in diseases with GPCR dysregulation.
15842577 Valdecoxib is associated with improved dyspepsia-related health compared with nonspecific 2005 May OBJECTIVES: Dyspepsia and related gastrointestinal (GI) symptoms are commonly reported by patients taking nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs) and significantly impact treatment effectiveness, cost, and quality of life. This study sought to evaluate dyspepsia-related health in osteoarthritis (OA) and rheumatoid arthritis (RA) patients taking valdecoxib compared with patients taking nonspecific NSAIDs. METHODS: Analysis of two separate, double-blind, placebo-controlled studies: one in RA patients randomized to placebo, valdecoxib (10 and 20 mg once daily [o.d.]) and naproxen (500 mg twice daily [b.i.d.]); one in OA patients randomized to placebo, valdecoxib (10 and 20 mg o.d.), diclofenac (75 mg b.i.d.), or ibuprofen (800 mg three times daily [t.i.d.]). Study population comprised patients with RA in flare or clinically documented OA who required chronic symptomatic treatment with NSAIDs/analgesics. Dyspepsia-related health was evaluated at baseline and weeks 2, 6, and 12 (or early termination) using the validated Severity of Dyspepsia Assessment (SODA) questionnaire. This patient self-report tool consists of scales for evaluating dyspepsia pain intensity, nonpain symptoms, and satisfaction. Analysis was based on the intent-to-treat population with the last observation carried forward. RESULTS: Valdecoxib was significantly better at endpoint than standard doses of naproxen, diclofenac, and ibuprofen for pain intensity scores (p < 0.05), and provided significantly improved nonpain symptom and satisfaction scores compared with naproxen for patients with RA (p < 0.05). For RA patients, the difference between valdecoxib and naproxen pain intensity scores were clinically meaningful; at all the time points, significantly fewer patients receiving valdecoxib reported severe dyspepsia pain intensity increases (>/=10 points) than those receiving naproxen. At 12 wk, fewer patients receiving valdecoxib reported severe dyspepsia pain intensity increases versus those receiving ibuprofen and diclofenac. CONCLUSIONS: The GI tolerability of valdecoxib is superior to that of nonspecific NSAIDs, and therefore can potentially have a favorable impact on patient quality of life.
16507128 Switching TNF antagonists in patients with chronic arthritis: an observational study of 48 2006 The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications.
15823993 Depression in adults with disabilities, in primary care. 2005 Feb 4 PURPOSE: This research was design to answer the question: Does the prevalence of depression differ between adults with and without disability, in the same family medicine practice? METHOD: A retrospective cohort design was used, to study depression among adults, with and without primary disabling conditions, receiving primary care in either a university based urban or rural family practice setting. RESULTS: When we compared individuals with disability to those without disability, and controlled for individual characteristics, the relative risk for depression was significantly lower for individuals with autism (Relative Risk (RR) 0.20: 95% Confidence Interval (CI) 0.05-0.55), cerebral palsy with mental retardation (RR 0.40: 95% CI: 0.24-0.65), and MR (RR 0.56: 95% CI: 0.39-0.77). The risk for depression was significantly higher for those with cerebral vascular accidents/stroke (RR 2.18: 95% CI: 1.72-3.76) and traumatic brain injury (RR 2.55: 95% CI: 1.72-2.77). The earliest onset of depression was among individuals with traumatic disabilities and milt mental retardation. Our estimate of depression prevalence for the non-disabled and disabled primary care patients was 22.8% and 24.9% respectively, when patients with disabilities were grouped together (p = 0.008). CONCLUSION: It is important for physicians to recognize the higher prevalence of depression among patients with adult onset disabilities (e.g. stroke, traumatic brain injury). In addition, they should be aware of lower prevalence of depression among many individuals with lifelong disabilities, such as mental retardation, cerebral palsy, and autism.
16585064 ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric mat 2006 May Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. The physiological enzyme(s) that degrade COMP, however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search for proteins that associate with COMP to identify an interaction partner that might degrade it. One screen using the epidermal growth factor (EGF) domain of COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595 amino acids, and this protein exhibits higher expression in the musculoskeletal tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with the other three functional domains of COMP, whereas the four C-terminal TSP motifs of ADAMTS-7 are required and sufficient for association with COMP. The recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn2+ and appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and synovium of patients with rheumatoid arthritis is significantly increased as compared to normal cartilage and synovium. ADAMTS-7 is the first metalloproteinase found to bind directly to and degrade COMP.
14722732 Manometric assessment of esophageal motility in patients with primary Sjögren's syndrome. 2005 May OBJECTIVE: The aim of this study was to assess the esophageal motility by manometry in patients with primary Sjögren's syndrome. METHODS: Esophageal manometry was carried out in 40 patients with primary Sjögren's syndrome (SS), 15 with rheumatoid arthritis (RA), 15 with RA and secondary SS, and 21 healthy volunteers. RESULTS: We found that the mean lower esophageal sphincter (LES) pressures measured by station pull-through and rapid pull-through techniques were significantly higher in primary SS patients than with healthy controls and RA patients with or without SS (P<0.05). Our study did not show any major differences when comparing the three patient groups (P>0.05). However, peristaltic contraction velocity was lower and peristaltic contraction duration significantly higher at the middle and lower thirds of the esophagus in primary SS patients than in healthy controls (P<0.05). CONCLUSION: The results of our study support the view that various esophageal motility disorders can be found in patients with primary SS which could be related to an increase in LES pressure. We also found no correlation of the esophageal abnormalities with other factors studied, suggesting that the cause of dysphagia is multifactorial in nature.
16234182 Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy 2005 Sep OBJECTIVES: To determine whether the tumour necrosis factor-alpha (TNF-alpha) antagonist adalimumab (Humira) can be efficacious after secondary loss of efficacy (i.e. loss of clinical response in patients who had initially demonstrated clinical response) to infliximab (Remicade) or etanercept (Enbrel). PATIENTS AND METHODS: We studied 36 patients from the Stockholm TNF-alpha follow-up registry (STURE) who received adalimumab after secondary loss of efficacy to infliximab (group A, n = 27) or etanercept (group B, n = 9), and 26 patients who were started on adalimumab as the first TNF-alpha antagonist (group C). RESULTS: In group A, the baseline disease activity score 28 (DAS28) at infliximab institution was 5.5+/-0.2. During infliximab treatment, the mean best DAS28 was 3.7+/-0.2 (p<0.001), but increased to 5.2+/-0.3 when infliximab was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.5+/-0.3 (p<0.003), and then to 4.2+/-0.2 at 6 months (p<0.001). In group B, the baseline DAS28 at etanercept institution was 6.6+/-0.5. During etanercept treatment, the mean best DAS28 was 4.6+/-0.5 (p<0.01), but increased to 5.7+/-0.4 by the time etanercept was stopped. After 3 months on adalimumab, the mean DAS28 decreased to 4.8+/-0.3 (p<0.005), and to 4.1+/-0.2 at 6 months (p<0.001). In group C, the mean baseline DAS28 was 5.6+/-0.3. After 6 months of adalimumab therapy, the DAS28 decreased to 3.5+/-0.4 (p<0.001). ACR20 responses with adalimumab in groups A, B, and C were similar (70-78%). CONCLUSIONS: For patients with secondary loss of efficacy from infliximab or etanercept, switching to adalimumab can restore a good clinical response.
15940758 Mononuclear cell response to lipopolysaccharide in patients with rheumatoid arthritis: rel 2005 Jun OBJECTIVE: To analyze tumor necrosis factor-alpha (TNF-alpha) synthesis by mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with rheumatoid arthritis (RA). METHODS: TNF-alpha molecular expression and extracellular release were assessed in the peripheral blood mononuclear cells (PBMC) of 27 RA patients and 16 healthy blood donor controls during 8 hours of LPS stimulation. We also analyzed the mRNA expression of tristetraprolin (TTP), the major TNF-alpha mRNA destabilizing factor. TNF receptor p75 (TNFR 2) plasma concentrations were also tested in all patients. RESULTS: Controls and patients demonstrated a comparable wide range of TNF-alpha release capability, but patients achieved the peak value of protein release more quickly. Defining the median TNF-alpha release in controls as the cutoff value to distinguish high and low LPS-induced TNF-alpha-releasing phenotypes, patients with early RA (disease duration < 1 yr) belonged mainly to the low TNF-alpha producer subgroup, whereas patients with long-standing RA (> 1 yr) were prevalently high TNF-alpha producers. TTP molecular expression was higher in patients with shorter, than in patients with longer, disease duration. The profile of TNF-alpha release in patients with early RA changed significantly when retested after 6 months of therapy, while patients with long-standing disease maintained the same behavior as at baseline. Finally, a baseline low TNF-alpha-producer phenotype predisposed to a better responsiveness to disease modifying antirheumatic drugs. CONCLUSION: The LPS-induced TNF-alpha-releasing phenotype differs between cells obtained from RA patients with different disease durations and seems to influence the therapeutic outcome.
16700887 Filarial nematode secreted product ES-62 is an anti-inflammatory agent: therapeutic potent 2006 May 1. The 'hygiene hypothesis' postulates that the recent increased incidence of allergic or autoimmune diseases (e.g. asthma, type I diabetes) in the West reflects an absence of appropriate priming of the immune response by infectious agents, such as parasitic worms, during childhood. 2. Consistent with this, it has long been recognized that several autoimmune disorders, such as rheumatoid arthritis (RA), a T helper (Th) 1-mediated autoimmune disease characterized by excess production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha, exhibit reduced incidence and severity in geographical regions with high parasite load, suggesting that environmental factors may subtly alter disease progression. 3. Infection with worms also appears to suppress Th2-biased inflammatory disorders, such as asthma, because there also appears to be an inverse correlation between parasite load and atopy. This is perhaps more surprising, given that helminths often induce strong Th2-type immune responses characterized by release of specific cytokines, such as interleukin (IL)-4, IL-5 and IL-13. 4. Therefore, these findings suggest that the co-evolution of helminths with hosts, which has resulted in the ability of worms to modulate inflammatory responses in order to promote parasite survival, may also have generated a predisposition for the host to develop autoimmunity and allergy in the absence of infection. 5. The mechanisms underlying such immunomodulation are not clear, but appear to involve the release of parasite-derived molecules that allow the worms to modulate or evade the host immune response by a number of mechanisms, including skewing of cytokine responses and the induction of T regulatory cells. 6. In the present review we discuss the properties of one such filarial nematode-derived immunomodulatory molecule, namely ES-62, its anti-inflammatory action and the therapeutic potential of small molecule derivatives and peptides that mimic its action.
16134726 TGF-alpha and ErbB2 production in synovial joint tissue: increased expression in arthritic 2005 May OBJECTIVE: Cell types present in synovial joint tissues and during synovitis are known to produce epidermal growth factor receptor (EGFR)/ErbB-1/HER-1 and the potent EGFR-ligand transforming growth factor-alpha (TGF-alpha) in vitro. Concomitant expression of TGF-alpha, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF-alpha and members of the EGFR/EGFR-ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF-alpha, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis (RA). METHODS: TGF-alpha protein was immunodetected in knee synovial fluid (SF) collected from 23 RA patients, eight patients with other arthritic conditions, two osteoarthritis (OA) patients, and six post-traumatic patients (control). TGF-alpha mRNA and TGF-alpha, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF-alpha mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT-PCR) and/or the Northern blot technique. RESULTS: TGF-alpha protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF-alpha levels were significantly higher (p < 0.001) in SF of RA patients than controls, TGF-alpha protein and mRNA were increased and more widespread in SM of RA patients. In addition, white blood cells collected from RA SF expressed TGF-alpha mRNA. Immunoreactivity for ErbB2 was found in SM and was more widespread in RA patients than in controls. CONCLUSION: The presence of TGF-alpha in normal SF and SM may indicate a physiological maintenance function. The increased expression of TGF-alpha and ErbB2 in RA SF and SM may give rise to an abnormal growth pattern, contributing to inflammatory synovial hyperplasia.
15713699 Novel monoclonal antibodies detect elevated levels of the chemokine CCL18/DC-CK1 in serum 2005 May CC chemokine ligand 18/dendritic cell-chemokine 1 (CCL18/DC-CK1) is a CC chemokine, preferentially expressed by DC, which acts as a chemoattractant for naive T cells and mantle zone B cells. Applying a newly developed CCL18/DC-CK1 sandwich enzyme-linked immunosorbent assay, we demonstrate that DC secrete high amounts of CCL18/DC-CK1 and that this expression can be increased by interleukin-10. High levels of CCL18/DC-CK1 were also detected in human serum (average of 88 ng/ml). Moreover, elevated CCL18/DC-CK1 levels were detected in synovial fluid from rheumatoid arthritis patients and in drain fluid (average of 254 ng/ml and 122 ng/ml, respectively). Immunoprecipitation experiment using anti-CCL18/DC-CK1 monoclonal antibodies revealed a protein of 6-7 kDa in serum and drain fluid that was indistinguishable from recombinant CCL18/DC-CK1 on Western blot and in re-aggregation assays. The concentration of CCL18/DC-CK1 found in human serum is in the same order of magnitude as was previously reported to completely inhibit CCL11/eotaxin-induced CC chemokine receptor 3 (CCR3) activation and consequent migration of eosinophils. CCL18/DC-CK1 may therefore function as an agonist (for naive T and B cells) and as an antagonist for CCR3-expressing leukocytes such as eosinophils.
16146664 [Whipple's disease endocarditis: report of 5 cases and review of the literature]. 2005 Oct PURPOSE: Endocarditic lesions (infectious endocarditis) associated with Whipple's disease are exceptional. We report five cases from the cardiovascular and pneumologic hospital Louis Pradel in Lyon. METHOD: We have collected all cases of Tropheryma whipplei endocarditis diagnosed between 1995 and 2004. RESULTS: Five men with a mean age of 53 years at time of diagnosis. The symptoms were essentially cardiovascular: murmur, embolism in 3 cases, and heart failure secondary to valvular insufficiency in 2 cases. The valvular involvement, double in 3 cases, was more often aortic. Vegetations were present in all patients and valvular destruction sometimes very important. A low grade fever was present in 4 cases, associated with weight loss in 2 cases. The only extra-cardiac symptoms were arthralgias or arthritis in all cases, considered in 3 patients as seronegative rheumatoid arthritis, B27+ spondylarthritis, and psoriasic arthritis. Their was no other clinical manifestations of Whipple's disease, particularly digestive, ocular, neurologic or adenopathy, and duodenal biopsies secondarily performed in 4 cases were non contributive. This differs from literature as an extra-cardiac location was identified in 11 out of 17 cases. The diagnosis was obtained by histology and PCR on the cardiac valves, as all the patients underwent surgery. The evolution was favourable with a prolonged antibiotic therapy. CONCLUSIONS: These report confirms the existence of endocarditic forms of the Whipple's disease, in which the single extra-cardiac manifestation is rheumatologic, and reminds us the usefulness of histology and PCR on the cardiac valves at the time of valvular surgery.
15539410 Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in preg 2005 Jun OBJECTIVE: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). METHODS: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon gamma (IFNgamma), interleukin (IL) 1beta, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. RESULTS: Low levels of IL10 were found sporadically, whereas IFNgamma and IL1beta were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. CONCLUSIONS: IFNgamma and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity.
17053051 Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. 2007 Feb 1 The interleukin-12 (IL-12) cytokine induces the differentiation of naive T cells to the T helper cell type 1 (Th1) phenotype and is integral to the pathogenesis of Th1-mediated immunologic disorders. A more recently discovered IL-12 family member, IL-23, shares the p40 protein subunit with IL-12 and plays a critical role in the generation of effector memory T cells and IL-17-producing T cells. We introduce a novel compound, STA-5326, that down-regulates both IL-12 p35 and IL-12/IL-23 p40 at the transcriptional level, and inhibits the production of both IL-12 and IL-23 cytokines. Oral administration of STA-5326 led to a suppression of the Th1 but not Th2 immune response in mice. In vivo studies using a CD4+CD45Rbhigh T-cell transfer severe combined immunodeficiency (SCID) mouse inflammatory bowel disease model demonstrated that oral administration of STA-5326 markedly reduced inflammatory histopathologic changes in the colon. A striking decrease in interferon-gamma (IFN-gamma) production was observed in ex vivo culture of lamina propria cells harvested from animals treated with STA-5326, indicating a down-regulation of the Th1 response by STA-5326. These results suggest that STA-5326 has potential for use in the treatment of Th1-related autoimmune or immunologic disorders. STA-5326 currently is being evaluated in phase 2 clinical trials in patients with Crohn disease and rheumatoid arthritis.
16532349 Enhancement of anti-inflammatory tendency by SB203580, p38alpha specific inhibitor, in hum 2006 Sep Interleukin-1 beta (IL-1beta) is an abundant cytokine, which, together with TNF-alpha, mediates inflammatory events in rheumatoid arthritis (RA). IL-1beta is known to induce the induction of inflammatory cytokines and metalloproteinases (MMPs) in rheumatoid synovial cells. Here, we assessed these inflammatory events by measuring IL-1beta levels in the human synovial cell line, MH7A. We observed that the activation of p38 MAP kinase by IL-1beta was involved in the induction of inflammatory cytokines, as well as several genes, including MMP-1 and MMP-3. SB203580, a specific p38 MAP kinase inhibitor, inhibited the production of IL-1beta-induced cytokines and MMPs, while the levels of the tissue inhibitor of metalloproteinase (TIMPs) were unchanged by treatment with SB203580. Moreover, the induction of suppressor of cytokine signaling 3 (SOCS3) and interferon regulatory factor 1 (IRF-1) were both found to be induced by the inhibition of p38 MAP kinase. Therefore, we suggested that the inhibition of p38 MAP kinase might enhance anti-inflammatory tendencies in the MH7A cells.
15748657 Natural radioactivity in sand used in thermal therapy at the Red Sea Coast. 2005 The development of climatotherapy in Safaga opens the field of medical tourism in Egypt, in order to detect any harmful radiation that would affect the patients during treatment and is becoming important economic resource. Studies and survey of natural radiation and radioactivity in upper Egypt conducted since 1990, included monitoring of the concentration of natural radionuclides in environmental samples. The results of the study reveals that, for all sand samples, the mean activity concentration of 40K (618+/-122-548+/-82 Bq kg(-1)) are much higher than that of both 226Ra (25.3+/-14-20.6+/-10 Bq kg(-1)) and 232Th (21.4+/-10-22.4+/-10 Bq kg(-1)). Different radiation hazard indices were calculated, the radiation dose to which workers are subjected is not negligible (26.5-50.9 nGy h(-1)), although depending on the inhalation of dust.
15271770 When a DMARD fails, should patients switch to sulfasalazine or add sulfasalazine to contin 2005 Jan OBJECTIVE: To evaluate the efficacy and safety of adding sulfasalazine to leflunomide treatment compared with switching to sulfasalazine alone in patients with RA with an inadequate response to leflunomide monotherapy. METHODS: Patients with active RA ((DAS28) >3.2) who were enrolled in the first open label phase of the RELIEF study received leflunomide for 24 weeks. Inadequate responders then entered the double blind phase and received a further 24 weeks' treatment with leflunomide (20 mg once daily) plus sulfasalazine (final dose 2 g once daily), or placebo plus sulfasalazine (dose as above). The primary efficacy variable was the DAS28 response rate, and secondary efficacy outcomes were ACR 20%, 50%, and 70% response rates. Adverse events, including standard laboratory tests, were recorded. RESULTS: 106 inadequate responders entered the double blind phase; 56 received leflunomide plus sulfasalazine, and 50 placebo plus sulfasalazine. In the intention to treat population, more patients receiving leflunomide plus sulfasalazine (25/56 (45%)) achieved a DAS28 response than those receiving placebo plus sulfasalazine (17/50 (34%)) (p = 0.179). In week 24 completers, more patients receiving leflunomide plus sulfasalazine (17/56 (30%)) were DAS28 responders than those receiving placebo plus sulfasalazine (10/50 (20%)) (p = 0.081). Comparable numbers in each group were ACR 20% responders; the ACR 50% response rate was significantly higher in the leflunomide plus sulfasalazine group (8.9%) than in the placebo plus sulfasalazine group (0%) (p = 0.038). The safety profiles of both groups were comparable. CONCLUSION: Patient numbers are small and firm conclusions cannot be reached, but a non-significant benefit is indicated for combining leflunomide with sulfasalazine compared with switching to sulfasalazine alone in patients inadequately responding to leflunomide.
16804707 Visual field and multifocal electroretinography and their correlations in patients on hydr 2006 May PURPOSE: To evaluate the effects of hydroxychloroquine on visual field and multifocal electroretinography (mfERG) and their correlations in patients taking hydroxychloroquine. METHODS: This was a cross-sectional study in which patients on hydroxychloroquine therapy underwent automated 10-2 threshold static visual field examination and mfERG recordings. Non-parametric unadjusted and age-adjusted Spearman correlation coefficients rho were calculated between the cumulative dose of hydroxychloroquine and the visual field mean deviation (MD) and pattern standard deviation (PSD) values; and the mfERG response amplitudes and peak latencies. Correlation analysis was also performed between the visual field MD and PSD values and the mfERG response amplitudes and peak latencies. RESULTS: A total of 26 eyes in 13 patients were analyzed. The mean duration of hydroxychloroquine therapy was 4.9 years and the mean cumulative dose was 574 g. No significant correlation was found between the cumulative dose of hydroxychloroquine and the visual field MD and PSD values. There were significant correlations between the cumulative dose of hydroxychloroquine and mfERG N1 and P1 response amplitudes for the central rings (ring 1-3). The correlations between the dose of hydroxychloroquine and mfERG N1 and P1 response amplitudes were strongest for the paracentral ring 2 (rho =-0.63 and rho =-0.62, respectively, P = 0.001). Significant correlations were also found between the visual field MD values and mfERG response amplitudes of various ring eccentricities. CONCLUSIONS: In patients on hydroxychloroquine, mfERG response amplitude correlated with both the 10-2 visual field MD values and with the cumulative dose of hydroxychloroquine used. The use of mfERG can provide objective measurement of retinal function in patients on hydroxychloroquine and may provide supplementary quantitative information to visual field findings.