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ID PMID Title PublicationDate abstract
24003678 [The existence of geographical clusters of rheumatiod arhritis according to their origin i 2013 The objective was to analyse epidemiological tendencies of rheumatoid arthritis (RA) in Dalmatia County in order to identify possible spatial clusters of RA. Patient-interviewers were trained to administer telephone surveys. 197 RA patients controlled at Rheumatology and immunology department of Clinical hospital of Split were mapped to place of residence by telephone survey. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. Four clusters were identified; the largest one was in the region of Sinj. The female/male ratio was 5.79:1. Majority of RA patients were among age 50 to 59 (30.45 %). The results show inter-regional variations with the marked clusters in the north of Dalmatia suggesting that clusters with higher incidence of RA have specific genetic and environmental background. Prevalence of RA in female was higher than in current literature, while the age of onset 50-59 years is similar with data from recent studies.
23911669 Preventive and therapeutic anti-TNF-α therapy with pentoxifylline decreases arthritis and 2013 Sep 17 AIMS: The association between rheumatoid arthritis (RA) and periodontal disease (PD) has long been studied and some reports suggest that treating RA may improve the associated PD, and vice versa. This study aimed to evaluate the effects of an anti-tumor necrosis factor (TNF)-α therapy with pentoxifylline (PTX) in an experimental model of RA-associated PD. MAIN METHODS: Male C57BL/6 mice were subjected to chronic antigen-induced arthritis (AIA) and daily treated with PTX (50mg/kg, i.p.) using preventive (Pre-PTX) or therapeutic (The-PTX) strategies. Fourteen days after the antigen challenge, mice were euthanized and knee joints, maxillae and serum were collected for microscopic and/or immunoenzymatic analysis. KEY FINDINGS: AIA triggered significant leukocyte recruitment to the synovial cavity, tissue damage and proteoglycan loss in the knee joint. Pre-PTX and The-PTX regimens decreased these signs of joint inflammation. The increased levels of TNF-α and IL-17 in periarticular tissues of AIA mice were also reduced by both PTX treatments. Serum levels of C-reactive protein, which were augmented after AIA, were reduced by the PTX regimens. Concomitantly to AIA, mice presented alveolar bone loss, and recruitment of osteoclasts and neutrophils to periodontal tissues. Pre-PTX and The-PTX prevented and treated these signs of PD. PTX treatment also decreased TNF-α and increased IL-10 expression in the maxillae of AIA mice, although it did not affect the expression of IFN-γ and IL-17. SIGNIFICANCE: The current study shows the anti-inflammatory and bone protective effects of preventive and therapeutic PTX treatments, which decreased the joint damage triggered by AIA and the associated periodontal co-morbidity.
24654994 A nationwide cross-sectional overview of patients with rheumatoid arthritis followed in ou 2014 OBJECTIVES: We aimed to conduct a cross-sectional overview of patients with rheumatoid arthritis (RA) in outpatient specialized clinics in Finland. METHOD: Consecutive patients were enrolled in the study. The data collected comprised demographic, disease- and treatment-related variables. RESULTS: Between November 2011 and May 2012, 890 patients with RA (77% female) were enrolled from 14 sites. The median age was 59.8 years and the time from diagnosis 7.2 years. Values for the Disease Activity Score using 28 joint counts (DAS28) ranged from 0.28 to 6.61 (median 2.55) with 52% and 70% of patients reaching remission and low disease activity, respectively. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were evident in 70% and 63% of patients, respectively. Median Health Assessment Questionnaire (HAQ) scores with and without aids and devices were 0.75 [interquartile range (IQR) 0.13-1.38] and 0.63 (IQR 0.13-1.13), respectively. Conventional disease-modifying anti-rheumatic drugs (DMARDs) were used by 91% of patients. A triple therapy of methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SSZ) was used by 15%, other MTX-based combination by 30%, MTX alone by 20%, and other DMARDs alone or in combination by 26% of patients. In addition, glucocorticoids and biologics were taken by 58% and 21% of patients, respectively. Of the 184 biologics users, 18% were not using DMARDs concomitantly. CONCLUSIONS: Our cross-sectional review of patients with RA revealed that > 50% of patients were in remission according to DAS28. Comparison with previous studies revealed a reduction in disease activity of prevalent RA cases, possibly resulting from increased use of aggressive anti-rheumatic treatments.
24764267 High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a m 2014 Oct OBJECTIVE: The B cell chemoattractant chemokine ligand 13 (CXCL13) is emerging as a new biochemical marker in RA. This study was undertaken to dissect the relationship between CXCL13 expression levels in the synovium and clinico-pathological variables relevant to RA pathogenesis and outcome. METHODS: Synovial tissues from 71 RA patients were evaluated by immunohistochemistry. Thirty paired samples were used for comparative gene expression analysis by quantitative real-time PCR. CXCL13 levels were analysed in relation to cellular, molecular and clinical features of inflammation, lymphocyte activation and joint damage. RESULTS: In patients with early disease (<12 months duration), CXCL13 expression correlated significantly with synovial markers of local disease activity and systemic inflammation. Such correlation was less evident in established RA. Notably, the association with lymphocyte infiltration and with expression of B/T cell-related activation and proliferation genes, such as activation-induced cytidine deaminase, IFN-γ and IL-2, remained highly significant independent of disease duration and local disease activity. Patients featuring the highest levels of CXCL13 were more frequently ACPA positive and IgG ACPA titres were increased in the high CXCL13 expression group. Furthermore, the frequency of erosive disease on radiographs was significantly higher in the upper tertile of CXCL13 expression (P = 0.01 with adjustment for disease duration and ACPA). Accordingly, synovial CXCL13 and the local receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) ratio significantly co-varied (ρ = 0.52, P < 0.01), independent of the level of local inflammation. CONCLUSION: Synovial CXCL13 appears to be a marker of a more severe pattern of RA disease, characterized by increased lymphocyte activation and bone remodelling beyond the level of conventional markers of inflammation.
25139185 Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and 2015 May AIM: The purpose of this work was to evaluate epicardial adipose tissue (EAT), carotid intima-media thickness (CIMT), and flow-mediated dilatation (FMD) of the brachial artery in rheumatoid arthritis (RA) patients using ultrasonographic methods. Interrelationships between these three parameters in RA patients were also investigated. METHODS: EAT thickness, CIMT, and FMD were measured by ultrasonography. We measured the disease activity score (DAS28), health assessment questionnaire (HAQ) score, and C-reactive protein (CRP) levels. Spearman or Pearson correlation analysis was used to evaluate the association between clinical findings, CIMT, FMD, and EAT. RESULTS: A total of 90 RA patients [19 men, mean age 54 years (range 21-76 years)] and 59 age- and gender-matched control subjects [17 men, mean age 54 years (range 26-80 years)] were included in the study. Patients with RA had a mean 4.34 DAS28 points (range 0-40 points) and the mean duration of the disease was 77.1 months (range 1-360 months). We found that RA patients had thicker EAT (7.7 ± 1.7 mm vs 6.2 ± 1.8 mm, p < 0.001), increased CIMT [0.9 (0.5-1.2) mm vs 0.6 (0.4-0.9) mm, p < 0.001], and decreased FMD values [5.7 % (- 23.5 to 20 %) vs. 8.5 % (- 4.7 to 22.2 %), p = 0.028] when compared to control subjects. CRP levels were significantly higher in the RA group [0.81 (range 0.1-13.5) vs 0.22 (range 0.05-12), p < 0.001]. EAT thickness was negatively correlated with FMD (r = - 0.26, p < 0.001) and positively correlated with CIMT values (r = 0.52, p < 0.001). CIMT also negatively correlated with FMD (r = - 0.29, p < 0.001). CONCLUSION: EAT can be simply measured by echocardiography and correlated with FMD and CIMT. It can be used as a first-line measurement for estimating burden of atherosclerosis in RA patients.
23292116 A review of therapeutic challenges and achievements of methotrexate delivery systems for t 2013 May PURPOSE: Methotrexate (MTX) is one of the most widely studied and effective therapeutics agents available to treat many solid tumors, hematologic malignancies, and autoimmune diseases such as rheumatoid arthritis; however, the poor pharmacokinetic and narrow safety margin of the drug limits the therapeutic outcomes of conventional drug delivery systems. For an improved delivery of MTX, several pathophysiological features such as angiogenesis, enhanced permeability and retention effects, acidosis, and expression of specific antigens and receptors can be used either as targets or as tools for drug delivery. METHODS: There are many novel delivery systems developed to improve the pitfalls of MTX therapy ranged from polymeric conjugates such as human serum albumin, liposomes, microspheres, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, polymeric micelles, in situ forming hydrogels, carrier erythrocyte, and nanotechnology-based vehicles such as carbon nanotubes, magnetic nanoparticles, and gold nanoparticles. Some are further modified with targeting ligands for active targeting purposes. RESULTS: Such delivery systems provide prolonged plasma profile, enhanced and specific activity in vitro and in vivo in animal models. Nevertheless, more complementary studies are needed before they can be applied in human. CONCLUSION: This review deals with the challenges of conventional systems and achievements of each pharmaceutical class of novel drug delivery vehicle.
23946435 Impact of biologic therapy on functional status in patients with rheumatoid arthritis--a m 2013 Dec OBJECTIVE: Using meta-analysis methods, this study aimed to estimate the impact of biologic agents on physical function in patients with RA. METHODS: A systematic literature search was conducted independently by two investigators. Double-blind randomized controlled trials (RCTs) investigating the efficacy of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab or rituximab in approved dosages in comparison with treatment with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) and placebo were included. The outcome parameter was improvement in function measured by the standardized mean difference (SMD) of HAQ scores. The SMD is the difference of the change in HAQ between biologic and DMARD comparator groups divided by the pooled standard deviation. Mixed effect models were applied separately for RCTs with DMARD-naive patients and those with DMARD inadequate responders (IRs). RESULTS: Thirty-five RCTs were included in the analysis, 10 with DMARD-naive patients and 25 with DMARD IRs. Overall, biologics led to a greater improvement of physical function than nbDMARDs, with an SMD of the HAQ of 0.44 (95% CI 0.38, 0.50). The improvement was greater for DMARD IRs (SMD 0.48, 95% CI 0.41, 0.56) than for DMARD-naïve patients (SMD 0.32, 95% CI 0.23, 0.41). There were no significant differences between individual biologics in both groups. CONCLUSION: Treatment with biologics led to a clinically relevant greater improvement in physical function than treatment with nbDMARDs. Our results suggest that the improvement found on the group level was caused by a clinically relevant improvement on the patient level in more than 50% of the patients.
25263964 Polymorphisms in the TNF-α, TNFR1 gene and risk of rheumatoid arthritis in Chinese Han po 2014 Dec Recent advances have highlighted a major genetic contribution to the pathogenesis of rheumatoid arthritis (RA).The aim of this study was to investigate whether polymorphisms of TNF-α (rs1800630, rs1800629) and TNFR1 (rs767455) were associated with susceptibility to and clinical outcome of RA in Chinese Han population. The target gene polymorphisms were genotyped in 256 patients with RA and 331 healthy controls using a high resolution melting (HRM) method. ESR, CRP, RF anti-CCP and anti-GPI level were also assayed and compared in genotypes of each polymorphism. Significant difference was observed in the genotype distributions and allele frequencies of TNF-α rs1800629 (P = 0.001, P < 0.001, respectively) between patients with RA and controls. There is no evidence to suggest an association between genotypes of the 3 SNPs according to age, gender, disease duration, DAS28 and serum level of autoantibodies. This study identifies a potentially important role for TNF-α rs1800629 polymorphisms in the susceptibility to RA.However, further studies in larger cohorts are required.
22978451 Correlation between DAS-28 and neopterin as a biochemical marker of immune system activati 2013 Feb OBJECTIVE: The objective of this study was to evaluate neopterin plasma concentrations in patients with early Rheumatoid Arthritis (RA) and correlate them with disease activity. METHODS: This is a 28-month prospective study carried out on 65 individuals. There were 27 patients with early RA and 38 healthy volunteers as control group. Enzyme immunoassay was used to measure concentrations of neopterin and anti-cyclic citrullinated peptide (CCP) antibodies. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured turbidimetrically, and antinuclear antibodies (ANA) were detected by immunofluorescence. Patients with early RA disease activity were divided into 4 groups according to DAS-28 criteria. Neopterin concentrations in RA patients were compared to conventional RA diagnostic serological markers. RESULTS: Healthy volunteers had a mean neopterin concentration of 5.63 ± 0.38 [1.36-9.93] nmol. L(- 1). A statistically significant elevation of neopterin mean concentration was found on early RA patients: mean value of 8.92 ± 0.93 [3.94-28.3] nmol. L(- 1) (p < 0.001). Pearson product moment correlation suggests a correlation between neopterin concentrations and DAS-28 (r = 0.208, p = 0.065). The analysis of the mean values grouped according with the DAS-28 criteria showed a correspondence between these means, with a Pearson correlation coefficient r = 0.979, p = 0.021. CRP concentrations also showed a similar trend. Anti-CCP antibodies and RF revealed a positive relationship with RA activity. Such a correlation was not found with ANA results. CONCLUSIONS: The elevation of plasma neopterin concentrations in early RA patients may indicate stimulation of immune response. Good correlation between neopterin concentrations and DAS-28 may facilitate assessing disease activity.
24279308 Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response t 2013 Nov 26 BACKGROUND: This meta-analysis was conducted to determine the efficacy, safety and tolerability of tofacitinib in the treatment of rheumatoid arthritis in patients with an inadequate response or intolerance to at least one of the nonbiologic or biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: Electronic based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), MEDLINE and Cochrane library. The studies included in the meta-analysis were double-blind randomized clinical trials that were conducted in treatment-refractory or intolerant patients with rheumatoid arthritis. The odds ratios (OR), standardized mean differences (SMD) and the 95% confidence intervals (95% CI) were determined by using the random effects model. Heterogeneity among the included studies was evaluated by I² statistics. RESULTS: The odds of tofacitinib treated patients who met the criteria for an at least a 20% improvement in the American College of Rheumatology scale (ACR 20) was more than 4 times higher than placebo treated patients (overall OR = 4.15; 95% CI, 3.23 to 5.32). Even though the discontinuation rate due to adverse events was not different from placebo groups, tofacitinib was associated with infections (overall SMD = 1.96, 95% CI = 1.428 to 2.676), reduction in neutrophil counts (overall SMD = -0.34, 95% CI = -0.450 to -0.223) and elevated levels of LDL cholesterol and liver enzymes. CONCLUSIONS: Tofacitinib was effective in the treatment of active rheumatoid arthritis in patients with an inadequate response or intolerance to at least one DMARDs. However, treatment with tofacitinib was associated with infections and laboratory abnormalities.
23900228 Charcot arthropathy of the foot and ankle associated with rheumatoid arthritis. 2013 Nov BACKGROUND: Diabetic peripheral neuropathy is now well recognized as the most common cause of Charcot arthropathy of the foot and ankle, but it may be associated with other peripheral neuropathies. While not well known, it is well documented that rheumatoid arthritis is correlated with peripheral neuropathy. However, despite rheumatoid neuropathy, Charcot arthropathy has never been associated with rheumatoid arthritis. We report a series of Charcot arthropathy patients with concomitant rheumatoid arthritis. METHODS: The medical records of patients treated between 1986 and 2009 with Charcot arthropathy and rheumatoid arthritis were reviewed. Recorded data included neuropathy risk factors, medications, history of ulcerations, ambulatory status, shoe wear, and treatment course. Radiographs of Charcot joints were categorized according to the Brodsky anatomic classification. Patient care was based on published treatment algorithms, emphasizing accommodative, nonoperative treatment with selective surgical interventions. Surgery was indicated for recalcitrant, nonhealing lesions of the soft tissue and/or unbraceable, nonplantigrade feet. A successful outcome was considered an ambulatory patient without amputation and a closed skin envelope at last follow-up. RESULTS: Four men and 16 women met the diagnostic criteria, resulting in 33 feet in the series. Average age was 61 years, and average follow-up was 4.3 years. In addition to rheumatoid arthritis, 4 patients (7 feet) had hypothyroidism, 4 patients (6 feet) had diabetes, 1 patient (2 feet) had megaloblastic anemia and diabetes, and 1 patient (1 foot) had hypothyroidism and diabetes; however, 17 feet (52%) had no known sources for neuropathy. Charcot involvement was type 1-midfoot in 21 feet (64%), type 2-hindfoot in 7 (21%), type 3a-ankle in 4 (12%), and type 3b-calcaneus in 1 (3%). Twenty-three feet (70%) were treated with conservative modalities. Ten feet (30%) required 15 surgeries, of which an exostectomy was the most common procedure. Of the 33 feet, 3 had persistent ulcerations and 1 underwent major amputation, representing 4 failures. CONCLUSIONS: Raising awareness within the orthopaedic community, we report a Charcot arthropathy population with a concomitant rheumatoid arthritis diagnosis, emphasizing a relationship between the 2 diseases. Through a conservative treatment regimen combined with selective surgical interventions, satisfactory outcomes were achieved in 88% of the rheumatoid Charcot feet. While several patients had additional neuropathy sources which could cause Charcot arthropathy (eg, diabetes), the majority of feet had no etiologies accounting for neuropathy or neuroarthropathy except rheumatoid arthritis. Further study is required to expand on this relationship between the 2 diseases. LEVEL OF EVIDENCE: Level IV, retrospective case series.
23314652 Development and preliminary validation of the pancreatic cancer disease impact score. 2013 Jun OBJECTIVE: Patient-reported outcomes are important for clinical practice and research, and should reflect what patients perceive as important. The objective of this study was to develop and preliminarily validate a brief, patient-derived, disease-specific tool, the pancreatic cancer disease impact (PACADI) score. METHODS: The development was performed in two phases. Forty-one patients with confirmed pancreatic cancer (PC) selected dimensions of health related to the impact of the disease. A weighting of the eight most frequently reported dimensions was performed in a second sample of 80 PC patients who also rated the impact on eight numeric rating scales (NRS, range 0 to 10). The relative weights and the scores from the NRS were used to compute the PACADI score (range 0 to 10). The patients also completed Edmonton Symptom Assessment System (ESAS) and EQ-5D. RESULTS: Dimensions reported by more than 20% of the patients were included in the PACADI score (relative weights in parenthesis): pain/discomfort (0.16), fatigue (0.16), anxiety (0.15), bowel/digestive problems (0.14), loss of appetite (0.13), dry mouth (0.11), itchiness (0.08), and nausea (0.07). The PACADI score in the 80 PC patients had a mean (SD) value of 3.26 (2.06) (95% CI 2.80, 3.71), was moderately to strongly correlated to ESAS sense of well-being (r = 0.69) and EQ-5D (r = -0.52), and discriminated significantly between patients with and without PC. CONCLUSION: The PACADI score is a new eight-item, patient-derived, disease-specific measure. Preliminary validation regarding construct validity and discrimination encourages further validation in independent patient samples.
23840239 Baicalin inhibits IL-17-mediated joint inflammation in murine adjuvant-induced arthritis. 2013 T-helper-17 (Th17) cells are implicated in a number of inflammatory disorders including rheumatoid arthritis. Antagonism of Th17 cells is a treatment option for arthritis. Here, we report that Baicalin, a compound isolated from the Chinese herb Huangqin (Scutellaria baicalensis Georgi), relieved ankle swelling and protected the joint against inflammatory destruction in a murine adjuvant-induced arthritis model. Baicalin inhibited splenic Th17 cell population expansion in vivo. Baicalin prevented interleukin- (IL-) 17-mediated lymphocyte adhesion to cultured synoviocytes. Baicalin also blocked IL-17-induced intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IL-6, and tumor necrosis factor-alpha mRNA expression in cultured synoviocytes. Collectively, these findings suggest that Baicalin downregulates the joint inflammation caused by IL-17, which is likely produced by an expanded population of splenic Th17 cells in experimental arthritis. Baicalin might be a promising novel therapeutic agent for treating rheumatoid arthritis in humans.
24506005 Prevalence of hepatitis B infection in rheumatoid arthritis patients. 2013 Aug 1 Rheumatoid arthritis is a progressive and destructive inflammatory disease of the joints. They had increased mortality depend to use of immunosuppressive drugs. Hepatitis B virus infection is also a health problem in the world. Iran is moderate prevalence endemic area for Hepatitis B virus and it is come too reduced recently by children vaccination. Aim of this study is determined prevalence and screening of Hepatitis B virus infection in rheumatoid arthritis patients. This study is a descriptive cross-sectional which all patients with rheumatic arthritis recruited to study in Tehran in 2012. Then HbsAg and HbcAb assayed for each subjects. In 268 rheumatoid arthritis patients which (82.2%) were female and the average age is 46 +/- 14 years old. HbsAg and HbcAb were positive in 4 (1.49%) and 9 (3.35%), respectively. Only between duration of rheumatoid arthritis and HbcAb had significant association (p < 0.014). The present study highlights Rheumatoid arthritis patients treated with immunosuppressive drugs are at increased risk to reactivation of hepatitis B virus, so screening for Hepatitis B virus infection should be performed prior to immunosuppressive therapy.
24022872 Patient-rheumatologist communication concerning prescription medications: getting to the g 2014 Apr OBJECTIVE: Fuzzy trace theory was used to develop a coding scheme that captures the gist that patients extract from information about medication risks and benefits and to explore the extent to which different patients extract different gist representations from the same information. METHODS: Data were collected from 2003-2007 in a study that included audiotape recording office visits that rheumatoid arthritis (RA) patients had with their rheumatologists. Each patient (n = 365) had up to 3 visits audiotape recorded. The audiotapes were transcribed to facilitate content analysis. Four patients with RA who did not participate in the original study guided development of the coding scheme and used it to code the transcripts. RESULTS: The coding scheme contains 14 gist themes centering on medication effectiveness, need, and safety. There was considerable variation among the gist coders in the specific themes they extracted from individual transcripts. We observed the greatest intercoder agreement for the 4 gist theme variables related to whether the rheumatologist wanted to make changes to the medication regimen. Furthermore, the coders rarely used the "not clear" category to code these 4 variables. In contrast, intercoder agreement for the remaining gist themes, which were designed to capture issues central to the communication of information about medication risks and benefits, was low and the "not clear" category was used more frequently. CONCLUSION: Our study findings suggest that different people exposed to the same information may form different gist representations. Patient-provider communication concerning medication risks and benefits might be enhanced by better understanding the factors that influence the gist extraction process.
24697663 Chronic inflammatory diseases: do immunological patterns drive the choice of biotechnology 2014 Aug Chronic inflammatory diseases represent a heterogeneous group of conditions that can affect practically any organ or system. An increasing number of biologic agents have been developed to selectively target the cell populations and signaling pathways involved in chronic inflammation, including cytokines, monoclonal antibodies and engineered receptors. This approach has been remarkably successful in alleviating some of the signs and symptoms of refractory autoimmune diseases. The use of this therapeutic strategy is likely to increase with the introduction of biosimilar agents. The different nature of these biological products makes the comparison of their pharmaceutical and clinical characteristics difficult, including safety and potency and these issues may be particularly relevant in the case of biosimilars. In addition, the heterogeneity of autoimmune diseases and of autoimmune patients, further adds to the complexity of choosing the right drug for each patient and predicting efficacy and safety of the treatment. In this review, we summarize actual knowledge about current biological agents and their use in autoimmune diseases, with a special emphasis for rheumatoid arthritis, inflammatory bowel diseases and psoriasis. The purpose of this analysis is to address the most critical issues raised by the rapid advancements in this field over recent years, and to acknowledge the potentially valuable gains brought about by the increasing availability of these new biologic agents.
24502044 Clinical and epidemiological study on the prevalence of rheumatoid arthritis in some demog 2013 Jul The structure of the epidemiological process of rheumatoid arthritis (RA) is integrated in a broader framework of multiple interactions between intrinsic predisposing factors and the external environmental factors that may have a triggering or stimulating effect. The summative phenom enon is the result of the additive effect of risk factors, the individualized response of body structures and functions, depending on the genetic makeup explain the complexity of the epidemiologic study. AIM: To evaluate the epidemiological, clinical and biological features of a series of RA patients. MATERIAL AND METHODS: The study included 103 RA patients admitted to the Rheumatology Clinic of the Iasi Rehabilitation Hospital in the interval January, 2010 - December, 2012. RESULTS: The analysis of epidemiological data provided information on pre-existing infections caused by the living environment conditions, diet, etc., that may cause damage at cellular and molecular level. CONCLUSIONS: The present clinical and epidemiological study describes the biological mechanisms and phenomena dependent on physical and social environment. These mechanisms favor and stimulate the occurrence, expansion and development of the disease at population level.
23317165 Recent developments of p38α MAP kinase inhibitors as antiinflammatory agents based on the 2013 Rheumatoid arthritis (RA) and other chronic inflammatory diseases are always the major therapeutic challenges. Recent research efforts provided new insights into the molecular basis of these diseases and new opportunities for developing improved anti-inflammatory drugs. The p38 mitogen-activated protein (MAP) kinase plays a central role in the regulation of the biosynthesis and release of several proinflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Hence, inhibition of the p38 MAP kinase is regarded as a promising therapeutic strategy for controlling inflammatory diseases. A diverse range of p38α MAP kinase inhibitors have been developed as potential anti-inflammatory agents, and some of them have entered the phase II clinical trials. The imidazole derivatives are known as competitive inhibitors at the ATP binding site of the p38α MAP kinase. Modifications on the imidazole scaffold have led to a large amount of potent p38α MAP kinase inhibitors. This review will summarize the developments of small molecule p38α MAP kinase inhibitors based on the imidazole core scaffolds in recent 10 years. Variations at the N1, C2, C4 and C5 positions of imidazole were introduced, and the structure-activity relationships of these imidazole inhibitors were also discussed.
24307257 A general multistage procedure for k-out-of-n gatekeeping. 2014 Apr 15 We generalize a multistage procedure for parallel gatekeeping to what we refer to as k-out-of-n gatekeeping in which at least k out of n hypotheses ( 1 ⩽ k ⩽ n) in a gatekeeper family must be rejected in order to test the hypotheses in the following family. This gatekeeping restriction arises in certain types of clinical trials; for example, in rheumatoid arthritis trials, it is required that efficacy be shown on at least three of the four primary endpoints. We provide a unified theory of multistage procedures for arbitrary k, with k = 1 corresponding to parallel gatekeeping and k = n to serial gatekeeping. The theory provides an insight into the construction of truncated separable multistage procedures using the closure method. Explicit formulae for calculating the adjusted p-values are given. The proposed procedure is simpler to apply for this particular problem using a stepwise algorithm than the mixture procedure and the graphical procedure with memory using entangled graphs.
23710436 1,25-dihydroxyvitamin D3 inhibits the RANKL pathway and impacts on the production of pathw 2013 OBJECTIVES: To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA). METHODS: Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN- γ , IL-6, TNF- α , IL-17, and IL-4 were examined in 54 patients with incipient RA using a cytometric bead array (CBA) or an enzyme-linked immunosorbent assay (ELISA). RESULTS: After 72 hours of incubation of peripheral blood mononuclear cells (PBMCs) with 1,25(OH)2D3 in RA patients, the levels of RANKL, TNF- α , IL-17 and IL-6 significantly decreased compared to those of the control. 1,25(OH)2D3 had no significantly impact on the levels of OPG, RANKL/OPG, and IL-4. CONCLUSIONS: The present study demonstrated that 1,25(OH)2D3 reduced the production of RANKL and the secretion of TNF- α , IL-17, and IL-6 in PBMCs of RA patients, which indicated that 1,25(OH)2D3 might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines.