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ID PMID Title PublicationDate abstract
25366571 Does coenzyme-Q have a protective effect against atorvastatin induced myopathy? A histopat 2015 Mar INTRODUCTION: In addition to their lipid-lowering effect, statins have pleiotropic effects that may extend their use to the treatment and prevention of various other diseases such as cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, type 2 diabetes, and Alzheimer's disease. Consequently, the number of patients taking statins is expected to increase. A side effect of statins, statin-induced myopathy, which may result from reduced muscular coenzyme Q10 levels, limits their use. The current study investigates if supplementing with CoQ10 could ameliorate statin induced myopathy. MATERIALS AND METHODS: Forty adult male albino rats were randomized into 4 groups, with 10 rats per group. The following was administered to the rats using oral gavage for 4 weeks: Group 1: 2 ml of 0.5% carboxymethyl cellulose once daily. Group 2: 100 mg/kg/ day coenzyme Q10 dissolved in 2 ml of cotton seed oil. Group 3: 10 mg/kg once daily atorvastatin dissolved in 0.5% carboxymethyl cellulose. Group 4: concomitantly received CoQ10 and atorvastatin similar to groups 2 and 3 respectively. Plasma creatine kinase levels were measured by using spectrophotometer. The right extensor digitorum longus muscle sections were stained for histological (Haematoxylin & Eosin, Masson trichrome and Phosphotungstic acid haematoxylin) and immunohistochemical (cytochrome C and Bax) examinations. Quantitative measures of cytochrome C and Bax were carried out using image analyzer. RESULTS: Atorvastatin induced increased total creatine kinase, skeletal muscle variations in the sizes and shapes, necrosis, disorganization, nuclear pyknosis, karyorrhexis, karyolysis, dismantled plasma membrane, excess collagen fibers and lipid deposition in addition to loss of cross striation. Atorvastatin increased the intensity of the immune-positive reactions of cytochrome C and Bax. These changes were ameliorated by concomitantly giving coenzyme Q10. CONCLUSION: CoQ10 may ameliorate atorvastatin induced skeletal muscle injury.
24812308 Detecting local haplotype sharing and haplotype association. 2014 Jul A novel haplotype association method is presented, and its power is demonstrated. Relying on a statistical model for linkage disequilibrium (LD), the method first infers ancestral haplotypes and their loadings at each marker for each individual. The loadings are then used to quantify local haplotype sharing between individuals at each marker. A statistical model was developed to link the local haplotype sharing and phenotypes to test for association. We devised a novel method to fit the LD model, reducing the complexity from putatively quadratic to linear (in the number of ancestral haplotypes). Therefore, the LD model can be fitted to all study samples simultaneously, and, consequently, our method is applicable to big data sets. Compared to existing haplotype association methods, our method integrated out phase uncertainty, avoided arbitrariness in specifying haplotypes, and had the same number of tests as the single-SNP analysis. We applied our method to data from the Wellcome Trust Case Control Consortium and discovered eight novel associations between seven gene regions and five disease phenotypes. Among these, GRIK4, which encodes a protein that belongs to the glutamate-gated ionic channel family, is strongly associated with both coronary artery disease and rheumatoid arthritis. A software package implementing methods described in this article is freely available at http://www.haplotype.org.
24616552 HO-1 induction by CO-RM2 attenuates TNF-α-induced cytosolic phospholipase A2 expression v 2014 Rheumatoid arthritis (RA) is characterized by chronic inflammatory infiltration of the synovium and elevation of proinflammatory cytokines. Cytosolic phospholipase A2 (cPLA2) is involved in the development of inflammatory diseases. Heme oxygenase-1 (HO-1) has been shown to possess anti-inflammatory properties. The objective of the study was to investigate the detailed mechanisms of TNF-α-induced cPLA2 expression and to determine whether carbon monoxide releasing molecule-2 (CO-RM2) suppresses TNF-α-induced expression of NF-κB-related proinflammatory genes, including cPLA2, via HO-1 induction in RA synovial fibroblasts (RASFs). Here, we reported that TNF-α-induced cPLA2 expression was mediated through TNFR1/PKCα-dependent signaling pathways, including NADPH oxidase (NOX) activation/ROS production and NF-κB activation. CO-RM2 significantly suppressed TNF-α-induced cPLA2 expression by inhibiting the ROS generation and the phosphorylation of NF-κB p65 and IKK α/β, but not the phosphorylation of p38 MAPK and JNK1/2. These results were further confirmed by a ChIP assay to detect the NF-κB DNA-binding activity. Our results demonstrated that induction of HO-1 by CO-RM2 exerted anti-inflammatory and antioxidant effects which were required in concert to prevent the activation of NF-κB leading to induction of various inflammatory genes implicated in the pathogenesis of RA.
24440038 Fasting: molecular mechanisms and clinical applications. 2014 Feb 4 Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.
25213826 Comparison of perioperative complications after total elbow arthroplasty in patients with 2014 Nov BACKGROUND: Few studies have analyzed the effect of diabetes on outcomes after total elbow arthroplasty (TEA). We investigated the perioperative complications after TEA in patients with and without diabetes. METHODS: We evaluated the Nationwide Inpatient Sample (NIS) database from 2005 to 2010 for patients who underwent a TEA. Our retrospective study included 3184 patients based on International Classification of Diseases-Ninth Revision, Clinical Modification codes. We compared outcomes in 488 patients with diabetes and in 2696 patients without diabetes. RESULTS: Patients with diabetes had a significantly older mean age (66.8 vs 58.5 years, P < .001). There was no statistically significant difference when comparing length of stay (4.1 vs 3.7 days, P = .056) and cost of surgery ($56,582 vs $56,092, P = .833). A significantly higher percentage of diabetic patients underwent TEA for the indication of fracture (73.4% vs 65.3%), but a lower percentage for rheumatoid arthritis (10.2% vs 19.2%). They also had significantly increased rates of pneumonia (odds ratio [OR], 2.7), urinary tract infection (OR, 2.2), blood transfusion (OR, 2.1), and nonroutine discharge (OR, 1.9). After adjusting for significantly increased rates of comorbidities in diabetic patients, our multivariate analysis showed that having diabetes was independently associated with an increased risk of pneumonia (relative risk [RR], 2.6), urinary tract infection (RR, 1.9), and cerebrovascular accident (RR, 9.1). However, diabetes was not independently associated with hospital length of stay (P = .75), after correction, hospital cost (P = .63), or proportion of routine discharges (P = .12). CONCLUSION: Patients with diabetes have higher rates of comorbidities and perioperative complications after TEA.
24789001 Tuberculosis risk in patients treated with non-anti-tumor necrosis factor-α (TNF-α) targ 2014 May This review aimed to evaluate the risk of active tuberculosis (TB) occurrence in patients with rheumatic disorders receiving non-anti-tumor necrosis factor (TNF) targeted biologics anakinra (ANK), tocilizumab (TCZ), rituximab (RTX), abatacept (ABA), and recently approved anti-TNF golimumab (GOL), and certolizumab pegol (CTP). In recent findings, no cases of active TB were recorded in patients with rheumatoid arthritis (RA) and other rheumatic conditions treated with anti-CD20+ RTX and anti-CD28 ABA. No patient receiving anti-interleukin 1 (IL-1) ANK developed active TB, and an increased risk was excluded in a Canadian database. In contrast, 8 active TB cases were observed in 21 trials of patients with RA receiving anti-IL-6 TCZ, while no increased TB risk resulted from Japanese postmarketing surveillance. Among GOL-treated and CTP-treated patients, 8 and 10 active TB cases occurred, respectively, while no data are available from registries. However, all but 1 TB case recorded in patients treated with TCZ, GOL, and CTP occurred in TB-endemic countries. No TB risk resulted for ANK, RTX, and ABA, suggesting pretreatment screening procedures for latent TB infection detection are unnecessary. Because all TB cases occurred in countries at high risk for TB, where TB exposure could have occurred during treatment, no definitive conclusions can be drawn for TCZ, GOL, and CTP.
24084655 Autoimmune liver disease, autoimmunity and liver transplantation. 2014 Jan Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune process is not clear. In this manuscript, we review novel findings about disease processes and mechanisms that lead to autoimmunity in the liver and their possible involvement in the immune response vs. the graft after LT.
23588232 Immunomodulaton and attenuation of lethal influenza A virus infection by oral administrati 2013 Jun Herbal medicine is used to treat many conditions such as asthma, eczema, premenstrual syndrome, rheumatoid arthritis, migraine, headaches, menopausal symptoms, chronic fatigue, irritable bowel syndrome, cancer, and viral infections such as influenza. In this study, we investigated the antiviral effect of KIOM-C for the treatment of influenza A virus infection. Our results show that oral administration of KIOM-C conferred a survival benefit to mice infected with the 2009 pandemic H1N1 [A(H1N1)pdm09] virus, and resulted in a 10- to 100-fold attenuation of viral replication in ferrets in a dose-dependent manner. Additionally, oral administration of KIOM-C increased the production of antiviral cytokines, including IFN-γ and TNF-α, and decreased levels of pro-inflammatory cytokines (IL-6) and chemokines (KC, MCP-1) in the Bronchoalveolar lavage fluid (BALF) of A(H1N1)pdm-infected mice. These results indicate that KIOM-C can promote clearance of influenza virus in the respiratory tracts of mice and ferrets by modulating cytokine production in hosts. Taken together, our results suggest that KIOM-C is a potential therapeutic compound mixture for the treatment of influenza virus infection in humans.
26265276 CD20+inflammatory T-cells are present in blood and brain of multiple sclerosis patients an 2014 Sep BACKGROUND: A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. OBJECTIVE: To determine the presence and phenotype of CD20+T-cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. METHODS: Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. RESULTS: Peripheral blood (n=11) and chronic but not active lesions of MS patient brains (n=5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-γ. ScFvRit:sFasL triggered CD20-restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T-cells, but not CD20+B-cells. CONCLUSION: CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion.
25542985 Anti-inflammatory effects of a novel ricinoleic acid poloxamer gel system for transdermal 2015 Feb 1 Our previous study showed that the use of ricinoleic acid as an oil phase resulted in the formation of a stable pluronic lecithin organogel (PLO gel) with better thixotropic properties and higher permeation of ketoprofen than the isopropyl palmitate PLO gel. This study aims to evaluate and compare the in vitro and in vivo anti-inflammatory effects of the ricinoleic acid PLO gel system with isopropyl palmitate PLO gel. Ketoprofen was used as a model drug. In vitro anti-inflammatory activity and cell viability tests were performed in human rheumatoid arthritis synovial fibroblast cell line using a blank ricinoleic acid PLO gel and compared to that of the isopropyl palmitate PLO gel. In vivo anti-inflammatory activity of ricinoleic acid PLO gel containing 10% ketoprofen was evaluated and compared with the isopropyl palmitate PLO gel in a carrageenan-induced rat paw edema model. The results from the in vitro study showed that the blank ricinoleic acid PLO gel possessed significantly higher anti-inflammatory activity than isopropyl palmitate PLO gel at 1 mM concentration (p<0.05), while both the gel formulations had no significant cytotoxic activity. Further in vivo testing of the formulation showed that the ricinoleic acid PLO gel formulation was significantly more effective in reducing pain and edema when compared to the isopropyl palmitate PLO gel. In addition, the ricinoleic acid PLO gel formulation markedly inhibited the synthesis of prostaglandin E2. In conclusion, the efficacy of PLO gels used in pain management may be enhanced by using ricinoleic acid instead of isopropyl palmitate as an oil phase.
25318864 Diagnosis of latent tuberculosis infection with T-SPOT(®).TB in a predominantly immigrant 2015 Feb PURPOSE: The objective of this study is to compare how likely positive tuberculin skin test (TST) and T-SPOT(®).TB (TSPOT) results predict risk factors for tuberculosis in a predominantly immigrant patient population at risk of latent TB infection (LTBI) and with rheumatologic conditions requiring immunomodulatory therapy (IMT). METHODS: Prospective study conducted at a referral rheumatology clinic. Inclusion criteria included patients on various IMT, including immunosuppressive drugs that could predispose to TB progression. We studied risk factors associated with LTBI, test results, and tests' agreement. RESULTS: We studied 101 patients. Eighty (79.2 %) were from countries where TB is prevalent and Bacille Calmette-Guérin vaccination is placed routinely. Seventy-four (73.3 %) had rheumatoid arthritis and 92 (90.7 %) were on IMT. Among patients with both TST and TSPOT results, 25 (30.9 %) were TST(+) and 20 (24.7 %) had TSPOT(+) results. Fifteen patients (18.5 %) had TST(+)/TSPOT(+) results, and 51 (63.0 %) had TST(-)/TSPOT(-) results (agreement = 81.5 %; kappa = .54 [95 % CI, .34-.74; P < .001]). Each TSPOT(+) and TST(+) results were independently associated with immigrant status and prior residence in a TB prevalent country after adjustment for immunosuppressive therapy: Adjusted OR(TSPOT+)=6.6 (95 % CI, 1.2-123.3; P = .027); and adjusted OR(TST+)=11.2 (95 % CI, 2.0-209.5; P = .003). Seven out of 10 TST(+)/TSPOT(-) cases had a TST ≥15 mm induration, including three cases with history of TST conversion. CONCLUSIONS: TST(+) and TSPOT(+) results predict risk factors associated with LTBI independent of immunosuppressive IMT. Some TST(+)/TSPOT(-) results were unlikely to be false-negatives. The combined use of TST and TSPOT appears to be a reasonable diagnostic strategy to evaluate for LTBI in this population.
25267270 Rotator cuff fatty infiltration and atrophy are associated with functional outcomes in ana 2015 Feb BACKGROUND: Shoulder arthroplasty provides reliable pain relief and restoration of function. However, the effects of fatty infiltration and atrophy in the supraspinatus and infraspinatus muscles on functional outcomes are not well understood. QUESTIONS/PURPOSES: The purposes of this study were to (1) compare preoperative with postoperative fatty infiltration and atrophy of the supraspinatus and infraspinatus muscles after primary shoulder arthroplasty; and (2) identify any associations between these variables and outcome measures. METHODS: A retrospective analysis was undertaken of 62 patients with a mean age of 67 years (range, 34-90 years) who underwent shoulder arthroplasty. CT scans were conducted preoperatively and at 12 months postoperatively. Outcome variables included the degree of supraspinatus and infraspinatus fatty infiltration (percent fatty infiltration and Goutallier grade), muscle area (percent muscle area and Warner atrophy grade), shoulder strength, and the Western Ontario Osteoarthritis Score (WOOS), American Shoulder and Elbow Surgeons score, and Constant outcome score. RESULTS: Preoperatively, the mean percent fatty infiltration (FI) within the supraspinatus and infraspinatus was identical at 14%. One year after shoulder arthroplasty, both muscles had less fatty infiltration (6% and 7%, respectively; p<0.001). Similarly, the Goutallier grade significantly improved postoperatively for the supraspinatus (p=0.0037) and infraspinatus (p=0.0007). Conversely, measures of muscle atrophy remained unchanged postoperatively (p>0.251). Preoperatively, greater supraspinatus percent FI was negatively associated with preoperative shoulder strength (r=0.37, p=0.001) and Constant score (r=0.38, p=0.001). Postoperative infraspinatus percent FI was negatively associated with postoperative strength (r=0.3, p=0.021) and Constant score (r=0.3, p=0.04). Multivariable regression analysis of possible predictive factors demonstrated that preoperative supraspinatus percent muscle area (p=0.016) and the diagnosis of osteoarthritis (p=0.017) were associated with better followup WOOS scores, and preoperative supraspinatus strength was associated with postoperative strength (p=0.0024). Higher degrees of preoperative percent FI were not associated with worse patient-reported outcomes postoperatively. CONCLUSIONS: Supraspinatus and infraspinatus fatty infiltration improves after shoulder arthroplasty, whereas muscle area remains unchanged. Although further study of these variables is required, the negative associations identified between preoperative supraspinatus atrophy and the diagnosis of rheumatoid arthritis and postoperative quality-of-life outcome scores may aid the clinician in selecting the best treatment option for glenohumeral arthrosis and in the management of patient expectations. LEVEL OF EVIDENCE: Level III, prognostic study.
25035256 Formulation design and characterization of an elementary osmotic pump tablet of flurbiprof 2014 Jul Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. The objective of the present study was to develop elementary osmotic pump tablets containing Flurbiprofen using an inclusion complex. Formation of complex was confirmed by Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy. A 3(2) factorial design was applied systematically; the amount of osmotic agent (X1) and size of delivery orifice (X2) were selected as independent variables. Batches were prepared by the direct compression method and evaluated for percent cumulative drug release (%CDR) at 9 h as dependent variables. The amount of osmotic agent and size of the delivery orifice had a significant effect on %CDR. The results of multiple linear regression analysis revealed that elementary osmotic pump tablets should be prepared using an optimum concentration of osmotic agent and size of delivery orifice to achieve a zero-order drug release. Contour plots as well as response surface plots were constructed to show the effects of X1 and X2 on %CDR. A model was validated for accurate prediction of %CDR by performing checkpoint analysis. The computer optimization process, contour plots, and response surface plots were predicted at the concentration of independent variables X1 and X2 (78.38 mg and 0.99 mm, respectively), for maximized response. The drug release from the developed formulation was found to be independent of pH and agitational intensity. The above optimized batch was also evaluated by different pharmacokinetic models like zero-order, first-order, Higuchi, Korsmeyer Peppas, and Hixson Crowell models. Stability study of the optimized batch was conducted at accelerated conditions for 6 months, and was found stable. This study strongly indicates application of osmotic tablets of Flurbiprofen for the treatment of rheumatoid arthritis, as well as osteoarthritis. LAY ABSTRACT: The aim of this study was to develop an elementary osmotic pump tablet of Flurbiprofen and to deliver the drug at a zero-order rate. Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. Elementary osmotic pump tablets containing an inclusion complex of Flurbiprofen was prepared by the direct compression method. The amount of osmotic agent and size of delivery orifice were selected as independent variables. Percent cumulative drug release at 9 h was evaluated for all batches, and it was found that amount of osmotic agent and size of delivery orifice had a significant effect on percent cumulative drug release. The drug release from the developed formulation was found to be independent of pH and agitational intensity. It was also observed that the optimized formulation followed zero-order kinetics and was stable for 6 months at accelerated conditions.
24991788 Esculentic acid, a novel and selective COX-2 inhibitor with anti-inflammatory effect in vi 2014 Oct 5 Esculentic acid (EA), a pentacyclic triterpenoids compound extracted from the Chinese herb Phytolacca esculenta, has long been used in traditional Chinese medicine for the treatment of rheumatoid arthritis, edema, hepatitis and bronchitis disease. The present study aimed to investigate the anti-inflammatory effect of EA in vivo and in vitro and the effect of EA on cyclooxygenase (COX) protein expression. To gain insight into the anti-inflammatory effect of EA both in vivo and in vitro and its effect on COX-2 expression, we used animal inflammatory models and lipopolysaccharide (LPS)-induced mouse peritoneal macrophages to examine the anti-inflammatory action of EA. Our findings demonstrated that EA possessed potent anti-inflammatory activity both in vivo and in vitro, while the anti-inflammation action in vitro may be attributed to the inhibition of the level of TNF-α and IL-6 pro-inflammatory cytokines and PGE2 inflammatory mediator in macrophages. Meanwhile, the production of PGE2 was possibly associated with COX-2 protein expression which was similar to that of NSAIDS. The study extends our understanding of the anti-inflammatory effect of EA both in vivo and in vitro and provides clarification of the molecular mechanisms underlying the effect of EA on PGE2 production, extending a novel aspect to the pharmacological activity of EA.
24931275 Synthesis and evaluation of N⁶-substituted apioadenosines as potential adenosine A₃ re 2014 Aug 1 Adenosine receptors (ARs) trigger signal transduction pathways inside the cell when activated by extracellular adenosine. Selective modulation of the A₃AR subtype may be beneficial in controlling diseases such as colorectal cancer and rheumatoid arthritis. Here, we report the synthesis and evaluation of β-D-apio-D-furano- and α-D-apio-L-furanoadenosines and derivatives thereof. Introduction of a 2-methoxy-5-chlorobenzyl group at N(6) of β-D-apio-D-furanoadenosine afforded an A₃AR antagonist (10c, Ki=0.98 μM), while a similar modification of an α-D-apio-L-furanoadenosine gave rise to a partial agonist (11c, Ki=3.07 μM). The structural basis for this difference was examined by docking to an A₃AR model; the antagonist lacked a crucial interaction with Thr94.
24812290 Lower etanercept levels are associated with high disease activity in ankylosing spondyliti 2015 Oct BACKGROUND: Previous data have shown that etanercept levels are associated with clinical response in rheumatoid arthritis. However, for ankylosing spondylitis (AS), data regarding this topic are inconclusive. OBJECTIVES: To investigate the relationship between etanercept levels and clinical response in patients with AS. METHODS: Observational prospective cohort study of 162 patients with AS =treated with etanercept, monitored during 24 weeks of treatment. Etanercept trough levels were determined, retrospectively, using an ELISA. Disease activity was measured using AS Disease Activity Score (ASDAS), including C-reactive protein (CRP) and Bath AS Disease Activity index (BASDAI). Active disease was defined as ASDAS≥2.1. Since etanercept is a drug administered at home there might have been some variation in trough level sampling. RESULTS: At 24 weeks etanercept levels were significantly higher in patients with ASDAS<2.1, (3.8 mg/L; IQR 2.5-5.2) compared with patients with ASDAS≥2.1 (2.3 mg/L; IQR 1.2-3.4; p≤0.001). Generalised estimating equation analysis demonstrated a statistically significant association between etanercept levels and ASDAS, BASDAI, CRP and erythrocyte sedimentation rate (all p<0.001). When patients were categorised into quartiles according to etanercept levels, the lowest quartile (etanercept<1.80 mg/L) comprised 35% of all patients with ASDAS≥2.1 while the highest quartile comprised only 14%. CONCLUSIONS: Disease activity and inflammation are associated with etanercept levels in patients with AS at 24 weeks of treatment. Measuring etanercept levels might help in identifying overtreatment and undertreatment and optimise etanercept therapy in AS.
24692523 Effect of urate-lowering therapies on renal disease progression in patients with hyperuric 2014 May OBJECTIVE: To evaluate the association between hyperuricemia and renal disease progression in a real-world, large observational database study. METHODS: We conducted a population-based retrospective cohort study identifying 111,992 patients with hyperuricemia (> 7 mg/dl) from a large medical group. The final cohort were ≥ 18 years old, urate-lowering therapy (ULT)-naïve, and had the following laboratory results available: at least 1 glomerular filtration rate (GFR) level before the index date and at least 1 serum uric acid (sUA) level and GFR in the followup 36-month period. The cohort was categorized into 3 groups: never treated (NoTx), ULT time receiving therapy of < 80% (< 80%), and ULT time receiving therapy of ≥ 80% (≥ 80%). Outcomes were defined as a ≥ 30% reduction in GFR from baseline, dialysis, or GFR of ≤ 15 ml/min. A subanalysis of patients with sUA < 6 mg/dl at study conclusion was performed. Cox proportional hazards regression model determined factors associated with renal function decline. RESULTS: A total of 16,186 patients met inclusion criteria. There were 11,192 NoTx patients, 3902 with < 80% time receiving ULT, and 1092 with ≥ 80% time receiving ULT. Factors associated with renal disease progression were age, sex, hypertension, diabetes, congestive heart failure, hospitalizations, rheumatoid arthritis, and higher sUA at baseline. Time receiving therapy was not associated with renal outcomes. Patients who achieved sUA < 6 mg/dl had a 37% reduction in outcome events (p < 0.0001; HR 0.63, 95% CI: 0.5-0.78). CONCLUSION: Hyperuricemia is an independent risk factor for renal function decline. Patients treated with ULT who achieved sUA < 6 mg/dl on ULT showed a 37% reduction in outcome events.
24531518 Features of pressure ulcers in hospitalized older adults. 2014 Mar BACKGROUND: The objectives of this study were to examine the prevalence and risk of pressure ulcers (PrUs) among hospitalized patients 65 years or older in a university hospital setting and to assess the potential for prevention and healing in that population. METHODS: The retrospective study conducted at the general medicine departments of Ege University Hospital in Izmir, Turkey, included 209 patients (115 females, 94 males) 65 years or older, who had been admitted to the hospital for a variety of reasons between April 1, 2011, and October 1, 2011. The following tools were used to collect data: a data collection form to identify the sociodemographic and medical characteristics of the patients, the Braden Risk Assessment Scale to assess the risk of PrUs, and a form to monitor PrUs, which included the site of the PrU, the category, and the PUSH (Pressure Ulcer Scale for Healing) score, a tool for tracking changes in PrUs status applied at weekly intervals. RESULTS: The mean patient age was 73 (6.4) years. The prevalence of PrUs was 5.8% during the hospital stay. Pressure ulcers appeared most frequently in the ischeal tuberosity area (40%), and 45.2% of all PrUs observed were category II. The comorbidities of the patients who had PrUs were as follows: rheumatoid arthritis, 40% (n = 5); acute renal failure, 24% (n = 3); multiple myeloma, 8% (n = 1); chronic renal failure, 8% (n = 1); pneumonia, 8% (n = 1); and acute lymphoblastic leukemia, 8% (n = 1). CONCLUSIONS: Pressure ulcers are a common healthcare complication in the older adult population, with potentially severe consequences. The most important intervention that healthcare professionals can make to reduce PrUs is to determine and address risk factors.
24333429 Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the 2014 Jan 10 Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.
24283670 High seroprevalence of human herpesvirus 8 infection in patients with systemic lupus eryth 2013 Dec AIM: Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with genetic and environmental factors and microbial infection. With respect to microbial infection, the Epstein-Barr virus (EBV) has been a widely discussed issue in recent decades. Human herpesvirus 8 (HHV-8) belongs to the same γ-herpesvirus subfamily as EBV and is closely related to it. Until now, only one paper has reported the prevalence of HHV-8 infection in SLE patients. The goal of this study was to detect the prevalence of HHV-8 infection in SLE patients to elucidate the relationship between HHV-8 and SLE. METHODS: We assessed the seroprevalence of HHV-8 in SLE patients by immunofluorescence assay. In addition, we quantified the HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) from SLE patients by real-time polymerase chain reaction (PCR). RESULTS: The prevalence of HHV-8 antibodies in SLE and normal controls was 57.8% (26/45) and 19.2% (5/26), respectively. These data were highly significant (P = 0.001). No HHV-8 DNA was detected by real-time PCR in SLE patients' PBMCs. In addition, we analyzed the prevalence of HHV-8 infection in patients with rheumatoid arthritis and ankylosing spondylitis. There was no significant difference between the patients and normal controls. CONCLUSION: A high seroprevalence of HHV-8 infection was found in patients with SLE. The negative DNA load and high seropositive rate indicate that most patients might have latent infection.