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ID PMID Title PublicationDate abstract
24872899 Severe Pulmonary Suppuration with Infection-Induced Systemic Inflammatory Response Syndrom 2014 A 65-year-old woman with rheumatoid arthritis treated by tocilizumab (TCZ) presented with tongue squamous cell carcinoma. While surgery was performed without any complications the aspiration pneumonia rapidly worsened by postoperative day 2 and severe pulmonary suppuration in the right lung field with infection-induced systemic inflammatory response syndrome (SIRS) was diagnosed. Antibiotic and respirator treatment improved her condition. The anti-inflammatory effect of TCZ may mask the symptoms and signs of severe infection with SIRS.
23620660 Profile of certolizumab and its potential in the treatment of psoriatic arthritis. 2013 Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis (PsO). PsA could be considered an enthesal disease because of the link between mechanical stress (entheses) and immunologically active tissue (synovium). Evidence of efficacy of anti-tumor necrosis factor alpha (TNF-α) is supported by reduction of histological vascularity and immune cell infiltrates in synovial tissue after treatment. Certolizumab pegol (CZP) is a polyethylene glycolylated (PEGylated) Fab' fragment of a humanized monoclonal antibody that binds and neutralizes human TNF-α. The PEG moiety of the Fab fragment, markedly increases the half-life of CZP and confers to the drug a unique structure that differs from the other anti-TNF-α agents tested for the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, axial spondyloarthritis, nonradiographic spondyloarthritis, PsO, and PsA. In contrast to other anti-TNF-α agents, CZP did not mediate increased levels of apoptosis, suggesting that these mechanisms are not essential for the anti-TNF-α efficacy in Crohn's disease. As CZP, infliximab, and adalimumab, but not etanercept, almost completely inhibited lipopolysaccharide-induced interleukin-1 beta release from monocytes, this cytokine-production inhibition may be relevant for drug efficacy. Due to these characteristics, it has been demonstrated in clinical studies that CZP effectively improves signs and symptoms of arthritis and physical function and skin manifestations of PsO, with a safety profile similar to rheumatoid arthritis. This drug can be considered as a valid treatment in patients affected by PsA. The efficacy and tolerability profiles suggest CZP as a suitable antipsoriatic drug in the treatment of PsA.
25525340 Perceived need to take medication is associated with medication non-adherence in patients 2014 BACKGROUND: This is the first cross-sectional study that aims to examine associations between beliefs about medication and non-adherence in patients with rheumatoid arthritis (RA) using disease-modifying antirheumatic drugs, taking potential psychological confounders into account. METHODS: Eligible patients (diagnosed with RA for ≥1 year or ≥18 years, using greater than or equal to one disease-modifying antirheumatic drug) were included by their rheumatologist during regular outpatient visits between September 2009 and September 2010. Included patients received questionnaires. The Beliefs about Medicines Questionnaire was used to measure the perceived need to take medication (necessity beliefs), the concerns about taking medication (concern beliefs), general medication beliefs, and attitudes toward taking medication. Medication non-adherence (no/yes) was measured using the Compliance Questionnaire Rheumatology (CQR). Associations between beliefs and non-adherence, and the influence of demographical, clinical, and psychological factors (symptoms of anxiety/depression, illness cognitions, self-efficacy) were assessed using logistic regression. RESULTS: A total of 580 of the 820 eligible patients willing to participate were included in the analyses (68% female, mean age 63 years, 30% non-adherent to their medication). Weaker necessity beliefs (OR [odds ratio]: 0.8, 95% CI [confidence interval]: 0.8-0.9) and an unfavorable balance between necessity and concern beliefs (OR: 0.9, 95% CI: 0.9-1.0) were associated with CQR non-adherence. Also, having an indifferent attitude toward medication (no/yes) was associated with CQR non-adherence (OR: 5.3, 95% CI: 1.1-25.8), but the prevalence of patients with an indifferent attitude toward medication was low. The associations were barely confounded by demographical, clinical, and psychological factors. CONCLUSION: Increasing necessity beliefs about medication in clinical practice might be worthwhile in improving medication adherence in RA patients.
27708898 Potential role of interleukin-18 in patients with rheumatoid arthritis-associated carotid 2014 Dec OBJECTIVE: Plasma interleukin-18 (IL-18) has been reported to be associated with homeostasis model assessment of insulin resistance (HOMA-IR). It also has been described as one of the factors that, in addition to insulin resistance, may also contribute to atherosclerosis. Parameters of systemic inflammation are also significantly associated with circulating IL-18. Our objective was to investigate whether IL-18 is associated with insulin resistance and atherosclerosis in patients with rheumatoid arthritis (RA) in which accelerated atherogenesis develops. MATERIAL AND METHODS: Fifty-one female RA patients and 30 female controls were enrolled in the study; 31 of them were without disease-modifying antirheumatic drug (DMARD) treatment and had a relatively short disease duration. Disease activity was assessed by Disease Activity Score (DAS) 28 index. HOMA-IR method was used to detect insulin resistance. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fasting plasma glucose (FPG), insulin, tumor necrosis factor alpha (TNF-α), and IL-18 levels were evaluated. Also, carotid intima-media thickness (cIMT) was measured. RESULTS: There were no differences between patients and the control group according to age, sex, and body mass index. ESR, CRP, insulin, FPG, HOMA-IR, TNF-α, IL-18 levels, and cIMT measurements were significantly high in the patient group. HOMA-IR and cIMT measurements were similar and high in both the DMARD and non-DMARD patient groups. HOMA-IR correlated with TNF-α (r=0.308, p=0.028), but no correlation was found between IL-18 and HOMA-IR. However, IL-18 was correlated positively with cIMT (r= 0.318, p=0.028) and negatively with BMI (r=-0.360, p=0.01). CONCLUSION: IL-18 is associated with atherosclerosis in RA patients. However, no significant relation was found with insulin resistance. IL-18 may be a marker for early evaluation of atherosclerosis in RA patients.
29702811 Medical and Productivity Costs of Rheumatoid Arthritis in The Czech Republic: Cost-of-Illn 2014 Sep OBJECTIVE: International pharmacoeconomic studies suggest that functional impairment can be a significant predictor for the evaluation of direct and productivity costs for rheumatoid arthritis (RA). We calculated the direct and productivity costs for five Health Assessment Questionnaire (HAQ) groups of patients (HAQ scores <0.6, 0.6 ≥ 1.1, 1.1 ≥ 1.6, 1.6 ≥ 2.1, and ≥2.1) in the Czech Republic. METHODS: This was a retrospective cross-sectional study. We included 261 patients with RA, aged 18 to 84 years. We applied a bottom-up method by retrospectively reviewing individual patient medical records. Patients' demographic characteristics, patient-reported outcome, and clinical parameters were gathered at the time of data collection. For the calculation of productivity costs, we used the friction cost approach, based on patient absenteeism with a friction period of 130 workdays, with average monthly income used as the denominator. Costs were expressed as a mean value per patient with RA in each HAQ group. RESULTS: Mean patient age was 56.4 years. average time from diagnosis was 14.5 years, the mean HAQ score was 1.15, and the Disease Activity Score in 28 joints was 3.45. A total of 47.5% patients were treated with biologics. Mean annual direct medical costs for each HAQ group were €5315, €7357, €7697, €7716, and €8968, respectively. The mean annual indirect costs associated with productivity loss were €1414, €1459, €1610, €1876, and €2307, respectively. CONCLUSIONS: Direct costs and productivity costs for patients with RA are closely related to the value of the HAQ score. The annual mean total (direct plus productivity) costs per patient 1) treated with biologics, 2) without biologic treatment, and 3) from the overall cohort were €14,763, €3,559, and €8,882, respectively.
25391376 Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into inter 2015 May The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis.
23856045 Porphyromonas gingivalis peptidylarginine deiminase substrate specificity. 2013 Oct While a group of oral commensals have been implicated in the aetiology of chronic periodontitis; the asaccharolytic Gram negative anaerobe Porphyromonas gingivalis is most commonly reported to be associated with severe forms of the disease. Although a variety of human tissues can produce a number of peptidylarginine deiminase (PAD), enzymes that convert peptide bound arginine residues to citrulline, P. gingivalis is one of the few prokaryotes known to express PAD. Protein and peptide citrullination are important in the development of rheumatoid arthritis and in recent years a number of authors have suggested a possible link between periodontitis and rheumatoid arthritis (RA). Indeed, some have linked P. gingivalis directly to RA via the action of PAD. Accordingly, the prime purpose of this study was to further characterise PAD in P. gingivalis cells particular emphasis on substrate specificity, using arginine containing peptides and RA relevant proteins. METHODS: P. ginigvalis W50 was anaerobically cultured in BHI broth, cells harvested and resuspended in assay buffer. A colourimetric assay was developed to measure citrulline and employed to determine enzyme activity using the substrate BAEE. The assay was employed to investigate the effects of environmental pH and temperature on activity. Citrullination of BAEE by sonicated cells allowed the proportion of intracellular enzyme to be estimated. Enzyme specificity and substrate preference were investigated by using various arginine containing peptides, proteins and arginine analogues, as substrates and measuring the rate of citrullination. The influence of gingipains on citrullination was assessed by measuring the rates of citrullination of bovine serum albumin in the presence of protease inhibitors. RESULTS: Enzyme activity decreased by 13% following exposure of cells to 60 °C for 10 min. A comparison of intact and disrupted cells indicated that 90% of PAD activity is cell surface associated and the remainder cytoplasmic. Optimal pH for enzyme activity was between pH 7.5 and 8. All small arginine-containing peptides were citrullinated with reaction rates faster than that for free arginine with rates that varied with arginine residue position and number. Arginine analogues exhibited minimal effect and influence when tested as either substrates or competitive inhibitors. Cells were able to citrullinate yeast enolase, human vimentin and fibrin at varying rates. All proteins were modified at slower rates than those for peptide substrates. Inhibition of gingipains had no influence on the rate of protein citrullination. CONCLUSIONS: P. gingivalis PAD is a primarily cell surface associated, heat stable, enzyme that exhibits optimal activity under alkaline conditions similar to those present in the inflammatory environment. The enzyme displays high specificity for arginine residues in peptides and modified arginine in all positions and the gingipains did not influence the rate of protein citrullination. The ability of the enzyme to convert arginine residues in all proteins tested would indicate that its presence in inflamed tissue may promote autoimmune reactions by creation of altered host epitopes.
25426122 Obesity as a risk and severity factor in rheumatic diseases (autoimmune chronic inflammato 2014 The growing body of evidence recognizing the adipose tissue (AT) as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low-grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the AT on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases.
25097790 Lung sarcoidosis in etanercept treated rheumatoid arthritis patient: a case report and rev 2014 We report a 55-year-old female with seropositive rheumatoid arthritis for 10 years who developed large mediastinal and hilar adenopathy while receiving etanercept therapy. Chest high resolution computed tomography (HRCT) showed mediastinal lymph nodes with size of 2.3 × 3.1 centimeters. Right paratracheal lymph node biopsy showed nonnecrotizing epithelioid granulomata. All infectious studies of pulmonary lymph node tissues were negative. Etanercept was discontinued. Follow-up HRCT 6 months later showed resolution of mediastinal lymph nodes. This report should increase awareness of pulmonary sarcoidosis development in patient treated with tumor necrosis factor-alpha blocking agent, etanercept.
23970975 Oral janus kinase inhibitor for the treatment of rheumatoid arthritis: tofacitinib. 2013 Since the introduction of immune modulators in the treatment of rheumatoid arthritis (RA), there has been hope that orally effective biologic agents would be developed. Tofacitinib, a Janus kinase inhibitor, has become the first oral biologic to receive approval for use in active RA patients. This paper reviews the efficacy and safety profile of Tofacitinib at dosages of 5 mg and 10 mg twice daily. Remarkable improvement in terms of ACR 20 response and HAQ-DI score was noted at month 3 and month 6. DAS 28-4 ESR < 2.6 achievement was noticeably obvious at month 6 for both dosages. No significant serious adverse events, serious infections, neutropenia, or anaemia were observed compared to placebo. In fact, Tofacitinib 5 mg was even found to have significant protective effect of anaemia in the meta-analysis (P = 0.004). Tofacitinib has a noticeable efficacy in controlling disease activity in RA with a manageable safety profile. However, longer studies are needed for its long-term safety profile.
24665841 Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen- 2014 Jul Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti-C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR) surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was demonstrated in a multiple-dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR.
24583103 Therapeutic effects of dichloromethane fraction of Securidaca inappendiculata on adjuvant- 2014 Apr 28 ETHNOPHARMACOLOGICAL RELEVANCE: Securidaca inappendiculata (SI) is a traditional antirheumatic medicine used in China. The present study was designed to investigate the therapeutic efficacy of dichloromethane fraction of SI (SID) at three different doses on adjuvant induced arthritis (AA) rats. METHODS: Arthritis severity was evaluated by arthritic score, body weight loss, paw circumference, histological changes and hyperplasia of lymphatic tissues. Serum samples were collected for estimation of superoxide dismutase (SOD), glutathione (GSH), hydroxy radical (OH·), nitric oxide (NO), malondialdehyde (MDA), N-acetyl glucosaminidase (NAG), sialic acid (SA), alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT). The levels of GSH, MDA, NAG and SA in liver were also assessed. The levels of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) were determined using ELISA method. Another portion of blood was used for total and differential leucocyte counts. RESULTS: Administration with SID (at high dose with 100 mg/kg) significantly ameliorated the AA severity, suggested by the modulatory effects on body weight loss, paw swelling, hyperplasia of lymphatic tissues and synovial membrane, neutrocytosis and lymphocytosis. It also decreased levels of NO, MDA and OH·, restored SOD and GSH levels in serum. The abnormal increased levels of AST, ALT, ALP, NAG and SA significantly were reverted (compared with AA rats, P<0.01). A similar result was observed in livers. Levels of IL-1, TNF-α, MCP-1 and VEGF were reduced dramatically by SID too. CONCLUSION: The results suggest SID possesses substantial anti-arthritic activity. The therapeutic efficacy may be due to immumodepressive effects, cytokines regulation, increasing membrane stability and antioxidantive activity.
25414848 Multi-omic landscape of rheumatoid arthritis: re-evaluation of drug adverse effects. 2014 OBJECTIVE: To provide a frame to estimate the systemic impact (side/adverse events) of (novel) therapeutic targets by taking into consideration drugs potential on the numerous districts involved in rheumatoid arthritis (RA) from the inflammatory and immune response to the gut-intestinal (GI) microbiome. METHODS: We curated the collection of molecules from high-throughput screens of diverse (multi-omic) biochemical origin, experimentally associated to RA. Starting from such collection we generated RA-related protein-protein interaction (PPI) networks (interactomes) based on experimental PPI data. Pharmacological treatment simulation, topological and functional analyses were further run to gain insight into the proteins most affected by therapy and by multi-omic modeling. RESULTS: Simulation on the administration of MTX results in the activation of expected (apoptosis) and adverse (nitrogenous metabolism alteration) effects. Growth factor receptor-bound protein 2 (GRB2) and Interleukin-1 Receptor Associated Kinase-4 (IRAK4, already an RA target) emerge as relevant nodes. The former controls the activation of inflammatory, proliferative and degenerative pathways in host and pathogens. The latter controls immune alterations and blocks innate response to pathogens. CONCLUSIONS: This multi-omic map properly recollects in a single analytical picture known, yet complex, information like the adverse/side effects of MTX, and provides a reliable platform for in silico hypothesis testing or recommendation on novel therapies. These results can support the development of RA translational research in the design of validation experiments and clinical trials, as such we identify GRB2 as a robust potential new target for RA for its ability to control both synovial degeneracy and dysbiosis, and, conversely, warn on the usage of IRAK4-inhibitors recently promoted, as this involves potential adverse effects in the form of impaired innate response to pathogens.
25104994 Beneficial role of antioxidants on clinical outcomes and erythrocyte antioxidant parameter 2014 Jul BACKGROUND: This study aims to investigate the effect of antioxidants supplement on clinical outcomes and antioxidant parameters in rheumatoid arthritis (RA). METHODS: The pre-post study was conducted on 40 female patients with RA in 12 weeks that taken daily one Selenplus capsule contained 50 μg selenium, 8 mg zinc, 400 μg vitamin A, 125 mg vitamin C, and 40 mg vitamin E. About 5 mL venous blood sample was taken from all participants and disease activity score (DAS) was determined by DAS-28 formula and high-sensitive C-reactive protein (hs-CRP). Glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured by spectrophotometric kit and catalase (CAT) was measured by Abei method. Total antioxidant capacity (TAC) was determined by spectrophotometric kit. Distribution of the variables was assessed using histogram with normal curve as well as Kolmogorov-Smirnov test and data were analyzed with paired t-test for differences between pre-post data using SPSS software version 13.5. CONCLUSIONS: Our findings showed that antioxidants may improve disease activity significantly, but it did not affect the number of painful and swollen joints and increased erythrocyte antioxidant levels. Antioxidants may be useful for controlling of clinical outcomes and oxidative stress in RA.
27025404 Acceptance of New Technology: A Usability Test of a Computerized Adaptive Test for Fatigue 2014 Dec 4 BACKGROUND: Little is known about the acceptance and usability of computerized adaptive tests (CATs) among patients with rheumatoid arthritis (RA). The main difference between completing a CAT and a traditional questionnaire concerns item presentation. CATs only provide one item at a time on the screen, and skipping forward or backward to review and change already given answers is often not possible. OBJECTIVE: The objective of this study was to examine how patients with RA experience a Web-based CAT for fatigue. METHODS: In individual sessions, participants filled in the CAT while thinking aloud, and were subsequently interviewed about their experience with the new instrument. The technology acceptance model (TAM) was used to structure the results. RESULTS: The participants were 15 patients with RA. They perceived the CAT as clear, brief, and easy to use. They were positive about answering one question per screen, the changing response options, layout, progress bar, and item number. There were 40% (6/15) of the participants that also mentioned that they experienced the completion of the CAT as useful and pleasant, and liked the adaptive test mechanism. However, some participants noted that not all items were applicable to everybody, and that the wordings of questions within the severity dimension were often similar. CONCLUSIONS: Participants perceived the "CAT Fatigue RA" as easy to use, and also its usefulness was expressed. A 2.0 version has been improved according to the participants' comments, and is currently being used in a validation study before it will be implemented in daily clinical practice. Our results give a first indication that CAT methodology may outperform traditional questionnaires not merely on measurement precision, but also on usability and acceptance valuation.
25709792 Effect of conjugated linoleic Acid, vitamin e, alone or combined on immunity and inflammat 2014 Dec BACKGROUND: Little information about the effects of conjugated linoleic acids (CLAs) on inflammation and immune function in humans is available. This study investigated the effects of CLAs, with and without Vitamin E on immunity and inflammatory parameters in adults with active rheumatoid arthritis (RA). METHODS: In a double-blind clinical trial, 78 patients were randomly divided into four groups, each group receiving one of the following daily supplement for 3 months; group C: 2.5 g CLAs, group E: 400 mg Vitamin E, group CE: CLAs plus Vitamin E, group P: Placebo. Cytokines, matrix metalloproteinase 3 (MMP-3) and citrullinated antibody (CCP-A) were measured by ELISA method and Vitamin E by high-performance liquid chromatography. RESULTS: Consider statistical methods there were no significant differences between groups in cytokines interleukin-2 (IL-2), IL-4, tumor necrosis factor-α (TNF-α), IL-1β, IL-2/IL-4, CCP-A white blood cells and neutrophils, lymphocyte, monocytes, and eosinophils numbers. TNF-α decreased in all groups, but its reduction was significant in group CE. IL-1β increased in groups P (P = 0.004) and E (P = 0.041) but the difference between group P and CE was significant. IL-4 decreased in groups C, CE and E (P = 0.03, P = 0.03, P = 0.07 respectively). IL2 did not change significantly within groups. CCP-A increased in groups P (P = 0.035) and E (P = 0.05), while it decreased in groups CE (P = 0.034). CCP-A and MMP-3 decrease were significant between groups P and CE. MMP-3 reduction was significant in group CE. CONCLUSIONS: Co-supplementation CLAs and Vitamin E may be effective in the level of inflammatory markers in RA patients.
23685361 Emodin suppresses inflammatory responses and joint destruction in collagen-induced arthrit 2013 Sep OBJECTIVE: Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is one of the active components present in the root and rhizome of Rheum palmatum. It has been shown to contain biological activity (antitumour, antibacterial, diuretic and vasorelaxant effects). However, the mechanisms underlying the anti-arthritic effect of emodin have not been elucidated. Here we investigated whether emodin treatment would modulate the severity of the disease in an experimental arthritis model. METHODS: We evaluated the effects of emodin on CIA mice in vivo. RESULTS: The pathological processes of RA are mediated by a number of cytokines and MMPs. Expression of these proinflammatory mediators is controlled by nuclear factor-κB (NF-κB). This study was performed to explore the effect of emodin on control of the NF-κB activation pathway and to investigate whether emodin has anti-inflammatory effects in CIA mice in vivo. Emodin inhibited the nuclear translocation and DNA binding of NF-κB subunits, which were correlated with its inhibitory effect on cytoplasmic IκBα degradation in CIA mice. These events further suppressed chemokine production and MMP expression. In addition, emodin inhibited the osteoclast differentiation induced by M-CSF and receptor activation of NF-κB ligand in bone marrow macrophages. CONCLUSION: These findings suggest that emodin exerts anti-inflammatory effects in CIA mice through inhibition of the NF-κB pathway and therefore may have therapeutic value for the treatment of RA.
23474929 Thalidomide for systemic onset juvenile idiopathic arthritis. 2013 Feb Systemic onset juvenile idiopathic arthritis (SOJIA) is the most common autoimmune auto inflammatory disease in childhood. A sizeable number of these patients run a recalcitrant disease course, resistant to the conventional line of management, ultimately resulting in permanent disability from joint destruction, local growth deformities or iatrogenic side effects. The new biological agents although very effective, are beyond the affordability of most in our country. Thalidomide, a cheaper option has been shown to be very effective in the disease control of patients with SOJIA. We report three Indian children with a chronic refractory course of SOJIA, all of whom had failed conventional line of treatment but improved with thalidomide.
23745349 [Juvenile Sjögren's syndrome: case report]. 2013 Mar INTRODUCTION: Sjögren's syndrome (SS) is an autoimmune disease of unknown etiology, clinically manifested by dry eyes (xerophthalmia) and dry mouth (xerostomia). In childhood SS is a rare disease, clinically atypically or asymptomatic and is often unrecognized. We report a girl with asymptomatic, juvenile form of primary Sjögren's syndrome (JSS). CASE OUTLINE: A 13-year-old girl was initially observed for several months due to elevated sedimentation rate (ESR 75-90 mm/h) without signs of inflammation or other symptoms and disease signs. Subjective symptoms of dryness of the eyes and mouth were absent at the beginning. Ophthalmologic examination demonstrated hypolacrimia although the patients had no subjective signs of xerophthalmia. Ultrasonography (US) revealed mild enlargement and heterogeneity of large salivary glands parenchyma. Increased rheumatoid factor (RF), anti SS-A/Ro, anti SS-B/La antibodies were found in serum. Ophthalmologic examination demonstrated decreased lacrimation.JSS was confirmed on the basis of ophthalmologic examination, immunological tests, histological findings of biopsy of small and US of major salivary glands. During a 12-years follow-up period systemic or extraglandular manifestations of JSS and other autoimmune diseases were not observed. CONCLUSION: Our experience suggests that in the differential diagnosis of unexplained elevated ESR the primary form of JSS should be also taken into consideration. Ultrasonographic changes of major salivary glands in the absence of symptoms of xerostomia point out that this noninvasive method has an important role in the diagnosis and management of patients with JSS.
25114906 Therapeutic efficacy of vitamin E δ-tocotrienol in collagen-induced rat model of arthriti 2014 Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily involving inflammation of the joints. Although the management of the disease has advanced significantly in the past three decades, there is still no cure for RA. The aim of this study was to determine the therapeutic efficacy of δ-tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was induced by intradermal injection of collagen type II emulsified in complete Freund's adjuvant. CIA rats were orally treated with δ-tocotrienol (10 mg/kg) or glucosamine hydrochloride (300 mg/kg) from day 25 to 50. Efficacy was assessed based on the ability to reduce paw edema, histopathological changes, suppression of collagen-specific T-cells, and a reduction in C-reactive protein (CRP) levels. It was established that δ-tocotrienol had the most significant impact in lowering paw edema when compared to glucosamine treatment. Paw edema changes correlated well with histopathological analysis where there was a significant reversal of changes in groups treated with δ-tocotrienol. The results suggest that δ-tocotrienol is efficient in amelioration of collagen-induced arthritis. Vitamin E delta-tocotrienol may be of therapeutic value against rheumatoid arthritis.