Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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26850868 | Sialendoscopy of Salivary Glands Affected by Sjögren Syndrome: A Randomized Controlled Pi | 2016 Jun | PURPOSE: Sialendoscopy of the major salivary glands could alleviate the oral symptoms of Sjögren syndrome (SS) and restore salivary function. The aim of this pilot study was to evaluate the effect of sialendoscopy of the major salivary glands on salivary flow, saliva composition, and mouthfeel in patients with SS and to collect data for sample size analysis for a larger clinical trial. MATERIALS AND METHODS: Twenty patients diagnosed with SS were randomly assigned to a nonintervention control group or a sialendoscopy group. Unstimulated whole saliva flow, stimulated whole saliva flow, Clinical Oral Dryness Score, Xerostomia Inventory score, and EULAR Sjögren's Syndrome Patient Reported Index score were obtained 1 week before (T0), 1 week after (T2), and 8 weeks after (T3) sialendoscopy. Unstimulated whole saliva was analyzed for amylase concentration, activity, and mucin 5B concentration. Amylase and mucin 5B output were calculated. RESULTS: In the sialendoscopy group, unstimulated and stimulated whole saliva flows were numerically higher at T2 and T3 compared with T0. Xerostomia Inventory score was significantly lower in the sialendoscopy group at T2 compared with T0 (P = .03). Unstimulated and stimulated whole saliva flows were higher in the sialendoscopy group compared with the control group at T2 and T3 (not meaningful). Significant differences were found between groups for the EULAR Sjögren's Syndrome Patient Reported Index score at T2 (P = .03) and T3 (P = .001). Xerostomia Inventory score and Clinical Oral Dryness Score in the sialendoscopy group were lower compared with the control group at T2 (P = .02) and at T3 (P = .04), indicating less oral dryness. CONCLUSION: This pilot study indicates a positive effect of sialendoscopy on some parameters, but it cannot yet be concluded that it has a positive effect on salivary flow in patients with SS. These preliminary results need to be verified in a randomized controlled trial with a larger sample and longer follow-up period. | |
26320391 | Arthroscopic elbow joint release with radial head resection arthroplasty: 12 cases. | 2015 Oct | BACKGROUND: Elbow arthritis typically affects manual labourers aged 40 to 50 years and usually starts in the lateral compartment. The objective of this study was to evaluate the medium-term clinical, functional, and radiological outcomes in 12 patients after arthroscopic elbow joint release and radial head resection arthroplasty. HYPOTHESIS: Our main hypothesis was that pre-operative damage to the radio-capitellar joint was associated with poorer clinical outcomes after elbow joint release. MATERIAL AND METHOD: Consecutive patients treated by a single surgeon at a single centre between July 2006 and May 2014 were studied retrospectively. The 12 patients - 10 males and 2 females with a mean age of 54.5±9.3 years (33-69 years) - had osteoarthritis confined to the radio-capitellar compartment with elbow stiffness and pain and underwent arthroscopic elbow joint release with radial head resection arthroplasty. Among them, 9 had a history of trauma or micro-trauma and 3 had rheumatoid arthritis. The Broberg and Morrey osteoarthritis grade on the pre-operative radiographs was 1 in 4 patients, 2 in 6 patients, and 3 in 2 patients. RESULTS: Mean follow-up was 38.1±33.7 months (5-97). One patient required total elbow arthroplasty. Mean arc of motion was 79.6°±20.5° (30-110) pre-operatively, 123.6±18° (90-140) immediately after surgery, and 109°±11.7° (90-120) at last follow-up. At last follow-up, mean values were 81.4±12.5 (65-100) for the Mayo Elbow Score, 11.1±11.1 (2.3-31.8) for the Quick DASH score, and 1.1±1.6 (0-4) for the visual analogue scale pain score. The radiological assessment at last follow-up showed no evidence of osteoarthritis progression. CONCLUSION: In our case-series, arthroscopic elbow joint release with radial head resection arthroplasty produced good outcomes with a motion arc greater than 100° and little or no pain after a mean follow-up of 3.1 years. LEVEL OF EVIDENCE: IV, retrospective study. | |
27914689 | Efficacy of biologic therapy across individual juvenile idiopathic arthritis subtypes: A s | 2017 Apr | OBJECTIVE: To determine the efficacy of differing biologic therapies amongst individual juvenile idiopathic arthritis (JIA) subtypes rather than JIA overall. METHODS: A systematic literature review was conducted between January 1975 and November 2014. Studies included were randomised controlled trials, controlled trials, non-randomised prospective studies or case-control studies. Subjects were required to have a diagnosis of JIA and were ≤20 years of age at study entry. Studies were deemed suitable for inclusion only when the authors reported the efficacy of biologic drugs within individual ILAR subtypes rather than JIA overall. RESULTS: Of 7663 articles identified in the original search, 25 were deemed eligible for inclusion in this review. These articles included over 4000 participants classified as having JIA, with mean age groups ranging from 3 to 13 years. Systemic JIA was the largest represented subtype, whilst the persistent oligoarthritis subtype was represented by the lowest number of participants (n = 54). Concerning etanercept, children with extended oligoarticular JIA were more likely to achieve inactive disease than other subtypes, with rheumatoid factor (RF) negative patients achieving inactive disease more frequently than RF positive children. Prospective data showed similar responses to etanercept in persistent oligoarticular groups compared to other subtypes. Etanercept was also shown to be efficacious in ERA and PsA, although the drug was not successfully discontinued in any of these patients without recurrence of the disease. In a study of abatacept, no differences were seen across subtypes. Systemic JIA appeared to be less responsive to etanercept when compared to tocilizumab over 12 weeks (etanercept: ACR30 58-78% and tocilizumab: ACR30 85%). However, longer term response over 12 months was more similar (etanercept: ACR30 83-100% and tocilizumab: ACR30 87-98%). CONCLUSIONS: This review has provided some evidence of a differing response to individual biologics according to JIA subtype and highlighted the under-representation of certain subtypes in published studies. Comparison of efficacy of individual biologics within subtypes is limited as published studies use variable methodology and head-to-head trials of biologics are lacking. Future trial design should consider differences in treatment response across and within ILAR subtypes to enable clinicians to make more relevant treatment decisions and achieve better patient outcomes. | |
27813150 | Impact of a sodium carbonate spray combined with professional oral hygiene procedures in p | 2017 Jun | OBJECTIVES: The aim of this study was to make an initial estimation on the effects of a sodium bicarbonate and xylitol spray (Cariex(®) ), associated with non-surgical periodontal therapy, in participants with primary Sjögren's syndrome. BACKGROUND: Sjögren's syndrome (SS) is a multisystem autoimmune disease that predominantly involves salivary and lachrymal glands, with the clinical effect of dry eyes and mouth. MATERIALS AND METHODS: A prospective cohort of 22 women and two men has been evaluated. They were randomized into three groups (eight patients each): Group A) those treated once with non-surgical periodontal therapy, education and motivation to oral hygiene, associated with the use of Cariex(®) ; Group B) treated only with Cariex(®) ; Group C) treated only with non-surgical periodontal therapy, education and motivation to oral hygiene. Clinical variables described after treatment were unstimulated whole salivary flow, stimulated whole salivary flow, salivary pH, reported pain (using Visual Analogue Scale) and the Periodontal Screening and Recording index. RESULTS: Salivary flow rate improved in all groups, but the difference was statistically significant only in those treated with Cariex(®) , alone or in combination with periodontal therapy. Gingival status improved in participants who underwent periodontal non-surgical therapy while remained unchanged in those only treated with Cariex(®) . Reported pain decreased in all groups, showing the best result in participants treated with periodontal therapy together with Cariex(®) . CONCLUSIONS: We propose a practical approach for improving gingival conditions and alleviating oral symptoms in patients with SS. Future randomized and controlled trials are however required to confirm these results as well as larger population, and also assessing other parameters due to oral dryness, possible oral infections and more comprehensive periodontal indices. | |
27441838 | Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren's | 2016 | Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diagnose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway. | |
26804757 | Secreted autoantibody repertoires in Sjögren's syndrome and systemic lupus erythematosus: | 2016 Apr | The structures of epitopes bound by autoantibodies against RNA-protein complexes have been well-defined over several decades, but little is known of the clonality, immunoglobulin (Ig) variable (V) gene usage and mutational status of the autoantibodies themselves at the level of the secreted (serum) proteome. A novel proteomic workflow is presented based on affinity purification of specific Igs from serum, high-resolution two-dimensional gel electrophoresis, and de novo and database-driven sequencing of V-region proteins by mass spectrometry. Analysis of anti-Ro52/Ro60/La proteomes in primary Sjögren's syndrome (SS) and anti-Sm and anti-ribosomal P proteomes in systemic lupus erythematosus (SLE) has revealed that these antibody responses are dominated by restricted sets of public (shared) clonotypes, consistent with common pathways of production across unrelated individuals. The discovery of shared sets of specific V-region peptides can be exploited for diagnostic biomarkers in targeted mass spectrometry platforms and for tracking and removal of pathogenic clones. | |
26155625 | [Primary hepatic lymphoma in a female patient with Sjögren's disease: A case report and l | 2015 | The paper describes a case of primary hepatic diffuse large B-cell lymphoma in a 52-year-old woman with a 27-year history of Sjögren's disease. It gives the data available in the literature on the etiology, diagnosis, and morphological characteristics of primary hepatic lymphoma and touches upon the issues of differential diagnosis. | |
25966927 | Adherence to online monitoring of patient-reported outcomes by patients with chronic infla | 2015 Nov | OBJECTIVES: The objective of this report is to investigate the feasibility of collecting patient-reported outcomes (PROs) via e-questionnaires delivered to patients with chronic inflammatory diseases (CIDs). METHODS: Consecutive outpatients with a confirmed diagnosis of systemic lupus erythematosus, primary Sjögren's syndrome or inflammatory bowel disease were followed at two medical departments. Patients received monthly e-mails containing the SF36, Hospital Anxiety and Depression scale and an analogue symptom scale over a six-month period. Participation rate, socio-demographic characteristics and patients' satisfaction were analysed. RESULTS: A total of 128 patients were included (79% female; mean age: 42 ± 12 years). Eighty-two per cent of questionnaires were returned. The monthly participation rate ranged from 89% to 77%, with a six-month attrition rate of 13%. The mean completion rate of questionnaires was 98%. Factors significantly associated with increased answer rate were: married/couple status, greater number of children at home and previous participation in online surveys. The main reasons for non-response were: 'too busy to participate' (35%) and 'away from home Internet access' (31%). Overall, 68% of the participants found the study convenient and 96% agreed to continue at a monthly or bimonthly frequency. CONCLUSION: Online home self-assessment of PROs was feasible in the setting of CIDs. Patients were satisfied and willing to continue the survey. The Internet allows immediate and sophisticated presentation of PROs to clinicians. Future studies are warranted to determine how PRO monitoring may contribute to routine care in CIDs and other diseases. | |
26090503 | Distribution of Peripheral Lymphocyte Populations in Primary Sjögren's Syndrome Patients. | 2015 | Purpose of this study was to evaluate the lymphocyte populations' distribution changes in peripheral blood of patients with primary Sjögren's syndrome (pSS). Lymphocyte populations' distribution changes in peripheral blood of pSS patients were investigated in 52 patients with pSS and in 28 healthy controls by flow cytometry. We found decreased absolute count of CD3(+) T cell population in pSS patients. Analysis of CD4(+) T cell population showed significant proportion and absolute count differences in pSS patient's blood with SSA/SSB antibodies (Abs) in comparison to controls. No significant differences were observed analyzing CD4(+) and CD8(+) Treg subpopulation. Proportion and absolute counts of Th17 cells were significantly lower in pSS patient's blood. Absolute counts of CD8(+) T cells were significantly lower in pSS patients in comparison to controls and also impaired proportion and absolute counts of CD8(+) subpopulations according to CD27(+) and CD57(+) were observed. Absolute counts of NKT and NK cells were decreased in pSS with Abs. B cells proportion was increased only in blood of pSS with Abs. Lymphocyte distribution impairment can be due to genetically determined lymphopenia or lymphocyte migration from periphery to inflammatory sites or/and increased susceptibility to apoptosis. | |
25297553 | Acute longitudinal myelitis following Cryptococcus laurentii pneumonia in a patient with s | 2015 Jan | Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is reported in about 50% of patients. Among the neuropsychiatric features of SLE, myelopathy, including acute transverse myelitis (ATM) or acute longitudinal myelitis (ALM), represents an uncommon event. A possible vascular aetiology of SLE myelopathies has been hypothesized and it seems to be much more associated to SLE-associated antiphospholipid syndrome (APS). Furthermore, a possible infectious cause of ATM or ALM in healthy subjects has been described. SLE patients are susceptible to infection due to the disease itself or to the immunosuppressive therapy. Cryptococci non-neoformans have been rarely associated to infections in humans. Here we describe the case of a 47-year-old woman with SLE and Sjögren Syndrome who developed an ALM concurrently with a Cryptococcus laurentii pneumonia. The patient was treated with antimycotics, high doses of glucocorticoids and intravenous immunoglobulins with a significant clinical and radiological improvement. As far as we know, this is the first case of Cryptococcus laurentii infection and ALM in a patient with SLE who later developed a seronegative APS. Even though myelopathy may be considered primarily associated to SLE, a possible role of the infection in ALM development cannot be excluded. | |
27872515 | Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ(12,14)-Prostaglandin J(2) (15d-PG | 2016 | The prostaglandin, 15-deoxy Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ(2) in an experimental model of arthritis. Daily administration of 15d-PGJ(2) attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ(2) treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ(2)-treated arthritic mice. The specific and polyclonal CD4(+) Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ(2) increased the expression of FOXP3, GITR, and CTLA-4 in the CD4(+)CD25(-) population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4(+)CD25(-) cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ(2) ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ(2) may represent a potential therapeutic strategy in RA. | |
25784649 | Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatme | 2015 Jun | c-Jun N-terminal kinases (JNKs) participate in many physiologic and pathologic processes, including inflammatory diseases. We recently synthesized the sodium salt of IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime) and demonstrated that it is a high-affinity JNK inhibitor and inhibits murine delayed-type hypersensitivity. Here we show that IQ-1S is highly specific for JNK and that its neutral form is the most abundant species at physiologic pH. Molecular docking of the IQ-1S syn isomer into the JNK1 binding site gave the best pose, which corresponded to the position of cocrystallized JNK inhibitor SP600125 (1,9-pyrazoloanthrone). Evaluation of the therapeutic potential of IQ-1S showed that it inhibited matrix metalloproteinase 1 and 3 gene expression induced by interleukin-1β in human fibroblast-like synoviocytes and significantly attenuated development of murine collagen-induced arthritis (CIA). Treatment with IQ-1S either before or after induction of CIA resulted in decreased clinical scores, and joint sections from IQ-1S-treated CIA mice exhibited only mild signs of inflammation and minimal cartilage loss compared with those from control mice. Collagen II-specific antibody responses were also reduced by IQ-1S treatment. By contrast, the inactive ketone derivative 11H-indeno[1,2-b]quinoxalin-11-one had no effect on CIA clinical scores or collagen II-specific antibody titers. IQ-1S treatment also suppressed proinflammatory cytokine and chemokine levels in joints and lymph node cells. Finally, treatment with IQ-1S increased the number of Foxp3(+)CD4(+)CD25(+) regulatory T cells in lymph nodes. Thus, IQ-1S can reduce inflammation and cartilage loss associated with CIA and can serve as a small-molecule modulator for mechanistic studies of JNK function in rheumatoid arthritis. | |
26809799 | Younger patients with primary Sjögren's syndrome are more likely to have salivary IgG ant | 2016 Mar | Acetylcholine type 3 receptor (M3R) is recognized as an autoantigen in primary Sjögren's syndrome (pSS). Assay of anti-M3R antibody levels in serum is fraught with low sensitivity for diagnosis of pSS. Salivary assay is more likely to improve the diagnostic accuracy. Patients with pSS classified either by the American European Consensus Group (AECG) or American college of Rheumatology (ACR) criteria, attending rheumatology clinic between October 2014 and July 2015 were included. Hospital staff and lupus patients constituted healthy and disease controls, respectively. Evaluation of pSS included clinical evaluation, laboratory tests, ESSDAI and ESSPRI scoring. Unstimulated saliva was collected by the spitting method. Salivary IgG antibody against M3R (anti-M3R) was quantified by indirect ELISA. In this study, 43 patients with pSS, 34 with lupus and 42 healthy controls were recruited. The frequency of anti-M3R antibody levels was 55.81, 17.64 and 7 % for pSS, lupus and healthy controls, respectively. Area under the Receiver Operator Characteristic was 0.7791 (95 % CI,, 0.67-0.87). Sensitivity and specificity of the assay for diagnosis of pSS were 44.19 and 88.16 %, respectively. Salivary anti-M3R IgG antibody positivity was associated with lower age, shorter disease duration and higher globulin levels in our cohort. Salivary anti-M3R IgG antibody assay has high specificity in pSS; younger patients and those with hyperglobulinemia more frequently tested positive for this antibody. | |
26589963 | Gene-expression analysis of adult-onset Still's disease and systemic juvenile idiopathic a | 2015 Nov 20 | BACKGROUND: Adult-onset Still's disease (AOSD), a rare autoinflammatory disorder, resembles systemic juvenile idiopathic arthritis (SJIA). The superimposable systemic clinical features of AOSD and SJIA suggest both clinical phenotypes represent the same disease continuum with different ages of onset. To further characterize the similarity between AOSD and SJIA at the molecular level, 2 previously identified response gene sets in SJIA were used to investigate how genes that respond to interleukin (IL)-1β inhibition with canakinumab in SJIA patients behave in AOSD patients with active disease prior to IL-1β targeting therapy, relative to healthy subjects. FINDINGS: All genes downregulated in SJIA patients following canakinumab treatment were upregulated in most patients with active AOSD prior to canakinumab treatment, relative to healthy subjects. A few patients with milder AOSD had expectedly gene-expression patterns that resembled those in healthy subjects. Comparison of the gene-expression patterns with neutrophil counts showed a correlation between elevated neutrophil numbers and upregulation of canakinumab-responsive genes. Correspondingly, most genes upregulated following canakinumab treatment in patients with SJIA patients were downregulated in the majority of AOSD patients. CONCLUSIONS: These results further support the concept of a Still's disease continuum that includes both a pediatric/juvenile onset (SJIA) and adult onset (AOSD) form. | |
26770214 | Clinical Observation of Employment of Umbilical Cord Derived Mesenchymal Stem Cell for Juv | 2016 | Juvenile idiopathic arthritis (JIA), known as Juvenile rheumatoid arthritis, is the most common type of arthritis in children aged under 17. It may cause sequelae due to lack of effective treatment. The goal of this study is to explore the therapeutic effect of umbilical cord mesenchymal stem cells (UC-MSCs) for JIA. Ten JIA patients were treated with UC-MSCs and received second infusion three months later. Some key values such as 28-joint disease activity score (DAS28), TNF-α, IL-6, and regulatory T cells (Tregs) were evaluated. Data were collected at 3 months and 6 months after first treatment. DAS28 score of 10 patients was between 2.6 and 3.2 at three months after infusion. WBC, ESR, and CRP were significantly decreased while Tregs were remarkably increased and IL-6 and TNF-α were declined. Similar changes of above values were found after 6 months. At the same time, the amount of NSAIDS and steroid usage in patients was reduced. However, no significant changes were found comparing the data from 3 and 6 months. These results suggest that UC-MSCs can reduce inflammatory cytokines, improve immune network effects, adjust immune tolerance, and effectively alleviate the symptoms and they might provide a safe and novel approach for JIA treatment. | |
25645739 | Effects of exercise on depression in adults with arthritis: a systematic review with meta- | 2015 Feb 3 | INTRODUCTION: Previous randomized controlled trials have led to conflicting findings regarding the effects of exercise on depressive symptoms in adults with arthritis and other rheumatic conditions (AORC). The purpose of this study was to use the meta-analytic approach to resolve these discrepancies. METHODS: The inclusion criteria were: (1) randomized controlled trials, (2) exercise (aerobic, strength training, or both) ≥4 weeks, (3) comparative control group, (4) adults with osteoarthritis, rheumatoid arthritis, fibromyalgia or systemic lupus erythematosus, (5) published studies in any language since January 1, 1981 and (6) depressive symptoms assessed. Studies were located by searching 10 electronic databases, cross-referencing, hand searching and expert review. Dual-selection of studies and data abstraction was performed. Hedge's standardized mean difference effect size (g) was calculated for each result and pooled using random-effects models, an approach that accounts for heterogeneity. Non-overlapping 95% confidence intervals (CI) were considered statistically significant. Heterogeneity based on fixed-effect models was estimated using Q and I (2) with alpha values ≤0.10 for Q considered statistically significant. RESULTS: Of the 500 citations reviewed, 2,449 participants (1,470 exercise, 979 control) nested within 29 studies were included. Length of training, reported as mean ± standard deviation (±SD) was 19 ± 16 weeks, frequency 4 ± 2 times per week and duration 34 ± 17 minutes per session. Overall, statistically significant exercise minus control group reductions were found for depressive symptoms (g = -0.42, 95% CI, -0.58, -0.26, Q = 126.9, P <0.0001, I(2) = 73.2%). The number needed-to-treat was 7 (95% CI, 6 to 11) with an estimated 3.1 million (95% CI, 2.0 to 3.7) United States adults not currently meeting physical activity guidelines improving their depressive symptoms if they began and maintained a regular exercise program. Using Cohen's U3 Index, the percentile reduction was 16.4% (95% CI, 10.4% to 21.9%). All studies were considered to be at high risk of bias with respect to blinding of participants and personnel to group assignment. CONCLUSIONS: Exercise is associated with reductions in depressive symptoms among selected adults with AORC. A need exists for additional, well-designed and reported studies on this topic. | |
27554099 | The anti-arthritic, anti-inflammatory, antioxidant activity and relationships with total p | 2016 Aug 23 | BACKGROUND: Oxidative stress predisposes the human and animal body to diseases like cancer, diabetes, arthritis, rheumatoid arthritis, atherosclerosis and chronic inflammatory disorders. Hence, this study seeks to determine the antioxidant, anti-inflammatory and anti-arthritic activities of acetone leaf extracts of nine South African medicinal plants that have been used traditionally to treat arthritis and inflammation. METHODS: The anti-inflammatory activity of the extracts was determined by investigating inhibition of nitric oxide production in lipopolysaccharide activated RAW 264.7 macrophages as well as 15-lipoxygenase enzyme inhibition. An anti-protein denaturation assay was used to determine the anti-arthritic properties of the extracts. The antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and ferric reducing antioxidant power (FRAP). The total phenolic and total flavonoid concentration of extracts were determined by using standard methods. RESULTS: All extracts inhibited nitric oxide production in a dose-dependent manner in the LPS-stimulated RAW 264.7 macrophages. Extracts of Maesa lanceolata and Heteromorpha arborescens inhibited NO production by 99.16 % and 89.48 % at a concentration of 30 μg/ml respectively. Elaeodendron croceum and Calpurnia aurea extracts had strong activity against 15-lipoxygenase activity with IC50 values of 26.23 and 34.70 μg/ml respectively. Morus mesozygia and Heteromorpha arborescens extracts had good in vitro anti-arthritic activity with IC50 values of 11.89 and 53.78 μg/ml, the positive control diclofenac sodium had IC50 value of 32.37 μg/ml. The free radical scavenging activity of the extracts in DPPH assays ranged between 7.72 and 154.77 μg/ml. Trolox equivalent antioxidant capacity (TEAC) and FRAP values ranged from 0.06 to 1.32 and 0.06 to 0.99 respectively. CONCLUSIONS: Results from this study support the traditional use of the selected medicinal plants in the management of arthritis and other inflammatory conditions. The free radical scavenging capacity of the extracts may be related to an immune boosting potential. | |
26379475 | Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2 | 2015 | BACKGROUND: The activity of one of the major catechins in Green Tea, the polyphenol (-)-epigallocatechin-3-gallate (EGCG), has been shown to have a variety of health benefits. Recent studies suggest that EGCG can modulate both the innate and adaptive arms of the immune system. The goal of the current studies was to examine the immunomodulatory effects and mechanisms of action of EGCG on experimental arthritis in mice. METHODS: EGCG (10 mg/kg) was administered by oral gavage after CIA induction, while control mice were administered phosphate buffered saline (PBS). Disease mechanisms were studied in both groups of mice. Phenotypes were examined using repeated measure analysis of variance (ANOVA) and data from in vitro and ex vivo experiments were analyzed for significance using the Mann-Whitney U test. RESULTS: EGCG treatment ameliorated clinical symptoms and reduced histological scores in arthritic mice. Serum type-II collagen-specific immunoglobulin (Ig) IgG2a antibodies were significantly lower in EGCG-fed mice compared to PBS-treated mice. EGCG significantly suppressed T cell proliferation and relative frequencies of CD4 T cells, CD8 T cells and B cell subsets including marginal zone B cells, T1 and T2 transitional B cells, while increasing the frequency of CD4(+) Foxp3(+) regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) expression by CD11b(+) dendritic cells (DC). Splenic CD11b(+) DC from EGCG fed mice induced an increased frequency of Tregs via an IDO-dependent mechanism in in vitro cultures. Importantly, joint homogenates from EGCG-fed mice exhibited significantly increased levels of Nuclear Factor, Erythroid 2-Like 2 (Nrf-2) and Heme oxygenase-1 (HO-1) compared with PBS-fed mice. CONCLUSIONS: This is the first report of upregulation of the Nrf-2 antioxidant pathway in EGCG-mediated immunoregulation. EGCG ameliorated experimental arthritis in mice by eliciting IDO-producing DCs, increasing frequencies of T regs and inducing the activation of the Nrf-2 antioxidant pathway. It remains to be established whether EGCG is useful for the prevention and treatment of rheumatoid arthritis and other inflammatory disorders. | |
26713406 | Synthesis of Depo-Medrol-chitosan hydrogel as new drug slow-release appliance and investig | 2016 Sep | The present study deals with preparation and optimization of a novel chitosan hydrogel-based matrix by suspension cross-linking method for controlled release of Depo-Medrol. The controlled release of Depo-Medrol for effective Rheumatoid arthritis disease has become an imperative field in the drug delivery system. In this context, it was intended to optimize loading circumstances by experimental design and also study the release kinetics of Depo-Medrol entrapped in the chitosan matrix in order to obtain maximal efficiency for drug loading. The optimum concentrations of chitosan (2.5 g), glutaraldehyde (3.05 μL) and Depo-Medrol (0.1 mg) were set up to achieve the highest value of drug loaded and the most sustained release from the chitosan matrix. In vitro monitoring of drug release kinetic using high-performance liquid chromatography showed that 73% of the Depo-Medrol was released within 120 min, whereas remained drug was released during the next 67 h. High correlation between first-order and Higuchi's kinetic models indicates a controlled diffusion of Depo-Medrol through the surrounding media. Moreover, recovery capacity >82% and entrapment efficiency of 58-88% were achieved under optimal conditions. Therefore, the new synthesized Depo Medrol-chitosan is an applicable appliance for arthritis therapy by slow release mechanism. Copyright © 2016 John Wiley & Sons, Ltd. | |
26491241 | Recurrent rates and risk factors associated with recurrent painful bullous keratopathy aft | 2015 | OBJECTIVE: To assess the recurrent rate, mean survival time, and risk factors associated with recurrent painful bullous keratopathy (BK) after primary treatment with phototherapeutic keratectomy. METHODS: Medical records from 72 patients (72 eyes) who had phototherapeutic keratectomy for painful BK were evaluated. Data for sex, age, duration of BK, associated ocular and systemic diseases (hypertension, diabetes mellitus, ischemic heart disease, asthma, dyslipidemia, and rheumatoid arthritis), frequency and degree of pain (grade 1-3), visual acuity, corneal thickness, intraocular pressure, and laser setting were extracted and analyzed. RESULTS: The mean age of the patients was 64.2±11.4 years. The mean preoperative duration of BK was 15.0±11.0 months. Most patients had pseudophakic BK (69.40%). Majority of the cases had grade 3 degree of pain (48.60%). Glaucoma and hypertension were markedly found among these patients (51.40% and 19.40%, respectively). Preoperative mean intraocular pressure and corneal thickness were 13.70±4.95 mmHg and 734.1±83.80 µm, respectively. The mean laser diameter and depth were 8.36±1.22 mm and 38.89±8.81 µm, respectively. Systemic disease was significantly associated with the risk for developing recurrent painful BK (P=0.022, hazard ratio [HR] 1.673, 95% confidence interval [CI] 1.08-2.58). The overall recurrent rate was 51%. The average duration time of recurrent painful BK was 17.3±12.9 months (range 1-50 months). The median survival time before recurrence was 29.0±6.6 months. CONCLUSION: Systemic disease was found to be the only risk factor significantly associated with the development of recurrent painful BK. Low recurrent rate and long mean survival time showed that phototherapeutic keratectomy was effective in relieving recurrent painful BK and can be used as an alternative procedure for patients waiting for corneal transplantation. |