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ID PMID Title PublicationDate abstract
27167565 Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army S 2016 Jul 1 IMPORTANCE: Posttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity. OBJECTIVE: To discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). DESIGN, SETTING, AND PARTICIPANTS: Two coordinated genome-wide association studies of mental health in the US military contributed participants. The New Soldier Study (NSS) included 3167 unique participants with PTSD and 4607 trauma-exposed control individuals; the Pre/Post Deployment Study (PPDS) included 947 unique participants with PTSD and 4969 trauma-exposed controls. The NSS data were collected from February 1, 2011, to November 30, 2012; the PDDS data, from January 9 to April 30, 2012. The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015. MAIN OUTCOMES AND MEASURES: Association analyses for PTSD used logistic regression models within each of 3 ancestral groups (European, African, and Latino American) by study, followed by meta-analysis. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated. RESULTS: The NSS population was 80.7% male (6277 of 7774 participants; mean [SD] age, 20.9 [3.3] years); the PPDS population, 94.4% male (5583 of 5916 participants; mean [SD] age, 26.5 [6.0] years). A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 × 10-8) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 × 10-8) in the African American samples from the NSS. A genome-wide significant locus was also found in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 × 10-8) in the European American samples from the NSS. Similar results were not found for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses. Single-nucleotide polymorphism-based heritability was nonsignificant, and no significant genetic correlations were observed between PTSD and 6 mental disorders or 9 immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis. CONCLUSIONS AND RELEVANCE: In the largest genome-wide association study of PTSD to date, involving a US military sample, limited evidence of association for specific loci was found. Further efforts are needed to replicate the genome-wide significant association with ANKRD55-associated in prior research with several autoimmune and inflammatory disorders-and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis.
27390293 Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active 2017 Jan OBJECTIVE: To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. METHODS: Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid-like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). RESULTS: Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P < 0.001), particularly in those with CLP (P < 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation. CONCLUSION: Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.
25381666 Co-culture system of human salivary gland epithelial cells and immune cells from primary S 2015 Apr Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates in the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. The efficacy of Rituximab (RTX) in pSS is still open to debate. This study delineates the signaling pathway involved in RTX-mediated down-regulation of pro-inflammatory factors in a co-culture system of pSS salivary gland epithelial cells (SGEC) with syngeneic pSS B-lymphocytes. In addition, the effects of RTX on the activation of the Raf-1/ERK1/2 pathway in pSS SGEC co-cultured with syngeneic pSS T-lymphocytes were also investigated. This study demonstrated that RTX may interfere with the ERK1/2 pathway in a syngeneic co-culture of pSS SGEC with pSS B-lymphocytes, leading to decreased cytokine production by SGEC. These novel findings reveal that syngeneic co-culture of pSS SGEC with pSS B-lymphocytes leads to a down-regulation of Raf-1 in epithelial cells that adversely regulates the activity of the ERK1/2 pathway and determines a subsequent reduction of the release of pro-inflammatory factors.
27888057 Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune diseases 2017 Jan Autoimmune diseases often share common susceptibility genes. Most genetic variants associated with susceptibility to systemic lupus erythematosus are also associated with other autoimmune diseases. The X-linked variant rs2294020 is positioned in exon 7 of the CCDC22 gene. The encoded protein functions in the regulation of NF-κB, a master regulator in immune response. The aim of this study is to investigate whether the rs2294020 polymorphism may be a general susceptibility factor for autoimmunity. We evaluated case-control association between the occurrence of rs2294020 and different autoimmune diseases, including new data for systemic lupus erythematosus and previous genome-wide association studies (GWAS) (though most did not analyse the X chromosome) of psoriasis, celiac disease, Crohn's disease, ulcerative colitis, multiple sclerosis, vitiligo, type-1 diabetes, rheumatoid arthritis, and ankylosing spondylitis. Cases from patients affected by amyotrophic lateral sclerosis and type-2 diabetes were also included in the study. We detected nominal significant associations of rs2294020 with systemic lupus erythematosus (additive model test: p=0.01), vitiligo (p=0.016), psoriasis (p=0.038), and in only one of two studies of multiple sclerosis (p=0.03). Our results suggest that rs2294020 is associated with the risk of several autoimmune diseases in European populations, specifically with diseases that present themselves, among else, in the skin.
27697141 Follicular T helper cells and IL-21 in rheumatic diseases. 2016 Oct Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are lifelong diseases with increased mortality and chronic pains. They are both characterized by immunological imbalances causing the immune system attack and destroy the bodies own tissues (called autoimmune disease). The best treatment, we are currently able to offer these patients, cause significant side-effects and can not prevent significant loss of quality of life. At the heart of the disease mechanisms in RA and SLE are subsets of immune cells called T and B cells. These cell types produce proteins (called antibodies), which under normal circumstances protect the body against disease. In RA and SLE these cells produce antibodies that are directed at the bodies own tissues (called autoantibodies), causing inflammation and tissue damage. The cause of this loss of tolerance is still unknown. Interleukin 21 (IL-21) is thought to exert key functions in controlling and directing the T and B cell responses leading to formation of antibodies and autoantibodies alike. IL-21 is a signaling molecule secreted by a subpopulation of T cells called follicular T helper (Tfh) cells. IFNα is another signaling molecule of key importance in autoimmune disease. Stratification of SLE patients by their responsiveness to IFNα has proven a crucial tool in stratifying patients in terms of disease development and treatment response. The aim of this PhD study is to investigate the role of IL-21 and IFNα, and their effects on Tfh cells and B cells and the formation of autoantibodies in RA and SLE. The first part of this study addresses whether plasma levels of IL-21 influence disease activity in rheumatic disease. We further investigate the distribution of IL-21-producing Tfh cells in these patients. We find that IL-21 plasma levels correlate to disease activity and radiological progression in RA, and that the IL-21-producing Tfh cell are increased in the blood and synovial fluid of these patients. These findings support the idea that IL-21 and Tfh cells are linked to the development and perpetuation of these diseases. In the second part of this we investigate how small RNA molecules, called microRNAs, can regulate immunological processes. We find that microRNA-155 can regulate IL-21's capacity to signal, while microRNA-21 is important for survival of T cells. The third, and last part of this, concerns IFNα signaling and its impact on the development of SLE and the formation of autoantibodies. We find that IFNα signaling is altered in a murine model of SLE, and that inhibition of this signaling pathway leads to severe kidney disease. The latter is of key importance as inhibition of IFNα is currently in early trial as a new treatment form for SLE patients. In SLE patients, we find that IFNα responsiveness, as measured by a so-called IFN signature, is crucial in terms of development of the disease as well as serious complications such as kidney disease and involvement of the central nervous system. Interferon alpha does this by affecting intracellular signaling responses and the formation of autoantibodies. The data presented in this thesis supports that IL-21 and Tfh cells have a key role in the disease processes characterizing RA and SLE. We further describe a novel mechanism for microRNA-155 and microRNA-21 in regulating immunological processes in these diseases. Finally we show, that IFNα has important functions in the formation of autoantibodies in SLE. In conclusion, this thesis adds new and important knowledge on the interplay between Tfh cells and B cells and their formation of autoantibodies in rheumatic disease. This knowledge will guide and further the development of new treatment strategies to better patient outcome.
27447967 Repurposing the anti-malarial drug, quinacrine: new anti-colitis properties. 2016 Aug 16 BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with an increased risk of colorectal cancer in 8-10 years after disease onset. Current colitis treatment strategies do not offer a cure for the disease, but only treat the symptoms with limited success and dangerous side-effects. Also, there is no preventive treatment for either UC or colorectal cancer. Quinacrine is an anti-malarial drug with versatile use in the treatment of diseases involving inflammatory response such as rheumatoid arthritis and lupus erythematosus. It also has putative anti-cancer effect. Quinacrine's anti-inflammatory, anti-oxidant properties, and anti-tumorigenic properties make it a potential small molecule preventive agent for both UC and associated colorectal cancer. RESULTS: There were obvious changes in the CDI, histology, and inflammatory load in quinacrine-treated groups in a dose and time dependent manner in both models of UC, induced by chemical or haptenating agent. MATERIALS AND METHODS: We tested quinacrine at two different doses as a colitis treatment agent in two mouse models of UC - the dextran sulfate sodium and oxazolone. The clinical disease index (CDI), histological changes of the colon, levels of inflammatory markers (Cox-2, iNOS, p53) and overall health vitals were evaluated. CONCLUSIONS: We demonstrate that quinacrine successfully suppresses colitis without any indication of toxicity or side-effects in two mouse models of UC.
27446959 Association of Complement Receptor 2 Gene Polymorphisms with Susceptibility to Osteonecros 2016 Osteonecrosis of the femoral head (ONFH) is a complex and multifactorial disease that is influenced by a number of genetic factors in addition to environmental factors. Some autoimmune disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are associated with the development of ONFH. Complement receptor type 2 (CR2) is membrane glycoprotein which binds C3 degradation products generated during complement activation. CR2 has many important functions in normal immunity and is assumed to play a role in the development of autoimmune disease. We investigated whether CR2 gene polymorphisms are associated with risk of ONFH in SLE patients. Eight polymorphisms in the CR2 gene were genotyped using TaqManâ„¢ assays in 150 SLE patients and 50 ONFH in SLE patients (SLE_ONFH). The association analysis of genotyped SNPs and haplotypes was performed with ONFH. It was found that three SNPs, rs3813946 in 5'-UTR (untranslated region), rs311306 in intron 1, and rs17615 in exon 10 (nonsynonymous SNP; G/A, Ser639Asn) of the CR2 gene, were associated with an increased risk of ONFH under recessive model (P values; 0.004~0.016). Haplotypes were also associated with an increased risk (OR; 3.73~) of ONFH in SLE patients. These findings may provide evidences that CR2 contributes to human ONFH susceptibility in Korean SLE patients.
27270678 Review of the novelties from the 31st ECTRIMS Congress, 2015, presented at the 8th Post-EC 2016 Jun 16 Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice.
27232500 Characterization of NF-κB Reporter U937 Cells and Their Application for the Detection of 2016 Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies belonging to distinct immunoglobulin classes and subclasses but not the net biological effect of the combination of these antibodies. We set out to develop a biosensor that is suitable for the detection and characterization of antigen specific serum antibodies. We genetically modified the monocytoid U937 cell line carrying Fc receptors with a plasmid encoding NF-κB promoter-driven GFP. This clone, U937-NF-κB, was characterized with respect to FcR expression and response to solid-phase immunoglobulins. Human IgG3, IgG4 and IgG1 induced GFP production in a time- and dose-dependent manner, in this order of efficacy, while IgG2 triggered no activation at the concentrations tested. IgA elicited no response alone but showed significant synergism with IgG3 and IgG4. We confirmed the importance of activation via FcγRI by direct stimulation with monoclonal antibody and by competition assays. We used citrullinated peptides and serum from rheumatoid arthritis patients to generate immune complexes and to study the activation of U937-NF-κB, observing again a synergistic effect between IgG and IgA. Our results show that immunoglobulins have distinct pro-inflammatory potential, and that U937-NF-κB is suitable for the estimation of biological effects of immune-complexes, offering insight into monocyte activation and pathogenesis of antibody mediated diseases.
26807990 Rett syndrome: An autoimmune disease? 2016 Apr Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis-associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti-CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT.
26137418 CD20(+) T cells have a predominantly Tc1 effector memory phenotype and are expanded in the 2015 Apr Recently, a small subset of T cells that expresses the B cell marker CD20 has been identified in healthy volunteers and in patients with rheumatoid arthritis and multiple sclerosis. The origin of these CD20-positive T cells as well as their relevance in human disease remains unclear. Here, we identified that after functional B cell/T cell interaction CD20 molecules are transferred to the cell surface of T cells by trogocytosis together with the established trogocytosis marker HLA-DR. Further, the presence of CD20 on isolated CD20(+) T cells remained stable for up to 48h of ex vivo culture. These CD20(+) T cells almost exclusively produced IFNγ (∼70% vs. ∼20% in the CD20(-) T cell population) and were predominantly (CD8(+)) effector memory T cells (∼60-70%). This IFNγ producing and effector memory phenotype was also determined for CD20(+) T cells as detected in the peripheral blood and ascitic fluids of ovarian cancer (OC) patients. In the latter, the percentage of CD20(+) T cells was further strongly increased (from ∼6% in peripheral blood to 23% in ascitic fluid). Taken together, the data presented here indicate that CD20 is transferred to T cells upon intimate T cell/B cell interaction. Further, CD20(+) T cells are of memory and IFNγ producing phenotype and are present in increased amounts in ascitic fluid of OC patients.
25984669 Serum Cyr61 is associated with clinical disease activity and inflammation in patients with 2015 May Our previous studies have shown that secreted extracellular matrix-associated protein Cysteine rich angiogenic inducer 61 (Cyr61), a novel proinflammatory factor, is involved in the pathogenesis of rheumatoid arthritis (RA). However, whether Cyr61 has any effect in systemic lupus erythematosus (SLE) remains unknown. This study aims to assess the level of serum Cyr61 and to investigate the association of serum Cyr61 and clinical disease activity in SLE. We found the level of serum Cyr61 in patients with SLE was significantly higher than healthy controls (P < 0.001), and Cyr61 was high expressed in renal tubule of lupus nephritis compared to control. The sensitivity of Cyr61 in diagnosis of SLE was 47.3%. In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.830, with a 95% confidence interval (CI) from 0.776 to 0.885. Cyr61 was present in 60.0%, 54.5%, and 41.5% of anti-double stranded DNA (dsDNA), anti-antinuclear antibodies (ANA), and anti-Sm negative SLE patients, respectively. Serum Cyr61 levels were significantly higher in high systemic lupus erythematosus disease activity index (SLEDAI) group than that in low SLEDAI group (P = 0.003). Correlation analyzes showed a significant negative correlation between serum Cyr61 and complements (C3) (P = 0.015), C4 (P = 0.04). Moreover, increased Cyr61 level in SLE was associated with serum level of TNF-α, interleukin 6 (IL-6), and IL-17. In conclusion, serum Cyr61 was increased in patients with SLE which was associated with clinical disease activity and inflammation in SLE, suggesting Cyr61 may be a novel potential auxiliary marker for the diagnosis of SLE.
25886761 A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): fin 2015 Mar 1 BACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.
24845166 In vitro immunosuppressive and cytotoxic activities of Tripterygium wilfordii extract. 2015 Apr Tripterygium wilfordii Hook. f. (TW) is a traditional herbal medicine which has been widely used for the treatment of rheumatoid arthritis and other autoimmune diseases. However, adverse reactions of TW such as hepatotoxicity and nephrotoxicity have been frequently reported in clinic. With the aim to evaluate the potency and toxicity of TW, we collected eleven batches of TW from different localities across Chinese mainland, and investigated the inhibition of their methanol extracts on the proliferation of mouse spleen lymphocytes, normal human hepatocyte (L-02) cells and African green monkey kidney (COS-7) cells. TW extracts with three different concentrations were designed as the experimental groups. Our present findings provided consistent evidence that TW had significant concentration-dependent inhibitory action on lymphocytes, L-02 and COS-7 cells. At the concentrations of 0.75 and 1.5 mg/mL, most TW groups showed statistically significant inhibition of lymphocyte proliferation when compared with the control group (p < 0.01), and the inhibition of TW extract on lymphocytes was almost equal to 1.0 mg/mL aspirin (p > 0.05). In most test groups, significant toxicities were shown on L-02 cells at 0.6 and 3.0 mg/mL (p < 0.01), and on COS-7 cells at 3.0 mg/mL (p < 0.01). At 3.0 mg/mL, almost all TW groups exerted obvious toxicities toward L-02 and COS-7 cells which were equal to or even higher than 1.0 mg/mL aspirin. In view of these results, further studies are needed to elucidate the relations among the effective component, curative effect and toxicity of TW to ensure its effectiveness and safety for human consumption.
27701428 Krill Oil Improves Mild Knee Joint Pain: A Randomized Control Trial. 2016 BACKGROUND: Krill oil is an edible oil extracted from krill, a small red-colored crustacean found in the Antarctic Ocean. The administration of krill oil is reported to mitigate inflammation in patients with cardiac disease, rheumatoid arthritis, or osteoarthritis. However, the effect of krill oil on mild knee pain has not yet been determined. OBJECTIVE: To assess the effect of krill oil on mild knee pain. DESIGN: A randomized, double-blind, parallel-group, placebo-controlled trial of fifty adults (38-85 years old) with mild knee pain attending the Fukushima Orthopedic Clinic (Tochigi, Japan) between September 2014 and March 2015. INTERVENTIONS: Participants were randomized to receive 2 g per day of either krill oil or an identical placebo for 30 days. OUTCOMES: The primary outcome was improvement in subjective symptoms of knee pain as assessed by the Japanese Knee Osteoarthritis Measure (JKOM) and Japanese Orthopaedic Association score (JOA). Secondary outcomes included blood and urine biochemical parameters. RESULTS: Both the placebo and krill oil groups showed significant improvements in the questions in the JKOM and JOA questionnaires after administration. After the intervention, krill oil group showed more improvements than placebo group in two questions regarding the pain and stiffness in knees in JKOM. Controlling for age, sex, weight, and smoking and drinking habits, krill oil significantly mitigated knee pain in sleeping (P < 0.001), standing (P < 0.001) and the range of motion of both right and left knees (both P = 0.011) compared to placebo. Krill oil administration raised plasma EPA (P = 0.048) and EPA/AA ratio (P = 0.003). CONCLUSION: This study indicates that krill oil administration (2 g/day, 30 days) improved the subjective symptoms of knee pain in adults with mild knee pain. TRIAL REGISTRATION: UMIN-CTR; ID UMIN000014413.
27316593 Are the clinical guideline recommendations on gastroprotection being followed? A review in 2016 Jul INTRODUCTION AND AIMS: The chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause complications in the gastrointestinal tract. The use of proton pump inhibitors (PPIs) is recommended in high-risk patients to prevent them. OBJECTIVE: The aim of this article was to evaluate the gastroprotection measures taken in persons with chronic NSAID use. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted. The clinical records were reviewed of patients seen as outpatients at the Rheumatology Department over a 4-month period, choosing those with chronic NSAID use, and intentionally looking for gastroprotection measures according to the recommendations published by the American College of Gastroenterology. RESULTS: A total of 417 patients (347 women; mean age: 48.12±14.2 years) were included. The most frequent diagnosis was rheumatoid arthritis (65%). Nine patients (2.1%) had a history of peptic ulcer, 48 (11.5%) patients were 65 years of age or older, 26 (6.2%) patients took NSAIDs and aspirin, and 130 (31.2%) took NSAIDs with steroids. Tests for Helicobacter pylori infection were done in just 53 cases, and there were positive results in only 9 (16%). Some risk for gastrointestinal toxicity was established in 211 cases and only 65 (30.8%) received gastroprotection. In contrast, 31 (15%) patients received gastroprotection when there was no indication for it. CONCLUSION: Prophylaxis with PPIs in chronic NSAID users was inadequately employed. It was not prescribed in the majority of patients (69.2%) and it was used with no justification in others (15%).
27131766 Immunological and inflammatory processes in systemic autoimmune disease may not only cause 2016 Jul 15 PURPOSE: Systemic autoimmune disease (SAD) frequently affects the pericardium, and pathology is characterized by both immunological and inflammatory processes. We hypothesized that these processes simultaneously influence mitral-valve (MV) deterioration and left-ventricular (LV) wall thickening in SAD subjects. METHODS: 101 SAD subjects were selected (76 female; 53±17years; systemic-lupus-erythematosus, 26%; vasculitis, 20%; scleroderma, 14%; polymyositis/dermatomyositis complex, 10%; mixed connective tissue disease, 11% and rheumatoid-arthritis, 2%). MV anterior-mitral-leaflet (AML) length, AML thickness index, AML doming height and LV mass index (LVMI) were measured using transthoracic-echocardiography (TTE) and the presence of MV calcification, MV sub-valvular thickening and pericardial effusion (PE) were estimated. AML thickness index was calculated as the ratio of AML thickness to aortic posterior wall thickness. The correlation between LVMI and ECG V1S+V5R voltage was used to assess the etiology of LV wall thickening. RESULTS: 19 subjects (19%) had significant PE. PE subjects had a significantly greater AML thickness index (1.55±0.48 vs. 1.14±0.32, P<0.001), AML doming height (1.26±1.54mm vs. 0.03±0.91mm, P<0.001), more frequent MV sub-valvular thickening (26% vs. 5%, P=0.003) and greater LVMI (104.7±34.6g/m2 vs. 80.6±21.0g/m2, P=0.002). Significant correlation was observed between LVMI and ECG V1S+V5R voltage in 79 subjects without PE (R=0.39, P<0.001). However, in 18 subjects with PE, no such correlation was observed (R=0.30, P=0.23). CONCLUSIONS: MV, MV sub-valvular deterioration and increased LVMI, unrelated to high voltage ECG criteria, were frequently detected in SAD subjects with PE. Immunological and inflammatory processes in SAD may not only cause pericardium inflammation, but may also cause MV deterioration and LV wall thickening.
27100349 Genes associated with T helper 17 cell differentiation and function. 2016 Jun 1 Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFalpha. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn's disease. However, the full extent of their contribution to diseases is being investigated. The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells.
27062937 Do Demographics and Functional Abilities Influence Vehicle Type Driven by Older Canadians? 2016 Jun In this study, we examined the Candrive baseline data (n = 928; aged 70 to 94; 62% were men) to determine whether driver characteristics (i.e., age, gender, height, weight, BMI) and certain functional abilities (i.e., Rapid Paced Walk, Timed Up and Go) influenced the types of vehicles driven. There were significant differences with respect to type of vehicle and mean driver age (F = 3.58, p = 0.003), height, (F = 13.32, p < 0.001), weight (F = 14.31, p < 0.001), and BMI (F = 4.40, p = 0.001). A greater proportion of drivers with osteoporosis (χ2 = 21.23, p = 0.020) and osteo/rheumatoid arthritis (χ2 = 21.23, p = 0.020) drove small and medium-sized cars compared to larger ones. Further research is needed to examine older driver-vehicle interactions, and the relationship to demographics and functional abilities, given the vulnerability of this age group to automotive-related injuries.
27052323 Can anti-osteoporotic therapy reduce adjacent fracture in magnetic resonance imaging-prove 2016 Apr 6 BACKGROUND: Adjacent fracture of the cemented vertebrae result from crushed fragile trabeculae during follow-up, suggesting impaired bone marrow integrity. This study aimed to determine if anti-osteoporotic therapy can decrease the risk of adjacent fracture in patients after vertebroplasty. METHODS: This retrospective study reviewed of cases of osteoporotic patients with magnetic resonance imaging (MRI)-proven acute vertebral fractures between 2001 and 2007. Osteoporotic patients were investigated as determined by pre-operative MRI with subsequent adjacent fracture of the cemented vertebrae and for the possibility of anti-osteoporotic therapy decreasing the progression of collapse after a minimum of 6 months follow-up. All associated co-morbidities were recorded, as well as the use of anti-osteoporotic drugs (i.e., bisphosphonate, raloxifen, calcitonin, and teriparatide). Cox regression analysis was also performed. RESULTS: The 192 vertebral fractured patients who underwent vertebroplasty and anti-osteoporotic therapy had a mean age of 74.40 ± 6.41. The basic characteristics of patients with and without adjacent fracture differed in age, body mass index, rheumatoid arthritis, and use of glucocorticoids and anti-osteoporotic drugs (Table 1). Using the Kaplan-Meier curve, anti-osteoporotic therapy after vertebroplasty had a significant effect on adjacent fracture (p = 0.037, by log rank text). After adjusting for potential confounders, patients with anti-osteoporotic therapy still had a lower adjacent fracture rate than patients without anti-osteoporotic therapy (p = 0.006; HR: 2.137, 95 % CI: 1.1238-3.690). The adjacent fracture rate also increased in old age (p = 0.019; HR: 1.049; 95 % CI:1.008-1.039) and among smokers (p = 0.026; HR: 3.891; 95 % CI: 1.175-12.890). CONCLUSIONS: In this study, adjacent fracture of cemented vertebrae is inevitable after vertebroplasty but can be mitigated by anti-osteoporotic therapy to increase bone mass.