Inflammation enhanced by accumulation of reactive oxygen species plays an essential role in the progression of cardiovascular diseases. Using the 2D-oxyblot analysis and 2D-difference image gel electrophoresis (2D-DIGE), we compared the levels of ROS-induced carbonyl modification of myocardial proteins in the whole left ventricles between 6-week-old hamsters with dilated (TO-2) and hypertrophic cardiomyopathy (Bio14.6) and control hamsters (F1B). Then, 2D electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry detected 18 proteins with increased carbonyl level in cardiomyopathy hamsters compared with control hamster. Carbonyl modification of proteins related to ATP synthesis, including citric acid cycle and electron transport system, was observed in the hearts of hamsters with both types of cardiomyopathy. Further analysis indicated that left ventricular carbonyl production correlated negatively with succinyl-CoA:3-ketoacid-coenzyme A transferase 1 activity (r
Conclusion: Using Fine-Gray proportional hazard regression, we demonstrated that RF positivity was related to a higher discontinuation rate of TNFi therapy due to ineffectiveness in bio-naïve RA patients.
Given the hypothesis that inflammation plays a critical role in the progression of cardiovascular diseases, the aim of the present study was to identify new diagnostic and prognostic biomarkers of myocardial proteins involved in early-phase cardiac impairment, using proteomics analysis. Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression of proteins in the whole left ventricles between control hamsters, dilated cardiomyopathic hamsters (TO-2), and hypertrophy cardiomyopathic hamsters (Bio14.6) at 6 weeks of age (n = 6, each group). Proteomic analysis identified 10 protein spots with significant alterations, with 7 up-regulated and 3 down-regulated proteins in the left ventricles of both TO-2 and Bio 14.6 hamsters, compared with control hamsters. Of the total alterations, peroxiredoxin 2 (PRDX2) showed significant upregulation in the left ventricles of TO-2 and Bio 14.6 hamsters. Our data suggest that PRDX2, a redox regulating molecule, is involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.
RA patients are prone to ulnar deviation and swan-neck deformity even early after onset of the disease. Limitation of finger joint range of motion due to hand-finger deformation brings restriction to ADL in the workplace as well as in the home. Patients and caretakers of patients are often burdened by these limitations; however, RA hand-finger deformation experience equipment have not been developed to experience these limitations. We have developed a novel RA hand-finger deformation experience equipment with opened fingertips (RSE; RA hand/finger simulation equipment).
Objectives
To assess the utilisation of RSE in healthy volunteers (HV) to experience RA hand-finger dysfunction using DASH (Disabilities of the Arm, Shoulder and Hand), STEF (Simple Test for Evaluating Hand Function), and Purdue Pegboard.
Methods
We developed the following equipment: Type U to imitate extension limitation of metacarpophalangeal (MCP) joints seen in ulnar deviation; Type B which imitates flexion deformity of the distal interphalangeal (DIP) joints by seen in boutonniere deformity; and Type S which imitates flexion limitation of proximal interphalangeal (PIP) and interphalangeal (IP) joints by reversing the upper and lower ends of the Oval-8 Finger Splint (Fukui Co. Ltd, Japan). Types U and S were fitted on HV (index to pinky). RSE was evaluated using DASH, STEF and Purdue Pegboard in hand-finger function evaluation. Twenty-four RA patients with hand-finger deformation and Forty-one HV were included in this study to evaluate the equipment.
Results
Mean ±SD ages for RA patients was 67.4±8.0 years (95.8% female) and 38.2±17.7 for HV (63.4% female), respectively. Total hand-finger deformities for RA patients were 23 hands for ulnar deviation, 66 fingers for swan-neck deformity, and 33 fingers for boutonniere deformity. Randomization for RA patients was as follows: 13 DASH, 5 (10 hands) STEF, and 6 Purdue Pegboard. 10 HV were assigned to DASH, 10 to Purdue Pegboard, and 14 (28 hands) to STEF. HV were evaluated with RSE and without RSE. For DASH, STEF, and Purdue Pegboard, RA patients showed significant functional loss compared to HV. Significant function loss in RA patients was also observed with the RSE. However, no differences were seen between the RA group and the HV with RSE group (figure 1).
Conclusions
We developed the RSE, which allows for one to experience the decrease in function with RA hand-finger deformity. Our study showed that RSE use can indeed allow this experience. By using RSE, health care workers, patient caretakers and early RA patients can experience joint limitation of RA for educational purposes, personalised rehab programs, and development of self-help tools.
A few studies on antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treatments have shown the therapeutic efficacy of mycophenolate mofetil (MMF). However, the therapeutic efficacy of MMF compared with that of cyclophosphamide (CYC) in patients with AAV has not been established. We conducted a systematic review and meta-analysis to assess the efficacy of MMF as a remission induction therapy in patients with AAV comparing it with the efficacy of CYC.We searched randomised controlled trials (RCTs) comparing the efficacy of MMF with that of CYC in patients with AAV on three different websites: PubMed, Cochrane Library and Google Scholar. We compared the difference in the relative risk (RR) of each outcome based on a Mantel-Haenszel random-effects model.We analysed data from four RCTs with 300 patients for the study. The 6-month remission rate (RR 1.09, 95% CI 0.86 to 1.38, p=0.48), the 6-month ANCA negativity (RR 1.31, 95% CI 0.91 to 1.90, p=0.15) and the long-term relapse rate (RR 1.36, 95% CI 0.80 to 2.31, p=0.26) were all similar between the two treatments. The rates of death, infection and leucopenia were also similar between the two groups (RR 1.05, 95% CI 0.40 to 2.74, p=0.93; RR 1.26, 95% CI 0.79 to 2.01, p=0.33; RR 0.45, 95% CI 0.16 to 1.32, p=0.15, respectively).We found no difference between the therapeutic efficacy of MMF and that of CYC in patients with AAV. MMF may be an alternative remission induction therapy in patients with non-life-threatening AAV.
Interferons (IFN), such as IFNα and IFNγ, are known to play a pivotal role for the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). These IFNs enhance the expression of mCD64. We recently have reported a tight correlation between mCD64 expression levels and SLE disease activity index (SLEDAI) (r=0.68, p<0.001) (Lupus 24(10):1076–80, 2015) and shown that mCD64 expression is a simple and useful biomarker for evaluating disease activity in SLE patients. Although neuropsychiatric manifestations are critical to the management of SLE, there have been no precise and convenient biomarkers assessing the activity of NPSLE. In this study, we investigated the utility of mCD64 expression as a biomarker for NPSLE. Method mCD64 expression levels were assessed quantitatively by using flow cytometry in five patients with NPSLE. The mCD64 expression levels were compared with SLEDAI and other conventional SLE activity markers, such as anti-dsDNA antibody, complements and cerebrospinal fluid (CSF) IL-6.
Result
The NPSLE events included three headaches, two aseptic meningitis and one acute confusion. At the active phase of these NPSLE events, mCD64 expressions were significantly enhanced at the median of 38 541 (range 31,693–73,287) molecules/cell compared to the treated inactive phase. Additionally, mCD64 expression was significantly higher in CSF IL-6 high (more than 4.3 pg/ml) group than the low group (p=0.011). The mCD64 expression levels were significantly decreased at the inactive phase of the NPSLE after treatment (p=0.027) shown in figure 1. The changes of mCD64 expression levels correlated with SLEDAI (r=0.74, p=0.014). Conclusions mCD64 expression may be a potential biomarker for evaluating not only the disease activity but also the response of treatment in NPSLE.
Background: Under a hypothesis that inflammation enhanced by reactive oxygen species (ROS) accumulation plays an essential role in the progression of cardiovascular diseases, we investigated ROS-in...
Severe infections that complicate rheumatoid arthritis may cause significant morbidity and mortality. The Modified Health Assessment Questionnaire (MHAQ) is one of the scores most used for measuring the functional status of rheumatoid arthritis (RA) patients. However, the relationship between the MHAQ score and severe infection risk has not been well studied [1].
Objectives
To examine the relationship between disease-associated functional status (MHAQ) and severe infection events (SIE) in rheumatoid arthritis patients.
Methods
We used data from the "MiRAi" cohort in Japan. In total, 2174 RA outpatients were examined at the Osaka Minami Medical Center between January 2012 and October 2017. The risk factors were identified and evaluated by multivariate logistic regression, linearity analysis. Interactions of SIE risk between MHAQ and treatment were also observed.
Results
The cohort contributed to 8206 patient-years of follow-up. Overall, 251 SIEs were observed and the incidence of SIE was 3.0 infections per 100 patient-years. The mean age at first observation was 61.7 years and the mean disease duration was 10.3 years. The use of glucocorticoids (GCs), methotrexate (MTX), and biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs/tsDMARDs) was 59.2%, 63.8%, and 40.3%, respectively. The mean Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Scores of 28 joints (DAS28), and MHAQ at first observation were 9.76±6.39, 10.1±6.87, 2.67±0.96, and 0.43±0.58, respectively. Disease duration, the MHAQ score, and prednisolone dose (p=0.015, 0.007, and <0.001, respectively) were significantly associated with SIE risk (Figure). Age, sex, stage, bDMARDs/tsDMARDs use, DAS28-CRP, and MTX dose (mg/week) did not predict a significant increase in SIE. The risk of SIE increased linearly with the MHAQ. The SIE risk increased rapidly from 0 to 5 mg of prednisolone, and then increased gradually over 5 mg. The SIE risk peaked at around 20 years disease duration. No significant interaction between MHAQ and bDMARDs/tsDMARDs or glucocorticoid use were observed (p=0.307, 0.282, respectively).
Conclusion
An increased MHAQ score was lineally associated with SIE, and did not show significant interactions with bDMARD/tsDMARD use or the oral glucocorticoid dose. Therefore, the MHAQ score is considered to be a strong, independent risk factor for infection in RA patients.
Reference
[1] Yamanaka H, Askling J, Berglind N, Franzen S, Frisell T, Garwood C, Greenberg JD, Ho M, Holmqvist M, Novelli Horne L, et al: Infection rates in patients from five rheumatoid arthritis (R017, 3(2):e000498A) registries: contextualising an RA clinical trial programme. RMD Open 2017, 3(2):e000498.
