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1.
Acute Whole-Body Vibration Exercise Promotes Favorable Handgrip Neuromuscular Modifications in Rheumatoid Arthritis: A Cross-Over Randomized Clinical.
Coelho-Oliveira, AC, Lacerda, ACR, de Souza, ALC, Santos, LMM, da Fonseca, SF, Dos Santos, JM, Ribeiro, VGC, Leite, HR, Figueiredo, PHS, Fernandes, JSC, et al
BioMed research international. 2021;:9774980
Abstract
OBJECTIVE Rheumatoid arthritis (RA) causes progressive changes in the musculoskeletal system compromising neuromuscular control especially in the hands. Whole-body vibration (WBV) could be an alternative for the rehabilitation in this population. This study investigated the immediate effect of WBV while in the modified push-up position on neural ratio (NR) in a single session during handgrip strength (HS) in women with stable RA. METHODS Twenty-one women with RA (diagnosis of disease: ±8 years, erythrocyte sedimentation rate: ±24.8, age: 54± 11 years, BMI: 28 ± 4 kg·m-2) received three experimental interventions for five minutes in a randomized and balanced cross-over order: (1) control-seated with hands at rest, (2) sham-push-up position with hands on the vibration platform that remained disconnected, and (3) vibration-push-up position with hands on the vibration platform turned on (45 Hz, 2 mm, 159.73 m·s-2). At the baseline and immediately after the three experimental interventions, the HS, the electromyographic records (EMGrms), and range of motion (ROM) of the dominant hand were measured. The NR, i.e., the ratio between EMGrms of the flexor digitorum superficialis (FDS) muscle and HS, was also determined. The lower NR represented the greater neuromuscular efficiency (NE). RESULTS The NR was similar at baseline in the three experimental interventions. Despite the nonsignificance of within-interventions (p = 0.0611) and interaction effect (p = 0.1907), WBV exercise reduced the NR compared with the sham and control (p = 0.0003, F = 8.86, η 2 = 0.85, power = 1.00). CONCLUSION Acute WBV exercise under the hands promotes neuromuscular modifications during the handgrip of women with stable RA. Thus, acute WBV exercise may be used as a preparatory exercise for the rehabilitation of the hands in this population. This trial is registered with trial registration 2.544.850 (ReBEC-RBR-2n932c).
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The Bioequivalence of Two Peficitinib Formulations, and the Effect of Food on the Pharmacokinetics of Peficitinib: Two-Way Crossover Studies of a Single Dose of 150 mg Peficitinib in Healthy Volunteers.
Shibata, M, Toyoshima, J, Kaneko, Y, Oda, K, Kiyota, T, Kambayashi, A, Nishimura, T
Clinical pharmacology in drug development. 2021;(3):283-290
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Abstract
The marketed tablet formulation of peficitinib differs from the tablet used during the clinical trials. The bioequivalence of the marketed formulation and developmental tablet, and the food effect on the marketed formulation, were analyzed in 2 Japanese open-label, randomized, 2-way crossover studies in healthy male volunteers. Volunteers received a single oral dose of the marketed 150-mg peficitinib tablet under fasted conditions (bioequivalence), and under fed or fasted conditions (food effect). Bioequivalence was compared with the developmental 150-mg tablet. Samples for pharmacokinetic analysis were collected before dose and ≤72 hours after dose. Safety assessments included adverse events, vital signs, and laboratory variables. In total, 40 and 18 subjects were randomized to the bioequivalence and food effect studies, respectively. The 2 peficitinib formulations were bioequivalent (90% confidence intervals of the geometric mean ratios for Cmax and AUCt of peficitinib were within predefined limits of 0.8 to 1.25). The AUClast and the Cmax of the marketed tablet were 36.8% and 56.4% higher, respectively, under fed versus fasted conditions. Peficitinib was well tolerated. The marketed 150-mg tablet formulation of peficitinib was bioequivalent to the developmental 150-mg formulation, with no discernible safety differences. Bioavailability increased under fed conditions with the marketed tablet formulation.
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Therapeutic Implications of Diet in Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory Diseases.
Jiang, Y, Jarr, K, Layton, C, Gardner, CD, Ashouri, JF, Abreu, MT, Sinha, SR
Nutrients. 2021;(3)
Abstract
Despite being a focal issue to patients, the effect of diet on adult inflammatory bowel disease (IBD) remains underexplored with limited guidance. While promising clinical trials are currently underway, there is a need for further evidence-based recommendations. As such, we summarize the current evidence on various diets used in the treatment of IBD and also explore the potential applications of dietary data from related immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and psoriasis, to provide additional information to inform IBD providers. To date, there have been multiple diets investigated as adjunctive therapy in IBD, but many associated studies are small, non-randomized, and not controlled. Mediterranean, vegetarian/vegan, and reduced-calorie/fasting diets have been studied and have shown some positive results in other IMIDs, which may suggest potential applicability to those with IBD, but larger, well-designed clinical trials are needed for further guidance. Gluten-free and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)diets do not appear to have an impact on IBD disease activity, but low FODMAP may potentially be helpful for those with concurrent functional gastrointestinal symptoms. Specific carbohydrate diets have been mainly assessed in children but show some potential in small adult studies.
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Alcohol Consumption in Rheumatoid Arthritis: A Path through the Immune System.
Azizov, V, Zaiss, MM
Nutrients. 2021;(4)
Abstract
Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing TFH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol's negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate's effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.
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The effect of black barberry hydroalcoholic extract on immune mediators in patients with active rheumatoid arthritis: A randomized, double-blind, controlled clinical trial.
Aryaeian, N, Hadidi, M, Mahmoudi, M, Asgari, M, Hezaveh, ZS, Sadehi, SK
Phytotherapy research : PTR. 2021;(2):1062-1068
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. In this trial, we aimed to investigate the Immunomodulatory effect of hydroalcoholic extract of black barberry on immune mediators in patients with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled clinical trial, 80 women with active RA were randomly assigned into two groups of two capsules, each containing 1,000 mg black barberry extract (n = 40) or maltodextrin placebo (n = 40) daily for 12 weeks. Demographic indices, physical activity, dietary intake, and disease activity were investigated using suitable questionnaires. Concentration of cytokines IL-2, IL-4, IL-10, and IL-17 in blood sample were measured using PBMC method. Statistical analysis was performed using SPSS (version 22). At baseline, there were no differences between the two groups in terms of demographic indices, physical activity, and dietary intake (p > .05). Black barberry supplementation reduced the severity of RA. It showed no significant effect on IL-2 and IL-4 cytokines (p > .05). IL-17 levels decreased significantly after the intervention within the black barberry group, while IL-10 had a significant increase in this group (p < .05). Barberry extract may reduce inflammatory and increase anti-inflammatory cytokines in RA, and stimulates the immune response by increasing Th2 production.
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The Emerging Roles of Endocrine Hormones in Different Arthritic Disorders.
Bertoldo, E, Adami, G, Rossini, M, Giollo, A, Orsolini, G, Viapiana, O, Gatti, D, Fassio, A
Frontiers in endocrinology. 2021;:620920
Abstract
The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.
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Prevalence of hydroxychloroquine retinopathy with long-term use in a cohort of Indian patients with rheumatic diseases.
Manoj, M, Sahoo, RR, Singh, A, Hazarika, K, Bafna, P, Kaur, A, Wakhlu, A
Rheumatology international. 2021;(5):929-937
Abstract
The study aims to estimate the prevalence of hydroxychloroquine (HCQ) retinopathy in a cohort of Indian patients and analyse the associated factors. Adult patients with rheumatological disorders aged ≥ 18 years using HCQ for more than 5 years and/or having received a cumulative dose > 400 g were included. Demographic and clinical data were collected and all underwent ophthalmological tests which included Humphrey automated visual fields (AVF) and spectral domain optical coherence tomography (SD-OCT). The various clinical characteristics of the patients were compared. The study included 110 patients with a mean age of 43.5 ± 10.1 years and predominantly females. Eleven patients (10%) were diagnosed with definite HCQ retinopathy. The mean daily dose of HCQ (mg/kg of real body weight) was significantly different in the groups with and without retinopathy (5.7 ± 0.9 vs 5.1 ± 0.8, p = 0.04). Patients with retinopathy had significantly more colour vision abnormalities (odds of 16.9; confidence interval 4.1-69.1, p = 0.0001) and higher prevalence of both parafoveal and perifoveal thinning (p < 0.0001). Age, gender, duration of HCQ use, cumulative HCQ dose and body mass index were not found to be associated with retinopathy. Four out of 11 patients had abnormalities only on 30-2 protocol for AVF testing, two had abnormalities only on 10-2 protocol, whereas five patients had abnormalities on both protocols. SD-OCT abnormalities were present in all patients with retinopathy. Hydroxychloroquine retinopathy was prevalent in the study cohort and significantly associated with a higher daily dose of HCQ (mg/kg real body weight).
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Comparative study evaluating antihistamine versus leukotriene receptor antagonist as adjuvant therapy for rheumatoid arthritis.
Mostafa, TM, Hegazy, SK, El-Ghany, SEA, Kotkata, FAE
European journal of clinical pharmacology. 2021;(12):1825-1834
Abstract
PURPOSE Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.
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What dose of folic acid to use with methotrexate in rheumatoid arthritis?
Bramley, D
Drug and therapeutics bulletin. 2021;(7):103-106
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Comprehensive microRNA and transcriptomic profiling of rheumatoid arthritis monocytes: role of microRNA-146b in pro-inflammatory progression.
Ciechomska, M, Wojtas, B, Bonek, K, Roszkowski, L, Gluszko, P, Benes, V, Maslinski, W
Rheumatology (Oxford, England). 2021;(11):5424-5435
Abstract
OBJECTIVE To explore global miRNA and transcriptomic profiling of monocytes from RA patients compared with healthy controls in order to predict which aberrantly expressed miRNA can negatively modulate inflammatory molecules. METHODS Using next-generation sequencing, we have performed simultaneous global analysis of miRNA (miRNA-seq) and transcriptome (RNA-seq) of monocytes from RA patients and healthy controls. Global analysis of miRNA of SSc monocytes was also performed. Following differential analysis and negative correlation, miRNA-RNA pairs were selected. RESULTS We found that 20 specific miRNA candidates are predicted to silence inflammatory mediators, out of 191 significantly changed miRNAs in RA monocytes. Based on the highest scoring in terms of negative correlation (r = -0.97, P = 1.75e-07, false discovery rate = 0.04) and the number of seeds in miRNA responsible for negative regulation, we selected miRNA-146b and its target gene anti-inflammatory retinoic acid receptor alpha (RARA). Similarly to next-generation sequencing, qPCR analysis also confirmed negative correlation between miRNA-146b and RARA expression (r = -0.45, P = 0.04). Additionally, miRNA-146b expression in RA monocytes significantly correlated with clinical parameters including DAS28 for RA with CRP (DAS28-CRP) and ESR (DAS28-ESR), whereas overexpression of miRNA-146b was able to functionally reduce RARA expression in the human monocytic cell line THP-1. Finally, circulating miRNA-146b expression in sera and SFs was significantly elevated in RA patients. CONCLUSIONS Overall, in this study we have identified a new miRNA-146b candidate that is predicted to negatively regulate the anti-inflammatory RARA transcript, whereas circulating miRNA-146b level can be used as a biomarker predicting pro-inflammatory RA progression and disease activity.