Owing to its intricate autoimmune pathophysiology and significant risks of progression to other rheumatic co-morbidities (i.e., osteoporosis and osteoarthritis), a plausible therapeutic regimen is mandatory for early-stage management of rheumatoid arthritis (RA). Nevertheless, the conventional therapeutic agents particularly the corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) have shown grander success in the treatment of RA; however, long-term use of these agents is also associated with serious adverse events. To combat these issues and optimize therapeutic efficacy, nanotechnology-based interventions have been emerged as viable option. While, nanomedicines signposted superiority over the conventional pharmacological moieties; there are still many pharmacokinetic and pharmacodynamic challenges to nanomedicines following their intravenous or intra-articular administration. To circumvent these challenges, significant adaptations such as PEGylation, surface conjugation of targeting ligand(s), and site- responsive behavior (i.e., pH-, biochemical-, or thermal-responsiveness) have been implemented. Besides, multi-functionalization of nanomedicines has been emerging as an exceptional strategy to overcome pharmacokinetic challenges, improve targetability to inflamed synovium, maximise internalisation into the activated macrophages, and improved therapeutic outcomes for treatment of RA. Therefore, this review aims to conceptualize and recapitulate the substantial evidences regarding the pharmacokinetic and pharmacodynamic superiority of multi-functionalized nanomedicines over the naked nanomedicines for site-selective targeting to inflamed synovium and rational treatment of RA and other rheumatic co-morbidities. Pharmaceutical sustainability of the multi-functionalized nanomedicines for improved biocompatibility, profound interaction with the targeting tissue/cells/sub-cellular domain, and diminished systemic toxicity has also been pondered.
Methyl salicylate-lactose physical mixture (1:1 and 1:1.5 ratios) was incorporated into calcium alginate beads by a coacervation method involving an ionotropic gelation/polyelectrolyte complexation approach.
The aims of this study were to determine damage index in systemic lupus erythematosus (SLE) patients based on Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) and to determine the laboratory and clinico-demographic factors affecting SDI.This is a retrospective cohort study of 94 SLE patients attending rheumatology clinics in 2 local hospitals in Kelantan, Malaysia. The patients were divided into 2 groups based on SDI score assigned by the attending physician, 0 (without damage) or ≥1 (with damage). Newly diagnosed SLE patients with disease duration less than 6 months were excluded.A total of 45 (47.9%) SLE patients showed damage by SDI score. Majority of the subjects had neuropsychiatric damages (21/94; 22.3%) followed by skin (12/94; 12.8%) and musculoskeletal (6/94; 6.4%) damage. SDI score was significantly associated with higher disease duration (6.2 ± 6.57 years vs 4.5 ± 3.7 years; P = .018), lower prednisolone dose (8.74 ± 10.89 mg vs 4.89 ± 3.81 mg; P
BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area.
METHODS: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness.
RESULTS: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area.
CONCLUSIONS: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.
KEYWORDS: Cumulative dose; OCT; hydroxychloroquine; retinal thickness
Janus kinase (JAK) inhibitors, a novel class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), have shown their safety and efficacy in rheumatoid arthritis (RA) and are being intensively tested in other autoimmune and inflammatory disorders. Targeting several cytokines with a single small compound leads to blocking the physiological response of hundreds of genes, thereby providing the background to stabilize the immune response. Unfortunately, blocking many cytokines with a single drug may also bring some negative consequences. In this review, we focused on the activity of JAK inhibitors in the cardiovascular system of patients with RA. Special emphasis was put on the modification of heart performance, progression of atherosclerosis, lipid profile disturbance, and risk of thromboembolic complications. We also discussed potential pathophysiological mechanisms that may be responsible for such JAK inhibitor-associated side effects.
Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.