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ID PMID Title PublicationDate abstract
26089907 Safety, Tolerability, and Efficacy of Tocilizumab in Rheumatoid Arthritis: An Open-Label P 2015 This open-label study investigated the safety and efficacy of tocilizumab in Middle Eastern patients with rheumatoid arthritis (RA). Patients whose Disease Activity Score based on 28 joints (DAS28) was >3.2 received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks. Patients receiving aTNF ± nonbiologic disease-modifying antirheumatic drug(s) (DMARD(s)) switched to tocilizumab; patients receiving nonbiologic DMARD monotherapy added tocilizumab. Primary end points were adverse events (AEs), serious AEs (SAEs), and laboratory parameters; secondary end points were DAS28, Health Assessment Questionnaire-Disability Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Eighty-eight of 95 patients completed 24 weeks. Overall, 125 AEs were reported in 43 (45%) patients; the most common were increased hepatic enzymes (16%) and cholesterol (11%). Eight patients experienced SAEs. Significant changes from baseline to week 24 occurred for hemoglobin, neutrophils, platelets, total cholesterol, and liver enzymes (P < 0.05). DAS28, CRP, and ESR decreased significantly from baseline at each visit (P < 0.0001). At week 24, the proportions of patients reporting DAS28 clinically meaningful improvement (decrease ≥1.2), low disease activity (DAS28 ≥2.6 to ≤3.2), and remission (DAS28 <2.6) were 92%, 23%, and 64%, respectively. Safety and efficacy of tocilizumab were consistent with values reported in Western patients.
25821469 The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid a 2015 Background. Autoantibodies to citrullinated peptides have been shown to be valuable in the diagnosis of rheumatoid arthritis (RA). The expanding repertoire of antibodies to citrullinated peptide antigens (ACPA) has been a topic of great interest in recent reviews and research studies, as has the ability of these autoantibodies to predict disease outcome. Objectives. The aim of this review was to provide an update on the relevance of ACPA as prognostic markers in RA. The ability to identify patients predisposed to an aggressive outcome at the time of initial diagnosis greatly facilitates the selection of appropriate and cost-effective treatment. Methods. A systematic review of the literature was carried out. Studies from 1967 up to June 2014 with data on prognostic value of ACPA were included. Quality assessment was done by using the modified Hayden list for prognostic studies. Meta-analysis was performed using BioStat software. Results. The results of 25 studies were selected for the final review. A total of 6421 patients with RA were included, mainly in inception cohorts, with follow-up duration ranging from one year to ten years. All studies carried prognostic data on all available isotypes of anticyclic citrullinated protein (CCP), while four had data on antimutated citrullinated vimentin (MCV). There was a single relevant study each on anticitrullinated enolase peptide 1 (CEP1) and antichimaeric fibrin/filaggrin citrullinated peptide 1 (CFFCP1). All studies showed ACPA to be strong predictors of joint erosions in RA. Other factors, particularly baseline erosions, showed an additive effect. Anti-MCV appeared to be a marker of a more aggressive form of disease. Ten studies had data on which a meta-analysis could be performed. This gave an overall odds ratio of 4.85 for ACPA (anti-CCP/MCV) positivity being predictive for the development of joint erosions. Two studies with data on anti-CEP1 and anti-CFFCP1 also showed this positive predictive role of ACPA for joint erosions. Conclusions. ACPA are strong predictors of severity in RA. Their use should be part of routine rheumatology practice.
25484055 Antibodies to watch in 2015. 2015 The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 7 antibody therapeutics (secukinumab, evolocumab, mepolizumab, dinutuximab, nivolumab, blinatumomab, necitumumab) are undergoing a first regulatory review in the EU or US. Of the 39 novel mAbs currently in Phase 3 studies, a marketing application for one (alirocumab) may be submitted in late 2014, and marketing application submissions for at least 4 (reslizumab, ixekizumab, ocrelizumab, obiltoxaximab) are expected in 2015. Other 'antibodies to watch' are those in Phase 3 studies with estimated primary completion dates in late 2014 or 2015, which includes 13 for non-cancer indications (brodalumab, bimagrumab, bococizumab, MABp1, gevokizumab, dupilumab, sirukumab, sarilumab, tildrakizumab, guselkumab, epratuzumab, combination of actoxumab + bezlotoxumab, romosozumab) and 2 (racotumomab and clivatuzumab tetraxetan) undergoing evaluation as treatments for cancer. In addition to the novel antibody therapeutics mentioned, biosimilar infliximab and biosimilar trastuzumab are 'antibodies to watch' in 2015 because of their potential for entry into the US market and regulatory review, respectively.
26856389 Urinary metabolite profiling provides potential differentiation to explore the mechanisms 2016 Sep To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Sprague-Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures-discriminant analysis. Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright © 2016 John Wiley & Sons, Ltd.
24842480 Pathogenesis of systemic inflammatory diseases in childhood: "Lessons from clinical trials 2015 Jan Inflammation has often been considered to be a nonspecific response and to play a bridging role in the activation of adaptive immunity. However, it is now accepted that inflammation is the product of an independent innate immune system closely linked to the adaptive immune system. The key mediators of inflammation are inflammatory cytokines, as determined by multiple lines of evidence both in vitro and in vivo. Due to the crucial role of inflammatory cytokines in the pathogenesis of autoimmune disorders, anti-cytokine treatment has been developed as a therapy for rheumatoid arthritis, juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases. We recently completed several clinical trials of anti-cytokine treatment for children with systemic inflammatory diseases: anti-IL-6 receptor monoclonal antibody (tocilizumab) for children with two subtypes of JIA (poly-JIA and systemic JIA), anti-TNF-α monoclonal antibody (infliximab) for children with Kawasaki disease, and anti-IL-1-β monoclonal antibody (canakinumab) for children with cryopyrin-associated periodic syndrome. This review summarizes the basis of inflammation in terms of innate immunity and adaptive immunity in these systemic inflammatory diseases, clinical efficacy, and tolerability of these biologic agents, and attempts to determine the roles of individual inflammatory cytokines in disease pathogenesis.
26272193 The potential therapeutic role of myeloid-derived suppressor cells in autoimmune arthritis 2016 Feb OBJECTIVE: The aim of this review is to evaluate the roles of myeloid-derived suppressor cells (MDSC) in autoimmune arthritis. METHODS: The terms "myeloid-derived suppressor cells," "regulatory T cell," "Th17 cell" and "autoimmune arthritis" were used for literature search from the PubMed. The publications about the characteristics of MDSC, the immunosuppression of MDSC, the role of MDSC in the regulation of Tregs and Th17 cells, and the potential clinical applications of MDSC against rheumatoid arthritis (RA) were identified, retrieved and reviewed. RESULTS: MDSC are defined as a heterogeneous population of pathologically activated immature and mature myeloid cells consisting of granulocytic and monocytic subsets. Published data showed that the role of MDSC in Tregs and Th17 cells expansion were inconsistent. Given their role in suppressing T-cell responses, MDSC have been tested for their capability of preventing RA. CONCLUSIONS: Although MDSC hold promise in the treatment of RA, their exact role in the expansion of Tregs and Th17 cells is unclear during RA. The definite effect of MDSC in RA therapy needs to be studied further.
26968301 [Juvenile idiopathic arthritis: Definition and classification]. 2016 Apr Juvenile idiopathic arthritis (JIA) is a group of diseases defined by the presence of arthritis of more than 6 weeks duration in patients aged less than 16 years and with unknown etiology. The international classification based on clinical and biological criteria define each type of JIA: systemic, oligoarticular, polyarticular with and without rheumatoid factor, enthesitis-related arthritis, and psoriatic arthritis. However, some discussions persist concerning systemic-onset juvenile idiopathic arthritis, whose clinical symptoms and pathogenic mechanisms are quite similar to those observed in autoinflammatory diseases, arthritis with antinuclear factors (poly- and oligoarticular) that could be considered as a homogenous group, and a family history of psoriasis that frequently led to unclassified arthritis. Better knowledge of the pathogenic mechanisms should improve the initial clinical classification with more homogeneous groups of patients and reduce the number of unclassified cases of arthritis.
26932524 Inflammatory arthritis in HIV positive patients: A practical guide. 2016 Mar 1 BACKGROUND: Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. METHODS: We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. RESULTS: There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. CONCLUSIONS: This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients.
27621213 Utility of circulating serum miRNAs as biomarkers of early cartilage degeneration in anima 2017 Mar OBJECTIVE: The purpose of this study was to determine if serum microRNA (miRNA) signatures were biomarkers of early cartilage degeneration in preclinical mouse models of post-traumatic osteoarthritis (OA) and inflammatory arthritis. METHODS: Cartilage degeneration was induced in 10-12 week old male C57BL6 mice by destabilization of the medial meniscus (DMM) or intra-articular injection of methylated-bovine-serum-albumin (AIA), with sham-operated or saline-injected control animals (n = 6/treatment/time). Total serum RNA and knee joints were isolated at 1, 4 and 16 weeks post-induction. Cartilage degeneration was scored histologically. Serum miRNA expression profiling was performed using Agilent microarrays and validated by qPCR. RESULTS: DMM-operated and AIA mice had characteristic cartilage degeneration (proteoglycan loss, chondrocyte hypertrophy, structural damage), that increased significantly with time compared with controls, and with distinct temporal differences between arthritis models. However, expression profiling revealed no statistically significant dysregulation of serum miRNAs between AIA vs saline-injected or DMM vs sham-operated control mice at the critical early disease stages. The inability to detect DMM or AIA serum miRNA signatures compared with controls was not due to the insensitivity of the expression profiling approach since significant changes were observed in miRNA expression between the arthritis models and between time points. CONCLUSION: While distinct patterns of progressive cartilage degradation were induced in the arthritis models, we were unable to identify any serum miRNAs that were significantly dysregulated in early stages of disease compared with controls. This suggests circulating serum miRNAs may not be useful as cartilage biomarkers in distinguishing the early or progressive stages of arthritis cartilage degeneration.
26253095 PUF60: a prominent new target of the autoimmune response in dermatomyositis and Sjögren's 2016 Jun OBJECTIVES: Autoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60 kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient's serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody. METHODS: A new 60 kDa specificity was detected by immunoblotting HeLa cell lysates. The targeted autoantigen was identified as poly(U)-binding-splicing factor 60 kDa (PUF60) using (i) a human protein array and (ii) two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing. Anti-PUF60 antibodies were assayed by ELISA using sera from patients with primary Sjögren's syndrome (SS; n=84), systemic lupus erythematosus (SLE; n=71), DM (n=267), polymyositis (n=45), inclusion body myositis (n=45) and healthy controls (n=38). RESULTS: PUF60 was identified as a new autoantigen. Anti-PUF60 antibodies were present in 25/84 (30%) patients with SS, 6/71 (8.5%) patients with SLE and 2/38 (5.0%) control subjects (SS vs controls, p=0.002; SLE vs controls, p=0.711). Anti-PUF60 antibodies were present in 48/267 (18.0%) patients with DM versus 4/45 (8.9%) and 5/45 (11.1%) patients with inclusion body myositis and polymyositis, respectively. The antibody was significantly associated with anti-Ro52 antibodies, rheumatoid factor and hyperglobulinemia in the patients with primary SS. In patients with DM, the antibody was associated with anti-transcription intermediary factor 1 gamma seropositivity and Caucasian race. CONCLUSIONS: PUF60 represents a novel autoantigen in patients with SS and DM. PUF60 antibodies are associated with distinct clinical features and different immune responses in different diseases.
25923821 Calcitonin gene-related peptide in the joint: contributions to pain and inflammation. 2015 Nov Arthritis is the commonest cause of disabling chronic pain, and both osteoarthritis (OA) and rheumatoid arthritis (RA) remain major burdens on both individuals and society. Peripheral release of calcitonin gene-related peptide (CGRP) contributes to the vasodilation of acute neurogenic inflammation. Contributions of CGRP to the pain and inflammation of chronic arthritis, however, are only recently being elucidated. Animal models of arthritis are revealing the molecular and pathophysiological events that accompany and lead to progression of both arthritis and pain. Peripheral actions of CGRP in the joint might contribute to both inflammation and joint afferent sensitization. CGRP and its specific receptors are expressed in joint afferents and up-regulated following arthritis induction. Peripheral CGRP release results in activation of synovial vascular cells, through which acute vasodilatation is followed by endothelial cell proliferation and angiogenesis, key features of chronic inflammation. Local administration of CGRP to the knee also increases mechanosensitivity of joint afferents, mimicking peripheral sensitization seen in arthritic joints. Increased mechanosensitivity in OA knees and pain behaviour can be reduced by peripherally acting CGRP receptor antagonists. Effects of CGRP pathway blockade on arthritic joint afferents, but not in normal joints, suggest contributions to sensitization rather than normal joint nociception. CGRP therefore might make key contributions to the transition from normal to persistent synovitis, and the progression from nociception to sensitization. Targeting CGRP or its receptors within joint tissues to prevent these undesirable transitions during early arthritis, or suppress them in established disease, might prevent persistent inflammation and relieve arthritis pain.
25201389 Juvenile idiopathic arthritis in relation to maternal prenatal smoking. 2015 May OBJECTIVE: Cigarette smoking increases the risk of seropositive adult rheumatoid arthritis. The relationship of smoking with juvenile idiopathic arthritis (JIA), a heterogeneous group of 7 mutually exclusive categories of chronic childhood inflammatory arthritides, is unknown. Our objective was to evaluate the association between JIA and its categories with maternal prenatal smoking. METHODS: This case-control study used International Classification of Diseases, Ninth Revision codes from hospital records to identify 1,196 JIA cases born in Washington state and diagnosed at a quaternary pediatric center from 1997-2010. Controls (n = 5,618) were randomly selected from birth records of children without JIA, frequency matched on birth year. Prenatal smoking exposure was assessed from subjects' birth certificates. Chart review categorized JIA into International League of Associations for Rheumatology categories. Adjusted odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated using logistic regression. RESULTS: We did not observe an increased risk of JIA in relation to maternal prenatal smoking. Prenatal smoking was reported less often among mothers of JIA cases (11%), than among control mothers (17%; OR 0.71 [95% CI 0.58-0.87]), a relationship somewhat more marked for oligoarticular/extended oligoarticular JIA. Although this relationship persisted after adjustment, we cannot rule out that the effect may have been due to residual confounding by socioeconomic status. CONCLUSION: We did not observe an increased risk of JIA or its individual categories with maternal prenatal smoking.
26359802 CXCL13 and CCL11 Serum Levels and Lymphoma and Disease Activity in Primary Sjögren's Synd 2015 Dec OBJECTIVE: Non-Hodgkin's lymphoma (NHL) is a severe complication of primary Sjögren's syndrome (SS). Ectopic germinal centers (GCs) in the salivary glands are predictors of the occurrence of NHL. Given the association between CCL11 and CXCL13 and ectopic GCs, we assessed the link between these chemokines and NHL, as well as the association between these chemokines and disease activity, in patients with primary SS. METHODS: Serum levels of CCL11 and CXCL13 were evaluated by multiplex assay in 385 patients included in the Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. The association between chemokine levels, B cell biomarkers, and patient subsets was assessed using Spearman's test for continuous data and the nonparametric Mann-Whitney U test for categorical data. Multivariate analyses were performed to identify parameters associated with lymphoma and disease activity. RESULTS: Seventeen patients had a history of lymphoma, and 5 of them had developed NHL during followup. The median serum levels of CCL11 and CXCL13 in the total cohort were 106.48 pg/ml (interquartile range 69.33-149.85) and 108.31 pg/ml (interquartile range 58.88-200.13), respectively. Patients with lymphoma had higher levels of CXCL13 than did patients without lymphoma (P = 0.006) and a trend toward a higher level of CCL11 (P = 0.056). Low C4 and high BAFF levels were associated with NHL on multivariate analysis (P = 0.01 and P = 0.0002, respectively). CCL11 and CXCL13 levels correlated positively with the rheumatoid factor titer, the κ-to-λ free light chain ratio, and the β2 -microglubulin level. CXCL13 was the only parameter associated with disease activity on multivariate analysis. CONCLUSION: These findings demonstrate a link between CXCL13 and CCL11 and disease activity and lymphoma. This highlights the continuum between chronic B cell activation, disease activity, and lymphomagenesis in patients with primary SS.
26302733 Nasal septal perforation associated with pyoderma gangrenosum. 2015 Jan BACKGROUND: Pyoderma gangrenosum (PG) is a skin condition characterized by necrotic ulcers and most commonly occurs on the legs in association with inflammatory bowel disease and rheumatoid arthritis; however, PG rarely involves the head and neck, and very rarely causes nasal septal perforation. OBJECTIVE: Here, we describe a case report of PG causing nasal septal perforation in a 71-year-old male with truncal lesions in the absence of either inflammatory bowel disease or autoimmune arthritis. METHODS: Case report with histologic description. RESULTS: Histology from nasal mucosal biopsies showed chronic inflammation and reactive change without evidence of malignancy. Together with serologic and nonserologic testing, as well as clinical evaluation, we were able to rule out other causes of septal perforation including Wegener's granulomatosis, lymphoma, and vasculitis, and concluded that the cause of nasal septal perforation was most likely PG. CONCLUSION: Septal perforation etiology should include a complete history and physical to evaluate for systemic etiologies, including rare ones such as PG.
25394289 Pound the alarm: danger signals in rheumatic diseases. 2015 Mar Damage-associated molecular patterns (DAMPs) are chemically heterogeneous endogenous host molecules rapidly released from damaged or dying cells that incite a sterile inflammatory response mediated via pattern recognition receptors (PRRs). The sources of DAMPs are dead or dying cells or the extracellular matrix and can signal through the PRRs, the Toll-like receptors or cytosolic Nod-like receptors, culminating in nuclear factor κB (NF-κB) activation and pro-inflammatory cytokine secretion. Together, these molecules are involved in sterile inflammation and many are associated with rheumatic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythromatosus, psoriatic arthritis and systemic sclerosis. These diseases are associated with inflammation and many danger signals are found in sites of sterile inflammation and mediate inflammation. The present review examines the role of DAMPs in rheumatic conditions and suggests avenues for their therapeutic modulation.
26082818 Polish Medical Society of Radiology and Polish Society of Rheumatology Recommendations for 2015 This document presents the recommendations of the Polish Medical Society of Radiology (PLTR) and the Polish Society of Polish Society of Rheumatology (PTR) regarding the standards of collaboration between radiologists and rheumatologists so as to optimize the diagnostics and treatment of patients with rheumatic diseases of the musculoskeletal system, including rheumatoid arthritis and spondyloarthropathies.
27366339 HIV Infection and Osteoarticular Tuberculosis: Strange Bedfellows. 2016 We report the case of a 47-year-old female patient with rheumatoid arthritis and HIV infection presenting with a 3-week history of a painful swollen knee, increased serum inflammatory markers, and a low CD4 lymphocyte count. The diagnosis of TB arthritis was made by synovial fluid culture, GeneXpert/PCR, and confirmed by histopathology of a synovial biopsy. A mini literature review suggests that although HIV infection is associated with extrapulmonary TB, osteoarticular TB is a relatively unusual presentation in an HIV positive patient. The diagnostic utility of the GeneXpert test is explored. We also describe the patient's good response to an intra-articular corticosteroid injection in combination with standard anti-TB therapy.
27089641 [New synthetic and biologic treatments for spondylarthritis]. 2016 Mar 9 The only biological treatments recognized and reimbursed for spondylarthritis in Switzerland are anti TNF. Other effective agents in rheumatoid arthritis were found to be of little use in this indication. Fortunately, in recent years appeared biological molecules blocking cytokines involved in new pathways of inflammation in particular that of IL7. They have been very effective against psoriasis and have a high potential in psoriatic arthritis and spondylarthritis. In parallel, synthetic small molecules capable of modulating the production of intracellular cytokines begin to be marketed. They also are potentially active in the same rheumatic diseases. The purpose of this article is to review these new drugs, in particular to review the progress of their development and commercialization status.
28371438 Agranulocytosis and mixed-type autoimmune hemolytic anemia in primary sjögren's syndrome: 2016 Dec Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that presents with sicca symptoms of the main mucosal surfaces. Patients with pSS have a broad spectrum of laboratory features, such as cytopenias and hypergammaglobulinemia. Although hematological abnormalities are usually seen in pSS patients, agranulocytosis and autoimmune hemolytic anemia (AIHA) are rare. Here we describe a 40-year-old woman with pSS who developed both agranulocytosis and mixed-type AIHA. An increased risk of malignancies has also been reported in pSS patients with hematological changes. Although there is no evidence of malignancies, this patient should be closely followed up in case of developing lymphoma.
26293545 Glycation, carbonyl stress and AGEs inhibitors: a patent review. 2015 INTRODUCTION: The glycation process, comprising a series of reactions, results in the formation of heterogeneous adducts, known as advanced glycation end products (AGEs). AGEs are involved in several pathologies, including diabetes-associated late complications, atherosclerosis, Alzheimer's disease and inflammatory arthritis. Several inhibitors of AGEs and/or reactive carbonyl species have been identified from various sources, including natural products and synthetic molecules, and have been investigated for their mechanism of action. AREAS COVERED: This review covers the literature on AGEs inhibitors published as patents between 2001 and 2014. Initially, the earlier reported molecules with AGEs inhibitory properties, their mechanism of actions and reported adverse effects are discussed. The main focus has been on the chemical structures, methods for evaluation of the activity, modes of action, pharmacokinetics and therapeutic outcomes. The potential of these AGEs inhibitors in the treatment and management of a number of diseases are also discussed in this review. EXPERT OPINION: The reactive carbonyl species and AGEs have recently emerged as novel therapeutic targets for the prevention and treatment of several diseases. Currently, the major concerns with the use of AGEs inhibitors as therapeutic agents are low effectiveness, poor pharmacokinetics and undesirable side effects. Many of the AGEs inhibitors reviewed here possess potent antiglycation activity and are devoid of undesirable side effects. These small molecules inhibitors can, therefore, serve as scaffolds for the development and designing of new AGEs inhibitors as clinical agents.