Asymmetric dimethylarginine levels in Behçet's Disease

Abstract

Objective: Behçet's disease (BD) is a chronic, inflammatory, multisystem vasculitis and the etiology is not yet fully understood. Nitric Oxide (NO) is an important molecule for the vascular system which synthesised by the Nitric Oxide Synthase (NOS) enzyme. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. Therefore, we aimed to investigate levels of the ADMA and its relation with exacerbations in BD patients. Methods:The subjects enrolled in this study were recruited from 34 patients with BD and 34 healthy controls. Serum levels of ADMA, arginine and citrulline were measured by HPLC with fluorescence detection. The ESR and CRP levels analyzed by routinely used methods. Results: In contrast to information in the literature, ADMA levels were found to be decreased in BD patients when compared to control. Inversely, Arginine and Citrulline levels were significantly increased in BD patients. Increased Arginine/ADMA ratios were found in the patient group. There was an inverse relation between ADMA and CRP levels. Arginine values were also correlated CRP and Citrulline levels. Conclusion: One of the reasons of high number of BD attacks in young age may be low levels of ADMA. Our study suggests that the reduced levels of ADMA in patients group may impose a possible preventive role to ADMA through decrease of NO-mediated inflammation and exacerbations of BD with aging. and myocardial infarction; (c) diabetes mellitus, renal and hepatic diseases, active infectious diseases; (d) other known chronic inflammatory diseases. The body mass index (BMI) and blood pressure were recorded. It was also noted that whether the subjects smoke or not. Each subject was evaluated in active and inactive disease periods. At the time of examination, the presence of two or more of the following Behçet's clinical features was considered as active disease: Oral ulceration, genital ulceration, skin lesions, ocular lesions, active major vessel disease, and active major organ involvement including active gastrointestinal or neurological lesions. Subjects with one lesion or lesion-free period were regarded in inactive disease period.The protocol was approved by the Ethics Committee of the Selcuklu Medical Faculty (24.06.2010Faculty (24.06. -2010) and all subjects volunteered for the trial and written consent was obtained according to the Declaration of Helsinki.Blood samples were centrifuged with 2000 x g for 10 min at +4°C, followed by serum removal for assays. All serum samples were stored at -80°C until analysis.Measurements of ADMA, arginine and citrulline levels were accomplished by high performance liquid chromatography (HPLC), using the method described by Taner et al [17]. In brief, 20 mg 5-sulfosalisilic acid was added to 1 ml serum, and the mixture was left in an ice bath for 10 min. The precipitated protein was removed by centrifugation at 2,000×g for 10 min. Ten µl of the supernatant was filtered using a 0.45-μm pore size filter, which was then mixed with 100 μl derivatization reagent [prepared by dissolving ...

Meta-Analysis of Asymmetric Dimethylarginine Concentrations in Rheumatic Diseases

“…A p < 0.05 was considered statistically significant, and 95% confidence intervals (CIs) were reported. In two studies 22,23 the mean and standard deviation were inferred from median and IQR as previously reported 36 , while in two further studies 30,37 the mean and standard deviation were inferred from median and range as previously reported by Hozo et al . 38 .…”

“…In our subgroup meta-analysis, we found no difference in ADMA SMD on the basis of the analytic method employed or biological matrix tested, suggesting that the large heterogeneity between studies is not explained by techniques variability. However, as reported in Table 1, the range of mean plasma and serum ADMA concentrations in CTRLs was extremely large (from 0.10 to 3.22 μmol/L) with reported mean values not falling within the expected range in a large number of studies 30,33,34,37,52,57,75 . We think that this finding might be related to variability in the selection of healthy controls, pre-analytical and analytical issues, potentially accounting for the large heterogeneity of pooled estimates in this meta-analysis.…”

“…53 , PolandRApELISA62931.716/130.67 ± 0.182941.07/220.77 ± 0.20Öztürk et al . 30 , TurkeyBDsLC-FLR63433.319/153.22 ± 0.72°3437.519/152.25 ± 0.97°Berg et al . 19 , NorwayASpLC-FLR613452.778/560.49 ± 0.0815149.292/590.54 ± 0.12Yilmazer et al .…”

“…However, the results of studies reporting the association between ADMA and RDs have been contradictory: although most studies demonstrated a significant association between ADMA and RDs 13,14,16,17,19–24,26,28,29,31–34,44–50,52–56,63 , other studies failed to report a significant relationship 15,18,25,27,30,37,57 . The different results might be at least partially explained by the small sample size of each study.…”

“…Increased circulating ADMA concentrations, initially reported in rheumatoid arthritis (RA) patients free of cardiovascular risk 13 , have also been observed in psoriatic arthritis (PsA) 14,15 , ankylosing spondylitis (AS) 16–20 , systemic lupus erythematosus (SLE) 21 , Sjogren’s syndrome (SSj) 22 , systemic sclerosis (SSc) 23–29 and Behçet’s disease (BD) 30–34 .…”