Background:According to modern concepts, rheumatoid arthritis (RA) refers to severe autoimmune rheumatic diseases. The activation of free radical oxidation processes is essential in the development of this disease [1]. Xanthine oxidoreductase is a significant reactive oxygen species source [2]. Despite the great advances in the treatment of rheumatoid arthritis (RA) associated with the introduction of innovative drugs and especially the improvement of the strategy for their use into clinical practice, glucocorticoids still remain an important component of RA pharmacotherapy in actual clinical practice.Objectives:to evaluate the changes in activities of xanthine oxidoreductase interconvertible forms (xanthine oxidase, ЕС 1.17.3.2 and xanthine dehydrogenase, ЕС 1.17.1.4) in lysed red blood cells of RA patients in relation with glucocorticoid treatment.Methods:47 RA patients with verified RA and 30 healthy controls were enrolled in the study. The diagnosis was verified using the 2010 ACR/EULAR criteria 2010. All patients have moderate DAS28 scores. RA patients were randomized into 2 groups comparable in gender, age and the principal clinical manifestations. Methylprednisolone (Metipred, Orion Corp.), average dose 30 mg/day, and betamethasone (Diprospan, Schering-Plough), single dose7 mg, were administered intramuscularly in the respective groups. Хanthine oxidase (XO) and xanthine dehydrogenase (XDG) activities were measured in lysed red blood cells by spectrophotometric method as previously described [3]. The changes of these enzymes activities were studied in RA patients before and after the injection of glucocorticoids. Statistical comparison tests were selected in according to common guidelines, differences were considered significant when p<0.05. Central tendencies were expressed as means±SEM.Results:Mean age of patients in methylprednisolone group was 41.8±1.05 years, and mean RA duration (± SEM) was 7.9±0.21 years. Mean age of patients in diprospan group was 40.9±1.07 years, and mean RA duration was 8.0±0.33 years. Significant decreases of XO activity and increase of XDG activity were observed in lysed red blood cells of RA patients just after the injection of each glucocorticoid drug. Changes of the enzymatic activities in lysed red blood cells were more pronounced in methylprednisolone group. However enzymatic activity did not reach the level of healthy controls. As described previously, decreased XO activity and increased XDG activity were observed in plasma of RA patients just after the injection of the average therapeutic doses of glucocorticoids, as well as in lysed lymphocytes just after the injection of methylprednisolone [4].Conclusion:Treatment with methylprednisolone and betamethasone can affect the balance of XO/XDG activity and increase the antioxidant potential of the blood. This effect can exert beneficial influence on autoimmune inflammation in RA.References:[1]Mateen S., et al. Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS ONE 2016;11(4):e0152925.[2]Çimen M.Y., et al. Oxidant/antioxidant status of the erythrocytes from patients with rheumatoid arthritis. Clin Rheumatol 2000;19(4):275-277.[3]Zborovskaya I.A., et al. Influence of analgetics on plasma and lymphocytic activity of the purine metabolism enzymes in rheumatoid arthritis patients. Russian Journal of Pain 2018;3:47.[4]Mozgovaya E.E., et al. Xanthinoxidase and xanthine dehydrogenase activities in rheumatoid arthritis after glucocorticoid treatment. Osteoporosis International 2019;30(2):S433-434.Disclosure of Interests:None declared

Background:Cardiovascular disease in rheumatoid arthritis (RA) is more common than in general population. Particular attention should be paid to cardiac dysfunction, as their timely diagnosis strongly affects the general outcome.Objectives:To assess the prevalence of arrhythmias and conduction disorders in patients with seropositive RA without clinical manifestations of coronary artery disease, as well as to determine their relationship with activity and duration of RA.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 48 patients with seropositive RA were included in the study. The exclusion criteria were: age over 60 years; obesity; congenital heart defects; coronary artery disease; peripheral atherosclerosis; thyroid disease; diabetes mellitus. All patients were assessed using general physical, laboratory and instrumental survey including CBC, blood chemistry panel, as well as ECG. RA diagnosis was verified using the 2010 ACR / EULAR classification criteria. Central tendencies were expressed as mean ±SD.Results:All the included persons were women. Their average age was 50.50 ± 7.22 years, and average duration of the disease was 8.13 ± 2.34 years. All patients had articular form (without systemic manifestations) of moderate and high activity. The patients were treated with basic and NSAIDs therapy; no glucocorticoids were applied at the time of the examination. Using 12-lead ECG arrhythmias and conduction disorders were revealed in 27 (56.25%) of RA patients. Sinus rhythm deviations had the highest (31.25%) prevalence for all arrhythmias, comprising sinus tachycardias (18.75%), sinus bradycardias (6.25%), and sinus arrhythmias (6.25%). Premature beats were registered in 12.5% cases, being supraventricular and ventricular ones in equal proportions. We have found left anterior bundle branch block in 6 (12.5%) of patients. Despite absence of any angina symptoms, 9 (18.75%) of patients had myocardial repolarization disturbances, either as ST depression deeper than 0.1 mV or as negative T wave appearance, which were quite similar to silent myocardial ischemia manifestations. All the patients with these two features had RA history of more than 10 years. There was no relationship between the prevalence of the manifestations and radiographic stage of RA.Conclusion:Arrhythmias and conduction disorders are quite frequent finding in seropositive RA (56.25% and 18.75%, respectively). Their incidence and severity do not coincide exactly with the radiographic progression in joints, while their prevalence generally increases with disease duration.These data highlight the importance of additional Holter ECG monitoring in RA for revelation and treatment of silent life-threatening cardiovascular complications.Disclosure of Interests:None declared

Background:The oxidative-related enzymes are involved in the pathogenesis of various stages of systemic sclerosis (SSc). SSc is a chronic autoimmune disorder that is intimately associated with vascular damage and therefore with chronic perfusion/reperfusion and oxidative organ injury. Mesenchymal cell activation in SSc is now also considered to be mediated primarily through oxidative burst. Regulation of oxidative stress by specific enzymes including several purine metabolism enzymes is likely to play an important role in SSc progression.Objectives:to characterize interrelationships among circulating xanthine oxidase (XO), xanthine dehydrogenase (XDH), superoxide dismutase (SOD) activities and SSc activity.Methods:The study was performed according to bioethical standards. 51 patients with verified SSc and 30 healthy controls were included in the study. The diagnosis was verified according to ACR/EULAR 2013 criteria. We assessed SSc activity in compliance with the original activity scale that is commonly used in Russia [Guseva N.G., 1993] and by the 2001 European Scleroderma Study Group Activity Index. XO (EC 1.17.3.2), XDH (EC 1.17.1.4), and SOD (EC 1.15.1.1) plasma activities were measured using spectrophotometric techniques as previously described [Dubinina E.E., 1986; Karpova O.V., 2006]. Results are expressed as mean±SD. The Mann-Whitney U test and Spearman’s correlation coefficient were used for statistical analysis.Results:Mean age of patients was 42.8±1.3 years, mean SSc duration was 7.9±0.7 years. Mean enzymatic activities in normal controls were 3.43±0.56 nmol/ml min (for XO), 5.19±0.71 nmol/ml min (for XDH), and 5.40±1.03 units (for SOD). The respective enzymatic activities in SSc group were 3.91±0.62 nmol/ml min, 7.10±0.71 nmol/ml min, and 7.10±2.19 units. All these mean activities were significantly higher in SSc patients comparing to healthy individuals (p<0.001). XO and XDH activities positively correlated with SSc activity (r=0.499, p<0.001, and r=0.741, p<0.001, respectively). The opposite but weaker trend was observed for SOD activity and SSc disease activity (r=-0.190, p=0.188).Conclusion:SSc is characterized by an increase in the intensity of oxidative and antioxidant processes, more pronounced in high disease activity. A close relationship between function of prooxidant/antioxidant enzymes and some of the key SSc pathogenetic mechanisms, especially vascular disease and fibroblast activation, is widely considered. Overall increase of oxidative stress in patients with higher disease activity, as well as depletion of antioxidant capacity can be also linked with disturbance of purine metabolism through XO and XDH modulation. Pathogenetic influence of this imbalance can also be mediated through initial phase of neutrophil extracellular traps (NETs) formation, an eventual source of nucleoprotein containing autoepitopes.Disclosure of Interests:None declared

Background:Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anticitrulline autoantibodies. Recent evidences suggest that impairment of neutrophil extracellular traps (NETs) could exert substantial influence on RA pathogenesis. The production of NETs depends heavily on the ROS generation. One of its mechanisms is xanthine oxidoreductase (XOR) mediated degradation of purine metabolites. Analysis of pro-oxidant activity of the enzymatic complex XOR and its constituents, xanthine oxidase (XO) and xanthine dehydrogenase (XDG), is an issue of considerable interest in this context.Objectives:Evaluation of XO and XDG activities in RF-positive and RF-negative RA using both plasma and lysed lymphocyte samples.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. Diagnosis of RA had been verified using ACR/EULAR 2010 criteria. Enzymatic activities in plasma and lymphocytes were measured spectrophotometrically and expressed as nmol/min/ml. Enzymatic activities in lymphocytes were also normalized to 1×107 cells/ml. Statististical tests were selected in line with common guidelines. Differences were considered significant when p<0.05. Reference ranges were calculated as means ±2SD.Results:75 adult RA patients (52 females and 23 males, mean age 43.9±0.97 years, mean disease duration 8.5±0.3 years) from the rheumatology unit of Volgograd Clinical Emergency Hospital #25 as well as 35 healthy controls were included in the study. RF-positive RA and RF-negative RA were observed in 49 (65.3%) and 26 (34.7%) patients, respectively. Reference ranges for plasma and lymphocyte XO activities were 2.60-3.96 and 14.2-27.8 nmol/min/ml, respectively. Similar ranges for XDG activities were 4.49-5.93 and 22.5-40.7 nmol/min/ml, respectively. Enzymatic profile of RA patients is characterized by significantly increased XO activity in plasma and decreased XO and XDG activities in lymphocytes (р<0.001). XO activity is increased (p<0.001), XDG activity is decreased (p<0.001) in blood plasma of patients with RF-negative RA, while the activity of both enzymes is decreased in lymphocytes (p<0.001). XO activity (p<0.001) and XDG activity (p<0.05) is increased in blood plasma, XO activity and XDG activity are decreased (p<0.001) in lymphocytes of patients with RF-positive RA. Plasma XO and XDG activities are also higher, and lymphocyte XO and XDG activities are lower in patients with RF-positive RA than in patients with RF-negative RA (р<0.001).Conclusion:Our study revealed the relationship between enzyme parameters and rheumatoid factor presence. More pronounced changes in the enzyme activities were observed in patients with RF-positive RA. These results demonstrate that activation of the xanthine oxidase/xanthine dehydrogenase enzyme complex is an substantial factor of induction and continuation of the autoimmune rheumatoid inflammation.Disclosure of Interests:None declared

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