Rheumatoid arthritis (RA) that is a brilliant representative of the large family of autoimmune diseases remains to be, by and large, a disease that is far from being adequately investigated. This concerns the etiology and pathogenesis of the disease and effective approaches to its treatment. The review gives the data available in the literature on the role of epigenomic mechanisms regulating the functioning of genes in both immunocompetent cells and synovial fibroblasts, the major targets of autoimmune cells. The presence of a few sources of hypomethylated DNA in RA patients suggests that these molecules make a considerable contribution to the pathogenesis of the disease. Furthermore, the found hypermethylation of certain genes, besides the pathogenetic value of this phenomenon, may be used to develop new approaches to treating RA, which are based on the demethylation processes of these genes.

Objective: to study the time course of changes in laboratory biomarkers in patients with rheumatoid arthritis (RA) 2, 4, and 8 weeks after the initiation of tocilizumab (TCZ) therapy.
Subjects and methods. Forty-two RA patients receiving two intravenous infusions of TCZ (8 mg/kg each) at a 4-week interval during steady-state therapy with disease-modifying anti-inflammatory agents and glucocorticoids were examined. At week 8 of therapy, there were good and moderate effects in 21 and 20 patients, respectively, according to the EULAR criteria; no effect was found in 1 patient. Erythrocyte sedimentation rate (ESR) was determined by the Westergren method; the serum levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) were measured by the nephelometric method; anti-cyclic citrullinated peptide antibodies (ACCPA) were estimated by an ummunoluminescence assay. Serum interleukin (IL) 6 concentrations were measured by multiplex analysis; IgA RF, anti-modified citrullinated vimentin (anti-MCV) antibodies, and soluble IL-6 receptors (sIL-6R) were determined by enzyme immunoassay. Results. The patients who showed a response to TCZ therapy had the basal values: Me (RI 25-75 percentile) was 42 (30-70) mm/hr for ESR, 35.2 (19.2-62.7) mg/l for CRP, 263.0 (95.3-663.0) IU/ml for IgM RF, 347.0 (131.2-789.0) IU/ml for IgA RF, 378.8 (85.8-500.0) IU/ml for ACCPA, 778.6 (190.7-2393.1) IU/ml for anti-MCV, 182.2 (106.1-462.3) pg/ml for IL-6, and 267.2 (212.5-310.0) ng/ml for sIL-6R. At TCZ therapy week 2, there were reductions in ESR [12 (6-18) mm/hr], CRP [0.5(0.3-0.9) mg/l], IgM RF [174.0 (40.8-513.0) IU/ml], and IgA RF [227.2 (62.1-570.8) IU/ml]; at week 4, anti-MCV titers were 313.5 (79.9-960.3) IU/ml, which remained until week 8 (p < 0.01). IL-6 concentrations were increased at week 2 and reduced at week 8; these were 418.4 (287.0-678.3) and 103.4 (39.1-208.5) pg/ml, respectively (p < 0.01). The elevated sIL-6R level of 1250.0 (1250.0-1475.0) ng/ml was recorded at weeks 2 to 8 of TCZ use (p < 0.01).
Conclusion. The interim analysis of the efficacy of two TCZ infusions 2, 4, and 8 weeks after the initiation of the therapy suggests that TCZ is able to induce steady-state positive changes in immune-inflammatory markers very rapidly in patients with RA

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular medications to relieve the symptoms of rheumatoid arthritis (RA). However, NSAIDs can cause serious gastrointestinal, cardiovascular, and renal complications. To take into account risk factors and to use safer NSAIDs and gastroprotectors allow the frequency of gastrointestinal tract (GIT) complications to be reduced. These preventive methods have been extensively used in recent years.
Objective: to estimate the time course of changes in the incidence of upper GIT pathology in patients with RA in 1995-1996 and 2008-2009 and to identify the factors influencing these changes.
Subjects and methods. The results of endocopic studies were analyzed in all RA patients aged over 18 years, who had been admitted to the Clinic of the Research Institute of Rheumatology, Russian Academy of Medical Sciences, and undergone this procedure in 1995-1996 (n = 984; Group 1) and in 2008-2009 (n = 1018; Group 2). In Groups 1 and 2, the patients' gender and age did not differ: women were 90.3 and 89.0% and the mean age was 48.2±15.6 and 44.1±16.3 years, respectively. NSAIDs were taken by all the patients in Group 1 and most (81.9%) of those in Group 2. In the 1990s, all the patients used nonselective NSAIDs; following 12 years, 61.4% received selective NSAIDs. Significantly more patients in Group 2 took glucocorticoids (37.6 and 52.6%) and cytotoxic agents (21.3 and 56.5%) (p < 0.001). Many patients had risk factors: an ulcer history in 18.7 and 20.9%, age over 65 years in 13.8% and 12.0%, respectively; in Group 2, 6.3% of the patients took low-dose aspirin (unknown percent in Group 1). In Group 2, 8.7% of the patients used proton pump inhibitors (PPIs). In the 1990s, the latter were not used to prevent NSAID gastropathy yet.
Results. Endoscopic ulcers were found 2.5 times more frequently in Group 1 than in Group 2: 15.3 and 6.5%, respectively (p < 0.001). This pathology was detected more often in the presence of risk factors. For example, among Group 1 and 2 patients having an ulcer history, ulcers were identified in 33.2 and 12.7%; among the subjects over 65 years of age, these were in 20.5 and 9.7%, respectively. In Group 2 patients who had received aspirin, ulcers occurred 1.5 times more frequently than those in the whole group (9.7%). In all cases, the difference was statistically significant (p < 0.05). Erosive esophagitis was detected only in a small number of patients with RA. It was observed only in 4 (0.4%) and 21 (2.1%) patients in Group 1 and 2, respectively (p = 0.038).
Discussion. The rate of NSAID gastropathy in RA declined. This resulted from more active disease-modifying therapy that permitted a reduction in the need for NSAIDs, from the use of safer NSAIDs, such as aceclofenac, meloxicam, nimesulide, and coxibs, and from that of PPIs. At the same time, there was an increase in the frequency of esophageal complications. This trend requires further investigation.

Objective: to evaluate upper gastrointestinal (GI) motor disorders in diclofenac sodium-treated patients with rheumatoid arthritis (RA), by using 24-hour pH-metry, and their association with the clinical manifestations of gastropathy induced by nonsteroidal anti-inflammatory
drugs (NSAIDs) (NSAID gastropathy).
Subjects and methods. A study group included 39 patients diagnosed as having RA, 14 subjects formed a control group. All the included subjects underwent a clinical examination, endoscopic studies of the esophagus, stomach, and duodenum, and 24-hour gastric and esophageal pH monitoring (Gastroscan-24, Istok-Sistema Research-and-Production Association, Fryazino, Moscow Region). Results and discussion. Comparing the results of 24-hour intraesophageal and intragastric pH studies in RA patients and healthy individuals revealed differences in nocturnal acidity values. The RA group showed lower nocturnal pH values than the controls (p < 0.05). The obtained pH values may indirectly suggest that the RA patients have duodenogastroesophageal reflux. Analysis of 24-hour pH metric readings indicated the concurrence of gastroesophageal and duodenogastric refluxes in 37%. It is in this group that displayed a clinical decussation of pain and dyspeptic syndromes (p < 0.05).
Conclusion. The upper GI motor disorders found in the RA patients taking NSAIDs may play an important role in the development of clinical manifestations of NSAID gastropathy and, probably, a certain group of patients must undergo medical correction of the symptoms related to dysmotility.

Objective: to study the time course of changes in the cytokine profile, the parameters of lipid peroxidation (LPO), antioxidant defense, and lipid spectrum during Arthra therapy in patients with primary osteoarthritis (POA).
Subjects and methods. The study was conducted in 26 POA patients (aged 39.5+5.4 years) with knee and hip joint lesions in the absence of synovitis. The efficiency of treatment was evaluated by pain intensity and WOMAC index. The levels of proinflammatory cytokines, lipids, LPO primary and intermediate products, and antioxidant defense were compared in patients with PAO prior to and 12 and 24 weeks after Arthra therapy.
Results. Positive changes in articular manifestations were determined after 24 weeks of therapy, by using the WOMAC scale. The mean concentration of C-reactive protein (CRP) was halved in the patients 24 weeks following the start of Arthra therapy. The blood levels of IL-1β, IL-6, IL-18, TNF-α decreased just after 12 weeks of therapy as compared to the baseline level and continued to decline by the end of the therapy. There were reductions in LPO primary and intermediate products in serum and red blood cells. There was activation of antiradical protection (increases in serum and red blood cell catalase activities and serum antioxidant activity and a decrease in the number of hemolyzed red blood cells). After a course of therapy, there were reduced blood concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with POA.
Conclusion. The POA patients treated with Arthra displayed improvements in LPO profile and antioxidant defense and lower blood concentrations of cholesterol and LDL cholesterol along with a decline in the levels of the blood cytokines IL-1β, IL-6, IL-18, TNF-α, and CRP.

Objective: to make the results of treatment for coxarthrosis better via prosthetic synovial fluid replacement, by improving drug delivery into the joint cavity.
Subjects and methods. The clinical trial enrolled 359 outpatients treated for coxarthrosis. A control group comprised 50 patients receiving the intraarticular combination drug Alflutop under ultrasound (US) guidance. A study group included 309 patients treated using a new three-stage procedure. At stage 1, the patients were given periarticular injections of the current enzyme preparation longidase with a hyaluronidase activity of 3000 IU. At stage 2, postisometric relaxation sessions were performed. At stage 3, after defining the optimal access, synovial fluid prosthetic devices were inserted into the joint cavity under US guidance (a total of 2-3 injections) once weekly. To evaluate the efficiency of the developed treatment option, the authors used a number of standard tests, WOMAC index, Leken's index, integral index of lower limb dysfunction, needs for nonsteroidal anti-inflammatory drugs; total treatment scores given by a physician and a patient; quality of life estimation using the SF-36 questionnaire.
Results. The developed treatment option could significantly reduce the clinical and functional WOMAC index and Leken's index, and inadequate joint function in the immediate period and a year after the treatment performed. It also considerably improved quality of life in patients with hip osteoarthrosis, which appeared as a significant increase of its rating according to eight SF-36 scales during more than a year.

Objective: to define the role and place of joint-sparing surgical interventions into the anterior foot in patients with rheumatoid arthritis
(RA).
Subject and methods. Eighty-six patients, the majority (n = 84) of young and middle-aged women, mainly with minimal disease activity, late-stage RA, and moderate limitation of functional capacity were examined and treated. One hundred and thirty arthrodeses of the first metatarsophalangeal joint (MPJ), 80 resections of the heads of the second-to-fifth metatarsal bones, and 58 Weil osteotomies were performed. Results. The American Orthopaedic Foot and Ankle Society (AOFAS) scale was used to assess arthrodesis of the first MPJ and resection of the second-to-fifth metatarsal bones (n = 141).
This comparison shows higher scores for the operated limb in the postoperative period, but these changes cannot suggest the complete function of the feet operated on.
Arthrodesis of the first MPJ and Weil osteotomy of the second-to-the first metatarsal bones were assessed by the AOFAS scale (n = 141). While assessing this surgical technique versus the previous method, there was an increase in scores for the second-to-fifth toes to almost normal values, which is in favor of the practically complete function recovery in the feet operated on.
Conclusion. The Weil-osteotomy group showed the preservation and partial salvage of osteotomized heads, which promoted the recovery of swinging function of the foot. The new procedures made it possible to prevent recurrent valgus and hammer toe deformities and callus formation in the late postoperative period, to improve quality of life, and to reduce the time of rehabilitation and the length of hospital stay.

The paper gives the results of clinical and epidemiological studies conducted among adolescents in different years. It shows their more complaints about the state of the locomotor apparatus than their more polyclinic visits and presents data on the diagnosis of a specific rheumatic disease. Transfer of adolescents to be served at children's polyclinics has not improved the detection rates for locomotor system diseases. Attention is drawn to the fact that it is necessary to set up an independent rheumatology service at the children's polyclinics and it is expedient to return the adolescent service to the general practice network.