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The cytokine interleukin-6 is involved in the pathogenesis of rheumatoid arthritis. Olokizumab, a humanized monoclonal antibody targeting the interleukin-6 cytokine directly, is being tested for the treatment of rheumatoid arthritis.In a 24-week, phase 3, multicenter, placebo- and active-controlled trial, we randomly assigned (in a 2:2:2:1 ratio) patients with rheumatoid arthritis and an inadequate response to methotrexate to receive subcutaneous olokizumab at a dose of 64 mg every 2 or 4 weeks, adalimumab (40 mg every 2 weeks), or placebo; all patients continued methotrexate therapy. The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% fewer tender and swollen joints and ≥20% improvement in three of five other domains) at week 12, with each olokizumab dose tested for superiority to placebo. We also tested the noninferiority of each olokizumab dose to adalimumab with respect to the percentage of patients with an ACR20 response (noninferiority margin, -12 percentage points in the lower boundary of the 97.5% confidence interval for the difference between groups).A total of 464 patients were assigned to receive olokizumab every 2 weeks, 479 to receive olokizumab every 4 weeks, 462 to receive adalimumab, and 243 to receive placebo. An ACR20 response at week 12 occurred in 44.4% of the patients receiving placebo, in 70.3% receiving olokizumab every 2 weeks (difference vs. placebo, 25.9 percentage points; 97.5% confidence interval [CI], 17.1 to 34.1), in 71.4% receiving olokizumab every 4 weeks (difference vs. placebo, 27.0 percentage points; 97.5% CI, 18.3 to 35.2), and in 66.9% receiving adalimumab (difference vs. placebo, 22.5 percentage points; 95% CI, 14.8 to 29.8) (P0.001 for the superiority of each olokizumab dose to placebo). Both olokizumab doses were noninferior to adalimumab with respect to the percentage of patients with an ACR20 response at week 12 (difference, 3.4 percentage points [97.5% CI, -3.5 to 10.2] with olokizumab every 2 weeks and 4.5 percentage points [97.5% CI, -2.2 to 11.2] with olokizumab every 4 weeks). Adverse events, most commonly infections, occurred in approximately 70% of the patients who received olokizumab. Antibodies against olokizumab were detected in 3.8% of the patients receiving the drug every 2 weeks and in 5.1% of those receiving it every 4 weeks.In patients with rheumatoid arthritis who were receiving maintenance methotrexate, olokizumab was superior to placebo and noninferior to adalimumab in producing an ACR20 response at 12 weeks. Larger and longer trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis. (Supported by R-Pharm; CREDO2 ClinicalTrials.gov number, NCT02760407.).

The purine signaling system is represented by purine and pyrimidine nucleotides and nucleosides that exert their effects through the adenosine, P2X and P2Y receptor families. It is known that, under physiological conditions, P2 receptors play only a minor role in modulating the functions of cells and systems; however, their role significantly increases under some pathophysiological conditions, such as stress, ischemia or hypothermia, when they can play a dominant role as a signaling molecule. The diversity of P2 receptors and their wide distribution in the body make them very attractive as a target for the pharmacological action of drugs with a new mechanism of action. The review is devoted to the involvement of P2 signaling in the development of pathologies associated with a loss of muscle mass. The contribution of adenosine triphosphate (ATP) as a signal molecule in the pathogenesis of a number of muscular dystrophies (Duchenne, Becker and limb girdle muscular dystrophy 2B) is considered. To understand the processes involving the purinergic system, the role of the ATP and P2 receptors in several models associated with skeletal muscle degradation is also discussed.

The article provides information on the organization and functioning achievements of the Republican Arthrology Center (RAC), which has become the first specialized clinic in the Russian Soviet Federative Socialist Republic (RSFSR) that provided arthrological assistance to the population. The result of the organizational and methodological efforts of the RAC employees was the development of a network of rheumatology rooms in almost all territories of the country, along with the organization of the orthopedic rheumatology service and its separation from the cardiovascular rheumatology service. In the RAC, scientific developments were successfully carried out on the problems of arthroplasty of large joints, surgical and conservative treatment of patients with rheumatoid arthritis, osteoarthritis of large joints, prevention of contractures of the knee joint. Saratov Research Institute of Traumatology and Orthopedics (SRITO) hip joint endoprosthesis, a collapsible endoprosthesis and other constructions that have received wide recognition were created at the RAC. In the absence of international experience in creating an orthopedic rheumatology service network, the RAC was, on one hand, a pioneering phenomenon in world health care, and on the other hand, a natural consequence of the power vertical centralization in the USSR. At the same time, it should be emphasized that the need to create the RAC in the Russian Federation was caused by the growth in morbidity of rheumatic diseases, along with population aging and the prospects of orthopedic rheumatology associated, first of all, with the active introduction of total joint replacement with artificial structures in developed countries of the world. Over three decades of its existence, the RAC has been an organizational, methodological, medical, scientific and consulting center providing an orthopedic care to patients with diseases and injuries of large joints throughout the Russian Federation.

The article elucidates the establishment of Saratov orthopedic school, along with contributions of the most prominent Saratov scientists and practitioners in the field, Sergey Mirotvotsev, Leonid Deryabin, Alexander Eletsky and Alexey Demidov.

The paper proposes a method for determining the future needs of the market in helicopter technology. Its feature is the construction of a forecast for the quantitative values of helicopter supplies in a specific market segment based on the generated list of indicators and factors affecting demand. The method allows us to evaluate and determine the potential market share available in the future for the manufacturer, which is necessary to set the optimal performance of the production program and when planning production as a whole. The described method can also be applied to other complex high-tech products. Its flexibility allows for some adaptation in terms of clarifying the list of indicators and factors affecting the dynamics of market demand for specific products.

The research rationale is a significant increase in the need for energy resources and their irrational use. The world should follow the path of implementing the innovative energy concept. The basis of its long-term development is not only mining, production, and export of traditional energy carriers, but also their substantial rationalization based on the latest scientific achievements, which would ensure the development of a new energy system and provide energy consumption quality while maintaining the indigenous environment. The global future development vision of the world energy buildout should be based on the predicted changes in the economy and the consumer society, which form the demand for energy products and services, as well as on its defining requirements, setting its social and political development priorities. The possibilities of changing the global energy system (financial, organizational, and technological), which is forced to adapt to qualitatively new demands, cannot be overlooked as well. Even the most developed states’ efforts are not enough to solve this task in case if they are single forces. The whole world community should be concerned about this and mobilize resources for building the innovative energy future. An urgent task is the institutional regulation of energy conversion processes on an interstate scale, attracting the world scientific potential to solve its strategic development tasks, searching for new breakthrough energy sources and nonstandard technological solutions, developing the energy-saving culture among energy producers and consumers. This would allow to increase the various energy types production, reduce losses, work steadily, move to such a work with fair competition conditions in the free energy services market. The research purpose is to present a systemic, global vision of ways (a) to create a new model for the sustainable energy development, which would be based on a qualitative change in the energy potential; (b) to ensure sustainable development of territories, energy security, and energy digitalization; (c) to change the structure of energy sources; (d) to preserve the indigenous human environment and industry intellectual potential; (e) to ensure the competent use of alternative and small power energetics; (f) to form the technological and organizational base of innovative energy. The article materials can be practically used by power engineers and economists, politicians, state and municipal authorities, educational institutions, and all those interested in the issues of innovative energy development.

The aim of this study was to evaluate the effects of adenosine 5'-triphosphate (ATP) and adenosine on the contractility of mammalian skeletal muscle under hypothermic conditions.Contractions of isolated rat soleus muscle were induced by either electrical stimulation (ES) or carbachol at physiological temperatures (37°C) and hypothermic conditions (30-14°C) and recorded in the presence of ATP, adenosine, suramin, and 8-(p-sulfophenyl)-theophylline (8-SPT).At 37°C, incubation of the muscles with ATP inhibited ES-induced contractions; the inhibitory effect of ATP disappeared at 14°C. Adenosine inhibited ES-induced contractions at all temperature levels; 8-SPT fully prevented the action of adenosine. ATP and adenosine did not significantly affect carbachol-induced contractions at 37°C, while at lower temperatures ATP potentiated them. Suramin fully prevented effects of ATP.ATP is involved in both pre- and postsynaptic regulation of rat soleus muscle contractility, and these processes are significantly more pronounced at low temperatures. Muscle Nerve 55: 417-423, 2017.

Alzheimer's β-amyloid peptide (βAP) is known to possess a wide range of toxic effects on neurons in vitro and in vivo; however, there is little information available regarding its impact on other excitable tissues such as skeletal muscles, which, apart from brain cells, are thought to also be targets of βAP.Utilizing the combination of electrophysiology and myography, we investigated whether βAP also impairs the functioning of myocytes in frogs and mice.Although application of βAP in the range of 10(-6) to 10(-8) M induced depolarization of muscle fibers in both species, it impaired contractility in frogs but not in mice, by reducing endplate potential amplitude and increasing the threshold potential.Unchanged contractility in the mouse in the presence of βAP is due to a higher safety factor of neuromuscular transmission in mammals compared with amphibians. Possible clinical implications are discussed.

Skeletal muscles play key roles in the development of various pathologies, including bronchial asthma and several types of auto-immune disorders, e.g. polymyositis. Since most of these maladies have an immunological/allergic element, this paper is devoted to assessing the impact of immunobiological reorganization on the functional properties of isolated skeletal muscles in mice. A combination of two methods (myography and electrophysiology) was used to evaluate extensor digitorum longus (EDL) and diaphragmatic muscle (DM) in this regard. Conventional myographic technique showed that ovalbumin-induced sensitization (OS) produced different changes in the contractile properties of EDL and DM. The amplitudes of carbachol (CCh)-induced contractions increased in DM but decreased in EDL. Those changes were inversely related to OS-mediated changes of non-quantal acetylcholine (ACh) release intensity within the muscle endplate, as shown by the electrophysiologically measured H-effect. These results clearly show that OS-mediated changes of non-quantal ACh release alter the functional properties of postjunctional ACh receptors and therefore contribute to the disturbance of CCh-induced contractility of skeletal muscles. Other mechanisms of OS-mediated changes of skeletal muscle contractility are also proposed and discussed.