Results of studying the effect of a calcium modifier of 10KhSND low-alloy steel on its physicomechanical characteristics are presented. The rolled sheets of commercially produced shipbuilding steel, ...wherein before teeming during melting a ferroalumocalcium alloy was added, were used for investigation. The corrosion rate of examined steel in a model aggressive medium, as well as its fatigue resistance in salt water in torsion, axial loading, and bending tests against the calcium concentration, was elucidated. The effect of calcium concentrations on the austenite grain sizes and dispersity of nonmetallic inclusions, as well as the fracture toughness characteristics (critical stress intensity factor and crack opening) at different temperatures was examined. The microstructure of fracture facets of shipbuilding steel specimens of long-term service on brittle fracture along pearlite grains and ductile fracture along ferrite ones for as-received steel was revealed. Nonmetallic inclusions in specimen fractures of shipbuilding steel at different calcium concentrations were studied. Their quantity grows considerably with its service terms, which exerts negative influence on the corrosion and mechanical properties of the metal. The calcium alloying of steel is shown to contribute to its corrosion resistance and fracture toughness on long-term service in seawater. The recommendations are given as regards optimal modifier concentrations in the shipbuilding metal, which is consistent with minimum austenite grain sizes and dispersity of nonmetallic inclusions.
It was established that with increased concentrations of chlorides, sulfate-reducing bacteria, heterotrophic bacteria, thionic and iron bacteria the corrosion rate of the studied specimens of ...reinforcing steels sharply increases. The 40KhN and 09G2S steels had the highest resistance to corrosion, and the St.20 steel had the lowest resistance. The obtained data correlate with the results of numerical experiments reported in the publications of domestic and foreign researchers. For the first time, the data obtained from a series of experimental tests of reinforcing steels for cyclic strength showed that the steels characterized by low corrosion resistance also have a low resistance to cyclic strength, which can be explained by their degradation. The authors believe that, in the process of long-term operation of reinforced concrete structures in an aggressive environment, carbonization and chloritization of concrete, that is, its destruction occur. Further hydrogen charging of reinforced concrete causes embrittlement and reduction of the visco-plastic properties of the reinforcement, which in turn leads to the destruction of metal. The obtained results make it possible to develop metallurgical and technological measures to increase the durability of reinforced concrete structures: the use of chromium, nickel, and manganese alloyed steels for the manufacture of reinforcement with subsequent proper heat treatment; the use of modern high-strength concrete, which will ensure strong adhesion of concrete mortar to the surface of reinforcing bars.
A mechanophysical model for crack growth kinetics computation on stress corrosion fracture of modified 06G2BA and 08KhMCHA pipe steels is adequately expressed through the plane stress-strain state
dα
.../
dt
and
dJ
/
dt
ratios that are dependent on the strain crack tip rate. The crack growth accelerated by an aggressive environment occurs under static and cyclic loading due to transient dissolution and repassivation processes at the crack tip. Such accelerations are divided into three categories, determined by the strain rate: mechanical cracking (fatigue crack and stationary plastic crack), corrosion-accelerated mechanical cracking (corrosion fatigue and corrosion-accelerated plastic crack), and sulfide stress corrosion fracture. Metallographic studies revealed the change in the crack nucleation and propagation mechanisms, from transcrystalline to intercrystalline, related to the viscoplastic and brittle structure of steel specimens cyclically loaded and simultaneously affected by a corrosive environment.
The results of the experimental study of the degradation of steel structures of sewer underground constructions are presented. The distribution of harmful gas elements (sulfur, hydrogen, oxygen) over ...the wall thickness of sewer pipes along corrosion defects in the form of pits, as well as the character of changes in the microhardness of the metal depending on the hydrogen content and service life, are shown. To confirm the metal softening with increasing hydrogen concentration, the stresses of the crystal lattice (distortion stresses) were measured.
Fractogram analysis shows that deep scratches, particles of titanium and chromium carbides and other elements were found on the friction surfaces. Moreover, in the braking devices there was damage to ...the large size of the brake pads of trucks. The transfer of particles of borides and carbides to the surface of the wheels can be explained by the processes of metal flooding with their subsequent embrittlement, which inevitably leads, as a rule, to the destruction of friction wheel pairs. It is established that such types of wear as fretting corrosion significantly (by 1.5-2 times) reduce the fatigue limit of parts. Also significantly reduce the cyclic strength of metal friction pairs oxide films on their surface in the absence of lubricant. The service life of friction wheel pairs has a particularly strong impact on fatigue strength. The main reason for the decrease in endurance due to the processes of setting on the working surfaces of friction units is a high concentration of stresses caused by deep tears, cuts, microcracks. The process of destruction of brake pads from fatigue begins from the surface of the part. In this regard, the quality of the surface, its structural-phase composition, physical and mechanical properties of the surface layer in most cases are decisive for the intensity of the development of wear processes of parts from fatigue of the tribosystem (friction wheel pairs), which are operated under cyclic loads. The peculiarity of the influence of friction and wear processes on the fatigue strength of metal is that at the time of running-in there is a change in surface roughness, structure and properties of surface layers. As the analysis of literature sources has shown, the effectiveness of the influence of friction and wear processes on the characteristics of fatigue resistance in the case of repeatedly alternating (cyclic) loads is essential, and therefore ignoring this effect during the traditional assessment of the reliability of parts by individual criteria, for example, wear resistance, often leads to an incorrect assessment of the operational durability of the elements of the tribological system of road or rail transport. The long-term (cyclic) strength of brake pads was determined on a specialized unit model 1251 by Instron company (Great Britain). The basis for spraying and surfacing of different types of coatings was normalized steel 35. Tensile-compressive deformations at zero average stress and a cycle frequency of 20 Hz were studied on the laboratory unit. Most of the tests were carried out in salt solutions (NaCℓ of industrial purity was used).The process of destruction of brake pads from fatigue begins with the surface of the part. In this regard, the quality of the surface, its structural-phase composition, physical and mechanical properties of the surface layer in most cases are decisive for the intensity of the development of wear processes of parts from fatigue of the tribosystem (friction wheel pairs), which are operated under cyclic loads. Endurance limits in the case of simultaneous exposure to friction forces and cyclic loads will depend on the sliding speed of the tangent surfaces of the normal contact load, which determines the friction force, and the composition of the environment.
The review describes the history of development of organic chemistry in higher schools of Russia over a period of 170 years, since the emergence of organic chemistry in our country till now.
Modern approaches to the treatment of type 2 diabetes mellitus (T2DM) are aimed not only at glycemic control, but also at reducing cardiovascular risks. The increasing prevalence of the disease and ...the need for effective treatment options highlight the importance of glucagon-like peptide-1 (GLP-1) receptor agonists in the pharmacotherapy structure.
The aim
of the work was to review the literature regarding the physiology of GLP-1 and the therapeutic potential and development trends of its agonists.
Materials and methods.
The search for the review materials was carried out using the abstract databases of PubMed, Google Scholar and e-Library. The search was carried out for publications from 2000 to 2023, using the following keywords: “GLP-1”; “GLP-1R agonists”; “GIP”; “exenatide”; “liraglutide”; “dulaglutide”; “semaglutide”; “lixisenatide”; “albiglutide”; “taspoglutide” taking into account various spellings.
Results.
The interaction of almost all food components with enteroendocrine cells of the intestine leads to the secretion of incretins (primarily GLP-1) into the blood, triggering a complex of physiological reactions aimed primarily at the rapid utilization of incoming glucose (regulation of insulin and glucagon secretion), as well as the central regulation of dietary behavior (slowing gastric emptying and the formation of a feeling of satiety). A wide distribution of the GLP-1 receptor in various tissues and organs, its connection with intracellular signaling cascades aimed at launching energy-consuming remodeling (recovery) processes in endothelial cells, heart, neurons, beta cells, etc., is the basis for a wide range of pleiotropic effects of GLP-1 unrelated to its hypoglycemic effect. The discovery of synthetic GLP-1 receptor agonists with a long period of action has made it possible not only to therapeutically influence various parts of carbohydrate metabolism disorders, but also to increase the functional reserves of the target diabetes organs, reducing the risk of developing complications of the disease. Incretin-like drugs are well tolerated, with nausea being the most common side effect. The factors limiting a wider use of the drugs include their high cost and the preferred form of a subcutaneous solution. The current research is focused on the development of long-acting, oral, dual and triple agonists, fixed-dose combinations, and small molecule drugs.
Conclusion.
GLP-1 receptor agonists are a class of effective and safe drugs for the treatment of diabetes and obesity, which is rapidly developing in the most advanced areas of pharmacy. A further development of this group and the solution of the identified problems will open up new opportunities for the treatment of diabetes and its complications.
The aim
of the work was to conduct an analysis of the current state and current trends in the approval of drugs, as well as some aspects of the methodology for their development based on biological ...molecules and registration.
Materials and methods.
The material for the analysis was taken from the abstract databases of PubMed, Google Scholar and e-library.ru. The search was carried out using publications for the period from 2008 to 2023, the keywords were as follows: “biologicals”, “new drug approval”, “drug authorization”, “drug development”, “biosimilar”, taking into account various spellings.
Results.
Over the past 15 years, scientists have been observing revolutionary trends and processes in the field of the drug development, especially biopharmaceuticals. Significant advances have been made in gene, immune and cell therapies, resulting in the approval of such drugs more than doubling over the past ten years. The development of biological drugs includes the identification and testing of molecular targets and requires a deep understanding of the structure and functioning of the polypeptides involved in the development of the effect. The features of these active pharmaceutical substances are a high molecular weight, a complex three-dimensional structure and a high immunogenic potential. Preclinical and clinical studies of biologics have unique challenges. Selecting appropriate animal species, understanding the immunogenicity, and assessing pharmacodynamics and toxicological properties require a multilevel, detailed approach. The article discusses the regulatory framework under which these drugs are registered, summarizing the guidelines provided by international organizations such as the International Council for Harmonization and various national agencies.
Conclusion.
The analysis highlights the current advances and prospects in the development of biologics, highlighting their key role in future transformations in the treatment of rare diseases and oncology, approaching the era of personalized medicine. Monitoring the development directions and technological approaches, as well as the commitment to global methodological and regulatory aspects can become a catalyst in the development of the Russian pharmacology.
Objective
: to study the pathomorphological changes in the vessels of the lungs at different times of death in patients with COVID-19.
Material and methods
: autopsy protocols of 40 deaths from ...COVID-19 with histological, histochemical examination, and photoregistration. To determine the degree of pulmonary vascular lesions, the authors developed and applied a semi-quantitative assessment scale for the sign based on counting the affected lung vessels in 10 fields of view, expressed as a percentage: no sign – (0%), weak sign + (1-25%), moderate sign ++ (26-50%), expressed sign +++ (51-75%), highly expressed sign +++ (76-100%).
Results
: during the first 14 days of the disease, stasis and swelling of individual endotheliocytes were noted in the vessels of the microvasculature. After 15-21 days of the development of COVID-19, signs of alterations in endothelial cells and microthrombosis were observed in microvessels. After 22-28 days of the disease, the phenomena of repair and hyperplasia of endothelial cells were detected. At different times of the development of the disease in the lung tissue, the phenomena of acute respiratory distress syndrome, interstitial pneumonia, and focal pneumofibrosis were observed.
Conclusions
: the authors believe that COVID-19 is associated with a progressive microvascular endotheliopathy in the lungs which is characterized by swelling, alteration, and later, by hyperplasia, and regeneration of endothelial cells in combination with microthrombosis. Destructive changes in the walls of the microvessels of the lungs have superficial character without the destruction of the reticular frame and basal membranes. Endotheliopathy, microthrombus formation of microvessels of the lungs, and interstitial pneumonia create a vicious circle of severe respiratory failure, which must be taken into account in the clinic to correct the treatment of patients with COVID-19.
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