Vol 19, No 1 (2021)

Little is known about the etiology of neuropsychiatric disorders. Glutamate-mediated excitotoxicity is one of the main pathological mechanisms occurring in various types of acute and chronic diseases of the central nervous system. Glutamate is the major excitatory neurotransmitter in the central nervous system. Recently, it has become evident that not only glutamate excess can cause massive brain damage. Several types of anti-glutamate receptor antibodies were found in serum and cerebrospinal fluid of patients with various mental and neuroinflammatory disorders. These antibodies can lead to the death of neurons and impaired neuronal function inducing various pathological mechanisms in the central nervous system. The discovery of autoantibodies binding to NMDA receptors and causing neurological and psychiatric symptoms has led to the hypothesis that autoimmune mechanisms may underlie some cases of mental disorders. This paper reviews the pathological mechanisms of antibodies against NMDA receptors based on the disorder defined as anti-NMDA receptor encephalitis. Anti-NMDA receptor encephalitis is a synaptic autoimmune disorder in which IgG autoantibodies against the NR1 subunit of the NMDA receptors occur and trigger pathological processes, manifesting with psychiatric symptoms in particular. The research in other mental and neuroinflammatory disorders also showed the presence of anti-NMDAR antibodies in a small part of patients. But the role of antibodies against the NMDA receptors in the development of psychotic symptoms is not fully understood and requires further research. Studies in this area are extremely promising, opening up new opportunities for understanding the pathogenesis of this group of disorders and developing new diagnostic and therapeutic approaches.

Sarcopenia is a progressive and generalized pathology of skeletal muscles of multi-factor nature. The present review focuses on the analysis of molecular genetic markers that may contribute both to sarcopenia risk formation and the variability of diagnostically relevant signs for a given disease. According to GWAS, polymorphic variants of369genes are associated with such a diagnostically significant sign for sarcopenia as “muscle mass”. According to information provided in the database «DisGeNet» on sarcopenia-associated genes, and in «Gene Ontology» on genes involved in regulation of muscle atrophy (GO:0014737, GO:0014732, GO:0014736) and muscle regeneration (GO:0014839), 69 genes can be considered as candidate sarcopenia genes. Genes associated with muscle mass and candidate genes for sarcopenia have pleiotropic properties, are involved in the regulation of a wide range of biological processes (including the metabolism of hormones, carbohydrates, lipids, proteins; response to stimuli (sex hormones, nutrients), in the regulation of gene expression , protein/serine kinase activity and MAPK signaling pathway); these genes are associated with multi-factorial diseases that are comorbid with sarcopenia; sensitive or determine the response to drugs, hormones, nutrienes (including creatine, corticosteroids, aldosterone, aldosterone antagonists, metformin, protein. Differences are recorded between healthy individuals and sarcopenia sufferers in the level of DNA methylation and in the level of gene expression (including in muscles), the products of which are involved in metabolic pathways significant for maintaining homeostasis in muscles. The methylation pattern and the level of gene expression is influenced by a wide range of factors, including the age of individuals, their hormonal background, the level of physical activity and the type of physical exercise, the consumption of nutrients. Thus, by now, a wide range of molecular genetic markers have been identified at the genomic, epigenome, and transcriptomic levels, which, along with traditional risk factors (and in interaction with them), can contribute to the risk of developing sarcopenia.

Introduction. The therapeutic effect of orotic acid (OA) is limited by the low absorption of the drug from the gACTrointestinal tract, which can be overcome when the drug is processed by mechanical activation. The aim of the study is a comparative experimental research of the action of mechano-modified orotic acid in the conditions of hepatopathy caused by hyperhomocysteinemia. Methods. Preparations of orotic acid were administered in the initial form (IOA) and after mechanical activation (MOA) to white outbred rats with hyperhomocysteinemia. The blood was examined for liver enzymes, bilirubin, cytological blood analysis was performed. Histological research included calculation of density of cell location, the area of the functional parenchyma, the nuclear apparatus, the microvascular bed (100 μm2). Results. The use of MOA shows the more pronounced reduction of АЛТ - by 1.5 times; AP - 1.2 times; total bilirubin - 1.2 times (p<0.05), WBC - by 36.06%, PLT - by 11.4%. The administration of MOA increases the level of red blood cells and hemoglobin. Histological research shows MOA to provide a more pronounced positive effect on the total area of the functional parenchyma (higher than in IOA by 23.2%), the number of nuclei and the total area accounted for by the nuclear apparatus of hepatocytes (higher than in IOA by 1.44 times higher). Conclusion. The mechano-modified preparation of orotic acid has many advantages in comparison with the original analog, which allows us to offer its clinical testing as a therapeutic agent for various types of toxic liver damage.

Introduction. Timely diagnosis and a personalized approach to the treatment of diseases is accepted to be one of the most important modern tasks in medicine and in particular, dentistry. The use of pharmaceuticals for the diagnosis and treatment of various diseases is the basis of a new method - theranostics. Biological tissues have a complex multi-component structure; therefore, the diffusion of substances in them is non-linear. The quantitative determination of the permeability of biological membranes for marker agents is an urgent task of medical biophysics. Purpose of the study. In this work, the permeability of the attached pig gingiva is determined concerning an aqueous solution of a thiazine dye, widely used in dentistry - Methylene Blue (MB). Methods. The determination of permeability is based on the calculation of the effective diffusion coefficient of MB into the gingiva tissue in the wavelength range from 200 to 800 nm using diffuse reflection spectroscopy. Using the second Fick law and the Bouguer-Lambert-Beer law, there was obtained an equation to relate the kinetics of the change in effective optical density and the diffusion coefficient of the preparation into biological tissue. Results. For the first time, the permeability of the tissue of the attached pig gingiva was determined for an aqueous MB solution, which was р=(9.91+1.36)-101 cm2/s, the effective diffusion coefficient was D=(4.56±0.72)-1D~7 cm2/s (n=4) with a thickness of the samples of the gingival mucosa l=0.46±0.09 cm. Conclusion. The results obtained in the work correlate with published data for other biological tissues and can be used in clinical treatment protocols using MB. Since this dye has photosensitizing properties, the results must be taken into account when conducting photodynamic therapy sessions, during both light therapy and diagnostic procedures with the use MB as a marker for pathological areas of the oral mucosa.