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Due to the rapid growth in the number of patients with diabetes in a complicated epidemiological picture, the question of the possibility of exposure of a substance to several targets becomes more important. It is noted that the most common infectious diseases in patients with diabetes mellitus are infections of the respiratory and urinary tract, skin and soft tissues, diabetic foot ulcers, otitis media and periodontal infections. Antimicrobial agents can have both direct and indirect hypoglycemic effects. Quinazolinones belonging to the group of heterocyclic derivatives exhibit a wide range of pharmacological activity. The use of the PASS program for the purpose of computer prediction of pharmacological activity showed a high probability of the hypoglycemic effect of new derivatives. The obtained results motivated the authors to search for the relationship between antimicrobial action and hypoglycemic effect within the general direction of studying the multi-targeting of drug ligands. Analysis of the literature data, as well as own studies of new quinazolinone derivative pharmacological activity make it possible to divide all ligands into functional groups that cause additional binding to the target molecule. The quinazolinone fragment, characterized by the uniqueness of its structure, can be reasonably attributed to multi-target ligands. The triazole cycle and the sulfonamide group can also purposefully bind to the target molecule. A carbamide residue, a fragment of sulfonylurea and an acetamide group, depending on the structure of the substance they are part of, can function both as a specific ligand and as a functional group involved in the stabilization of the intermediate transition state. The results obtained by the authors, as well as other researchers, allow us to formulate an assumption about the relationship between the mechanisms of antimicrobial and hyperglycemic activity.

Background. The current trend of growing antibiotic resistance among pathogenic microorganisms remains one of the urgent and significant problems of mankind. The constant spread of resistant strains of microorganisms requires the development of innovative methods and the search for medicinal compounds with a highly effective mechanism of action. One of these multi-resistant pathogens that are difficult to eradicate is the causative agent of tuberculosis — Mycobacterium tuberculosis. The aim is to study the effect of newly synthesized pyrimidine derivatives on the growth of Mycobacterium tuberculosis culture, as well as on the structural changes in cells.Material and methods. In order to assess the effect of a number of pyrimidine derivatives on the growth of Mycobacterium tuberculosis culture, 6 samples of 5-(arylmethylene) hexahydropyrimidine-2,4,6-triones (TAG1 — TAG6), 7 samples of 5-hetarylmethylidene-2,4,6-triones (TAG7 — TAG13), and 2 new samples of 3-(2-Benzyloxy-2-oxoethyl)quinazoline-4(3H)-one and 3-[2-(1-Naphthyl)-2-oxoethyl]quinazoline-4(3H)-one were screened under the laboratory ciphers VMA-13-03 and VMA-13-04 in the course of the study. M.tuberculosis H37RV strain was used as a test culture; it was provided by the bacteriological laboratory of the Regional Infectious Clinical Hospital named after A. M. Nichoga. A 4-week culture of M.tuberculosis, synchronized by cold (+4°C) for 72 hours, was used to prepare a suspension of mycobacteria. The number of mycobacteria in the suspension was determined using the McFarland 0.5 turbidity standard. 0.2 ml of M.tuberculosis working suspension was added to each tube of a series of successive dilutions of the studied substances, including the control. The study was carried out in 4 series of replicates. The minimum bactericidal concentration of the compounds, at which no colony growth was detected, as well as the minimum inhibitory concentration, at which mycobacterium growth was delayed by 50% compared to the control, were determined. Smears were prepared from the sediment for staining using theZiehl-Neelsen method to determine the presence of acid-resistant and non-acid-resistant forms of mycobacteria, as well as to study the effect of pyrimidines and a comparison drug on structural changes in M.tuberculosis cells.Results. In the course of the study, the TAG4, TAG6, and TAG8 compounds were found to have the closest antibacterial activity to the comparison drug isoniazid, according to the indicator of mycobacteria growth retardation. The greatest bactericidal activity against M.tuberculosis was observed in TAG4, TAG7, and VMA–13–04. The remaining compounds have shown minimal inhibitory effect on the growth of M.tuberculosis. Microscopic studies have shown that under the influence of TAG3, TAG4, TAG7, TAG12, VMA-13-03, and VMA-13-04, the main structural components of M.tuberculosis cells undergo fragmentation and morphological changes compared to mycobacterium cells without exposure.Conclusion. As a result, it was found that all the studied compounds possess antimycobacterial activity. Compounds under the laboratory ciphers TAG1, TAG4, TAG7, and TAG13 were comparable to isoniazid by the nature of the inhibitory effect on the growth of M.tuberculosis, and the TAG3 compound even slightly exceeded the effect of the comparison drug. Compounds under the laboratory codes VMA-13-03, and VMA-13-04 had the least pronounced anti-tuberculosis effect. Compounds under the laboratory codes TAG5, TAG6, TAG11, and TAG12 showed the least antimycobacterial activity.

Quinazolin-4(3H)-one derivatives exhibiting a wide spectrum of a pharmacological activity, represent a promising class of substances used to obtain antibacterial agents, which is especially important in the context of the emergence of pathogenic microorganisms’ resistance to drugs used in medicine. It has been proved that compounds having a naphthyl radical in the molecule, as well as an amide group bound to the benzene ring as quinazolinone substituents, are characterized by a pronounced antimicrobial activity against Staphylococcus aureus and Streptococcus pneumoniae.The aim of the research is a primary microbiological screening of the in vitro antimicrobial activity of new quinazolin-4(3H)-one derivatives against Staphylococcus aureus and Streptococcus pneumoniae, as well as the assessment of the relationship between the pharmacological effect and the structural transformation of the substance molecule, lipophilicity and the possibility of forming resistance to them.Materials and methods. The experimental studies have been carried out using well-known nosocomial pathogens of infectious and inflammatory diseases Staphylococcus aureus and Streptococcus pneumoniae by a serial dilution method.Results. A compound containing a naphthyl radical in its structure, which contributes to an increase in the hydrophobicity of the substance and its solubility in the membrane of a bacterial cell, has a bacteriostatic effect against both Staphylococcus aureus and Streptococcus pneumoniae. A similar pharmacological effect is exhibited by a derivative with an amide group as a substituent of the quinazolinone nucleus linked to a phenyl radical, which probably contributes to an increase in the degree of binding to active sites of enzymes involved in the DNA replication, and protein synthesis. Obviously, the increased lipophilicity, which promotes better binding to the efflux protein, cannot serve as objective characteristics of the emergence possibility of the pathogen’s resistance to this substance.Conclusion. Among the synthesized compounds, the leading substances that exhibit an antimicrobial activity against Staphylococcus aureus and Streptococcus pneumonia, have been identified. The assessment of the chemical structure made it possible to substantiate their pharmacological action and draw conclusions about the possibility of developing resistance to it in microbial cells.

Introduction. Human Noroviruses (HuNoV) are highly contagious pathogens responsible of acute human norovirus infection (HuNoVI). GII.4 is the prevailing norovirus genotype in the incidence of gastroenteritis worldwide. Currently there are no studies on the molecular monitoring and phylogenetic analysis of HuNoV in the territory of the Sverdlovsk region, therefore it is not possible to objectively assess their genetic diversity. The aim of the study is to carry out genotyping and phylogenetic analysis of HNoVI in municipalities of the Sverdlovsk region: Ekaterinburg, Nizhny Tagil, Kamensk-Uralsky in 2022. Materials and methods. Fecal samples were collected from children suffering from HuNoVI in the municipalities of the Sverdlovsk region. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction with degenerate primers flanking the ORF1/ORF2 junction. The amplified samples were genotyped by Sanger sequencing. Multiple sequence alignments were carried out and phylogenetic trees were constructed. Results. The total number of studied samples was 220. According to sequencing results, 73 positive sequences of HuNoV were typed, which represents 33% of the total volume of the studied samples. The largest share of genotypes is occupied by noroviruses GII (58%), noroviruses GI (42%). Noroviruses GII.17, GI.3 were the dominant genotypes. Phylogenetic analysis demonstrates that the identified sequences on the territory of the Sverdlovsk region have the smallest genetic distance, which gives grounds for their unification into a common cluster. Conclusion. For the first time, a genetic analysis of HuNoV was carried out in the territory of the Sverdlovsk region. The norovirus genotyping system based on the amplification of the ORF1/ORF2 region makes it possible to successfully identify various genotypes of noroviruses from the Sverdlovsk region. It has been confirmed that GII noroviruses remain the dominant genetic group. The results of phylogenetic analysis demonstrate the greatest homology in the formed clusters between isolates from Ekaterinburg, Nizhny Tagil, Kamensk-Uralsky.

More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation of the cardiovascular system and regeneration processes. In recent years, more and more facts have been accumulating that demonstrate a close relationship between arginine metabolic pathways and immune responses. This opens new opportunities for the development of original ways to treat diseases associated with suppressed or increased activity of the immune system. In this review, we analyze the literature describing the role of arginine metabolism in the immunopathogenesis of a wide range of diseases, and discuss arginine-dependent processes as a possible target for therapeutic approaches.

Abstract The Chadobets alkaline-carbonatite complex (Siberian craton) is a natural laboratory for all varieties of ultramafic lamprophyres, including damtjernites formed by fluid-explosion mechanisms, which contain a large number of pelletal lapilli. Data obtained from comprehensive mineralogical, structural and chemical studies of these pelletal lapilli show strong similarity with the main magmatic mineral assemblage of damtjernites, suggesting a juvenile composition for them. The composition of phlogopite, carbonate and fluorapatite in pelletal lapilli is mostly constrained toward primitive compositions (beginning) of mineral crystallization trends in ultramafic lamprophyres. According to the petrographic and mineralogical features found in pelletal lapilli from damtjernites, these can be divided into three types based on the conditions and depth of formation. Estimated late magmatic temperatures of pelletal lapilli mica and fluorapatite formation vary from 815 to 990 °C.

E.Yu. Yupatov1,2, T.E. Kurmanbaev3, I.G. Mustafin4, R.M. Nabiullina4, N.A. Safina4, E.V. Frederiks5, M.D. Leonova5, A.T. Khaertdinov2, N.I. Fattakhova2, V.D. Starikova4 1Kazan State Medical Academy — Branch of the Russian Medical Academy of Continuous Professional Education, Kazan, Russian Federation 2Kazan Federal University, Kazan, Russian Federation 3S.M. Kirov Military Medical Academy, St. Petersburg, Russian Federation 4Kazan State Medical University, Kazan, Russian Federation 5Maternity Hospital No. 13, St. Petersburg, Russian Federation Preeclampsia is one of the so-called major obstetrical syndromes and a cause of maternal and neonatal morbidity worldwide. In addition, preeclampsia increases the risk of maternal and neonatal cardiovascular disorders and cerebrovascular diseases in the future. During pregnancy, the pregnant mother undergoes significant changes in the functions of various organ systems to accommodate the developing fetus. The onset of preeclampsia can cause dysfunction of multiple organs and systems, including the homeostasis system. Its dysfunction is associated with the most serious thrombohemorrhagic complications (premature detachment of normally situated placenta, thrombosis, embolism, and bleeding). It is important to understand the relationship between the maternal and fetal homeostasis system functioning. The homeostasis system functioning in the fetus and newborn infant has specific characteristics expressed not only in the quantitative composition and the level of activity of its main links, but also in the qualitastive composition, as well as in the functioning mechanisms which differ from those in adults. The above specific characteristics help to achieve an important balance in the homeostasis system functioning. Preeclampsia, associated conditions and complications can disturb the existing balance and homeostasis system functioning in the fetus and newborn infant with the development of thrombohemorrhagic complications. Keywords: homeostasis system, newborn infants, preeclampsia, specific characteristics of functioning, preterm newborn infants, pregnancy. For citation: Yupatov E.Yu., Kurmanbaev T.E., Mustafin I.G. et al. Hemostasis functioning in neonates: normal condition and condition in preeclampsia (literature review). Russian Journal of Woman and Child Health. 2023;6(2):199–205 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-199-205.

The microbiota of the respiratory tract remains a relatively poorly studied subject. At the same time, it is involved in modulating the immune response to infectious agents in the host organism, just like the intestinal microbiota. A relationship between the composition of the respiratory microbiota and the likelihood of development and the severity of COVID-19 may be assumed. In this study, we applied the 16S rRNA metagenomic sequencing to analyze the oropharyngeal swabs from 120 COVID-19 patients collected during the first and the second waves of the COVID-19 epidemic in Russia. Differential abundance analysis with respect to comorbidities suggested association of Neisseria oralis, Neisseria mucosa, unidentified Veillonella spp., Lautropia mirabilis species with more severe lung damage, and Streptococcus salivarius, Capnocytophaga sputigena and Haemophilus parahaemolyticus with a milder course of the disease. We hypothesize that the latter bacteria (or some of them) might be beneficial for the respiratory tract and might be able to alleviate the course of the COVID-19 disease.

The capability of bis(dioxolene) ligands to access multiple redox states makes them ideal candidates to tune the electronic properties of metal complexes, for example to achieve valence tautomerism (VT). In this study, a family of dinuclear cobalt complexes have been isolated with the bridging bis(dioxolene) thean− ligand in the cat2−‐cat2−, cat2−‐SQ⋅− and SQ⋅−‐SQ⋅− states (cat2−=catecholate, SQ⋅−=semiquinonate): [{CoIII(tpa)}2(theacat−cat)](PF6)2 (1), [{CoIII(tpa)}2(theacat−SQ)](PF6)3 (2), and [{CoIII(tpa)}2(theaSQ−SQ)](PF6)4 (3) (theaH4=2,3,6,7‐tetrahydroxy‐9,10‐dimethyl‐9,10‐dihydro‐9,10‐ethanoanthracene, tpa=tris(2‐pyridylmethyl)amine). Multi‐technique analysis confirms that 1, 2 and 3 adopt low spin‐CoIII containing {CoIII‐cat‐cat‐CoIII}, {CoIII‐cat‐SQ‐CoIII} and {CoIII‐SQ‐SQ‐CoIII} states, respectively. Compound 1 undergoes thermally‐induced {CoIII‐cat‐cat‐CoIII} ⇌ {CoIII‐cat‐SQ‐CoII} VT in the solid‐ and solution‐states above 300 K, involving high spin‐CoII. This interconversion is contrary to expectations, as tpa typically stabilizes low spin‐CoIII‐catecholate. Compound 2 is mixed‐valence class II/II–III, indicating a localized electronic structure, with electron transfer faster than the EPR and solvent rearrangement timescales, but slower than the infrared timescale. Compound 3 exhibits strong antiferromagnetic exchange. The overlap between the dioxolene π‐orbitals in thean− increases the accessibility of the cat2−‐SQ⋅− state, resulting in VT for 1. This study demonstrates that thean− can be isolated in multiple oxidation states in metal complexes, which is promising for applications in magnetic materials. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effects of the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine at therapeutically relevant concentrations on beta‐cell mass and function. Methods: Viability was quantified in mouse insulinoma (MIN6) beta cells and mouse islets after 48‐h exposure to sertraline (1–10 μM) or paroxetine (0.01–1 μM) using the Trypan blue exclusion test. The effects of therapeutic concentrations of these SSRIs on insulin secretion were determined by static incubation and perifusion experiments, while islet apoptosis was investigated by Caspase‐Glo 3/7 assay, TUNEL staining and quantitative PCR analysis. Finally, proliferation of MIN6 and mouse islet beta cells was assessed by bromodeoxyuridine (BrdU) enzyme‐linked immunosorbent assay and immunofluorescence. Results: Sertraline (0.1–1 μM) and paroxetine (0.01–0.1 μM) were well tolerated by MIN6 beta cells and islets, whereas 10 μM sertraline and 1 μM paroxetine were cytotoxic. Exposure to 1 μM sertraline and 0.1 μM paroxetine significantly potentiated glucose‐stimulated insulin secretion from mouse and human islets. Moreover, they showed protective effects against cytokine‐ and palmitate‐induced apoptosis of islets, they downregulated cytokine‐induced Stat1 and Traf1 mRNA expression, and they significantly increased proliferation of mouse beta cells. Conclusions: Our data demonstrate that sertraline and paroxetine act directly on beta cells to enhance glucose‐stimulated insulin secretion and stimulate beta‐cell mass expansion by increasing proliferation and decreasing apoptosis. These drugs are therefore likely to be appropriate for treating depression in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

On the one hand, the relevance of the studied issue is determined by growing lag of rural territorial units in socioeconomic development, and one the other by their significance in such important aspects of the country, as ensuring food supply security, preservation of the available land, production, ecological, demographic and human potential. The aim of the article is to develop the conceptual model of sustainable development of rural areas, which is based on the system of indicators of quality of living of rural population. The leading method for studying this issue is modeling, which allows to consider it as a targeted and organized process of formation of the concept of sustainable development of the rural sector of the regional economy using the example of the studies of experience of sustainable development of the Kinel-Cherkassky municipal district of the Samara region. The results: the analysis of consistence and tendencies of development of agrarian potential of rural areas of the Samara region was carried out for the purpose of implementation of the conceptual model of sustainable development and assessment of further prospects in the production sphere of the village; the main reasons for disproportion in sustainable development of rural areas of the Samara region are identified. The materials of this article can be used for theoretical conclusions, methodological developments and working knowledge in activities of bodies of the regional government and local self-government when developing the concept and programs of sustainable development of rural municipalities.