Vol 19, No 3 (2021)

Over the past few decades, nanoparticles of metals, and in particular silver, with a diameter of less than 100 nm have significantly expanded their field of application for various biomedical purposes. So, silver nanoparticles have great potential in a wide range of applications as antimicrobial agents, coatings for biomedical products, carriers for drug delivery, bioengineering, since they have discrete physical properties and wide biochemical functionality. Studies have shown that the size, morphology, stability and properties (chemical and physical) of metal nanoparticles are strongly influenced by the conditions of the experiment, the kinetics of the interaction of metal ions with reducing agents and the adsorption processes of the stabilizer with metal nanoparticles. This review aims to analyze the use of silver nanoparticles in modern medicine based on data from domestic and foreign literature over the past five years. The study confirmed the high biological activity of drugs with nanoserebrum as anti-inflammatory, antimicrobial agents, antifungals, the presence of an inhibitory effect on protozoa, antioxidant and anticancer effects, and substantiated the relevance of use in bioengineering and dentistry. However, rapid advances and advances in technology have led to concerns about the potential risk associated with the use and application of silver nanoparticles to human health and the environment. Therefore, this review attempts to characterize and quantify the potential harmful effects of silver nanoparticles on the health of laboratory animals and humans, and focuses on ways to neutralize or reduce the toxic effects of silver nanoparticles on the human body.

It is believed that hypoxia-induced factor (HIF1) is the key mediator of oxygen metabolism. It was first identified as a transcription factor activated in cells and tissues by lowering the partial pressure of oxygen (O₂). The HIF1 activator spectrum includes both external factors – hypoxia, psycho-emotional stress and in ternal factors and varies from hormones to iron chelators. This review is dedicated to the molecular mechanisms of HIF1 activation, some of its natural activators HIF1, the potential for which is due to the low level of toxicity and the reduced likelihood of undesirable side effects. In turn, this opens up new options to treat diseases associated with local and general ischemia and hypoxia, the possibilities of their prophylactic use for researchers and clinicians in order to reduce the degree of damage in the event of an unforeseen condition of acute injurious to organs and tissues by hypoxia and reperfusion after it.

The purpose of this review is the analysis of the molecular mechanisms of lipid metabolism, their disorders leading to atherosclerosis, and the influence of modern antiatherogenic and antihyperlipidemic agents on atherogenic mechanisms. At the beginning of the review, a general description of atherosclerosis as pathology, its main characteristics and factors is given. The question of the complexity of the treatment of atherosclerosis and the problems arising in connection with the complexity is considered. Current models of the nature of atherosclerotic lesions are described. Next, we consider modern anti-atherosclerotic drugs used in clinical practice. Their nomenclature is given. Their basic biochemical mechanisms and the nature of their action are analyzed. Their negative effects and side effects are also considered. Then, the molecular and genetic mechanisms associated with atherosclerosis are analyzed in detail. The genes associated with lipid metabolism and the formation of atherosclerotic plaques, their expression and regulation are considered. The question of the influence of known anti-atherosclerotic agents on their expression is also covered. A group of azole drugs and their effect on lipid metabolism are considered in the context of the search for new anti-atherogenic drugs. The final part of the review examines the relevance of the search for new anti-atherosclerotic agents and methods for modeling dyslipidemia as a model of conditions that correlate with anti-atherosclerotic vascular lesions. It was concluded that the search for antiatherogenic drugs among imidazole derivatives is promising.

Interaction of slow-wave rhythmic components of cardiac, respiratory and motor activities was analyzed in non-narcotized of newborn 1-day-old (P1) and 16-day-old (P16) Wistar rat pups under normal and impaired cholinergic regulation. Functional activity of these three systems is rhythmic, and coordination of their functioning is an important element of the mechanism of adaptive rearrangements under changing factors of the external and internal environment. The acetylcholinesterase inhibitor physostigmine (eserine) was used to increase the level of endogenous acetylcholine and enhance cholinergic effects. To reveal the role of N-cholinoreceptors in intersystemic somatovisceral interactions (ISI), we performed blockade of this receptor type with benzohexonium. Administration of physostigmine leads to the development of a number of pathological reactions and a decrease in the level of ISI in all ranges of modulating rhythms in rats of both ages. ISI in younger rats appear to be more resistant to changes in the level of cholinergic activation. Blockade of N-cholinoreceptors causes inhibition of ISI at P1 and partially to their potentialization at P16. The activation of cholinoreactive structures, which occurred against the background of cholinoreceptors blockade, reduces the pathological effects of physostigmine in animals of both ages, but at the same time leads to an attenuation of ISI. This weakening is more pronounced in 16-day old rats, which may indicate the formation of the definitive level of cholinergic regulation in the first weeks of postnatal ontogenesis.

AIM: Of the investigation was to assess the therapeutic efficacy of ointment based on benzosulfonate 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) imidazolium, an imidazol derivative, on healing of a thermal skin damage (burn wound) in rats.

MATERIALS AND METHODS: In experiments on 150 male rats weighing 180–200 g, the wound-healing effect of an ointment based on benzosulfonate 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) imidazolium (IEM-1181) after experimental thermal skin damage was studied. The ointment containing 10% of the compound IEM-1181 was prepared by the pharmacopoeial method based on lanolin. The control was the placebo effect (the basis of the ointment). For comparison, we used Solcoseril^© (ointment, Solco, Switzerland). Thermal damage to the skin of rats under ether anesthesia was carried out with a special device consisting of a metal plate and a temperature controller. The surface of the plate with a diameter of 1,5 cm was heated for 15 minutes to a temperature of 80°С, and then applied to the pre-cut skin of the rat’s back (from the scapula caudally) for 15 seconds. After 24 hours, the skin of the animals developed damage to the epidermis and partially underlying dermis, corresponding to a grade II burn. The dynamics of changes in the burn wound was evaluated by 5, 10, 15, 20, 30, 40, 45, 50, 60, 70 days along the length of the contour bounding the affected area, using a curvimeter.

RESULTS: It was found that 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) imidazolium benzosulfonate has a wound-healing effect in thermal skin damage in rats. With topical application of the ointment containing the test compound, the time of complete healing of the wound formed at the site of the burn defect was reduced by 30%, healing took place without signs of inflammation, with the formation of an elastic scar.

CONCLUSIONS: Based on the conducted studies, it can be concluded that the ointment based on benzosulfonate 1-ethyl-3-methyl-4,5-bis(N-methylcarbomoyl) it has a wound-healing effect in thermal damage to the skin comparable in terms of the duration and degree of healing of burn defects with Solcoseril and can be the drug of choice for the treatment of grade II burns.

BACKGROUND: Until now, the neurotropic effect, in particular the effect on the emotional behavior of oxy-coumarins, has not been adequately studied. There are only few data on their central action. Currently, research is underway on the synthesis of new compounds based on natural oxy-coumarins, which will potentially have a higher biological activity.

AIM: Was to study the central action of new oxycoumarin-based compounds – IEM-2886, LVM-99, LVM-S144, in particular, on compulsive behavior in rats.

MATERIALS AND METHODS: To assess the behavior of Wistar rats, the “Marble-test” and “Elevated plus maze” methods were used. Oxycoumarin derivatives (IEM-2886, LVM-99, LVM-S144) were injected intraperitoneally at doses of 1, 10 and 25 mg/kg. The effectiveness of the drugs was judged by the number of balls buried in the “Marble test” and by the duration of staying in the open and closed sleeves of the “Elevated plus maze”. Results. It was shown that in the Marble test, oxycoumarin-based compounds (IEM-2886, LVM-99, LVM-S144) caused a decrease in the number of buried balls, which shows their anti-compulsive effect. After administration of IEM-2886, LVM-99, LVM-S144 (1–25 mg / kg) compounds, dose-dependent effects were observed (p < 0.05). The “elevated plus maze” test did not show the anxiolytic effect typical for tranquilizers. Moreover, after the administration of IEM-2886 and LVM-S144 at a dose of 25 mg / kg, an increase in the time spent in the closed sleeve of the maze (p < 0.05) was observed, i.e. an anxiogenic effect.

CONCLUSION: Thus, oxy-coumarin-based compounds are selective for the assessment of anticompulsive effects.

The data on the factors of development of postoperative immunosuppression (PI) are presented. Among them, an important role in the development of PI belongs to hyperactivity during operations of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal system. It has been shown that PI is prevented by regional anesthesia, primarily epidural anesthesia and postoperative epidural analgesia, as well as prolonged ganglioplegia. It is concluded that the preventive action of regional anesthesia in relation to the development of PI is largely associated with the sympatholytic component of action.