Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad’s disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.

Background. Advances in electrophysiological research have led to a modern understanding of the mechanisms of atrial fibrillation — the most common sustained cardiac arrhythmia, which poses a risk of severe, often disabling, and fatal complications. Although there have also been advances in pharmacology and rapid progress in interventional treatment methods, atrial fibrillation still cannot be completely eliminated in patients. Objectives. To examine the key stages in the development and improvement of medical care for patients with atrial fibrillation from a historical perspective, taking into account the widely accepted rate and rhythm control strategies and using data from both international and Russian scientific literature. Methods. An analysis of literature sources by international and Russian authors dedicated to the issues of diagnosis, pharmacological, and non-pharmacological treatment of atrial fibrillation was carried out. In order to search for the sources, the Russian scientific electronic library eLibrary.ru and the biomedical research search engine PubMed were used. Results. Throughout the 20th and 21st centuries, antiarrhythmic drugs capable of successfully restoring sinus rhythm were developed; however, the challenge of its long-term maintenance with such medications has remained unresolved. The development and increasingly widespread use of surgical, and especially catheter ablation in the left atrium, have the potential to improve the effectiveness of atrial fibrillation treatment. Recently, the importance of individualizing the management strategy for patients with atrial fibrillation has been growing, with mandatory consideration of their clinical characteristics. The main direction for future research could be the development of more effective and safer antiarrhythmic drugs for their rational use in combination with innovative non-pharmacological treatment technologies for atrial fibrillation. Conclusion. This paper presents the most important advances in medical care for patients with atrial fibrillation. It outlines potential approaches to minimizing its negative impact on patients’ quality of life and prognosis

Introduction: Combined inflammatory and destructive processes affecting the dental pulp and tissues of the periodontal complex are among the most problem diseases of the dental system. Current therapy with use of available pharmacological agents does not always allow achieving the expected positive result. In addition, often the lack of information about morphological processes in the tissues of the dental system, in particular the gums, with endodontic-periodontal lesion (EPL) limits the ability of dentists to carry out targeted pharmacotherapy with both traditional and, in particular, new medications. The aim of the study was to evaluate the morphological characteristics of gum tissues in a therapeutic context of N-isopropenylimidazole zinc complex derivative in experimental endodontic-periodontal lesion in rats.  Materials and Methods: A simulation of EPL in rats was performed in two ways: simultaneous induction of acute periodontitis and parodontitis by pulp extraction and natural infection of the pulp cavity, as well as by ligation of the necks of lower incisors. The research protocols included 5 groups of animals: 1^st – intact group (control-1); 2^nd – animals with simulated EPL (control-2); 3^rd – animals with simulated EPL and treated with Metrogyl Denta^® gel (M-D); 4^th – animals with simulated EPL and treated with N–isopropenylimidazole zinc complex derivative gel under the laboratory code Pilim-1; and 5^th – animals with simulated EPL and treated with the combination of M-D + Pilim-1. The gum of the lower incisors was taken for morphological studies. Slides were stained with hematoxylin and eosin. Computer morphometry was performed using the ImageJ software. Results and Discussion: The substances M-D, Pilim-1 and, especially, the combination of M-D+Pilim-1 (against the background of chlorhexidine bigluconate used as oral rinse) for 14 days in rats with simulated EPL cause a significant improvement of the morphological structure of the gum with minimal residual dystrophy and sclerosis. The combination M-D + Pilim-1 led to a 1.3-time increase in epithelial thickness, and a 1.5-time decrease in acanthosis depth in comparison with M-D, while the number of capillaries and their diameter had no significant differences. Compared with Pilim-1, the epithelial thickness increased 1.5 times, and the acanthosis depth and the number of capillaries decreased 1.6 and 1.4 times, respectively, whereas the diameter of the capillaries did not change significantly. The pronounced protective effect of the combination M-D + Pilim-1 on the morphological structure of the gingival mucosa of rats with simulated EPL may be associated with antimicrobial, anti-inflammatory, regenerating, angioprotective and antioxidant properties of both M-D and Pilim-1 separately, and, possibly to a greater extent, of the combination M-D + Pilim-1. Conclusion: The substances M-D, Pilim-1 and, especially, the combination M-D + Pilim-1 (against the background of chlorhexidine bigluconate used as oral rinse) for 14 days in rats with simulated EPL have a protective effect on the epithelial structure and the connective tissue of the proper mucous plate, manifested in active normalization of pathological changes and significant restoration of their organotypic structure.

Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative. Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD₅₀ for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically. Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity. Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.

Introduction: For effective and safe pharmacotherapy of pain, it is important to evaluate the mechanisms and spectrum of action of non-steroidal anti-inflammatory drugs (NSAIDs), including their effect on the proteom, central effect, as well as pain relieving and anti-inflammatory effects. The aim of the study was to evaluate the complex of differences between the promising candidate-molecule of indole derivative SV-1010 and the well-known NSAIDs. Materials and Methods: Chemoproteomic moduling of pharmacological effects of SV-1010 and NSAID diclofenac, nimesulide and ketorolac on the rat proteom by means of topological analysis of chemographs. Results: The significant differences in the effects of the studied molecules were found for 820 proteins of the rat proteom. SV-1010, to a lesser degree than the other molecules, can inhibit dopamine D1- and D2-type receptors and, at the same time, stimulate the release of dopamine in the neostriatum (EC50 = 27 nM). SV-1010, to a greater extent than the other molecules, can inhibit the GABA conveyor (EC50 = 65 nM) and the NMDA receptors Grin1/Grin2b (IC50 175 nM). SV-1010 can activate Cannabinoid CB2 receptors, inhibit enzymes of leukotriene biosynthesis, CC receptors of pro-inflammatory chemokines and leukotrienes. Conclusion: The chemoreactomic and chemoproteomic profiling of SV-1010 indicated its potential central effect through dopaminergic and GABA-neurotransmission and additional anti-inflammatory mechanisms, which can help increase pain-relieving effects.

Introduction: The combination treatment of patients with dentition problems including endodontic-periodontal lesions (EPL) is known to widely involve anti-inflammatory drugs, including non-steroidal anti-inflammatory agents, and antimicrobial drugs, in particular antibiotics and antiseptics, from which the former often lead to the development of gastro- and neuropathy, lesions of kidneys and liver, as well as the cardiovascular system, and the latter, in addition to serious side effects, lead to the development of steady resistance of pathogenic microorganisms and dysbacteriosis. This necessitates search for and development of new molecules with a wide range of therapeutic effects aimed to block the infectious and inflammatory process and to restore the functional ability of teeth in EPLs as much as possible (depending on a lesion severity). The aim of the study was to examine the anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats. Materials and Methods: EPL simulation in experiments on the anesthetized rats was conducted in the following way: first, the pulp cavity of lower incisors was opened and left exposed to infection; then periodontal inflammation was induced using a ligature. Thirty days later, EPL developed in the animals. An N-isopropenylimidazole zinc metal complex derivative (laboratory code Pilim-1, prepared in form of gel), reference drug Metrogyl Denta® (M-D, dental gel), as well as the combination Pilim-1 + M-D were applied daily for 14 days on the lower incisors and appropriate gums, and also placed in the gingival pockets and pulp cavities, with pulp partially removed beforehands. After euthanasia of the animals on the 15th day of the experiments, gingival homogenates were assayed for the activity of elastase, urease, catalase, the level of malondialdehyde, and the antioxidant-prooxidant index was calculated, while pulp homogenates were assayed for the activity of elastase, urease, alkaline and acidic phosphatases, and the mineralizing index was calculated. Results and Discussion: In the gum in EPL, Pilim-1 and, especially, the combination Pilim-1+M-D more significantly than M-D have a pronounced anti-inflammatory, antioxidant and antimicrobial (reduce a microbial content level) effects. In the pulp in EPL, Pilim-1 and, to a greater extent, the combination Pilim-1 + M-D in a more pronounced way than M-D have anti-inflammatory, antimicrobial (reduce a microbial content level) and mineralizing effects. In the therapeutic action mechanisms of Pilim-1 and, especially, the combination Pilim-1 + M-D in EPL conditions, their ability to have an antihypoxic effect and an inhibitory effect on cyclooxygenase and 5-lipoxygenase is likely to play a very important role, in addition to their identified effect on the examined metabolic processes. Besides, a certain role may be played by the presence of zinc and imidazole in the structure of Pilim-1, as they have a wide range of biological activity. Conclusion: The presented results of studying Pilim-1 and its combination with M-D indicate their high therapeutic efficiency, especially when using the latter in the experimental EPL in rats, which makes it possible to consider Pilim-1 and Pilim-1 + M-D as potential therapeutic agents to treat EPL.