The effect of zinc complex of N-isopropenylimidazole on the morphological characteristics of gum tissues in experimental endodontic-periodontal lesions in rats Authors

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: 1st – intact group (control-1); 2nd – animals with simulated EPL (control-2); 3rd – animals with simulated EPL and treated with Metrogyl Denta® gel (M-D); 4th – animals with simulated EPL and treated with N–isopropenylimidazole zinc complex derivative gel under the laboratory code Pilim-1; and 5th – 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

Effects of new antiarrhythmic agent SS-68 on excitation conduction, electrical activity in Purkinje fibers and pulmonary veins: Assessment of safety and side effects risk

The compound SS-68 has been selected among numerous new derivatives of indole and demonstrated antiarrhythmic effects in animal models. The present study concerns several aspects of SS-68 safety and efficacy as a potential antiarrhythmic drug. The first estimation of atrioventricular conduction in mammalian heart under SS-68 has been carried out; effects of SS-68 in Purkinje fibers and myocardium of pulmonary veins have been investigated. The drug weakly affects cardiac atrioventricular conduction: only high concentrations of SS-68 (≥10 μmol/L) significantly decrease this parameter. Also, the drug weakly affects Purkinje fibers automaticity, but effectively alters action potential waveform in Purkinje fibers in a concentration-dependent manner. SS-68 (0.1–100 μmol/L) failed to induce any early or delayed afterdepolarizations in Purkinje fibers both in basal conditions and under provocation of proarrhythmic activity by norepinephrine (NE). Moreover, 10 μmol/L SS-68 suppressed NE-induced extra-beats and rapid firing in Purkinje fibers. In pulmonary veins only high concentrations of SS-68 significantly increased action potential duration, while lower concentrations (0.1–1 μmol/L) were ineffective. Also, 0.1–100 μmol/L SS-68 was unable to elicit arrhythmogenic alternations of action potential waveform in pulmonary veins. In conclusion, SS-68 has no proarrhythmic effects, such as afterdepolarizations or abnormal automaticity in used experimental models

The influence of non-selective arginase inhibitors on some reparative regeneration indexes of experimentally resected liver

The impact of L-norvaline, a non-selective arginase inhibitor, on the state of the resected liver of Wistar strain white male rat, was evaluated. The resection of the liver was made on the second day of the experiment to the extent of 70%. L-norvaline ("WIRUD JmgH", Hamburg) was intragastrically administered, at a daily dose of 18mg/kg for the first seven days of the experiment, every 48 hours. The effect of the drug on the state of the resected liver was assessed according to the mortality rate, time of the volume recovery, the structure and functions of the organ. The mortality rate was being assessed in the experimental animal groups for the first ten days after the surgery. The animals were withdrawal from the experiment on the second, seventh, fourteenth, twenty-first, and twenty-eight days after the surgery. The cytolysis degree was assessed according to the AlAT, AsAT, and LDH indexes in the blood of the experimental animals, by an ultraviolet kinetic method. The synthesis function of the liver was evaluated according to the coagulogram indexes (APPT, INR, fibrinogen). The level of microcirculation in the liver was determined by laser doppler fluorometry. The morphological study was performed on the material of the standard liver sites taken after the animal had been withdrawal from the experiment. It was shown, that the non-selective arginase inhibitor, L-norvaline, stimulates liver regeneration after resection, which is manifested by decreased lethality, a significant decrease in the post-resection liver failure in comparison with the control group; significant earlier restoration of the volume, structure, and functions of the resected organ compared with the control group

The effectiveness of Soderm® – forte gel and a new injectable dosage form of Rexod® in the complex treatment of experimental periodontitis in rats

Introduction: Insufficient effectiveness of traditional drug therapy in a treatment of patients with chronic generalized periodontitis, as well as high social significance of this problem, determines the need to search for new drugs and their compositions aimed at solving it. Aim of the study: To increase the efficacy of complex treatment of periodontitis with the administration of Soderm®-Forte gel and a new injectable form of Rexod®. Materials and methods: Experiments were performed in 50 male Wistar rats. Experimental periodontitis (EP) was simulated by ligation of the necks of lower incisors. We studied the animals with intact periodontium, untreated EP, and when traditional drug therapy (TDT), as well as the combinations of TDT with Soderm®-Forte gel and additionally with the new injectable dosage form (NIF) of Rexod® were administered. The general condition, behavior, nutrition and body weight of the animals were evaluated. The Schiller-Pisarev test and the Muhlemann-Cowell bleeding index were used, and the amount of crevicular fluid (CF) was measured. The contamination of the marginal gum with microorganisms was determined. Results and discussion: The TDT in EP has a moderate therapeutic effect, which does not lead to a sufficiently high pharmacotherapeutic effect, whereas the combinations of TDT with Soderm®-Forte and, to a greater extent, TDT with Soderm®-Forte and NIF of Rexod® have high therapeutic efficacy, which is statistically confirmed by a sharp decrease in the amount of CF, the Schiller-Pisarev test and the Muhlemann-Cowell bleeding index, as well as absolute suppression of pathogenic microorganisms. Conclusion: The combinations of TDT with Soderm®-Forte gel and NIF of Rexod® in EP in rats can significantly increase the effectiveness of the treatment. The data obtained indicate the expediency of the administration of Soderm®-Forte gel, as well as its combination with NIF of Rexod® in dental practice in the complex therapy of patients with periodontitis

The effect of the composition of Soderm®-Forte gel and the new injectable form of Rexod® on pathology findings in gingival tissue in experimental periodontitis in rats

Introduction: Periodontitis is the most important problem of modern dentistry. The development of new medicines and treatment regimens for patients with periodontal complex lesions is a strategic direction of modern pharmacology and dentistry. In this view, pride of place goes to morphological research, which allows not only to study the effect of drugs on pathomorphological changes in periodontal tissues, but also to estimate their therapeutic effectiveness. Aim of the study: to determine the nature of the effect of the composition of Soderm®-Forte gel and the new injectable form of Rexod® on the pathology findings in gingival tissue of rats with experimental periodontitis. Materials and methods: Experimental periodontitis (EP) was induced in rats by ligature method. The study was performed according to the following algorithm: animals with intact periodontium; animals with untreated EP; animals with EP treated with traditional drug therapy (TDT); animals with EP treated with combinations of TDT with Soderm®-Forte gel and TDT with Soderm®-Forte gel and the new injectable form (NIF) of Rexod®. For pathomorphological examination, biopsy specimen was taken from the gingival margin of the lower incisors. The ImageJ software was used for computer morphometry. Results and discussion: Examination of the gum samples revealed moderate therapeutic effects of the TDT. The combinations of TDT with Soderm®-Forte gel and, to a greater extent, TDT with Soderm®-Forte gel and the NIF of Rexod® showed high pharmacotherapeutic efficacy, manifested in rapid regeneration of the gingival tissues. Conclusion: The combination of TDT, Soderm®-Forte gel and the NIF of Rexod® shows the most beneficial effect on the pathological processes in the gum. The pharmacotherapeutic effect of the studied combination promotes the earliest regeneration of damaged gum tissues and reduces the risk of persistent pathology changes in them

COMPARATIVE ANALYSIS OF ACTOPROTECTIVE PROPERTIES OF NEW CHEMICAL COMPOUNDS

Aim. This study was aimed at searching and investigating new substances among phenylethyl derivatives of 3-hydroxypyridine, which exhibit a high actoprotective activity under the conditions of normoxia and acute hypobaric hypoxia.Materials and methods. New compounds of phenylethyl derivatives of 3-hydroxypyridine under the SC code (n = 23) were investigated in comparison with bemethyl and bromantane. The actoprotective activity of new compounds was assessed in experimental animals using a treadmill running test under the conditions of normoxia and acute hypobaric hypoxia. The studied chemical substances and comparative drugs were administered 1 hour prior to exposure of animals to the test. Statistical processing of the obtained experimental results was performed using Microsoft Excel and Statistica for Windows 6.0 software.Results. Among the studied substances, active compounds exhibiting an actoprotective effect have been distinguished. SC-119 chemical substance was revealed, which exceeds the other studied chemicals and bemethyl and bromantane reference actoprotectors in terms of the range of effective doses and actoprotective activity under the conditions of normoxia and acute hypobaric hypoxia.Conclusion. According to the results of the study, the SC-119 compound seems to be a prospective candidate for further research into highly effective actoprotective drugs

Community-acquired pneumonia: the dynamics of senior medical students’ knowledge

Community-acquired pneumonia (CAP) is an acute infectious disease. Inflammation of the lower respiratory system, interstitium, and microvasculature, mainly of bacterial etiology, is a typical pathological sign of this disease. It is one of the leading causes of death from infectious diseases. The survey was conducted within the KNOCAP multicenter research project (the full name of the project “The assessment of students' and physicians' knowledge of community-acquired pneumonia basics”). We have assessed the knowledge and preferences of doctors and 85 senior medical students from Belgorod National Research University majoring in Medicine by surveying them two times – before and after the conduction of educational activities. The first stage of the project was carried out in 2017-2018, the second one – in 2018-2019. Educational activities were held during the educational process (in particular, during Clinical Pharmacology). The greatest difficulties appeared when answering the questions: the choice of the main criterion for the terminating antimicrobial therapy (AMT); the choice of the main diagnostic sign when examining a CAP patient; the choice of the criterion for CAP diagnosis confirmation. This study makes a significant contribution to the development of a practical health care system because it allows both identifying "weak spots" and improving the quality of CAP patients’ management tactics. There is a necessity to conduct more studies about this matter since the current health care system is experiencing changes, and new clinical guidelines are published

The influence of the vagus nerve and indole derivative SS-68 on excitation processes in the SA node

Introduction: Atrial fibrillation (AF) is the most common form of cardiac arrhythmias. Studying the pathogenesis of this pathological process will make it possible to look for new methods of treating AF and to predict its occurrence in a more targeted way. The aim of the study was to identify the components of the takeover process of central rhythmogenesis by the SA node in the conditions of atrial fibrillation when stimulating the vagus nerve and using substance SS-68. Materials and Methods: The experiments were conducted on 30 frogs and 90 cats. In frogs, the activity of the regions of the medulla oblongata synchronous with the heart rhythm was determined in a high-frequency electromagnetic field. In cats, proximal and distal foci of luminescence in the vagus nerve (VN) and pools of pacemaker cells (PCs) in the sinoatrial node were visualized under topical and general anesthesia, using a KELSY scanner with a microscope video capture unit while stimulating VN and using SS-68. Results and Discussion: The stimulation of VN with volleys of electrical impulses and the introduction of SS-68 increase the foci of luminescence in the nerve and unite the PC pools. This way, under general anesthesia in comparison with topical anesthesia, the area of the proximal focus of VN luminescence decreased by 83.8%, and the distal focus – by 44.9%. Against the background of general anesthesia, the area of the proximal focus of luminescence when stimulating VN with volleys of electrical impulses was by 76.0% larger than before stimulation, and the distal focus – by 72.5%. After the administration of SS-68, there was an increase in the foci of luminescence: under general anesthesia, when compared with topical anesthesia, the area of the proximal foci of luminescence decreased by 86.8%, and the distal one – by 67.1%. Under general anesthesia, the area of the proximal focus of luminescence under conditions of stimulating VN with volleys of electrical impulses was by 82.2% larger than before stimulation and the distal one – by 78.2%. When signals from the brain arrive simultaneously through VN at the PC pools, they are absorbed by the PC pools; the focus of early depolarization becomes wide, which prevents the development of AF. The increased synchronizing influence of VN may be one of the methods for treating autonomic AF, and if its influence decreases, it can be a prognostic factor for the occurrence of recurrent AF. Conclusion: The tonic effect of VN on the heart rhythm through electrical stimulation of the former and the use of SS-68 is manifested in a decreased heart rate: the difference between the initial heart rhythm and the minimal synchronization range boundary. A decrease in the heart rate under the influence of VN prevents paroxysms of AF, but does not completely eliminate the influence of ectopic foci on it