Journal «MEDICINA» 4/2019

The article presents a critical analysis of recommendations on oral anticoagulants use, cited (with reference to the Beers criteria) in the 2018 Russian expert opinion «Features of diagnosis and treatment of chronic heart failure in elderly and senile patients».

Key words: dabigatran, rivaroxaban, apixaban, edoxaban, elderly, Beers criteria

In the review, the main sources of the nitrosamines formation in drugs were established, as well as the main mechanism of the toxic effect of this impurities group on the human body. The reason of the increased nitrosamines content in the group of sartan drugs is the use of nitrous acid in the manufacturing process. Nitrous acid interacts with common organic solvents, that contain an amino group, forming toxic compounds. Moreover, impurities of nitrosamines can be formed during the degradation of the principal or auxiliary substances. The results of the review are conclusions about the necessity of further studies of the formation pathways and the toxicity mechanism, besides the development of methods for their determination in pharmaceutical substances and drugs.

Key words: genotoxic impurities, nitrosamines, valsartan

The aim was to study the characteristics of the venous circulation of the lower extremities in cases of chronic venous diseases (CVD) in men with arterial hypertension (AH). A comparative analysis of the parameters of the venous blood flow of the lower extremities between two groups of men with hypertension aged 30-50 years was performed: a test group with hypertension and CVD (63 people) and a control group with hypertension without CVD (30 people). Type of research – single-step. AH was diagnosed according to ESC/ESH (2018). The presence of CVD was assessed by the CEAP classification and the results of ultrasound diagnostics of pathological refluxes in the superficial, deep, and perforating veins of both limbs. Using the Doppler study, the following parameters were recorded at rest (lying) in the superficial, deep, and perforating veins on the left: diameter and area of the vessel lumen, venous blood flow velocity, and venous pressure. In the test group higher values for diameter and area of the lumen of the superficial veins, blood flow velocity in the superficial, deep and perforating veins were recorded. The test group was characterized by a higher venous pressure than the control group. Conclusion. Expansion of the veins, acceleration of blood flow and an increase in venous pressure should be considered a characteristic feature of hypertension and chronic venous insufficiency. AH and CVD have a common pathogenetic mechanism – phlebohypertension, the presence of which must be taken into account when prescribing antihypertensive therapy to patients with AH and CVD.

Key words: arterial hypertension, chronic venous diseases, men

The results of experimental studies of pharmaceutical factors affecting the release of drugs from ointments using seven ointment bases and model drugs: salicylic acid, insoluble in bases and water, and resorcinol, soluble in water, glycerol and fatty oils are presented. The method of diffusion in gelatin gel showed that the main factors affecting the release of drugs from ointments are the basis and technology. The most rapid and complete release of the active substances occurred from 5% gel sodium carboxymethylcellulose.

Key words: ointments, bases for ointments, technology, salicylic acid, resorcinol

Nowadays a high prevalence of nutritional status disturbances (under- and overnutrition) among the youth is called «the double burden» in a foreign literature. An actual cause of deviations in children’s health is eating disorders including psychosomatic disorders. This determines the necessity to develop and implement of a unified diagnostic system, primary prevention and correction of nutritional status disturbances in children and adolescents. Purpose of the study. This is an analytical review of Russian and foreign literature about the assessment of youth’s nutritional status formulating of modern methodical approaches in diagnostics of children’s and adolescents’ nutritional status. Study material and research methods. Analytical methods of processing scientific significant information about the object of study were used in a research article. A critical evaluation of various methods (somatometric, laboratory, clinical, functional) for diagnostics of nutritional status of the studied contingent was given. A design of multi-level system for assessment and correction of nutritional disorders and risk of alimentary dependent diseases was introduced. Conclusion. In spite of numerous studies of nutritional status the unsolved problems are the following: absence of unified adequate informative and easy-to-use criteria for assessment the nutritional status for different age groups; absence of software on assessment and correction of nutritional status, taking into account age differentiation that does not allow to realize the principle of early diagnostics and modern correction of nutritional disorders.

Key words: nutritional status, diagnostic criteria, children and adolescents, overnutrition, undernutrition, obesity, standard deviation

An experimental study was conducted on 60 white laboratory rats. This work was carried out on female rats of the out-bred population of the «Wistar» line weighing from 150 to 170 grams and the age of one year. All animals were divided into the following 3 research groups (20 animals each): group I (control intact group), which was not given alcohol; group II (the first experimental group), in which 70% ethyl alcohol was administered orally every day for 6 months at a dosage of 1 ml; group III (the second experimental group of rats) included offspring from the first experimental group after drinking alcohol; they also received 70% ethyl alcohol by oral route for 6 months every day at a dosage of 1 ml. To assess the results, the animals underwent laparotomy under ether anesthesia with subsequent liver biopsy and histological verification. In the course of research on laboratory animals, an experimental model of the negative effect of alcohol on the liver was created.

Key words: alcohol, laparotomy, white rats, histological preparations, biopsy, liver, pregnancy, offspring

The purpose of the review was to systematize modern views on some extra-gastrointestinal manifestations of Helicobacter pylori infection, having the immune-metabolic nature. Based on the analysis of the literature data, the concept of «continuum of Helicobacter pylori infection», previously including mainly gastrointestinal manifestations of Helicobacter pylori, was expanded. The variety of functional and organic disorders resulting from the presence of this infection is shown. Proven and potential mechanisms of Helicobacter-associated pathology development, systematized according to the principle of the affected organs and systems isolation, are revealed. The predominant role of immune and metabolic disorders in the pathogenesis of most of the considered pathological conditions is emphasized. Thus, Helicobacter pylori-infection, a classic example of «therapeutic infections», traditionally considered as the cause of the pathology of the gastroduodenal zone, has recently acquired features of a polymorphic disease with multiple clinical masks and heterogeneous mechanisms for the implementation of pathological effects, sometimes forming vicious circles and revealing a synergistic effect.

Key words: Нelicobacter pylori, extragastrointesinal signs, therapeutic infections

Purpose. To perform the comparative analysis of the threshold contrast sensitivity in myopic patients using spectacle correction as well as orthokeratological correction. Material and methods. The parameters of monochrome spatial sensitivity were examined in 24 patients (48 eyes) diagnosed with average myopia. All patients were divided into two groups. Group I included patients using orthokeratological lens not less than 6 months. Group II included patients with spectacle correction. To determine threshold contrast sensitivity the computer software «Zebra» (version 3) was applied. Results. The comparative analysis showed that the valid values of threshold contrast sensitivity were higher in patients with orthokeratological correction at the medium spatial frequencies (4 and 8 cycles/deg). At the low and high spatial frequencies no significant differences were detected. Conclusion. The positive influence of the orthokeratological lens on the spatial contrast sensitivity at the medium frequencies allows us to recommend this method of correction to receive the best central vision in patients with average myopia in comparison with spectacle correction.

Key words: ophthalmology, spatial contrast sensitivity, myopia

The article focuses on the use of molecular docking for the enzyme E. Coli hydrolase (S. Aureus) in the study of the «structure-activity» relationship in the series of substituted amides and hydrazides of N-aroyl anthranilic acids. For the construction of the structure-activity model, we used the results of molecular docking on the enzyme peptide deformylase (hydrolase) E.Coli and S.Aureus of substituted amides and hydrazides of N-aroyl anthranilic acids. During the docking, E. Coli hydrolase enzymes (PDB ID code: 1LRU) and S. Aureus (PDB ID code: 1Q1Y) were used, the structures of which were obtained from the RCSB Protein Data Bank database. Before carrying out molecular docking, optimization and quantum-chemical calculation of the structures of the studied compounds was performed using the PM3 semiempirical method applying Gaussian 03 software. Significant parameters were determined: total electric field strength Σ (Е), potential Σ (φ) and the absolute value of charge Σ (|q|) on the atoms of oxygen, nitrogen, carbon and hydrogen. We carried out theoretical calculation of the physicochemical descriptors of the compounds under study: lipophilic constants (log P_calc), acidity constants (pKa_calc) and basicity (pKв_calc). Ligand-receptor interaction modeling was performed by the AutoDock 4.0 software as part of the MGL Tools 1.5.6 software package, using the Lamarkian genetic algorithm. As a result of docking for enzymes hydrolase E.Coli and S.Aureus, scoring functions were obtained: binding energy (Binding energy (Be_E.Coli and Be_S.Aureus)), intermolecular energy (Intermolecular energy (Ime_E.Coli and Ime_S.Aureus)) and inhibition constant (Ki_E.Coli and Ki_S.Aureus) characterizing the interaction of the ligand with the receptor. Studies of the dependence of antimicrobial activity (AA) from scoring functions and physicochemical descriptors were carried out. Structure-activity models were compiled by conducting multiple linear regression analysis using the Statistica 6 program. Four correlation equations were compiled relating the scoring functions and physico-chemical descriptors with antimicrobial activity using 20 compounds. A check was performed for the models created using the example of 4 compounds. Linear dependences of AA_calc. from experimental values of AA_exp. (MIC_exp.(E.Coli) and MIC_{exp.(S.Aureus)} for equations 2 and 4, made up of four, with correlation coefficients (R_pred. (2) = 0.961 and R_pred. (4) = 0.911), show a high degree of communication AA_calc. with AA_exp..

Key words: amide, hydrazide, аnthranilic acid, molecular docking, antimicrobial activity, quantum chemical parameters, structure-activity

Introduction. Gamma-interferon plays an important role in the pathogenesis of bacterial infections. It was shown that some microorganisms, as well as the use of antibiotics, can specifically repress the synthesis of endogenous gamma-interferon. Therefore, the additional effect of exogenous gamma-interferon can play the role of the immune system inducer in a reduced response to antibiotic therapy conditions. Objective. To evaluate the efficacy and safety of gamma-interferon as part of antibiotic therapy in patients with community-acquired pneumonia. Materials and methods of research. Open randomized controlled trial in parallel groups. The studied group of patients received, in addition to the basic antibacterial therapy, gamma-interferon; the control group of patients received the combined antibacterial therapy: ceftriaxone and azithromycin. Study Results and Discussion. Of the 114 randomized patients, 110 completed the study. The actual distribution of patients was as follows: 54 patients in the study group and 60 patients in the control group. The average duration of hospital stay in the control group was significantly longer – by almost two days compared with the study group. The similar trend was observed in the subpopulation of bacteria resistant patients, although due to the small sample of patients no statistically significant differences between the groups were demonstrated. Changes in the Borg scale compared to the screening visit showed statistically significant differences between the groups in favor of the study group. By the 8-10th days of therapy, a decrease in the total score on the BCSS scale also reached statistically significant differences between the groups in favor of the study group. In the study group a significantly greater dynamics of a decrease in the level of leukocytes was also observed. The remaining criteria of effectiveness did not show statistically significant differences between groups. In terms of adverse reactions, both groups were similar and did not differ statistically. Conclusions: The results of the study positively demonstrated clinical efficacy and safety of gamma-interferon as part of antibiotic therapy in patients with community-acquired pneumonia, including patients with bacteriologically confirmed pathogen resistance. The use of gamma-interferon was accompanied by a significant reduction in the length of sickness and the duration of hospital stay.

Key words: gamma-interferon, antibiotic therapy, community-acquired pneumonia, bacterial resistance, ceftriaxone, azithromycin, white blood cell count