Vol 23, No 7 (2020)

The search for new compounds with anti-inflammatory and analgesic effects is relevant. The goal - the search for compounds with anti-inflammatory and analgesic activities among monosubstituted amides and hydrazides of 1, 4-dicarboxylic acids. Material and methods. Objects of study - acylamides and acylhydrazides of 1, 4-dicarboxylic acids. A study of anti-inflammatory activity was carried out for 11 compounds on white non-linear rats of both sexes weighing 190-220 g (6 animals) in a model of acute inflammatory edema (administration of 0.1 ml of a 1% aqueous solution of carrageenin). An increase in foot volume was evaluated on-cometrically before administration and 3 hours after administration of carrageenin. The test substances were administered orally at a dose of 50 mg / kg 1 hour before the administration of the phlogogenic agent. Standard: the drug «Nimesulide-MBF» Control: animals not receiving the drug. The presence of anti-inflammatory action was judged by the severity of inhibition of the inflammatory reaction. Analgesic activity was determined for 9 compounds on white non-linear mice weighing 25-30 g (8 animals) according to the method of «hot plate». Compounds were administered intraperitoneally 30 minutes before testing at a dose of 50 mg / kg. Standard: the drug «Metamizole Sodium» The animals were placed on a metal surface heated to 56 ° C. The time was recorded from the moment it was placed on a hot surface until a behavioral response to pain irritation appeared. A criterion for the analgesic effect was considered a significant increase in the latent period of the reaction after administration of the substance. The animals of the control group were injected with an equivolume amount of physiological sodium chloride solution. Results. It was found that maleic acid 2-pyrimidylamide, 4-methyl-2-pyridylamide and citraconic acid 2-thiazolylamide showed pronounced anti-inflammatory activity. High analgesic activity was found for 3-hydroxy-4-carboxyphenylamide maleic acid and 4-methoxybenzoylhydrazide phthalic acid. 4-Methyl-2-pyridylamide of citraconic acid exceeds the effect of the drug «Metamizole sodium» and has an anti-inflammatory effect at the level of the drug «Nimesulide». Findings. It is recommended to continue the search among the derivatives of 1,4-dicarboxylic acids for compounds with antiinflammatory and analgesic effects.

Relevance. The collagenase producers search is of great interest for various areas of human activity. The study of various enzymes synthesized by microorganisms and the possibility of their practical application is one of the most relevant areas of biotechnology. These biologically active compounds are widely used in a number of the national economy sectors, in medical practice and also in research purposes. These enzymes include collagenases, which are the part of medicines used to remove scars, keloids and in the treatment of burns and ulcers. However, in domestic medical practice, mainly imported drugs are used for these purposes. Objective. The work is devoted to the search of these enzymes producers among the collection strains of mycelial fungi of All-Russian Scientific Research Institute of Medicinal and Aromatic Plants. Material and methods. It was conducted with using of surface cultivation on media with the replacement of sucrose on collagen. It is known that the growth of microorganisms on substrates containing insoluble proteins as the only source of carbon allows us to estimate their potential proteolytic activity. The appearance of protein lysis zones around colonies is an indicator of enzyme secretion into the environment. Results. The article shows that all studied mycelial fungi grew well on media with the replacement of easily metabolized carbohydrate on the collagen. During surface cultivation micromycetes formed lysis zones which indicates the synthesis and secretion of hydrolases into environment. Conclucion. In the result of a detailed study of 14 fungal strains, as well as regression and correlation analysis, 6 micromycetes promising for study as collagenase producers were selected.

Background. Beta-lactamases are widely spreadin methicillin-susceptible Staphylococcus aureus (MSSA) isolates and confer this pathogen spenicillin-resistance. At the same time 50% of isolates that are penicillin-susceptible in disk diffusion test are beta-lactamase producers. Antibiotic resistance evaluation is time-consumin gand prolongs the process of adequate treatment prescribing. So the introduction of express-tests for antibiotic resistance evaluation is an actual problem. The aim of this study. The estimation of iodine test sensitivity for penicillin susceptibility and potential beta-lactamase activity in staphylococci (i.e. isolates with beta-lactamase operon in their genomes). Materials and methods. Beta-lactamase activity of 81 MSSA clinical isolates was evaluated by iodine test with preliminary stimulation of beta-lactamase production and without it. To estimate the sensitivity and specificity of this method for identification of penicillin-resistant isolates and potential beta-lactamase producers the results of the iodine test were compared with the data about beta-lactamase operon presence in isolates genomes recived in real-time PCR and statements of penicillin-resistance in disk diffusion test. Results. Iodine test was highly sensitive for identification penicillin-susceptible MSSA isolates. The sensitivity of iodine test for penicillin-resistant is olates was 61% if the test was formed without preliminary stimulation or 86% if the test was performed after stimulation. In the same time iodine test was low-sensitive for isolates that contain beta-lactamase operon in their genomes identification, the iodine test sensitivity in this case was less than 63%. So iodine test without preliminary stimulation maybe regarded as possible screening method for penicillin-susceptible MSSA identification immediately after pathogen isolation, that will be helpful to decrease the time-loss for decision making in antibiotic treatment choose. Conclusion. Despite the low sensitivity of iodine test for identification of beta-lactamase operon containing MSSA, this method is attractive for fast identification of penicillin-resistance in S. aureus.

Relevance. In different diseases, when the cell immune system is involved into the pathogenesis and/or is affected by a respective pathologic process, neopterin concentration reflects the disease progression and can be used in clinical practice for early diagnosis of one or another type of an infectious complication of chronic lymphocytic leukemia (CLL), for achievement of an optimal result of prognostic and diagnostic measures, for reduction of the number of recurrences and for well-timed ordering of preventive treatment. Study objective. To examine neopterin concentration in patients with chronic lymphocytic leukemia at different stages of the main disease progression, as well as depending on the etiological factor of the infectious complication and its form (localized or generalized). Material and methods. Data of 177 patients with CLL were analyzed. Methods for examining etiologic agents of infectious complications were applied according to Order No.535 "On Unification of Microbiological (Bacteriological) Examination Methods, Applied in Treatment and Diagnostic Laboratories of Medical and Preventive Institutions" dated April 22, 1985. ELISA method was applied to identify antibodies (IgM and IgG) to the viruses Varicella zoster, Cytomegalovirus (CMV). Neopterin concentration in the blood serum was measured with ELISA method with the use of test systems "Neopterin ELISA" of IBL INTERNATIONAL GMBH Company, Hamburg, Germany. Results. Differences in neopterin concentration depending on CLL phase are as follows: the maximum increase of its level in the active phase (60.84±2.77 nmol/l), and an increase of neopterin level in the newly diagnosed patients (42.44±3.59 nmol/l) in comparison with the group of outpatients (stable phase 32.76±2.23 nmol/l). Prevalence of the influence of bacteriological agents on neopterin concentration was revealed (76.59±2.82 nmol/l), which is 3 times higher than under viral complications of CLL (22.10 ± 0.93 nmol/l). Mycotic complications of CLL caused an increase of neopterin level in the blood serum up to an average of 33.38 ± 1.68, which is connected both with specific immunologic mechanisms of combating this group of complications. Under the onset of additional infectious complications demonstrated significant exceeding of neopterin level indicators, especially those that progress with generalization of the pathologic process - a 1.5-2 increase in comparison with the local processes. Findings. Analysis of neopterin average concentrations in the blood serum of patients with CLL under infectious complications of bacterial, viral and mycotic etiology identified a significant increase of neopterin average level under all types of pathogens, complication forms and CLL stages in comparison with the group of patients without infectious complications. There is credible evidence of a statistically significant effect of each type of agents on the increase of neopterin level in the blood serum, including at the stage of symptomless manifestation of complications.