Analysis of General Toxicity of Ergoferon.

For antibody-based drugs, it is important and relevant to study their toxic effects, which can often become limiting when prescribing this type of therapy. General toxicity of antiviral drug Ergoferon based on technologically processed antibodies was studied on sexually mature animals. Analysis of acute toxicity showed the absence of lethal outcomes when the drug was administered to adult rats at the maximum tolerated doses. In a study of repeated dose toxicity, no adverse effects of the drug were detected.

Safety of the Drug Prospekta: a Preclinical Study of Acute and Repeated Dose Toxicity.

General toxic effect of the drug Prospekta (modified affinity purified antibodies to the brain-specific S100 protein) was studied on mature male and female mice and rats: acute toxicity with double intragastric and intraperitoneal administration of the maximum permissible doses at a 2-h interval, repeated dose toxicity with intragastric administration of the maximum permissible and close to therapeutic doses for 6 months. No lethal and toxic effects on animals were observed, including no toxic effects on vital systems, i.e., CNS and cardiovascular system, as well systems with the functions that may be temporarily disrupted (excretory and digestive systems). All the differences between animals of the experimental and control groups varied within the physiological range. It can be concluded that the drug produces no general toxic effect on laboratory animals.

Evaluation of the influence of the analytical characteristics of the microbiological blood study in bacteremia in a multidisciplinary hospital.

The culture method continues to be the "gold" standard for microbiological diagnosis of bloodstream infections. This is primarily due to the fact that the definition of the etiology of a generalized infectious process determines the etiotropic antibiotic therapy. To do this, it is necessary to conduct periodic microbiological monitoring of the prevailing microflora. To do this, in the present study, a retrospective analysis of the results of a microbiological blood test for sterility was performed in case of suspected bloodstream infections in a multidisciplinary hospital to assess the influence of analytical stage factors on the laboratory data obtained. Automatic hematological cultivators were used, identification was carried out based on the biochemical characteristics of microorganisms, as well as using time-of-flight mass spectrometry with matrix-activated laser desorption / ionization (MALDI-TOF MS). More than 10,000 research results were analyzed, the average microflora seeding rate was 15.1%. The analysis of the isolated microflora was carried out in 2 groups of positive results: at the beginning, the data obtained in the presence of growth in two vials at once were evaluated, then the positive results of blood cultures obtained in any one vial from a pair were studied. The predominance of gram-positive flora in the structure of microorganisms isolated from whole blood was revealed, the influence of cultivation conditions and the composition of thenutrient medium on the isolated flora was not found, however, a number of microorganisms, due to the specific characteristics of metabolism, were characterized by growth under strictly defined cultivation conditions. The presented study actualizes the need for constant microbiological monitoring in order to determine the prevailing hospital microflora, which can contribute to a timely response in order to limit the spread of highly virulent, aggressive, resistant strains of microorganisms leading to the development of generalized bloodstream infections.

[Non-invasive methods for studying age-related skin changes in various morphotypes of aging.]

The purpose of the work is to assess changes in the functional state of the microvasculature, study of the features of the morphological parameters of the skin by non-invasive research methods for various morphotypes of aging. The study involved 55 patients with involutional changes in the lower third of the face aged 35 to 65 years, included according with the inclusion and exclusion criteria. 4 morphotypes of aging were identified, depending on which patients were divided into corresponding groups: 1st - 19 patients with deformational type, 2nd - 17 with tired type, 3rd - 8 with fine wrinkled type, 4th - 11 with mixed morphotype of aging. To study the condition of the patients' skin, laser Doppler flowmetry and ultrasound examination of the skin (22 Mhz) were used. The method of laser Doppler flowmetry revealed significant changes when comparing microcirculation indices and the ultrasound method for examining deformational and fine wrinkled type (p<0,05). In the deformational type and mixed type, a predominantly atonic type of microcirculation was observed (9,42±3,71 and 9,56±2,31 perf. u., respectively), and in fine wrinkled spastic type of microcirculation (7,86±1,6 perf. u.), in the oral morphotype the microcirculation index was within the normal range of 7,86±1,6 perf. u. The data of ultrasound examination of the skin made it possible to reveal in the deformational morphotype of aging high values of the thickness of the epidermis (125,94±27,84 µm), the dermis (1 439±118,11 µm) and the density of the dermis (12±2,59 a. u.) compared with the thickness of the epidermis 85±22,01 µm, the thickness of the dermis (1 130±68,55 µm) and the density of the dermis (7,87±2,1 c. u.) in the fine wrinkled morphotype of aging.

Molecular profile of oral fluid in new coronavirus infection.

Oral fluid is an alternative biological material that confirms correlations with blood parameters in various pathological conditions of the body. In order to find a non-invasive approach to stratification of patients with COVID-19 disease, molecular biomarkers of the oral fluid have been determined in patients with moderate coronavirus infection in comparison with clinically healthy individuals. It has been shown that proteomic, carbohydrate, macro- and microelement profiles of the oral fluid in coronavirus infection can be used for diagnostics. The features of protein metabolism were revealed: an increase in the content of total protein, urea; increased activity of enzymes aspartate aminotransferase, gamma glutamyl transpeptidase, creatine phosphokinase, alkaline phosphatase; changes in carbohydrate metabolism, which is expressed by an increase in glucose and lactate levels, an increase in lactate dehydrogenase activity, sodium, chloride, calcium, magnesium, iron content.

[Assesment of the nutrition and antioxidant activity of biological liquids in students].

Studying of quality of nutrition of students is of great importance as it is one of the major factors defining the state of health, especially during the periods of adaptation to the changing conditions of the environment and stressful situations. Stability or, on the contrary, predisposition to stressor violations is defined by numerous factors including the nutritive status of an organism. The purpose of the research was the analysis of the actual diet of the studying youth during educational process and assessment antioxidant activity of biological liquids of an organism. 74 students shared in a research: 30 young men and 44 girls. For assessment of the actual nutrition a method of the food diary within 5 days, excepting days off and holidays, has been used. It has been established that frequency of a meal at most of students was 3-4 times a day. Most of students consumed the first dishes1-2 times a week (56.7% of young men and 63.6% of girls), at the same time these dishes were absent in a diet at 13.6% of girls. The second dishes were present in the diet of all students. In both groups the average index of body weight was in limits of norm (18.5-25.0 kg/m2). At the same time body weight was reduced at 6.7% of young men and 11.4% of girls; excess body weight was revealed at 20.0% of young men and 6.8% of girls. 73.3% of young men and 81.8% of girls had normal body weight. In young men the calorie content of the diet, the protein and fat content slightly differed from the norm. At the same time, a carbohydrate imbalance was observed - an increase in the proportion of simple carbohydrates (sugars) (p≤0.05) and a decrease in the content of starch and dietary fiber (p≤0.05). In girls, protein intake was below the normal level and a similar carbohydrate imbalance was noted (p≤0.05). The content of vitamins in the diet of both boys and girls was reduced. Youngsters had a deficiency of ß-carotene and vitamin C, in girls it was aggravated with vitamins B1 and B2 (p≤0.05). In the diet of the surveyed, a deficiency of such minerals as calcium and magnesium was noted; in girls - potassium, phosphorus and iron in addition (p≤0.05). Excessive element in the diet was sodium. In the diet of young men the content of phosphorus and iron exceeded the norm. Thus, the analysis of the diet of students indicated a lack and imbalance in the content of both macroand micronutrients, which was most pronounced in girls. The total antioxidant activity of biological liquids of an organism - blood serum, urine and saliva (determined by amperometric method using a system for liquid chromatography) decreased among: urine, blood serum, saliva. Blood serum of young men possessed greater antioxidant activity than in girls; while in urine the dependence was reversed. Thus, in order to increase the antioxidant status of the organism during periods of adaptation and stress, a qualitative and quantitative balance of the diet and increased consumption of antioxidants is necessary.

Spatial Memory in the Progeny of Rats Subjected to Different Types of Experimental Preeclampsia.

Spatial memory was studied in 2-month-old offspring of rats subjected to different types of experimental preeclampsia (replacement of drinking water with 1.8% NaCl from day 1 to 21 of gestation or intraperitoneal administration of non-selective NO-synthase inhibitor L-NAME to pregnant rats in a daily dose of 25 mg/kg for 7 days on gestation days 14-20). Spatial memory was evaluated in an elevated 8-arm radial maze. Both types of experimental preeclampsia impaired spatial (long-term and short-term) memory and can be used in the development of drugs correcting negative effects of this pregnancy complication on memory.

Preclinical Toxicological Study of Release-Active Preparations for Prediction of Their Pharmacological Activity and Side Effects.

We studied chronic toxicity of a few release-active preparations: Dietressa (release-active preparation of affinity-purified antibodies to type 1 cannabinoid receptor), Divasa (releaseactive preparation containing a combination of affinity-purified antibodies to brain-specific S-100 protein and endothelial NO-synthase), Cardostin (release-active preparation containing a combination of affinity-purified antibodies to C-terminal fragment of angiotensin II type 1 receptor and endothelial NO-synthase), and Bation (release-active preparation containing a combination of affinity-purified antibodies to IFN-γ and CD4). We evaluated not only side and toxic effects, but also the relationships between these effects and pharmacological activities of the preparations. The data of preclinical toxicological studies of the release-active preparations can be used for prediction of their pharmacological activity.

[The results of primary audiological examination of the children presenting with intrauterine growth retardation and normotrophics born after multifetal and singleton pregnancies].

The objective of the present work was the comparative study of the state of the acoustic analayzer in the full-term and premature infants born after multifetal (MP) or singleton (SP) pregnancies with the body weight at birth corresponding to the gestational age (normotrophics) and presenting with intrauterine growth retardation (IUGR). The method of distortion product otoacoustic emissions (DPOAEs) was employed in the study. It has demonstrated that the normotrophic babies born at the gestational age over 34 weeks after singleton pregnancy pass the DPOAEstest significantly more frequently than normotrophics of the same gestational age born after multifetal pregnancy. Moreover, the unilateral impairment of hearing in the full-term infants born after multifetal pregnancy occurs more frequently than in those born after singleton pregnancy.

Comparison of physical development and rate of formation sensory-motor reflexes offspring of rats with different experimental model of preeclampsia.

Summary: A comparative study of the physical development and the rate of formation of sensory-motor reflexes offspring of rats with experimental preeclampsia (EP) was carried out. In the first experimental group EP was modeled intraperitoneal conduct of L-NAME at a dose of 25 mg/kg from 14 to 21 days of gestation, the second experimental group - the replacement of drinking water by 1.8% sodium chloride solution for the entire period of gestation. In the offspring of both groups, there was a delay of physical development, which was reflected in the later timing of the hair coat development, incisor eruption, pinna detachment as compared to the pups in the control group. It also noted the gap in the formation of sensory-motor reflexes and vestibular reactions. This was manifested in the delayed appearance of the olfactory response, auditory sensitivity, later performing tests «righting reflex¼, «negative geotaxis¼, «aerial righting reflex¼, «cliff avoidance¼, «horizontal wire test¼, «raising the head and forelegs¼, «supporting their bodies on hind legs¼ as compared to the indices of the pups of the female rats with an uncomplicated pregnancy. The most pronounced lag in postnatal development was observed in the offspring of rats with EP, which instead of drinking water was prepared 1.8% sodium chloride during the entire period of gestation. The purpose: To make a comparative study of the impact of ADMA-like preeclampsia (PE) and preeclampsia modeled by the replacement of drinking water consumed by female rats during gestation with 1.8% NaCl solution on the physical development and the rate of the maturation of sensory motor reflexes of their offspring. Methods: The study was performed on three groups of pregnant female rats aged 3-4 months whose original weight was 210-250 g and their pups. They were divided into three groups: 1: Control group including female rats with an uncomplicated pregnancy (n = 6) and their pups (n = 49); 2. Experimental group 1 - pregnant female rats with PE (n = 6) induced by intraabdominal introduction of L-NAME at a dose of 25 mg/kg from 14 to 21 day of gestation (ADMA-like preeclampsia) and their offspring (n = 35); 3. Experimental group 2 - pregnant female rats with PE (n = 6) modeled by the replacement of drinking throughout gestation with 1.8% NaCl solution and their pups. When studying the physical development of the pups we considered the terms of pinna detachment, hair coat development, incisor eruption and the time when they began to open their eyes. To estimate the rate of the maturation of sensory motor reflexes and motor coordination of the pups of the rats with PE we analyzed the time when they started to support their bodies on hind legs, lift their bodies off the floor, crawl, raise their head and forelegs, show the aerial righting reflex and the righting reflex, negative geotaxis, reactions to auditory and olfactory stimuli as well as the time they managed to stay on the horizontal wire. Results: The pups of the female rats with PE of both experimental groups were found to have later pinna detachment, incisor eruption and hair coat development as compared to the indices of the control group. In addition, the offspring of the experimental groups demonstrated a delay in the performance of the following tests: «righting reflex¼, «negative geotaxis¼, «aerial righting reflex¼, «cliff avoidance¼, «horizontal wire test¼, «raising the head and forelegs¼, «supporting their bodies on hind legs¼, «reaction to an olfactory stimulus¼ and «reaction to an auditory stimulus¼ as compared to the indices of the pups of the female rats with an uncomplicated pregnancy. Conclusion: PE induced by the introduction of ADMA to pregnant female rats and by the replacement of drinking water consumed by female rats during gestation with 1.8% NaCl solution causes a delay in physical development, maturation of sensory motor reflexes and vestibular reactions in their offspring.

[Study of Mental Functions Offspring of Rats with Experimental Preeclampsia in Postnatal Ontogenesis].

The postnatal development of offspring's mental functions from rats with experimental preeclampsia caused by the replacement of drinking water by 1.8% sodium chloride solution from the 1st day of pregnancy until delivery was studied. Animals born by females with complicated pregnancy have a high level of anxiety, de- creased, motor, orienting-investigative activity, cognitive impairment in postnatal ontogenesis, compared with the offspring from rats of the control group. This model can be used in research related to the evaluation of animals born to females with the EP, as well as to search for new, effective agents for the purpose-of correcting deviations in nental development in children born to mothers with preeclampsia.

Experimental study of the efficiency of Dietressa preparation on body weight reduction in mice feeding high-fat ration.

We studied the efficiency of Dietressa on body weight reduction in C57Bl/6 male mice feeding standard high-fat ration (24%). After 5-month daily intragastric administration of Dietressa, body weight gain was the lowest in comparison with other groups and did not differ from that in mice receiving the reference substance sibutramine for 5 months. In contrast to sibutramine, Dietressa did not increase motor activity of animals in the open field test and produced no anorectic effect. The mean body weight gain per each 1000 kcal of consumed food in the group of animals receiving Dietressa was lower than in the control group and mice receiving sibutramine.

[Gravidaprotective action of phenibut in experimental pre-eclampsia].

It was established that the replacement of drinking water by 1.8% NaCl solution in female rats during pregnancy causes experimental pre-eclampsia (EP), as evidenced by an increase in the blood pressure, proteinuria, and edema in the control group as compared to pregnant female rats with normal drinking regime. Animals with EP exhibited disturbance of vasodilating endothelial function, microcirculation disorder, and increased coagulation and thrombogenic potential of blood. In addition, the group with EP showed evidence of the activation of lipid peroxidation (LPO) due to lower activity of antioxidant enzymes. Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes.

[Comparative study of the effects of new neuroactive amino acid derivatives on the postnatal development of the rat's offspring with experimental preeclampsia].

BACKGROUND: Our aim was to investigate the effect of derivatives of GABA and glutamate on the postnatal development of the offspring of rats with experimental preeclampsia. METHODS: The experiments were performed on 35 albino female rats aged 5-7 months, weighing 220-240 g, and their offspring in the amount of 284 individuals. Experimental preeclampsia was modeled by replacing the drinking water by 1.8% NaCl solution to pregnant females from 7 to 21 days ofgestation. Glutamic acid--compound RSPU-135 at a dose of26mg/kg, GABA derivative - compound RSPU-242 at a dose of 23 mg/kg and the reference drug sulodexide in a dose of 30 mg/kg administered to female orally daily, since the 7th day of gestation prior to delivery. Evaluated the physical development of offspring, sensory-motor reflexes, mental functions. RESULTS: It was found that the experimental preeclampsia causes a delay in physical development and maturation of sensory-motor reflexes in the offspring, as indicated by the later periods of eruption of the incisors and eye opening, response to the emergence of audio and olfactory stimuli, forming vestibular stability and coordination of movements compared to pups from females with physiological pregnancy. Offspring from females with experimental preeclampsia were noted for lagging behind in mental development, as evidenced by the decline of the orienting-exploratory activity, learning and memory, increase of anxiety level. Compound RSPU-135, to a greater extent, improves physical development, increases the rate of maturation of sensory-motor reflexes, RSPU-242--stimulation of cognitive functions, keeping the memory trace, orienting-exploratory, spontaneous locomotor activity, and reduce of anxiety level. CONCLUSION: The neuroactive amino acid derivatives limit the negative effects of experimental preeclampsia on the offspring.

Study of the absolute bioavailability of citrocard, a new GABA derivative.

The main pharmacokinetic parameters attest to short elimination half-life and mean retention time of a single citrocard molecule. The average rate of plasma concentration decrease of the compound determined small area under the pharmacokinetic curve. Steady-state distribution volume was low and only slightly surpassed the volume of extracellular body fluids in rat, which indicated moderate capacity of citrocard to distribution and accumulation in the tissues, which is seen from low systemic clearance (Cl) despite the quick elimination of the compound. Absolute bioavailability was 64%.

[Hepatoduodenal circulation and excretion of the new GABA derivative citrocard].

Pharmacokinetic investigation of a new gamma-aminobutyric acid (GABA) derivative cirtocard showed that, upon the intravenous introduction, the drug is determined in high concentrations in organs of elimination--the liver and kidneys. The tissue accessibility amounts to 1.341 for the liver and 4.053 for the kidneys and the separation factor is 1.041 for the liver and 4.486 for the kidneys. The study of drug excretion showed that cirtocard is determined in the urine for 48 h, its nephritic clearance being 0.047 L/h and extra-nephritic clearance, 0.33 L/h. For the unchanged substance, a large significance ofhepatoduodenal circulation is low probable, since no more than 1 - 2% of the introduced dose was isolated with bile over entire experiment. It is established that the removal of the unchanged substance does not exceed 10% of the introduced dose. There is high probability of hepatoduodenal circulation and excretion of the preparation in the form of metabolites.

Experimental study of the effects of Dietressa, a new weight-reducing drug.

The capacity of a new drug containing ultra-low doses of antibodies to cannabinoid receptor type 1 (Dietressa) to reduce body weight gain in mice on a high-calorie diet was evaluated, possible mechanisms of drug action were analyzed, and its safety (abuse potential in the reaction of self-stimulation) was evaluated. Dietressa was not inferior to sibutramine in reducing body weight gain in mice and exhibited no abuse potential.

[The mode of spot test of plague and pseudotuberculosis agents mix cultures].

It is supposed to implement the polymerase chain reaction with mix of two pairs of "chromosome" primers "vlm12for'/"IS216rev" and "JS for"/JSrev" species-specific for Y. pestis and Y. psdtbc correspondingly in spot test of plague and pseudotuberculosis. The additional immunodiagnostics is applied to find defective and full-fledged on plague bacteria F1-antigen synthesis in the volume agglomeration reaction and paragglutination with diagnosticums of plasmid-dependent F1 antigen and chromosome FV determined antigen. This mode is characterized by more effectiveness and lesser labor intensiveness. It accelerates the detection of the mix of two agents in bacterial inoculations, organs bioassays and other materials. Also this mode facilitates the analysis of mix cultures of agents of plague and pseudotuberculosis, obtained in "mixed" nidi, the component identification, differentiation and isolation of pure growths of both Yersinia.

[Comparison of efficacy of tests for differentiation of typical and atypical strains of Yersinia pestis and Yersinia pseudotuberculosis].

AIM: To characterize species specificity of officially recommended tests for differentiation of Yersiniapestis and Yersinia pseudotuberculosis and propose additional tests allowing for more accurate identification. MATERIALS AND METHODS: Natural, laboratory and typical strains oftwo Yersinia species were studied using microbiological, molecular and biochemical methods. For PCR species-specific primers complementary to certain fragments of chromosomal DNA of each species as well as to several plasmid genes of Y. pestis were used. RESULTS: It was shown that such attributes of Y. pestis as form of colonies, fermentation ofrhamnose, melibiose and urea, susceptibility to diagnostic phages, nutritional requirements could be lost in pestis bacterial species or detected in pseudotuberculosis species. Such attribute as mobility as well as positive result of CoA-reaction on fraction V antigen are more reliable. CONCLUSION: Guaranteed differentiation of typical and changed according to differential tests strains is provided only by PCR-analysis with primers vlml2for/ISrev216 and JS respectively, which are homologous to certain chromosome fragments of one of two Yersinia species.

Some aspects of toxicological activity of kardosten after chronic 6-month administration to rats.

Chronic treatment of rats with kardosten for 6 months had a positive effect on some ECG values and behavior without disordering the hepatorenal functions. All effects of the drug observed during a course of treatment were leveled and the parameters reached the basal values within 2 weeks after drug discontinuation, this confirming its safety.