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INTRODUCTION. In the current practice of preclinical safety studies of pharmacologically active substances, standard neurotoxicity assessment procedures are mainly aimed at diagnosing higher nervous activity and behavioural disorders. However, it is the structures of the peripheral nervous system that are particularly susceptible to drug-induced neurotoxicity, which renders these structures an easy target and leads to a high incidence of neurotoxic side effects. These circumstances dictate the importance of refining methodological approaches to the assessment of toxic injury in the peripheral nervous system.AIM. The study aimed to analyse the current methodological level of clinical and functional tests for assessing the toxic effects of pharmacologically active substances on the structures of the peripheral nervous system, as well as to formulate practical recommendations for using these tests in preclinical studies in rodents.DISCUSSION. Rodents are considered the optimal test system for preclinical studies of pharmacologically active substances, but it is impossible to reproduce the entire neurological examination that is conducted to identify clinical equivalents of neurotoxicity in humans using these animals. This article presents a systematic approach to using available diagnostic tests to increase the translatability of data. The article briefly describes the neurological deficits due to adverse drug reactions in humans, as well as the main toxidromes that can also occur in animals. Based on a literature review and experience, the authors provide practical recommendations for performing basic tests to study the strength and tone of muscles, the state of physiological reflexes, the coordination of movements, and various types of sensitivities in rodents. The article provides a brief overview of the diagnostic utility of electrophysiological testing for identifying toxic damage to the peripheral nervous system. The following tests are recommended as a minimum list of primary screening techniques for detecting neurotoxic side effects in study animals: a resting posture assessment, the beam walking test, the horizontal bar test, the digit abduction score assay, the tail flick test, and the Preyer reflex test.CONCLUSIONS. The results of a comprehensive assessment of neurological deficits in rodent experiments should be analysed from a clinically relevant perspective— that is, with a focus on topical diagnosis and common pathological process components. It is advisable to verify the pathological process at the level of the peripheral nervous system using a set of electrophysiological techniques.

INTRODUCTION. The tendency towards reducing the use of laboratory animals in pharmaceutical quality assessment, along with the development of new technologies for gonadotrophin production, necessitate the development of novel assays to determine the biological activity of natural and recombinant anterior pituitary preparations.AIM. This study aimed to select the optimum conditions for the determination of the biological activity of luteinising hormone (LH) in urinary and genetically engineered LH preparations by tests in randombred and Sprague Dawley rats.MATERIALS AND METHODS. The biological activity of urinary and recombinant LH preparations was determined in vivo in a three-dose randomised Steelman–Pohley bioassay, which compared the biological activity of the test samples to a reference standard (RS). The analysis used two years’ worth of test results. The RS used was the WHO international standard containing 183 IU of follicle stimulating hormone bioactivity and 177 IU of LH bioactivity per ampoule. The bioassay was performed in immature male randombred and Sprague Dawley rats; the bioassay conditions were selected according to the rat type.RESULTS. The results of the in vivo determination of LH biological activity in male rats were compared by the standard deviation to slope ratio (s/b), which helps estimate response variation and dose dependence at the same time. The study demonstrated the possibility of using Sprague Dawley rats (s/b=0.82±0.44) for the determination of LH biological activity along with randombred animals (s/b=0.68±0.58). The s/b ratios were close, although Sprague Dawley rats and randombred rats were used in the assay at a 1:2 ratio.CONCLUSIONS. It is possible to determine the biological activity of LH from menopausal gonadotrophin preparations in both randombred and Sprague Dawley male rats. The use of Sprague Dawley rats for testing can confirm the reliability of test results using fewer animals than needed for standard tests; this is not only humane but also cost effective.

INTRODUCTION. Functional examination of the urinary system, and particularly the kidneys, is an important challenge in preclinical studies. Currently, there is no generally recognised and detailed approach to drug-induced nephrotoxicity detection in vivo, nor are there clear criteria for its assessment.AIM. This study aimed to analyse and systematise instrumental and laboratory methods for the assessment of urinary system function in laboratory animals and to identify the basic principles for studying drug-induced nephrotoxic effects.DISCUSSION. The study analysed the advantages and limitations of the methods used to study the nephrotoxicity of medicinal products, with considerations for the use of these methods in small and large laboratory animals. The effects of a test substance on the urinary system should first be evaluated using minimally invasive methods. One of these methods is urinalysis. For urinalysis, important considerations include the sampling technique, the volume of the biomaterial, and the turnaround time between urine collection and analysis. Ultrasonography is the most accessible instrumental method in preclinical studies. Ultrasonography can assess organ position, size, structure, and echogenicity and detect abnormalities and changes in real time. Dif ferent method settings are preferred for each species of laboratory animal. Further analysis can include macroscopic examination of organs, measurement of their masses, and microscopic analysis of tissues. Visual assessment should cover the size, colour, and consistency of the ureters, bladder, and kidneys. Nephrotoxicity may manifest as increased apoptosis, vacuolation of renal tubular epithelial cells, epithelial degeneration or dystrophy, oedema, diapedesis-associated haemorrhages, acute tubular and papillary necrosis, necrosis of the Bowman–Schumlansky capsule, casts and crystals in the tubular lumen, glomerulopathy with the corresponding changes, and inflammatory and vascular reactions.CONCLUSIONS. The study analysed and systematised instrumental and laboratory methods for assessing the functional state of the urinary system in preclinical studies. The authors outlined the basic principles for a structured and comprehensive study of the potential nephrotoxicity of novel medicines. The assessment of nephrotoxicity should start with simple and minimally invasive laboratory and instrumental methods, which include general urinalysis and microscopic examination of urine sediment. These methods can detect organ dysfunction that has not yet presented with an associated anatomical lesion. A more in-depth analysis should involve histological and immunohistochemical methods to examine the urinary tissues of laboratory animals.

The ultimate goal of preclinical studies is to generate data that can be used to make conclusions about the potential effects of a new medicine on the human body and to properly proceed to clinical trials. In this interview, Marina N. Makarova, Doctor of Medical Sciences, Director of the RMC “HOME OF PHARMACY”, shares her views on conducting preclinical studies in Russia.

Aim of the study was to compare the results of mathematical modelling of the dependence between brain ventricle size and capillary pressure for humans and animals based on the equations of multicomponent poroelastic filtration for brain parenchyma. Material and methods. The study included two groups of animals - 4 male mice of each inbred line C57Bl/6 and BALB/C at the age of 12 weeks – and 4 healthy volunteers. The brain and cerebrospinal fluid system images of mice were obtained using an 11.7 T horizontal MR scanner, group of humans were examined using the Ingenia 3.0 T MRI scanner. An axial section at the level of –0.5 mm from bregma in the mouse groups and a frontal slice at the level of the middle of the bodies of the lateral and third ventricles, posterior to the foramen of Monroe in the human group were chosen as the geometry for mathematical modelling. Mathematical modelling is based on the stationary mathematical model of multicomponent poroelastic filtration. Multiple linear regression of mean ventricular wall displacement on fluid media interaction parameters was constructed to compare results obtained. Regression coefficients were compared using nonparametric analysis of variance based on the Kraskell–Wallis criterion and post-hoc Dunn’s criterion with Hill’s correction Results. A qualitative coincidence in the behavior of capillary pressure and mean ventricular wall displacement was demonstrated for the human and mouse groups. No significant differences were found between the two animal lines. For the animals characterized by small ventricular size (BALB/c), greater similarity to humans is observed than for the genetic line with hypertrophied ventricles (C57Bl/6). A significant difference between humans and mice is observed only for capillary-venous interaction. Conclusions. The low variance within groups and insignificant discrepancy between groups indicate the possibility of further accumulation of empirical data to establish correction coefficients of the animal model, which will bring it more in line with the model for humans. Thus, the analyzed models are sufficiently comparable with each other.

Aim: To adapt a mathematical model describing the interaction between fluid media and brain matter for the purpose of definition of the dependence between brain ventricle size and capillary pressure in laboratory animals of two genotypes, BALB/c and C57BL/6. Material and methods. The study included 4 male mice of each inbred strain C57BL/6 and BALB/c at the age of 12 weeks. The brain and cerebrospinal fluid system images were obtained using an 11.7 T horizontal MR scanner (Bruker, BioSpec 117/16 USR, Germany). An axial section at the level of -0.5 mm from bregma was chosen as the geometry for mathematical modelling. To describe the data obtained, the mathematical model was adapted by selecting a scale factor based on the known values of the cerebrospinal fluid formation rate for humans and mice. Results and discussion. The same qualitative pattern of relationship between capillary pressure and mean ventricular wall displacement was observed for all animals considered. Although the selected genetic strains of BALB/c and C57Bl mice differ significantly in terms of cerebral ventricle size, these differences in animal genotype did not affect the nature of this relationship. Changing the parameters of the fluid media interaction in the area of compression or moderate ventricular dilation almost does not lead to an exit from the physiologically acceptable capillary pressure value. In this case, the size of the ventricles changes significantly. In the area of large ventricular dilation, in contrast, there is little change in ventricular size, and this is accompanied by a dramatic increase in capillary pressure far beyond physiologic limits. Thus, the change in ventricular size is an adaptive process associated with pressure fluctuations caused by changes in intracranial fluid flow. The mere fact that some of the values reach the zone of physiologically unacceptable pressures associated, in fact, with death, provided that there is practically no change in ventricular size indicates that such a situation is rarely realized and is possible in case of violation of intracranial fluid media flows associated with the fact that the increase in ventricular size limits adaptive capabilities. Conclusions. The presented animal model will further increase the understanding of the pattern we have established and allow us to move on to attempts at prediction.

Protein hydrolysates are a promising active component in specialized food products. Due to the presence of bioactive peptides with enzyme inhibiting activity in their composition, protein hydrolysates exert different physiological effects. The aim of the research was to establish the potential hypoglycemic activity of the protein hydrolysate of broiler chicken stomachs in whey and to develop a beverage on its basis for patients with diabetes mellitus. Protein hydrolysates obtained from microbial fermentation of muscular stomachs of broiler chickens in whey were assessed by UHPLC coupled to mass-spectrometry. Using the BioPEp database, the molecular weight distribution of peptides in the hydrolysates was determined. In addition, bioactive peptides showing the inhibitory activity toward enzymes dipeptidyl peptidase‑4 and amylase were revealed. Based on the obtained hydrolysates, recipes of beverages for patients with diabetes mellitus were modeled in the Excel software program with regard to the recommendations for nutrition of this population group. According to the obtained recipes, beverages were produced in the laboratory conditions and their taste was assessed. An effect of the beverage on glucose reduction in the blood of laboratory animals was assessed upon single peroral administration with a dose of 1.3 ml before the main meal. The results of the investigation of the peptide composition of protein hydrolysates showed the presence of bioactive peptides (SY, VW, SW) in them with the inhibitory activity toward enzymes dipeptidyl peptidase‑4 and amylase confirmed by the BioPep database. The highest amount of the above indicated bioactive peptides (37.1 mg/100 g hydrolysate) was in the protein hydrolysate produced by fermentation of raw materials with propionic acid bacteria. The beverage produced on the basis of the protein hydrolysate and lemon juice was more acceptable for consumers in terms of taste than the beverage with the taste of cacao. The results of the in vivo trials showed that the beverage based on the protein hydrolysate was effective in reducing sugar in blood of both healthy rats and rats with diabetes mellitus. The blood sugar level in the healthy animals of the G1 group (without using the beverage) increased by 151% relative to the initial values, which was a higher value compared to the G2 group (with the use of the beverage), where an increase was 87%. A more significant growth in the blood sugar level (61% relative to the initial values) was also observed in the ill animals in the G3 group (without using the beverage), while this increase was 46% in the G4 group (with the use of the beverage). Thus, the results of the study show the prospects of using the protein hydrolysates from broiler chicken stomachs in whey as an active hypoglycemic component in beverages for patients with diabetes mellitus. However, more profound research is necessary including studies on the representative group of patients.

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The use of new drugs on productive animals is possible only after identifying the long-term effects of the use of substances included in the composition on the functional state of organs, tissues and systems. As a result, the goal of our work was to study the chronic toxicity of the developed composition and the possibility of using it on highly productive cows in the treatment of mastitis. The studied composition was developed at the I.Ya. Postovsky Insititute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciencesand corresponds to the composition: silicon glycerolates – 3,0%, nisin – 0,3%, glycerin – 10%, distilled water – up to 100 %. Chronic toxicity studies were performed on female non-linear white laboratory rats (n=40) using hematological, biochemical, pathomorphological and histological research methods. When conducting hematological studies, it was found that the indicators of the composition of the blood elements of laboratory rats when using the studied composition in different dosages were within the limits. A study of the biochemical parameters of the blood of laboratory animals receiving the composition at a dose of 500 mg/kg and 1000 mg / kg found that the metabolic parameters corresponded to physiological values. Feeding of the studied composition at a dose of 750 mg / kg led to changes in the form of an increase in the enzymatic activity of alkaline phosphatase, a decrease in cholesterol, however, the data obtained cannot confirm the negative effect of the studied dose on the liver, due to the absence of pathological changes in this organ at the cellular level. Histological studies have established that the developed composition can cause changes in organs depending on the dosage used. Based on the research results, we determined that the composition can be recommended for clinical trials on productive animal species at a dose of no more than 500 mg/kg. The use of a dose of 750 mg / kg is recommended to be used with caution in animals with severe liver dysfunction. During further tests, it is necessary to refrain from the critical dose of 1000 mg / kg, which leads to deeper changes in the organs.

Hernias of the anterior abdominal wall remain one of the most common surgery pathologies. There is no unified approach to modeling anterior abdominal wall hernias in the world scientific community. In order to systematize the available knowledge in this field and to contribute to the formation of a unified idea of how to create a hernia model in a laboratory animal, it seems logical to study the accumulated experience of researchers in the field of experimental herniology. We found out that hernia defects generally modeled on male laboratory rats. To understand the tissue reaction to the prosthetic material a fenestration was performed in the anterior abdominal wall (including peritoneum) except for the skin and subcutaneous fat. A replacement or prosthetic material tailored to the fenestration was sutured end-to-end into the abdominal wall. We chose laboratory rats because they are easy to take care of and cheaper than larger laboratory animals.

This review is dedicated to the peculiarities of pathogenesis of the experimental Bolivian hemorrhagic fever (BHF) - the disease, caused by Machupo virus (Arenaviridae family). The authors come to the conclusion that for carrying out preclinical researches of the medical means of protection (MMP) in vivo on small laboratory animals it is expedient to use guinea pigs, infected with a strain of Chicava or with a variant of Carvallo strain, adapted for these animals. The use of guinea pigs as small laboratory animals when studying pathogenesis of the disease caused by Machupo virus allows to carry out statistically reliable definition of quantitative indices of an experimental infection and to select medicines for the final stage of preclinical assessment. As arenaviruses block the process of formation of interferon (IFN) in the infected organism, mice, defective by IFN formation, are the perspective animal models for the study of BHF pathogenesis and may be used for the study of attenuated variants of Machupo virus. The Javanese macaques (Macaca fascicularis) are the laboratory animals, modeling the pathogenetic manifestations of BHF in humans. They can be used when carrying out the final stages of preclinical assessment of means of medical protection.

The aim of the work was a preclinical assessment of acute toxicity, skin resorptive, irritant effects, cumulative and catalase activity, as well as sensitizing properties of the local gel composition “Benzidaflaziverdine” (GCB) used for the treatment of periodontal diseases in orthodontic patients. Materials and methods. 119 animals were involved in the experiment, assigned to seven main and two control groups. GCB was administered intragastrically in doses of 300–600 mg/kg and intradermally of 200 μg into the outer surface of the ear. The native solution of GCB was applied to the skin and mucous membranes, administered orally by the method of “subchronic toxicity” and to the surface of the chorioallantoic membrane (CAM) of chicken embryos. The intensity of lipid peroxidation (LPO) was assessed by the level of diene conjugates (DCs) and malondialdehyde (MDA), and the antioxidant system by catalase activity. The specific leukocyte agglomeration reaction (SLAR), the specific leukocyte lysis reaction, and neutrophil damage indicators were used. Results. The median lethal dose LD50 for rats and mice of both sexes exceeded 5000 mg/kg. The irritant effect of GCB on the mucous membranes was manifested by hyperemia on the second day. Symptoms of irritation disappeared after 3–4 days without medical intervention. An analysis of the CAM blood vessels after exposure to GCB in two observations at the 120th second showed the beginning of hemorrhages. In one observation, GCB caused minor hemorrhages at the 300th second of the experiment. It was found that the coefficient of GCB irritant action was 5 (the mean score of Me (Q1; Q3) was 5 (4; 5)). The coefficient of cumulation (Kcum) exceeded 8.2. An insignificant increase in the median or mean values of catalase enzyme activity, DCs, and the amount of LPO end product such as MDA was observed compared to the control group animals. The SLAR test indicated the development of a delayed-type allergic reaction under the influence of GCB in a 1:10 dilution. One-hundred-fold dilution did not cause significant changes in the indicator in the main group compared to the control one. Conclusions. GCB belongs to the 4th class of toxicity – practically non-toxic substances, does not have sex- and species sensitivity, has weak cumulative activity, minimal effect on the system of LPO. GCB can be recommended for the use in clinical periodontology for medical support of orthodontic patients.

To date, there is no registered injectable dosage form of levocarnitine for veterinary use on the territory of the Russian Federation. Based on the above, the purpose of our work was to conduct preclinical studies of L-carnitine of subchronic toxicity for veterinary use in laboratory animals. Experiments to test the toxicity were performed on outbred rats in October 2021 at the vivarium of St. Petersburg State University of Veterinary Medicine. The study involved females weighing 190210 grams, purchased from RAPPOLOVO Laboratory Animal Nursery. To study subchronic toxicity via subcutaneous injection, L-carnitine was administered in 2 dose levels. The doses were determined based on the results of the acute toxicity experiment: 1/5 and 1/10 of the maximum tolerated dose. The first experimental group (n=10) received the drug subcutaneously at a dose of 0.08 mg/kg (1/5 of 2000 mg/kg). The second experimental group (n = 10) received the drug subcutaneously at a dose of 0.04 mg/kg (1/10 of 2000 mg/kg). The control group (n = 10) received sodium chloride 0.09 % subcutaneously at a dose of 1/5 of 2000 mg/kg. The drug was administered subcutaneously daily for 42 days. Killing and blood sampling from the second half of the animals was carried out after assessing the recovery period (10 days after drug cancellation). As a result of studies of subchronic toxicity of subcutaneously administered L-carnitine for veterinary use in laboratory animals, it was found that the dosage of 1/5 of the maximum tolerated, and the dosage of 1/10 of the maximum tolerated, do not cause external signs of toxicosis and death of rats. No significant changes in the hematological parameters of blood of animals from the experimental and control groups were found.

According to the World Health Organization, the most common (up to 90% of cases) hematological pathology is anemia, a condition characterized by a decrease in the level of hemoglobin in the blood due to a decrease in the total number of red blood cells or a violation of hemoglobin synthesis, which can have serious consequences for the body, such as decreased immunity, impaired respiratory and metabolic processes. Currently, it is necessary to improve the methods of prevention and treatment of anemia. To test new drugs for these purposes, it is necessary to create new models, including on laboratory animals. The aim of the study was to develop experimental models of iron deficiency (IDA) and hemolytic anemia (HA) on laboratory animals. The objects of the study were sexually mature male laboratory rats of the Wistar breed, aged 7 months and weighing 260 ± 20 g. 38 animals were involved in the experiment (for IDA n= 24, for HA n= 14). Laboratory animals were kept in the same external conditions for 3-4 individuals in a cage. To simulate IDA, rats were subcutaneously injected with the drug “Desferal”. To simulate GA, rats were intraperitoneally injected with the drug “Hydrochloric acid phenylhydrozine”. At each stage, blood was taken by cutting off the tip of the tail. A detailed blood test was performed on a hematological analyzer “Heska Element HT5”. As a result, it was found that when the drug “Desferal” was administered at concentrations of 125 and 250 mg / 100g per animal weight, hematological changes were observed in rats, such as an increase in red blood cells, platelets, leukocytes by stage 2 and a decrease to control values by stage 4. When the drug “Hydrochloric acid phenylhydrozine” was administered, hematological changes were detected in rats only within the experimental group. There was an increase in the indicators of erythrocytes, platelets, leukocytes by stages 2 and 3 and a decrease to control values by stage 4. Thus, when the studied drugs were administered in the presented dosages in vivo, a change in the hematological parameters of the blood was detected in the direction of an increase in their number due to adaptation to the effects of substances.

In view of increased incidence of IgE-mediated diseases in Russia and worldwide, the efforts of various research groups are focused on studying the mechanisms that trigger the process of switching B-lymphocytes to IgE synthesis upon human exposure to harmless allergens, including the role of various antigen-presenting cells (APCs) in this process. However, the role of distinct APCs upon long-term penetration of low antigen doses via the tissue barriers, is yet poorly understood, as well as specific features of these events upon entrance of the antigen through the subcutaneous adipose tissue which contains tissueassociated lymphoid clusters (TALC).The aim of this work was to determine the relationship between the local accumulation of various APCs in the subcutaneous adipose tissue and development of early IgE production in a clinically relevant experimental model of allergy with long-term administration of low allergen doses. In this experimental model, specific IgE synthesis is induced, with minimal concomitant IgG production, thus mimicking the situation observed in patients with clinically sound allergies. BALB/c mice were immunized for 4 weeks subcutaneously in the withers area or intraperitoneally with low (100 ng) or high (10 μg) doses of the model allergen (ovalbumin). Blood samples were taken weekly from mice for ELISA testing, to determine the production of specific antibodies. Provocation tests were performed with high dose of the allergen, and adipose tissue samples were taken from the site of antigen injection for flow cytometric assays, in order to evaluate the contents of various APC subpopulations. Specific IgE production was induced mainly by subcutaneous injection of the antigen at low doses (100 ng) into the area of withers. When using this experimental regimen, we observed accumulation of classical CD11b+ cells in adipose tissue at the withers site, but not in the peritoneal adipose tissue, in absence of CD11b- classical, inflammatory or plasmacytoid, dendritic cells. These findings coincided in time with increased production of specific IgE on days +14 to +21. Accumulation of CD11b+CD11c- macrophages and their CD206+ M2 subpopulations at early terms (days +7 and +21) was also observed only after subcutaneous injection of the antigen into the withers area. The high-dose antigen injection (10 μg) which mediated IgG1 production to greater extent than production of IgE, led to earlier accumulation of CD11b+ classical dendritic cells (on day 7th), and to the absence of macrophage accumulation at later stages (day 21th). Thus, the early start of specific IgE production upon low-dose injection of the antigen into the subcutaneous adipose tissue may be associated with its presentation by CD11b+ classical dendritic cells in the presence of CD11b+CD11c- macrophages.

Background. A typical extreme factor is hypoxia, which significantly affects the ability to perform tasks of professional activity, in particular, physical activity of various intensity. Physical and neuro-emotional stress under conditions of hypoxia can cause the breakdown of compensatory and adaptive mechanisms with the development of extreme and critical conditions.The aim of the study. Quantitative assessment of the effect of hypoxia on the physical performance of laboratory animals at different levels of their natural resistance.Research methods. Modeling of hypoxia was carried out by the methods of pressure chamber rise of laboratory animals and the administration of a methemoglobin former. Resistance to hypoxic hypoxia was assessed by the criterion of the threshold elevation, to hemic hypoxia – by the lifetime. The criterion for the functional state of laboratory animals was their ability to perform physical activity, which was created by treadmill run or swimming with a load.Results of the study. An altitude of 3500 m causes a decrease in the physical performance of male rats by a third of normoxia level; an altitude of 5000 m – decrease by two times; an altitude of 6500 m – decrease by four times, and at an altitude of 8000 m makes running physical activity by rats impossible. A mild degree of hemic hypoxia causes a decrease in swimming time by almost 2 times, which corresponds to the effect of an altitude of 5000 m on the working capacity; and a moderate degree of hemic hypoxia causes a decrease in swimming time by more than 3 times, which approximately corresponds to the effect of an altitude of 6000 m. The level of resistance to hypoxia has a moderate effect on physical performance, and the factor of a low level of physical performance has almost no effect on the resistance to hypoxia (28 % and 7 % of the trait variability respectively). In animals with an initially low level of resistance to hypoxia, there is also a decrease in working capacity by an average of 20 %.Conclusion. Hemic hypoxia is an adequate model in studies with a complex effect of various extreme factors. Simulation of mild hypoxia caused by the administration of 30 mg/kg of sodium nitrite is an optimal method.

Experiments with small laboratory animals are required for better understanding of a disease flow, for studying the mechanisms of it’s development and for the development of new therapeutic strategies. A significant part of experimental studies involve anesthesia. In this regard, the choice of the optimal anesthesia protocol is an important point of research, since an inadequate depth of anesthesia or the influence of undesirable factors can lead to death; the type, duration, and goals of the procedure should be also taken into account.We have aimed to find out what has changed in anesthesia of laboratory animals lately, which drugs are currently relevant and what is the reason for their popularity.Anesthesia of mice is challenging for several reasons: animal size, metabolic rate, and high risk of hypothermia and hypoglycemia. In addition, anesthetics affect physiological parameters and therefore even more affect the results of experiments. At the moment, there is a large list of drugs used in laboratory animals. Since they are divided into groups depending on the routes of administration, we selected the following drugs from a number of articles: injectable anesthetics (medetomidine, dexmedetomidine, zoletil‑100, ketamine, xyla, propofol) and inhalation anesthetics (isoflurane, sevoflurane). Advantages and disadvantages of the drugs and their combinations were studied and described.An analysis of the literature showed that injection anesthesia is considered the main method of anesthesia for experimental animals and is relatively well tolerated by animals; it also does not require additional bulky equipment and additional staff qualifications, there are antagonists for a number of drugs, and is also affordable.In the majority of studies inhalation anesthesia was used in long-term complex manipulations/operations, since it is more manageable, agents require minimal metabolism, and in some cases do not require additional sedation.

Peptides have high biological activity and are used in the composition of medicines. Peptides are not widely used in food technology as they are sensitive to the action of proteolytic enzymes of the gastrointestinal tract and are characterized by rapid decomposition reducing their effectiveness. Colostrum of cows is a promising source of peptides with different functional orientations. One of the ways contributing to the expansion of using peptides when administered orally is their microcapsulation. The aim of the research is to develop a technology and method for microcapsulating peptides extracted from cow colostrum after calving and to assess their subchronic toxicity. The development of an installation for microencapsulation of peptides was carried out taking into account the diameter of the wide part of the cone of the working chamber and the speed of soaring of small particles of peptide conglomerates. For the experiment on the comparative assessment of the subchronic toxicity of encapsulated and free peptides, 4 groups of nonlinear mice were formed, 10 in each. Group 1 of mice was a control, group 2 (experimental) received an extract of the fabricium bag of broiler chickens containing peptides of various molecular weights at a dose of 15,000 mg/kg, group 3 – free peptides extracted from cow colostrum serum in an amount of 1,500 mg/kg, group 4 – encapsulated peptides in an amount of 15,000 mg/kg. Hematological blood analysis was performed using the analyzer PCE-90Vet. The mice were weighed on the 7th, 9th, 14th, 21st and 28th days of the experiment. Biochemical analysis of animal blood sera was carried out using the analyzer StatFax 3300. During the study, it has been found that the treatment of peptides with maltodextrin solution for 1.0–1.5 minutes forms a protective coating with a thickness of more than 2 microns. The diameters of the wide and narrow parts of the cone of the device and the velocity of the gushing streams for the smallest and largest particles of the peptide conglomerate have been calculated. The absence of toxicity of microcapsulated peptides has been proven.

Foundation. Chronic plantar fasciopathic pain syndrome is a pathology that significantly affects the quality of life of patients of all age categories. Insufficient knowledge of the etiological and pathogenetic factors in the development of fasciopathies explains the multiplicity, and sometimes inconsistency, of conservative and surgical treatment regimens. The choice of the optimal variant of therapeutic or surgical intervention may be associated with experimental modeling of fasciopathies and the study of the dynamics of the pathological process.The aim. To study the morphological changes in structures identical to the human plantar aponeurosis in experimental modeling of fasciopathy in animals.Research methods. The material for the study was fragments of the tendonaponeurotic complex of the foot of laboratory animals (control group: animals with the introduction of physiological sodium chloride solution (n = 12); main group: animals with the introduction of alprostadil (n = 12)). The methods of light microscopy (staining with alcian and toluidine blue, according to Van Gieson, Weigert – Van Gieson and Picro-Mallory) and morphometry were used.Results and discussion. As a result of the study, it was found that the four-fold administration of alprostadil had a significant effect on the structure of the dense fibrous connective tissue of the plantar foot of laboratory animals. The mechanisms of damage (edema, microhemorrhages, infiltration by lymphocytes, plasmocytes and leukocytes, dystrophy by the type of mucoid and fibrinoid swelling, delamination and rupture of collagen fibers), adaptation and regeneration (the appearance of a large number of activated fibrocytes, fibroblasts, microvessels, neoplasm of collagen fibers) were activated. All this together led to spatial focal histotopographic changes, consisting in an increase in the cellular composition of connective tissue structures against the background of a noticeable violation of their spatial orientation.Conclusion. Modeling of fasciopathy using alprostadil was accompanied by the appearance of mosaic reversible and irreversible heteromorphic and heterochronous changes in all connective tissue aponeurotic structures. Such histotopographic changes should be considered as one of the reasons for the clinical manifestations of plantar fasciopathies, causing functional insufficiency and explaining the clinical recurrent nature of the pathological process.

Introduction Functional recovery of the finger flexor tendon after surgical treatment is a problem due to formation of unavoidable blocking adhesions. For prevention of the adhesions, the mechanical separation of the sliding surfaces of the tendon and the wall of the fibro-osseous canal with a polymer tube was proposed. However, despite good clinical results, it is not possible to morphologically confirm the healing of the suture zone after such an intervention. Objective To present an experimental model and technique of surgical intervention on the calcaneal tendon of laboratory animals for isolation and blocking with a polymeric tube, longitudinally cut, for obtaining and studying the regenerate in the suture site Materials and methods In an experiment under inhalation anesthesia with Isoflurane on both hind paws of 10 laboratory Wistar rats, the tendon suture was simulated with blocking and isolation of the tendon suture (n = 14) and the control operation without isolation (n = 6). The tendons were excised three weeks post-surgery, and the appearance and histological picture of the regenerates in the suture zone were examined. Results The surgery model with isolation of the suture site on the calcaneal tendons of rats reproduces well and adequately simulates the operation on the human hand tendons. The morphology of the obtained regenerates demonstrates the restoration of continuity with the formation of tendon-like tissue at the junction. In the experiment, subtotal isolation did not lead to tendon necrosis, but slowed down the healing of the suture zone. The tube prevented the formation of adhesions and maintained tendon nutrition through the fissure space. Conclusion Modeling of the operation of tendon suture on the rat calcaneal tendon with its isolation provides material for demonstration the primary tendon regeneration in vivo. Regeneration of the suture site during subtotal isolation slows down and occurs due to the cells of the tendon itself.

Peptides are biologically active. This quality depends on the technological modes of protein hydrolysis. The research objective was to isolate peptides from the bursa fabricii and evaluate their immunotropic effect on mice of various lines with experimental immunodeficiency and the morphofunctional state of their immunopoiesis organs, i.e., thymus and spleen. The research featured bursa fabricii hydrolysate and peptides, as well as thymus and spleen of male mice. Amine nitrogen was determined according to State Standard R 55479-2013; molecular weight of peptides was determined by gel electrophoresis. The morphometry of the thymus and spleen was calculated using VideoTesT-Morphology 5.0. The research revealed the rational modes of enzymatic hydrolysis of the bursa fabricii protein by papain with subsequent isolation of peptides by ultrafiltration. According to the content of amine nitrogen in the bursa fabricii hydrolysate, the rational concentration of the papain enzyme was 0.15%. The molecular weight of peptides after ultrafiltration of bursa fabricii hydrolysate through membranes with a 43 kDa permeability had different values and depended on the concentration of papain, hydrolysis time, and temperature. The maximal amount of 27–18 kDa peptides was isolated at 36°C (85%) when the concentration of papain was 0.15% (73%), the hydromodule was 1:3 (78%), and the hydrolysis time of the raw material was 6 h (82%). The rational technological parameters of the hydrolysis of the bursa fabricii protein were as follows: concentration of papain – 0.15%, temperature – 36°C, hydromodule – 1:3, and hydrolysis time – 6 h. In immunodeficient mice, bursal peptides prevented a decrease in total cellularity in the thymus, sustained the content of CD3+ cells, activated the maturation of T-lymphocytes and proliferation of B-lymphocytes, and reduced the immunocytotoxic effects of cyclophosphamide. The article offers a new technology for obtaining peptides with a pronounced immunotropic effect that can be used in functional food production.

Excessive use and abuse of disinfectants over the past century has created problems associated with the emergence of resistant microorganisms. In addition, there is always a potential risk to human and animal health, as the use of aggressive disinfectants can lead to diseases. The purpose of the study was to investigate the toxicity of an ex perimental disinfectant to determine the possibility of its use in the presence of humans and animals. Study material – an experimental product (water-soluble disinfection powder). Experimental studies were conducted at the premises of a certified vivarium of the ECOMEDCHIM regional centre of Sumy State University and Sumy National Agrarian University. Acute toxicity of the preparation was studied on 30 white mice weighing 19.5±1.0 and 15 white rats weighing 200±15.0 g. Determination of toxicity by prolonged oral administration was studied in two analogous groups of white rats, 6 animals each with a bodyweight of 185±10.0 g. The effect of the preparation on the state of internal organs was evaluated by comparing relative mass coefficients. The local irritating effect of the preparation was determined by skin applications on 10 rabbits weighing 2.97±0.3 kg. The disinfectant, when administered orally once at doses of 1,250, 2,500, and 5,000 mg/kg of body weight, did not cause the death of experimental mice and rats. When administered orally for 30 days at a dose of 2,500 mg/kg of body weight, the disinfectant did not cause any negative and toxic effects on the body of experimental rats, did not affect the growth and development of rats, and did not cause changes in the relative mass of internal organs. It was found that the average manifestation of erythema in rabbits is 2.46. According to the study results, it was found that the disinfectant can be classified as Hazard Class 4 according to the international standard GOST 12.1.007-76, or Category 5 according to the international global classification Global Harmonised System (GHS) (LD50 with oral administration exceeds 5,000 mg/kg of body weight). The results obtained give grounds to assert the possibility of using an experimental disinfectant in the presence of humans and animals

The use of biologically active substances of tissue origin for the creation of biologically active additives and immunomodulatory drugs is an important area of scientific research in the field of nutrition and pharmacology. The aim of the work is to evaluate the effect of enzymatic hydrolysate from the fabricium bag of broiler chickens on the cytotoxicity and nonspecific immunity of mice against the background of experimental salmonella infection using biotechnological methods. For the experiment, three equal experimental groups of white mongrel mice were formed. All laboratory animals were fed daily for seven days with enzymatic hydrolysate at a dose of 750 mg/kg (therapeutic dose), 150 mg/kg (0.2 therapeutic dose) and 3,750 mg/kg (five therapeutic doses). At the same time, the control group of animals received intragastric water in the same volume. 24 hours after the last intake of the enzymatic hydrolysate, the animals were intraperitoneally infected with a culture of Salmonella enteritidis 92. The study reveals the absence of cytotoxic properties and impaired cell viability in cultures L929, J774.1A, HeLa S3, K562, and HST116 against the background of exposure to various concentrations of enzymatic hydrolysate from 0.02 to 10 mg/ml. It should be noted that there is a pronounced cytotoxic effect on MCF-7 tumor cells of the concentration of enzymatic hydrolysate in culture of 5 and 10 mg/ml, which suggests the possibility of using enzymatic hydrolysate for the prevention of tumor diseases. As a result of the experiment, it has been proved that the administration of enzymatic hydrolysate to mice increased the LD50 index and the survival rate of mice infected with the culture of the causative agent of salmonellosis by 1.5 times. Based on the conducted studies, it has been shown that the enzymatic hydrolysate of the lymphoid tissue of broiler chickens does not violate the viability of mammalian cells and does not exhibit cytotoxic properties on the metabolism of healthy mammalian cells, which indicates its safety. In an experiment on mice, the effect of enzymatic hydrolysate of the fabricium bag of broiler chickens on the activation of nonspecific immunity against salmonella infection has been revealed.

Authors have studied the antitumor efficacy of contact radiation therapy (CRT) in combination with a chlorin-based photosensitizer (PS) in an experiment on laboratory animals with transplanted tumors. The experimental study was performed in 50 white outbred rats weighing 250±50 g. Subcutaneously transplanted Pliss lymphosarcoma (PLS) and alveolar liver cancer RS1 (RS1) were used as tumor models. Chlorinbased PS photolon (RUE «Belmedpreparaty», Republic Belarus) was injected intravenously at a dose of 2.5 mg/kg. The radiation sessions were carried out 2.5–4 hours (depending on the tumor model) after the administration of the PS using the device «microSelectron HDR V3 Digital» («Nucletron», Netherlands) with a 192-Ir radiation source in single focal doses 5 and 10 Gy. All laboratory animals (for PLS and RS1) were subdivided into 5 groups of 5 animals each: intact control, CRT 5 Gy, CRT 10 Gy, PS + CRT 5 Gy, PS + CRT 10 Gy. For the PLS tumor model – on the 14th day from the beginning of the experiment Vav. in groups were 26.31±5.81; 22.45±6.97; 18.99±4.86; 10.75±5.18 and 28.06±2.85 cm3, respectively (p˂0.05). The coefficients of tumor growth inhibition in the experimental groups were 14.67%, 27.82%, 59.14% and 6.65%, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0%, 20%, 20%, 60%, and 20%, respectively. On RS1 tumor model – on the 14th day from the beginning of the experiment Vav. in groups were 4.48±1.03; 0.80±0.21; 0.29±0.09; 0.19±0.07 and 0.32±0.08 cm3, respectively (p=0.009). The coefficients of tumor growth inhibition in the experimental groups were 82.14%, 93.53%, 95.76% and 92.86%, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0%, 0%, 20%, 0%, and 0%, respectively. Systemic administration of chlorin-based PS before the CRT session increases the antitumor efficacy of radiation therapy in animals with transplantable tumors of different histological structure and growth patterns. The data obtained indicate that further studies of the radiosensitizing properties of PS are promising.

The rapid development of the latest innovative technologies that improve human life have tragic consequences. The irreversible and cruel reverse side of the progress is the emergence of various diseases and pathologies. Cardiovascular diseases occupy a leading position in the morbidity and mortality of people of different ages in the world. Functional food products can be used to prevent diseases of the heart, the blood vessels and the thyroid gland. One of the ways to increase immunity of the population can be the expansion of specialized food production that are balanced in the content of macro- and microelements, take into account the peculiarities of metabolic processes, pathological conditions that occur at different ages in people. Pork, enriched with microelements in its lifetime, is a promising raw material for improving the technology of organic pork production. The developed technology for obtaining organic meat raw materials has passed various tests in the farms of the Krasnodar Territory, which are the main suppliers of pork for the manufacture of specialized functional products. For the manufacture of a specialized meat product, meat without lard has been used. The article presents studies of nutritional and biological value, nutritional adequacy of pork and by-products enriched while alive. Specialized pasteurized meat products enriched with microelements (iodine and selenium) have been developed, and the qualitative composition of a specialized meat product has been disclosed, which can be used to prevent cardiovascular diseases and diseases of the thyroid gland. Experiments have been carried out on laboratory animals (white rats) to confirm the biological effectiveness of a specialized meat product.

Introduction. Acute toxicity of naltrexone hydrochloride nasal spray during intragastric administration to mice and local irritant effect on rabbits was studied. At all stages of the experiment, observations were made on the General condition of the animals. The state of homeostasis was evaluated using functional, hematological and morphometric methods. According to the results of research, there was no local irritant effect on the eyes of rabbits, as well as no toxic effect of high doses of the drug on animals. Introduction. Naltrexone hydrochloride in doses of 1.5– 5 mg/day has shown its effectiveness in the treatment of a number of diseases. Due to the lack of such a "low-dose" naltrexone registered on the pharmaceutical market, we have developed the composition of the nasal spray naltrexone hydrochloride. One of the stages of our research is to study the safety of the drug being developed. The first step in this direction was to study its acute toxicity and local irritant effect.Aim. Study of acute toxicity and local irritant effect of naltrexone hydrochloride nasal spray.Materials and methods. The object of the study was a nasal spray of naltrexone hydrochloride. Acute toxicity studies were performed on outbred adult mice (females). Study of local irritant effect on Soviet chinchilla rabbits (males).Results and discussion. The study of acute toxicity showed that the drug, at a dose significantly higher than the estimated maximum daily therapeutic dose for humans, did not have a significant toxic effect on the body of laboratory animals. The presence of a local irritant effect in the studied drug was not established in the framework of the experiment.Conclusion. As part of the experiment, the drug under study did not have a local irritant or toxic effect on the animal body. The results obtained allow us to continue the development and study of the nasal spray naltrexone hydrochloride.

The aim was to evaluate the effectiveness of using the “Sterius 60” microwave disinfection system (Russia) for decontamination of objects infected with PBA of groups I–IV emerging as a result of working with infected laboratory animals.Materials and methods. Effectiveness verification of disinfection of biological waste generated as a result of the life of laboratory animals by SHF radiation was carried out in the microwave system “Sterius 60”, recommended by the manufacturer for disinfection of epidemiologically hazardous and extremely dangerous medical waste, including biological ones (classes B and C), by volumetric SHF heating. Carcasses of uninfected laboratory animals (white mice, Guinea pigs, suckling rabbits), granulated feed and bedding material (wood shavings), which are objects directly in contact with biomodels, were used as vivarium waste to be decontaminated. The following microorganisms were utilized as model test ones: Bacillus subtilus VKM B-911, Bacillus stearothermophilus VKM B-718, Bacillus licheniformis G VKM B-1711-D, Alcaligenes faecalis 415, Yersinia pestis EV, Bacillus anthracis STI. Laboratory utensils (plastic Petri dishes, porcelain mortars and pestles) were used as a mock-up chamber filler for model test microorganisms.Results and discussion. As a result of the study, data were obtained indicating that the microwave system for disinfection of medical waste “Sterius 60” is ineffective for decontamination of biological waste in laboratories working with biomodels infected with PBA of groups I–II. The established standard mode of disinfection of this system was effective only for non-spore forms of microorganisms, pathogenicity groups III–IV. Therefore, in our opinion, it is advisable to use it for decontamination of laboratory utensils infected with PBA of groups III–IV, directly at sites of waste generation.

Introduction. In recent years, there has been a steady increase in gastroenterological diseases in many countries due to adverse environmental conditions and unsustainable nutrition. Diseases of digestive organs are not only chronic, but also combined, and varieties of synthetic drugs are widely used in therapy. The range of official multicomponent plant collections recommended in the therapy of diseases of the digestive system is limited, and their disadvantage is especially felt in the treatment of chronic hepatitis, gastric ulcer, cholecystitis.Aim. Search and creation of new multicomponent agents for prevention and complex treatment of digestive system diseases.Materials and methods. The objects of the study were developed multi-component means: «Pentafit», «Octafit», «Hexafit». To assess the pharmacotherapeutic effect of the developed agents «Pentafit» hepatoprotective activity studied in experimental models tetrachloromethane and D-galactosamine hepatitis, «Octafit» gastroprotective activity studied in models of acute aspirins, neurogenic and chronic butadione ulcer, сholeretic activity of «Hexafit» as studied in models of experimental cholecystitis and toxic liver damage using laboratory animals. The results of the studies processed statistically using the Statistica 10 program.Results and discussion. Based on the obtained data, the general patterns in molecular biological action of the studied multicomponent agents revealed, which consist in their ability to inhibit the free radical oxidation of lipids and stabilize the biological membranes of gastric cells and organs of the hepatobiliary system. «Pentafit» profitably distinguished by its multilateral nature of influence on the functional state and structure of the organs of the liver. «Octafit» provides accelerated healing and restoration of damaged structures of functional systems of the stomach. «Hexafit» secreted by the polyvalent spectrum of action in case of damage to the hepatobiliary system.Conclusion. Developed multicomponent drugs will expand the register of medicines of plant origin of domestic production for the prevention and treatment of digestive diseases.

The object of the study was to analyze radionuclide detection techniques for in vivo animal imaging. Material and Methods. A total of 49 publications available from Scopus, Web of Science, Google Scholar eLIBRARY and Pubmed and published between 2013 and 2019 were reviewed. Results. The nuclear medicine techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are the most suitable imaging modalities for in vivo animal imaging. Besides traditional radiopharmaceuticals, such as [18F]-FDG and [99mTc]-MDP, the new radiolabeled tracers, such as [99mTc]-3PRGD2, [ 99mTc]-HisoDGR targeted to integrin, [18F]- tetrafluoroborate, labeled antibodies and others have been used for the noninvasive detection of tumors and for monitoring their response to treatment in mice and rats. 111In and 89Zr –labeled monoclonal antibodies are used to evaluate the expression level of many receptors such as EGFR, HER-2 and others in different tumors. PET imaging has demonstrated a good efficacy in tumor hypoxia imaging with [64Cu]-ATSM, [18F]-FMISO. PET and SPECT can also be used for early evaluation of anticancer therapy response. Nuclear imaging techniques may assist in the vivo assessment of DNA damage (doubleand single-strand brakes) as well as apoptosis intensity in tumor and normal tissues. [99mTc]- duramycin is the most commonly used tracer for imaging of apoptosis. Changes in tumor cell proliferation in response to anticancer therapy can be assessed by PET imaging with [18F]-FLT. Conclusion. Nuclear medicine offers a unique means to study cancer biology in vivo and to optimize cancer therapy.

Preparations such as XilaVet, Zoletil 100 as well as Aeranne (Isoflurane) are successfully applied for animal anesthesia in veterinary practice. We assessed a possibility of using parenteral narcosis with Zoletil 100 in combination with muscle relaxant Xila for producer-rabbits involved in manufacturing of natural rabbit serum subsequently deployed for production of diagnostic serum and immunoglobulin preparations. Administration of preparations into auricular vein is easy to do, while animals are sedated immediately allowing for safe fixation on restraining table and causing no additional stress for biomodels. This type of narcosis provides for expected depth of anesthesia and its maintenance until the end of blood-letting procedure. Parameters characterizing the state of cardiovascular system due to anesthetic products remained within the permitted limits. These preparations do not reduce heart beat rate allowing for collecting sufficient blood volumes. Application of inhalation anesthesia with Aeranne in laboratory animals provides for the specified depth of anesthesia and its maintenance until the end of the whole procedure. However, it requires specialized equipment and highly trained personnel with appropriate skills. Usage of Xila as a mono narcosis is not recommended as exhibits weak analgesic effects and strong hypotensive activity by decreasing quantity of collected blood volume. It was found that anesthetics such as Xila, Zoletil 100, Aeranne did not affect specific activity of immune sera in case of total dehematizing procedure. Moreover, antibody titers were not declined throughout entire observation (12 months) period and complied with the requirements of regulatory documentation. In addition, a feasibility of replacing old-fashioned anesthesia method with diethyl ether for a combination of safer contemporary preparations of Zoletil 100 and Xila was demonstrated while manufacturing tableted chemical cholera vaccine in experimental series with suckling rabbits used at diverse stages of raw material verification during surgical interventions. Xila, Zoletil 100, and Aeranne examined by us had no impact on the amount of blood obtained from donor-animals, immunological properties of the sera and ready-to-use diagnostic preparations. Such drugs were safe for all-age animals that comply with the requirements to anesthesia of animal biomodels and producer-animals in manufacturing of immunobiological preparations. Thus, our study allowed to conduct experiments with laboratory animals in a more humane manner.

The problem of modern poultry farms is arising number of hens in a limited area causing risk of microbial contamination, direct infection and transmission of diseases is increasing. The complex ADG disinfectant combines active substances with a neutral pH and low corrosion activity. It is worth-while to conduct experiments with laboratory animals to determine the toxicity of new modern disinfectants for introduction and use in poultry farms. The purpose of our studies was to determine the acute toxicity of ADG disinfectant to laboratory animals. The task was to determine the lethal and median lethal dose of ADG disinfectant. The acute toxicity of ADG was calculated by intra-gastric administration to white rats. The median lethal doses of disinfectant were determined according to G. Kerber (1931). The results obtained on white rats were LD50=3800 mg/kg and LD100=7200 mg/kg. Symptoms of ataxia, impaired motor activity, increased excitability, impaired stimuli, bradypnea, tachycardia were observed in surviving animals from the first to the tenth day. Intra-gastric administration of 0,1 % working concentration disinfectant solution caused LD50=5000 mg/kg, LD100=8400 mg/kg. During postmortem examination we detected next: the stomach is filled with mucus, the walls are thickened, the mucous membrane is hyperemic. The mucous membrane of small intestine was thickened, swollen, has catarrhal-hemorrhagic exudate. The large intestine was without visible changes. Our studies have shown that 0,1 % concentration of ADG is come under the 4th toxicity notion (low toxicity). To test the ADG disinfectant in a poultry environment is the ultimate goal of our further investigations and observations.

We studied the histological condition of the pulp of the tooth on 1, 3, 7, 14, 28 day after exposure microsecond Nd:YAG laser with 4 W after removing stamped crowns and composite fillings. The absence of the pathological effect on the tooth pulp microsecond radiation Nd:YAG laser with a water jet cooling after removal restorations from composite material, as well as water spray cooling during removal of dental prosthetics.

We chose diisononyl phthalate as our experimental research object; this compound is an isononyl ester of phthalic acid based on n-butene (CAS No. 28553-12-0). Our research goal was to establish peculiarities and regularities related to toxic effects produced by diisononyl phthalate on experimental animals’ bodies and give scientific substantiation for fixing its permissible quantities that could migrate from polymer materials and medical products. We accomplished our research applying a set of toxicological, physiological, hematologic, biochemical, immunologic, cy-togenetic, morphological, organoleptic, sanitary-chemical, and statistical techniques. We were the first to establish peculiarities of toxic impacts exerted by diisononyl phthalate after intragastric introduction into white rates. Those impacts were dose-dependent toxic effects produced both on a whole body and specific organs and systems with typical disorders in functional and morphological parameters, cell differentiation, and an increase in number of cells with changes in their genetic apparatus. We revealed that overall toxic effects as well as specific damaging ones produced by diisononyl phthalate on the endocrine and reproductive systems in experimental animals’ bodies became apparent via functional disorders in the thyroid gland and gonads, embryogenesis, and offspring post-natal development. A chronic experiment allowed us to determine quantitative regularities and how toxic effects produced by diisononyl phthalate manifested themselves; so we were able to determine limiting parameters and a biological marker as well as fix a threshold of its hazardous impacts on a body, and substantiate fixing permissible quantities that could migrate from polymer materials and medical products. Our experiment results gave grounds for creating a hygienic standard for diisononyl phthalate that provided hygienic assessment and safe distribution of materials and medical products made of polymers that contained the compound.

To date, cancer diseases are one of the leading causes of mortality and morbidity in the world. Recent advances in understanding the molecular genetic mechanisms of oncogenesis and anti-cancer immune responses open new opportunities for the development of novel effective therapeutic strategies against cancer diseases; the strategies that would be more specific to tumor cells and less toxic to the host. Immunotherapeutic anti-cancer vaccines and oncolytic viruses are among the most promising approaches of this kind. For rapid and reliable screening and preclinical testing of new therapeutic approaches the relevant animal models are of critical importance. Such models provide the ability to partially reproduce tumor microenvironment and vascularization, as well as to reproduce at some extent the immune system reactions. Allograft and xenograft tumor models are the most common in cancer research. Allogenic transplantation involves the cancer cells or tumor fragments transfer between the organisms of the same species. Xenoplastic transplantation involves the transfer of tumor cells or tissues between the organisms of distinct species. Both tumor cell lines and patient-derived tumor cells and fragments obtained with biopsy can be used for xenotransplantation. Over the past decades the researchers developed numerous strains of immunodeficient mice and rats, suitable for xenografting human tumors. However, despite the widespread of immunodeficient laboratory animals as in vivo models in experimental oncology, these models do also have significant limitations associated with inability to fairly reproduce the tumor microenvironment and human immune system functions in mice, and also with the development of graft versus host reactions. Thus, when planning the experiments, it is necessary to carefully analyze all the advantages and disadvantages of animal strains, supposed to be used in experimental oncology studies.

Allergenic and genotoxic effects of the medical device «Resorbable collagen material "COLLOST® gel» were studied in laboratory animals. It was shown than immediate-type hypersensitivity reaction is not detected in mice by the cutaneous anaphylaxis test after once weekly sensitization during 30 days. Conjunctival test revealed no hypersensitivity to medical device in guinea pigs after three times sensitization for every 48 hours. Guinea pig maximization test did not reveal any skin-sensitizing effect of the medical device. Bone marrow chromosome aberration test did not detect genotoxic effects of the medical device.

Today, within the context of harmonisation of requirements in the international pharmaceutical market, there is a trend towards development of common standards, including in the field of preclinical studies. The reliability and reproducibility of experimental data obtained in various laboratories using animals cannot be guaranteed unless the 3Rs principles are observed (the principles of humane experimental technique) to ensure the welfare of animals. The present paper analyses Russian and foreign recommendations on different administration routes and administered volumes as applied to mice, rats, guinea pigs, and rabbits – the most frequently used laboratory animals. The paper systematises literature data on oral/intragastric, subcutaneous, intramuscular, intravenous and intraperitoneal routes of administration. It assesses potential complications of each route of administration, and negative effects on both health and well-being of laboratory animals, as well as on the results of experiments. The paper also touches upon some anatomical and physiological characteristics of laboratory animals, potential opportunities for feed and water deprivation, ways of reducing pain in animals. The results of comparison of administered volumes helped to determine optimal recommended and maximum administered volumes.

Current international and major part of national documents, regulating experiments on laboratory animals, is set out in Bioethics Convention 3”R”. Presently this 3”R” principle is still relevant and commonly accepted global standard. Objective of the study was to verify the compliance of the staff at the institute with the ethical principles of biological safety when handling laboratory animals infected with pathogenic biological agents (PBA) of the I-II groups, performing diagnostic, experimental, and manufacturing activities. Results and discussion. Carried out analysis of ethical principle implementation, when working with biomodels infected with pathogenic biological agents of the I-II groups, performing scientific and manufacturing activities shows that operational procedures comply with the requirements of biological safety and regulations of ethical code, as well as international standards for humane treatment to animals in biomedical investigations. Conclusions. The work with laboratory animals infected with PBA of the I-II groups at the premises of RusRAPI “Microbe” meets the requirements of biological safety and norms of ethical code. Experiments on animals are aimed at obtainment of new scientific knowledge, preservation and improvement of human health, and also monitoring of natural foci of particularly dangerous infections following the rules of 3“R” bioethical concept.

One of the main problems in the area of influenza prophylaxis and pandemic prevention is the development of cross-reactive vaccines, i.e. vaccines directed against all subtypes of human influenza viruses. Such vaccines are being developed in many countries for more than 10 years. A number of vaccines are presently undergoing clinical trials. We created Uniflu candidate vaccine based on recombinant HBc4M2e protein consisting of 4 tandem-connected copies of the highly conserved ectodomain of M2 protein of the influenza A virus. These 4 copies were genetically fused to the carrier protein, namely hepatitis B core antigen. Commercially available Derinat was used as adjuvant in the candidate vaccine. Preclinical studies on laboratory animals (mice, ferrets) demonstrated that immunization with Uniflu leads to significantly higher level of specific immunoglobulins in the blood and bronchoalveolar lavages. Moreover, it produces immunoglobulins belonging to subtype IgG2a that is the most important mediator of antibody-dependent cytotoxicity. The vaccine under review stimulates the proliferation of T-lymphocytes, as well as the formation of CD4+ and CD8+ T-cells synthesizing ɣ-IFN. When infected with the lethal doses (5 LD50) of influenza A viruses of the subtypes H1N1, H2N2, H3N2, and H1N1pdm09, immunized animals typically developed mild form of illness. This kept them alive in 90-100% of cases, which demonstrated almost complete protection from death. Replication of the virus in the lungs of immunized mice was reduced by 1.8-4.8 log10. High immunogenicity of the vaccine, and reduced clinical symptoms following experimental infection, were demonstrated in ferrets as well. The developed recombinant vaccine Uniflu has high specific activity and cross-protection. Uniflu can be proposed as pre-pandemic vaccine, provided that it passes clinical trials.

The analysis of the international experience in conducting preclinical studies and application of the principle of good laboratory practice was made. The issues associated with the use of laboratory animals for scientific purposes in Russia and abroad were discussed. The prospects of improvement of legislative base of the Russian Federation in the field of preclinical studies with the application of the principle of good laboratory practice and use of laboratory animals for scientific purposes were identified.

The article reviews methodological approaches to the assessment of pharmaceutical substances neurotoxicity. It describes the main battery of animal tests that are conducted prior to clinical trials in order to assess drug effects on the functioning of vital body systems. The article addresses the choice of animal species, dosage and duration of pharmaceutical substance administration, as well as the conduct of clinical trials, functional tests and histological studies. It points out that an adequate justification of the study programme may help substantially reduce the number of tests. The authors assert the need to use at least two animal species in neurotoxicity studies, one of which must be a non-rodent species, in order to be able to investigate the drug safety profile during preclinical studies in as much detail as possible and to assure the required safety level for people when moving on to Phase I of clinical trials.

The authors have analyzed international experience in creating legal documents regulating the use of animals for scientific purposes. Topical issues related to the use of laboratory animals for scientific purposes in the Russian Federation, including for the purpose of preclinical studies on the efficacy and safety of new medicines, are discussed. The negative effects of the lack a clear and consistent legal framework for the organization and limits of the use of laboratory animals for research purposes in the Russian Federation are identified. Particular attention is paid to the issue of bioethics, the principles of ethical expertise of research activities involving laboratory animals and the issues of bioethical committees activities. The basic directions of perfection of normative-legal acts and methodological documents in the field of organization and limits of the use of laboratory animals for research purposes are proposed.

This review briefl y discusses the experience of organizing and carrying out experimental studies in our center in order to increase the validity of the researches. The rules of organizational and methodological approaches aimed at increasing the suitability of the results of experimental studies are also given. Each research work in which experiments on laboratory animals are supposed to be carried out should be organized, planned and carried out in accordance with national and international ethical standards. Discussion and publication of both planned and conducted experimental work makes it possible to make the research process more open and objective. The experimental investigation is carried out in the following algorithm: the formulation of the problem and the hypothesis on the basis of the literature data; development of the purpose and objectives of the study with adequate methods and selection of equipment; distribution of material to control and trial groups; creation of a plan for monitoring the indicators during the experiment; processing and interpretation of results; preparation of a scientifi c report.

The interest of scientists, physicians, pediatricians, general practitioners to the problem of intestinal dysbiosis is caused by the fact that there are very close relations between the intestinal microbiocenosis disorders and organic and functional pathology not only of the gastrointestinal tract, but also of other organs. For more than 50 years probiotics have been the leading tool for correction of intestinal microbiocenosis. However, the response of intestinal microbiota to exogenous intake of probiotics is variable, or is completely absent. The article presents the analysis of the literature data and results of our own experimental studies on human volunteers, fully confirming previous findings on laboratory animals, according to which the probiotic microorganisms are foreign and do not survive in the gastrointestinal tract of humans and animals, and their interaction with the host organism has the character of «host against probiotic». The results of the comparative study on the effectiveness of 18 modern preparations for correction of intestinal microbiocenosis at antibiotic-associated dysbiosis in experiments on animals are given. The comparative experimental research on the effectiveness of modern preparations that are frequently used in clinical practice as well as recent innovative commercial and experimental preparations (Actoflor-C. Stimbifid plus, Stimex) regarding intestinal microbiota recovery at antibioticassociated dysbiosis in conventional white mice was carried out.

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Our research object was hexyl ether of 5-aminolevulinic acid applied as plants growth regulator which was synthe-sized with an original technology by Bioorganic Chemistry Institute of Belarus National Academy of science. Our research goal was to determine peculiarities of toxic effects exerted by this new plants protector on experimental models in vivo/in vitro and to give grounds for hygienic standards of its contents in various media which were to provide its safe production and application. We conducted our research with the use of toxicological, physiological, hematological, biochemical, immu-nologic, cytogenetic, cytological, and statistical methods. We were the first to perform toxicological assessment of this new plants growth regulator under different regimes, doses and ways of introduction into laboratory animals' bodies and it helped us to detect its toxicometric parameters and peculiarities of its biological effects which became apparent through skin-resorptive and cumulative properties, irritating impacts on mucous tunics, moderate reproductive toxicity without sub-stantial signs of gonadotropic, mutagenic, and allergenic impacts on a body. We detected that toxic impacts exerted by the examined substance on a body was combined with membrane-tropic and cytotoxic effects. We determined criteria and limit-ing parameters of hazardous effects exerted by hexyl ether of 5-aminolevulinic acid in the course of a chronic experiment, and it gave us grounds for fixing allowable daily dose for a man and for working out a number of regulations on the sub-stance contents in environmental objects (working area air, water, and soil), in food raw materials, and in food products (grain, rape, rape and linen oil). The obtained results were used as a basis for fixing 9 hygienic standards and were used for the state registration of this plant growth regulator; it will provide its safe production and application in agriculture.

The proposed article touches upon the study of metabolism of new synthetic cannabinoids. In the work the data on synthetic cannabinoid 3-(Naftalin-1-yloxomethyl)-1-(5-fluoropentyl)-1H-indazole (THJ-2201), as well as the products of its metabolism in the laboratory rats of the Wistar line are given, i. e. Mass spectra and chromatograms of the native substance (THJ-2201) obtained by high-performance liquid chromatography with mass-selective detection (HPLC-MS) and gas chromatography with mass-selective detection (GC-MS) are given. The paper presents a complex technique for qualitative determination of cannabimimetics THJ-2201 and methods for obtaining a metabolic profile model for the test substance that can be useful for the tasks of qualitative detection and detection of new psychoactive substances in biological objects for the purposes of forensic analysis.The aim of this work was to develop methods for determination of the test substance (THJ-2201) and its metabolites in the urine of laboratory animals, as well as the study of the metabolic characteristics of synthetic cannabinoids on the whole.Materials and methods. The following equipment was used for the experiment: a liquid chromatograph from the firm “Shimadzu LCMC-8050” in combination with a mass-selective detector. The detector type is a triple quadrupole with a double ionization source (chemical ionization at atmospheric pressure and electrospray). The separation of the substances occurred in a chromatographic column (the material is stainless steel, the characteristics are: 150 * 3.0 mm, Luna 3uC18 (2), 100A). The Sorbent is reversed-phase. The investigations were carried out on Agilent 7890A gas chromatograph with Agilent 5975C mass spectrometer and a 103 polar HP-5ms column of 28 m × 0.25 mm. The animals were mature male white laboratory rats of the Wistar line, aged 4–6 months, weighing 190-230 grams.Results and discussion. As a result of the studies, a comprehensive methodology for determining the synthetic cannabimimetics of THJ-2201 and its metabolites in the urine of laboratory animals was developed, chromatograms and mass spectra of the metabolic profile of animals were obtained by HPLC-MS and GC-MS methods, and the similarity of the metabolic profiles of the studied substances in humans and animals was determined.Conclusion. The conclusions were made about the suitability of the proposed complex analysis methodology under the given laboratory conditions and the significant degree of interspecific similarity of human metabolic profiles and laboratory rats’ for substances chemically close to the studied.

The data characterizing the effectiveness of hypocholesteronemic action of rapeseed and sunflower lecithins in experiments on laboratory animals are prsented. It has been established that rapeseed and sunflower lecithins exhibit hypocholesteronemic properties. It has been found that the degree of reduction in the mass fraction of total cholesterol and low-density lipoprotein cholesterol in the blood serum of animals of the experimental group that received cholesterol + rapeseed lecithins in addition to the usual diet is higher compared to this index reduction in the blood serum of the animals of the experimental group that received, cholesterol + sunflower lecithins in addition to the usual ration.

Leprosy (Hansen’s disease) is a chronic granulomatous bacterial disease which mainly affects skin and peripheral nervous system. Leprosy is caused by the obligate intercellular pathogen known as Mycobacterium leprae. Creating experimental models of leprosy is associated with serious problems due to biological characteristics of the pathogen. Numerous attempts to develop experimental models on different types of animals resulted in a few reproducible models on mice and nine-banded armadillos. Strains of knockout mice with genetic defects caused by site-directed mutagenesis are used as a basis for different leprosy models. Experimental models of leprosy are used for screening of anti-leprosy drugs, detection of drug resistance, studies on the pathogenesis of leprosy, production and evaluation of viability of M. leprae, developing of anti-leprosy vaccines.

Safety assessment of new nanostructured treatments and substances requires special attention from producers during synthesis and technological cycle and from the medical staff examining the persons contacting them. Toxicity studies should be conducted before the beginning of their use, in order not to allow producing of nanopreparations with detrimental effects on human health. In the current economic climate, use of wastes from the production of metal silicon is promising. The article deals with the safety problems resulting from contact with wastes from the production of metal silicon. Concentrate of nanostructures based on silicon dioxide contained separate 1 μm nanoparticles and agglomerates from 1 to 45 ßm has been investigated. This concentrate is a perspective additive to increase sustainability properties of building materials. The objective of the research was to examine biological properties of siliceous dust administered to rats through various routes. Acute toxicity, species and sexual sensitivity after oral administration of the concentrate of nanostructures in mice and rats of both sexes, acute skin irritation from a single exposure were studied. The concentrate of nanostructures based on silicon dioxide can be classified in V category of hazard based on acute oral toxicity by classic toxicological methods (DL50 > 2000 mg/kg, no sexual and specific sensitivity). It produces slight irritating effect in acute dermal toxicity test that will disappear completely within 16 hours of exposure.

This article presents the results of studying the effect of homogeneous model meat systems produced using enzyme preparation containing fungal protease and microbiological starter culture of Lactobacillus plantarum on the allergic reactions within specific immunity in vivo. According to the results, it is established that experimental products have no negative effect on the clinical parameters of laboratory animals. During the experiment, with the introduction of experimental products into diet, the dynamics of body weight changes in all groups of animals was positive. At the end of the experiment, there were smaller increase in the weight of rats and lower values of weight gain (Group 1 — 14.0 %, Group 2 — 15.9 %, Group 3 — 20.2 %). This is possibly due to the adaptation processes occurring in response to introduction of meat systems into the diet, which confirms the leveling of the daily weight gain of experimental and intact animals since the 16th day of the experiment. According to the results of clinical blood analysis of the animals consuming experimental products, an increase is detected in leukocytes and lymphocytes by up to 18 %; in granulocytes by up to 35 %; and in monocytes by up to 8 %; in hemoglobin concentration, hematocrit and mean corpuscular hemoglobin concentration by more than 3 %; in red cell distribution width and mean corpuscular volume by up to 2 %, in comparison with intact animals. The correlation of these data with ELISA parameters for serum of experimental animals (histamine and immunoglobulin E) allowed to suggest the expression of reaginic antibodies and interaction on the surface of basophils and mast cells, which led to the degranulation and release (increase) of histamine, as a vasoactive factor, by 40 % compared with intact animals.The overall conclusion of the studies is that experimental model meat systems may trigger the activation of specific immune responses in laboratory animals. This is possibly due to protease-mediated formation of greater amount of indigestible polypeptides and peptides that invoke local adaptation responses.