The toxicity of the drug Cisplatin after intragastric administration was assessed on humanized transgenic mice with human genes Nat1hom . The evaluation was conducted in comparison with mice lines C57BL6/Y ("fast" type of acetylation) and line SHK ("slow" type of acetylation). LD50 for mice Nat1hom amounted to 56,3 mg/kg, for mice of the C57BL6/Y - 35,1 mg/kg, for mice line SHK - 33,7 mg/kg. The death of animals C57BL6/Y and SHK line was observed within 1-6 hours after administration and in mice Nat1hom - a day after the introduction. There were lethargy, lack of exercise, a sharp decline in muscle tone with episodic generalized convulsive episodes, collapsing on its side in animals of all lines closely to lethal condition. The autopsy of the dead animals showed signs of congestive venous plethora of internal organs, edema of the meninges with a single bleeding under the lining of the brain. After administration of Cisplatin at a dose of 45-55 mg/kg in histological research there were detected cerebral edema with signs of acute encephalopathy and changes in the myocardium, which indicate the early development of acute heart failure. Venous plethora manifested in all internal organs and in the brain. Lower level of toxicity of Cisplatin in mice with human genes Nat1hom, authors explain the presence of the human gene with the "fast" type of acetylation. It is concluded that in the metabolism and detoxification of Cisplatin, as well as reducing its toxicity, more than 60% N-acetyltransferase processes. The creation of transgenic humanized mice can be based on the use of CRISPR/Cas9 technology. Proposed a new model of humanized transgenic mice with the gene Nat1hom for preclinical researches of anticancer drugs.

The article presents a comparative analysis of the parameters of ultrasonic vocalizations of mini-pigs of Svetlogorsk population in the state of wakefulness and when exposed to electric sleep. Similar characteristics of both conditions is the prevalence of the power spectral density of ultrasound at frequencies of 15-20 kHz. The states of wakefulness and electric sleep have different spectral power density in the intervals 20-30 and 32-38 kHz. These effects may reflect the relationship of ultrasonic vocalizations and breathing cycle. The analysis of ultrasonic vocalization of animals when exposed to electric sleep can be recommended as a modeling method of evaluating of the hipnogen effects of pharmacological means, and also preclinical researches of the means possessing sleeping pill and other similar actions.

The article describes the behavioral test that uses the chemical effect to determine the analgesic activity and evaluation of the inflammatory process. It meets contemporary requirements for a study of the pharmacologically active materials with analgesic activity, and to ethical treatment of experimental animals.

Interpretation of a psychoemotional state of laboratory animals according to the analysis of their free behaviour and parameters of ultrasonic vocalization is the valuable instrument of preclinical research of medical technologies and pharmacological agents.

This article addresses the issues concerning assessment of generic drugs and their correspondence to original drug product. The review highlights issues concerning pharmaceutical, pharmacokinetic (biological) and therapeutic equivalence. It is shown that in developed countries for drugs with a narrow therapeutic range, it is recommended to limit the dynamic range value from 0.9 to 1.11. The problem of governmental regulation of quality and submission for obtaining marketing authorization for generic drug products in Russia are discussed.

In order to detect changes in the post-stimulus electrical activity of neurons in sensorimotor cortex (SMC) induced by the influence of different concentrations of bacterial melanin, high-frequency tetanic activation of cortical neurons was studied in response to stimulation of peripheral nerves of rat hindlimb. The corresponding post-tetanic short (STP) and/or long-term (LTP) changes in the activity of cortical neurons, caused by the mobilization of a mediator, were registered. The nature of the impact was directly dependent on the concentration of the tested solution. The method of intramuscular injection is recognized as the best method for this research. The pattern of posttetanic responses was almost identical after direct application and intramuscular and/or intraperitoneal injection of melanin at use of the same concentration. The increase of neuronal activity was noted by introduction of low concentration of solution of melanin. The most reliable concentration is the concentration of 4.5 mg/ml, which induces stable and long-lasting increase in the activity of the cortical neurons. Activating effect of bacterial melanin can contribute to the recovery processes in neurodegenerative diseases.

Dietary supplements based on prebiotics contribute to the normalization of psychoemotional state of rats, keeping it at a high level of comfort and have a sedative effect, which is reflected in the ultrasonic vocalizations of animals. A course of consumption of dietary supplements on the basis of lactulose, succinic acid and glycine does not alter the normal behavioral responses of rats, which may testify to lack of negative influence of these means. Analysis of free behavior and ultrasonic vocalization of rats can serve as an objective method for assessing the effects of prebiotics, dietary supplements and other means of similar effect.

Results of research of influence of solutions of a hitozan, sodium salt of a sukcinoil of a hitozan and their polymer-colloidal complexes with colloidal particles of silver iodide on the structural and functional properties of erythrocyte membranes on the model of an acid hemolisis are presented in article. The analysis of acid eritrogramms allowed to define that the studied combinations have essential impact on a functional condition of membranes of blood cells of rats. The effect of test substances on the distribution of red blood cells in terms of their sustainability and on kinetic parameters (the beginning, intensity and completion of process of their destruction) under the influence of the damaging agent (HCl) is shown. The comparative analysis of results convinces that solutions of a hitozan, a sukcinoil of a hitozan and of a disperse systems on the basis of polymer-colloidal complexes of a hitozan, a sukcinoil of a hitozan with colloidal particles of iodide of silver are capable to modulate variously matrix properties of erythrocytes of blood.

The article is presented the review of literature on experimental modeling of pemphigus - heavy autoimmune dermatosis which is characterized by formation of blisters and erosion on skin and/or mucous membranes. The models are created in vitro (models with using cultures of keratinocytes, organ cultures of skin) and in vivo , on laboratory animals (models with passive transfer of antibodies and active disease: models with transfer of the autoreactive lymphocytes, transgenic models, forced immunization models). The models reproduce clinical, histologic and immunological signs of pemphigus. Experimental models are necessary for studying the aspects of pemphigus pathogenesis and development of new therapy approaches.

On the base of EEG spectral analysis we’ve studied the effects of nootropics and its combinations with Melaxen during cerebral blood flow disturbances in a rat global cerebral ischemia model. It was established that preventive combined Vinpocetine and Melaxen usage significantly reduces the number of deaths and circulatory ischemia adverse effects influence on survived experimental animals’ brain functional state. The obtained results can be used in clinical practice for the treatment of ischemic and neurodegenerative brain diseases.

For estimation of anxiety and antidepressant action of the seed extract Nelumbo nucifera Astrakhan population we studied behaviour of animals at the Suok-test and the Porsolt test. Our results indicate the presence of the expressed psychotropic action of the Nelumbo nucifera seed extract.