The article discusses various types of variance analysis: one-factor, two-factor, repeated measurements, including detailed analysis of variance categorical data. The criteria of multiple comparisons are described: according to Bonferroni, according to Newman-Kales, according to Dunnet, according to Scheffe. All the methods considered are accompanied by examples of analysis of pharmacological data.

Relevance. Alzheimer's disease (AD) is a neurodegenerative disease, the drug therapy of which can only slow the progression of the disease, due to the variety of existing pathogenetic processes. A possible effective approach to the correction of symptoms can be the use of compounds with a complex mechanism of action — phosphorylacetohydrazides, capable of simultaneously acting on different parts of the pathological process, the most effective representative of which is the compound 2-chloroethoxy-para-N-dimethylaminophenyl phosphorylacetohydrazide (CAPAH). Target. To study the possibility of correcting cognitive and behavioral disorders in rats with a stereotaxic model of AD using the CAPAH compound, which affects different parts of the pathological process. Methods. 24 female Wistar rats were used in the work. AD was modeled in rats by stereotaxic bilateral injection of β-amyloid into the hippocampal region in a phosphate buffer solution, then on day 11, CAPACH (10 mg/kg) was administered intraperitoneally for 10 days, after which tests were performed using the ≪Elevated Plus Maze≫, ≪Open Field≫ and ≪Morris Water Maze≫. Statistical processing was carried out in the GraphPad Prism 8.0.1 program using one-way ANOVA analysis. Results. Multiple administration of CAPAH contributed to a decrease in the level of anxiety in the ≪Elevated Plus Maze≫ method, increasing the time spent in open arms by 4.6 times (p < 0.05) compared to rats without treatment. In the ≪Morris Water Maze≫ and ≪Open Field≫ tests, normalization of memory and motor activity processes was observed, respectively, the platform search time and the number of crossed lines did not differ from those of control animals. Conclusion. CAPAH reduces anxiety and memory processes in rats with a stereotaxic model of Alzheimer's disease caused by the introduction of β-amyloid into the hippocampus.

Effects of multiple-dose regimens (oral, daily, once a day for 15 days) of cyclooxygenase (COX) inhibitors etoricoxib (1 and 10 mg/kg), diclofenac sodium (1 and 5 mg/kg) and their combinations with 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol 25 mg/kg) on rat behavior were studied in the open field test, rotarod test and elevated plus maze test. Exploratory (in open field test) and locomotor (in rotarod test) behavior of rats was significantly weakened only by the non-selective COX inhibitor diclofenac sodium at 5 mg/kg, which is due to the peripheral side effect of the drug. The selective COX-2 inhibitor etoricoxib increased the time in the central area of the elevated plus maze at 1 and 10 mg/kg and reduced the latent period of locomotion in the open field test at 10 mg/kg. A combination of diclofenac sodium (1 mg/kg) with mexidol neither reduced exploratory behavior nor caused motor deficit in contrast to diclofenac sodium at 5 mg/kg. However, a combination of etoricoxib (1 mg/kg) with mexidol inhibited locomotor activity in the rotarod test. Nevertheless, it produced no significant effects on the exploratory behavior or anxiety of animals in the open field test and elevated plus maze test.

Purpose of the study. Comparative evaluation of echocardiographic and morphometric dimensions of the rat heart left ventricle. Materials and methods. The study included 10 outbred male rats weighing 160–180 g. The size of the heart left ventricle was assessed using echocardiography and morphometry. The measurements were carried out according to standard protocols. To perform morphometric measurements, hearts were stopped in systole with a lethal dose (1.0 mg/kg) of 0.025 % strophanthin K solution, and in diastole, by immersing the hearts in a chilled physiological solution (calcium-free medium). Results. It was shown that the systolic size of the left ventricle of the heart according to echocardiography is 1.79Ѓ}0.10 mm, and morphometry 1.64Ѓ}0.09 mm (p = 0,302); diastolic size of the left ventricle, respectively, 3.42Ѓ}0.16 mm and 3.66Ѓ}0.17 mm (р = 0,318). The detected discrepancies do not exceed 10 % and, apparently, are due to the fact that the physiological dimensions of the heart left ventricle are measured by a non-invasive echocardiographic method, and for morphometric measurements of the dimensions in the systole, the heart was stopped by injection of strophanthin K, which entails an overload of heart cells with Ca2+ ions and as a result, contracture of cardiomyocytes; post-mortem cardiac arrest in diastole, in a calcium-free environment, is accompanied by a loss of cardiac muscle tone and, therefore, dilatation of the left ventricle will naturally be greater than physiological. Conclusion. Noninvasive echocardiographic measurement of the size of the heart left ventricle fully reflects the actual size of the left ventricle of the rat heart (the difference does not exceed 10 %), i. e. echocardiographic measurements are valid.

Article describes results of study of antitumor and antimetastatic action of dipeptide mimetic of the nerve growth factor amide N-monosuccinyl-L-glutamyl-L-lysine (compound GK-1) in comparison with gemcitabine. Two injections of gemcitabine in total dose of 100 mg/kg resulted in significant tumor growth inhibition by 60–61% on 7th, 9th and 15th days of tumor development. Course administration of GK-1 in doses of 10 mk/kg from 2nd to 15^th day of tumor development resulted in significant tumor growth inhibition by 57,8 %. Metastasis inhibition index (MII) of gemcitabine was 75,8 %. MII of GK-1 in doses of 10 mg/kg or 30 mg/kg was 44,9 % and 47,7 % accordingly. It was shown that GK-1 in studied range of doses exerts antimetastatic activity.

Relevance. Assay of acute toxicity is a mandatory step in a preclinical safety study of medicines and pharmaceutical substances. The purpose of this study was to determine the parameters of acute toxicity of the substance GIZH-298. Methods. GIZH-298 was administered once orally to outbred mice of both sexes at doses of 350–550 mg/kg. Control mice received 0.5 ml of 1 % starch solution under the same conditions. During the experiment, the death of animals, signs of intoxication were observed, and the clinical picture was recorded. Pathological anatomical autopsy of the dead mice was performed as they died. Surviving mice were autopsied 14 days after the start of the experiment, immediately after their euthanasia. Results. The average lethal doses of the GIZh-298 substance when administered orally to mice were determined: LD50 in females was 356 mg/kg, LD50 in males was 438 mg/kg. Conclusion. Compound GIZH-298 for oral administration according to the classification of Sidorov K.K. (1973) is a moderately toxic substance and can be assigned to the 3rd class of toxicity, and in accordance with GOST 12.1.007-76 — to the 3rd hazard class.

Relevance. Trastuzumab is the drug of choice for the HER2+ breast cancer treatment. To determine the trastuzumab pharmacodynamics in personalized therapy a validated bioanalytical method for measuring the concentration of the drug in biological fluids is required. The aim: creation and assessment of the suitability (validation) of a test system based on enzyme-linked immunosorbent assay (ELISA) for the quantitative determination of trastuzumab concentration in human serum/plasma. Materials and methods. The presented test system is a classic ELISA kit with a 96-well polystyrene plate, the wells of which are coated with monoclonal antibodies specific to trastuzumab, secondary goat antibodies to the Fc fragment conjugated with horseradish peroxidase (HRP), substrate solution — (3,5,3',5')-tetramethylbenzidine (TMB) and stop solution. Quality control solutions were prepared by diluting known concentrations of trastuzumab in blank serum. Results. In the course of the work the limit of detection (0.84 ng/ml) and the lower limit of quantitative determination (1.41 ng/ml) of trastuzumab in serum/plasma were established and the high selectivity of analyte determination in a multicomponent matrix was proved. The found average values of trastuzumab concentrations did not deviate from the nominal values by more than 14 % in the entire range of determined concentrations, the intraand interseries precision of the test system did not exceed 8%, and the total method error was 20.1 %. The demonstrated dilution linearity allows the assay to be used to analyze a wide range of trastuzumab concentrations in biological samples. The stability of the components of the test system is defined as at least 1 year under storage conditions. Conclusion. The presented ELISA test system complies with international validation requirements and it is suitable for practical use.