METHODS OF BIOMEDICAL RESEARCHES
A discriminant method was proposed for modeling and quantifying the consistency of regulatory mechanisms in the cardiovascular system (CVS) of apparently healthy volunteers and those suffering from circulatory disorders associated with cervical spine osteochondrosis (OCS) and somatoform autonomic dysfunction (SAD). The congruence of the parameters of ECG intervalometry (DCI) and pulse wave duration (PWD) according to the volunteers’ photoplethysmograms (PPG) was established by calculating the disparity measure and deviations from the mean values using the coeffi cients of displacement, slope of the approximating straight line, as well as by comparing the reliability and correlation of the trend model with the initial data. We discovered gross violations of congruence in the work of efferent and afferent regulatory CVS mechanisms, mismatch and decrease in comparison with the norm of DCI and PWD, a signifi cant decrease in their approximation in the SAD volunteers. In volunteers with OCS, deviations in DCI and PWD from their mean values are much lower than in those with SAD, being inferior compared to healthy volunteers. Similar to SAD, these patients are inferior to healthy volunteers in terms of the disparity measure.
The “learned helplessness” (LH) model in rats is widely used in a battery of tests to assess depression-like behaviour and the effects of antidepressants. The model is considered to be suffi ciently valid, though having some limitations with reproducibility. This review discusses the possibilities of using the model for assessing the symptoms of a depressive-like state and the pathogenesis of depression, as well as the effects of antidepressants. The factors affecting the reproducibility of the LH model are described, the most important of which is the different sensitivity of animals to stress. Several protocols for the induction and testing of LH, which are used by different research teams, are presented. Due to the diffi culty of comparing the results obtained using different LH protocols, LH models should be standardized for use in individual laboratories. LH models are worth using in preclinical studies of potential drugs exhibiting antidepressant activity.
The aim of this research was to study the possibilities and limits of conducting acute medical experiments from the moral and legal aspect. Modern Russian and foreign literature sources, as well as the latest scientifi c works on the problem under study, were reviewed. It was found that acute experiments are applied in a wide range of scientifi c research studies. The existing alternative methods cannot abolish the use of laboratory animals. Laboratory animals remain a suitable bio-model for conducting preclinical tests and experiments. Currently, vivisection is a necessary research method due to the lack of adequate alternatives.
Under the conditions of a chronic methionine diet (daily addition of amino acids to food (0.15 g/100 g) and water (1% solution)) during 2–12 weeks, the dynamics of liver tests, infl ammatory changes in the blood and blood lipids was monitored. It was found that a methionine diet (MD) leads, starting from 4 weeks of MD, to medium hyperhomocysteinemia, an increase in liver enzymes (AsAT – 1.73, AlAT – 1.5 times, p<0.05) and bilirubin (by 62.25%), which indicates the formed hepatopathy. Further (12 weeks of MD), the condition is aggravated by an abnormality of excretory liver function and the development of cholestasis (an increase in alkaline phosphatase by 1.65, bilirubin – by 3.31 times, p<0.05).
The article presents the results of evaluation of actoprotective activity of combined dimethylaminoethanol compounds containing intermediates of the citric acid cycle (L-malate, α-ketoglutarate, succinate and fumarate). The effect of long-term intragastric administration of pharmacological agents for 4 weeks at a dose of 75 mg/kg on the static, dynamic endurance, motor coordination and body weight gain of “trained” laboratory animals was assessed in comparison with reference actoprotector ethylthiobenzimidazole (25 mg/kg, intragastrically). It was found that the most promising substances for further study are alpha-ketoglutarate and succinate compounds. After 1 month of training, dynamic endurance and coordination of movements were most infl uenced by DMAE-malate (increase by 60%, p=0.011), static endurance was increased during the 2nd week by DMAE-malate (by 16%, p=0.005) and DMAE-ketoglutarate (by 15.8%, p=0.006), on the 4th week – DMAE-ketoglutarate (by 19.7%, p=0.0001) and DMAE-succinate (by 12.2%, p=0.003). A pronounced body weight increase was observed in the group receiving DMAE-ketoglutarate (by 29%, p=0.022). In general, combined compounds of dimethylaminoethanol with alpha-ketoglutarate, malate and succinate showed the highest actoprotective activity.
NON-CLINICAL RESEARCH IN BIOMEDICINE
A derivative of the beta-carboline alkaloid harmine — the drug harmine hydrochloride was studied for the presence of antihypoxic properties in models of hypobaric hypoxia and normobaric hypoxia with hypercapnia. It was found that harmine hydrochloride does not have a signifi cant compensatory effect in the normobaric hypoxia test with hypercapnia. At the same time, harmine hydrochloride in small doses (2.5 and 5 mg/kg) has antihypoxic activity in the hypobaric hypoxia test, which is expressed in a statistically signifi cant increase in the life expectancy of animals treated with the drug, compared with the control, in conditions of hypoxia. According to the antihypoxic effect, harmine hydrochloride at doses of 2.5 and 5 mg/kg was found to be comparable with the reference drug (mexidol, 100 mg/kg).
This work presents the results of a comparative in vitro study into the biocompatibility of titanium samples, the surface of which was pre-treated using various methods: milling, machining with acid etching and irradiation with a powerful ion beam (PIB) for creating a relief with the required roughness and the shape of asperities. A study of the effectiveness of attachment and growth of Balb/NIH 3T3 fi broblasts on titanium products with various types of surface treatment demonstrated that irradiation of a titanium surface with a powerful ion beam (PIB) leads to its active colonization with cells having a fl attened and stellate shape, which confi rms their active growth. An assessment of migration of metal impurities from the titanium alloy VT 1-0 was evaluated using the x-ray fl uorescence method
This review analyzed the literature data on the in vitro preclinical study of the cytotoxic properties of organotin compounds, as well as the main mechanisms of their action. The latter consist in interacting with SH groups of proteins, initiating oxidative stress, binding to DNA, interacting with receptors, as well as activate apoptosis by increasing the expression of caspases, proapoptotic proteins, and decreasing antiapoptotic proteins. Organotin compounds, depending on the donor ligand, exhibit specifi c cytotoxicity towards certain tumor cell lines. The high cytotoxic potential indicates the possibility of further development in vivo and research of organotin compounds as candidates for the creation of drugs for anticancer and antimetastatic therapy.
ISSN 2713-0428 (Online)