Bulletin of Experimental Biology and Medicine最新文献

Combined proton-neutron therapy can be the best opportunity for neutron radiation therapy due to highly conformal proton irradiation and high relative biological effectiveness of neutrons. The study compares 4 schemes of sequential in vitro exposure of Chinese hamster fibrosarcoma cells B14-150 to 14.5 MeV neutrons and a scanning beam of protons. Treatment efficiency increased with increasing the contribution of the neutron component to the total dose from 30 to 40% and the delivery of the neutron dose as the first fraction in the two-fraction proton-neutron exposure.

The dynamics of heart rate variability (HRV) during acute stress was studied in male nonlinear rats that received single injection of serotonin (200 μg/kg) or dopamine (60 μg/kg), regular (4-fold) injections of central serotonin receptor blockers (ketanserin and granisetron, 0.1 mg/kg each) or central dopamine receptor blockers (0.1 mg/kg SCH-23390 and 10 mg/kg sulpiride), as well as a combination of central receptor blockers with the administration of serotonin or dopamine, respectively. During stress against the background of serotonin receptors blockade, a weak tachycardia, low stress index, high rhythm variability, especially in the low-frequency range were recorded; against the background of dopamine receptors blockade, increased reactivity to stress at high HR, an initial increase in the stress index, and a decrease in rhythm variability, followed by an increase in the proportion of very low frequency waves in the spectrum were revealed. Serotonin and dopamine, by stimulating peripheral receptors, predominantly weakened stress-induced changes in HRV (especially serotonin), but in combination with blockade of the corresponding central receptors contributed to maintaining tachycardia, reduced rhythm variability, and potentiated the effects of blockers in relation to stress induced changes in the wave structure of the HRV spectrum. We believe that central and peripheral serotoninergic and dopaminergic structures are involved in the formation of HRV by modulating the activity of components of the autonomous and central circuits of HR regulation, respectively.

The development of chronic heart failure (CHF) was induced in 24-month-old male Wistar rats weighing 550-600 g by 4 subcutaneous injections of isoproterenol hydrochloride (ISO) at a dose of 10 mg/kg with 3-day intervals. The control group received injections of saline. The rats were euthanized 60 days after the last ISO/saline injection. The mortality rate in the group of rats with CHF was 30%. Histological studies showed morphological changes in the myocardium, kidneys, and lungs typical of CHF. The presented scheme of ISO administration can be used for modeling CHF in 24-month-old rats.

The problem with modern nerve conduits is inability to transmit nerve impulses to the distal part of the damaged nerve. Cationic conductivity is a necessary characteristic of the nerve conduit ensuring effective regeneration of the peripheral nerves. We performed a functional assessment of the regeneration of rat sciatic nerve using a nerve conduit based on an ion-exchange membrane. A sciatic nerve defect was experimentally simulated in Wistar rats with further implantation of the LF-4SK membrane. On days 60 and 90 after surgery, the sciatic functional index and the ratio of the shin girth of the operated limb to the intact limb were calculated; on day 90, an electrophysiological assessment of nerve recovery was carried out. The results of the study showed that the conduit based on the LF-4SK membrane optimizes the functional recovery of the sciatic nerve defect.

The effect of the selective μ₂-opioid receptor agonist endomorphin-1 in reperfusion injury in male Wistar rats was studied in vivo and in vitro. The in vivo experiment included coronary artery occlusion (45 min) and reperfusion (120 min); in in vitro experiments, 45-min global ischemia of the isolated rat heart was followed by 30-min reperfusion. Endomorphin-1 was administered intravenously 5 min before in vivo reperfusion (at a dose 50 μg/kg) or added to the perfusion solution at the onset of reperfusion of the isolated heart (in a concentration of 152 nmol/liter). In vivo endomorphin-1 reduced the infarct size by 33% compared to the control group. In experiments on isolated heart, endomorphin-1 improved the contractile function during reperfusion and reduced the creatine kinase level in the coronary effluent. Hence, stimulation of cardiac μ₂-opioid receptors increases heart tolerance to the pathogenic effects of reperfusion.

Disorders in the composition of the microbiota are often associated with pathological processes in the body. The use of new biotherapeutic drugs containing bacteria from normal microflora to correct these disorders may contribute to more effective treatment. The Bacteroidaceae family dominating in microflora is a candidate for inclusion in bacterial preparations. The adhesion properties of five bacterial strains from the Bacteroidaceae family were analyzed using the Caco-2 cell line and their effect on the transepithelial electrical resistance parameters (TEER) was assessed to determine the extent of their impact on the cell monolayer integrity. This approach allowed the selection of strain B. intestinalis 181, which was characterized by a moderate adhesion activity combined with a relatively low effect on the TEER parameter.

The activities of NAD- and NADP-dependent isocitrate dehydrogenases (NAD-ICDH and NADP-ICDH), NAD- and NADP-dependent glutamate dehydrogenases (NAD-GDH and NADP-GDH), and NAD- and NADP-dependent malate dehydrogenases (NAD-MDH and NADP-MDH) in ovarian veins lymphocytes in 183 women of reproductive age with pelvic varicose veins (PVV) and 30 women in the control group were determined. The indicators of intracellular enzymatic activity showed multidirectional changes with increasing severity of the disease. Compared to the control group, women with stage II of PVV had higher median values for lactate dehydrogenase (16.69), NAD-GDH (39.48), NADP-GDH (7.48), NADP-MDH (9.06) and lower values of NAD-ICDH (65.41). Women with stage III of PVV had lower median values for succinate dehydrogenase (9.27), NAD-MDH (26.19), and higher values for glucose-6-phosphate dehydrogenase (8.62), lactate dehydrogenase (24.67), NAD-GDH (63.81), NADP-MDH (21.05) compared to the control group. Studying the activity of NAD(P)-dependent dehydrogenases in lymphocytes at the local level during PVV allows us to evaluate the intensity and dynamics of local varicose veins progression, as well as to optimize its correction.

The involvement of DNA synthesis in the mechanisms of long-term memory reconsolidation in edible snails trained for conditioned food aversion was investigated. Administration of nucleoside analogs, such as 5-bromo-2'-deoxyuridine or 3'-azido-3'-deoxythymidine, which inhibit DNA synthesis, 1 h before or 1-3 h, but not 5 h after reminder with the conditioned stimulus led to memory impairment. One day after the inhibitor application and memory reactivation, a weakly expressed memory impairment (amnesia) was observed, which progressed over the next few days to the complete disappearance of behavioral memory expression. In snails with formed aversive memory for two food conditioned stimulus, a specific memory impairment was observed only for the stimulus that was paired with the presentation of an inhibitor during the reminder, while the memory for the other non-reactivated conditioned stimulus remained intact. It is suggested that DNA synthesis in the brain plays a specific role in the genetic mechanisms of reconsolidation and maintenance of long-term conditioned food aversion memory in snails.

A promising area in the search for effective and safe methods of pharmacotherapy for gastric ulcers is the study of bioactive substances of natural origin and derivatives synthesized on the basis of these substances. The review presents modern information on various peptide-based substances that are pharmacologically active against gastric ulcer, including analogues of natural neuropeptides, synthetic substances with a specific amino acid sequence, as well as drugs derived from biological peptide complexes. Based on the results of the analysis, we have assessed the prospects of this pharmacological approach and outlined the areas for further research.

It was found that 28-day immobilization stress in male Wistar rats leads to significant increase in the serum concentrations of proinflammatory cytokines IL-1β, IL-6, IFNγ, and monocyte chemoattractant protein-1 (MCP-1) and a decrease in the content of anti-inflammatory IL-10, as well as the ratio IL-1β/IL-10, IL-6/IL-10, and IFNγ/IL-10 compared to non-stressed animals. Administration of the heptapeptide tuftsin-Pro-Gly-Pro produced a corrective effect on cytokine concentrations under stress conditions: at a dose of 750 μg/kg, the peptide decreased the concentrations of IL-1β, IFNγ, and MCP-1 and cytokine ratios (IL-1β/IL-10 and IFNγ/IL-10), while at a dose of 250 μg/kg, it increased IL-10 levels and decreased IL-6/IL-10 and IFNγ/IL-10 ratios.