Volume 167, Nº 2 (2019)

We studied the effects of exogenous NO donor (sodium nitroprusside) and NO synthesis blocker (100 μM L-NAME) on baseline electrical activity of postganglionic fibers in the sympathetic superior cervical in rats during postnatal ontogeny. Starting the age of 20 days, sodium nitroprusside increased the mean discharge amplitude and the spectrum power in the respiratory (0.7-1.5 Hz) and cardiac (4-7 Hz) frequency bands. In contrast, application of L-NAME for 1 h decreased the spectrum power in these bands. Both agents produced no significant effect on the rhythmic sympathetic discharges at frequencies >8 Hz.

We studied age-associated changes in contractile activity of isolated cervical and mesenteric lymph nodes in rats. In young and middle-aged rats, no significant changes in contractile activity of lymph nodes were revealed. In old rats, the amplitude of spontaneous contractions of lymph nodes was lower and their rate was higher than in young and middle-aged animals; the sensitivity of lymph nodes to vasoactive agents was reduced and the threshold of the response was higher in old rats.

We evaluated the serum level of neuregulin-1 in humans with traumatic brain injury. The highest levels of neuregulin-1 were revealed in patients with developing post-traumatic epilepsy and the lowest concentrations of this peptide were found in healthy controls. The patients with traumatic brain injury not aggravated by the development of post-traumatic epilepsy had intermediate levels of neuregulin-1.

Relationship between the method of hypothermic exposure and ploidometric characteristics of hepatocyte nuclei of rats were studied immediately after hypothermic exposure and during the posthypothermic period. The following cooling modes were used: single submersion into 5°C water (until rectal temperature drop to 20-25°C; deep hypothermia) and single exposure at air temperature of -25°C (until rectal temperature drop to 30°C; moderate hypothermia). A manifest destructive effect of deep hypothermia on rat liver was detected: the exposure caused manifest alteration of hepatocytes (alteration index increased 81-fold immediately after the exposure and remained 16-fold higher than normally after 14 days) and an increase of DNA accumulation index with predominance of hepatocytes with 5c-8c nuclei (60% of the population) during the entire period of observation, which indicated intensification of the compensatory and adaptive processes in the liver with predominating high-ploid population of hepatocytes. Hepatocyte alteration processes in response to moderate hypothermia were less intense (hepatocyte alteration index increased 19-fold immediately after the exposure and remained 3-fold higher than normally after 14 days). The DNA accumulation index increased moderately immediately after the exposure and returned to normal after 14 days, with emergence of 2c hepatocytes and an increase in the level of 4c hepatocytes (51% of the population), which indicated realization of a different strategy of liver regeneration — recovery of the cell population intrinsic to intact animals.

We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 μg/kg 15 min before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.

We studied the effect of NO synthesis blockade on the hydrouretic function and the state of renal interstitial matrix in WAG rats with normal blood vasopressin level and Brattleboro rats lacking endogenous vasopressin. In WAG rats, impaired osmotic concentration accompanied by an increase in the content of histochemically detectable glycosaminoglycans in the inner medullary interstitium was observed under conditions of NO synthesis blockade. In Brattleboro rats, NO synthesis inhibition, on the contrary, induced an antidiuretic response without significant changes in the renal extracellular matrix. These findings attested to a significant influence of NO on the urine concentration process. Morphofunctional changes in the kidneys under conditions of NO synthesis blockade are determined by blood vasopressin level.

NO-mediated vasodilatation can be realized via two pathways: dependent and independent on soluble guanylate cyclase; the latter is implemented through NO interaction with ionic channels. We evaluated the contribution of these pathways into NO-induced relaxation of isolated pulmonary arteries in rats. In pulmonary arteries, in contrast to systemic vessels, soluble guanylate cyclase-independent mechanisms is more important, because it mediates relaxation in response to low concentrations of NO donor. The role of soluble guanylate cyclase-dependent mechanisms in the mechanisms of vasodilatation increases with increasing NO donor concentrations.

We studied the particularities of osteo- and angiogenesis in albino rats after implantation of polycaprolactone scaffolds mineralized with vaterite with adsorbed tannic acid in the femoral bone defect. It was found that the processes of angio- and osteogenesis in the bone tissue after scaffolds implantation depend on their biocompatibility. Implantation of non-biocompatible scaffolds was followed by activation of angio- and osteogenesis aimed at separation of these scaffold from surrounding tissues. Implantation of polycaprolactone/vaterite scaffolds containing tannic acid stimulated angio- and osteogenesis leading to vascularization and bone tissue formation in the matrix. This demonstrate prospects of clinical approbation of these scaffolds for stimulation of bone regeneration in traumatological and orthopedic patients.

We studied the effects of Selank on morphological parameters of the liver in Wistar male rats subjected to chronic foot-shock stress. Selank was injected intraperitoneally in doses of 100, 300 and 1000 μg/kg 15 min before each stress session. Morphological and morphometrical analysis showed that chronic foot-shock stress induced hydropic degeneration of hepatocytes, an increase of the nucleus/cytoplasm ratio due to an increase in the area of nuclei and reduction of the cytoplasm area, the appearance of focal necroses, and lymphohistiocyte infiltration. Injection of Selank in all doses reduced the intensity of stress-induced degenerative changes. Administration of Selank in doses of 300 and 1000 μg/kg restored the nucleus/cytoplasm ratio in hepatocytes. The maximum stress-limiting effect was attained after administration of 300 μg/kg Selank.

The effects of helium cold plasma on some parameters of metabolism of rat erythrocytes were studied after a course exposure (10 daily procedures, 1 min each). The intensity of free-radical processes in erythrocyte membranes, malondialdehyde concentration, and aldehyde dehydrogenase activity were analyzed. The exposure to helium cold plasma led to a significant increase in malondialdehyde level mostly associated with inhibition of its utilization. These changes were not related to activation of malondialdehyde synthesis in LPO reactions.

Taurine is an important endogenous agonist of glycine receptors (GlyR). Using the patchclamp technique, we measured chloride current induced by a short (600 msec) application of taurine (I_Tau) on isolated rat pyramidal neurons. pH of taurine solution in the applicator pipette was neutral (7.4) or acidic (7.0-5.0). Application of protons to a neuron causes a dosedependent decrease in the peak amplitude and acceleration of I_Tau desensitization. Addition of 100 nM β-amyloid peptide (Aβ) to the perfusate caused acceleration of I_Tau desensitization. The effects of Aβ and H⁺ on the rate of I_Tau desensitization were not additive. In addition, Aβ attenuated the effect of H⁺ on the peak amplitude of I_Tau. We also studied the effect of protons on the chloride current caused by activation of GABA receptors. In contrast to H⁺ effects on GlyR, Aβ did not modulate the effects of H⁺ on GABA receptors.

Possible otoprotective properties of cocarboxylase were studied on the model of amikacin-induced ototoxicity in immature rabbits. Auditory function was evaluated by the short-latency auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests. Administration of cocarboxylase after modeling of amikacin-induced ototoxicity resulted in a decrease in the ABR peak I threshold and prevented damage to the outer hair cells.

The safety of Grippol vaccine was assessed by macro- and microscopic methods in the experiment. The morphological features of group lymphoid nodules of the small intestine were studied on days 4, 7, 14 and 30 after vaccination. The structural morphological dynamics of lymphoid tissue under these conditions is shown. Because of the use of the vaccine, the lymphocytopoietic processes in the body are activated, which indicates the formation of an immune response.

We studied the expression of genes encoding enzymes of carbohydrate and lipid metabolism ketohexokinase (Khk), glucokinase (Gck), pyruvate kinase (Pklr), acetyl-Co-carboxylase (Acaca), fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd), and their transcription regulators ChREBP (Mlxipl), SREBP-1c (Srebf1), and PPARα (Ppara) in rat liver. Control group rats received a semisynthetic ration over 20 weeks. Experimental group 1 received a semisynthetic ration and 20% fructose solution instead of drinking water. Experimental group 2 rats received a semisynthetic ration with quercetin (0.1% fodder weight) and 20% fructose solution. Consumption of 20% fructose solution (experimental group 1) led to an increase in Scd expression in comparison with the control and did not affect the expression of other genes. Addition of quercetin to the ration (experimental group 2) led to a decrease in the expression of Khk, Gck, Fasn, Scd, Mlxipl, and Ppara genes in comparison with experimental group 1. The results suggest that quercetin reduced the expression of genes of carbohydrate and lipid metabolism enzymes in the liver of rats receiving high-fructose ration.

Prognostic value of N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) was analyzed in patients with multiple myeloma complicated by dialysisdependent renal failure. The prospective study included 20 patients with newly diagnosed multiple myeloma. The concentrations of NT-proBNP were measured before antimyeloma chemotherapy. The median age of the patients was 67 (63-76) years. The median glomerular filtration rate was 4 (4, 5) ml/min/1.73 m². For overall survival, the area under ROC curve was 0.75 and the cut-off point was 7000 pg/ml. At median follow-up of 17.3 months, the overall survival was 76.6±14.8 and 27.3±13.4% (p=0.02) for cases with NT-proBNP levels below and above the cut-off point, respectively. There were no cases of death due to cardiovascular causes. We concluded that the increase in serum concentration of NT-proBNP>7400 pg/ml is associated with the severity of kidney damage and the risk of non-cardiac mortality.

Magnetic resonance imaging (MRI) is one of the most perspective methods of noninvasive visualization in medicine, and use of contrast agents significantly its potentialities extends. Iron oxide nanoparticles are promising contrast agents, but in fact all the data on their efficiency were obtained in high-field tomographs for experimental animals. We studied the possibility of using magnetic nanoparticles for MRI visualization of rat brain glioblastoma at the most common clinical field 1.5 T The data indicate the efficiency of iron oxide magnetic nanoparticles as contrast agents for 1.5 T MR tomographs.

We studied the effects of hypogravity modeled by water immersion on cognitive functions and physiological parameters of monkeys. Cognitive capacities of monkeys were evaluated using computer-controlled joystick task with food reward in case of target hit. Water immersion (3 days for 3 h) affected in cognitive functions, body temperature, and blood parameters. The intensity of changes depended on the type of monkey behavior. In animals with non-aggressive behavior, the number of target hits did not decrease after water immersion, and even slightly increased. On the contrary, aggressive monkeys showed poorer test performance. Body temperature after each cycle of water immersion was decreased slightly in non-aggressive monkeys, while in aggressive animals, the changes were significant. At the same time, changes in the erythrocyte count, hemoglobin concentration, and hematocrit were significant in non-aggressive monkeys. Our results are in line with previous data performed on BION biosatellites and correspond to changes of physiological parameters in astronauts during space flights.

Two models of retinal ischemia/reperfusion were developed in an experiment on rats and structural changes in eye tissues in the early and late postischemic periods were studied. Ischemia/reperfusion was modeled by elevation of intraocular pressure to 110 mm Hg for 30 min with air injection into the anterior chamber of the eye with a special device or subconjunctival administration of 0.2 ml 4×10^–6 M endothelin-1. Morphological studies of the retina of enucleated eyes were performed in 3, 7, and 30 days after ischemia/reperfusion. In 3 days, signs of retinal ischemia were seen (retinal edema and ganglion cell damage). In the late post-ischemic period (30 days), atrophy of the outer nuclear and outer plexiform layer of the retina was observed in animals with retinal ischemia/reperfusion caused by intraocular pressure elevation and complete destruction of neuronal cells was found after administration of endothelin-1.