Vol 160, No 3 (2016)

Organized activity of the myocardium manifested in dominant frequency structure of EСG was typical of the first 10 min of ventricular fibrillation in canine heart. The first minute of fibrillation was characterized by the most pronounced changes in the structure of oscillation frequency and transition from domination of high frequency oscillations (13-17 Hz) to domination of medium (8-12 Hz) and then low frequency (4-7 Hz) oscillations. The second minute was characterized by transition from domination of low frequency oscillations to domination of low and medium frequency oscillations; minutes 3-10 were characterized by domination of low and medium frequency oscillations; after 10 min, non-dominant ventricular oscillations were recorded.

Activity of glutamine synthetase in the hepatocytes of healthy animals and animals with chronic CCl₄-induced hepatitis was studied on white mature female rats after liver resection (15-20% of organ weight) and hyperbaric oxygenation (3 atm, 50 min, 3 times). Surgically operated left and non-operated middle lobes of the liver were analyzed on day 3 after liver resection and exposure to hyperbaric oxygenation. On day 65 of CCl₄ poisoning, activity of glutamine synthetase decreased in both lobes and did not recover on day 3 after toxin cessation. Liver resection under conditions of CCl₄-induced hepatitis restored reduced activity of glutamine synthetase in both liver lobes to the normal level. In healthy rats, the increase in glutamine synthetase activity after liver resection was found only in the middle lobe of the liver. Hyperbaric oxygenation enhanced the stimulatory effect of liver resection on glutamine synthetase activity in hepatocytes during chronic CCl₄-induced hepatitis. In healthy animals with liver resection, activity of glutamine synthetase did not change after hyperbaric oxygenation, while normally oxygenation inhibited glutamine synthetase activity.

We studied the possibility of preventing disturbances caused by administration of low doses of toxicants by adaptation to interval hypoxia and hyperoxia. The preventive protective effect of adaptation to hypoxia–hyperoxia manifested in suppression of free radical oxidation, decrease in the levels of HIF-1α and inducible HOx-1, and improvement of tolerance to physical exercises.

Here we studied the cytoprotective effect of lithium chloride and sodium valproate in the in vivo model of neonatal cerebral ischemia/hypoxia and analyzed the influence of these substances on the death of the major neurovascular unit components in experimental ischemia in vitro. Lithium chloride and sodium valproate effectively prevented death of neurons, astrocytes, and endothelial cells in the oxygen-glucose deprivation. This treatment protected the brain of newborn rats from ischemia/hypoxia injury. The results suggest that lithium and sodium valproate can be used for the treatment of neurodegenerative pathologies associated with hypoxia and ischemia in newborns.

During exacerbation of cytomegalovirus infection during pregnancy, cytomegalovirus proteins penetrate across the external membrane of placental villous syncytiotrophoblast and suppress activities of ATPase and Bcl-2 protein. Simultaneous increase in the content of annexin V and caspase 3 leads to structural disturbances in DNA in syncytiotrophoblast nuclei and stimulates their apoptosis. Structural abnormalities in the syncytiotrophoblast during exacerbation of cytomegalovirus infection are dangerous for fetal development.

Analysis of antioxidant activity of synthesized selenourea derivatives showed that N,N’-substituted selenoureas inhibited Fe(III)-induced LPO in rat brain homogenate. On the other hand, oxygen- and sulfur-containing analogs exhibited no antioxidant activity or even slight prooxidant activity. Intramolecular alkylation of selenium atom also led to loss of antioxidant activity. Thus, antioxidant activity of the compounds was due to the presence of a nonalkylated selenium atom in N,N’-substituted selenourea analogs.

Antiviral properties of Hexoral (0.1% solution and 0.2% aerosol for local application) and its constituent hexetidine against viruses causing human respiratory tract infections and herpes virus were studied in vitro. It was found that non-cytotoxic concentrations of hexetidine (alone and as a component of Hexoral) attenuated infectious properties of highly virulent influenza virus A/H5N1, pandemic influenza virus A/H1N1pdm, respiratory syncytial virus, and herpes simplex virus type 1 after a short-term exposure (30 sec) by 100 or more times. It was found that hexidine mostly contributes to the virucidal effect of Hexoral.

Morphological and ultrastructural study of the kidney was performed in rats with oxalate nephrolithiasis. Specific features of endoplasmic reticulum stress were evaluated during nephrolithiasis and treatment with α-tocopherol. We observed the signs of endoplasmic reticulum stress with activation of proapoptotic pathways and injury to the cell lining in nephron tubules and collecting ducts. Ultrastructural changes were found in the organelles, nuclei, and cell membranes of epitheliocytes. A relationship was revealed between endoplasmic reticulum stress and oxidative damage, which developed at the early state of lithogenesis.

We studied the effect of bleomycin (1 mg/kg) in 1-day-old rat pups (single intraperitoneal injection) and 4-day-old pups (3 injections on postnatal days 1, 2, and 3). The formation of hyaline membranes against the background of oxidative stress was documented in all bleomycin-treated rats. Repeated injection of bleomycin (4-day-old pups) led to more pronounced destructive alterations in the lungs characterized by the formation of microcysts and atelectases as well as hypertrophy of the interstitial connective tissue. These alterations persisted in 14-day-old rats. Administration of bleomycin during the neonatal period can be a promising approach to simulation of hyaline membrane disease (respiratory distress syndrome).

In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level beclin-1 protein and morphology of the left ventricular myocardium on days 1, 3, and 5 after the onset of focal ischemia caused by ligation of the descending branch of the left coronary artery. The morphological alterations in the left ventricular myocardium were accompanied by intensification of cardiomyocyte autophagia, which attained maximum on postligation day 1.

We studied the density and structure of the microvascular network of the pia mater, the blood flow rate and oxygen saturation in the sensorimotor cortex of young spontaneously hypertensive rats (SHR). The density of the microvascular network in hypertensive animals was by ~1.4 times lower than in normotensive Wistar-Kyoto rats (control) and arteriolar bed density was lower by ~1.9 times. The blood flow rate in tissue and oxygen saturation in the sensorimotor cortex in SHR rats were significantly lower than in control animals.

Synthetic antioxidant S-nitrosoglutathione suppressed the expression of MMP-1 mRNA in HT1080 cells exposed to hypoxic hypoxia; hyperexpression of superoxide dismutase 2 increased and hyperexpression of catalase inhibited the expression of MMP-1 mRNA in HT1080 cells.

Screening study of the effects of sweet flag (Acorus calamus L.) rhizome and clover (Trifolium pratense L.) aerial part on the production of NO by mouse macrophages was carried out. The polysaccharides were separated by ion exchange chromatography into fractions differing by monomeric composition and ramification type and were used in concentrations of 20, 40, and 100 μg/ml. Four fractions of Acorus calamus L. (PSF-101, PSF-102, PSF-103, and PSF-105), used in different concentrations, moderately stimulated nitrite production by macrophages. Three of five Trifolium pratense L. polysaccharides (PS62-3, PS62-4, and PS62-5) exhibited a significant specific effect on NO production. Rhamnogalactouronans from clover PS63-3 in all concentrations and from PS62-5 in a concentration of 100 μg/ml exhibited the highest activity, comparable to the NO-stimulatory activity of the reference LPS, while polysaccharide PS62-3 in a concentration of 40 μg/ml exhibited even higher activity.

Application of NO-producing lactobacilli to a rat jejunum segment induced muscle relaxation that was potentiated after activation of bacterial NO production with NO synthase substrate L-arginine. Similar changes in the intestinal contractile activity were observed in response to exogenous NO formed by sodium nitroprusside. These results indicated the involvement of NO synthesized by probiotic lactobacilli in the regulation of the intestinal motor function.

The effects of recombinant analog of natural Ebola virus protein vp24 in configurations virulent (vp24-ad) and avirulent (vp24-w) for guinea pigs on interferonogenesis were studied in vivo and in vitro. Amino acid differences were determined by His186 substitution in avirulent (nonlethal) configuration for Tyr in the virulent (lethal) one. Recombinant analogs vp24-w and vp24-ad inhibited interferonogenesis in vivo and in vitro. Inhibition by the two protein configurations was virtually the same.

Studies of collagen gene polymorphisms associated with predisposition to early recurrent miscarriages revealed significant differences in the distribution of COL1A1 C-1997A C>A (rs1107946) genotypes and alleles in the group of pregnant patients with early miscarriages in comparison with controls (normal pregnancy). Identification of COL1A1 C-1997A C>A (rs1107946) collagen gene polymorphisms at the stage of pregnancy planning will make it possible to form early miscarriage risk groups for more thorough preparation to gestation and optimization of follow up of this patient population.

MCF-7 breast cancer cells and HBL-100 breast epithelial cells were cultured with N-ethylmaleimide, a blocker of SH groups. Changes in redox potential of the glutathione system, activities of glutathione reductase, glutathione peroxidase, and intensity of apoptotic cell death were evaluated. The results indicate that incubation with N-ethylmaleimide led to glutathione system imbalance, reduced tumor cell redox potential, and induced their programmed death, which seemed useful for prospective target therapy of tumor diseases.

We developed a model of hepatitis E virus infection in common marmosets (Callithrix jacchus) and determined optimal route of infection, duration, clinical and virological characteristics of infection in laboratory animals. Using this model, we demonstrated that replication of hepatitis E virus primarily occurs in the liver, while virus replication presumed to take place in the intestine was not confirmed in this experiment.

We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds.

Structural-and-functional reorganization of the synovial membrane and articular cartilage in the knee joint was studied in rats with experimental chronic heart failure. Separation of fibers, decrease in the relative volume density of microcirculatory vessels, and increase in the expression of MMP-9 and caspase 3 were found in the synovial membrane. A decrease in the thickness of the surface layer (tendency to erosion), vacuolization and necrosis of chondrocytes, and increase in their readiness to programmed cell death were observed in the articular cartilage. Changes in the content of type II collagen and metachromasia were revealed in the cartilage matrix. These changes illustrate the development of degenerative arthropathy in cartilage components.

A novel method of ground simulation in humans of physiological effects induced by the stay on the surface of celestial bodies with hypogravity was developed and successfully tested. This method is based on the change of gravity force angle, which decreases the gravitational component of the blood hydrostatic pressure characteristic of human vertical posture on the Earth and the load-weight onto the locomotor apparatus to the lower values expected at celestial bodies with hypogravity. The methodological requirements for ground simulation of the physiological effects of lunar gravity on human body are specified and substantiated by theoretical calculations. The experimental study revealed redistribution of liquid media in the human organism, functional changes in the cardiorespiratory system, and a decrease in the load-weight applied to the locomotor apparatus.