Vol 162, No 3 (2017)

Zinc level in the blood plasma and brain of rats was studied by inductively coupled plasma mass spectrometry. Maximum amount of zinc was observed in the cerebellum (15.0±5.5 μg/mg wet tissue). Single intraperitoneal administration of a zinc donor acyzol (24 mg/kg) did not change the content of this element in the tissues. Repeated injections of acyzol (7 injections over 14 days) significantly increased zinc level in rat plasma and brain. This elevation was most pronounced in the forebrain (cortex and subcortical structures). The rise in zinc concentration in blood plasma correlated with its level in the brain.

Specificity of behavioral and neuronal mechanisms of impairment of long-term memory reconsolidation was studied in edible snails trained for associative skill of rejection of two types of food: raw carrots (conditioned stimulus 1) and apple (conditioned stimulus 2). In 2 days after training, the snails received protein synthesis inhibitor cycloheximide and a reminder (conditioned stimulus 1 or 2). In 3 and 14 days after cycloheximide/reminder, we observed the absence of aversive responses to the conditioned stimulus used as the reminder and preserved responses to the conditioned stimulus not used as the reminder. Moreover, we observed specific suppression of synaptic responses of command neurons of snail defensive behavior induced by the conditioned stimulus used as the reminder after cycloheximide injection and preserved synaptic responses of neurons to the other conditioned stimulus. It was hypothesized that protein synthesis-dependent synapse-specific plasticity of command neurons can be a mechanism of selective preservation of conditioned food aversion memory in snails.

Sex differences in the morphogenesis and adaptation of the mechanisms controlling myocardium contractility during physiological and pathological hypertrophy of the right ventricle were demonstrated in mature rats. The study revealed sex-dependent effects of physiological and pathological cardiac hypertrophy on the coefficient of variation of the cardiomyocyte diameter, length-dependent control of the contractile force, and the maximum velocity of isotonic shortening.

Blood levels of nonesterified fatty acids, total cholesterol, triglycerides, and LDL increased in rats subjected to forced swimming stress. Administration of opioid peptides dynorphin A(1-13), DSLET, or DAGO reduced stress-induced disturbances in lipid metabolism. Dynorphin A(1-13) and DAGO produced the most pronounced effects and prevented an increase in concentrations of nonesterified fatty acids, triglycerides, total cholesterol, and LDL as soon as 39 h after treatment. Only DSLET increased HDL content in the plasma of stressed rats. The observed effects can be explained by the stress-limiting effects of opioids, e.g. attenuation of the effect of catecholamines on the adipose tissue and inhibition of the generation LPO products suppressing activity of the cholesterol metabolizing enzyme.

Specific features of LPO processes and antioxidant defense were studied in patients with polycystic ovarian syndrome (PCOS) and infertility. Changes in LPO processes in patients with PCOS were compensatory, which manifested in increased α-tocopherol and retinol concentrations and moderate decrease in superoxide dismutase activity. Intensification of prooxidant processes was found in the group of patients with infertility without PCOS. The observed changes necessitate differentiated approach to the treatment of these patients.

Changes in pregnenolone and corticosterone production by the adrenal glands of normoglycemic rats receiving the course of intraperitoneal mifepristone or NaCl administration were co-directed, but differed in magnitude. In rats with hyperglycemia, corticosteroid production increased after NaCl administration over 5 days and returned to the initial values after 15-day administration. On the contrary, pregnenolone and corticosterone production was suppressed after 5-day course of mifepristone, but significantly increased after mifepristone administration for 15 days. Intraperitoneal mifepristone administration almost completely abolished the response of rat adrenal glands with normo- and hyperglycemia to ACTH in vitro; this effect did not depend on the duration of administration.

Hepatoprotective properties of a new pyrimidine derivative — L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one, synthesized on the basis Xymedon, were assessed in white rats exposed to CCl4. The compound under study administered prior to exposure to CCl₄ reduced the deviation of biochemical parameters from reference values and severity of structural and morphological changes in liver, when compared to the control. Hepatoprotective properties of the studied compound were more pronounced than those of Xymedon.

Effect of Tramadol infusion (5 mg/ml) on oxytocin-induced uterine contractile activity was studied in chronic experiment on female rabbits with different degrees of biological readiness for parturition. In case of sufficient biological readiness for parturition, Tramadol did not change the number of uterine contractions, but increased the amplitude and duration of each contraction against the background of increased creatine phosphate consumption by the myometrium. At the same time, Tramadol infusion to females without biological readiness for partirition suppressed induced uterine contractile activity by reducing the amplitude of each uterine contraction.

An original model of nephrogenic hypertension in rats was used for histochemical mapping of NADPH diaphorase (NO synthase) in various renal segments to examine the effect of hypotensive drugs furosemide, bendazol, and clonidine on the time course of nitroxide production in the kidneys. In various nephron segments, these drugs modulated NO synthesis in different ways. Clonidine induced a stable up-regulation of NO synthesis, which can maintain active vasodilation and gradually diminish the rennin production. Bendazol also enhanced NO synthase activity in renal glomeruli and collecting tubules, but this effect was less pronounced and short lasting. During the first week after injection of bendazol, insignificant elevation of NO synthase activity was observed in the proximal nephron segments. Furosemide exerted the least effect on NO production in kidneys.

We revealed an association of IL6 gene -174G>C polymorphism with the development of nonalcoholic steatohepatitis in the Russian population. The risk is significantly higher in carriers of C allele: OR=1.77 (1.04; 3.02). The effects of -174G>C substitution in IL6 gene involving caspase 9 gene transcripts in peripheral blood leukocytes and on blood content of TNF-α in healthy individuals without clinical manifestations of nonalcoholic steatohepatitis were detected. The content of caspase 9 gene transcripts in peripheral blood leukocytes and plasma level of TNF-α were significantly higher in healthy subjects carrying C allele than in carriers of GG genotype. The levels of caspases 3, 6, 8, and 9 gene transcripts in peripheral blood leukocytes and plasma concentrations of TNF-α in patients with nonalcoholic steatohepatitis did not depend on IL6 genotype by -174G<C marker.

Antitumor efficiencies of cytostatics dioxadet, cisplatin, mitomycin C, melphalan, and paclitaxel after a single intraperitoneal or intravenous injection in doses of 1.5, 4, 1.5, 2, and 5 mg/kg, respectively, were studied on the model of transplanted ovarian tumor in 124 rats. The antitumor effects were evaluated by the increase in median survival. Dioxadet, cisplatin, and melphalan injected intraperitoneally significantly prolonged the lifespan median – by 79, 88, and 114%, respectively, and were in fact ineffective, when injected intravenously. Intraperitoneal mitomycin C prolonged lifespan median by just 35%, intravenous – by 152%. Paclitaxel injected intraperitoneally and intravenously prolonged the lifespan median by 45 and 81%, respectively.

We described a new model of risk behavior in rats that allows selection of animals predisposed to risk behavior in the absence of other biological motivations. Phenazepam administration did not change the intensity of risk behavior in “risky” animals, but stimulated risk behavior in rats that were not predisposed to it. Nicotine inhibited risk behavior in “risky” animals and strengthened it in “cautious” rats. In the intermediate group, the drugs did not induce significant changes. A similar effect of the drugs was observed in the previous models. More complex effect of nicotine on the risk behavior may be explained by the absence of severe food motivation typical for the early models.

Selective agonist of δ₂-opioid receptors deltorphin II and its retroenantio analog (0.12 mg/kg intravenously) were preventively injected to male Wistar rats 15 min prior to 45-min coronary occlusion or 5 min before 120-min reperfusion. Administration of deltorphin II before artery occlusion and before reperfusion decreased the infarct size/area at risk ratio. Deltorphin II prevented the appearance of ischemia-provoked ventricular arrhythmias and exerted no effect on HR and BP (systolic and diastolic). The retroenantio analog of deltorphin II produced no antiarrhythmic or infarct-limiting effects, but reduced HR without affecting BP. Deltorphin II can be viewed as a promising prototype for a medicinal remedy to treat acute myocardial infarction.

Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host—parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell—cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

We studied the effect of camphecin (1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol) on mouse behavior in the open-field test. Camphecin possesses antiviral activity and inhibits viral replication, but its influence on the nervous system is poorly studied. Single camphecin injection produced no significant changes in behavioral patterns. Chronic camphecin administration (5 times over 2 weeks) to mice of different strains had no significant influence on open field behavior (motor, exploratory activity, anxiety, emotional state and vegetative functions). The findings are discussed in the context of neutral influence of camphecin on animal behavior.

We studied the effect of carbon monoxide (60-, 75-, and 90-min exposure) on the expression of antiapoptotic proteins (survivin and Bcl-2) in human blood lymphocytes in the presence of recombinant IL-2 in an apoptosis-inducing dose (0.1 ng/ml). Incubation of cells in atmosphere with carbon monoxide in the presence of recombinant IL-2 was accompanied by accumulation of Bcl-2 protein with simultaneous decrease of survivin content. It was concluded that carbon monoxide plays a role in the dysregulation of apoptosis of human blood lymphocytes Bcl-2 (i.e. CO inhibits the proapoptotic effect of recombinant IL-2).

We performed diagnostic classification of plasma specimens from patients with non-metastatic and metastatic prostate cancer based on pairs of miRNA that have no individual diagnostic significance. Of 230 miRNA detected in plasma specimens, 3 pairs were diagnostically significant. The miRNA pair hsa-miR-19b-3p and hsa-miR-297 demonstrated highest sensitivity and specificity. Among common target genes of these miRNA, CFL2 gene associated with cell mobility was detected.

A relationship between transfer of monkeys from yard to individual cage and duration of stay in individual cage and the serum biochemical parameters is detected in Macaca mulatta males.

We studied the effects of nanodispersed ceria on wound healing in vitro and in vivo. It was found that cerium dioxide stimulated wound healing, which manifested in shrinkage of burn wound area (by 1.5 times) and intensification (by 2.4 times) marginal epithelialization.

The regenerative potential of stem and progenitor cells from ischemic testes of C57Bl/6 mice was studied in vitro (cell culture) and in vivo (mouse model of busulfan-induced suppression of spermatogenesis). Spermatogonial stem cells with phenotypes CD117^—CD90⁺ and CD51^—CD24⁺CD52⁺ from ischemic testes demonstrated 33-fold and 7-fold increments of cell mass and generated colonies in vitro. Epithelial (CD45^—CD31^—Sca-1⁺CD49f⁺) and endothelial (CD45^—CD31⁺) precursors exhibited lower self-renewal capacity. On day 30 after injection of stem and progenitor cells from ischemic testes to the rete testis zone of the testes of busulfantreated animals, an increase in the count of CD117^—CD90⁺ spermatogonial stem cells, total count, and mobile sperm count in the testes of recipient mice was observed. In addition, we observed an increase in Sca-1⁺ cell count, recovery of the spermatogenic epithelium in the seminiferous tubules, and appearance of immature Leydig cells in “busulfan” testes; the level of tissue testosterone and fertility index also increased.

Hypovolemic shock leads to severe cerebral ischemia and increases spectral amplitudes of cerebral blood flow oscillations in respiratory frequency range.