Bulletin of Experimental Biology and Medicine最新文献

We studied the effects of Semax on spontaneous fluctuations of intracellular calcium ion concentration [Ca²⁺]_i in pyramidal neurons on hippocampal slices and on proton-induced increase in [Ca²⁺]_i in cerebellar granule cells in cerebellar slices. Application of Semax (1 μM), significantly increased the frequency of spontaneous [Ca²⁺]_i fluctuations in the pyramidal layer cells of the hippocampal CA1 field, but had no significant effect on proton-stimulated increase in [Ca²⁺]_i in cerebellar granule cells. These data provide insight into the localization of cellular targets and elucidate the dynamics of the initial stages of interaction between the peptide and the hippocampal neuronal network. The primary mechanism of the neuroprotective effect of Semax appears to be unrelated to attenuation of calcium entry through acid-sensing ion channels in cerebellar granule cells.

It was shown that blocking of glycolysis by 2-deoxy-D-glucose (DG) inhibits LPS-induced NO production in glial cell cultures and reduces the mitochondrial membrane potential. Lactate partially prevented the decrease in the mitochondrial membrane potential of gliocytes, but did not affect the inhibitory effect of DG. Immunocytochemical typing showed the presence of a large number of astrocytes and microglia in the culture. In the control, microglial cells had a large number of processes, which is typical of nonactivated cells, whereas in LPS-treated cultures, microglia had a flattened amoeboid morphology typical of activated microglia. In cultures treated with LPS against the background of DG, both cells with processes and amoeboid cells were present. Our results indicate that inhibition of glycolysis is a strong modulating factor in inflammation.

The biological properties of nine clinical isolates of Pseudomonas aeruginosa obtained from five patients with cystic fibrosis were assessed. Six different sequence types of P. aeruginosa with different biofilm-forming abilities were detected. It was found that at the initial stage of adhesion, four isolates were tobramycin-resistant, while in the formed biofilm, almost 100% survival was recorded. The properties of the isolates were associated with the sequence type: when it changed, the biofilm-forming ability decreased, but the number of viable cells resistant to tobramycin at a concentration of 2 μg/ml increased. The study shows that the existence of a biofilm is a key factor ensuring, despite constant antimicrobial therapy, the long-term persistence of P. aeruginosa in patients with cystic fibrosis.

The anticonvulsant activity of the diterpene alkaloid 12-epinapelline N-oxide isolated from the aboveground part of Aconitum baicalense was demonstrated in experiments on mice with modeled maximal electroshock-induced seizure and pentylenetetrazol-induced seizures. Taking into account the mechanism of seizure development in the studied models, we can hypothesize that the anticonvulsive activity of the alkaloid is determined by its interaction with Na⁺ channels and GABA_A receptors.

We performed a comparative analysis of lipid and cholesterol metabolism disorders, as well as liver condition in male Wistar rats receiving high-fat diets with different cholesterol contents. Addition of 2% cholesterol to the diet resulted in a marked aggravation of fatty liver disease, characterized by extreme accumulation of fat and cholesterol. A diet supplemented with 0.5% cholesterol resulted in serum cholesterol accumulation and liver steatosis, but had no effect on weight gain or body composition. Introduction of 1% cholesterol to the diet induced similar abnormalities as 2% cholesterol, but without the extreme cholesterol and fat accumulation in the liver. This model can be used in the future to evaluate the effectiveness of the studied functional foods.

We measured the plasma levels of adrenomedullin in normotensive Wistar rats and spontaneously hypertensive rats (SHR) was investigated, and evaluated changes in its level under conditions of increased blood viscosity. Blood viscosity was increased by the method of isovolumic hemoconcentration (replacement of 10% of circulating blood with the same volume of packed erythrocytes of donor rats). The initial concentration of adrenomedullin in Wistar rats was 1912 ± 195 pg/ml, while in SHR it was 40% lower (p = 0.007). In Wistar rats, an increase in blood viscosity was accompanied by a decrease in the concentration of adrenomedullin by 1.8 times in comparison with the initial value, while in SHR it did not lead to significant changes in adrenomedullin level. The absence of changes in the plasma adrenomedullin concentration in SHR in response to blood viscosity elevation may indicate that the mechanotransduction mechanism is excluded from the regulation of vascular tone, which is probably one of the forms of endothelial dysfunction associated with its impaired sensitivity to shear stress changes.

This review considers cell therapy and possible mechanisms underlying beneficial effects of cells in prevention of neurodegenerative changes as a promising approach to the treatment of Alzheimer's disease. The results of using various types of cells in experimental models of Alzheimer's disease and their effect on the regeneration of the brain and recovery of cognitive functions are presented.

The TNFα content in the blood serum of 109 patients with uterine fibroids was studied. Cytokine concentrations ranged from 4.65 to 25.88 pg/ml regardless of the clinical parameters of the disease, but were associated with complex genotypes of different structural and functional organization (TNFA, IL1B, IL4, IL6, IL8, IL10, IL17A, VEGFA, MMP2, MMP3, MMP9). The interaction of multiple genes that affect the level of serum TNFα production has been revealed. In particular, on the one hand, the complex genotype TNF-308GG/VEGF-2578CA is positively associated with high levels of TNFα (OR = 10.00, p_cor = 0.0274), and on the other hand, the combined genotype of 4 polymorphisms TNF-308GG/TNF-238GG/VEGF-2578AA/MMP2-1306CC is closely associated with its low level (OR = 25.00, p_cor = 0.0469). The obtained results allow better understand the mechanisms of the manifestation of the genetic predisposition to uterine fibroids associated with the presence in the genome of highly specific gene compositions that underlie tumorogenesis in this disease.

We studied the effect of a protein kinase A (PKA) inhibitor and the content of different types of progenitor cells in the subventricular zone of the brain of 16-month-old male C57BL/6 mice (characterized by pathological endogenous amyloid formation in the brain) and on the mental status of these mice. The pharmacological agent ameliorated disorders of orientation and exploratory behavior and conditioned response performance in experimental animals. At the same time, an increase in the content of resident neural stem cells and committed neuronal precursors in the nervous tissue was found.

The valproate model of autism was used to evaluate the effect of a course of dimephosphone administration (intragastric, 50 mg/kg, 30 days) on contractions of the isolated bladder of rats induced by application of carbacholine (10^-7-10^-5 M), α,β-methylene-ATP (10^-7-10^-5 M), and stimulation with an electric field of different frequencies (1-20 Hz). In rats with the valproate model of autism, the strength of carbacholine-induced bladder contractions was significantly higher than in control (intact) rats. Against the background of dimephosphone administration, carbacholine-induced contractions reached the control level. Similar results were obtained with electric field stimulation. However, when evaluating the effect of dimephosphone on bladder contractions caused by α,β-methylene-ATP, no significant changes were found. Dimephosphone, when administered in a course, normalizes bladder contractility in rats with the valproate model of autism.