Involvement of NMDA and GABA(A) receptors in modulation of spontaneous activity in hippocampal culture: Interrelations between burst firing and intracellular calcium signal.

Spontaneous burst firing is a hallmark attributed to the neuronal network activity. It is known to be accompanied by intracellular calcium [Са2+]i oscillations within the bursting neurons. Studying mechanisms underlying regulation of burst firing is highly relevant, since impairment in neuronal bursting accompanies different neurological disorders. In the present study, the contribution of NMDA and GABA(A) receptors to the shape formation of spontaneous burst -was studied in cultured hippocampal neurons. A combination of inhibitory analysis with simultaneous registration of neuronal bursting by whole-cell patch clamp and calcium imaging was used to assess spontaneous burst firing and [Са2+]i level. Using bicuculline and D-AP5 we showed that GABA(A) and NMDA receptors effectively modulate burst plateau phase and [Са2+]i transient spike which can further affect action potential (AP) amplitudes and firing frequency within a burst. Bicuculline significantly elevated the amplitude and reduced the duration of both burst plateau phase and [Са2+]i spike resulting in an increase of AP firing frequency and shortening of AP amplitudes within a burst. D-AP5 significantly decreases the amplitude of both plateau phase and [Са2+]i spike along with a burst duration that correlated with an increase in AP amplitudes and reduced firing frequency within a burst. The effect of bicuculline was occluded by co-addition of D-AP5 revealing modulatory role of GABA(A) receptors to the NMDA receptor-mediated formation of the burst. Our results provide new evidence on importance of NMDA and GABA(A) receptors in shaping burst firing and Ca2+transient spikes in cultured hippocampal neurons.

[The most important stages of the mechanism of action in vivo of carcinogen diethylnitrosoamine and its effect on the synthesis of RNA, proteins, DNA, and deoxyribonucleotides].

The mechanisms of nitric oxide (NO) generation from exogenous and endogenous sources, induced by the addition of the carcinogen diethylnitrosoamine (DENA) to rat organism have been studied. Within 15 h after the addition of DENA, the carcinogen itselt acts as an exogenous NO donor. The products of protein degradation (the process induced by DENA) act as endogenous donors of NO. It was shown that the generation of nitric oxide from diethylnitrosoamine leads to deep hemic and tissue hypoxia and induces the inactivation of oxygen-dependent enzymes, including ribonucleotide reductase, and the inhibition of ATP synthesis. Under these conditions, the protein synthesis and as a consequence the synthesis of deoxyribonucleotides and DNA are strongly suppressed; i.e., diethylnitrosoamine produces the effect similar to the action of the antibiotic cycloheximide, an inhibitor of translation. The administration of cycloheximide to the animal organism also led to the appearance of a considerable amount of nitric oxide in the blood. It is assumed that nitric oxide initiates (on the administration of the carcinogen) or at least enhances (on the administration of cycloheximide) the blockage of the synthesis of the protein, deoxyribonucleotides, and DNA. In response to the disturbance of protein synthesis, the complex of enzymes is activated that accomplish the utilization of the degradation products of proteins, including the inducible form of NO synthase.

[Pharmacological properties of complex iron oxide nanoparticles entering in magnetic resonance tomography contrast agent].

A colloidal solution of iron oxide nanoparticles has been obtained that ensures an increase in the accuracy of diagnostic information from magnetic resonance tomography (MRT) due to the acceleration of proton relaxation in tissues, which improves the contrast of T1- and T2-weighed images. Improved visualization of small vessels in rat brain has been observed after intravenous injection of 0.1 ml solution containing 5.0 mg of contrasting iron nanoparticles. The paramagnetic properties of iron oxide nanoparticles were studied by the method of proton relaxation, and their size was determined by the method of transmission electron microscopy. The toxic properties ofnanoparticles were determined by their effect on cultured HeLa cells (MTT test). It is recommended to use a colloidal solution of superparamagnetic nanoparticles (size, 8.2 nm) for obtaining a pharmaceutical form of the new magnetic-resonance contrast medium Ferotrast.

Some physico-chemical and thermodynamic characteristics of maize starches hydrolyzed by glucoamylase.

Glucoamylolysis of maize starch at 55 °C has been studied by means of scanning electron microscopy (SEM), wide-angle X-ray diffraction spectroscopy (WAXD), and differential scanning calorimetry (DSC). It was found that hydrolysis is accompanied by changes in thermodynamic parameters of diluted aqueous dispersions of partially hydrolyzed starches. Such changes are ensured by two processes directly from hydrolysis and accompanying annealing. At relatively low degrees of hydrolysis (less than 30%), changes in thermodynamic parameters are mainly controlled by annealing. At the same time, at high degrees of hydrolysis (more than 40%), the main contribution to changes in thermodynamic parameters of partially hydrolyzed starch granules is due to the hydrolysis itself. It has been established that the main controlling parameter is the thickness of crystalline lamellae Lcrl, which, when annealed, increases, but tends to decrease at deeper glucoamylolisis. It has been established that the thickness Lcrl of crystalline lamellae, which increases with annealing, but shows a tendency to decrease with deeper glucoamylolysis is the most representative parameter of changes in maize starch after hydrolysis.

[The role of the vascular factor in the reorganization of water metabolism in denervated liver after bacterial endotoxin poisoning].

Intoxication with bacterial lipopolysaccharide (endotoxin) is accompanied by considerable rearrangements in the systems of blood microcirculation and water metabolism of the liver. These rearrangements are manifested as increased sinusoid area, changed total area of the cytoplasm and nuclei as well as the nucleocytoplasmic ratio in hepatocytes, increased content of total water in the organ, and changed magnetic relaxation properties (spin-lattice and spin-spin relaxation times). Preliminary parasympathetic denervation of the liver (vagotomy) changes the pattern of the organ response to bacterial endotoxin poisoning as indicated by the kinetics of studied morphological and biophysical parameters.

[Changes in the morphofunctional status of the liver in rats with acute tetrachloromethane poisoning and their correction with antihypoxants, antioxidants and actoprotectors]. / Izmeneniia morfofunktsional'nogo sostoianiia pecheni krys pri ostroi intoksikatsii tetrakhlormetanom i ikh korrektsiia antigipoksantami, antioksidantami i aktoprotektorami.

The acute tetrachlormethane intoxication leads to structural and metabolic alterations in the rat liver. Morphological changes include centrolobular necroses and blood stasis in dilated sinusoidal capillaries. Metabolic changes are manifested by an increase in the water content and time of the spin-lattice (T1) and spin-spin (T2) relaxation (this indicates a lesser degree of water structuralization and its enhanced lability), and distortion of the correlation between T1 and T2. The prophylactic administration of one of the antihypoxants, antioxidants or actoprotectors normalizes the morphofunctional condition of the liver. According to the degree of the therapeutic efficacy, the examined preparations form the following series: dibunol > gamma-sodium hydroxybutyrate > tomerzol.

[Morpho-biochemical study of the liver and serum albumins during tetrachloromethane intoxication and administration of antihypoxants, antioxidants, and actoprotectors]. / Morfobiokhimicheskoe issledovanie sostoianiia pecheni i sistemy syvorotochnykh al'buminov v usloviiakh intoksikatsii tetrakhlorometanom i vvedeniia antigipoksantov, antioksidantov i aktoprotektorov.

Organism intoxication with tetrachloromethane induces a complex of transformations in the liver and serum albumins system manifested in the liver as necroses in the central lobe, dilatation of sinus capillaries and blood stasis in them, increased content of total water, and changed magneto-relaxation properties indicating decreased structurization of water. The system of serum albumins shows decreased total concentration of albumins in the serum, decreased constant of 1-(phenylamino)-8-sulfonaphthalene probe binding, increased mean number of probe binding per albumin molecule, and increased accessibility of probe in the protein-probe complex for the quencher indicating changed type of interaction between the protein and fluorescent probe. Introduction of a antihypoxant, antioxidant, or actoprotector has a positive effect on the condition of the liver and serum albumins system: The studied indices are nearly completely normalized.

[Use of antihypoxants and antioxidants for pharmaco-correction of disorders of water metabolism in the liver and small intestine after vagotomy]. / Primenenie antigipoksantov i antioksidantov dlia farmakokorrektsii narushenii metabolizma vody v pecheni i tonkoi kishke posle vagotomii.

Bilateral subdiaphragmatic vagotomy in rats leads to hepatic and small intestinal water metabolic disorders appeared as higher levels of total water, longer spin-grid (T1) and spin-spin (T2) relaxation and impaired correlation between T1 and T2. The time course of changes in water metabolism in the liver is one-sided (maximum after 7 days) at the same time in the small intestine is two-sided (maximum after 7 and 30 days). The antihypoxant tomerzole and the antioxidant dibunol produce a partial normalizing effect on water metabolism in the studied viscera of the animals vagotomized (at day 30), the highest efficiency was demonstrated by dibunol whose pharmacological activity is the greatest in the small intestine.

[The role of the nervous factor in regulation of oxygen supply to the small intestine]. / Znachenie nervnogo faktora v reguliatsii kislorodnogo snabzheniia tonkoi kishki.

The experimental model of rat bilateral subdiaphragmatic stem vagotomy was used to study the role of parasympathetic nervous system in regulation of circulation and oxygen supply to the small intestine. Cut of the vagus nerves is shown to cause redistribution of the blood flow between gastroduodenal organs, to slow down local circulation, to reduce oxygen tension in the muscular lining of the jejunum, to raise water content in the wall and change magnetorelaxational characteristics. Morphologically this manifested in altered arteriolar and capillary configuration, dilation of the capacity microvessels, dystrophia of microvessel wall, red cell aggregation in capillaries and venules, defective permeability of the vascular wall. The above indices changed most 7 and 30 days after vagotomy. It is evident that impaired vagus innervation produces secondary circulation hypoxia in the small intestine.