[EXPRESSION OF DOUBLECORTIN AND NeuN IN THE DEVELOPING CEREBELLAR NEURONS IN RAT].

This work was performed on the offspring of 5 outbred female albino rats to give a comparative immunohistochemical evaluation of doublecortin (DCX) and NeuN expression in the neurons of the cerebellar cortex and nucleus interpositus in the early postnatal ontogenesis (postnatal days 2-15). DCX expression was detected in postmitotic neurons of the external granular layer and migrating neurons of the cerebellar cortex. At postnatal days 2 and 7 DCX expression in neocerebellum was higher than in paleocerebellum. NeuN expression was found to appear in migrating granule neurons, and reach the maximum in mature neurons of internal granular layer. DCX expression was not detected in Purkinje cells and in the nucleus interpositus of the cerebellum. In neurons of the nucleus interpositus the expression of NeuN progressively increased from postnatal days 2 to 15. Thus, a comparative immunohistochemical study of the dynamics of the expression of the pair of molecular markers studied proved to be an effective way of the assessment of the development of granular neurons of the cerebellum in early postnatal ontogenesis.

[DYNAMICS OF HISTOLOGICAL CHANGES IN THE FRONTAL CORTEX OF THE BRAIN OF RATS SUBJECTED TO PRENATAL ALCOHOL.EXPOSURE].

The purpose of the present investigation was a comparative study of the effect of prenatal exposure to alcohol on the histological characteristics of neurons in the frontal cortex of the rats of different ages. The study was conducted on 175 outbred albino rats ­ the offspring of 25 females given a 15% solution of ethanol as a source of drinking throughout pregnancy. The cortex was examined at Days 2­90 after birth using histological, histochemical and morphometric methods. An increase (Days 2, 5), followed by the reduction (Days 10 and 90) of the thickness of the cortex and the size of neurons (Days 20­90) were detected, together with the decrease in the number of neurons in layer V of the cortex, reduction of the number of normochromic and an increase of the number of shrunken hyperchromic neurons and ghost cells in all study periods. Antenatal alcoholization was found to cause a variety of histological changes in the frontal cortex of rat brain in postnatal ontogenesis that had a long-term and progressive nature.

[THE SYNAPTOGENESIS IN THE DEVELOPING CEREBELLUM OF THE RAT].

The aim of this study ­ qualitative and quantitative evaluation of synaptogenesis in the developing cerebellum of the rat (postnatal Days 2­45) using immunohistochemical detection of synaptophysin (SYP) as the the marker. The expression of SYP was demonstrated in postmitotic neurons of the external granular layer and migrating precursors of granular neurons of the cerebellum. During the whole period studied, an increase in the width of the zone of synaptogenesis in the molecular layer took place together with the decrease of SYPimmunoreactivity. The reduction in the number of SYP-immunopositive synapses was noted around Purkinje cell perikarya from Day 7 till Day 15. In the internal granular layer, SYP-immunopositive dots were observed that increased in size from Day 2 to Day 45 due to the formation of cerebellar glomeruli. In the cerebellar interposed nucleus, the number and sizes of axosomatic synapses around neuronal perikarya were found to increase during the whole period examined. In the neuropil, the uneven aggregates of SYP-immunopositive axodendritic synapses were observed.

[Morpho-functional changes in the liver and the possibility of their correction in the offspring of rats with cholestasis].

The study aims to clarify the influence of experimental cholestasis mother on the structure of the liver of young rats in early postnatal development (Day 2) and to explore the possibility of the correction of these disturbances with Ursofalk drug. Material was obtained from 30 outbred albino rat pups and studied using histological, histochemical, morphometric and electron microscopic methods. It was found that under the influence of maternal cholestasis, the liver of the offspring demonstrated the dilation of sinusoidal capillaries, the decreased activity of succinate dehydrogenase and increased activity of NADH dehydrogenase in hepatocyte cytoplasm, the development of significant ultrastructural abnormalities (disappearance of lipid droplets, accentuated heterogeneity of mitochondrial size and shape, increased number of lysosomes). The application of Ursofalk partially restored hepatocyte structure and metabolism.

[COMBINATION OF TAURINE WITH ZINC DIASPARTATE FOR CORRECTION OF METABOLISM DISTURBANSES IN NEPHRONS AND RENAL FUNCTION IN RATS WITH CONTRAST-INDUCED NEPHROPATHY].

The nephroprotective properties of a combination of taurine with zinc diaspartate (taucin) in rats with contrast-induced nephropathy have been estimated. It is established that the combination of taurine with zinc diaspartate (20 and 1 g/mol, respectively, ingested in doses 250 and 500 mg/kg in the stomach during 14 days) produces a dose-dependent nephroprotective action on rats with contrast-induced (sodium and meglumin amidotrizoates, 800 mg/kg/day intraperitoneally, 14 days) nephropathy.

[Ultrastructural changes in brain histaminergic neurons under the influence of alcohol].

The aim of the present study was to investigate the ultrastructural changes developing in histaminergic neurons of the brain of 24 outbred albino male rats-after administration of ethanol in the acute experiment (single intraperitoneal dose of 1 and 4 g/kg), subacute exposure (as the sole source of drinking at a dose of 4 g/kg for 7 days), or chronic administration (at a dose of 2-3 g/kg/day for 6 months). After alcohol administration histaminergic neurons were found to develop various ultrastructural changes of their nucleus and organelles. They reflect the processes of neuron destruction, as well as adaptive changes aimed at restoring and maintaining their functions. These changes were nonspecific and -depended on the dose, time after injection and duration of alcohol administration. In general they corresponded to the structural and histochemical changes observed at light-microscopic level.

[The effects of alcohol on the developing brain].

In the review the literature data on the effect of alcohol on the developing brain of human and animals are summarized. The information is presented on the neuroimaging, histological, cellular and molecular-genetic disturbances in the brain in fetal alcohol syndrome and following exposure to alcohol during the early postnatal period. The structural developmental abnormalities of the different parts of the brain, disorders of neurogenesis and neuronal apoptosis, changes in metabolism, receptors and secondary signals system of neurons are described. Prenatal alcohol exposure causes significant, various long-term disturbances of the brain structures at the organ, tissue, cellular and subcellular level, which may lay in the basis of the observed neurological, behavioral and metal disorders.

[Structural and histochemical changes in the rat cerebellum Purkinje cells after cholestasis].

The aim of the study was the estimation of structural and metabolic changes in the rat cerebellum Purkinje cells (PC) in the dynamics of subhepatic cholestasis. Histological, histochemical and electron microscopic methods were used. It was found that the cholestasis induced the progressive intensification of the structural and metabolic disturbances in the cerebellar PC reaching their maximum on days 10-20 and resulting in PC death and PC number reduction. In the cytoplasm of these cells the reduction of the activities of succinate dehydrogenase, NADH-diaphorase, glucose-6-dehydrogenase was recorded together with the decrease of RNA content and the activation of lactate dehydrogenase and acid phosphatase. The disturbances of PC at the ultrastructural level included the destruction of the nucleus and organelles (especially, of the mitochondria), associated with the increase of phagosome size and number, augmentation of relative free ribosome number, appearance of close contacts between mitichondria and cell nucleus and organelles. After 45-90 days in survived animals gradual normalization of PC structure and metabolism took place apparently as a result of spontaneous cholestasis elimination due to the development of new bile ducts.

[Morphofunctional state of vessel endothelium at the early stage of cerebral ischemia-reperfusion and the effect of taurin administration].

Experiments in a group of 28 male rats with ischemic-reperfusive brain damage showed (i) the presence of endothelial dysfunction manifested by an increase in the number of circulating endothelial cells and a decrease in the activity of alkaline phosphatase, (ii) activation of the platelet and coagulation hemostasis, (iii) modification of the frontal brain cortex. The administration of taurin led to correction of the endothelial dysfunction, removal of morphological changes in the brain cortex, and improvement in the aggregation of platelets and blood coagulation.

[Structural and histochemical changes in rat parietal cerebral cortex neurons subjected to biliary drainage].

The aim of this study was the estimation of structural and metabolic changes in the rat parietal cortical neurons during complete external biliary removal. Quantitative histological, histochemical and electron microscopic methods were used. Biliary drainage was found to result in the progressive increase of the number of hyperchromic, shrunken neurons and ghost cells, cell death and the reduction of the number of neurons, with the increase of the glial cell number in all layers of parietal cortex. Gradual decrease of size, loss of sphericity and elongation of neurons were also recordered. In neuronal cytoplasm, the activity of succinate, NADH, NADPH and glucose-6-phosphate dehydrogenases, as well as RNA content were decreased, while lactate dehydrogenase and acid phosphatase activities were increased. Partial destruction of the nucleus and organelles (mitochondria, endoplasmic reticulum, Golgi complex) was also observed, accompanied by the increase in lysosomal number and size, activation of nuclear apparatus and the increase in relative amount of free ribosomes. Thus, the loss of bile by the organism lead to the progressive structural and metabolic disturbances in parietal cerebral cortex neurons, that resulted in the death of some of these cells and compensatory changes in the others.

[Brain histaminergic neurons in rats subjected to the acute effect of alcohol].

The purpose of the present investigation was to examine the effect of single injection of alcohol on histaminergic neurons of rat brain. The study included 41 male albino rats, histological, histochemical, electron microscopic and morphometric methods were used. It was found that 1 hour after the intraperitoneal administration of ethanol in a dose of 4 g/kg the neurons become more spherical, the activity of NADH and glucose-6-phosphate dehydrogenases in their cytoplasm decreased, but the activity of lactate dehydrogenase, type B monoaminooxidase and acid phosphatase increased, at the same time significant ultrastructural disturbances were observed. Six hours following alcohol administration, the signs of histaminergic neuronal damage were reduced while the features of structural and metabolic adaptation became more expressed.

[Therapeutic effect of acetylcysteine on rats with gentamicin-induced nephropathy].

Gentamicin (60 mg/kg, i.p., once per day for 10 days) produces a nephrotoxic effect in rats, which is manifesting by the epithelium necrosis of proximal convoluted tubules (especially of cortical nephrons), decreasing creatinine clearance, and increasing protein in the urine. Acetylcysteine (40 mg/kg, i.p., once per day for 10 days) significantly decreases manifestations of the gentamicin nephrotoxicity. Acetylcysteine administration leads to the appearance of normal tubules (absent in rats treated by gentamicin), decreases the number of necrotized proximal convoluted tubules of cortical nephrons and reduces their internal diameter, and increases the height of paving epitheliocytes. The content of detrite in tubules of juxtamedullar nephrons decreases, while the activity of alkaline phosphatase in proximal convoluted tubules of cortical and juxtamedullar nephrons and the activity of lactatedehydrogenase in cortical nephrons increases.

Structural-metabolic changes in histaminergic neurons of the rat hypothalamus in conditions of loss of bile.

The aim of the present work was to evaluate structural and metabolic changes in histaminergic neurons in hypothalamic nucleus E2 in rats in conditions of complete external drainage of bile. Studies were performed on male Wistar rats (n = 45). Controls consisted of animals subjected to sham surgery with preservation of physiological bile flow throughout the experiment. Quantitative histological and histochemical methods were used. Serial frontal cryostat sections cut from the posterior hypothalamus were used for detection of the activity of the following enzymes: monoamine oxidase B, succinate dehydrogenase, NADH dehydrogenase, NADPH dehydrogenase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and acid phosphatase. Morphological studies of histaminergic neurons were performed on preparations stained with thionine. These studies showed that complete external drainage of bile led to transient size reductions and rounding of cell perikarya. Metabolic changes were seen within a day of bile loss and subsequently progressed. All energy metabolic pathways were suppressed and acid phosphatase activity was increased on day 5.

Metabolic changes in rat brain histaminergic neurons during subhepatic cholestasis.

The aim of the present work was to assess metabolic changes in histaminergic neurons in the rat brain during subhepatic cholestasis. Studies were performed on male Wistar rats using quantitative histochemical methods. The results showed that in cholestasis, histaminergic neurons in the rat hypothalamus developed significant changes in succinate dehydrogenase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activity, in NADH and NADPH, and in acid phosphatase and monoamine oxidase B. These changes depended on the duration of cholestasis and had a dynamic, wave-like nature. The changes were apparent after five days of cholestasis, reached a maximum at 10-20 days, decreased at 45 days, and completely disappeared at 90 days.

[Metabolic changes in rat brain histaminergic neurons in dynamics of subhepatic cholestasis].

The aim of the study was the estimation of metabolic changes in rat brain histaminergic neurons in dynamics of subhepatic cholestasis. The investigation was carried out in male Wistar rats using the quantitative histochemical methods. It was found that cholestasis induced significant changes in the activity of dehydrogenases of succinate, lactate, glucose-6-phosphate, NADH and NADPH, as well as of acid phosphatase and type B monoamine oxidase in hypothalamic histaminergic neurons. These changes depended on the duration of cholestasis and had the dynamic, undulating pattern. They were demonstrated already after 5 days of cholestasis, reached their maximum by 10-20 days, were decreased at 45 days and disappeared after 90 days.

[Structural and metabolic changes in the rat hypothalamic histaminergic neurons induced by the bile loss].

The aim of the study was the estimation of structural and metabolic changes in histaminergic neurons of rat hypothalamic E2 nucleus induced by total external bile drainage. The investigation was carried out on male Wistar rats (n=45). The control group comprised the sham-operated animals, in which the physiological bile drainage was preserved during the whole experimental period. Quantitative histological and histochemical methods were used. In serial frontal cryostat sections of posterior hypothalamus, the activity of the following enzymes was demonstrated histochemically: monoamine oxidase B, succinate dehydrogenase, NADH- dehydrogenase, NADPH-dehydrogenase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase and acid phosphatase. Morphometric study of histaminergic neurons was performed in thionin-stained sections. It was found that total external bile drainage resulted in a temporary reduction of the sizes and rounding of neuronal perikarya. Metabolic changes were detected already after 1 day of bile loss, and they were found to progress henceforth. All the pathways of energy metabolism were suppressed, while the acid phosphatase activity was increased, on day 5.

Spatial organization and morphometric characteristics of histaminergic neurons in the rat brain.

We report here a study addressing the spatial organization, densities, numbers, sizes, and shapes of histaminergic neurons in the rat hypothalamus. Studies were performed on 50 rats using histochemical and morphometric methods, computer image analysis, and three-dimensional reconstruction of the histaminergic nuclei of the hypothalamus. The results demonstrated that the total bilateral volume of the histaminergic nuclei of the rat brain amounts to 0.5 mm(3): the E2 nucleus occupies 40% of the total volume, E4 occupies 35%, E3 occupies 13%, E5 occupies 9%, and E1 occupies 3%. The distribution density of monoamine oxidase B neurons in the histaminergic nuclei of the rat hypothalamus decreased in the order E1 > E3 > E2 (the "compact" nuclei) > E4 (an "intermediate" density nucleus) > E5 (the "diffuse part"). The mean number of histaminergic neurons in the rat hypothalamus was 37200 +/- 2800; the E2 nucleus contained 54% of these cells, E3 contained 23%, E4 contained 6%, E1 contained 7%, and E5 contained 0.32%. The E1-E3 nuclei were dominated by small and intermediate-sized neurons, round in shape, and the E5 nucleus was dominated by intermediate and large neurons, fusiform in shape. A subpopulation of giant histaminergic neurons was detected in the E4-E5 nuclei.

[Spatial organization and morphometric characteristic of histaminergic neurons of the rat brain].

The aim of the study was the estimation of the spatial organization, the density of distribution, number, sizes and shape of histaminergic neurons of the rat hypothalamus. The investigation was carried out in 50 adult Wistar rats, using the methods of histochemistry, morphometry, computer image analysis and 3D reconstruction of hypothalamic histaminergic nuclei. It was found that the total bilateral volume of rat brain histaminergic nuclei was equal to 0.5 mm3 : E2 nucleus occupied 40% of their total volume, while E4 occupied 35%, E3 - 13%, E5 - 9% and E1 - 3%. The density of distribution of monoamineoxidase B-positive neurons was decreased in a series E1 > E3 > E2 (compact nuclei) > E4 (intermediate nucleus) > E5 (diffuse part). The average number of histaminergic neurons in rat hypothalamus was equal to (372 +/- 28) x 10(2): E2 nucleus contained 54% of that amount, E3 - 23%, E4 - 16%, E1 - 7%, E5 - 0.32%. In E1-E3 nuclei, small and medium neurons round in shape were prevalent, while in E5 these were medium and large neurons of fusiform shape. The subpopulation of giant histaminergic neurons was found in E4-E5.

[Comparative evaluation of the action of oxythiamine and its derivatives on animals with Erhlich's ascitic cancer]. / Sravnitel'naia otsenka deistviia oksitiamina i nekotorykh ego proizvodnykh na zhivotnykh s astsitnym rakom Erlikha.

It is found that hydroxythiamine ester with sebacic acid surpassed hydroxythiamine in its antitumour effect on Ehrlich ascites tumour in albino mice. A linear correlation is observed between the values of activity coefficients of hydroxythiamine and its esters with dicarboxylic acids and some morphometric data.

Alcohol action on liver: dose dependence and morpho-biochemical correlations.

BACKGROUND: Since the duration and the dose of alcohol administration are acknowledged as factors that influence the risk of liver injury, it was interesting to compare the character and degree of liver damage following various doses and methods of alcohol administration. In addition, it was assumed to compare the degree of liver damage histologically and on the activity of marker liver enzymes in blood plasma in the same animals. METHODS AND RESULTS: The several experiments on heterogeneous stock rats with the various daily dose, duration and method of alcohol administration have been carried out. It was found, that the 9-month intake of 15.20% (v/v) ethanol solution as the only source of drinking (the consumption of absolute alcohol was about 4 g/kg/day) did not affect the normal development of animals and did not induce any harmful morphological changes in liver. Moreover, the liver parenchyma looks even better in the context of lesser inflammatory infiltration and vacuolisation of hypatocytes. The activities of the marker liver injury enzymes: alanine and aspartate amino transferases (ALT and AST), alkaline phosphatase (AP) as well as alcohol dehydrogenase (ADH) in blood were also not changed. The intragastric administration 25% (v/v) ethanol (3.5 g/kg twice a day, during 14 days) induced some morphological disturbances in the liver: an extension of blood capillaries and veins in parenchyma and insignificant increasing of the hepatocyte vacuolisation degree (from 0.7 +/- 0.1 points in control to 1.2 +/- 0.2 points in alcohol treated animals). In blood serum, a slight elevation of ADH (from 1.2 +/- 0.2 microM/min/l in control to 1.7 +/- 0.3) and AP (from 236 +/- 19 microM/min/l in control to 278 +/- 25) activities were found. The liquid alcohol diets (mean consumption of absolute alcohol was 14-18 g/kg/day, during a month) induced the more pronounced liver injury: extension of the liver blood vessels, inflammatory infiltration (from 1.1 +/- 0.1 points in control to 2.0 +/- 0.3; P, 0.05) and destruction of hepatocytes (from 0.5 +/- 0.01 points in control to 1.2 +/- 0.1; p < 0.05). Another liquid alcohol diet (mean consumption of absolute alcohol was 20-24 g/kg/day, during a month) induced the expressive hepatocyte vacuolisation (from 0.5 +/- 0.1 points in control to 1.5 +/- 0.2; p < 0.05). In both the experiments, the weaker staining of hepatocyte cytoplasms, basophilia in particular, were found. The activity of blood plasma ADH was insignificantly increased by 47% and 134% and that of AP--by 15% and 38%. The activity of ALT insignificantly increased in the third experiment only and AST remained unchanged. Some correlations among the morphological and biochemical indexes were found in the above experiments: between the degree of hepatocytes vacuolisation and the blood ADH or AP activities (r = 0.62; p < 0.01 and r = 0.54; p < 0.05), accordingly. The oxyphilia intensity correlated with the AST activity (r = 0.64; p < 0.01) and the intensity of hepatocyte basophilia with the ADH activity (r = 0.67; p < 0.01). The negative correlation was also found between the degree of extension of liver blood vessels and the activity of AST (r = -0.57; p < 0.05). CONCLUSIONS: The data obtained confirm the earlier observations concerning the dependence of the degree of liver injury on the dose and manner of alcohol administration as well as great individuality in the liver response to alcohol in heterogeneous stock rats. There are the significant correlations between the some morphological and biochemical markers of alcohol liver injury; among the biochemical markers studied, the ADH activity was the most sensitive.