Publications by authors named "FROLKIS V"

Based on the authors' own data and a review of current literature, the role of vasopressin (VP) in the mechanisms of age-related changes, development of stress-reactions and pathology onset is discussed. In aging, the VP concentration in blood and cerebrospinal fluid increased, its level in pituitary rose and that in hypothalamus fell. Under stress (emotional-painful stress, water deprivation) the potential capabilities of the VP-ergic system decreased with age.

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General characteristics and mechanisms of effects of nitric oxide (NO) and its role in the development of pathology are reviewed. Presented are the data about NO participation in the regulation of circulation and cardiovascular system; NO-dependent mechanism of regulation of cardiovascular reactivity against the background of dysfunction of endothelium; cGMP-independent mechanism of NO effect upon Ca homeostasis and the sensitivity of myofibrils of smooth muscle cells to Ca ions; pharmacological correction of disturbances of NO metabolism and related endothelial dysfunction; role of age changes of the endothelial function in the development of cardiovascular pathology.

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Experiments on the Wistar rats showed that neonatal daily injections of phenobarbital (35 mg/kg) during first 3 days of life resulted in the enzyme imprinting of liver microsomal monooxygenases. Rise in the activities of liver microsomal oxidation enzymes is constantly maintained during all the life leading to increase in average lifespan of rats. Analysis of the survival curves in Gompertz equation co-ordinates showed that enzyme imprinting by phenobarbital caused changes in mortality patterns at different stages of ontogenesis.

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The heart contractility and changes of lipid composition of isolated rat heart (n = 26) under total ischemia and ischemia-reperfusion was studied. The effect of N-stearoyl-ethanolamine under these conditions was investigated. N-stearoyl-ethanolamine leads to remodelling of fatty acyl chain composition of myocardial phospholipids: to drastic fall of polyunsaturated fatty acyl chains (18:2w6, 20:3w6, 20:4w6, 22:5w3, 22:5w6, 22:6w3 and 22:6w6) and enhancement of 18:0.

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The results obtained show the essential changes in functional state of hepatocyte's plasmatic membrane due to the implantation of human ApoA1 gene to the rat liver. The changes in phospholipid composition, hyperpolarization, increase in activity of membrane bound enzymes, cytochrome P-450 and biosynthesis of liver total proteins have been found. The essential changes characterizing cell effect were more marked in the adult rats, and membrane effect in the old ones.

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Studies were made of the effects of various classes of lipoproteins (LP) from the blood of rabbits with experimental hypercholesterolemia and human subjects with pronounced atherosclerosis on the vascular tone of rat thoracic aorta specimens. In hypercholesterolemia, there was a considerable weakening of a vasodilatory action of atherogenic LP fractions--LDL and VLDL. A vasodilatory effect of HDLP was not changed.

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It has been shown in the experiments on adult (6-8 mo) and old (26-28 mo) Wistar rats that in aging, due to an electrical stimulation of the hypothalamus, the liver induction of thyroxine aminotransferase, tryptophan-pyrrolase, glucose-6-phosphatase and fructose-1, 6-diphosphatase decreases. In old rats, the biosynthesis of RNA fractions gets activated at later periods. In contrast to adult animals, the electrical hypothalamic stimulation did not induce any marked changes in chromatin fractions ratio and transcriptional processes in old rats.

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Age peculiarities of partial hepatectomy effect on the hepatocytes plasma membrane Na+, K(+)-ATPase activity and its insulin-induced stimulation has been studied. It has been shown that partial hepatectomy does not change basal Na+, K(+)-ATPase activity in adult rats. In old partial hepatectomised rats Na+, K(+)-ATPase activity is slightly higher than in control old rats, although this increase is not statistically significant.

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The labelled steroid hormones [3H]hydrocortisone and [14C]testosterone, being injected into the gray matter of the rat spinal cord L5-L6 segments, were shown to be transported at a high velocity along the ventral (anterograde) and dorsal (retrograde) root fibres. The maximum velocity of axonal transport along the ventral and dorsal roots in adult rats was, on average, 3006 +/- 101 and 3028 +/- 48 mm/day for [3H]hydrocortisone and 4594 +/- 186 and 5185 +/- 485 mm/day for [14C]testosterone, respectively. In old rats, axonal transport of steroid hormones was markedly slower.

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Effect of the enzyme imprinting by phenobarbital upon alterations of hepatic microsomal monooxygenase activities and lifespan of Wistar rats has been studied. Phenobarbital-sodium (3.5 mg/100 g body weight per day, i.

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An internally contradictory character of individual development may suggest a new periodization of the latter. Etagenesis is an age-associated development of an organism from the zygote to death. Ontogenesis is the period of realization of the genetic program of the organism's development under effects of exogenic factors, the period of growth and shaping of its main structure and functions, and the period of formation of its reproductive function.

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In this work we used aorta coarctation as a model of myocardial hypertrophy. We studied the role of intracellular regulators of plasma membrane status-invertors-in the mechanisms of changes of membrane enzyme activities in the emergency stage of myocardial hypertrophy. We used Wistar rats of various ages: adult (6-8 months) and old (26-28 months) rats.

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The experiments were performed on adult (6-8 months) and old (22-24 months) Wistar rats. Insulin induced plasma membrane hyperpolarization and hepatocyte Na,K-ATPase activation in adult but not in old sham-operated rats. Partial hepatectomy had no effect on the invertor mechanism of Na,K-ATPase activity regulation in the liver of adult rats, while pronounced changes took place in old animals 4 weeks after partial hepatectomy.

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In rat experiments a new model of situational chronic stress, with the use of multicomponent natural stimulating influences, has been elaborated. The study revealed two subpopulations with longer and shorter lifespan in the group of stressed rats vs. control group.

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The experiments on the isolated hearts from adult and old rats have shown that during first hours of prolonged perfusion the contractile function decreased to a greater degree in adult rats compared to the old. Following a 3-h perfusion, there occurred a marked fall of the contractile function in old animals. The creatine phosphokinase activity in a perfusate grew sharply in the old rats and changed insignificantly in the adult.

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It has been found that the activation of protein biosynthesis in various cells (hepatocytes, adrenocorticocytes, thyrocytes and myocardiocytes), caused by different factors such as multiple hormones, regeneration, hyperfunction etc., leads to the development of plasmatic membrane hyperpolarization. It has also been shown that during protein biosynthesis activation under genome control there have been synthesized the intracellular regulators of plasmatic membrane state, called invertors.

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Transfer of human apoAI gene, within the molecular construction which provides its expression, to the liver of adult and aged rats resulted in the appearance of human protein in their blood, and was accompanied by changes in the content of high-density lipoproteins, as well as by the shifts in their protein and lipid composition. Administration of the human ApoAI gene was followed by changes of the vasoactive effects of HDL. Gene implantation is capable of enhancing the direct vasodilatory effects of HDL in old animals, being weakened by ageing, even against the background of normal age changes in the vascular wall tone.

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Article Synopsis
  • - Experiments on both adult and old rats showed that blood lipoproteins have a dilating effect on the thoracic aorta, but this effect decreases with age.
  • - Older rats exhibited lower sensitivity in their blood vessels to all lipoprotein fractions compared to younger rats, particularly noting HDL's reduced ability to cause vasodilation with age.
  • - Changes in HDL composition with age included a decrease in phospholipids and an increase in total cholesterol, while the vasodilatory effects of LDL and VLDL remained constant.
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In rats the rate of axonal transport (AT) or radiolabeled material decreased in the ventral roots of the spinal cord and the vagal and hypoglossal nerves with aging. A maximum AT deceleration in old age was observed in the vagus. The uncoupling of oxidative phosphorylation, inhibition of glycolysis and hypoxia induced a greater AT deceleration in old rats as compared to adults.

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Development and regression of experimental atherosclerosis in rabbits is an expressed age-related phenomenon, showing the increase in occurrence and pronouncement of atherosclerotic process with age. A new approach to the disease treatment by means of olivomycin is described. It has shown that while influencing considerably the protein biosynthesis of experimental animal, one can accelerate the regression of atherosclerosis by means of olivomycin and reduce protein and lipid metabolism indicators characterizing the disease development.

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Effect of insulin on Na, K-ATPase activity and phospholipid (PL) composition of myocardiocytes' plasma membrane (PM) was investigated in adult (6 months old) and old (28 months old) male Wistar rats. Administration of insulin increases Na, K-ATPase activity and phosphatidilethanolamin content, and decreases phosphatidilinositol content of myocardiocytes' PM in adult animals. Administration of insulin doesn't change Na, K-ATPase activity and decreases phosphatidilethanolamin content of myocardiocytes' PM in old rats.

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