Effect of emotional stress on biogenic amine content in the sensorimotor cortex of rats with experimental intracerebral hemorrhage.

Experiments on the model of an aggressive-conflict situation were designed to study the effect of emotional stress on biogenic amine content in the sensorimotor cortex of the right cerebral hemisphere in behaviorally active and passive rats with experimental hemorrhage in the left caudate nucleus of the brain. Prior exposure to stress in active and, particularly, in passive animals was shown to modify the type of neurochemical reactions in brain tissue during modeling of intracerebral hemorrhage. As differentiated from rats with experimental hemorrhagic stroke, passive specimens of this series were characterized by a slight increase in norepinephrine content and significant elevation of dopamine level in the sensorimotor cortex on day 3 of the study. An increase in dopamine content in brain tissue of stressed active rats was observed on days 1 and 3, which corresponded to the immediate and acute stages of the post-stroke period. Variations in serotonin content in the sensorimotor cortex of animals with post-stress intracerebral hemorrhage had the same dynamics, but were less pronounced than in non-stressed rats. Our results illustrate the specific involvement of brain biogenic amines in animals with various behavioral characteristics in the adaptive and compensatory processes, which occur during various stages of experimental intracerebral hemorrhage after stress exposure.

Specific features of biogenic amine content in the cerebral cortex during experimental intracerebral hemorrhage in rats with various behavioral characteristics.

Experiments on Wistar rats showed that modeling of hemorrhage in the left caudate nucleus of the brain in behaviorally passive specimens is mainly accompanied by an increase in biogenic amine content in the sensorimotor cortex of the right cerebral hemisphere (particularly on day 3 after the surgery). Norepinephrine content in the sensorimotor cortex of the right cerebral hemisphere in behaviorally active rats was reduced over 7 days after the development of intracerebral hemorrhage. The contents of dopamine and serotonin in brain tissue of behaviorally active animals most significantly increased on day 7 after experimental stroke. Our results indicate that experimental hemorrhage in the left caudate nucleus of rats with various behavioral characteristics is accompanied by specific changes in biogenic amine content in the sensorimotor cortex of the right cerebral hemisphere. We conclude that neurochemical processes in brain structures distant from the site of hemorrhage play an important role in the pathogenesis of hemorrhagic stroke.

Chromatographic determination of methyl glyoxal in blood plasma as the test for glycotoxicity and accumulation of glycation end-products.

We developed a method of measuring methyl glyoxal concentration in blood serum using HPLC with UV detection. Methyl glyoxal concentration was determined in healthy subjects. The method was developed for indirect but reliable measurement of the levels of glycation end-products in patients with diabetes, hyperlipidemia, and cardiovascular pathologies.

[Prevention of atherosclerosis. The positional specificity of blood triglycerides and lipases, the particular milk lipids, and the modification of the fatty acids of vegetable oils and animal fats].

Milk is a biological medium that bears no resemblance to any of the biological fluids and tissues in primates and mammals in the positional composition of fatty acids (FA) in triglycerides. This is determined by the fact that at the very early phylogenesis of mammals, milk is to ensure a high postnatal bioavailability (absorption) of saturated palmitic FA, a substrate for neonatal energy supply despite all obstacles that are formed in the baby's intestine in vivo. Milk is destined for infant nutrition in the biology-destined period (not more than a year); assimilation of triglycerides that are so structurally unusual requires a) high isomerization activity in the enterocytes and b) the ability of blood lipases to hydrolyze palmitate-oleate-palmitate triglycerides as a component of oleic very-low-density lipoproteins. After the period permitted by nature, there is virtually no possibility to physiologically consume milk that contains structurally unusual triglycerides. The use of whole milk and its products by adults impairs the active, receptor cell absorption of FAs as ligand lipoproteins via apoE/B-100-endocytosis and enhances the generation of small, dense low-density lipoproteins as biological debris. The impaired biological function of endoecology and the debris accumulation of the intercellular medium lead to the activation of atheromatosis, atherothrombosis, and coronary sclerosis. Nature has given no sanction for turning the mammals that are not on milk to those on milk for whole life. Up to one year of age, the baby has in vivo conditions for the absorption and hydrolysis of triglycerides with palmitic FA at the sn-2 position. After one year of age, the expression of these lipases and coenzymes is over; re-expression occurs only with the activation of the biological function of locomotion - long-term strenuous physical activity. High physical activity expresses other genes, enzymes, coenzymes, and carrier proteins, which activate the hydrolysis of triglycerides high in palmitic FA. These mechanisms are similar to those activated in vivo during the early postnatal period.

[Prevention of atherosclerosis. Excess of palmitic acid in food--a cause of hypercholesterolemia, inflammatory syndrome, insulin resistance in myocytes, and apoptosis].

Unity of the pathogenesis of atherosclerosis, type 2 diabetes mellitus, and metabolic syndrome gives rise to impaired biological function of adaptation, altered biological function of exotrophy (external feeding) and endoecology ("purity" of the intercellular medium). Biological reactions of inflammation and hydrodynamic pressure, or blood pressure, are in vivo activated to compensate for intercellular debris accumulation by endogenous phlogogens--ligand-free low density lipoproteins (LDL). The biological reactions jointly remove LDL from blood to the intima of elastic type arteries, to interstitial tissue for the local pool of the intravascular medium. The causes of formation of aphysiological LDLs are a preponderance of palmitate-oleate-palmitate triglycerides in the latter and impaired hydrolysis upon exposure to post-heparin lipase to give rise to small, dense LDLs; intimal macrophages utilize the debris only partially and develop atheromatosis from polyenic fatty acids (FA) etherified by cholesterol alcohol. Excess of palmitic saturated fatty acid (sFA) is responsible for the lowered permeability of the plasma membrane, cell death via the mechanism similar to apoptosis. Aphysiological protein palmitoylation (covalent interaction with palmitic sFA) increased the debris accumulation of the intercellular medium and the activity of both biological reactions. Elevated plasma palmitic sFA and its enhanced passive absorption in the form of unetherified FA, as well as high C-reactive protein levels are a cause of insulin resistance. The only way to prevent atherosclerosis in the population is to normalize the biological function of exotrophy when the energy value ratio of FA, proteins and carbohydrates is 1:1:1 and that of sFA, monoenic, and polyenic FA is also 1:1:1. The lower amount of palmitic sFA and the higher concentration of essential polyenic FA, the lower blood levels of cholesterol alcohol and triglycerides are. At the same time, simultaneously activations and the biological function of locomotion are a level of physical activity.

[Plasma antioxidant activity--a test for impaired biological functions of endoecology, exotrophy, and inflammation reactions].

The authors discuss the diagnostic value of a test for total serum antioxidant activity determined by an electrochemistry method on a liquid chromatograph (without a column), by using an amperometric detector, as well as the composition of the endogenously synthesized hydrophilic and hydrophobic acceptors of reactive oxygen species (ROS). Uric acid is a major hydrophilic acceptor of ROS; monoenic oleic fatty acid acts as its major lipophilic acceptor. The constant determined by the authors for of 03 oleic acid oxidation during automatic titration in the organic medium is an order of magnitude higher than that for alpha-tocopherol, beta-carotene and linoleic fatty acid; its concentration is also an order of magnitude higher. In oxidative stress, the adrenal steroid hormone dehydroepiandrosterone initiates oleic acid synthesis via expression of palmitoyl elongase and steatoryl desaturase. In early steps of phylogenesis in primates, spontaneous mutation resulted in ascorbic acid synthesis gene knockout; phylogenetically, further other mutation knocked out the gene encoding the synthesis of uricase and the conversion of uric acid to alantoin. In primates, uric acid became not only a catabolite of purine bases in vivo, but also the major endogenous hydrophilic acceptor of ROS. This philogenetic order makes it clear why the epithelium in the proximal nephron tubule entirely reabsorbs uric acid (a catabolite?) from primary urine and then secretes it again to urine depending on the impairment of biological functions of endoecology (the intercellular medium being contaminated with biological rubbish), the activation of a biological inflammatory reaction, the cellular production of ROS, and the reduction in serum total antioxidant activity. With each biological reaction, there was an increase in the blood content of uric acid as a hydrophilic acceptor of ROS, by actively lowering its secretion into urine. Uric acid is a diagnostic test of inflammation, or rather compensatory anti-inflammatory response syndrome.

Effects of chronic neuroticization on the monoaminergic systems of different structures in the brains of rats with different typological characteristics.

The levels of monoamines and their metabolites were studied by HPLC with electrochemical detection in homogenates of hypothalamus, hippocampus, prefrontal cortex, and amygdala in intact and neuroticized Wistar rats with different types of behavior in the open field and forced swimming tests. Intact rats with intermediate levels of activity and depressivity had higher serotonin concentrations in the hypothalamus and lower noradrenaline and hydroxyindoleacetic acid levels in the hippocampus than rats characterized by low activity and high depressivity. In neuroticization, the levels of study monoamines and their metabolites decreased in all the brain structures investigated with the exceptions of an increase in the dopamine concentration in the hippocampus and the dihydroxyphenylacetic acid concentration in the prefrontal cortex. The effect of neuroticization on the neurotransmitter systems in all study structures except the hypothalamus depended on the typological characteristics of the rats. This was most marked in rats with the extreme types of behavior--active and passive--in which changes in monoamine and metabolite contents were seen in all brain structures studied. Rats of the intermediate type showed no changes in any of the substances studied in the hippocampus.

[The influence of chronic neurotization on the monoaminergic systems of various brain structures in rats with various typological characteristics].

Typological behavioral features of Wistar rats were tested in the open field and in Porsolt test. Rats were assigned to groups with high (HAct), medium (MAct), and low (LAct) behavioral activities. The same rats were assigned to high (HDep), medium (MDep) and low depressive (LDep) groups. The release of norepinephrine, dopamine, serotonin and their metabolites in homogenates obtained from the hypothalamus, hippocampus, frontal cortex and amygdala was assessed by microdialysis and HPLC. In these groups, the monoamine concentrations were different: the level of serotonin was higher in the hypothalamus and norepinephrine and 5-HIAA levels were lower in the hippocampus of MAct - MDep rats as compared to LAct - HDep. Chronic neurotization caused changes in monoamine concentrations in the hypothalamus and amygdala in rats of all groups, whereas in the hippocampus and frontal cortex monoamine changes were observed in HAct - LDep and LAct -HDep rats. The most prominent changes in monoamines levels in neurotized rats with different types of behavior were found in the frontal cortex, amygdala and hippocampus. The results show a correlation between the typological of behavioral characteristics and the reaction to stress of monoaminergic systems of the hypothalamus, hippocampus, frontal cortex and amygdala.

[Comparative characterization of radioimmunologic and non-isotopic methods of hormonal analysis]. / Sravnitel'naia kharakteristika radioimmunologicheskgo i neizotopnogo metodov gormonal'nogo analiza.

Measurements of 8 hormones (prolactin, FSH, LH, thyrotropic hormone--TTH, estradiol, hydrocortisone, thyroxine, and triiodothyronine--T3) were carried out by the Amerleit system and radioimmunoassay. The hormones were measured in the same blood plasma samples of patients with various endocrine conditions, admitted for examinations to the Endocrinology Center of the Russian Academy of Medical Sciences. Employment of the Amerleit system for hormonal analysis helps obtain the results compatible with the results of RIA for the majority of the measured hormones. The methods for measuring LH, estradiol and T3 are to be improved. The Amerleit system is highly productive and permits getting the results within 3 hrs. A trained laboratory assistant can measure the hormonal levels in 120-160 blood samples within a day. High efficacy of the technology is indispensable in realization of the screening programs. The absence of radioactivity, safety, high productivity, reliability, accuracy and good storage of the kits (up to 6-8 months) are the principal advantages of the Amerleit system over the existent radioimmunologic systems.