[THE SPIRIT CHOLESTEROL, BIOLOGICA L ROLE AT STAGES OF PHYLOGENESIS, MECHANISMS OF INHIBITION OF SYNTHESIS OF STEROL BY STATINS, FACTORS OF PHARMACOGENOMICS AND DIAGNOSTIC SIGNIFICANCE OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

The hypolipidemic effect of statins is realized by inhibition of synthesis of local pool of cholesterol spirit in endoplasmic net of hepatocytes. The cholesterol spirit covers all hydrophobic medium of triglycerides with polar mono layer of phosphatidylcholines and cholesterol spirit prior to secretion of lipoproteins of very low density into hydrophilic medium. The lesser mono layer between lipase enzyme and triglycerides substrate contains of cholesterol spirit the higher are the parameters of hydrolysis of palmitic and oleic lipoproteins of very low density. The sequence of effect of statins is as follows: blocking of synthesis in hepatocytes and decreasing of content of unesterified cholesterol spirit in blood plasma; activation of hydrolysis of triglycerides in palmitic and oleic lipoproteins of very low density; formation of ligand lipoproteins of very low density and their absorption by cells by force of apoB-100 endocytosis; decreasing in blood of content of polyenoic fatty acids, equimolar esterified by cholesterol spirit, polyethers of cholesterol spirit and decreasing of level of cholesterol spirit-lipoproteins of very low density. There is no way to eliminate aphysiological effect of disordered biological function of trophology (nutrition) on metabolism of fatty acids in population by means of pharmaceuticals intake. It is necessary to eliminate aphysiological effect of environment. To decrease rate of diseases of cardiovascular system one has to decrease in food content of saturated fatty acids and in the first instance palmitic saturated fatty acid, trans-form fatty acid, palmitoleic fatty acids up to physiological values and increase to the same degree the content of polyenoic fatty acids. The saturated fatty acids block absorption of polyenoic fatty acids by cells. The atherosclerosis is a deficiency of polyenoic fatty acids under surplus of palmitic saturated fatty acid.

Changes in the content of protein and lipid oxidative modification products in tumor tissue at different stages of lung cancer.

The content of LPO products (conjugated dienes, MDA) and products of oxidative modification of proteins (protein carbonyl derivatives) is reduced in tumor tissue in comparison with normal tissue and varies depending on the disease stage.

[Effects of heptapeptide selank on the content of monoamines and their metabolites in the brain of BALB/C and C57Bl/6 mice: a comparative study].

The effect of heptapeptide selank on the content of neurotransmitter monoamines and its metabolites in the brain structures of BALB/C and C57Bl/6 line mice under conditions of the open-field test were studied. Significant interstrain differences in the content of norepinephrine (NE), dopamine (DA), serotonin (5-HT) as well as in the levels of their metabolites in hippocampus, hypothalamus, striatum and frontal cortex of C57Bl/6 and BALB/C mice were demonstrated. In particular, the content of 5-HT and its metabolite 5-oxyindolacetic acid (5-HIAA) in hippocampus of BALB/C mice (with passive stress response) was higher than in the same structure of C57Bl/6 (stress-susceptible) animals. The injection of selank (0.3 mg/kg) led to an increase in the NE level in the hypothalamus of both mice strains. At the same time, selank produced opposite effects on the content of DA metabolites: the concentrations of dioxyphenylacetic (DOPAC) and homovanillic (HVA) acids were found to increase in frontal cortex and hippocampus of C57Bl/6 mice, while the same parameters in BALB/C mice were demonstrated to decrease. Selank induced a decrease in 5-HT and 5-HIAA levels in the hippocampus of BALB/C mice, but did not affect these parameters in C57Bl/6 animals. The obtained results are indicative of selectivity of the anxiolytic effects of selank.

[Interstrain differences in the content of excitatory and inhibitory amino acids in the brain of DBA/2J, Balb/c and C57BL/6 mice: characteristics of the effect of a dipeptide antipsychotic drug dilept].

We have performed a comparative study of the content of glutamate (Glu), aspartate (Asp), taurine (Tau), glycine (Gly) and gamma-amino-butyric acid (GABA) in the cortex, hippocampus, and striatum of the DBA/2J, Balb/c and C57BL/6 mice brain. The levels of Glu, Tau and GABA in DBA/2J hippocampus was lower than those in other experimental strains. These findings are consistent with published data on the specific neurophysiological properties of DBA/2J (neuroleptic sensitive prepulse inhibition, deficit), thus allowing this strain to be used in modeling schizophrenia. Taking into account these facts, in the next step we investigated the effects of dilept, the new neurotensine-derived dipeptide with antipsychotic activity (GZR-123, methyl ester of N-caproyl-L-prolyltyrosine), on the content of neurotransmitter acids in DBA/2J mice brain structures. In a dose of 0.8 mg/kg (i.p.) dilept induced a statistically significant increase in the levels of Glu, Tau and GABA in striatum of DBA/2J, as well as insignificant increase in the levels of these amino acids in the cortex. These effects are quite similar to those described for the parent peptide neurotensine, in case of its intracerebral administration. The results of our study prove the necessity of the further development of dilept as a potential antipsychotic drug.

[Morphologic and biochemical heterogeneity of lysosomes]. / Morfologicheskaia i biokhimicheskaia geterogennost' lizosom

By means of isopycnic centrifugation in the continuous density gradient of sucrose two subfractions of lysosomes were isolated from rat liver homogenates: a "light" one (with the floating density p=1.13) and a "heavy" one (p=1.24). Electron microscopic, enzymatic and electron microscope enzymatic analysis of the isolated subfractions showed that the "light" subfraction consisted mainly of newly-formed primary lysosomes, while the "heavy" one was presented by secondary lysosomes. Parallel biochemical investigations demonstrated a considerable enzymatic heterogeneity of the two lysosomal subfractions: the "light" subfraction was characterized by a high specific activity of acid DNase, acid RNase and beta-galactosidase, and by almost total absence of beta-glucosidase activity, while the "heavy" one was characterized by a high specific activity of beta-glucosidase, beta-glucuronidase and beta-N-acetylglucosaminidase. Possible causes of enzyme heterogeneity of rat liver lysosomes are discussed.

[Morphologic, biochemical and functional properties of the mitochondria of the rabbit gastric mucosa]. / Morfologicheskie, biokhimicheskie i funktsional'nye svoistva mitokhondrii slizistoi zheludka krolika

Purified fractions of the rabbit gastric mucosa and liver mitochondria were isolated. Electrone microscopy and functional studies of mitochondria showed the most intact mitochondria of gastric mucosa to be localized in gradient fractions of p=1.16-1.18, and those of the liver in fractions with p=1.19-1.20. The gastric mitochondria differed from the liver mitochondria by specific localization in oxyntic cells, abundance of crists, small matrix volume, presence of high respiratory control at lesser values of pH, high respiratory activity, great amount of cytochromes of electron transport chain in inner mitochondria membrane, two-fold excess of cytochroma a in relation to b and c, absence of b5 and by presence of great amount of phosphathydilaethanolamine and unsaturated fatty acids.

[Molecular weight of multiple forms of rat liver and adrenal gland glucose-6-phosphate dehydrogenase]. / K voprosu o molekuliarnom vese mnozhestvennykh form gliukozo-6-fosfatdegidrogenazy pecheni i nadpochechnikov krys.

Estimation of molecular weights of the glucose-6-phosphate dehydrogenase (G6PD) multiple forms was carried out by the method of extended electrophoresis (within 24 hrs) in polyacrylamide gel with linear gradient of concentration (from 3.5% to 30%). Proceeding from the variations in molecular weight, the multiple forms of G6PD, found in liver tissue and adrenal glands, might be apparently classified as two types, designated as alpha-G6PD and beta-G6PD. The possible reasons are discussed for the existence of two types of G6PD in the one organ.

[Nutrition and disease]. / Pitanie i bolezn'

An essentially new concept of the effect of nutrition on the development and evolution of diseases has been advanced. At its root there lies the theory of metabolic current as a main path for maintaining the homeokinesis. In the aspect of this concept the pathogenesis of malnutrition diseases is considered as affections due to imbalanced alimentation at the cellular level. Changes in the biochemical status of the organism occurring under stressor effects and the part played by the nutrition factor in adaptive reactions of the organism in response to the stressor effects are analyzed. Investigations concerning the role of nutrition in the genesis of adiposity and atherosclerosis are summarized. The paper offers a summary of the material contained in numerous research works of the author and his collaborators, as well as information published in the world literature that leave no doubt as to the effectiveness of enzymological approaches and, in particular, the validity of the metabolis current concept, all this being essential for understanding the significance of alimentary factors in preventing and treatment of many diseases.

[Biological and nutritional value of food products]. / O biologicheskoi i pishchevoi tsennosti produktov pitaniia

The paper deals with a detailed analysis into the methods of study and of the validity of terminology adopted in denoting the usefulness of food products, proceeding from their chemical composition. The author proposes to distinctly subdivide the notions of the alimentary, biological and energy producing values, but unite them under a general term reflecting the totality of the useful qualities of the products that covers the estimation therein of a broad range of nutrients, which should be referred to as "nutritional value". The terms of biological and energy producing values are special designations. The first of them reflects the quality of proteinic components in the product which have to do both with the digestability of the protein and with the degree to which its amino acids compositions is balanced. Then it should be borne in mind that the indices of biological value may undergo substantial changes, both under the effect of rigid methods of technological treatment, that brings about a change in the structure of the protein molecules proper, and consequent upon their interaction with other nutrients, as well as during their long-term storage. An important advantage that offers the determination of the biological value indices is an analytical segregation from among numerous biological properties the ones which are related to the features specific for the structure precisely of the proteinic constituents of the food. The determination of this index allows it to differentiate the useful qualities of the protein from a great number of other factors that can significantly change the assimilation of the products by the organism, including the presence therein of extraneous substances. The term energy-producing value of the products characterizes the part of the energy that can be liberated from the nutrients in the course of biological oxidation and used in securing physiological functions of the organism. As a basis for expressing the alimentary (nutritional) value of the products a method of the integral score, reflecting the degree to which the chemical composition of the study product corresponds to the formula of balanced nutrition worked outhe author is suggested. The energy variant of the integral score presents definate advantages, for with it the author estimates the percentage of satisfied requirements of an adult person in nutrients with the consumption of products in an amount that corresponds to a definate portion of energy, 300 kcal, for example (which comprises roughly 10 per cent of an average diurnal requirement in energy). The energy variant of the score makes it possible to determine the "degree of completness" of the product's calories with essentian nutritional factors.

[Effect of tocopherol and protein deficiency on the activity of enzymes and their isoenzymatic spectra in rat testes]. / Vliianie nedostatochnosti tokoferola i belka na aktivnost' nekotorykh fermentov i ikh izofermentnye spektry semennikov krys.

The symptoms of E-avitaminosis against protein deficiency in the ration become manifest much earlier, i. e. in 12--16 weeks of the experiment instead of 24--36 weeks with the primary-deficient ration. This was marked by the development of the creatinuria, the falling blood serum and testes tissue tocopherol, a higher peroxidized erythrocytes hemolysis, the animals demonstrating a disturbed generative function. In the testes of the E-avitaminotic rats an appreaciably increased total activity of glucose-6-phosphate-dehydrogenase (G-6-PDG) and of the acid phosphatase (AP) was demonstrated, whereas the LDG remained essentially unchanged. An investigation of their isoenzymatic spectra revealed a considerable activity of the basic 5 G-6-PDG fractions with the appearance of additional ones, along with the disappearance of the specific LDG fraction--X-2 and a drastic fall in the activity of the specific fraction for the testes--LDG-X-1, with concurrent rise in the activity of the 5 basic fractions. In the isoenzymatic AP spectrum disappeared the AP-3 fraction of the degenerating testes tissues and a redistribution of the activity between the fractions took place.

[Effect of the nature of the nutrition and of the functional state of the hypophyseal-adrenal system on the "convulsion readiness" of the body]. / K voprosu o vliianii kharaktera pitaniia i funktsional'nogo sostoianiia gipofizarno-nadpochechnikovoi sistemy na "sudorozhnuiu gotovonost organizma'"

The effect of some amino acids, succinate and different doses of ACTH on the convulsion response readiness of the organism under the action of a strong sound stimulant was studied. With enrichment of the ration with glutamic acid and also following a parenteral introduction of large doses of succinate a definite protective effect was revealed and, conversely, administration of ACTH (intramuscularly, for 7 day in a dose of 5 Units per 100 g of body weight) increased the convulsion response readiness of the organism. A possible mechanism underlying the detected changes in the convulsion response readiness of the organism under the active factors under study are discussed.

[Body resistance to the exposure to sound against a background of unbalanced nutrition]. / Ustoichivost' organizma k zvukovomu vozdeistviiu na fone razbalansirovannogo pitaniia.

Subject to study was the influence exercised by the excess of a number of vitamins in the diet (thiamine, ascorbic acid, cyanocolbalamine, riboflavin and pyridoxine) on the spastic susceptibility of the organism under the effect of a strong sonic stimulant. Pyridoxine exerted a noticeable protective influence on audiogenic convulsions. Its protective effect increased with its combined application with riboflavin, succinate and glutamic acid. The possible mechanism of action of the studied vitamins and of their combinations with glutamic acid and succinate on the spastic susceptibility of the organism is discussed in the paper.

[Effect of a varying ascorbic acid allowance in guinea pigs on the metabolic indices in their bodies to cold exposure]. / Vliianie razlichnoi obespechennosti morskikh svinok askorbinovoi kislotoi na nekotorye metabolicheskie pokazateli v ikh organizme pri kholodovom vozdeistvii.

Changes in the content of ascorbic acid in the blood, urine and suprarenals and also of glucose and 11-oxycorticosteroids in guinea pigs with different vitamin C allowances under conditions of cold stress were studied. The data obtained suggest that the degree of the vitamin C allowances is essential for adequate reactions of the organism exposed to the action of cold, but the shifts in metabolic transformations point to the need for a more reserved utilization of high ascorbid acid doses.

[Effect of the fatty component of the food ration on the ionic permeability of bilaminar phosphatidylcholine membranes]. / Vliianie zhirovogo komponenta pishchevogo ratsiona na ionnuiu pronitsaemost' bisloinykh fosfatidilkholinovykh membran.

Five molecular types of phosphatidyl-cholines, viz. that of the chicken egg and of four others, isolated from the liver of rats fed on rations with qualitatively different fats, were used in forming double-layer membranes. A gas-chromatographic analysis established distinctive differences in the fatty acids composition of phosphatidylcholines obtained from the rat liver. The degree of their oxidation was controlled by determining the level of dienic conjugates. No relationship between the permeability for inorganic ions and the composition of the phosphatidyl-cholines fatty acids could be established. It appears that in phosphatidyl-choline membranes at the basis of ionic permeability there lies some other mechanism than in the case of uncharged low-molecular substances.

[Effect of retinol deficiency on the activity of phospholipase A lysosomal enzymes in rat testes]. / Vliianie nedostatochnosti retinola na aktivnost' fosfolipazy A i nekotorykh lizosomal'nykh fermentov v semennikakh krys.

In the testes homogenates of rats kept on a A-deficient ration and receiving additionally retinyl-acetate (control) and retinoic acid (experiment) the activity of the phospholipases A1 and A2, with 1-acyl-2(1-14C)-oleoyl-SN-glycero-3-galactosidase and acid phosphatase employed as a substrate, was investigated. In the testes of rats receiving retinyl-acetate the activity of the phospholipases A1 and A2 was greatly declining. An addition of retinyl to the testes homogenates of test rats contributed to re-establishing the activity of the phospholipases up to the control level. In the testes of rats receiving retinoic acid a reduced activity of the acid phosphatase and a rise of beta-galactosidase, as compared to their activity in controls was also demonstrable.

[Effect of retinol and alpha-tocopherol on the stability of phosphatidylcholine bilayer membranes]. / Vliianie retinola i alpha-tokoferola na stabil'nost' fisloinykh fosfatidilkholinovykh membran.

The modifying action of retinol and alpha-tocopherol on the stability of bilayer phosphatidyl choline membranes was studied under control of their oxidation. The membranous stability was determined by the time during which the value of the ionic conduction of the membrane in a stationary condition remained unchanged. It was shown that the stability of the membranes modified by the addition of retinol and alpha-tocopherol was not a monotonous function of the modifier concentration in the membrane (but it was achieved through maximum). The ionic conduction of bilayer membranes modified by vitamines was constant with all the tested concentrations at which the bilayers were formed while high concentrations of cholesterol decreased appreciably the ionic conduction.

[Nitrogen-containing fractions of Soviet hydrolysates for parenteral feeding]. / Ob azotsoderzhashshikh fraktsiiakh otechestvennykh gidrolizatov dlia parenteral'nogo pitaniia.

The content of free amino acids, non-precipitable and precipitable trichloro-acetic acid peptides in Soviet-made hydrolysates for parenteral alimentation was determined. As shown, it is aminopeptide and aminosol that contain the greatest amounts of amino acids, fibrinosol and caseine hydrolysate carrying their least quantities, with aminocrovine and hydrolysine occupying an intermediate place in this respect. The quality of hydrolysates was assessed according to their biological value and to do so chemical numbers of essential amino acids were calculated and limiting factors determined. Fibrinosol and aminosol and to a somewhat lesser degree--casein hydrolysate were found to be best balanced as concerns their amino acids composition. Aminopeptide, hydrolysine and especially aminocrovine were manifestly inadequate by their biological value, since they contain limiting amino acids (isoleucine, cystine and methionine).

[Effect of fatty acid triglycerides on lipogenesis and the makeup of plasma, fatty tissue and erythocyte membrane fatty acids in rats]. / Vliianie triglitseridov zhirnykh kislot na lipogenez i sostav zhirnykh kislot plazmy, zhirovoi tkani i membran éritrotsitov u krys.

The fatty acids middle-chain triglycerides (FAMCT) may be considered as a possible component of alimentary mixtures intended to lower the energy-giving efficiency of the nutritional ration. They do not join the tissue lipids, whereas their reconstruction into long-chain fatty acids requires an additional expenditure of energy. These facts were confirmed by the results obtained in tests on rats. Feeding of growing rats for 5 weeks on a ration containing 12 per cent of the FAMCT on condition of a sufficient administration of polyunsaturated fatty acids (PUFA) through addition of sunflower seed oil led to a significant fall of the body mass gain by comparison with that in rats receiving a ration whose main source of fat was lard. An increased tryglycerides synthesis in the liver was not accompanied by their accumulation in the organ. The triglycerides level in the serum was up. An analysis of the fatty acids composition in the epididymitic fatty tissue, plasma and erythrocytes confirmed that the FAMCT C2-fragments developing during metabolization are used up chiefly in lipogenesis, one of the basic products of which is palmitic acid. The metabolization of FAMC with sufficient PUFA proportion in the ration does not derange the plastic function of fat in the organism, i.e, securing biosynthesis of lipid components of the membranes.

[Determination of the N-nitrosamine content in meat and meat products]. / Opredelenie soderzhaniia N-nitrozaminov v miase i nekotorykh miasnykh produktakh.

Samples of meat and meat products for the content therein of carcinogenic N-nitrose-amines were subjected to a fluorometric analysis. In case of positive results the presence of NA was confirmed by cromate-mass-spectrometric and/or mass-spectrometric methods. The mean value for the concentrations of dimethyl-nitrose-amine, diethyl-nitrose-amine and nitrose-piperidine in meat products is within the ranges of 1.5-5.4, 1.0-6.1, 0.9-23.4 gamma/kg, respectively. NA was not found in meat.

[Effect of the quality characteristics of the fatty component of the diet on the fatty acid makeup of the erythrocytic and thrombocytic membranes in healthy persons]. / Vliianie kachestvennykh osobennostei zhirovogo komponenta ratsiona na zhirnokislotnyi sostav membran éritrotsitov i trombotsitov u zdorovykh liudei.

Practically healthy males received rations in which principal sources of fat in the descending order were butter, sunflower and mustard oil. The influence of qualitative properties of the ration's fat on the lipids metabolism in the plasma and the coefficient of the metabolization effectiveness of essential fatty acids (CEM) of the food into the membranes lipids was studied. The CEM was calculated by studying the fatty acids composition of the erythrocytes and thrombocytes stroma. Inclusion in the ration of butter alone, raised the cholesterol level, a fall of the plasma phospholipids level and a significant drop of the CEM. Substitution of sunflower oil for butter led to normalization of these figures. Mustard oil had no effect. Changes in the CEM of the erythrocytes stroma proceeded slowly, significant differences having been discovered only after 6 weeks of the butter consumption. The thrombocytes CEM changed quickly, a stable fatty acids composition of thrombocytes with this ration being established by the end of the 2nd week. The qualitative properties of the ration's fat exercise a sufficiently strong influence on the effective metabolization of fatty acids in the food into the lipid structures of the erythrocytes and thrombocytes membranes in a healthy subject, it being characterized by the CEM changes.