Free brain amino acids in rats variously tolerant to alcohol

Free amino acid concentrations were studied in the right and left hemispheres, cerebellum and brain stem of rat strains with different tolerance to ethanol (AT and ANT rats). The differences found may be significant in mechanisms of metabolic and neurogenic tolerance to alcohol. Within each of the rat strains, the distribution of some amino acids and their relationships markedly differed in the brain regions investigated.     

Regulation of the catalytic activity of the monooxygenase enzyme system depending of the substrate structure and phospholipid composition of the model membrane

A comparative study of pentoxy- and benzyloxyresorufin dealkylation by a monooxygenase enzyme system in dilauroylphosphatidylcholine micelles and in proteoliposomes was carried out. In proteoliposomes whose lipid matrix is formed by double phospholipid mixtures, a cooperative regulation of the oxidation reaction was found. It was shown that the cooperativity of this process depends on the substrate type as well as on the phospholipid composition of the vesicles and decreases during peroxide oxidation of lipids. The results obtained are discussed in terms of protein-protein and protein-phospholipid interactions in the oligomer ensembles consisting of several cytochrome P-450 LM2 molecules.     

The development of the epidemic process and the formation of humoral immunity to the hepatitis A virus in adolescent collectives

Additional observation on the formation of humoral immunity to hepatitis A virus has been carried out in 2,375 adolescents aged 15-17 years and belonging to 12 groups at 3 areas of the USSR. This observation has shown that in the presence of a high level of the immune stratum the spread of infection occurs, as a rule, outside the group under observation. Besides, as revealed in this study, the risk of seroconversion and the loss of specific antibodies are, respectively, directly and inversely related to the level of the immune stratum in the group. The level of the immune stratum in a given age group supposedly reflects the intensity of the development of the epidemic process at a definite area.     

Diazepam metabolism by multiple forms of cytochrome P-450 in rat liver microsomes

The synthesis of pharmacologically active diazepam metabolites (oxazepam, 4-hydroxydiazepam, N-demethyldiazepam) in liver microsomes of intact and phenobarbital-, 3-methylcholanthrene- and dexamethasone-induced male and female Wistar rats as well as in a reconstituted system with isolated forms of cytochrome P-450 (P-450a, P-450b, P-450c, P-450d and P-450k according to the Ryan nomenclature) was studied. Marked sex-dependent differences in the rates of diazepam metabolism in liver microsomes of intact and induced animals were revealed. The changes in the spectrum of diazepam metabolites in liver microsomes of induced rats (as compared to control animals) were revealed. In a reconstituted system only phenobarbital-induced cytochromes P-450b and P-450k were found to be active participants of diazepam N-demethylation; none of the isoenzymes tested were shown to be involved in diazepam hydroxylation.     

Effects of organic fluorosilicone compounds on the development of tumors in mice

The influence of new synthesized fluoro-silicium-organic complexes on the virus-induced Rauscher leukosis and cell-transferred MX-11 mouse sarcoma was studied. We also studied the cytotoxic effects of these complexes in vitro in the human CaOv cells. Two complexes from seven studied were cytotoxic for CaOv cells. Five complexes from seven studied diminished the mortality of animals with MX-11 tumors on the 27-th day of observation, but the total life duration of the animals in the experimental group was the same as in controls. One complex from seven studied increased the life duration of mice with MX-11 tumors. No effects were noted in relation to mice virus-induced Rauscher leukosis.     

Interconnection of physico-chemical characteristics of organic solvents and their denaturing ability in relation to proteins]

Reversible denaturation of several proteins (alpha-chymotrypsin, trypsin, laccase, chymotrypsinogen, cytochrome c and myoglobin) by a broad series of organic solvents of different nature was studied. The regularities of this process were analyzed, employing both experimental and literary data based on the results of kinetic and spectroscopic measurements. In all the systems under study denaturation proceeded in a threshold manner, i. e., an abrupt change in the catalytic and/or spectroscopic properties of the dissolved proteins was observed after a certain threshold concentration of the organic solvent had been reached. To account for the observed features of the denaturation process, a thermodynamic model of reversible protein denaturation by organic solvents was proposed. This model is based on the widely accepted viewpoint that the undisturbed water shell around the protein globule is necessary for maintaining the dissolved protein in the native state. Quantitative analysis of the model led to an equation establishing a relationship between the threshold concentration of an organic solvent and its physico-chemical characteristics, such as hydrophobicity, solvating ability and molecular geometry. This equation fits well in the experimental data for all the proteins tested. Based on the above thermodynamic model of protein denaturation, a novel quantitative parameter characterizing the denaturing strength of organic solvents (termed as the denaturation capacity or DC) was proposed. Different organic solvents arranged according to their DC values form the DC scale of organic solvents which permits to predict theoretically the threshold concentration of any organic solvent for a given protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

N-methylcytisine--a selective ligand of nicotinic receptors of acetylcholine in the CNS

The ability of cytisine and its N-methyl derivatives to bind to nicotinic acetylcholine receptors (nAChR) from different tissues was studied. Cytisine and N-methylcytisine have high affinity (KD = 50 nM) to nAChR from squid optical ganglia. N,N-dimethylcytisine did not show high affinity to this receptor. In the case of nAChR from T. marmorata, cytisine was the only effective inhibitor of 14C-tubocurarine specific binding (Ki = 700 nM). N-methyl- and N,N-dimethylcytisine did not displace 14C-tubocurarine at a concentration of 0.1 mM. The results obtained indicate that there are some differences in the structure of nAChR binding sites from squid and T. marmorata optical ganglia.