[Localization of fluorescent analogs of cholesterol and its esters in lipid models of membranes and lipoproteins]. / Issledovanie lokalizatsii fluorestsentnykh analogov kholesterina i ego éfirov v lipidnykh modeliakh membran i lipoproteinov.

The localization of the fluorescent cholesterol analogue--delta 5,7,9(11)-cholestatrien-3 beta-ol (B-CTE) and its methyl (M-CTE) and stearoyl (St-CTE) esters in model lipid particles were investigated by the radiationless energy transfer. It is shown that 67-100% of B-CTE molecules localize in the phospholipid monolayer of particles containing phosphatidylcholine and triolein (1:2 w/w). The replacement of a hydrogen atom in the hydroxyl by methyl resulted in immersion of 2/3 of the M-CTE molecules to the triolein core. This fact confirmed distribution of the fluorescent probe molecules in the whole volume of lipid particles. St-CTE was practically completely localized in the core of lipid particles. The results obtained evidence for the important role of 3-OH group in keeping the B-CTE molecules in the phospholipid monolayer of the investigated particles.

[Impairment of cholesterol-acceptor function of high density lipoproteins in patients with ischemic heart disease]. / Narushenie kholesterin-aktseptornoi funktsii lipoproteidov vysokoi plotnosti u patsientov s ishemicheskoi bolezn'iu serdtsa.

An ability of high density lipoproteins HDL3 to accept cholesterol from erythrocyte membranes was studied in healthy persons and in patients with ischemic disease of heart. The cholesterol-acceptory function was estimated as follows: by incorporation of fluorescent probes (cholestatriene and pyrene) into particles of HDL3, by elimination of cholesterol from erythrocyte membranes and by increase of the lipoproteins size evaluated using the method of quazi-resilient dispersion of laser light. In ischemic disease of heart the property of high density lipoproteins, specifically of HDL3 fraction, to accept cholesterol from cell membranes was impaired. Middle size of HDL3 particles was decreased in the patients with ischemic heart disease as compared with that of healthy persons.

[Catabolism of native and modified high-density lipoproteins in rabbits]. / O katabolizme nativnykh i modifitsirovannykh lipoproteidov vysokoi plotnosti v organizme krolika.

Rates of fraction catabolism of rabbit and horse total 125I-high density lipoproteins (HDL) were shown to be similar in rabbits, after intravenous administration, while catabolism of human, dog and, especially, of rat lipoproteins occurred at the higher rate as compared with rabbit HDL. Rabbit HDL containing modified epsilon-aminogroups, or guanidine groups, or carboxyl groups and native HDL were quite similarly eliminated from circulation of healthy animals, whereas the lipoproteins with modified tyrosine residues and, especially, succinated HDL exhibited the highest rate of elimination. Radioactivity of spleen tissue and lymphatic glands was several-fold higher after intravenous administration of succinated homologous 125I-HDL into rabbits as compared with the effect of native homologous 125I-HDL; in kidney, adrenal glands, liver tissue and small intestine the level of radioactivity was analogous after treatment with both homologous native and succinated 125I-HDL. During incubation with mice peritoneal macrophages modified lipoproteins were captured 1.5-fold more effectively as compared with native HDL. The data obtained suggest that the type of HDL catabolism prevailed in rabbits, which did not involve specific cell receptors to apoprotein components of these lipoproteins.

[The rate of elimination of homologous and heterologous native and modified high density lipoproteins from rabbit plasma after their intravenous administration]. / Skorost' éliminatsii gomologichnykh i geterologichnykh nativnykh i modifitsirovannykh lipoproteidov vysokoi plotnosti iz plazmy krovi krolika posle ikh vnutrivennogo vvedeniia.

Rates of catabolism of total fraction of human native high density lipoproteins (HDL) and their subfractions as well as horse and rabbit native and modified HDL were studied after intravenous administration of the HDL into healthy rabbits and the animals with experimental hypercholesterolemia. The following procedures were carried out for production of HDL derivatives: methylation, succination, blocking of Arg residues and of COOH-groups. Rates of catabolism were similar for rabbit and horse total fractions of 125I-HDL, whereas human HDL were catabolized at a slightly higher rates as compared with rabbit lipoproteins. After administration of human total HDL fractions their elimination, estimated by output of alpha-cholesterol (alpha-C), occurred at a higher rate in healthy rabbits as compared with the animals with hypercholesterolemia, whereas output of apoprotein (apo) A-I was similar in both these groups. As HDL are able to exhibit the properties of alpha-C donor in circulation, estimation of apo A-I should be a more reliable index of the HDL content in blood plasma as compared with alpha-C. Chemical derivatives of rabbit HDL were eliminated from circulation of control animals at a rate similar to that of native HDL rate, but exceeding the rate established for succinated HDL. As compared with native HDL all the modified horse HDL were eliminated at the higher rate from the circulation of healthy rabbits. In rabbits with hypercholesterolemia the higher rate of elimination was shown only for succinated and methylated HDL fractions. Succinated HDL were catabolized at the highest rate apparently due to marked negative charge of their molecules. The data obtained suggest that in rabbits HDL are catabolized via pathways which do not involve specific cell receptors.

[Fluorescent probe--a cholesterol analog: localization in plasma lipoproteins and in model lipid particles]. / Fluorestsentnyi zond--analog kholesterina: lokalizatsiia v lipoproteidakh plazmy krovi i v model'nykh lipidnykh chastitsakh.

The absorption spectrum of fluorescent probe--a cholesterol analog cholesta-5,7, 9(11)-trien-3 beta-ol has a vibrational structure with the maximum 326 nm. Its fluorescence spectra maximum is 370 nm. The localization of the probe in lipoproteins of high, low and very low density and in lipid spheres is studied. There are measured the areas, which occupied one molecule of cholesterol and phosphatidyl choline on the surface of lipid spheres and the radius of the lipid spheres. The localization of the probe in lipoproteins and lipid spheres is determined. The areas which occupied one molecule of phosphatidyl choline on the surface of lipid sphere is equal to the same area in mono- and bilayers. Cholesterol has the same condensing action on phosphatidyl choline in lipid spheres as in mono- and bilayers. All the probe molecules are localized on the surface of lipid spheres and lipoproteins and the B-ring of the molecule is immersed on 1.3 +/- 0.2 nm relative to polar groups. The hydroxyl group of cholesterol is arranged near the carbonyl group of phospholipid and the formation of the H-bond between these groups is possible.

[Hypolipidemic activity of glycine and its derivatives]. / Gipolipidemicheskoe deistvie glitsina i ego proizvodnykh.

A hypolipidemic action of glycine and its derivatives glycylglycine, clofibrylglycine, clofibrylglycylglycine was studied in intact and hyperlipidemic rats and guinea pigs.

[The rate of elimination of heterologous native and modified high-density lipoproteins from rabbit blood plasma after their intravenous administration]. / Skorost' éliminatsii geterologichnykh nativnykh i modifitsirovannykh lipoproteidov vysokoi plotnosti iz plazmy krovi krolika posle ikh vnutrivennogo vvedeniia.

Native and modified horse LPHD (methylated, succinylated, with blocked Arg-residues and COOH-groups) were administered intravenously (400 mg by protein) into healthy rabbits and into animals with hypercholesterolemia. Concentration of the modified LPHD decreased much more distinct in blood plasma of healthy rabbits as compared with native LPHD. The same results were obtained in rabbits with hypercholesterolemia after administration of methylated and succinylated LPHD. The higher rate of elimination of the modified LPHD appears to occur due to their phagocytosis by macrophages. The data obtained suggest that catabolism of LPHD in rabbits, contrary to LPLD catabolism, did not involve specific cell receptors.

[Interaction of low density lipoproteins with charged ligands: a study using the fluorescent probe 1-aniline naphthalene-8-sulfonate]. / Vzaimodeistvie lipoproteidov nizkoi plotnosti s zariazhennymi ligandami: issledovanie s pomoshch'iu fliuorestsentnogo zonda 1-anilinonaftalin-8-sul'fonata.

Heparin, chodroitin sulfates A, B, C, clofibrate and its derivatives as well as diphenyl disulfonate substituted the fluorescent probe I-aniline naphthalene-8-sulfonate in blood plasma low density lipoproteins. Constants of association for complexes of low density lipoproteins-heparin and chondroitin sulfate C, calculated on the basis of these data, were equal to 1.15.10(6) and 0,46.10(6) M-1, respectively. At the some time, the ligands studied altered the lipoprotein charges.

[Importance of the components of the complex ester group for the action of acetylcholine and dicarboxylic acid dicholine esters]. / Znachenie komponentov slozhnoefirnoi gruppy dlia deistviia atsetilkholina i dikholinovykh efirov dikarbonovykh kislot.

The substitution of ether oxygen by a methylene group in the acetylcholine molecule sharply decreases the muscarinic action, while the substitution of the carbonyl group by a methylene one reduces the nicotinic properties. Sebacoyldicholine possesses only nicotinic properties. The replacement of its ether oxygens by methylene groups lowers the stimulant action on the frog rectus abdominis muscle by two orders of magnitude, whereas the stimulant action on the cat sympathetic ganglion is 30-fold as decreased. The blocking action on the isolated rat diaphragm becomes 30-fold less potent, but the blocking action on the cat skeletal muscle remains as strong as that of sebacoyldicholine after cholinesterase inhibition. The replacement of sebacoyldicholine carbonyl groups makes the compound elicit a noncompetitive cholinolytic action on the frog muscle, while the blocking action on the cat skeletal muscle becomes as weak as that exerted by hexadecamethylene-bis-trimethyammonium.

[Study of skeletal muscle cholinoreceptors using alkylating agents]. / Izuchenie kholinoretseptorov skeletnoi myshtsy s pomoshch'iu alkiliruiushchikh agentov.

The ability of decamethonium containing beta-clorethylamino groups to alkylate the nicotinic cholinoreceptors of the frog tonic muscles was studied. D-tubocurarine prevented the action of the alkylating decamethonium (AD). The latter equally inhibited the effects of carbacholine and tetramethylammonium. The degree of alkylation did not change with pH varying from 6 to 11. AD did not produce any parallel shifts, but inhibited at once the maximal response to carbacholine both of the frog intact muscle and of a single tonic fibre. It is suggested that decamethonium blocks the cholinoreceptors anionic sites, which are represented by the carboxylate, or phosphate anions. The frog tonic muscle probably fails to posses any spare receptors.