[Cryohemosorption--a method of removal of lipoprotein-antibody immune complexes and other atherogenic substances in patients with atherosclerosis]. / Krioplazmosorbtsiia--metod udaleniia immunnykh kompleksov lipoproteid-antitelo i drugikh aterogennykh substantsii u bol'nykh aterosklerozom.

The efficacy of extracorporeal cryohemosorption was estimated in the treatment of atherosclerotic patients in terms of the autoimmune theory of the pathogenesis of this disease. There was a slight decrease in the plasma levels of total cholesterol and triglycerides, there was over 2-fold reduction in the plasma levels of fibrinogen and fibronectin. All major components of apo B-containing lipoproteins and immunoglobulin G were found as part of the cryoprecipitate. An extremely high concentration of lipid hydroperoxides in the precipitate suggest that cryoprecipitation removes not only autoimmune complexes, but highly-atherogenic peroxide-modified lipoproteins. The three-fold decrease in the levels of lipoprotein-antibody complexes resulted in lower atherogenicity of apo B-containing lipoproteins. It is suggested that the mechanism responsible for beneficial clinical action of cryohemosorption sessions is largely associated with the removal of autoimmune lipoprotein-antibody complexes and peroxide-modified apo B-containing lipoproteins than correction of lipid metabolism.

[The thrombocyte function of subjects with atherogenic hyperlipidemias during lovastatin treatment]. / Funktsional'naia aktivnost' trombotsitov u lits s aterogennymi giperlipidemiiami v protsesse lecheniia lovastatinom.

The effects of lovastatin on in vivo spontaneous and in vitro ADP-induced platelet aggregability were studied in the blood of 36 persons with primary hyperlipidemias (HLP) of Types IIIa and IIb. In addition to decreases in blood cholesterol levels by an average of 33% and the atherogenicity coefficient to the normal levels, there was an increase in spontaneous and/or ADP-induced platelet aggregability in the first 2-3 months of lovastatin therapy. Lovastatin-induced in anti- and proaggregatory potential in the platelet-vascular wall system towards of the latter and spontaneous intravascular platelet formation suggest that there is a higher risk for thromboembolic events in the examined patients with Type II HLP, especially if they have coronary heart disease, during early stages of the drug administration. Therefore, there are reasons for recommending that lovastatin should be given under the control of the platelet hemostatic system.

[Atherogenesis and the acute-phase reaction of the liver]. / Aterogenez i reaktsiia "ostroi fazy" pecheni.

Data from literature are given on the role of "acute phase" proteins in inflammation and their connection with lipoproteins. Intensive production of acute phase proteins is shown to take place in modelling of experimental atherosclerosis. The hypothesis is proposed that allows to consider the acute phase reaction of the liver as a very important condition of modified lipoproteins formation acquiring autoantigenic properties.

[Possibilities of more accurate evaluation of the degree of myocardial damage and the completeness of reparative processes in patients with acute myocardial infarction by studying the characteristics of monocytes]. / Vozmozhnosti utochneniia glubiny povrezhdeniia miokarda i zavershennosti reparativnykh protsessov u bol'nykh ostrym infarktom miokarda pri izuchenii kharakteristik monotsitov krovi.

Patients with acute myocardial infarction (MI) were found to have hyper- and dyslipidemias independent of the depth of myocardial lesions and, in addition, to have more severe granulo- and monocytosis, higher adhesive and phagocytic ability of blood mononuclears that are typical for penetrating MI. Examining biochemical and immunological indices in the time-course of acute MI enables one to assess the completeness of reparative process in the myocardium. A significant and long-term monocyte activation in patients with penetrating MI seems to be due to an extended necrotic area and further formation of a focus aseptic inflammation, from whose the product that stimulate the production and function of blood monocytes are absorbed.

[Experimental and clinical study of Vasosan P, a new form of pectin-enriched cholestyramine]. / Eksperimental'noe i klinicheskoe izuchenie vasozana P--novoi formy kholestiramina, obogashchennogo pektinom.

The bile acid sequestering agent Vasosan P is a new form of pectin-enriched cholestyramine (20%), saccharose (5%) and sorbic acid (0.18%). In comparison with cholestyramine Vasosan P has a more marked hypolipidemic effect in experiment. Vasosan P is remarkable for good organoleptic properties. It is effective in treating patients with type IIa hyperlipoproteinemia and practically has no side effects as cholestyramine.

[The efficacy of substances with antihypoxic action in experimental hyperlipidemia]. / Effektivnost' veshchestv antigipoksicheskogo deistviia pri éksperimental'noi giperlipidemii.

Experiments on rats, guinea pigs and rabbits with hyperlipidemia induced by high-cholesterol diet have revealed that the specific antihypoxic drug oliphen has hypolipidemic effect which is least pronounced in oral GABA. Oliphen causes a significant increase in alpha-cholesterol (antiatherogenic lipoprotein cholesterol) decreased by hyperlipidemia. It is suggested that oliphen improves hepatic receptor-dependent uptake and atherogenic lipoprotein degradation.

[The role of different pathways of mevalonate synthesis in the regulation of sterol and bile acid synthesis in the mammalian liver]. / Znachenie razlichnykh putei sinteza mevalonata v reguliatsii obrazovaniia sterinov i zhelchnykh kislot v pecheni mlekopitaiushchikh.

The role of various pathways of synthesis are considered for mevalonic acid, the first specific precursor of sterols, in the production of cholesterol and bile acids in the mammalian liver. It is emphasized that the mevalonate synthesis with participation of acetyl-CoA-carboxylase and hydroxymethylglutaryl-CoA-reductase not bound with the endoplasmic reticulum membranes results in formation of the pool of mevalonic acid and other precursors necessary mainly for the organism supply with bile acids under conditions of cholesterol synthesis inhibition.

[The hypolipidemic action of water-soluble enterosorbents of cholesterol and bile acids in an experiment]. / Gipolipidemicheskoe deistvie vodorastvorimykh énterosorbentov kholesterina i zhelchnykh kislot v éksperimente.

Experiments on rats, guinea pigs and rabbits with experimental dyslipoproteinemia have revealed that the new water-soluble high-molecular weight polymers containing digitonin (ED) or a quaternary nitrogen atom (EA) have a more marked hypolipidemic action than cholestyramine and normalize lipoprotein metabolism. The digitonin-containing enterosorbent has been shown to decrease the absorption of 4-14C-cholesterol, while the nitrogen-containing enterosorbent diminishes the absorption of 3H-cholic acid.

[The clinico-genetic aspects of familial hypercholesterolemia and their applied significance]. / Kliniko-geneticheskie aspekty semeinoi giperkholesterinemii i ikh prikladnoe znachenie.

Clinico-biochemical, genealogical evidence was compared to molecular-genetic findings on LDLP receptor gene in 4 families with a history of high blood cholesterol. It was found that members of the same family carrying the anomalous gene can demonstrate varying atherogenic shift in blood lipid fractions suggesting involvement of other endo- and exogenic factors. Molecular-genetic examination of subjects with family hypercholesterolemia discovered a family with structural derangement of the gene, two families with spot defects and a family in which the proband's hypercholesterolemia seemed unrelated to changes in the gene, but probably related to the gene controlling synthesis of apoB-protein.

[Effect of 2-phenyl-3-methyl-3-hydroxypentanoic and 2,3-diphenyl-3-hydroxypentanoic acids on the lipolytic activity of rat adipose tissue]. / Vliianie 2-fenil-3-metil-3-oksipentanovoi i 2,3-difenil-3-oksipentanovoi kislot na lipoliticheskuiu aktivnost' zhirovoi tkani krys

Aromatic derivatives of mevalonic acid (2-phenyl-3-methyl-3-hydroxy pentanic and 2,3-diphenyl-3-hydroxy pentanic acids) decreased the yield of unesterified fatty acids from adipose tissue by about 28-36 percent after subcutaneous administration into rats within one or two weeks and under conditions of incubation of the adipose tissue in vitro. Distinct decrease in the yield of glycerol was cause by 2,3-diphenyl-3-hydroxy pentanic acid (1 with 10-minus 3 = 5 with 10-minus 3 M) under conditions of lipolysis stimulated by adrenaline. Antilipolytic effect of the preparation was more pronounced than that of well-known hypolipidemic drug clofibrate (p-chlorophenhydroxy isobutyrate).

[The comparative activity of natural and synthetic enterosorbents in experimental hyperlipidemia]. / Sravnitel'naia aktivnost' nekotorykh prirodnykh i sinteticheskikh énterosorbentov pri éksperimental'noi giperlipidemii.

In-vitro experiments have shown that dietary fibre microcrystalline cellulose and lignin (polyphepan) possess high activity in binding sodium salt of cholic acid. This action is comparable with that of pectin and metamucile. Hypolipidemic effect of microcrystalline cellulose, polyphepan and synthetic enterosorbents carbonates was also seen in hyperlipidemic rats. It is concluded that microcrystalline cellulose and polyphepan hold promise as a dietary supplement for hyperlipidemic patients.

[Evaluation of various experimental dyslipoproteinemia models in the study of hypolipidemic agents]. / Otsenka nekotorykh modelei éksperimental'noi dislipoproteidemii pri izuchenii veshchestv gipolipidemicheskogo deistviia.

Models of experimental dyslipoproteinemias have been developed by using non-inbred rats (males and females) and guinea-pigs. Administration of cholesterol (C) with fats and supplementation of 4-hydroxy-6-methyl-2-thiouracil to male rats and that of C in the mixture of fats to guinea-pigs have been demonstrated to lead to the development of atherogenic dyslipoproteinemias. Genfibrozil, cholestyramine and vasosan II, a new pectin-enriched formulation, promoted normalization of the impaired serum lipoprotein spectrum caused by exogenous C administration. Bilateral ovariectomy in female rats induced atherogenic dyslipoproteinemia. The use of the estrogen derivative methyl ether of 6-oxa-D-homo-8-isoestrone normalized lipid and lipoprotein metabolic disturbances.

[Antagonism in the action of hydrocortisone and insulin in vivo on enzymes of pyruvate and malate metabolism in adipose tissue]. / Ob antagonizme deistviia gidrokortizona i insulina in vivo na fermenty obmena piruvata i malata zhirovoi tkani

Alloxan diabetes and injections of hydrocortisone into intact animals for 5-7 days resulted in a sharp decrease of NADP-dependent malate dehydrogenase in rat epididymal adipose tissue. Combined injection of insulin and hydrocortisone did not produce the decrease of the enzyme activity. Insulin injections into alloxan diabetic rats recovered the activity of NADP-malate dehydrogenase up to the control. Pyruvate kinase activity was decreased under diabetes, and insulin injections produced further decrease of the enzyme activity in diabetic rats. Activities of lactate dehydrogenase and NAD-dependent malate dehydrogenase were less decreased under diabetes. Comparison of lactate dehydrogenase isoenzymes spectrum in adipose tissue of normal and diabetic rats revealed a considerable increase of LDH-1 and a decrease of LDH-4 under diabetes. Insulin injections greatly normalized LDH isoenzyme spectrum.

[Isoelectric focusing of 3-hydroxy-3-methylglutaryl-CoA-reductase from the postmicrosomal fraction of rat liver]. / Izoélektrofokusirovanie 3-gidroksi-3-metilglutaril-CoA-redutazy postmikrosomnoi fraktsii pecheni krysy.

Using isoelectrofocusing, the existence of multiple forms of 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) in the postmitochondrial fraction of rat liver has been demonstrated for the first time. The isoelectric points for the enzyme isoforms are 6.25, 7.5 and 8.25.

[Does malonate take part in the synthesis of sterols?]. / Uchastvuet li malonat v sinteze sterinov?

The effect of acetyl-CoA-carboxylase activators, citrate and biotin, on cholesterol biosynthesis from acetate and malonate in rat liver and in cultured human lung fibroblasts was studied. Administration of citrate and biotin to animals and an addition of biotin to the fibroblast culture medium led to a significant stimulation of [2-14C]acetate incorporation into sterols but had no effect on the incorporation of [2-14C]malonate. The data obtained suggest that malonate is incorporated into sterols without preliminary decarboxylation.

[Formation of mevalonic acid, sterols and bile acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in the liver of rabbits with experimental hypercholesterolemia]. / Obrazovanie mevalonovoi kisloty, sterinov i zhelchnykh kislot iz [1-14C]atsetil-CoA i [2-14C]malonil-CoA v pecheni krolikov s éksperimental'noi giperkholesterinemiei.

The effect of cholesterol diet on the rate of mevalonic acid biosynthesis from 1-14C acetyl-CoA, 2-14C malonyl-CoA and the incorporation of these substrates into sterols and bile acids in rabbit liver were studied. Simultaneously, the activities of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and acetyl-CoA carboxylase and the biosynthesis of fatty acids from acetyl-CoA and malonyl-CoA were measured. Hypercholesterolemia was found to be concomitant with the inhibition of acetyl-CoA carboxylase activity only in cell-free (700 g) and mitochondrial fractions and slightly decreased the incorporation of acetyl-CoA and malonyl-CoA into fatty acids in the postmitochondrial fraction. The HMG-CoA reductase activity in all subcellular fractions except for the postmicrosomal one was inhibited under these conditions. A significant decrease of acetyl-CoA incorporation and an increase in malonyl-CoA incorporation into mevalonic acid in all liver fractions except for microsomal one were observed in rabbits with hypercholesterolemia. These data provide evidence for the existence of two pathways of mevalonic acid synthesis from the above-said substrates that are differently sensitive to cholesterol. Cholesterol feeding resulted in a decreased synthesis of the total unsaponified fraction including cholesterol from acetyl-CoA, malonyl-CoA and mevalonic acid. The rate of incorporation of these substrates into lanosterol was unchanged. All the indicated substrates (acetyl-CoA, malonyl-CoA, mevalonic acid) are precursors of bile acid synthesis in rabbit liver. Cholesterol feeding and the subsequent development of hypercholesterolemia resulted in bile acid synthesis stimulation, preferentially in the formation of the cholic + deoxycholic acids from these precursors.

[Biosynthesis of mevalonic acid, sterols and bile acids from acetyl-CoA and malonyl-CoA in the human liver]. / Biosintez mevalonovoi kisloty, sterinov i zhelchnykh kislot iz atsetil-CoA i malonil-CoA v pecheni cheloveka.

The biosynthesis of mevalonic acid, squalene, sterols, bile and fatty acids from [2-14C]malonyl-CoA and [1-14C]acetyl-CoA were studied. The activities of 3-hydroxy-3-methylglutaryl-CoA-reductase (GMG-CoA reductase) and acetyl-CoA carboxylase in subcellular fractions of human liver were determined. The livers of humans were used within 1.5-3 hours after clinical death. It was found that in all fractions studied (i.e. cell-free, 700 g, postmitochondrial, microsomal, cytosol) malonyl-CoA is incorporated into mevalonic acid more intensively than acetyl-CoA. The specific activity of GMG-CoA reductase in the microsomal and soluble fractions was essentially the same. Calculation of enzymatic activity per 1 g of wet mass of tissue showed that the bulk of activity is bound to the cytosol (soluble fraction) Malonyl-CoA can also act as a precursor of squalene, lanosterol, cholesterol and bile acids. The rate of malonyl-CoA incorporation into these compounds is practically the same as that of [2-14C] mevalonate but significantly exceeds that of acetyl-CoA at equal molar ratios of both substrates. Incorporation of malonyl-CoA into cholesterol occurs much more intensively in human liver than in rat liver, the cholesterol radioactivity reaching 18% of the total unsaponified fraction. Malonyl-CoA is a better substrate than acetyl-CoA both for fatty acid and for mevalonate, sterol and bile acid synthesis.

[Activities of 3-hydroxy-3-methylglutaryl-CoA reductase and acetyl-CoA carboxylase and rate of biosynthesis of mevalonic acid, squalene, sterols and fatty acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in rat liver: changes induced by daily rhythm]. / Aktivnost' 3-gidroksi-3-metilglutaril-CoA-reduktazy, atsetil-CoA-karboksilazy i skorost' biosinteza mevalonovoi kisloty, skvalena, sterinov i zhirnykh kislot iz [I-14C]atsetil-CoA i [2-14C]malonil-CoA v pecheni krysy: izmenenie v zavisimosti ot vremeni sutok.

The activity of 3-hydrosy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and the rate of mevalonic acid (MVA) synthesis from [I-14C]acetyl-CoA and [2-14C]malonyl-CoA in the soluble (X140000 g) and microsomal fractions of rat liver and in a reconstituted system containing the soluble and microsomal fractions were studied. The changes in the activity of HMG-CoA reductase and the rate of MVA biosynthesis in the fractions at different times of the day were analyzed. The daily rhythms of the rate of acetyl-CoA and malonyl-CoA incorporation into squalene, sterols and fatty acids in the postmitochondrial fraction and the daily changes in the acetyl-CoA carboxylase activity of the soluble fraction of rat liver were compared. The incorporation of labelled acetyl-CoA and malonyl-CoA into MVA showed that the latter can be synthesized from these two substrates both in the soluble and microsomal fractions. Malonyl-CoA is a preferable substrate for MVA synthesis in the soluble fraction. MVA synthesis from acetyl-CoA proceeds fastr in the intact and solubilized microsomes than in the soluble fraction. The activity of HMG-CoA reductase was found in the soluble and microsomal fractions in practically equal amounts. The enzyme activity was increased in the microsomal fraction after its solubilization. The rate of MVA biosynthesis from acetyl-CoA and the activity of HMG-CoA reductase in the soluble fraction are practically unaffected by day-to-night changes. The activity of HMG-CoA reductase and MVA biosynthesis from acetyl-CoA in the intact and solubilized microsomal fractions reached their maximal values in the middle of the dark period. The rate of MVA biosynthesis from malonyl-CoA was decreased in the middle of the dark period in all fractions studied and reached its maximum in the middle of the light period. The daily rhythms of the acetyl-CoA carboxylase activity in the soluble fraction and the rate of MVA biosynthesis from malonyl-CoA in all fractions show a coincidence. a comparison of incorporation by the postmitochondrial fractions of acetyl-CoA and malonyl-CoA into the total non-saponified lipid fraction and its components, e. g. squalene, lanosterol and cholesterol, as well as into sterols precipitated by digitonin, showed that malonyl-CoA incorporation into the total non-saponified lipid fraction was more intensive than that of acetyl-CoA. However, acetyl-CoA was far more efficiently incorporated into sterols precipitated by digitonin or isolated by TLC than malonyl-CoA. The rate of acetyl-CoA incorporation into the total non-saponified lipid fraction and into squalene, lanosterol and cholesterol was maximal in the middle of the dark period and minimal in the middle of the light period. On the contrary, the rate of malonyl-CoA incorporation into these products was minimal in the middle of the dark period and maximal in the middle of the light period. The rate of fatty acid biosynthesis from acetyl-CoA was increased in the middle of the light and dark periods...