Effect of Hypothermia-Induced Respiratory Arrest on Cerebral Circulation in Rats.

Intravital microscopy was employed to examine cerebral circulation in rats assessed by blood flow in the venules with diameter of 10-30 µ during immersion hypothermia continued to the moment of respiratory arrest and for 10 min thereafter. Circulation in the cerebral microvessels continued during severe hypothermia, and it went on even after hypothermic respiratory arrest while the heart was beating. In pial venules, the blood continued to fl ow for 8-10 min after respiratory arrest.

[The diagnostic value of the detection of hepatic fibrosis serum markers in chronic viral hepatitis].

The diagnostic significance of serum markers of fibrosis was investigated in 92 patients with chronic viral hepatitis (CVH) by studying the collagenolythic activity of blood, proteasic inhibitor activity, collagen metabolism products (oxyproline fraction), and fibronectin. At the same time, the patients underwent puncture biopsy of the liver, which made it possible to determine the degree of process activity and the stage of its chronization. As the degree of fibrosis grew, the collagenase serum activity increased significantly, while the alpha1-proteinase inhibitor activity fell, the content of oxyproline (its fractions) increased, and the fibronectin level decreased. Hence, the measurement of the noted parameters allows for noninvasive diagnostics of CVH stages.

[Mechanisms of disrupting the microcirculation in the brain during deep hypothermia development].

The number of the acts of leukocyte adhesion per unit of the vessel length was shown to increase gradually in the venous brain vessels during gradual cooling of the white rat from the body temperature in the rectum of approximately 37 to 13.5 +/- 0.2 degrees C. Upon a very deep hypothermia at the level of body temperature of 15 degrees C, the adhesion ofleukocytes to the walls of the brain microvessels gains a mass character. As the body temperature decreases to 13.5 +/- 0.2 degrees C, the respiration gets arrested. This coincides with an aspecially abrupt increase in the number of the acts of adhesion and with stretching the venules and smallest veins. The dynamics of these phenomena resembles the development of the mass adhesion of leukocytes during various kinds of hypoxia. There are reasons to believe that the adhesion of leukosytes during hypothermia disrupts the microcirculation and provokes the development of hypoxia in the cooled brain.

[The dynamics of leukocyte adhesion to the endothelium pial venules under massive blood loss]. / Osobennosti dinamiki adgezii leikotsitov k éndoteliiu pial'nykh venul pri massivnoi krovopotere.

The dynamics of leukocytes adhesion to brain microvenules endothelium of Wistar rats were studied under acute massive blood loss. Using the method of vital videomicroscope study of the influence of the influence of the blood volume reduction on the leukocyte-endothelium interaction is investigated. We studied vessels of the diameter under 30 mcm. It is shown that under progressing reduction of the system arterial pressure under 60 mm Hg, the number of leukocytes adhesion to venules' wall reached 20 +/- 3 on 100 mcm, but in terminal stage such acts are the greatest. It is supposed that as a result massive blood loss leukocytes turn out to be the direct reason of the deep pathological disturbances of microcirculation in the brain.

[Peripheral mechanisms of the pathogenesis of cervical dystonia]. / Perifericheskie mekhanizmy patogeneza tservikal'noi distonii.

Peripheral mechanisms of pathogenesis and formation of the symptoms of cervical dystonia (spastic torticollis--ST) were investigated. By means of orthopedic diagnosis and analysis of motor stereotype, traumas, algesic syndrome in 40 patients with ST, it was found a "short leg" on the side, opposite to the rotation of the head, frequent postural loads on the head and on the neck before ST rise, and algesic and other sensory symptoms in the same region. The data of neuromyography and of evoked skin sympathetic potentials show a presence of pathologic changes in sympathetic autonomic fibers as well as in axons of accessory nerve at both sides, mainly at the left. Such alterations were mainly peripheral and were found more frequently in a group of left-sided ST. The correlations observed between a side of the rotation of a head and a side of peripheral factor, permitted to suppose that peripheral factors (the factor of a "short leg" mainly) determined frequently a side of the rotation of the head. So, ST therapy must influence the peripheral mechanisms, but not only the central ones.

[Biosynthesis of cholic and chenodeoxycholic acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in a reconstituted system from the rat liver]. / Biosintez kholevoi i khenodezoksikholevoi kislot iz (1-14C)atsetil-CoA i (2-14C)malonil-CoA v rekonstruirovannoi sisteme pecheni krysy.

The possibility of biosynthesis of cholic (I) and chenodeoxycholic (II) acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in a reconstituted system of rat liver and the incorporation of acetyl-CoA into these bile acids under conditions of acetyl-CoA carboxylase activation by citrate or its inhibition by avidin were studied. The effects of Triton WR 1339 and cholesterol feeding on acetyl-CoA and malonyl-CoA incorporation into I and II were investigated. Teh incorporation of both substrates into the total unsaponifiable lipid fraction and fatty acids was demonstrated. The reconstituted system of rat liver was found able to synthesize and I and II not only from acetyl-CoA, but from malonyl-CoA as well. The rate of malonyl-CoA incorporation into the bile acids was somewhat higher than that of acetyl-CoA incorporation. Preincubation of the reconstituted system with citrate stimulated the rate of acetyl-CoA incorporation into I. Stimulation of biosynthesis of I occurred independently of the diurnal rhythm of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) activity. An addition of avidin to the reconstituted system preincubated with citrate caused inhibition of acetyl-CoA incorporation both into fatty acids and into I. The rate of biosynthesis of II remained practically unchanged in both cases. Treatment with Triton WR 1339 had only a slight effect, while cholesterol feeding significantly stimulated the incorporation of acetyl-CoA and malonyl-CoA into I and II. The results obtained suggest the participation of malonyl-CoA in formation of bile acids, preferentially cholic acid, and in a lesser degree, in sterol biosynthesis. Data from stimulation of bile acid biosynthesis under cholesterol feeding suggest that HMG-CoA reductase localized in the soluble fraction of rat liver is involved in bile acid biosynthesis.

[Decarboxylation of malonyl-CoA and biosynthesis of mevalonic acid in rat liver]. / Dekarboksilirovanie malonil-koA i biosintez mevalonovoi kisloty v pecheni krys.

Biosynthesis of mevalonic acid (MVA), total formation of 14CO2 from [1,3-14C]malonyl-CoA and the activity of malonyl-CoA decarboxylase in subcellular fractions of rat liver were studied. The dependence of the rate of MVA biosynthesis on malonyl-CoA concentration was found to be linear both in 140,000 g supernatant and solubilized microsomal fractions. It was shown that in a composite system (140,000 g supernatant fraction added to washed microsomes, 10 : 1) the optimal concentration ratio for the substrates of MVA biosynthesis (malonyl-CoA and acetyl-CoA) is 1 to 2. In the absence of acetyl-CoA decarboxylation of [1,3-14C]malonyl-CoA was prevalent. In all subcellular fractions studied decarboxylation of [1,3-14C]malonyl-CoA prevailed over its incorporation into MVA, total non-saponified lipid fraction and fatty acids. The degree of malonyl-CoA, decarboxylation was not correlated with the rate of its incorporation into MVA, i. e. the increase in the 14CO2 formation was not accompanied by stimulation of [1,3-14C]malonyl-CoA incorporation either into MVA or into total non-saponified lipid fractions. The incorporation of [1-14C]acetyl-CoA into MVA under the same conditions was considerably lower than that of [1,3-14C]malonyl-CoA. In all subcellular fractions under study the activity of malonyl-CoA decarboxylase was found. The experimental data suggest that a remarkable part of malonyl-CoA is incorporated into MVA without preliminary decarboxylation. A possible role of malonyl-CoA decarboxylase as an enzyme which protects the cell against accumulation of malonyl-CoA and its immediate metabolites -- malonate and methylmalonyl-CoA is disucssed.

[Hypolipidemic activity of substances structurally close to penphenone in rats and mice]. / Gipolipidemicheskaia aktivnost' veshchestv, strukturno blizkikh penfenonu, u krys i myshei.

Effect of substances, structurally related to penphenone (2-phenyl-3-methyl-3-hydroxypentanic acid sodium salt), was studied on the main patterns of lipid metabolism in blood of rats and mice, as well as on lipoprotein spectra of rat blood serum. All the compounds studied exhibited hypolipidemic effect, decreasing concentration of total cholesterol, cholesterol of alpha-lipoproteins and triglycerides in rat blood. The effect was less distinct in mice. 2-phenyl-3,4-dimethyl-3-hydroxypentanic acid sodium salt possessed the most pronounced hypolipidemic effect. A decrease in content of beta-and pre-beta-lipoproteins as well as of alpha-lipoproteins was observed after electrophoretic separation of blood serum lipoproteins in polyacrylamide gel in animals treated with the compound.

[The activity of beta-hydroxy-beta-methylglutaryl-CoA reductase in the soluble fraction of rat liver]. / Aktivnost' beta-gidroksi-beta-metilglutaril-KoA-reduktazy v rastvorimoi fraktsii pecheni krysy

Assay conditions are worked out for determination of activity of beta-hydroxy-beta-methylglutaryl-CoA reductase (HMG-CoA reductase) in 140.000 g supernatant fraction of the rat liver. Some kinetic properties of the enzyme are studied: the activity dependency on the incubation time, protein concentration, pH, glutathione, dithiothreitol and HMG-CoA contents in the incubation medium. The effect of Triton WR 1339 on the activity of HMG-CoA reductase in the liver 140.000 g supernatant and microsomal fractions is comparatively studied. Diurnal activity variations of soluble and microsomal enzymes are also investigated. It is suggested that the rat liver HMG-CoA reductase in the 140.000 g supernatant fraction is not identical to the enzyme located in the microsomal fraction.

[Possible role of acetyl-CoA-carboxylase in biosynthesis of mevalonic acid and sterols in rat liver]. / O vozmozhnom uchastii atsetil-KoA-karboksilazy v biosinteze mevalonovoi kisloty i sterinov v pecheni krysy.

Effect of citrate on acetyl-CoA incorporation into mevalonic acid, sterols and fatty acids after preliminary incubation of rat liver extracts under conditions optimal for acetyl-CoA carboxylase activation, was studied. 30 min preincubation with the citrate at 37 degrees C results in a 2--3-fold stimulation of the mevalonic acid biosynthesis from acetyl-CoA in the microsomal and soluble (140 000 g) fraction, and in that of sterols precipitated by digitonin or isolated by TLC in the mitochondria--free fraction. 2-14C-malonyl-CoA incorporation into the mevalonic acid and sterols and biosynthesis of sterols from 2-14C-mevalonic acid were not stimulated under those conditions. A correlation was shown to exist between the activity of acetyl-CoA carboxylase and the rate of acetyl-CoA incorporation into mevalonate and sterols; the activity of beta-hydroxy-beta-methylglutaryl-CoA reductase, limiting the rate of the sterol biosynthesis, was not changed. The stimulating effect of citrate was found to depend on the concentration of acetyl-CoA and NADPH in the medium. The data obtained suggest that the mevalonic acid biosynthesis in rat liver may occur in the presence of acetyl-CoA carboxylase through the formation of malonyl-CoA.

[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).