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Biomedical subjects

O Faergeman

Publications and source records attributed to O Faergeman.

At least 163 records · Page 9Linked to original sources
PubMed1981

The magnitude of metabolically induced changes in the density of human low-density lipoproteins.

Radiolabelled low-density lipoproteins (LDL), obtained from a patient with heterozygous, familial hypercholesterolaemia and from a normal subject, were injected into the patient and two normal subjects. Two approaches were made to evaluate the kinetics of metabolism of these LDL: (1) by serial measurements of radioactivity in serum, urine and the whole body; (2) by observing the density of the labelled LDL from serum using density-gradient ultracentrifugation. No significant change was seen in the model density of the LDL in either the patient or the normal subjects, but there were changes in the skewness of the radioactivity peaks. This contrasts with previously published findings in the guinea pig, in which LDL radioactivity gradually accumulated in the densest particles. The guinea pig findings suggested that lipoproteins in the LDL region are structurally modified during their intravascular circulation. The present study indicates that modification leading to changes in density does not occur to any significant degree in the human, whose LDL represent the end product of intravascular metabolism of apolipoprotein B-containing lipoproteins.

Adult↗
PubMed1978

Binding of bile acids to anion-exchanging drugs in vitro.

Equal amounts of anion exchanger of the drugs, Secholex, Colestipol, Cuemid, and Questran, were incubated at 37 degrees C with human duodenal fluid containing about 7 mM total bile acid. Binding of bile acid to Qestran, which contains about 45% cholestyramine, was fastest: concentration of unbound bile acid after 2 hours was less than 3 mM compared to about 5 mM in the solutions incubated with the other drugs, including Cuemid, which contains about 83% cholestyramine. After 24 hours, differences were less marked, but binding to Qestran was still greatest. Glycocholic acid was least efficiently bound, especially to Secholex and Cuemid. The differences in rates of binding were unaffected by preincubation of the drugs with 1 N HCl to simulate stomach conditions. Although differences between the cholestyramine components of Cuemid and Questran are not ruled out, it is possible that one or more of the other components of Questran significantly affect the in vitro binding of bile acids. Cholestryramine in the form of Questran may be the drug of choice in the treatment of hypercholesterolemia, in which reduction of the bile acid pool is desirable. In cholegenic diarrhoea, however, one of the drugs with lower affinity for glycocholic acid may be preferable.

Acacia↗
PubMed1977

Metabolism of cholesteryl esters of very low density lipoproteins in the guinea pig.

Very low density lipoproteins from guinea pig plasma, endogenously labeled with 3H in both the esterified and free cholesterol moieties, were obtained from serum collected 20 hr after the intravenous injection of 3H-cholesterol into donor animals. When these lipoproteins were injected into recipient guinea pigs, the esterified 3H-cholesterol was rapidly cleared from the plasma; 24% was in the liver in 5 min and 54% in 15 min. A smaller fraction of the esterified cholesterol appeared in other plasma lipoprotein fractions, with 3H in the low density lipoproteins reaching a peak of 9%-18% of the injected esterified 3H-cholesterol between 30 and 60 min after the injection. The results indicate that most of the esterified cholesterol in very low density lipoproteins of guinea pig plasma is removed directly by the liver and a minor fraction is transferred to low density lipoproteins. The pattern of labeling of cholesteryl esters of high density lipoproteins in these experiments suggests that their low concentration in the guinea pig is accompanied by a rapid turnover rate.

Animals↗
PubMed1975

Metabolism of cholesteryl esters of rat very low density lipoproteins.

Rat very low density lipoproteins (d smaller than 1.006), biologically labeled in esterified and free cholesterol, were obtained form serum 6 h after intravenous injection of particulate (3-H) cholesterol. When injected into recipient animals, the esterified cholesterol was cleared form plasma with a half-life of 5 min. After 15 min, 71% of the injected esterified (3-H) cholesterol had been taken up by the liver, where it was rapidly hydrolyzed. After 60 min only 3.3% of the amount injected had been transferred, via lipoproteins of intermediate density, to the low density lipoproteins of plasma (d 1.019-1.063). Both uptake in the liver and transfer to low density lipoproteins occurred without change of distribution of 3-H in the various cholesteryl esters. 3-H appearing in esterified cholesterol of high density lipoproteins (d greater than 1.063) was derived from esterification, presumably by lecithin: cholesterol acyltransferase, of simultaneously injected free (3-H) cholesterol. Content of free (3-H) cholesterol in the very low density lipoproteins used for injection could be reduced substantially by incubation with erythrocytes. This procedure, however, increased the rate of clearance of the lipoproteins after injection into recipient rats. These studies show that hepatic removal is the major catabolic pathway for cholesteryl esters of rat very low density lipoproteins and that transfer to low density lipoproteins occurs to only a minor extent.

Animals↗
PubMed1975

Characterization of remnants produced during the metabolism of triglyceride-rich lipoproteins of blood plasma and intestinal lymph in the rat.

The metabolism of intravenously injected large and small chylomicrons from intestinal lymph and of very low density lipoproteins from blood plasma was studied in functionally eviscerated "supradiaphragmetic" rats. For studies with lymph lipoproteins, recipient animals were injected with 4-amino-pyrazolopyrimidine 18 h before injection of lipoprotein to prevent secretion of very low density lipoproteins into their blood plasma. In all cases, most of the triglycerides (labeled with 14C) were rapidly metabolized, whereas cholesteryl esters (labeled with 3H) persisted in the blood. Most of the cholesteryl esters remained in smaller "remnant" lipoproteins, less dense that 1.006, which retained an apparently spherical shape, as determined by electron microscopy of negatively stained preparations. Whereas the diameters and chemical compositions of large chylomicrons were substantially different from those of small chylomicrons and very low density lipoproteins, all remnants were similar in these respects. Average remnant diameters were 400-600 A and remnants were enriched in cholesteryl esters and in protein insoluble in tetramethylurea. In addition to triglycerides, remnants were depleted of phospholiarticle size, the composition of remnants, like that of their precursors, was consistent with the "pseudomicellar" model of lipoproteins, in which a core of nonpolar lipids is covered by a monolayer of polar lipids and protein. These results domonstrate the fundamental similarity of the initial step in the metabolism of triglyceride-rich lipoproteins from intestinal mucosa and liver and show that loss of triglycerides from the core of the particles is accompanied by removal of polar components from the surface.

Animals↗
PubMed1975

Metabolism of apoprotein B of plasma very low density lipoproteins in the rat.

As an extension of metabolic studies of the cholesteryl ester component of rat very low density lipoproteins, we have studied the metabolism of the B apoprotein component labeled by intravenous injection of [3H]lysine. The B apoprotein separated from other apoproteins by delipidation and selective precipitation with tetramethylurea could not be distinguished from B apoprotein prepared by the conventional gel filtration technique. After injection of [3H]lysine, specific activity of B apoprotein was maximal in very low density and low density lipoproteins 1 and 11/2-h later, respectively, in a manner consistent with a precursor-product relationship. When protein-labeled very low density lipoproteins were injected into rats, the relationships of specific activity again indicated that B apoprotein of very low density lipoproteins may be the sole precursor of that of low density lipoproteins. However, less than 10% of the B apoprotein that disappeared from very low density lipoproteins appeared in density lipoproteins. To evaluate the sites of removal of B aproprotein of very low density lipoproteins from plasma, protein-labeled very low density lipoproteins were incubated with unlabeled high density lipoproteins to reduce radioactivity in non-B apoproteins selectively by molecular exchange. Most of the B apoprotein was rapidly removed by the liver. The extensive hepatic uptake of both the cholesteryl ester and B apoprotein components of rat very low density lipoproteins may explain the characteristically low concentrations of plasma low density lipoproteins in the rat.

Amino Acids↗
PubMed1975

Normal arterial blood gases during experimental hypertriglyceridemia in the rat.

The possible effect of high concentrations of plasma triglycerides on arterial oxygen tension was investigated in rats by infusion of lymph chylomicrons or a soybean oil emulsion (Intralipid). Mean triglyceride concentrations were raised from 130 to 1454 mg/100 ml without statistically significant change in arterial oxygen tension, oxygen saturation, carbon dioxide tension, or pH. The small reduction in arterial oxygen tension, content, or saturation observed in earlier studies may have been due to inadequate stabilization of fat emulsion then available for intravenous use. The present data suggest that high concentrations of plasma triglycerides produced by infusion of chylomicrons or Intralipid do not affect arterial blood gases in the normal rat.

Animals↗