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Biomedical subjects

C Lutton

Publications and source records attributed to C Lutton.

At least 55 records · Page 3Linked to original sources
PubMed1994

Lipid composition and structure of commercial parenteral emulsions.

In order to study the influence of the phospholipid/triacylglycerol (PL/TG) ratio of parenteral emulsions on the distribution and the physico-chemical properties of their fat particles, commercial 10, 20 or 30% fat formulas were fractionated by centrifugation into an upper lipid cake (resuspended in aqueous glycerol) and a subnatant or mesophase, from which a PL-rich subfraction (d = 1.010-1.030 g/l) was purified by density gradient ultracentrifugation. Chemical and 31P-NMR analyses of these fractions indicated that at least two types of fat particles coexist in parenteral emulsions: (i) TG-rich particles (mean diameter: 330, 400, 470 nm in the 10, 20, 30% emulsion) which contain practically all the TG and esterified phytosterols of native emulsions, but only a fraction of their PL, unesterified cholesterol and phytosterols, and other minor lipids; (ii) PL-bilayer particles or liposomes (mean diameter: 80-100 nm) which are constituted with the remaining PL and relatively very small amounts of TG and other lipids. The higher the oil content of the emulsion, the lower the amount of these PL-rich particles, which represent the major particle population of the mesophase. Indeed, minute amounts of TG-rich particles (probably the smallest ones) are also present in the mesophase, even in the PL-rich subfraction which contains the bulk of liposomal PL. Since the PL-rich particles of the infused emulsion generate lipoprotein X-like particles, only the large TG-rich particles can be considered as true chylomicron counterparts.

Centrifugation, Density Gradient↗
PubMed1994

Effect of simvastatin treatment on plasma apolipoproteins and hepatic apolipoprotein mRNA levels in the genetically hypercholesterolemic rat (RICO).

The effects of long-term treatment with simvastatin on plasma lipoproteins, plasma apolipoproteins, and on hepatic apolipoprotein gene expression were evaluated in genetically hypercholesterolemic (RICO) rats. Simvastatin administration caused a decrease in plasma triglyceride and phospholipid concentrations. Plasma cholesterol concentration was not changed by simvastatin, but cholesterol distribution among plasma lipoproteins was altered. Plasma apo B, apo A-I, and apo A-IV concentrations were lowered by simvastatin treatment whereas plasma apo E concentration was not affected by this drug. In the liver, simvastatin treatment induced a significant decrease of apo E mRNA level but had no effect on apo B, apo A-I, and apo A-IV mRNA abundances. It appears that simvastatin may modify plasma apolipoprotein concentrations by influencing their hepatic synthesis at both pre- and posttranscriptional levels.

Animals↗
PubMed1994

Cholesterol synthesis and high density lipoprotein uptake are regulated independently in rat small intestinal epithelium.

The rates of high density lipoprotein HDL uptake and cholesterol synthesis were compared in the normocholesterolaemic (SW) and genetically hypercholesterolaemic (RICO) rat intestine. The RICO rat has a hyperintestinal cholesterol synthesis. 14C sucrose, a marker which becomes irreversibly entrapped within the cells, was used to measure total rat HDL uptake over 24 hours in the various cells of the small intestinal mucosa. The rates of sterol synthesis were estimated in vivo with 1-14C acetate, as previously validated. The rates of HDL uptake in the upper villus cells were similar along the length of the small intestine in both types of rat, but the rates of sterol synthesis varied up to eightfold. When the mucosal epithelium was divided along the villus/crypt axis, HDL uptake increased two to threefold and cholesterol synthesis two to fivefold in the upper villus compared with the crypt cells in both SW and RICO rats. The high cholesterogenesis in the mucosal cells of the RICO rat is not related to a modified HDL cholesterol uptake. Thus, cholesterol synthesis and HDL uptake seem to be regulated independently in the rat small intestinal mucosa.

Animals↗
PubMed1994

Distribution of high density lipoprotein binding proteins among various tissues in the rat.

Levels of high density lipoprotein (HDL) in the blood are negatively correlated with heart disease and factors which regulate the levels and metabolism of this important lipoprotein are being investigated by many laboratories. Following the identification in liver of two candidate HDL receptors, HB1 and HB2, we undertook in the present studies, an examination of various other rat tissues for the identification of similar proteins. Using specific antibodies against each of the binding proteins, we identified both HB1 and HB2 in several other tissues (intestine, lung, kidney, ovary ...) and further, revealed relative differences in the expression of HB1 and HB2 between various tissues. A most interesting observation was the presence of HB1 but not HB2 in the spleen. Since the two proteins are not represented equally in all tissues, it is conceivable that these putative receptors have different functions in HDL metabolism or in other biological processes yet to be determined.

Animals↗
PubMed1993

Total parenteral nutrition and plasma lipoproteins in the rat: evidence for accelerated clearance of apo-A-I-rich HDL.

The effect of total parenteral nutrition (TPN) containing fat on plasma lipoproteins and apo-A-I-rich HDL catabolism was studied in the rat. TPN rats were intravenously infused for 5 days with a nutritive mixture containing amino acids, lipids (Intralipid 20%) and glucose. In spite of similar plasma levels of total cholesterol in TPN and control orally fed rats, density gradient ultracentrifugation of plasma samples gave evidence of marked differences in the lipoprotein profiles. In the density range 1.010-1.040, were found elevated amounts of apo-B-100 and apo-B-48 containing lipoproteins, as well as an increase in free cholesterol and phospholipids, the latter indicating that the plasma of TPN rats contained abnormal lipoprotein-X-like particles. The level of apo-E-rich HDL (density: 1.040-1.063) was not markedly changed, whereas that of typical HDL (d > 1.063) was lowered, with less apo-A-I and apo-A-IV, and low amounts of cholesterol and phospholipids were found in the most dense HDL3 fractions (d > 1.090) containing the bulk of apo-A-I-rich particles. After intravenous infusion of homologous [14C]sucrose-labelled HDL3, the clearance of these particles was 2-fold faster in TPN than in control rats, with a tissue uptake increased in the liver (+40%) and decreased in the small and large intestines (-60%). Because the pool of apo-A-I-rich HDL was dramatically reduced after 5 days of artificial feeding, the absolute catabolic rate of these lipoproteins was similar in the two groups. These data suggest that, in TPN rats lacking of chylomicron coat components as a source for HDL material, the fall in plasma levels of apo-A-I-rich HDL resulted mainly from accelerated turnover of these particles, mediated by increased uptake by the liver. Conversely, mucosa atrophy was probably involved in the reduced uptake of apo-A-I-rich HDL by the gastrointestinal tract.

Animals↗
PubMed1993

Hypolipidemic effects of beta-cyclodextrin in the hamster and in the genetically hypercholesterolemic Rico rat.

The effect of increasing amounts of a cyclic oligosaccharide, beta-cyclodextrin (BCD), included in the diet on plasma cholesterol and triglycerides, was investigated in two animal models, namely in male genetically hypercholesterolemic Rico rats and in male Syrian hamsters. The distribution of bile acids in the gastrointestinal tract and in the feces of hamsters was also determined. In the Rico rats and hamsters, plasma cholesterol and triglycerides decreased linearly with increasing doses of BCD. In these two species, 20% BCD as compared to control diet lowered cholesterolemia (-35%) and triglyceridemia (-70%). In the hamster, the BCD diet caused a marked decrease in cholesterol and triglycerides in chylomicrons and very low density lipoprotein, and in high density lipoproteins cholesterol. Composition and amounts of bile acids were modified in the gastrointestinal tract of hamsters receiving 10% BCD as compared to the control group. The total bile acid content of the gallbladder of treated hamsters was fourfold higher than in the control group, and the bile contained a large amount of hydrophilic bile acids. This trend was also observed in the small intestine, in which percentages and total quantities of cholic plus deoxycholic acids (cholic pathway) were higher than those of chenodeoxycholic plus ursodeoxycholic plus lithocholic acids (chenodeoxycholic pathway). The bile acid contents of the cecum and colon of treated hamsters were 2.7-fold higher than those of control animals, but the bile acid composition was similar in the two groups of hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cholesterol and bile acid biodynamics after total small bowel resection and bile diversion in humans.

BACKGROUND: In humans, the patterns of cholesterol and bile acid biodynamics in the absence of the small intestine are not yet known. They are described in two parenterally fed patients several months after total enterectomy and bile diversion. METHODS: After an intravenous pulse of [3H]cholesterol, a long-term study involved the analysis of both the decay in the specific activity of plasma cholesterol and the biliary outputs of sterols and bile acids. RESULTS: Plasma cholesterol input reached 2-3 g/day (vs. 1 g/day in healthy patients), mostly from synthesis. As assessed by sterol balance, whole body cholesterol synthesis approximated 6 g/day (vs. 0.6-0.8 g/day). Unusually, about 60% of the newly synthesized cholesterol was eliminated, without prior transit into the bloodstream, from the liver into the bile. Bile acid conversion concerned over 90% (vs. 40%-50%) of the cholesterol meant to be excreted, issued from plasma or hepatic synthesis. In addition to cholic and chenodeoxycholic acids, one patient secreted up to 1 g/day of 7-epicholic acid. CONCLUSIONS: The stimulation (up to 10-fold) of the cholesterol and bile acid synthesis, stronger than that observed following ileal bypass or resection or complete bile diversion, could well be partially linked to the absence of small bowel tissue per se.

Bile↗
PubMed1993

Metabolism and time-course excretion of murideoxycholic acid, a 6 beta-hydroxylated bile acid, in humans.

The metabolism and time-courses of urinary and fecal excretions of murideoxycholic acid (MDCA; 3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid), a 6 beta-hydroxylated bile acid, was investigated in man. The study was carried out in two groups of subjects. Six cholecystectomized patients fitted with a cystic duct drain ingested 100 mg of a tracer dose of 3H-MDCA. Time-course of radioactivity in plasma was then followed for an 8-h period. Biliary, urinary and fecal excretions of radioactivity were measured for a 5-day period and excreted MDCA metabolites were identified. Five lithiasic patients with intact enterohepatic circulation ingested 500 mg of the same tracer dose of 3H-MDCA. Radioactivity in plasma was followed for a 49-h period and urinary and fecal excretions of radioactivity were measured daily for 7 days. In the first group, the excretion of the radioactivity by the three routes (bile+urine+feces) reached 97.8 +/- 1.5% of the ingested dose but dropped to 75 +/- 8.3% (urine+feces) in patients in the second group. In cholecystectomized patients, the estimation of intestinal MDCA absorption was dependent on cystic duct drain flow rate and gave values ranging from 20% to 87%. The biological half-life of MDCA in lithiasic patients averaged 3.4 +/- 0.7 days. Radioactivity appeared in the plasma in the first hour and reached a maximum 6 and 3 h after the beginning of the experiment in group I and II respectively. In the second group, another peak of radioactivity in plasma was observed just after breakfast.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Metabolism of intestinal triglyceride-rich lipoproteins in the genetically hypercholesterolemic rat (RICO)

Experiments were carried out to compare the catabolism of intestinal lipoproteins between genetically hypercholesterolemic (RICO) and normocholesterolemic (SW) rats. Kinetics of plasma cholesteryl ester were studied after injection of cholesterol-labeled chylomicrons or VLDL. The chylomicron clearance is reduced in the RICO rat (rate constant, K = 7.2 +/- 0.1 h-1 vs. 10.7 +/- 0.1 h-1 in SW rat), while a much more minor alteration was observed in the catabolism of lymph VLDL (K = 4.3 +/- 0.6 h-1 in the RICO rat vs. 5.1 +/- 0.4 h-1). The injection of chylomicrons from SW rats to RICO rats and from RICO rats to SW rats showed that the fall in the rate of catabolism of chylomicrons in RICO rats was not secondary to an increase in the production rate, but was related to the lipoprotein particle itself without any alteration of the catabolic system. The reduction in the rate of catabolism of chylomicrons in the RICO rat could be related to a change in their apolipoprotein composition (increase in the proportion of apolipoprotein E = 12 +/- 2% vs. 3 +/- 1% in the SW rat).

Animals↗
PubMed1992

Overestimation of the lipoprotein fractional catabolic rate (FCR) measured in short duration experiments.

The aim of the study was to compare two methods classically used in rats to determine the fractional catabolic rate (FCR) of labeled high or low density lipoproteins: constant infusion and single pulse. The FC of [14C]-sucrose HDL (High density lipoprotein) was studied. For the short term experiment (8 hours), both methods gave similar FCR determined 8 hours after HDL constant infusion (9.4%.h-1 +/- 0.6) or single pulse (8.5%.h-1 +/- 0.4), values significantly higher than those measured 24 hr after the single pulse (6.2%.h-1 +/- 0.3). The identification and simulation of the model representing HDL movements between an intravascular and extravascular pool, after single pulse and constant infusion methods, demonstrated that FCR of lipoproteins cannot be precisely measured with techniques involving excessively short observation periods.

Animals↗
PubMed1992

[Metabolism of plasma cholesterol and lipoproteins after total resection of the small intestine in patients with parenteral nutrition. Effects of the amount of phospholipids infused].

The aim of this study was to investigate the plasma lipoprotein profile in 2 patients treated by parenteral nutrition for total small bowel resection over a 15 month period. According to the amount of infused phospholipids (6 g/d vs 3 g/d), infused during 4 non consecutive 6 month or 6 week periods, HDL-cholesterol, apolipoproteins AI and B plasma levels were 30 to 50% below normal values. During the higher phospholipid supply, cholesterolemia seemed normal; each phospholipid supply decrease was followed by a reduction of cholesterol, phospholipids and apolipoprotein B plasma levels of 40, 50 and 25%, respectively, while HDL-cholesterol and apolipoprotein AI plasma levels remained unchanged. Density gradient ultracentrifugation showed that plasma cholesterol changes were mainly due to cholesterol changes (as free cholesterol associated with phospholipids) located in the density range of 1.019-1.040, reflecting the presence of lipoprotein X-like particles, whose levels remained unchanged during each period. An apolipoprotein E, CII and CIII enrichment of plasma was observed and was more pronounced when patients received higher phospholipid infusion. These results show that, in patients without a small bowel, minor changes in phospholipids supply are responsible for serious alterations of the lipoprotein profile; formation of lipoprotein X-like particles could be favored by the low HDL levels in these patients.

Apolipoproteins↗
PubMed1991

In vivo effect of simvastatin on lipoprotein cholesteryl ester metabolism in normocholesterolemic volunteers.

A kinetic study on lipoprotein cholesteryl ester metabolism was carried out in 4 normolipidemic volunteers before and after treatment with simvastatin. They received LDL labelled with 3H-cholesteryl linoleate. A lipoprotein cholesteryl ester model was developed that fit the radioactivity in LDL, HDL and VLDL cholesteryl ester during 24 hours following injection. Before treatment, the model is consistent with previously reported data. Moreover our results suggest that, in normal fasting subjects, the efflux of plasma cholesteryl ester is almost exclusively derived from LDL. Administration of drug decreased LDL cholesteryl ester concentration by 35%. After treatment, the rate constant concerning LDL catabolism was increased by 25% and the model required the existence of a direct removal of VLDL cholesteryl ester (40% of total VLDL turnover). Our results suggest that the reduction in the LDL cholesteryl ester concentration induced by treatment with simvastatin is due to an increase in the uptake of LDL and LDL precursors (VLDL, VLDL remnants) by LDL receptors.

Adult↗
PubMed1991

Dietary cholesterol, membrane cholesterol and cholesterol synthesis.

After describing the main steps of cholesterol biosynthesis the author recalls that the cholesterogenesis rate is feedback-inhibited by dietary cholesterol and examines the various processes of modulation. Hydroxy-3-methylglutaryl (HMG) CoA reductase, the key rate-limiting enzyme, is a 97 kDa endoplasmic reticulum glycoprotein, anchored 7-fold in this membrane. The N-terminal membrane-bound domain plays a fundamental role in the modulation of reductase activity. This modulation is essentially mediated by decreased gene transcription and enhanced degradation of the protein. The possible modulation by a bicyclic cascade system involving phosphorylation (inactivation) and dephosphorylation (activation) of reductase does not seem to play an essential role in vivo. Finally, recent data show that the lipid composition (C/P molar ratio) of some reticular membranes (fibroblasts, for example) can strongly modulate the activity of this ubiquitous enzyme.

Animals↗
PubMed1991

Biodynamics of cholesterol and bile acids in the lithiasic hamster.

By using the isotopic equilibrium method in the young male Syrian hamster, the rates of cholesterol turnover processes, i.e. dietary cholesterol absorption, cholesterol synthesis, cholesterol excretion in the faeces and urine and cholesterol transformation into bile acids, were determined in the hamster receiving a control (C) or a lithogenic diet (L) for 7 weeks. At the end of this period the gall bladder of all animals in group L contained cholesterol gallstones. The coefficient of dietary cholesterol absorption was reduced by 26%, cholesterol synthesis and cholesterol faecal excretion were twofold higher in group L than in group C. Bile acid content in the small intestine was diminished in group L, but bile acid composition was similar in the two groups. The increase in cholesterogenesis in lithiasic animals essentially took place in the liver. Bile acid biosynthesis did not significantly differ in the two groups, but represented only 35% of total cholesterol input (dietary absorption + internal secretion) in group L v. 52% in group C. Thus, in the lithiasic hamster, hepatic synthesis of cholesterol and bile acids are not coupled. The molar percentage of cholesterol in bile was twofold higher in group L than in group C but those of bile acids and of phospholipids were not modified. In the lithiasic hamster the specific activity of biliary cholesterol was similar to that in plasma and liver. Consequently, biliary cholesterol does not derive directly from cholesterol newly synthesized in the liver but from hepatic cholesterol rapidly exchangeable with plasma cholesterol.

Animals↗
PubMed1990

Effects of intravenous infusions of commercial fat emulsions (Intralipid 10 or 20%) on rat plasma lipoproteins: phospholipids in excess are the main precursors of lipoprotein-X-like particles.

Like most commercial parenteral emulsions, Intralipid contains the same amount of phospholipids (12 mg/ml) to stabilize 100 or 200 mg of soybean oil (10 or 20% formula, respectively). By centrifugation, 10 or 20% Intralipid was separated into a supernatant, fat particles containing the bulk of triacylglycerols stabilized by a fraction of phospholipids and an infranatant--called mesophase--consisting mainly of phospholipids used in excess as emulsifier. We observed that the initial triacylglycerol/phospholipid ratio of the emulsion (100/12 and 200/12, respectively) determines the size of the triacylglycerol-rich particles (260 and 350 nm) as well as the phospholipid content of the mesophase (6.02 and 4.67 mg/ml). To understand the mechanism of the lipoprotein-X (LPX) accumulation generally reported after intravenous fat infusions, plasma lipid levels and lipoprotein profiles were first compared in the rats after infusion (at a constant rate of 0.5 or 1 ml/h for 43 h) of Intralipid 10 or 20%. For the same intravenous triacylglycerol load (100 mg/h), rats infused with Intralipid 10% at 1 ml/h displayed higher triacylglycerol levels than rats infused with the 20% emulsion at 0.5 ml/h, suggesting that the size of exogenous fat particles modulated the catabolic rate of their triacylglycerols. The plasma levels of LPX varied according to the infusion rate of phospholipids not associated with triacylglycerol-rich particles of the emulsion. Moreover, an apo E and apo B enrichment of plasma and an elevation of the apo B48/apo B100 ratio was always observed after Intralipid infusions. In order to confirm that phospholipids of the mesophase are the main LPX precursors, lipoprotein profiles were then compared in the rats after intravenous infusion, at a constant rate of 1 ml/h, of either the mesophase or a suspension of triacylglycerol-rich particles isolated from Intralipid 20%. As expected, significant LPX amounts were only detected in rats infused with the pure mesophase of the emulsion. It was concluded that products of the lipolysis of exogenous fat particles play only a minor role in the formation of LPX. In fact these abnormal lipoproteins are generated by phospholipids of the mesophase which, like infused liposomes, actively mobilize endogenous free cholesterol. Consequently, in order to be considered as true chylomicron models for safe fat delivery in parenteral nutrition and in order to prevent some detrimental effects on cholesterol metabolism, commercial emulsions should be cleared of phospholipid excess.

Animals↗
PubMed1990

Lipoprotein lipase and hepatic lipase activities in a hypercholesterolaemic (RICO) strain of rat. Effect of dietary cholesterol.

Hepatic lipase (HL) and lipoprotein lipase (LPL) were assayed in heparinized plasma from male normocholesterolaemic (SW) and genetically hypercholesterolaemic (RICO) rats. Both strains were fed on either a semi-purified control diet or the same diet enriched with 0.5% or 1% cholesterol. HL activity was similar in both groups of rats fed on the control diet. LPL activity was found to be significantly lower in RICO rats (35% decrease, P less than 0.05). Feeding with a high-cholesterol diet led to a decrease in HL activity (15-23%) in both groups of rats but no change was detected in LPL activity, which remained consistently lower in the RICO rats. Thus, with the control diet, LPL activity is lower in RICO rats but presumably is not rate-limiting for their triacylglycerol clearance, given the normal triacylglycerol levels present. After cholesterol feeding, however, the lower LPL activity may become rate-limiting together with the decrease in HL activity, as in these circumstances hypertriacylglycerolaemia was evident and the hypercholesterolaemia of this strain was further increased.

Animals↗