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Biomedical subjects

Y A Carpentier

Publications and source records attributed to Y A Carpentier.

At least 19 recordsLinked to original sources
PubMed2006

Intravenous lipid emulsions to deliver omega 3 fatty acids.

A rapid supply of n-3 polyunsaturated fatty acids (PUFA) may be indicated in some acute conditions because of the ability of n-3 PUFA to decrease inflammatory responses and cell sensitivity to various stimuli, and to improve endothelial dysfunction. To achieve these objectives, n-3 PUFA content needs to be quickly raised in cell membranes of key organs. Intravenous fish oil (FO) emulsions are available but their slow hydrolysis limits their infusion rate. Mixtures containing both FO triglycerides and medium chain triglycerides may overcome this problem. These new preparations are rapidly cleared from plasma and efficiently deliver n-3 PUFA to several tissues, largely via direct particle uptake. Recent data suggest that n-3 PUFA incorporation in phospholipids promptly modulates important cell functions. This review also focuses on a novel approach to rapidly supply n-3 PUFA to targeted organs which may offer interesting perspectives in the management of acute illnesses.

Fat Emulsions, Intravenous↗
PubMed2006

Alteration of adipocyte metabolism in omega3 fatty acid-depleted rats.

Presently an insufficient supply of long-chain polyunsaturated omega3 fatty acid is prevalent in Western populations leading to potential metabolic consequences. Based on this fact, this study deals mainly with various aspects of lipid metabolism in second generation female omega3-depleted rats. The parametrial fat and body weights were higher in omega3-depleted than control animals. This coincided with liver steatosis but did not alter heart triglyceride/phospholipid ratio. The net uptake of [U-14C] palmitate by adipocytes was also higher in omega3-depleted rats than in control animals. The uptake of D-[U- 4C] glucose or [1,2 (-14)C] acetate by adipocytes was lower, however in omega3-depleted than control animals and was unaffected by insulin in the former as distinct from latter animals. Despite comparable basal lipolysis, the increase in glycerol output from adipocytes provoked by theophylline was higher in omega3-depleted than control rats. The fatty acid pattern of lipids in adipose tissue was characterized in the omega3-depleted rats by a much lower omega3 content, higher apparent Delta 9-saturase and elongase activities, lower efficiency for the conversion of C18:2omega6 to C20:4omega6 and higher efficiency for the conversion of C18:3omega3 to C20:5omega3. These features were compared to those prevailing in liver and plasma lipids. The present study thus extends knowledge on the alteration of lipid metabolism resulting from a deficiency in long-chain polyunsaturated omega3 fatty acids.

Acetates↗
PubMed2006

Pancreatic islet function in omega-3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release.

Considering the insufficient supply of long-chain polyunsaturated omega-3 fatty acids often prevailing in Western populations, this report deals mainly with alterations of Ca(2+) fluxes and Ca(2+)-dependent insulin secretory events in isolated pancreatic islets from omega-3-depleted rats. In terms of (45)Ca(2+) handling, the islets from omega-3-depleted rats, compared with those from normal animals, displayed an unaltered responsiveness to an increase in extracellular K(+) concentration, a lower inflow rate and lower fractional outflow rate of the divalent cation, and higher (45)Ca(2+)-labeled cellular pool(s) at isotopic equilibrium. The latter anomaly was corrected 120 min after intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a control omega-3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM D-glucose, insulin release was higher in islets from omega-3-depleted rats vs. control animals, coinciding with a higher cytosolic Ca(2+) concentration. The relative magnitude of the increase in insulin output attributable to a rise in D-glucose as well as extracellular Ca(2+) or K(+) concentration, to the absence vs. presence of verapamil and to the presence vs. absence of extracellular Ca(2+), theophylline, phorbol 12-myristate 13-acetate, or Ba(2+), was always more pronounced in islets from omega-3-depleted rats injected with the MCT:OO compared with the MCT:FO emulsion. A comparable situation prevailed when comparing islets from noninjected omega-3-depleted and normal rats. In light of these and previous findings, we propose that an impairment of Na(+),K(+)-ATPase activity plays a major, although not an exclusive, role in the perturbation of Ca(2+) fluxes and Ca(2+)-dependent secretory events in the islets from omega-3-depleted rats.

Animals↗
PubMed2006

Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats.

A novel i.v. lipid preparation (MCT:FO) containing 80% medium chain-triacylglycerols and 20% fish oil was recently developed to rapidly replenish cell membrane phospholipids with omega 3 (n-3) polyunsaturated fatty acids (PUFA). In regard of this property, we investigated the effect of a single i.v. administration of MCT:FO on the recovery of cardiac function after ischemia in control and n-3-depleted rats. Results were compared with those obtained either with a control preparation, where FO was replaced by triolein (MCT:OO), or with saline. Saline (1 ml) or lipid preparation (also 1 ml) was injected as a bolus via the left saphenous vein. After 60 min the heart was removed and perfused for 20 min in normoxic conditions according to Langendorff. Thereafter, the heart was subjected to a 20 min zero-flow normothermic ischemia, followed by 40 min reperfusion. Cardiac mechanical and metabolic functions were monitored. In control rats, the previous administration of a lipid preparation (MCT:FO or MCT:OO) versus saline improved cardiac function during aerobic reperfusion post-ischemia. N-3-depleted rats showed decreased basal cardiac function and impaired recovery following ischemia. However, the bolus injection of MCT:FO opposed the deleterious effect of long-term n-3-deficiency and, in this respect, was superior to MCT:OO over the first 20 min of reperfusion. This novel approach to rapidly correct n-3 PUFA-deficiency might be clinically relevant and offer interesting perspectives in the management of acute ischemic accidents.

Analysis of Variance↗
PubMed2005

Beneficial effects of atorvastatin on sd LDL and LDL phenotype B in statin-naive patients and patients previously treated with simvastatin or pravastatin.

BACKGROUND: The presence of increased levels of small dense (sd) LDL (phenotype B) is associated with a substantial increase of cardiovascular disease risk. Since lowering of plasma low-density lipoprotein-cholesterol (LDL-C) by statins involves an up-regulation of the LDL receptor, we questioned whether LDL lowering by atorvastatin affects different LDL subfractions equally. METHODS: Fifty-four hypercholesterolemic patients, requiring treatment for prevention of coronary heart disease received atorvastatin (10, 20 or 40 mg/day), either as initial therapy (n=33), or as replacement therapy (n=21) for pravastatin or simvastatin (both at 40 mg/day). In addition to plasma lipid measurements, cholesterol LDL subfractions were separated and analysed before and after 3 months of treatment. RESULTS: In addition to the expected LDL-C decrease (-34%; p<0.0001), a major reduction in sd LDL occurred after atorvastatin therapy (-38.2%; p<0.0001). Interestingly, sd LDL decreased as much in patients previously treated with other statins (-36%; p<0.002). A close correlation (r=0.89, p<0.001) was found between reduction of sd LDL and that of LDL-C, in patients with phenotype B. Although high-density lipoprotein-cholesterol (HDL-C) was not affected by atorvastatin treatment, plasma triglycerides decreased by 27.4% (p<0.0001). Only a weak correlation (r=0.35, p<0.01) was found between the reduction of plasma triglycerides and the decrease of sd LDL after atorvastatin treatment. CONCLUSION: These results show that the reduction of LDL-C by atorvastatin largely reflects a lowering of sd LDL. Our data also suggest that triglyceride lowering plays only a partial role in sd LDL reduction.

Adolescent↗
PubMed2004

Metabolism of defined structured triglyceride particles compared to mixtures of medium and long chain triglycerides intravenously infused in dogs.

The present study aimed to determine whether including medium-chain fatty acids (MCFA) in specifically designed structured triglycerides (STG) with a MCFA in sn-1 and sn-3 positions and a long-chain (LC) FA in sn-2 position (MLM) would lead to different effects on plasma lipids and FA distribution into plasma and tissue lipids by comparison to a mixture of separate MCT and LCT molecules (MMM/LLL). The fatty acid (FA) composition was comparable in both lipid emulsions. Lipids were infused over 9h daily, in 2 groups of dogs (n = 6 each), for 28 days as a major component (55% of the non-protein energy intake) of total parenteral nutrition (TPN). Blood samples were obtained on specific days, before starting and just before stopping TPN. The concentration of plasma lipids was measured before starting and before stopping TPN on days 1, 2, 3, 4, 5, 8, 10, 12, 16 and 28. Biopsies were obtained from liver, muscle and adipose tissue 15 days before starting, and again on the day following cessation of TPN. In addition, the spleen was removed after the TPN period. FA composition in plasma and tissue lipids was analysed by gas liquid chromatography in different lipid components of plasma and tissues. No differences in either safety or tolerance parameters were detected between both lipid preparations. A lower rise of plasma TG (P < 0.05) was observed during MLM infusion, indicating a faster elimination rate of MLM vs MMM/LLL emulsion. In spite of the differences of TG molecules which would be assumed to affect the site of FA delivery and metabolic fate, FA distribution in phospholipids (PL) of hepatic and extrahepatic tissues did not substantially differ between both emulsions.

Animals↗
PubMed2004

Tocopherol in lipoproteins and blood cells after cardiac surgery.

Cardiac surgery was associated with a marked reduction in circulating LDL and HDL particles, which in turn largely affectd alpha-toc transport. alpha-toc was decreased in WBCs but not in PLTs and RBCs. An increased hydroperoxide content was observed in LDL and possibly in HDL after cardiac surgery.

Apolipoprotein A-I↗
PubMed2004

Lipid and apoprotein changes during atorvastatin up-titration in hemodialysis patients with hypercholesterolemia: a placebo-controlled study.

BACKGROUND: Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich, apoprotein B-containing "remnant" lipoproteins, small dense low-density lipoprotein, and low levels of high-density lipoprotein. They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin, a potent, broadacting lipid regulator. This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients, to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup. METHODS: In this randomized, placebo-controlled, double-blind study in hemodialysis patients with hypercholesterolemia (n = 42, mean total cholesterol 243 +/- 33 mg/dl (6.3 +/- 0.8 mmol/l)), the efficacy of 4-weekly increasing doses of atorvastatin (10 - 40 mg daily) was investigated. Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions. RESULTS: Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin (total cholesterol -33%, low-density lipoprotein cholesterol -43% after 12 weeks), while high-density lipoprotein cholesterol remained unchanged. Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg, while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III. At week 12, the fraction of small dense low-density lipoprotein was significantly reduced from 23% - 18%, and apoprotein B-containing intermediate-density lipoproteins were no longer detectable. CONCLUSION: In conclusion, atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis. Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated. Further prospective studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality.

Aged↗
PubMed2001

Incubation of lipid emulsions with plasma lipoproteins modifies the fluidity of each particle.

Lipid emulsions (LE) contain triglyceride (TG)-rich particles (TGRP) and phospholipid-rich particles (PLRP). Various lipid and protein exchanges take place during in vitro incubations of LE with lipoproteins. These composition changes affect physical properties of particles. The aim of this study was to determine the role of different LE particles and the effect of TG composition on physical modifications. Low density lipoproteins (LDL: 1.025 < d < 1.040 g/mL) or high density lipoproteins (HDL: 1.085 < d< 1.150 g/mL) were incubated with the following four LE or their TGRP or PLRP, which were manufactured with the same phospholipid emulsifier: long-chain triglycerides (LCT): 100% soybean oil; medium-chain triglycerides (MCT)/LCT (MCT/LCT, 5:5, w/w); FO (100% fish oil); and MLF541 (MCT/LCT/FO, 5:4:1, by wt). After incubation, modified LE particles and lipoproteins were analyzed by fluorescence polarization. Observed physical modifications were significant in emulsion particles (ordering effect) but not in lipoproteins and also were significant for TG composition effect. Since intact emulsion contained a large excess of TGRP over PLRP, it is not surprising that intact emulsion had the same behavior as TGRP alone, and that PLRP had the same physical characteristics as lipoproteins. TG loss and cholesterol and protein acquisitions by emulsion particles rigidify their envelope. The two emulsions containing FO were less ordered after incubation. In conclusion, incubation of LE with lipoproteins changes physical properties of each kind of particle, and TG composition of the emulsion affects emulsion particle changes but has no effect on LDL and HDL. These order modifications induce more effective exchanges between LE particles and lipoproteins and modify their metabolism; HDL changes may increase the reverse cholesterol transport.

Adult↗
PubMed2000

Advances in intravenous lipid emulsions.

Over the past decade, our views have considerably evolved with respect to the metabolism of intravenous lipid emulsions and their composition. Substantial progress has been made in understanding the metabolic pathways of emulsion particles and the delivery of their various components (fatty acids and vitamins) to specific tissues or cells. Although soybean long-chain triglycerides represent a valuable source of energy, concerns have been raised about their high content of polyunsaturated fatty acids (mainly n-6 essential fatty acids), which may adversely affect immune functions and antioxidant status. Introduction of medium-chain triglycerides or olive oil to lipid emulsions can largely help bypass these disadvantages. Recently, incorporation of n-3 fatty acids in lipid preparations was suggested to have potential application in several chronic and acute diseases because of their ability to reduce inflammatory and thrombotic responses and cell sensitivity to various stimuli. Hence lipid emulsions should no longer be considered only as a means of providing energy substrates; they also modulate key metabolic functions. Such improved knowledge may lead to optimizing the metabolic care of certain patients.

Dietary Fats, Unsaturated↗
PubMed1999

Clinical use of lipid emulsions.

Substantial progress has been made in the understanding of the metabolism of intravenous lipid emulsions and the delivery of their various components to specific tissues or cells. Lipid emulsions should be considered not only as a means of providing energy substrates but also specific compounds that participate in the regulation of key metabolic functions. Such improved knowledge should find applications in the metabolic care of different types of patients.

Dietary Fats, Unsaturated↗
PubMed1997

Lipoprotein metabolism during and after a 6-h infusion ofMCT/LCT vs LCT emulsion in man.

We studied, in man, the intravascular metabolism of two lipid emulsions differing in their triglyceride (TG) fatty acid pattern. One emulsion was composed exclusively of soy bean long-chain triglycerides (LCT), the other of a mixture containing a (1:1, wt:wt) ratio of medium-chain triglycerides (MCT) and LCT (MCT/LCT). Both emulsions contained 10% TG and 1.2% of the same egg yolk phospholipid emulsifier. Six healthy volunteers received both emulsions, in random order, at a rate of 0.2 g TG/kg.h for 6 h. An interval of 2 weeks separated the tests. Although the MCT/LCT emulsion provided 39% more TG molecules than the pure LCT emulsion, plasma TG increased to similar levels, indicating a faster elimination of MCT/LCT. The rise of plasma non esterified fatty acids was greater with MCT/LCT (P < 0.001). LDL-TG enrichment was higher with MCT/LCT (P < 0.025) while net transfer of TG to HDL was similar with both emulsions. Cholesteryl ester (CE) enrichment in the 'VLDL' fraction (largely composed of emulsion particles) was markedly less during MCT/LCT than LCT infusions (P < 0.01). CE enrichment of the 'VLDL' fraction persisted up to 6 h after cessation of both lipid infusions. In conclusion, TG from MCT/LCT emulsion appear to be eliminated faster than LCT during an in vivo infusion in man. In accordance with our previous in vitro data, MCT/LCT infusion was associated with a higher transfer of TG to LDL and in a reverse manner, with a lesser acquisition of CE by emulsion particles as compared to LCT infusion.

Journal Article↗
PubMed1997

Recent developments in lipid emulsions: relevance to intensive care.

For years, intravenous lipid supply has been considered as a means of providing an efficient fuel to many tissues of the body and of preventing or correcting essential fatty acid deficiency. The potential for lipid emulsions to modulate cell function via their content of specific fatty acids and of liposoluble vitamins has not received much attention yet. Soybean [long-chain triglycerides (LCT)] emulsions provide a valuable source of energy, but they are excessively rich in omega-6 essential fatty acids (FAs). Their infusion is associated with an accumulation of linoleate and a reduction of long-chain (> or = C20) omega-6 and omega-3 fatty acids in cell membrane phospholipids, as well as with a depletion of antioxidant status, associated with a reduction of alpha-tocopherol in plasma lipoproteins. Infusions of the mixed medium-chain triglycerides (MCT)/LCT (50%:50%; wt:wt) largely bypass these disadvantages. In addition, plasma elimination of MCT/LCT is faster than that of LCT. Recent advances indicate a great potential for omega-3 FAs incorporated into membrane phospholipids to modulate cell response to various stimuli and to influence several intracellular metabolic processes. Furthermore, some of these FA directly influence the production and the action of important mediators, the eicosanoids. In practical terms, an increased intake of omega-3 FAs may reduce inflammatory and thrombotic responses while protecting tissue microperfusion and immune defenses. Such properties may find interesting applications in several types of intensive care unit patients, provided that omega-3 FA incorporation takes place promptly. We recently had the opportunity to study in vitro and in vivo the metabolism of emulsions made of a mixture of MCT, soybean LCT, and fish oil triglycerides. Plasma elimination of such preparations appeared to be very fast, and their infusion was not associated with a prolonged residence of emulsion particles. In addition, uptake of remnants enriched with omega-3 FAs and liposoluble vitamins was fairly fast and occurred in several types of cells, leading to an efficient incorporation of omega-3 FAs in cell membranes within a few hours. The understanding that remnant uptake plays a significant role in the delivery of components included in lipid emulsions opens new areas of investigation and is likely to find several conditions of applications for new types of preparations.

Antioxidants↗
PubMed1997

[Dietary intake and hyperlipoproteinemias].

The role of nutrition on the prevalence of cardiovascular diseases is largely, but not exclusively linked to the effect of dietary intake on plasma lipids and lipoproteins. Among the regular nutrients, saturated fats, and to a lesser extent cholesterol, do raise plasma cholesterol, namely in the LDL fraction. Classical recommendations consist of reducing dietary lipids to < or = 30% and saturated fats to < or = 10% of total caloric intake. However, recent findings demonstrate that not all saturated fatty acids are exerting a similar effect on cholesterol metabolism. Likewise, whether saturated fatty acids should be most appropriately replaced by carbohydrates or monounsaturated lipids is a matter of controversy, especially when managing patients with high plasma triglycerides and/or insulin resistance. In contrast, there is currently some agreement for limiting the intake of polyunsaturated fatty acids; and for considering separately the essential n-6 or omega 6 fatty acids (largely present in many vegetable oils) and the n-3 or omega 3 derivatives (present in algae and fish oils). This leads to evaluate other properties of fatty acids (and of other dietary components) such as the capacity to modulate inflammatory responses and thrombotic reactions, as well as to influence cell sensitivity to stimuli, cell to cell communication, and cell proliferation. Finally, the confirmation that peroxidative processes are playing an important role in lipoprotein metabolism and the development of atherosclerotic lesions largely explains the present interest to antioxidants.

Arteriosclerosis↗
PubMed1996

Elimination of fat emulsion particles from plasma during glucose infusion.

To determine the optimal rate of infusion of a fat emulsion (long-chain triglycerides; LCTs) for parenteral nutrition, the rate of elimination of triglycerides from plasma was measured on two occasions in three healthy subjects, once while receiving LCTs alone (study I) and once while receiving a combined infusion of glucose and LCTs (study 2). In study 1 a hypertriglyceridaemic clamp was set up by raising the concentration of triglycerides to 2 mmol l(-1) (60-min priming infusion at 0.2 g LCTs per kg body-weight per h) and maintaining this value for 300 min. In study 2 a constant infusion of glucose at a rate of 0.32 g per kg body-weight per h was given throughout the 420-min test, and the hypertriglyceridaemic clamp was set up after 70 min. The infusion of glucose induced a progressive increase in the mean(s.d.) concentration of insulin from 4.3(0.4) microU ml(-1) to a plateau value of 11.0(0.2) microU ml(-1) which was sustained during the last 310 min of the study. During the steady state of the hypertriglyceridaemic clamp, the concentration of triglycerides (2.16(0.17) versus 2.12(0.20) mmol l(-1), P = 0.26), as well as the mean(s.d.) rates of infusion of LCTs (0.12(0.08) versus 0.12(0.04) per kg body-weight per h, P = 0.38), did not differ between studies 1 and 2. Thus, an infusion of glucose (and the associated physiological increase in the concentration of insulin) at doses commonly used in parenteral nutrition does not influence the rate of elimination of triglycerides from plasma in normal subjects.

Adult↗
PubMed1996

Incorporation of medium chain triacylglycerols into phospholipid bilayers: effect of long chain triacylglycerols, cholesterol, and cholesteryl esters.

The ability of water-insoluble molecules such as triacylglycerols to partition from oil phases into phospholipid interfaces may be crucial to their hydrolysis by lipases in the aqueous environment of plasma and cells. This study uses high resolution and magic angle spinning 13C NMR spectros-copy to measure the solubility of the 8-carbon medium chain triacylglycerol, trioctanoin, in the lamellar structure of phospholipids (vesicles and multilayers) in the presence of other neutral lipids that may compete for an interfacial location (long chain triacylglycerol, cholesteryl ester, and cholesterol). In the presence of a saturating concentration of triolein (approximately 3 mole%), the solubility of trioctanoin in egg phosphatidylcholine vesicles decreased from 10 mole% to 7 mole%. The presence of a saturating concentration of trioctanoin (approximately 10 mole%) decreased the interfacial solubility of long chain triolein to approximately 1 mole%. Cholesteryl oleate in phospholipid vesicles slightly diminished the incorporation of trioctanoin into the surface. The presence of cholesterol reduced the interfacial solubility of trioctanoin, but at a high level of cholesterol (30 mole%), trioctanoin had a solubility of 3 mole%. Thus, even in the presence of other competing neutral lipids, medium chain triacylglycerol retains a favorable location and surface concentration for efficient hydrolysis. 13C NMR analysis thus provides an explanation for preferential hydrolysis of medium, compared to long chain triacylglycerol, in a physical blend of medium and long chain triacylglycerol in a single emulsion particle, and in general, a valuable approach to determine substrate availability at phospholipid surfaces.

Caprylates↗
PubMed1996

Fish meal lecithin as alternative precursor of docosahexaenoate and choline.

Choline and docosahexaenoate (DHA) are essential nutrients for maintaining normal brain function. However, their existence in fish lecithin is ignored and excluded during the degumming step of conventional fish oil manufacturing process. The study aims to introduce fish lecithin as alternative precursor of choline and omega-3 fatty acids especially DHA for nutritional supplements. Four grades of Thai fish meals with protein contents ranging from 60-70% were used. Their lipid characteristics were examined. Fish meal's fats and lecithin were 9-15 and 2-3 g/100 g, respectively. Total fatty acids constitute 23-27% monoenes without erucic acid and 24-28% polyenes including 15-19% DHA. Lecithin with 50% purity was prepared from grade-1 fish meal by means of consecutive methanol/n-hexane/acetone extraction. The obtained lecithin contains choline upto 66-70 mole% with DHA reaches to 20-23%. Its peroxide value of 57 and acid value of 9 are accepted for food grade lecithin preparation, however, the further refinery process is still suggested. Since the world consumption of nutritional supplement foods is increasing steadily, the results of our study implies that fish lecithin is probably a promising source of choline and omega-3 fatty acids especially DHA for such an objective.

Choline↗