Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition.

BACKGROUND: There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic metabolism. RESULTS: n-3 PUFA depletion leads to a significant decrease in body weight despite a similar caloric intake or adipose tissue weight. n-3 PUFA depleted mice exhibit hypercholesterolemia (total, HDL, and LDL cholesterol) as well as an increase in hepatic cholesteryl ester and triglycerides content. Fatty acid pattern is profoundly modified in hepatic phospholipids and triglycerides. The decrease in tissue n-3/n-6 PUFA ratio correlates with steatosis. Hepatic mRNA content of key factors involved in lipid metabolism suggest a decreased lipogenesis (SREBP-1c, FAS, PPAR gamma), and an increased beta-oxidation (CPT1, PPAR alpha and PGC1 alpha) without modification of fatty acid esterification (DGAT2, GPAT1), secretion (MTTP) or intracellular transport (L-FABP). Histological analysis reveals alterations of liver morphology, which can not be explained by inflammatory or oxidative stress. However, several proteins involved in the unfolded protein response are decreased in depleted mice. CONCLUSION: n-3 PUFA depletion leads to important metabolic alterations in murine liver. Steatosis occurs through a mechanism independent of the shift between beta-oxidation and lipogenesis. Moreover, long term n-3 PUFA depletion decreases the expression of factors involved in the unfolded protein response, suggesting a lower protection against endoplasmic reticulum stress in hepatocytes upon n-3 PUFA deficiency.

Rapid reduction of liver steatosis in omega3-depleted rats injected with a novel lipid emulsion.

The bolus intravenous administration of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO) to normal subjects was recently found to increase within 60 min the amount of long-chain polyunsaturated omega3 fatty acids ( omega3) in platelet and leukocyte phospholipids and, hence, was proposed as a tool to prevent such pathological events as cardiac arrhythmia in selected patients who have to undergo urgent anesthesia and/or surgery. This study investigates whether other cells located outside the vascular bed may also benefit from this procedure for replenishing phospholipids with omega3. For such a purpose, the MCT:FO emulsion (1.0 ml) was injected into normal or omega3-depleted rats examined, one hour later, for the content and fatty acid pattern of liver triglycerides and phospholipids. Control experiments included the administration of saline or a medium-chain triglyceride:olive oil emulsion. The results reveal that the bolus intravenous injection of MCT:FO to the omega3-depleted rats resulted in the enrichment of liver phospholipids in omega3 and a marked reduction in hepatic steatosis. In conclusion, it is proposed that such a procedure may indeed allow a rapid supply of omega3 not only to circulating and vascular endothelial cells but also to extravascular cells, with a resulting correction of the biochemical and biophysical defects linked to a deficiency in these fatty acids.

Glucose intolerance associated to insulin resistance and increased insulin secretion in rats depleted in long-chain omega3 fatty acids.

An intragastric D-glucose tolerance test was performed, after overnight starvation, in female rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3D rats) and control rats of same age and gender. The plasma D-glucose and insulin concentrations, insulinogenic index, and HOMA for insulin resistance were all higher, after overnight starvation, in omega3D rats than in control animals. Over the 120-minute period following the intragastric administration of D-glucose, the area under the curve for the same four variables was also higher in omega3D rats than in control animals. In addition to visceral obesity, liver steatosis, hypertension, and cardiac hypertrophy, the omega3D rats thus display further features of the metabolic syndrome, namely glucose intolerance and insulin resistance, despite hyperinsulinemia.

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.

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.

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.

Metabolic effects of arginine addition to the enteral feeding of critically ill patients.

BACKGROUND: Some studies have suggested that the addition of arginine to enteral feeding solutions may improve outcome in critically ill patients, but the mechanism is incompletely explained. In particular, the availability and utilization of arginine administered enterally is not well defined. METHODS: This prospective, randomized, double-blind, placebo-controlled study performed in a Department of Medicosurgical Intensive Care included 51 patients likely requiring long-term enteral feeding. Thirty-seven patients (57 +/- 7 years, SAPS II 33 +/- 6) completed the 7-day study, of whom 20 received the formula enriched with free arginine (6.3 g/L) and 17 received an isocaloric and isonitrogenous control solution. Arginine absorption was assessed from plasma arginine concentrations in serial samples. Three pathways of arginine utilization were explored: (1) the production of nitric oxide, assessed by the plasma concentration of nitrite/nitrate (NOx) and citrulline, and 24-hour urinary excretion of NOx; (2) the protein turnover, estimated by the phenylalanine concentrations; and (3) the activity of arginase, reflected by the ornithine concentration. RESULTS: The plasma concentrations of arginine and ornithine increased in the group fed with the enriched formula (from 55 +/- 9 micromol/L to 102 +/- 9 micromol/L and from 57 +/- 7 to 135 +/- 11 micromol/L, respectively, p < .05), but not with the control formula. There was no difference between groups in either NO production or phenylalanine concentration. CONCLUSIONS: Supplemental arginine in enteral feeding is readily absorbed, and mainly metabolized into ornithine, presumably by the arginase enzyme.

[Atherosclerosis and micronutrients]. / Athéromatose et micronutriments.

Large epidemiological studies have shown a reduced incidence of cardiovascular diseases in relation to dietary intake of micronutrients such as n-3 fatty acids (FA), folic acid, and vitamin E. The meaning of such results has been extended to promote the consumption of several vitamin supplements. Such supplementation, which represents a huge market, is generally taken as self-medication, with no medical prescription or control. Recent prospective trials confirm the efficacy of n-3 fatty acids in the secondary prevention of cardiovascular diseases. N-3 FA markedly affect cell metabolism by interacting at different levels. Increased intake of folic acid, either through changes in dietary habits or via supplements, also appears to positively affect cardiovascular prevention. Folic acid acts, both as an antioxidant and by reducing serum homocysteine concentration. While increased dietary intakes of vitamin E are associated with a reduced cardiovascular risk, the clinical results of recent studies evaluating the effect of vitamin E supplementation have generally been disappointing and contrast with the demonstration of potent antioxidant properties, as well as protective effects on endothelial and immune functions.

Enteral feeding with a solution enriched with antioxidant vitamins A, C, and E enhances the resistance to oxidative stress.

OBJECTIVE: To assess whether dietary supplementation with the antioxidant vitamins A, C, and E enhances parameters of oxidative stress and influences the course of critically ill patients. DESIGN: Prospective, randomized, double-blinded, placebo-controlled study. SETTING: Department of medicosurgical intensive care of an academic hospital. PATIENTS: Fifty-one patients expected to require at least 7 days of enteral feeding. Thirty-seven of these patients (age, 57 +/- 7 yrs; Simplified Acute Physiology Score II, 33 +/- 6 points) completed the study. INTERVENTIONS: Twenty patients were randomized to receive the formula supplemented with vitamins A (67 microg/dL), C (13.3 mg/ dL), and E (4.94 mg/dL), and 17 patients received an isocaloric and isonitrogenous control solution. MEASUREMENTS AND MAIN RESULTS: Plasma levels of antioxidant vitamins, lipid peroxidation (estimated by the malonyldialdehyde assay), and low-density lipoprotein (LDL), and erythrocyte resistance to experimental oxidative stress were determined on samples drawn two consecutive days before the initiation of feeding and at the end of the 7-day period. Clinical outcome measures included documented infection and intensive care unit and 28-day survival. Administration of the supplemented solution increased significantly the concentration of plasma beta-carotene (from 0.2 +/- 0.0 microg/mL to 0.6 +/- 0.1 microg/mL; p < 0.01) and plasma and LDL-bound alpha-tocopherol (from 6.0 +/- 0.4 microg/mL and 2.9 +/- 0.9 microg/mL to 9.7 +/- 0.5 microg/mL and 4.3 +/- 1.2 microg/mL, respectively; p < 0.05), and improved LDL resistance to oxidative stress by 21 +/- 4% (p < 0.05). No such change was observed in the control group. There was no significant difference in clinical outcome between the two groups. CONCLUSIONS: Supplemental antioxidant vitamins added to enteral feeding solutions are well absorbed. Dietary supplementation with vitamins A, C, and E is associated with an improvement in antioxidant defenses, as assessed by ex vivo tests.

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.

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.

Cofactors in in vitro induction of apoptosis in HL60 cells by all-trans retinoic acid (ATRA).

The aim of this study was to determine the culture conditions that could modulate the induction of apoptosis by all-trans retinoic acid (ATRA). Cell viability was evaluated by trypan blue test, differentiation by nitro blue tetrazolium test, and apoptosis by morphological analysis. ATRA induced apoptosis in HL60 cells only when more than 100,000 cells/mL were seeded, while differentiation was induced regardless of the seeded cell concentration. Reduction in the concentration of foetal calf serum or glutamine in the medium led to a weak increase in apoptosis. In contrast, a dramatic enhancement of apoptosis occurred when the culture medium was supplemented with glucose or when the culture pH was decreased. These characteristics were independent of the mechanism of action of ATRA, but the action of glucose could be of significance in diabetic patients. An exchange of supernatants after 3 days of culture showed that supernatants from control cultures seeded at high cell density were better apoptosis inducers than supernatants from cultures treated with ATRA, but seeded at low cell density. Factor(s) in this supernatant which induced apoptosis was (were) removed by ultrafiltration. In conclusion, our results showed that ATRA alone cannot induce apoptosis, but can do so in conjunction with cofactors. The depletion of some components of the medium and the appearance of secreted macromolecule(s) could be cofactor(s) in the induction of apoptosis.

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.

Triglyceride hydrolysis of soy oil vs fish oil emulsions.

BACKGROUND: Fish oil triglycerides (TG) are being considered for use in IV lipid emulsions, but the characteristics of their lipase-mediated clearance from plasma are largely unknown. METHODS: We compared the in vitro hydrolysis of soy oil long-chain triglyceride emulsions (LCT) and fish oil emulsions (omega-3) using lipoprotein (LPL) and hepatic (HL) lipases, omega-3 emulsions contained 18% and 28% of total TG fatty acid as eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), respectively. RESULTS: Under conditions of maximal hydrolysis, total free fatty acid (FFA) release was two- to threefold greater with LCT compared with omega-3 emulsions. Also, EPA and DHA together contributed proportionally much less than other fatty acids (< 20%) to FFA released from omega-3 emulsions. In mixtures of LCT emulsion with omega-3 emulsions, the presence of > 20% of omega-3 particles substantially inhibited LCT emulsion hydrolysis (by up to 50%). CONCLUSIONS: Our results suggest that, during infusion of omega-3 emulsions, EPA and DHA may enter cells as TG or partial glycerides within emulsion particles and not as FFA and that coinfusion of omega-3 emulsion with LCT emulsion at low omega-3:LCT emulsion ratios (up to 20% of total triglyceride as omega-3) will not substantially inhibit LCT hydrolysis.

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.

Effect of dietary supplementation with fish oil on cyclosporine A-induced vascular toxicity.

We wished to determine whether dietary supplementation with fish oil prevents the vascular toxicity of cyclosporine (Cx). In a first set of experiments, we assessed the endothelial function of aortas isolated from rats supplemented for 6 weeks with fish oil (FO), administered by gavage, and providing 150 mg/kg/day of eicosapentaenoic acid and 100 mg/kg/day of docosahexaenoic acid. FO treatment altered neither acetylcholine- and histamine-induced relaxations, nor serotonin-induced contractions (NS vs. control group). Thereafter, three groups of rats were treated in parallel. Group 1 received FO supplementation (by gavage) for 6 weeks, and Cx (10 mg/kg/day po) was added during the last 2 weeks, group 2 received Cx only (10 mg/kg/day po) for 2 weeks, and group 3 served as a control. Both acetylcholine-and histamine-induced relaxations were reduced in group 2 compared with the control group, as indicated by the area under the curve (AUC), which was significantly higher: 296 +/- 17 vs. 138 +/- 32, and 392 +/- 38 vs. 318 +/- 25 for acetylcholine and histamine, respectively. In group 1, AUC for acetylcholine remained significantly different from the control (241 +/- 31 vs. 138 +/- 32), whereas AUC for histamine was 367 +/- 28 (NS vs. control). The serotonin-induced contractions were also enhanced in group 2 compared with those of the control group, and this alteration was not attenuated in group 1. After mechanical removal of the endothelium, the increased responsiveness to serotonin persisted in groups 1 and 2, suggesting this functional alteration to be located in the smooth muscle cells. Thus, in the rat the attenuation of Cx-induced vascular toxicity by fish oil supplementation is only partial, that is, it involves a slight improvement in endothelial function, but with persistence of functional changes in smooth muscle.

Manipulation of tissue fatty acid profile by intravenous lipids in dogs.

This study was undertaken to determine the effects on the fatty acid (FA) composition of various dog tissues of 4 different lipid emulsions (a 100% long-chain triacylglycerol (LCT) derived from soya bean oil emulsion, a mixed 50% medium-chain triacylglycerol (MCT)/50% LCT emulsion as well as both these emulsions supplemented with 10% fish oil (FO) triacylglycerols), when daily infused over 15 days as a substantial component of total parenteral nutrition. Lipids represented 55% of the non-protein energy. Blood samples as well as biopsies from liver, muscle and adipose tissue were taken 15 days before, and again immediately after TPN. In addition, the spleen was also removed immediately after TPN. Tissue FA composition was analysed by gas liquid chromatography of each lipid component after separation by thin layer chromatography. No differences in either safety or tolerance were detected between the different TPN preparations. In particular, infusion over 2 weeks of fat emulsions containing 10% fish oil was tolerated as well as conventional LCT and MCT/LCT emulsions. Relative linoleate content of tissue triacylglycerol (TG) was markedly increased in animals that received the LCT emulsions (e.g. from 22.6 +/- 2.5% to 32.2 +/- 0.6% in the liver), this effect being markedly reduced with MCT/LCT preparations. n-3FA were slightly incorporated into liver TG (from 0.0 +/- 0.0% to 2.3 +/- 0.7% and 1.2 +/- 0.4% for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) respectively, with LCT + FO), but remained undetectable in extrahepatic tissue TG. Of interest, medium chain FA were found in tissue TG after infusion of the mixed MCT/LCT emulsions. As expected, changes of tissue phospholipid (PL) composition involved only long-chain FA. Infusion of soya bean oil emulsion was associated with an increased content of linoleate in liver PL (from 13.6 +/- 0.4% to 17.7 +/- 0.4%), but not in other tissues. MCT/LCT did not markedly affect PL/FA pattern in any tissue. Supplementation with fish oil was associated with an efficient incorporation of n-3FA into tissue PL, particularly in the liver (from 0.4 +/- 0.1% to 2.5 +/- 0.3% for EPA and from 3.9 +/- 0.8% to 9.1 +/- 0.4% for DHA, with the LCT + FO emulsion).

Effects of selenium supplementation on immune parameters in gut failure patients on home parenteral nutrition.

The relationships between some parameters of the immune response and selenium were investigated in five patients receiving home parenteral nutrition for short-bowel syndrome. They were first submitted to a relative depletion by providing 20 micrograms selenium/day as L-selenomethionine for 1 mo. Then, daily selenium intake was raised to 200 micrograms for 2-4 mo. On entering the study, the patients presented a relatively good health status, and immunological parameters were at the lowest limit of the normal range. Four patients rapidly responded to the 200-micrograms supplementation by a continuous increase in their plasma selenium levels, whereas the fifth patient showed a moderate and late increase. At the end of the trial, there was an improvement in the lymphocyte response to pokeweed and phytohemagglutinin mitogens in four patients and to CD3 in three patients. The response to two of three antigens (Candidin, Varidase) tested was also enhanced in the same patients, but the response to the third antigen (tetanus toxoid) was uniformly low in all patients. The only patient showing essentially no immune improvement after selenium supplementation was the one with a low and delayed increase in plasma selenium. This study supports a role for selenium in the maintenance of an optimal immune response in humans.

Plasma lipid and plasma lipoprotein concentrations in low birth weight infants given parenteral nutrition with twenty or ten percent lipid emulsion.

Because 10% and 20% intravenously administered lipid emulsions (intralipid preparations) differ in their phospholipid/triglyceride ratio (0.12 and 0.06, respectively), 28 low birth weight infants requiring parenteral nutrition for at least 1 week were selected at random to receive either emulsion to determine the effects on plasma lipids and lipoproteins. Triglyceride intake was progressively increased to reach 2 gm/kg per day between days 4 and 7. During that period, all plasma lipids in samples taken 6 hours after infusion were higher in the 10% intralipid group. In comparison with day 0 values, triglyceride concentrations decreased (63 +/- 7 to 45 +/- 4 mg/dl; p less than 0.05) in the 20% group. Cholesterol levels increased in both groups, but the rise was more than twofold higher in the 10% group. Phospholipid increase was approximately 25% in the 20% group but more than 125% in patients receiving the 10% emulsion (p less than 0.005). The changes in plasma cholesterol and phospholipid levels were almost entirely in low-density lipoproteins. After 7 days, eight infants from each group were given the alternate emulsion, which resulted in a reversal of lipid patterns in each patient. We conclude that the higher phospholipid intake in 10% than in 20% intralipid is associated with higher plasma triglyceride concentrations and leads to accumulation of cholesterol and phospholipids in low-density lipoproteins. Emulsions with lower phospholipid content may be preferable for low birth weight infants and perhaps other patient populations with impaired removal of parenteral fat emulsions.