Lajos Szollár

Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil: a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition.

Objectives: Safety, tolerability, and efficacy of a novel lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOFlipid 20%) with reduced n-6 fatty acids (FA), increased monounsaturated and n-3 FA, and enriched in vitamin E were evaluated in premature infants compared with a soybean oil–based emulsion. Patients and Methods: Sixty (30/30) premature neonates (age 3–7 days, gestational age ≤34 weeks, birth weights 1000–2500 g) received parenteral nutrition (PN) with either SMOFlipid 20% (study group) or a conventional lipid emulsion (Intralipid 20%, control group) for a minimum of 7 up to 14 days. Lipid supply started at 0.5 g · kg body weight−1 · day−1 on day 1 and increased stepwise (by 0.5 g) up to 2 g · kg body weight−1 · day−1 on days 4 to 14. Safety and efficacy parameters were assessed on days 0, 8, and 15 if PN was continued. Results: Adverse events, serum triglycerides, vital signs, local tolerance, and clinical laboratory did not show noticeable group differences, confirming the safety of study treatment. At study end, γ-glutamyl transferase was lower in the study versus the control group (107.8 ± 81.7 vs 188.8 ± 176.7 IU/L, P < 0.05). The relative increase in body weight (day 8 vs baseline) was 5.0% ± 6.5% versus 5.1% ± 6.6% (study vs control, not significant). In the study group, an increase in n-3 FA in red blood cell phospholipids and n-3:n-6 FA ratio was observed. Plasma α-tocopherol (study vs control) was increased versus baseline on day 8 (26.35 ± 10.03 vs 3.67 ± 8.06 μmol/L, P < 0.05) and at study termination (26.97 ± 18.32 vs 8.73 ± 11.41 μmol/L, P < 0.05). Conclusions: Parenteral infusion of SMOFlipid was safe and well tolerated and showed a potential beneficial influence on cholestasis, n-3 FA, and vitamin E status in premature infants requiring PN.

Flow-Induced Constriction in Arterioles of Hyperhomocysteinemic Rats Is Due to Impaired Nitric Oxide and Enhanced Thromboxane A2 Mediation

Abstract —Hyperhomocysteinemia (HHcy) is thought to promote arteriosclerosis and peripheral arterial disease, in part by impairing the function of endothelium. Because flow-induced dilation is mediated by the endothelium, we hypothesized that HHcy alters this response by interfering with the synthesis/action of NO and prostaglandins. Thus, changes in the diameter of isolated, pressurized (at 80 mm Hg) gracilis skeletal muscle arterioles (diameter ≈170 &mgr;m) from control and methionine diet–induced HHcy rats were investigated with videomicroscopy. Increases in intraluminal flow (from 0 to 25 &mgr;L/min) resulted in dilations of control arterioles (maximum, 34±4 &mgr;m). In contrast, increases in flow elicited constrictions of HHcy arterioles (−36±3 &mgr;m). In control arterioles, the NO synthase inhibitor N&ohgr;-nitro-l-arginine-methyl ester significantly attenuated (≈50%) dilation, whereas the additional administration of indomethacin, an inhibitor of cyclooxygenase, eliminated flow-induced dilation. In the arterioles of HHcy rats, flow-induced constriction was not affected by N&ohgr;-nitro-l-arginine-methyl ester, whereas it was abolished by indomethacin or the prostaglandin H2/thromboxane A2 (TXA2) receptor antagonist SQ 29,548 or the TXA2 synthase inhibitor CGS 13,080. Thus, in HHcy, increases in intraluminal flow elicit constrictions of skeletal muscle arterioles due to the impaired NO and enhanced TXA2 mediation of the response, alterations that likely contribute to the development of peripheral arterial disease.

Effects of Early Nutrition on Free Radical Formation in VLBW Infants with Respiratory Distress

Objective: We studied the development of essential fatty acid deficiency (EFAD) and its effects together with those of vitamin E deficiency on the free radical formation of very low birth weight (VLBW) infants with respiratory distress. Methods: Infants were divided into three groups based on the way each was supplied with daily total energy intake: (1) by fat free parenteral nutrition only or by nutrition composed of (2) less than or (3) higher than 25% of total daily energy intake given in oral feeding. We measured plasma lipid parameters and autoxidative susceptibility (AOS) of red blood cells (RBCs). Results: Plasma concentrations of linoleic acid were low in all the groups. After at least 14 days of feeding, eicosatrienoic acid (EA) was not detected. One week after the introduction of oral feeding, the abnormal triene/tetraene ratio of the groups had decreased, but was not normalized. Vitamin E deficiency was associated with significantly increased AOS, but EFAD was not. The two factors together caused an increase of AOS, that was additive. Conclusions: Our data confirm that EFAD increases AOS of RBCs in VLBW infants. We assume that prevention of EFAD in VLBW infants could decrease the prevalence of complications associated with free radical formation.

Morphological evidence of lysosomal uptake of high-density lipoproteins by rat adrenocortical cells in vitro

The high-density lipoprotein (HDL) pathway in rat adrenocortical cells was studied at the electron microscopic level in vitro via colloidal gold labelling. Steroid hormone assays were performed to confirm that the cells remained intact, viable, responsive to ACTH under the applied conditions, and to reveal the steroidogenic effect of HDL. The gold-labelled HDL particles (HDL-Au) were observed on the surface of the parenchymal cells, often attached to the membranes of the microvilli, but rarely in coated pits and coated vesicles. HDL-Au was accumulated by non-coated vesicles, multivesicular bodies and lysosomes. The lysosomes were identified by means of a non-specific esterase reaction. It is concluded that HDL particles are internalized by both zona glomerulosa and zona fasciculata cells. HDL is required for the enhanced functional activity of these cells in long-term incubation, and the lysosomes are involved in the process.

Effects of Administration of Different Intravenous Lipid Emulsions on Plasma LP-X Concentrations in the Rat

BACKGROUND Prolonged parenteral nutrition with lipid emulsions is essential to provide sufficient energy supply and to avoid essential fatty acid deficiency in preterm infants. However, chronic administration of lipid emulsions may lead to the development of pathological plasma lipid and LP-X concentrations. The aim of this study was to evaluate the relative importance of the phospholipid-triglyceride (PL-TG) ratio and the source of phospholipid in lipid emulsions, with respect to plasma lipid and LP-X levels. METHODS Rats were infused for 9 days with IV lipid emulsion containing 10% (IL-10) or 20% (IL-20) egg lecithin or Lipofundin containing 20% soya lecithin (LF), with PL-TG ratios of .12, .06, and 0.75, respectively. RESULTS LF significantly increased plasma triglyceride concentration (p < .01), whereas the rise in cholesterol levels observed with all emulsions was primarily caused by the increase in low-density lipoprotein cholesterol concentrations. The plasma phospholipid concentration was increased most by IL-10 (p < .005). There was a strong correlation between the PL-TG ratio of emulsions and the developing plasma phospholipid and LP-X concentrations (r2 = .91 and .96, respectively), despite the different origin of phospholipids in the emulsions, suggesting that it is the PL-TG ratio, rather than the source of phospholipids in lipid emulsions that primarily influences developing plasma lipid and LP-X concentrations. CONCLUSION These results indicate that the administration of lipid emulsions with lower PL-TG ratios should be considered, to avoid the development of pathological plasma lipoprotein concentrations.

Binding of fibronectin to human lipoproteins

High molecular mass adhesive glycoprotein plasma fibronectin binds to isolated HDL and LDL lipoprotein fractions in a solid phase radioimmunoassay. Mean dissociation constants of interaction of fibronectin and immobilized HDL and LDL lipoproteins isolated from eight patients with type IIa and type IV hyperlipoproteinemia are 7.8 +/- 3.2 X 10(-7) mol/l and 6.8 +/- 2.6 X 10(-7) mol/l, respectively. Fibronectin can also bind to HDL and LDL isolated from six healthy subjects with mean dissociation constants of 2.07 +/- 0.45 X 10(-6) mol/l and 2.25 +/- 0.48 X 10(-6) mol/l, respectively. The binding is not dependent on the presence of divalent cations. Fibronectin-lipoprotein interaction is inhibited by soluble lipoproteins. There is no observable interaction between fibronectin and VLDL fraction. Binding of fibronectin to HDL and LDL lipoproteins can have an in vivo significance, since the interaction may play a role in the metabolism, deposition of lipoproteins into the vessel wall and in atherogenesis.

Colloidal gold-labeled lipoprotein binding and internalization in adrenocortical cells in vitro.

Human (normal and adenomatous) and rat (normal) adrenocortical cells were incubated in vitro with colloidal gold labeled low-density (LDL-Au) and high-density (HDL-Au) lipoproteins, respectively, in order to visualize lipoprotein binding and internalization at an electron microscopic level. Both normal and adenomatous human adrenocortical cells accumulated LDL-Au by receptor-mediated endocytosis via coated pits, coated vesicles, noncoated vesicles, and lysosomes. HDL-Au was not internalized. In rat adrenocortical cells, both HDL-Au and to a lesser extent LDL-Au were internalized. It is concluded that LDL-Au and HDL-Au conjugates can be used to identify lipoprotein receptors and to follow lipoprotein internalization in adrenocortical cells.

The composition of triacylglycerols in human blood lipoproteins, milk and adipose tissue.

Publisher Summary This chapter provides an overview of the composition of triacylglycerols in human blood lipoproteins, milk, and adipose tissue. Natural triglycerides are complex mixtures of individual triglyceride (TG) molecules. The structure of a TG mixture may be characterized by its fatty acid composition, the positional or stereospecific analysis of acyl groups on different –OH moiety of glycerol, and molecular fractionation, separating the largest possible number of individual component molecules. In an experiment described in the chapter, the obtained TG classes, with different degrees of unsaturation, were further fractioned into individual TG groups using reversed phase TLC. Quantitation of component TGs was made by direct gas-chromatographic separation of TGs, using triheptadecanoin as an internal standard. The fatty acid composition of each fraction was measured by gas chromatography of methyl esters. The peaks were identified by applying known standards, and peak areas were measured. The structure of human endogenous TGs is different; neither fatty acid composition nor triacylglycerol distribution is identical. It is found that the differences in TG distribution are markedly greater, than the differences in fatty acid composition. The structure of the TGs influences the physicochemical and other properties of a fat. The TGs synthetized in various organs have different physiological functions, and this might probably account for the different TG composition.

CONCLUDING REMARKS ON LIPOPROTEIN METABOLISM, APOLIPOPROTEINS, LIPID CONSTITUENTS

Publisher Summary This chapter examines some remarks on lipoprotein metabolism, apolipoproteins, and lipid constituents. All lipoproteins found in the plasma are present in the lymph. The interstitial space is about three times the plasma space so a substantial portion of the lipoproteins is present in the interstitium. The VLDL synthesis of the isolated hepatocytes corresponds to the rate measured in vivo . The composition of VLDL is similar to the particles synthetized in vivo , but it does contain less cholesterine and C apoprotein. The in vitro VLDL synthesis can be blocked by inhibitors of protein synthesis and by blocking the microtubular system. Feeding with sucrose causes a long term synthesis increase; however, the addition of fatty acid to the medium brings about a short time elevation of the VLDL secretion.