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.

Dysfunction of nitric oxide mediation in isolated rat arterioles with methionine diet-induced hyperhomocysteinemia.

In humans, increased plasma homocysteine (Hcy) has been shown to be correlated with occlusive arterial diseases and atherosclerosis. Studies of isolated conductance vessels of experimental animals suggest that Hcy may interfere with local vasoregulatory mechanisms, yet the effect of hyperhomocysteinemia (HHcy) on the function of microvessels, such as skeletal muscle arterioles, has not been investigated. Male Wistar rats were divided into 2 groups: control rats (C; plasma Hcy, 7.1+/-0.3 micromol/L; n=25), and rats made HHcy by 1 g/kg body weight daily intake of methionine in the drinking water for 4 weeks (plasma Hcy, 23.6+/-2.9 micromol/L; P<0.01 versus C; n=25). First-order arterioles ( approximately 130 micrometer in diameter) were isolated from gracilis muscle, cannulated, and pressurized (80 mm Hg, no-flow conditions). Changes in diameter were observed by videomicroscopy. Arteriolar constrictions to norepinephrine (NE; 3x10(-7) mol/L) were significantly (P<0.01) greater in HHcy compared with C rats (C, 37.7+/-4.9%; HHcy, 59.5+/-5. 2%). Removal of the endothelium (-E) augmented NE-induced constrictions only in arterioles from C rats, whereas it had no effect on responses of arterioles from HHcy rats (C-E, 55.9+/-6.9%; HHcy-E, 56.5+/-7.0%). Dilations to cumulative doses of acetylcholine (ACh; 10(-8) mol/L) were significantly reduced in arterioles from HHcy rats (C, 64.0+/-5.2%; HHcy, 24.1+/-6.8%). Inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine (L-NNA; 10(-4) mol/L) significantly decreased ACh-induced dilations of C arterioles, whereas it did not affect HHcy arterioles. Similar alterations were found in arteriolar dilations to histamine, another known NO-dependent agonist. Endothelium-independent dilations to the NO donor sodium nitroprusside were not different in arterioles from C and HHcy rats, either in the presence or absence of L-NNA. Presence of superoxide dismutase and catalase (scavenger of reactive oxygen metabolites) did not affect HHcy-induced alterations in the ACh response. We conclude that hyperhomocysteinemia reduces rat skeletal muscle arteriolar dilations in response to ACh and histamine, and enhances constrictions to NE, alterations that are likely to be caused by the reduced mediation of these responses by NO. The reduced activity of NO in arterioles may contribute to the microvascular impairment described in HHcy.

Noncovalent interactions in maintaining the native structure of low density lipoprotein.

The integrity and the surface charge distribution of native low density lipoprotein (LDL) are prerequisites of its binding to the LDL receptor. Oxidation is one of the most important physiological effects resulting in an altered structure and metabolism of LDL. To reveal forces responsible for maintaining the intact structure of LDL in the absence of cells we have determined the kinetics of lipid peroxidation, changes in electrophoretic mobilities and size distributions of LDL samples as a function of Cu++ induced oxidative modification in a cell-free system at two different (50 mM and 150 mM) ionic strengths by electrophoretic and dynamic light scattering. Our data show that the lipid peroxidation is almost complete before LDL is degraded at 50 mM while a slight extent of lipid peroxidation is enough to result in the same effect at 150 mM. These suggest that both ionic and hydrophobic interactions are necessary to maintain the integrity of the LDL molecule.

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.

Long-term effects of unsaturated fatty acid dominance on the release of free radicals in the rat.

The aim of this study was to investigate the effects of an abundance of unsaturated fatty acids, hyperoxia, and vitamin E on free radical formation in vitamin E-deficient rats. The excess of unsaturated fatty acids was achieved by i.v. administration of a lipid emulsion (Intralipid). To assess free radical formation, we measured the autooxidative susceptibility of red blood cells (AOS) and the thiobarbituric acid reacting substrates (TBARS) in LDL and HDL. Intralipid significantly increased all the measured parameters compared with controls (AOS: 1385 +/- 73 versus 1056 +/- 55; LDL-TBARS: 4955 +/- 422 versus 1050 +/- 33; HDL-TBARS: 6855 +/- 573 versus 1033 +/- 26 nmol TBARS/mmol). Hyperoxia alone increased AOS more than Intralipid alone, whereas LDL- and HDL-TBARS concentrations were affected less by hyperoxia than lipid emulsion. The combination of hyperoxia and Intralipid was most effective in raising all measured parameters (AOS: 2285 +/- 141; LDL-TBARS: 6716 +/- 318; HDL-TBARS: 14614 +/- 1000 nmol TBARS/mmol). Vitamin E completely prevented the increase in AOS, LDL-TBARS, and HDL-TBARS without fully reversing the increase in free radical formation caused either by Intralipid or by the combination of hyperoxia and Intralipid. These findings suggest that vitamin E supplementation is beneficial to counter increased free radical formation, such as that in response to hyperoxic attacks or lipid-containing parenteral nutrition, which is frequently encountered in the treatment of premature infants.

Effect of metoprolol and pindolol monotherapy on plasma lipid- and lipoprotein-cholesterol levels (including the HDL subclasses) in mild hypertensive males and females.

Forty-five patients with mild hypertension were treated for 2 months with either metoprolol or pindolol in a randomized, blind, crossover study. The effects of metoprolol (100-300 mg/day) and pindolol (5-15 mg/day) on triglyceride (TG), cholesterol (C), high-density lipoprotein cholesterol (HDL-C), and HDL subfraction (HDL2-C and HDL3-C) levels were compared in males and females separately. Pindolol and metoprolol significantly elevated (10% above baseline level) the plasma TG level in both males and females. After metoprolol treatment, the HDL-C level remained unchanged in both sexes; however, a shift was found between HDL2-C and HDL3-C:HDL2-C decreased and a concomitant elevation in HDL3-C was observed. Pindolol significantly decreased total C, HDL-C, and HDL2-C levels in males. A similar trend (although the changes were not significant) was found in females. The results demonstrate the role of beta blockers in the inhibition of TG-rich lipoprotein elimination. These findings suggest that during long-term administration of metoprolol and pindolol, risks and benefits from beta-blocker therapy must be carefully considered. Continuous monitoring of lipid profiles is suggested during this treatment in order to avoid the potential worsening effect of beta blockers on risk factors of ischemic heart disease.

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.

Lipid and lipoprotein measurements in a normal, adult Cuban population.

An attempt was made to determine the normal reference values of lipid- and lipoprotein levels (cholesterol), triglycerides, cholesterol in high- and low-density lipoproteins) in a selected, apparently healthy, Cuban population. Results were expressed as mean, and various percentiles of measured values; two ratios: Risk 1 (LDL-C/HDL-C) and Risk 2 (TC/HDL-C) were also calculated. Approximately 40% of the subjects aged 20 to 30 years had cholesterol values above 200 mg/dl. Females had significantly higher cholesterol HDL-C values than males, whereas the concentrations of LDL-C and LDL were higher in males. Risk 2 ratios were elevated in males. A correlation was shown between lipid levels and age. There was a strong negative correlation between HDL-C and relative body weight. It is suggested that obesity might be an individual risk factor in the population studied.

Lipid and lipoprotein profiles in Cuban children of three age groups.

We determined the lipid and lipoprotein levels in a selected group of apparently healthy adult Cuban subjects in a previous paper /27/. In this paper the basic lipid variables (TC, TG, HDL-C) in 271 healthy children are published. LDL-C levels were also calculated. A small, but continuous, rise was found in the TC level between 0 and 14 years in both sexes. The rise of TG was accompanied by HDL increase in girls but by LDL increase in boys. This phenomenon might explain the augmented susceptibility of men to ischaemic heart disease. Children at "high risk" should be identified (in case of positive family history of ischaemic heart disease) by cholesterol determinations, the borderline of the pathologic cholesterol levels seems to be very similar to that found in the USA, 170-190 mg/dl in the age group between 0 and 14 years.