Remodelling of primary human CD4+ T cell plasma membrane order by n-3 PUFA.

Cell membrane fatty acids influence fundamental properties of the plasma membrane, including membrane fluidity, protein functionality, and lipid raft signalling. Evidence suggests that dietary n-3 PUFA may target the plasma membrane of immune cells by altering plasma membrane lipid dynamics, thereby regulating the attenuation of immune cell activation and suppression of inflammation. As lipid-based immunotherapy might be a promising new clinical strategy for the treatment of inflammatory disorders, we conducted in vitro and in vivo experiments to examine the effects of n-3 PUFA on CD4+ T cell membrane order, mitochondrial bioenergetics and lymphoproliferation. n-3 PUFA were incorporated into human primary CD4+ T cells phospholipids in vitro in a dose-dependent manner, resulting in a reduction in whole cell membrane order, oxidative phosphorylation and proliferation. At higher doses, n-3 PUFA induced unique phase separation in T cell-derived giant plasma membrane vesicles. Similarly, in a short-term human pilot study, supplementation of fish oil (4 g n-3 PUFA/d) for 6 weeks in healthy subjects significantly elevated EPA (20 : 5n-3) levels in CD4+ T cell membrane phospholipids, and reduced membrane lipid order. These results demonstrate that the dynamic reshaping of human CD4+ T cell plasma membrane organisation by n-3 PUFA may modulate down-stream clonal expansion.

A Small Cohort Omega-3 PUFA Supplement Study: Implications of Stratifying According to Lipid Membrane Incorporation in Cardiac Surgical Patients.

BACKGROUND: Epidemiological studies and randomised clinical trials (RCTs) report disparate findings in relation to omega-3 polyunsaturated fatty acids (n-3 PUFA) benefit for cardiac patients. With RCTs interpretation is potentially confounded by background n-3 PUFA intake. The goal of this pilot, small cohort, pre-surgical supplementation study was to evaluate postoperative atrial fibrillation (AF) and cardiac molecular expression profiles employing two data analysis approaches - by treatment randomisation and by stratification using measured n-3 PUFA. METHODS: Patients (n=20) received 3g/day of fish or placebo oil (FO vs PO) in a double blind randomised protocol prior to elective coronary artery graft and valve surgery. Groups were matched for age, gender, and mean treatment duration (∼20 days). Resected atrial myocardium was sampled for assay of viability metabolic markers, and blood obtained for erythrocyte membrane lipid measurement. RESULTS: There was substantial overlap of cell membrane n-3 PUFA content across PO and FO groups, and no group treatment effects on AF incidence or myocardial molecular marker levels were detected. In contrast, data stratification using membrane n-3 PUFA content (at 8% total membrane lipid) achieved significant separation of patients (by n-6:n-3 PUFA ratio), a significant differential cardiac expression of the marker peroxisomal proliferator-activated receptor, but no difference in AF incidence. CONCLUSIONS: This small n-3 PUFA case study demonstrates that the same cohort may yield differing findings when evaluated using randomisation or stratification approaches based on direct molecular measures in cell membranes.

Vitamin C modulates the metabolic and cytokine profiles, alleviates hepatic endoplasmic reticulum stress, and increases the life span of Gulo-/- mice.

Suboptimal intake of dietary vitamin C (ascorbate) increases the risk of several chronic diseases but the exact metabolic pathways affected are still unknown. In this study, we examined the metabolic profile of mice lacking the enzyme gulonolactone oxidase (Gulo) required for the biosynthesis of ascorbate. Gulo-/- mice were supplemented with 0%, 0.01%, and 0.4% ascorbate (w/v) in drinking water and serum was collected for metabolite measurements by targeted mass spectrometry. We also quantified 42 serum cytokines and examined the levels of different stress markers in liver. The metabolic profiles of Gulo-/- mice treated with ascorbate were different from untreated Gulo-/- and normal wild type mice. The cytokine profiles of Gulo-/-mice, in return, overlapped the profile of wild type animals upon 0.01% or 0.4% vitamin C supplementation. The life span of Gulo-/- mice increased with the amount of ascorbate in drinking water. It also correlated significantly with the ratios of serum arginine/lysine, tyrosine/phenylalanine, and the ratio of specific species of saturated/unsaturated phosphatidylcholines. Finally, levels of hepatic phosphorylated endoplasmic reticulum associated stress markers IRE1α and eIF2α correlated inversely with serum ascorbate and life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo-/- mice.

Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients.

Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each two week-period was separated from the other by a six-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5 %, p< 0.001), and decreased platelet thromboxane B2 (-35 %, p< 0.001), urinary 11-dehydro-thromboxane B2 (-13.2 %, p< 0.001) and F2-isoprostane levels (-19.6 %, p< 0.001) associated with a significant increase of plasma and platelet vitamin E concentrations (+20 % and +11.8 %, respectively, p< 0.001). The proportions of DHA increased both in plasma lipids and in platelet phospholipids. After placebo treatment, there was no effect on any parameters tested. Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes.

Lipidomic analysis of fatty acids in erythrocytes of coeliac patients before and after a gluten-free diet intervention: a comparison with healthy subjects.

Coeliac disease (CD) patients may exhibit a pro-inflammatory profile and fatty acids (FA) can influence inflammation through a variety of cellular pathways in them. The aims of the present study were to (1) evaluate the FA composition of erythrocytes obtained from newly diagnosed CD patients by lipidomic analysis and compare it with that in healthy subjects and (2) determine the effects of 1-year gluten-free diet (GFD) intervention. A total of twenty CD patients (five men and fifteen women; mean age 34.0 (sem 1.7) years) were evaluated at diagnosis and after 1 year of GFD intervention. A total of twenty healthy subjects (seven men and thirteen women; mean age 40.2 (sem 2.5) years) served as controls. CD patients on an unrestricted diet exhibited a significant 2.08-fold higher concentration of arachidic acid when compared with healthy subjects, suggesting that it can be considered as a putative marker of CD. Besides, the arachidonic acid (AA):dihomo-γ-linolenic acid ratio was 2.01-fold significantly lower in CD patients than in healthy subjects (P< 0.01), underlying an inefficient synthesis of PUFA from their precursors in terms of desaturase activity. In addition, mainly due to lower concentrations of docosahexaenoic acid, the inflammation marker AA:docosahexaenoic acid ratio was 1.40-fold significantly higher in CD patients than in healthy subjects. After 1 year of GFD intervention, FA concentrations in CD patients were still different from those observed in healthy subjects. The lipidomic analysis of erythrocyte membranes confirmed the presence of an altered FA composition in CD patients and the GFD's ability to modify FA profile, even if 1-year GFD intervention seems to be not sufficient to restore FA concentrations to normality. This procedure, being easier and non-invasive compared with the evaluation of the FA pattern of the intestinal mucosa, could offer more potentiality for also evaluating therapeutic interventions in CD patients by using FA supplementation.

Modulation of (Na,K)-ATPase activity by membrane fatty acid composition: therapeutic implications in human hypertension.

Abstract Oxidative stress (OS) plays a key role in the pathophysiology of essential hypertension and is associated with changes in the cell membrane fatty acid composition and fluidity. As (Na,K)-ATPase is modulated by the surrounding lipid microenvironment, lipid peroxidation could alter the interactions of this enzyme with the membrane components. Thus, modifications in the membrane fatty acid profile will translate into effects on (Na,K)-ATPase activity. Accordingly, a decrease in this enzyme activity has been reported in hypertensive patients. The aim of this study was to evaluate the relationship between membrane fluidity and fatty acid composition and (Na,K)-ATPase activity in erythrocytes of essential hypertensive patients supplemented with antioxidant vitamins C and E. A double-blind, randomized, placebo-controlled study was conducted in 120 men with essential hypertension assigned to receive vitamin C (1 g/day) +E (400 IU/day) or placebo for 8 weeks. Measurements included OS related parameters: GSH/GSSG ratio, F2-isoprostanes and antioxidant capacity of plasma, (Na,K)-ATPase activity and erythrocytes membrane fatty acid composition (PUFA, polyunsaturated fatty acids; SAFA, saturated fatty acids). Associations were assessed by Pearson correlation and the differences by Student t-test (p<0.05). Supplemented hypertensive patients showed higher activity of (Na,K)-ATPase and proportion of PUFA, and lower blood pressure, OS markers and proportion of SAFA, versus placebo. The activity of (Na,K)-ATPase correlated negatively with the proportion of SAFA, but positively with that of PUFA in both groups. Supplementation with vitamins C+E resulted in decreased OS and increased fluidity and PUFA proportion in the membrane, both of which positively modulate (Na,K)-ATPase activity, accounting for the blood pressure reduction.

Ingestion of Chlorella reduced the oxidation of erythrocyte membrane lipids in senior Japanese subjects.

Accumulation of phospholipid hydroperoxide (PLOOH) in erythrocyte membranes is an abnormality found in patients with senile dementia, including those with Alzheimer's disease. In our previous studies, dietary xanthophylls (polar carotenoids such as lutein) were hypothesized to inhibit lipid peroxidation. In the present study, we conducted a randomized, double-blind, placebo-controlled human trial to assess the impact for a total of 2 months Chlorella supplementation (8 g Chlorella/day/person; equivalent to 22.9 mg lutein/day/person) on PLOOH and carotenoid concentrations in erythrocytes as well as plasma of 12 normal senior subjects. After 1 or 2 months of treatment, erythrocytes and plasma lutein concentrations increased in the Chlorella group but not in the placebo group. In the Chlorella-supplemented group, erythrocyte PLOOH concentrations after a total of 2 months of treatment were lower than the concentrations before supplementation. These results suggest that Chlorella ingestion improved erythrocyte antioxidant status and lowered PLOOH concentrations. These reductions might contribute to maintaining the normal function of erythrocytes and prevent the development of senile dementia.

Interaction of different extracts of Primula heterochroma Stapf. with red blood cell membrane lipids and proteins: antioxidant and antihemolytic effects.

In recent years, considerable attention has been paid to plants as potent natural drugs for their ameliorative roles against free-radical-mediated oxidative stress. Therefore, their interactions with cell membrane lipids and proteins, which generally serve as primary targets of lipid peroxidation, are of much interest. In the current investigation, in vitro and ex vivo studies are performed in order to estimate possible effects of different extracts of Primula heterochroma Stapf. on red blood cell membranes of rat erythrocytes using colorimetric methods. The results indicate that binding of the extracts to lipids and proteins of red blood cell membranes both significantly inhibits lipid peroxidation, and also increases red blood cell integrity against hemolysis. Moreover, a polyphenol extract, in particular, demonstrates notable antihemolytic activity in hydrogen peroxide-induced hemolysis model (IC(50) = 199.49 ± 9.1 µg ml(-1)).

Nafamostat mesilate, a noncalcium compound, as an anticoagulant, induces calcium-dependent haemolysis when infused with packed erythrocytes.

BACKGROUND: Nafamostat mesilate (NM), a protease inhibitor, is available for acute pancreatitis and disseminated intravascular coagulopathy and is used as an anticoagulant for haemodialysis in Japan. Co-infusion of red cell concentrates (RCC) and intravenous drugs is usually contraindicated. Because of limited venous access, adherence to the guidelines may be compromised in some clinical settings. Therefore, we investigated the influence of co-infusion of RCC and various anticoagulants on haemolysis in vitro. METHODS: We investigated the effect of co-incubation of RCC and various anticoagulant drugs [NM, gabexate mesilate (GM), heparin] in packed erythrocytes. We evaluated haemolysis using lactate dehydrogenase and free haemoglobin. In addition, we also evaluated the influence of co-incubation on phosphatidylserine (PS) expression on the erythrocyte membrane. RESULTS: GM and NM induced haemolysis in a dose-dependent manner, which was inhibited by removal of citrate and pretreatment with the calcium chelator, ethylenediaminetetraacetic acid. In a dynamic experiment using an infusion pump, NM not only induced haemolysis during co-infusion with RCC but also elevated PS expression dependent on extracellular calcium. CONCLUSION: NM and GM induce haemolysis in packed erythrocytes in the presence of citrate that is dependent on extracellular calcium.

Immune cell membrane fatty acids and inflammatory marker, C-reactive protein, in patients with multiple sclerosis.

Measurement of fatty acids in biological fluids and cell membranes including leucocytes from multiple sclerosis patients is inconsistent. The objective of the present study was to investigate the fatty acid composition within the different membrane phospholipid fractions in peripheral blood mononuclear cells in multiple sclerosis patients, and correlate with severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale and Functional System Scores. The fatty acid composition of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin and phosphatidylinositol phospholipids in the peripheral blood mononuclear cells of twenty-six multiple sclerosis and twenty-five control subjects were measured by GC, and C-reactive protein was measured in all subjects. The elongation product of 20 : 4n-6, 22 : 4n-6, was significantly decreased in membrane phosphatidylethanolamine and phosphatidylserine in multiple sclerosis patients (P = 0.01 and P = 0.03 respectively), and correlated inversely with severity of disease and C-reactive protein. Also an inverse correlation was observed between the C-reactive protein and membrane phosphatidylcholine and phosphatidylserine 20 : 4n-6. Cultural and ethnic differences, as well as dietary variability, especially in a diseased state have been implicated in the differences observed in the fatty acid composition in peripheral blood mononuclear cell membranes of patients with multiple sclerosis. The present results suggest that the disease state may in part explain the reported inconsistencies in fatty acid levels in multiple sclerosis patients.

Fish oil reduces heart rate and oxygen consumption during exercise.

Dietary omega-3 polyunsaturated fatty acids (PUFAs) are readily incorporated into heart and skeletal muscle membranes where, in the heart, animal studies show they reduce O2 consumption. To test the hypothesis that omega-3 PUFAs alter O2 efficiency in humans, the effects of fish oil (FO) supplementation on O2 consumption during exercise were evaluated. Sixteen well-trained men (cyclists), randomly assigned to receive 8 x 1 g capsules per day of olive oil (control) or FO for 8 weeks in a double-blind, parallel design, completed the study (control: n = 7, age 27.1 +/- 2.7 years; FO: n = 9, age 23.2 +/- 1.2 years). Subjects used an electronically braked cycle ergometer to complete peak O2 consumption tests (VO 2peak) and sustained submaximal exercise tests at 55% of peak workload (from the VO 2peak test) before and after supplementation. Whole-body O2 consumption and indirect measurements of myocardial O2 consumption [heart rate and rate pressure product (RPP)] were assessed. FO supplementation increased omega-3 PUFA content of erythrocyte cell membranes. There were no differences in VO 2peak (mL kg(-1) min(-1)) (control: pre 66.8 +/- 2.4, post 67.2 +/- 2.3; FO: pre 68.3 +/- 1.4, post 67.2 +/- 1.2) or peak workload after supplementation. The FO supplementation lowered heart rate (including peak heart rate) during incremental workloads to exhaustion (P < 0.05). In addition, the FO supplementation lowered steady-state submaximal exercise heart rate, whole-body O2 consumption, and RPP (P < 0.01). Time to voluntary fatigue was not altered by FO supplementation. This study indicates that FOs may act within the healthy heart and skeletal muscle to reduce both whole-body and myocardial O2 demand during exercise, without a decrement in performance.

Supplementation with 200 mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants.

BACKGROUND/AIMS: The supply of docosahexaenoic acid (DHA, 22:6omega-3), important for fetal/infant neurodevelopment, depends on the maternal fatty acid (FA) status, which may be marginal in central Europe. Therefore, we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids (RBC%), and in breast milk FA (%). METHODS: At 21 weeks' gestation, 144 women were enrolled into a randomised, double-blind clinical trial receiving daily: (1) a basic vitamin-mineral supplement (Vit/Min group), (2) Vit/Min plus 4.5 g fructo-oligosaccharide (FOS group), or (3) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA (DHA-FOS group). FAs were determined by capillary gas-liquid chromatography. RESULTS: While maternal RBC-DHA% at enrolment was not different, at 37 weeks gestation, and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group. The breast milk DHA% was twice as high in the DHA-FOS group (0.50%) than in the two others (0.25 %) (p < 0.001), and the ratio ARA/DHA in the DHA-FOS group was 1.0 +/- 0.43, in the others 2.1 +/- 0.43 (p < 0.001). The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher, and correlated significantly with maternal RBC-DHA% before and 3 months after delivery. CONCLUSIONS: In central Europe, a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants.

Trivalent chromium inhibits protein glycosylation and lipid peroxidation in high glucose-treated erythrocytes.

Epidemiological studies have shown lower levels of chromium among men with diabetes and cardiovascular disease (CVD) compared with healthy control subjects. The mechanism by which chromium may decrease the incidence of CVD and insulin resistance is not known. Using erythrocytes as a model, this study demonstrates that chromium inhibits the glycosylation of proteins and oxidative stress, both risk factors in the development of CVD. Erythrocytes were treated with high levels of glucose (mimicking diabetes) in the presence or absence of chromium chloride in the medium at 37 degrees C for 24 hours. Chromium supplementation prevented the increases in protein glycosylation and oxidative stress caused by the high levels of glucose in erythrocytes. This study demonstrates for the first time that chromium supplementation inhibits protein glycosylation in erythrocytes exposed to high glucose medium, which appears to be mediated by its antioxidative effect. This provides evidence for a novel mechanism by which chromium supplementation may decrease incidence of CVD in diabetic patients.

Trans fatty acids and atopic eczema/dermatitis syndrome: the relationship with a free radical cis-trans isomerization of membrane lipids.

The formation of trans FA residues in membrane phospholipids may be due to a free radical-catalyzed isomerization process occurring to the cis unsaturated FA moieties. Radical stress is well documented in inflammatory processes of atopic diseases, but no data are yet available about a possible association with trans FA detected in these patients. We investigated the presence of trans lipid isomers in the erythrocyte and T-lymphocyte membranes of 26 children affected by atopic eczema/dermatitis syndrome (AEDS). Trans lipid isomers were found in both cell membranes, up to a total content of 2.7 and 4.9% of the FA composition, respectively. By using the geometrical trans lipid library derived from in vitro models of thiyl radical-catalyzed isomerization, oleic and arachidonic acid isomers were detected. The statistical significance was evaluated by comparison with an age-matched control group. These results suggest the role of an endogenous free radical isomerization path occurring to membrane unsaturated lipids, complementary to the dietary contribution, which can be involved in the lipid impairment in AEDS. This study contributes to lipidomic research regarding the double bond structure and the influence of a geometrical change of membrane lipids in physiology and diseases.

Excess dietary vitamin E lowers the activities of antioxidative enzymes in erythrocytes of rats fed salmon oil.

In vitro studies suggest that high vitamin E supplementation has prooxidative activity, but very few studies have investigated this effect in vivo. We investigated the effect of excess vitamin E on the antioxidative status of rat erythrocytes and indicators of hemolysis. Six groups of growing male Sprague-Dawley rats were fed purified diets with three different vitamin E doses [100, 1000 and 10,000 mg all-rac-alpha-tocopheryl acetate (TA)/kg diet] and two different dietary fats (salmon oil and lard) for 8 wk. The rats whose diet contained salmon oil and 10,000 mg TA/kg had lower activities of superoxide dismutase (P < 0.05), glutathione peroxidase (P < 0.05), catalase (P < 0.05) and glucose-6-phosphate dehydrogenase (P < 0.05) and a lower concentration of glutathione (P < 0.05) in the erythrocyte cytosol than rats whose diet contained 100 mg TA/kg. The concentration of free hemoglobin and the binding capacity of haptoglobin in plasma, both indicators of in vivo hemolysis, did not differ between rats fed the salmon oil diet with 100 or 10,000 mg TA/kg. In the rats whose diet contained lard, the activities of antioxidant enzymes in erythrocytes and indicators of in vivo hemolysis were independent of the dietary vitamin E concentration. The results of the study suggest that an excessive vitamin E intake, when combined with salmon oil in the diet, lowers the activities of antioxidant enzymes in erythrocytes without affecting in vivo hemolysis.

[Changes in lipid metabolism in platelet membranes in patients with ischemic heart disease following meals with animal and vegetable fats]. / Izmeneniia okiclitel'nogo metabolizma lipidov v membranakh trombotsitov u bol'nykh ishemicheskoi bolezn'iu serdtsa posle pishchevykh nagruzok zhivotnym i rastitel'nym zhirom.

AIM: To evaluate changes in oxidative lipid metabolism in platelet membranes by content of lipid peroxidation (LPO) products and antioxidant defense (AOD) activity in patients with stable chronic ischemic heart disease (IHD) after single intake of animal fat or vegetable oil. MATERIAL AND METHODS: 30 IHD patients with stable angina of effort functional class II-III and 30 healthy controls had a single meal with animal fat or vegetable oil. Before the meal and 6 hours after it tests were performed for LPO activity and AOD in platelet membranes. RESULTS: Patients with stable chronic IHD showed LPO activation and suppressed enzymatic and non-enzymatic AOD. Single animal fat or vegetable oil intake cause insignificant shifts in oxidative platelet metabolism in healthy controls while animal fat in IHD patients activates LPO and promotes accumulation of initial and end peroxidation products in platelet membranes. Vegetable fat in IHD patients suppresses enzyme AOD. CONCLUSION: Animal fat and vegetable oil as a single diet load have a prooxidant effect at the levels of platelet membranes in IHD patients but not in healthy persons.

Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders?

The fatty acid compositions of red blood cell (RBC) phospholipids from a patient with autistic spectrum disorder (ASD) had reduced percentages of highly unsaturated fatty acids (HUFA) compared to control samples. The percentage of HUFA in the RBC from the autistic patient was dramatically reduced (up to 70%) when the sample was stored for 6 weeks at -20 degrees C. However, only minor HUFA reductions were recorded in control samples stored similarly, or when the autistic sample was stored at -80 degrees C. A similar instability in RBC HUFA compositions upon storage at -20 degrees C has been recorded in schizophrenic patients. In a number of other neurodevelopmental conditions, including attention deficit hyperactivity disorder (ADHD) and dyslexia, reduced concentrations of RBC HUFA have been recorded. The extent and nature of these aberrations require further assessment to determine a possible common biochemical origin of neurodevelopmental disorders in general. To facilitate this, a large scale assessment of RBC fatty acid compositions in patients with ASD, and related disorders, should be performed as a matter of urgency. Supplementing cells in culture with the tryptophan metabolite indole acrylic acid (IAA) affected the levels of cellular HUFA and prostaglandin production. Indole acroyl glycine (IAG), a metabolite of IAA excreted in urine, is found in high concentrations in patients with neurodevelopmental disorders including ASD, ADHD, dyslexia, Asperger's syndrome and obsessive compulsive disorder.

Effect of intravenous infusion of omega-3 and omega-6 lipid emulsions on equine monocyte fatty acid composition and inflammatory mediator production in vitro.

The effect of intravenous administration of lipid emulsions enriched with omega-3 (n3) and omega-6 (n6) fatty acids on equine monocyte phospholipid fatty acid composition and the synthesis of inflammatory mediators in vitro was evaluated. In a randomized crossover design, horses were infused intravenously with 20% lipid emulsions containing n3 or n6 fatty acids. Monocytes were isolated from the horses before and 0 h, 8 h, 24 h, and 7 days after lipid infusion. Monocyte fatty acid analysis demonstrated incorporation of the parenteral n3 and n6 fatty acids in monocyte phospholipids immediately after infusion, with changes in the fatty acid composition persisting for up to 7 days after infusion. In vitro production of the inflammatory mediators thromboxane B2/thromboxane B3 (TXB(2/3)) and tumor necrosis factor-alpha (TNFalpha) by peripheral blood monocytes was diminished by n3 lipid infusion and was unchanged or increased by n6 lipid infusion. The results of this study demonstrate that short-term infusions of n3 and n6 fatty acid-enriched lipid emulsions alter the fatty acid composition of equine monocyte phospholipids and modify the inflammatory response of these cells in vitro. These results also support further investigation into the use of parenteral n3 fatty acids as part of the supportive therapy of patients with multiple organ dysfunction (MODS) or systemic inflammatory response syndrome (SIRS).

Dietary long-chain fatty acids and visual response in malnourished nursing infants.

Polyunsaturated fatty acids (PUFAs) derived from essential fatty acids (EFAs) play an important role in prenatal visual and neural development. Protein-energy malnutrition affects PUFA supply, and hence the synthesis of structural lipids during growth. Recently, some physiological studies reported abnormalities in the visual function of formula-fed infants relative to breast-fed infants. The purpose of our study was to assess whether fatty acid composition of the malnourished infant diet modifies the visual function and erythrocyte phospholipid fatty acid composition. Three groups of full-term malnourished infants were selected. Two groups received commercial formulas. One of them supplied linoleic and alpha -linolenic acid: Formula I (FI), and the other supplied, in addition, long-chain PUFAs from n-3 and n-6 series: Formula II (FII). A reference group of breast-fed infants was also enrolled. Visual function was assessed using full-field flash electroretinography, and the erythrocyte phospholipid fatty acid composition was determined by gas-liquid chromatography. Those infants receiving the supplemented formula (FII) exhibited a similar retinal function to that of breast-fed infants. However, normal results were not achieved when infants were fed on the FI formula. In all groups, the results were correlated with the proportion of docosahexaenoic acid in erythrocyte phospholipid fatty acid composition. We conclude that in malnourished infants a nutrient formula enriched with long-chain fatty acids of n-6 and n-3 series could be helpful to achieve an erythrocyte fatty acid pattern and a visual function similar to that obtained in breast-fed infants.

Effect of oxidized fish oil and alpha-tocopherol on the peroxidation of erythrocyte membrane phospholipids in rats.

The effects of dietary oxidized fish oil and alpha-tocopherol on the thiobarbituric acid (TBA) values and phospholipid hydroperoxide levels of the erythrocyte membrane were studied in rats. No significant differences in the TBA values or phospholipid hydroperoxide levels of the membrane were observed between groups fed either oxidized fish oil or control diets. Furthermore, there were no marked differences in these values whether or not the groups were administered diets containing added alpha-tocopherol. These results suggest that the intake of oxidized fish oil and the supplementation with alpha-tocopherol do not influence the level of lipid peroxidation in the erythrocyte membrane.