Effect of olive oil-based emulsion on human lymphocyte and neutrophil death

Background The incorporation of lipid emulsions in parenteral diets is a requirement for energy and essential fatty acid supply to critically ill patients. The most frequently used IV lipid emulsions (LE) are composed with long-chain triacylglycerols rich in omega-6 polyunsaturated fatty acids (PUFA) from soybean oil, but these LE promote lymphocyte and neutrophil death. A new emulsion containing 20% soybean oil and 80% olive oil rich in (omega-9 monounsaturated fatty acids (MUFA) has been hypothesized not to cause impairment of immune function. In this study, the toxicity of an olive oil-based emulsion (OOE) on lymphocytes and neutrophils from healthy volunteers was investigated. Methods: Twenty volunteers were recruited and blood was. collected before a 6-hour infusion of an OOE, immediately after infusion, and again 18 hours postinfusion. Lymphocytes and neutrophils were isolated by gradient density. The cells were studied immediately after isolation and after 24 hours or 48 hours in culture. The following determinations were carried out: triacylglycerol levels and fatty acid composition and levels in plasma, lymphocyte proliferation, production of reactive oxygen species, and parameters of lymphocyte and neutrophil death (viability, DNA fragmentation, phosphatidylserine externalization, mitochondrial depolarization, and neutral lipid accumulation). Results: OOE decreased lymphocyte proliferation, provoked lymphocyte necrosis, and had no effect on the proportion of viable neutrophils. The mechanism of cell death induced by OOE involved neutral lipid accumulation but had no effect on mitochondrial membrane depolarization. Conclusions: The OOE given as a single dose of 500 mL induced low toxicity to lymphocytes from healthy volunteers, probably by necrosis.

Effect of medium/omega-6 long chain triglyceride-based emulsion on leucocyte death and inflammatory gene expression

Lipid emulsion (LE) containing medium/omega-6 long chain triglyceride-based emulsion (MCT/omega-6 LCT LE) has been recommended in the place of omega-6 LCT-based emulsion to prevent impairment of immune function. The impact of MCT/omega-6 LCT LE on lymphocyte and neutrophil death and expression of genes related to inflammation was investigated. Seven volunteers were recruited and infusion of MCT/omega-6 LCT LE was performed for 6 h. Four volunteers received saline and no change was found. Blood samples were collected before, immediately afterwards and 18 h after LE infusion. Lymphocytes and neutrophils were studied immediately after isolation and after 24 and 48 h in culture. The following determinations were carried out: plasma-free fatty acids, triacylglycerol and cholesterol concentrations, plasma fatty acid composition, neutral lipid accumulation in lymphocytes and neutrophils, signs of lymphocyte and neutrophil death and lymphocyte expression of genes related to inflammation. MCT/omega-6 LCT LE induced lymphocyte and neutrophil death. The mechanism for MCT/omega-6 LCT LE-dependent induction of leucocyte death may involve changes in neutral lipid content and modulation of expression of genes related to cell death, proteolysis, cell signalling, inflammatory response, oxidative stress and transcription.

Cell activation state influences the modulation of HLA-DR surface expression on human monocytes/macrophages by parenteral fish oil lipid emulsion

Abnormal surface expression of HLA-DR by leukocytes is associated with a poor prognosis in critical care patients. Critical care patients often receive total parenteral nutrition with lipid emulsion (LE). In this study we evaluated the influence of fish oil LE (FO) on human monocyte/macrophage (M phi) expression of surface HLA-DR under distinct activation states. Mononuclear leukocytes from the peripheral blood of healthy volunteers (n = 18) were cultured for 24 hours without LE (control) or with 3 different concentrations (0.1, 0.25, and 0.5%) of the follow LE: a) pure FO b) FO in association (1:1 v/v) with LE composed of 50% medium-chain trygliceride and 50% soybean oil (MCTSO), and c) pure MCTSO. The leukocytes were also submitted to different cell activation states, as determinate by INF-gamma addition time: no INF-gamma addition, 18 hours before, or at the time of LE addition. HLA-DR expression on M phi surface was evaluated by flow cytometry using specific monoclonal antibodies. In relation to controls (for 0.1%, 0.25%, and 0.5%: 100) FO decreased the expression of HLA-DR when added alone [in simultaneously-activated M phi, for 0.1%: 70 (59 +/- 73); for 0.25%: 51 (48 +/- 56); and for 0.5%: 52.5(50 +/- 58)] or in association with MCTSO [in simultaneously-activated M phi, for 0.1%: 50.5 (47 +/- 61); for 25%: 49 (45 +/- 52); and for 05 %: 51 (44 +/- 54) and in previously-activated M phi, for 1.0 % : 63 (44 +/- 88); for 0.25%: 70 (41 +/- 88); and for 0.5%: 59.5 (39 +/- 79)] in culture medium (Friedman p<0.05). In relation to controls (for 0.1%, 0.25%, and 0.5%: 100), FO did not influence the expression of these molecules on non-activated M phi [for 0.1 % : 87.5 (75 +/- 93); for 0.25%: 111 (98 +/- 118); and for 0.5%: 101.5 (84 +/- 113)]. Results show that parenteral FO modulates the expression of HLA-DR on human M phi surface accordingly to leukocyte activation state. Further clinical studies evaluating the ideal moment of fish oil LE infusion to modulate leukocyte functions may contribute to a better understanding of its immune modulatory properties.

Anti-inflammatory effect of parenteral fish oil lipid emulsion on human activated mononuclear leukocytes

Background & aim: To compare the effect of fish oil-based (FO) lipid emulsions (LE) for parenteral administration with standard LE and a new FO containing LE composed of four different oils on the antigen presentation and inflammatory variables. Methods: Phytohemagglutinin (PHA) activated human mononuclear leukocytes were cultured with different LE - Control: without LE; SO: soybean oil; SO/FO: soybean and FO (4:1); MCT/SO: medium chain triglycerides and SO (1:1); MCT/SO/FO: MCT/SO and FO (4:1) and SMOF: a new LE containing FO. Cytokine production was evaluated by ELISA, the expression of antigen-presenting and co-stimulatory surface molecules were analyzed by flow cytometry and lymphocyte proliferation was assessed by H(3)-Thymidine incorporation, after tetanus toxoid-induced activation. Results: All LE decreased the HLA-DR and increased CD28 and CD152 expression on monocytes/macrophages and lymphocytes surface (p < 0.05). SO/FO and MCT/SO/FO decreased lymphocyte proliferation (p<0.05). All LE decreased IL-2 product ion, but this effect was enhanced with MCT/SO/FO and SMOF (p < 0.05). MCT/SOTO decreased IL-6 and increased IL-10, whereas SO had the opposite effect (p < 0.05). Conclusion: FO LE inhibited lymphocyte proliferation and had an anti-inflammatory effect. These effects seem to be enhanced when FO is mixed with MCT/SO. SMOF had a neutral impact on lymphocyte proliferation and IL-6 and IL-10 production.

The exponentiated generalized inverse Gaussian distribution

The modeling and analysis of lifetime data is an important aspect of statistical work in a wide variety of scientific and technological fields. Good (1953) introduced a probability distribution which is commonly used in the analysis of lifetime data. For the first time, based on this distribution, we propose the so-called exponentiated generalized inverse Gaussian distribution, which extends the exponentiated standard gamma distribution (Nadarajah and Kotz, 2006). Various structural properties of the new distribution are derived, including expansions for its moments, moment generating function, moments of the order statistics, and so forth. We discuss maximum likelihood estimation of the model parameters. The usefulness of the new model is illustrated by means of a real data set. (c) 2010 Elsevier B.V. All rights reserved.