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Many epidemiological studies have suggested that consumption of green tea may decrease the risk of cancer. The chemopreventive effect of green tea polyphenols (GTP) has been demonstrated through the inhibition of cell proliferation and angiogenesis in cell culture and animal models of breast cancer. Metastasis of breast cancer is the major reason for the high mortality of breast cancer patients and is directly linked to the invasive behavior of breast cancer cells. Cancer metastasis consists of several interdependent processes including cancer cell adhesion, cancer cell migration, and invasion of cancer cells. In this study, we evaluated the effect of GTP on human breast cancer cells, and we show that in addition to inhibiting cell growth, GTP also suppressed the invasive behavior of MDA-MB-231 cells. These anti-invasive effects of GTP were the result of the inhibition of constitutively active transcription factors AP-1 and NF-kappaB, which further suppressed secretion of urokinase plasminogen activator (uPA) from breast cancer cells. Based on these results, it can be hypothesized that GTP treatment resulted in the inhibition of formation of signaling complexes responsible for cell adhesion and migration (uPA, uPA receptor, vitronectin, integrin receptor) and cell invasion (uPA, uPA receptor). Our results indicate that GTP may contribute to the anticancer effects of green tea by inhibiting the invasive behavior of cancer cells. [ABSTRACT FROM AUTHOR]

Military combat and training stress induce immune changes that increase the risk of infection and ultimately influence soldiers' performance and readiness. Strenuous military training/assessment provides a uniform stress and the opportunity to evaluate nutritional strategies to minimize stress-induced immune changes that predispose soldiers to infection. Immunological changes and effects of a novel nutritional immune formula (NNIF) were examined prospectively in a double-blind, controlled study of 200 soldiers attending Special Forces Assessment and Selection School. Immune function was measured by skin delayed-type hypersensitivity, lymphocyte phenotyping, mitogenic proliferative responses, and granulocyte function. Approximately 50% of soldiers completed the study (control, n = 57; NNIF, n = 50). Several stress-induced lymphocyte changes were observed (decreased mitogen-induced proliferation, T and total lymphocytes, and interferon-gamma-producing lymphocytes and increased percentage of neutrophils). NNIF modified several changes, including delayed-type hypersensitivity responses (NNIF, 78%; control, 59%; p < 0.05), increased proportions of helper T cells, activation of B cells, enhanced neutrophil phagocytosis, and attenuation of declines in certain functional subpopulations (i.e., cytotoxic/ suppressor lymphocytes). Soldiers who consumed NNIF experienced less stress-induced immune impairment, thereby lowering the risk of infection. [ABSTRACT FROM AUTHOR]

Background: α-Tocopherol (αT) is essential for fetal development. One study has shown that the human placenta preferentially transfers the natural stereoisomer, RRR -αT. But prenatal supplements generally contain synthetic αT (S-αT)., Objectives: We aimed to determine if umbilical cord plasma is enriched for RRR -αT in racially diverse neonates from both uncomplicated and complicated pregnancies and if cord RRR -αT enrichment is impacted by maternal αT stereoisomer profile., Methods: We measured αT and αT stereoisomers in plasma from a randomly selected subset of 66 predominantly black and Hispanic maternal-fetal pairs from the Camden Study involving control ( n  = 28) and complicated pregnancies ( n  = 38). We collected maternal plasma at study entry (week 16 gestation; w16) and week 28 gestation (w28) and cord plasma at birth., Results: RRR -αT was the predominant stereoisomer in all maternal and cord plasma samples, but S-αT stereoisomers were found in most samples and comprised a high percentage of αT in some maternal-neonate pairs. Cord plasma had a higher percentage RRR -αT ( P  < 0.05) and lower percentage S-αT ( P  < 0.0001) than w28 plasma. Pregnancy status did not impact maternal or cord plasma concentrations of αT, RRR -αT, or S-αT; except plasma from complicated pregnancies was higher in S-αT at w28 than at w16 ( P  < 0.05). Maternal w28 αT did not correlate with cord αT. However, both maternal w28 αT and S-αT positively correlated with both cord S-αT ( r  = 0.340, P  = 0.0049; r  = 0.538, P  < 0.00001) and percentage S-αT ( r  = 0.399, P  = 0.001; r  = 0.786, P  < 0.00001) but negatively correlated with cord percentage RRR -αT ( r = -0.399, P  = 0.0009; r = -0.786, P  < 0.00001)., Conclusions: The proportion of RRR -αT was higher in cord compared with maternal plasma in both uncomplicated and complicated pregnancies. Our data suggest that maternal S-αT raises cord S-αT and decreases the proportion of RRR -αT in the neonatal circulation. Because the bioactivities of RRR -αT and S-αT differ, this warrants future research to determine the importance of our observations to neonatal αT status., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: The Cognitive Ageing, Nutrition and Neurogenesis trial hypothesizes that a combined intervention with long-chain n-3 polyunsaturated fatty acids (n-3) and cocoa flavan-3-ols (FLAV) will mitigate the cognitive decline anticipated to naturally occur over 1 year in older adults., Methods: In a double-blinded, placebo-controlled parallel design, 259 individuals with mild cognitive impairment or subjective memory impairment were randomized to a control or n-3 FLAV group (1.5 g docosahexaenoic acid + eicosapentaenoic acid and 500 mg n-3 FLAV daily) for 12 months. Cognition was measured at 0, 3, and 12 months. The primary end-point is hippocampus-sensitive cognitive function (e.g., number of false-positives on the Picture Recognition Task of the Cognitive Drug Research test battery). Secondary outcomes include additional cognitive measures, brain atrophy and blood flow (assessed by magnetic resonance imaging), vascular function, circulating biomarkers of cardiovascular and cognitive health, gut microflora, red blood cell fatty acid status, and urine flavan-3-ol metabolites., Results: Screening began in 2015, with all baseline visits completed in March 2017. The intervention was finished in March 2018., Discussion: Cognitive Ageing, Nutrition and Neurogenesis aims to identify an effective diet-based intervention to prevent or delay cognitive impairment in cognitively at-risk individuals, which could ultimately contribute to a reduced population burden of dementia., Clinicaltrialsgov: NCT02525198.

With the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n 24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (P<0·05) and baseline adjusted AUC for plasma lutein at 48 and 336 h (P<0·001) as compared with subjects given lutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0-48 and 0-336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Research in the treatment of Crohn's disease (CD) supports anti-inflammatory benefits of n-3 fatty acids from fish oil, prebiotics, and antioxidants. A nutritionally balanced inflammatory bowel disease nutrition formula (IBDNF) enriched with these compounds has the potential to improve nutrition status and disease activity in CD., Methods: This is an open-label pilot study investigating the effects of IBDNF on nutrition status in CD patients. Twenty-eight patients with active CD on stable medication were asked to consume 16 oz of IBDNF/d for 4 months. Nutrition status was assessed with dual-energy X-ray absorptiometry scans and serum micronutrient levels. Disease activity and quality of life were measured using the Crohn's Disease Activity Index (CDAI) and the Inflammatory Bowel Disease Questionnaire (IBDQ)., Results: Twenty patients completed the final visit. After 4 months, there was a significant decrease in plasma phospholipid levels of arachidonic acid with increases in eicosapentaenoic acid (EPA) and docosahexaenoic acid. Ten patients had a final EPA concentration of >2%. There was improvement in fat-free and fat mass in patients with final EPA >2% (P = .014 and P = .05). Vitamin D (25-OH) levels improved in all patients (18.5-25.9 ng/mL, P < .001). Those with EPA >2% had significantly lower CDAI (116 ± 94.5 vs 261.8 ± 86.5; P = .005) and higher IBDQ (179.1 ± 26.6 vs 114.6 ± 35.9, P < .001) compared to those with EPA <2%., Conclusions: IBDNF has the potential to deposit fat-free and fat mass, improve vitamin D status, and improve quality of life in CD patients.

Objectives: To assess whether an experimental nutritional formula (EXP) supports immune function in seniors living in long-term care facilities., Design: Prospective, randomized, double-blind, controlled trial conducted September 2002 through January 2003., Setting: North central Florida nursing homes., Participants: Subjects aged 65 and older (n = 157)., Intervention: Subjects received 240 mL/d of EXP or standard liquid nutrition (CON) for 4 weeks before and 6 weeks after an influenza vaccination., Measurements: Influenza vaccine antibody responses, immunophenotyping, lymphocyte activation, cytokines, and clinical measures (fever, number of prescribed antibiotics)., Results: Ninety-two subjects (n = 40, CON; n = 52, EXP) completed the study. Geometric mean antibody titers were similar between groups, yet the percentage of subjects with H1N1 antibody titers greater than 100 postvaccination was higher in the EXP group than in the CON group (43% vs 23%, P=.047). Similar trends were found for the percentage of subjects (intent to treat) with fourfold increases against the B/Hong Kong component (64% vs 46%, P = .09) or with H3N2 antibody titers of 40 or more (97% vs 89%, P=.06). EXP subjects had higher levels of influenza-activated lymphocytes (CD69+ and CD25+). Cytokine production after mitogen activation was lower in EXP than CON subjects (interleukin (IL)-6: 20+/-3 vs 29+/-3 ng/mL, P = .045; IL-10: 310+/-60 vs 603+/-140 pg/mL, P = .06). Fewer EXP subjects were treated for fever (5% vs 16%, P = .02) or prescribed antibiotics (7 vs 11 new antibiotics/100 days of study, P = .06)., Conclusion: Seniors consuming the EXP formula demonstrated enhanced immune function, indicated by increased influenza vaccine response and lymphocyte activation, less fever, and fewer newly prescribed antibiotics than those consuming a standard ready-to-drink nutritional supplement.

Enteral nutrition is increasingly becoming the standard of care for critically ill patients with the goal of providing nutritional support that prevents nutritional deficiencies and reduces morbidity. Furthermore, the development of nutritional strategies that dampen inflammation is an encouraging advance in the management of patients who have acute respiratory distress syndrome. This article discusses evidence from randomized, controlled studies that the use of a specialized nutritional formula containing eicosapentaenoic acid plus gamma-linolenic acid and elevated antioxidants offer physiologic and anti-inflammatory benefits over standard formulas.

Background & Aims: N-3 fatty acids from fish oil, antioxidants, and short-chain fatty acids (SCFAs) produced during the fermentation of soluble fiber may attenuate inflammation associated with ulcerative colitis (UC). We assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil, fructooligosaccharides, gum arabic, vitamin E, vitamin C, and selenium on disease activity and medication use in adults with mild to moderate UC., Methods: A total of 121 patients with UC and a disease activity index (DAI) from 3-9 on a 12-point scale were block randomized for extent of disease and smoking status. In addition to their usual diet, patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for 6 months. Clinical and histologic responses were assessed at 3 and 6 months or at the final visit. A change in average prednisone use between groups was tested by using a linear mixed-effects model., Results: Eighty-six patients completed the study. Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group (7.3 +/- 1.3; n = 36) compared with the placebo group (6.2 +/- 2.0; n = 50) ( P < .05). Both groups showed significant and similar degree of improvement at 6 months in DAI (-2.5 for oral supplement and -2.8 for placebo) and histologic index (-1.9 for oral supplement vs. -2.0 for placebo). Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over 6 months as compared with the placebo group ( P < .001)., Conclusions: The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with UC.

Dietary supplementation of a high-gamma-linolenic acid canola oil (HGCO) containing approximately 36% (w/w) of gamma-linolenic acid (GLA, 18:3n-6) from the seeds of a genetically transformed canola strain, was assessed for its long-term biological effects. Growing Sprague-Dawley rats (n = 30) were fed a purified AIN93G diet containing 5, 10, or 15% (w/w) of HGCO as the fat source. For comparison, a separate group of rats (n = 10) was given the diet containing 15% (w/w) of borage oil (BO), which contained 22% (w/w) of GLA. After 12 weeks of feeding, the growth, relative organ weights, hematology, and serum biochemistry were found to be similar among rats fed the 5, 10, and 15% HGCO diets. The GLA levels in plasma and liver phospholipids (PL) were also similar. However, the levels of GLA in peripheral tissues (muscle PL and adipose triacylglycerols) were significantly higher in rats fed the 10 and 15% HGCO diets than those fed the 5% HGCO diet. When the above biologic parameters were compared between the 15% HGCO and 15% BO dietary groups, there were no significant differences except for lower final body weights and higher tissue levels of GLA, dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid (20:4n-6) in the 15% HGCO dietary group as compared with the 15% BO dietary group. This is due to a higher GLA content and possibly a more favorable stereospecific distribution of GLA in HGCO. Overall, long-term (12-week) feeding with diets containing up to 15% HGCO resulted in no adverse effects on growth, organ weight, hematology and serum biochemistry as compared to the diet containing 15% BO, suggesting that HGCO may be a safe alternative source of GLA.

Background: We previously showed that enteral feeding of a diet containing eicosapentaenoic acid, gamma-linolenic acid, and elevated antioxidants improved clinical outcomes compared with a control diet in acute respiratory distress syndrome (ARDS) patients. It has been suggested that oxidative stress may overwhelm endogenous antioxidant levels and allow free radicals to further damage lung tissue. Therefore, we determined whether these ARDS patients were under oxidative stress and whether the experimental diet could improve antioxidant status., Methods: Ninety-eight ARDS patients received either the experimental or control diet (minimum of 75% of basal energy expenditure x 1.3) for at least 4 to 7 days. Total radical antioxidant potential (TRAP), lipid peroxide levels (LPO), and plasma antioxidant concentrations were determined at baseline and study days 4 and 7. Sixty-two normal individuals were assessed for reference values., Results: At baseline, ARDS patients had significantly lower plasma beta-carotene, retinol, and alpha-tocopherol, lower TRAP, and higher LPO values compared with normals. After 4 days of feeding, beta-carotene and alpha-tocopherol levels were normalized and significantly increased in the experimental group compared with controls. TRAP and LPO were not significantly different between groups and study day 4 and 7 values were not different from baseline values. Retinol levels increased equally in both groups., Conclusions: Before treatment, ARDS patients were found to be in a state of oxidative stress and had reduced levels of antioxidants. Although enteral nutrition with the experimental diet for at least 4 to 7 days did not reduce oxidative stress as measured, it did restore plasma levels of beta-carotene and alpha-tocopherol to normal or higher levels and appeared to protect ARDS patients from further lipid peroxidation.

Previous research in rats and mice has suggested that gamma-linolenic acid (GLA) derived from borage oil (BO: 23% GLA) may be an appropriate source for increasing levels of long-chain n-6 FA in the developing brain. Recently, transgenic technology has made available a highly enriched GLA seed oil from the canola plant (HGCO: 36% GLA). The first objective of this study was to compare the effects of diets containing equal levels of GLA (23%) from either BO or HGCO on reproduction, pup development, and pup brain FA composition in mice. The second objective was to compare the effects of the HGCO diluted to 23% GLA (GLA-23) with those of undiluted HGCO containing 36% GLA (GLA-36). The diets were fed to the dams prior to conception and throughout pregnancy and lactation, as well as to the pups after weaning. The behavioral development of the pups was measured 12 d after birth, and anxiety in the adult male offspring was assessed using the plus maze. The findings show that despite equivalent levels of GLA, GLA-23 differed from BO in that it reduced pup body weight and was associated with a slight increase in neonatal pup attrition. However, there were no significant effects on pup behavioral development or on performance in the plus maze. An increase in dietary GLA resulted in an increase in brain 20:4n-6 and 22:4n-6, with a corresponding decrease in 22:6n-3. Again, despite their similar levels of GLA, these effects tended to be larger in GLA-23 than in BO. In comparison with GLA-23, GLA-36 had larger effects on growth and brain FA composition but no differences with respect to effects on reproduction and behavioral development. These findings suggest that the HGCO can be used as an alternative source of GLA.

Background: Tocotrienols have been reported to lower LDL-cholesterol and fasting glucose concentrations and to have potent antioxidant effects, but the results are contradictory., Objective: The objective was to study the relative effect of tocotrienol supplements of different compositions (mixed alpha- plus gamma-, high gamma-, or P25-complex tocotrienol) on blood lipids, fasting blood glucose, and the excretion of 8-iso-prostaglandin F(2alpha), a measure of oxidative stress, in healthy hypercholesterolemic men and women., Design: This was a double-blind, randomized, parallel-design study in which subjects (n = 67 men and women) consumed 1 of 3 commercially available tocotrienol supplements or a safflower oil placebo for 28 d. Blood and urine samples were obtained before and after the 28-d supplementation phase for analysis of fasting blood lipids, glucose, tocotrienols and tocopherols, and 8-iso-prostaglandin F(2alpha)., Results: Overall, serum tocotrienols were increased in subjects who consumed tocotrienols, which showed that the putatively active components were absorbed. No significant differences in mean lipid or glucose concentrations were observed among the 4 treatment groups at the end of the 28-d supplementation phase. However, when the values were expressed as a percentage change from the concentrations during the presupplementation run-in phase, LDL cholesterol increased slightly (7 +/- 2%) but significantly (P < 0.05) in the group consuming the mixed alpha- plus gamma-tocotrienol supplement when compared with LDL cholesterol in the group consuming the P25-complex tocotrienol. Neither mean concentrations nor the percentage change in 8-iso-prostaglandin F(2alpha) differed significantly among treatments., Conclusion: Supplementation with 200 mg tocotrienols/d from 3 commercially available sources has no beneficial effect on key cardiovascular disease risk factors in highly compliant adults with elevated blood lipid concentrations.

Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

We have utilized transgenic technology to develop a new source of gamma-linolenic acid (GLA) using the canola plant as a host. The aim of the present study was to compare the growth and fatty acid metabolism in rats fed equal amounts of GLA obtained from the transgenic canola plant relative to GLA from the borage plant. Young male Sprague-Dawley rats (n = 10/group) were randomized and fed a purified AIN93G diet (10% lipid by weight) containing either a mixture of high GLA canola oil (HGCO) and corn oil or a control diet containing borage oil (BO) for 6 wk. GLA accounted for 23%, of the triglyceride fatty acids in both diets. Growth and diet consumption were monitored every 2-3 d throughout the study. At study termination, the fatty acid composition of the liver and plasma phospholipids was analyzed by gas chromatography. The growth and diet consumption of the HGCO group were similar to the BO group. There were no adverse effects of either diet on the general health or appearance of the rats, or on the morphology of the major organs. There was no significant difference between the diet groups for total percentage of n-6 polyunsaturated fatty acids present in either the total or individual phospholipid fractions of liver or plasma. The relative percentage of GLA and its main metabolite, arachidonic acid, in each phospholipid fraction of liver or plasma were also similar between groups. The percentage of 18:2n-6 in liver phosphatidylethanolamine and phosphatidylinositol/serine was higher (P < 0.05) and 22:5n-6 was lower in the HGCO group than the BO group. This finding could be attributed to the higher 18:3n-3 content in the HGCO diet than the BO diet. Results from this long-term feeding study of rats show for the first time that a diet containing transgenically modified canola oil was well-tolerated, and had similar biological effects, i.e., growth characteristics and hepatic metabolism of n-6 fatty acids, as a diet containing borage oil.

Study Objectives: To investigate whether a diet enriched with fish and borage oils, with their high polyunsaturated fatty acid (PUFA) content, alters surfactant composition and function during endotoxemia., Design: Prospective, randomized, blinded, controlled animal study., Setting: Research laboratory at a medical center., Participants: Thirty-six 15- to 25-kg, disease-free, castrated male pigs. DIETS AND MEASUREMENTS: Three groups of pigs (n = 12 per group) were fed for 8 days diets containing either omega-6 fatty acids (FAs) (corn oil; diet A), or omega-3 FAs (fish oil; diet B), or a combination of omega-6 and omega-3 FAs (borage and fish oils; diet C). Eight of 12 pigs in each group received a 0.1-mg/kg bolus of Escherichia coli endotoxin followed by a continuous infusion (0. 075 mg/kg/h). One lung was subsequently isolated ex vivo, and pressure-volume curves were measured. The contralateral lung was lavaged, and surfactant was analyzed for total and individual phospholipids and FA composition. Minimum and maximum surface tension was measured by bubble surfactometry., Results: Pigs fed either diet B or C had increased oleic acid (C(18:1) omega-9), eicosapentaenoic acid (EPA; C(20:5) omega-3), docosahexaenoic acid (C(22:6) omega-3), and total omega-3 and monounsaturated FAs in their surfactant PUFA pools. The relative percentage of linoleic acid (C(18:2) omega-6) and total omega-6 FAs were significantly lower from pigs fed diets B and C compared with diet A. Palmitic acid (C(16:0)) concentrations, the primary FA in surfactant, had a tendency to be lower in pigs fed diets B and C. There were no demonstrable effects on surfactant function or pulmonary compliance., Conclusions: Diets containing EPA or EPA and gamma-linolenic acid altered the PUFA composition of pulmonary surfactant, but without demonstrable effects on surfactant function during porcine endotoxemia.

Objectives: Because vasoactive eicosanoids derived from arachidonic acid present in immune cell phospholipids promote lung inflammation in critically ill patients, novel experimental diets containing eicosapentaenoic acid from fish oil and gamma-linolenic acid from borage oil have been designed to limit arachidonic acid metabolism. However, excess dietary eicosapentaenoic acid impairs superoxide formation and bacterial killing by immune cells. The present study determined whether short-term enteral feeding with diets enriched with either eicosapentaenoic acid alone or in combination with gamma-linolenic acid would modulate alveolar macrophage eicosanoid synthesis without compromising bactericidal function., Design: Prospective, randomized, controlled, blinded study., Setting: University medical center., Subjects: Adult male Sprague-Dawley rats., Interventions: Rats underwent surgical placement of a gastroduodenal feeding catheter and were randomly assigned to receive one of three high-fat (55.2% of total calories), low-carbohydrate diets containing isocaloric amounts of lipids for 4 days. The control diet was enriched with linoleic acid, whereas the two test diets were low in linoleic acid and enriched with either 5 mole % eicosapentaenoic acid alone or in combination with 5 mole % gamma-linolenic acid. Alveolar macrophages were then procured to assess phospholipid fatty acid composition, eicosanoid synthesis after stimulation with endotoxin, superoxide formation and phagocytosis by flow cytometry, and killing of Staphylococcus aureus, Measurements and Main Results: Alveolar macrophage levels of arachidonic acid were significantly (p < .01) lower and levels of eicosapentaenoic and dihomo-gamma-linolenic acids were higher after feeding the eicosapentaenoic and gamma-linolenic acid diet vs. the linoleic acid diet. Ratios of thromboxane B2,/B3, leukotriene B4/B5, and prostaglandin E2/E1 were reduced in the macrophages from rats given either the eicosapentaenoic acid or eicosapentaenoic acid with gamma-linolenic acid diet compared with ratios from rats given the linoleic acid diet. Macrophages from rats given the eicosapentaenoic with gamma-linolenic acid diet released 35% or 24% more prostaglandin E1 than macrophages from rats given either the linoleic acid or the eicosapentaenoic acid diet, respectively. Macrophage superoxide generation, phagocytosis of opsonized zymosan, and killing of S. aureus were similar irrespective of dietary treatment., Conclusion: Short-term enteral feeding with an eicosapentaenoic acid-enriched or eicosapentaenoic with gamma-linolenic acid-enriched diet rapidly modulated the fatty acid composition of alveolar macrophage phospholipids, promoted a shift toward formation of less inflammatory eicosanoids by stimulated macrophages, but did not impair alveolar macrophage bactericidal function relative to responses observed after feeding a linoleic acid diet.

Objectives: Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS., Design: Prospective, multicentered, double-blind, randomized controlled trial., Setting: Intensive care units of five academic and teaching hospitals in the United States., Patients: We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study., Interventions: Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days., Measurements and Main Results: Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015)., Conclusions: The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

Comparison was made between the intestinal absorption and lymphatic transport of a randomly interesterified fish oil and medium-chain triglyceride (MCT) structured triglycerides (STG) vs. the physical mix in rat small intestine following ischemia and reperfusion (I/R) injury. Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both treatment groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 ml of the fish oil-MCT STG or physical mix (7 rats/group) through the gastric tube followed by an infusion of PBS at 3 ml/h for 8 h. Lymph was collected hourly for 8 h. Lymph triglyceride, cholesterol, and decanoic and eicosapentaenoic acids increased rapidly and maintained a significantly higher output (P < 0.01) with STG compared with physical mix in control rats over 8 h. After I/R, lymphatic triglyceride output decreased 50% compared with control. Gastric infusion of STG significantly improved lipid transport by having a twofold higher triglyceride, cholesterol, and decanoic and eicosapentaenoic acids output to lymph compared with its physical mix (P < 0.01). We conclude that STG is absorbed into lymph significantly better than physical mix by both the normal intestine and the intestine injured by I/R.

Short-term (i.e., 3 d) continuous enteral feeding of diets containing eicosapentaenoic (EPA) and gamma-linolenic (GLA) polyunsaturated fatty acids (PUFA) to endotoxemic rats reduces the levels of arachidonic acid (AA) and linoleic acid (LA) in alveolar macrophage (AM) and liver Kupffer and endothelial (K&E) cell phospholipids with attendant decreases in prostaglandin formation by these cells in vitro. Diets that contain alpha-linolenic acid (LNA) as a substrate for endogenous formation of EPA may not be as effective in facilitating these immune cell modifications given the limited activity of delta6 desaturase. In the present study we compared the effectiveness of an LNA-enriched diet vs. an (EPA + GLA)-enriched diet to displace phospholipid AA from AM and liver K&E cells in vivo in endotoxemic rats fed enterally for 3 or 6 d. We determined the fatty acid composition of AM and K&E cell phospholipids by gas chromatography. We found that AM and K&E cells from rats that had received the EPA + GLA diet for 3 d had significantly (P < 0.001) higher mole percentage of EPA and the GLA metabolite, dihomoGLA, than corresponding cells from rats given the LNA diet or a control diet enriched with LA. Rats given the LNA diet had relatively low levels of stearidonic acid, EPA and other n-3 PUFA, while rats given the LA diet had low levels of GLA and dihomoGLA. We conclude that diets enriched with LNA or LA may not be as effective as those enriched with EPA + GLA for purposes of fostering incorporation of EPA or dihomoGLA into and displacement of AA from macrophage phospholipids under pathophysiologic conditions commonly found in acutely septic patients.

n-3 Fatty acids from fish oil and short-chain fatty acids produced from fermentation of oligosaccharides may attenuate a portion of gut injury and inflammation associated with ulcerative colitis. The purpose of this study was to assess the effects of an enteral nutritional formula containing supplemental oligosaccharides, gum arabic and fish oil on serum metabolite profiles, haematology, plasma and red blood cell membrane phospholipid fatty acid profiles, urinary constituent, and safety in healthy human adult males. 30 subjects were randomly assigned to one of two treatments, a control formula (n = 10) and an ulcerative colitis nutritional formula (UCNF; n = 20). Formulas contained comparable levels of protein, fat and non-structural carbohydrates. Daily intake of the formulas provided nutrients to meet or exceed the recommended daily allowance. Intake was recorded daily while blood and urine samples were collected weekly on days 0, 7 and 14. Certain subjects consuming large quantities of the UCNF experienced some abdominal distention, gas and loose stools. Sole source intake of the UCNF was safe over 14 days as assessed by routine measurements of serum metabolite profiles, haematology and urinalysis compared with subjects fed the control formula. Substantial decreases in plasma and red blood cell phospholipid 18:2n-6 and increases in 20:5n-3 and 22:6n-3 within 1 wk of feeding the UCNF were noted.

Background: The authors compared the effect on eicosanoid production (prostaglandin E2 [PGE2], 6-keto PGF 1 alpha, and thromboxane B2) from peripheral blood mononuclear cells (PBMC) of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid (FOSL-HN) vs an isonitrogenous, isocaloric formula (O-HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies. A previous study, which used the same formulas and experimental design, suggested improved renal and liver function as well as a reduced number of gastrointestinal and infectious complications with the use of fish oil structured lipids. This study sought to investigate the potential mechanism for these effects by assessing eicosanoid production from PBMC with the two diets., Methods: This prospective, blinded, randomized trial was conducted in 20 patients who were jejunally fed either FOSL-HN or O-HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, and eicosanoid production from isolated PBMC, either unstimulated or stimulated with endotoxin, were measured at endotoxin baseline and on day 7. Comparisons were made in 10 and 8 evaluable patients based a priori on the ability to reach a tube feeding rate of > 40 mL/h., Results: Patients receiving FOSL-HN experienced no untoward side effects compared with patients given O-HN and demonstrated the same general trend toward improved hepatic, renal and immune function found in the previous study. There was a significant reduction in PGE2 (p < .03) and 6-keto PGF 1 alpha (p < .01) production from PBMC with endotoxin stimulation in patients receiving FOSL-HN., Conclusions: The results of early enteral feeding with FOSL-HN after surgery in this follow-up study provide further support to claims of safety, tolerance, and improved physiologic function. There was an associated reduction in eicosanoid production from PBMCs, which is presumed to be the principal mechanism for these effects.

Objective: Proinflammatory eicosanoids and cytokines are important mediators of local inflammation in acute lung injury. We determined if enteral nutrition with anti-inflammatory fatty acids, eicosapentaenoic acid, and gamma-linolenic acid would reduce the intrapulmonary synthesis of proinflammatory eicosanoids and cytokines and pulmonary neutrophil accumulation in a rat model of acute lung injury., Design: Prospective, randomized, controlled, double-blind study., Setting: Research laboratory at a university medical center., Subjects: Male Long-Evans rats (250 g)., Interventions: Rats were randomly assigned to three dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day) containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, or 20% fish and 20% borage oil for 21 days. On day 22, bronchoalveolar lavage was performed 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg) or saline. Bronchoalveolar lavage fluid was analyzed for leukotriene B4, leukotriene C4/D4, thromboxane B2, prostaglandin E2, 6 keto-prostaglandin F1alpha, tumor necrosis factor (TNF)-alpha, and macrophage inflammatory protein-2 (MIP-2). Lung myeloperoxidase activity (a marker for neutrophil accumulation) and phospholipid fatty acid composition were also determined., Measurements and Main Results: Lung phospholipid concentrations of arachidonic acid were lower and the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher with fish oil and fish and borage oil as compared with corn oil. Dihomo-gamma-linolenic acid, the desaturated and elongated intermediate of gamma-linolenic acid, increased with fish and borage oil as compared with fish oil and corn oil. The levels of leukotriene B4, leukotriene C4/D4, 6-keto-prostaglandin F1alpha, and thromboxane B2 with corn oil were significantly increased with endotoxin as compared with saline. In contrast to the corn oil group, endotoxin did not significantly increase bronchoalveolar lavage levels of leukotriene B4, leukotriene C4/D4, and thromboxane B2 above those of saline-treated rats with fish oil and fish and borage oil. Lung myeloperoxidase activity was significantly increased in endotoxin-treated rats compared with those rats given saline in all dietary treatment groups. However, lung myeloperoxidase activity was significantly lower with either fish oil or fish and borage oil as compared with corn oil after endotoxin. Although endotoxin increased the levels of TNF-alpha and MIP-2 with all dietary treatment groups as compared with saline-treated rats, there were no significant differences in the levels of either cytokine between the dietary treatment groups., Conclusions: These results indicate that dietary fish oil and fish and borage oil as compared with corn oil may ameliorate endotoxin-induced acute lung injury by suppressing the levels of proinflammatory eicosanoids (but not TNF-alpha or MIP-2) in bronchoalveolar lavage fluid and reducing pulmonary neutrophil accumulation.

Unlabelled: Arachidonic acid (AA) present in lung and liver immune cell phospholipids is the precursor of eicosanoids that promote neutrophil margination, leading to tissue injury and inflammation. Administration of novel enteral formulations low in linoleic acid (LA) and containing eicosapentaenoic acid (EPA) from fish oil and gamma-linolenic acid (GLA) from borage oil displaces AA and promotes cell formation of eicosanoids with reduced inflammatory potential. The present study was undertaken to determine whether or not short-term provision of enteral diets containing GLA, EPA, or both in a cyclic fashion modulated the fatty acid composition of rat alveolar macrophage (AM) and liver Kupffer and endothelial (K&E) cell phospholipids in vivo to the extent achieved during continuous feeding., Methods: Rats were isocalorically fed through a gastrostomy catheter for 3 or 6 days with high-fat, low-carbohydrate diets that were enriched with either LA (diet A), EPA (diet B), or EPA + GLA (diet C). The rats were randomized by infusion modality, ie, continuous vs cyclic (14 hours feeding with 10 hours fasting daily) feeding. AM and K&E were isolated and phospholipid fatty acid profiles were determined by gas chromatography., Results: The dietary effects on AM and K&E cell phospholipid fatty acids for a given feeding period were not significantly influenced by the infusion modality. AM and K&E cells from rats receiving either diet B or diet C for 3 days had significantly lower AA and LA and higher EPA and dihomo-GLA (DHGLA), respectively, than rats given diet A regardless of the infusion modality. The mole % of EPA and DHGLA in K&E cells were higher after 6 vs 3 days of cyclic feeding with diet C. Using the eicosanoid precursor ratio (EPA + DHGLA/AA), the potential for generation of AA-derived eicosanoids was lower in rats given die B or C vs diet A regardless of infusion modality., Discussion: Given the rapid changes in lung and liver immune cell phospholipid fatty acids, short-term provision of EPA and GLA-enriched diets cyclically or continuously may prove clinically relevant for modulating the fatty acid composition and potential eicosanoid formation by these cells.

Objectives: Proinflammatory eicosanoids (cyclooxgenase and lipoxygenase metabolites of arachidonic acid) released by alveolar macrophages play an important role in endotoxin-induced acute lung injury. We investigated the effect of prefeeding rats for 21 days with enteral diets that provided the anti-inflammatory fatty acids, eicosapentaenoic acid and gamma-linolenic acid (derived from fish oil and borage oil, respectively), as compared with an n-6 fatty acid-enriched diet (corn oil) on the following: a) lung microvascular protein permeability, arterial blood pressure, and platelet and white blood cells in a model of endotoxin-induced acute lung injury; b) alveolar macrophage prostaglandin and leukotriene synthesis; and c) liver and alveolar macrophage phospholipid fatty acid composition., Design: Prospective, randomized, controlled, double-blind study., Setting: Research laboratory at a university medical center., Subjects: Male Long-Evans rats, weighing 250 g., Interventions: Rats were randomized into four dietary treatment groups and fed nutritionally complete diets (300 kcal/kg/day), containing 55.2% of the total calories from fat with either 97% corn oil, 20% fish oil, 20% fish and 5% borage oil, or 20% fish and 20% borage oil for 21 days. On day 22, lung microvascular protein permeability, mean arterial pressure, and platelet and white blood cell counts were determined for 2 hrs after an intravenous injection of Salmonella enteritidis endotoxin (10 mg/kg). In a second group of prefed rats, the phospholipid fatty acid composition was determined in liver and alveolar macrophages. Alveolar macrophages were harvested by bronchoalveolar lavage and stimulated in vitro with a calcium ionophore (A23187), and the concentrations of leukotrienes B4 and B5, thromboxane A2, prostaglandin E2, and 6-keto-prostaglandin F1 alpha were measured in a third group of prefed rats., Measurement and Main Results: Lung permeability was greatest with corn oil and was significantly attenuated with 20% fish oil and 20% fish and 5% borage oil, and this effect approached significance with 20% fish and 20% borage oil (p = .06). The early and late hypotensive effects of endotoxin were attenuated with 20% fish oil, 20% fish and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Concentrations of leukotriene B4, prostaglandin E2, and thromboxane B2 released from A23187-stimulated alveolar macrophages were significantly lower with 20% fish oil and 20% fish and 20% borage oil, as compared with corn oil. The increase in lung microvascular protein permeability with 20% fish and 20% borage oil was not significantly different than the lung microvascular protein permeability that was found in animals receiving 20% fish oil (p = .20) and 20% fish and 5% borage oil (p = .31). Alveolar macrophage and liver phospholipid concentrations of arachidonic acid were lower, and the concentrations of eicosapentaenoic acid and docosahexaenic acid were higher, with 20% fish oil, and 5% borage oil, and 20% fish and 20% borage oil, as compared with corn oil. Dihomo-gamma-linolenic acid, the desaturated and elongated intermediate of gamma-linolenic acid, was increased with 20% fish and 20% borage oil, as compared with 20% fish oil and 20% fish and 5% borage oil., Conclusions: The severity of pulmonary microvascular protein permeability and the degree of hypotension were reduced with fish or fish and borage oil diets, as compared with corn oil, in endotoxic rats. The reduced synthesis of the proinflammatory arachidonic acid-derived mediators, leukotriene B4, thromboxane B2, and prostaglandin E2 from stimulated alveolar macrophages was indicative of a decrease in arachidonic acid and an increase in eicosapentaenoic acid and docosahexaenoic acid in cell membrane phospholipids.

Evidence supports a pathogenic role of arachidonic acid-derived inflammatory mediators within the gastrointestinal tract of patients with inflammatory bowel disease. The purpose of this study was to assess the effects of an ulcerative colitis nutritional formula (UCNF) containing oligosaccharides, fish oil, gum arabic and antioxidants on plasma and colonic phospholipid fatty acid and prostaglandin profiles in pigs. Twenty-four growing barrows in two replications were equally randomized among four killing times (d 0, 7, 14 and 21), and one of two diets, a control and the UCNF. Diets contained comparable levels of protein, fat, and nonstructural carbohydrate and met 100% of the energy requirements of the pig. Intake and body weight were recorded daily while blood, urine and tissue samples were collected at time of kill. Within 1 wk of ingestion of the UCNF, the composition of plasma phospholipid fatty acids showed an increase in 20:5(n-3) and 22:6(n-3) (P < 0.0001) and a decrease in 20:4(n-6) and 18:2(n-6) (P < 0.0001). Similar effects were observed for the phospholipids in the colonic and cecal mucosa. Plasma prostaglandin E was unaffected by treatment, whereas thromboxane B2 and 6-keto-prostaglandin F1 alpha levels were significantly decreased after 7 d of UCNF ingestion. Ingestion of the UCNF resulted in a suppression in the synthesis of proinflammatory prostaglandins by cecal and colonic mucosal cells. Levels of colonic and cecal prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were significantly decreased after 7 d of UCNF ingestion. These changes may have been mediated by rapid increases of (n-3) fatty acids into cellular phospholipids. Dietary supplementation with the UCNF may prove beneficial for patients with ulcerative colitis by modulating colonic prostaglandin synthesis.

To evaluate the hypothesis that stimulation of intestinal apolipoprotein (apo) A-IV by dietary fat depends upon assembly and transport of chylomicrons, we examined the effect of duodenal infusion of fatty acids of graded chain length on mucosal synthesis and lymphatic output of lipid and apo A-IV. Rats with duodenal cannulas and mesenteric lymph fistulas were given 8-h duodenal infusions of lipid emulsions containing either butyric (4:0), caprylic (8:0), lauric (12:0), myristic (14:0), stearic (18:0), oleic (18:1), linoleic (18:2) or arachidonic (20:4) acids, or tributyrin, tricaprylin or triolein. Lymph outputs of triglyceride, phospholipid and apo A-IV were measured at 0, 2, 4, 5, 6, 7 and 8 h after the start of lipid infusion. Significant increases in lymph lipid (triglyceride, phospholipid) and apo A-IV output were observed in response to long-chain fatty acids (14:0, 18:0, 18:1, 18:2, 20:4) or triolein; short- or medium-chain fatty acids (4:0, 8:0, 12:0) or tributyrin or tricaprylin produced no significant increase in lymph lipid output above basal levels. Similarly, increased jejunal mucosal synthesis of apo A-IV was observed in response to duodenal infusion of oleic acid but not butyric or caprylic acid. These results provide direct support for the hypothesis that stimulation of apo A-IV by dietary fat depends upon transport of absorbed lipid via chylomicrons in lymph.

: Recent studies have suggested that n-3 fatty acids from fish oil (FO) as well as short-chain fatty acids may attenuate some of the gut injury and inflammationassociated ulcerative colitic (UC). The objectives of this study were to (a) assess the antiinflammatory activity of sulfasalazine (SAZ), a drug known to be effective in the treatment of human UC in a model of chronic granulomatous colitis in rats and (b) determine whether enteral diets supplemented with either FO or two indigestible oligosaccharides (fructooligosaccharide, FOS; xylooligosaccharide, XOS) could attenuate the inflammation observed in a model of chronic granulomatous colitis. In one series of experiments, female Lewis rats were randomized into three groups consisting of a sham-operated control group, a colitic group, and a colitic group in which rats were given oral sulfasalazine (SAZ) immediately after induction of colitis and continued for 3 weeks. Chronic granulomatous colitis with liver and spleen inflammation was induced by subserosal (intramural) injection of purified peptidoglycan-polysaccharide (PG/PS) into the distal colon. Sham-operated rats were injected with human serum albumin. All rats received standard lab chow. In a second series of experiments, female Lewis rats were randomized into six groups consisting of four colitic groups fed enteral diets, a colitic group fed chow, and a sham-operated group fed a control enteral diet. Enteral diets (300 kcal/kg/day) contained either FO, FOS/ gum arabic, XOS/gum arabic, or no bioactive ingredient (control diet). All rats were fed for 1 week before induction of colitis. Rats consumed the diets for 3 additional weeks before being killed. SAZ significantly attenuated the PG/PS-induced increases in myeloperoxidase (MPO) activity as well as significantly reduced the PG/PS-induced increases in liver and spleen weights. Control (enteral diet) as well as the FO and XOS diets significantly attenuated the increase in colon weight when compared with chow-fed rats. We also found that the FO and XOS diets significantly attenuated the PG/PS-induced increases in colonic MPO activity and colon weight. The FOS and XOS diets significantly attenuated the PG/PS-induced increases in liver weights when compared with PG/PS + chow-fed animals. The antiinflammatory activity of these diets was confirmed by means of histological inspection showing an inhibition of inflammation and maintenance of crypt cell integrity. These results demonstrate that a complete enteral diet supplemented with either FO, FOS, or XOS exhibited antiinflammatory activity that was similar in efficacy to the known antiinflammatory drug SAZ in this model of colitis.

Objectives: The authors compared the safety, gastrointestinal tolerance, and clinical efficacy of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid (FOSL-HN) versus an isonitrogenous, isocaloric formula (O-HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies., Summary Background Data: Previous studies suggest that feeding with n-3 fatty acids from fish oil can alter eicosanoid and cytokine production, yielding an improved immunocompetence and a reduced inflammatory response to injury. The use of n-3 fatty acids as a structured lipid can improve long-chain fatty acid absorption., Methods: This prospective, blinded, randomized trial was conducted in 50 adult patients who were jejunally fed either FOSL-HN or O-HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, plasma and erythrocyte fatty acid analysis, urinary prostaglandins, and outcome parameters were measured at baseline and on day 7. Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour., Results: Patients receiving FOSL-HN experienced no untoward side effects, significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids, and a 50% decline in the total number of gastrointestinal complications and infections compared with patients given O-HN. The data strongly suggest improved liver and renal function during the postoperative period in the FOSL-HN group., Conclusion: Early enteral feeding with FOSL-HN was safe and well tolerated. Results suggest that the use of such a formula during the postoperative period may reduce the number of infections and gastrointestinal complications per patient, as well as improve renal and liver function through modulation of urinary prostaglandin levels. Additional clinical trials to fully quantify clinical benefits and optimize nutritional support with FOSL-HN should be undertaken.

We examined the effect of substituting linoleic acid (LA) with eicosapentaenoic acid (EPA) and gamma-linolenic acid (gamma-LA), precursors of trienoic and monoenoic eicosanoids, respectively, on acute lung injury (ALI). Three groups (n = 8/group) of pigs were fed enteral diets containing LA (diet A), EPA (diet B), or EPA+gamma-LA (diet C) for 8 days. ALI was then induced with a 0.1 mg/kg bolus of Escherichia coli endotoxin followed by a continuous infusion for 4 h (0.075 mg.kg-1.h-1). Pulmonary arterial and capillary wedge pressures, cardiac index (CI), arterial blood gases, arterial O2 content, and plasma thromboxane B2 (TxB2) were measured. Arterial PO2 decreased at 20 min in animals fed diet A. This change was attenuated with diets B and C. The EPA- and EPA + gamma-LA-enriched diets attenuated the fall in O2 delivery at 20 min, an improvement that was sustained throughout the 4-h study period with the EPA+gamma-LA-enriched diet only. This improvement in O2 delivery was due not only to the improved arterial PO2, but also to the maintenance of CI at 20 min in animals fed diets B and C and throughout the 4-h study period in animals fed diet C. At 4 h, TxB2 increased 10-fold over baseline in animals fed diet A, whereas in animals fed diets B and C the increase was only 3-fold. These decreased TxB2 levels in animals fed diets B and C correlate with an attenuation in the increase in pulmonary vascular resistance that was observed at 20 min after endotoxin infusion in animals fed diet A. These data suggest that specialized enteral diets enriched in EPA+gamma-LA improve gas exchange and O2 delivery, presumably in part through a modification of TxB2 production with a decrease in pulmonary vascular resistance and an increase in CI, during ALI.

We compared the intestinal absorption of trilinolein (1,2,3-tri-[1-14C]linoleyl-sn-glycerol) with two different structured triglycerides containing one linoleic acid (C18:2) and two octanoic acids (C8:0), 1,3-dioctanoyl-2-[1-14C]linoleyl-sn-glycerol (2-linoleate) and 1,2-di[1-14C]octanoyl-3-linoleyl-sn-glycerol (1,2-octanoate), respectively. Lymphatic radioactive lipid output of 2-linoleate resembled that of trilinolein rats but remained significantly lower during the lipid infusion. Radioactive lipid was recovered along the entire small intestinal lumen, with a significantly higher amount of [14C]lipid recovered in the lower small intestine and cecum in the 2-linoleate group. Delayed uptake of radioactive 2-linoleate was not due to poor digestion. In contrast, 1,2-octanoate was efficiently digested, and both the free fatty acid (FFA) and the monoacylglycerol (MG) containing octanoate were rapidly absorbed. Irrespective of its position on the triglyceride molecule, 14C-labeled octanoate was poorly transported into lymph. In addition, intestinal luminal and mucosal recovery of [14C]octanoate was significantly lower in the 1,2-octanoate group compared with [14C]linoleate recovery in the 2-linoleate or trilinolein groups. Total recovery of infused radioactive lipid was significantly less in the 1,2-octanoate group than in the 2-linoleate or trilinolein groups. Thus radioactive octanoate in the form of FFA or 2-MG was rapidly absorbed and transported via the portal vein. The infusion of either 2-linoleate or 1,2-octanoate did not affect the absorption and lymphatic transport of cholesterol compared with trilinolein. In summary, the type of the fatty acid on the structured triglyceride molecule affects its digestion, absorption, and lymphatic transport. Structured triglycerides containing octanoic acid in the 1- and 3-positions and linoleic acid in the 2-position may not be advantageous to use as a sole source of dietary lipid, but should be supplemented with long-chain triglycerides.

Objective: To study the effect of intravenous lipid emulsions enriched with gamma-linolenic acid on plasma fatty acids and series-2 prostaglandins to determine if the slow conversion of linoleic acid by delta-6-desaturase to gamma-linolenic acid could be bypassed to provide substrate for the formation of dihomo-gamma-linolenic acid, the immediate precursor for series-1 prostaglandins, in control and injured rats. Dihomo-gamma-linolenic acid can also compete with arachidonic acid for oxidative metabolism by cyclooxygenase to modulate series-2 prostaglandin biosynthesis., Design: Prospective, randomized, controlled, double-blind study., Setting: Research laboratory at a university medical center., Subjects: Thirty-three control and thirty-one injured male Sprague-Dawley rats were randomized into one of four parenteral dietary treatment groups., Interventions: Rats were injured by the combined actions of a 30% body surface area full-thickness skin burn and a nonlethal injection of endotoxin (1 mg/kg ip). The rats were parenterally fed 200 kcal/kg/day, 1.5 g nitrogen/kg/day, and 30% of nonprotein calories as lipid (20% soybean lipid emulsion enriched with 2.7%, 4.4%, or 6.1% gamma-linolenic acid derived from borage oil) for 3 days. Control rats were treated similarly but were not injured. A 20% soybean/safflower oil lipid emulsion was used as the control diet (0% gamma-linolenic acid). Plasma was analyzed on day 3 to determine the concentrations of total fatty acids, thromboxane B2, 6-keto-prostaglandin F1 alpha, and bicyclo-prostaglandin E., Measurements and Main Results: Parenteral nutrition with 2.7%, 4.4%, and 6.1% gamma-linolenic acid increased the plasma percentages (mol%) of gamma-linolenic acid and dihomo-gamma-linolenic acid in a dose-dependent fashion in control and injured rats. Supplementation with gamma-linolenic acid did not increase the plasma percentage of arachidonic acid as compared with the 0% gamma-linolenic acid lipid emulsion in control and injured rats. The ratio of dihomo-gamma-linolenic acid to arachidonic acid was significantly increased in response to 4.4% and 6.1% gamma-linolenic acid in both the control and injured groups. The plasma ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha was substantially reduced with gamma-linolenic acid compared with 0% gamma-linolenic acid in injured rats. Bicyclo-prostaglandin E concentration was significantly higher with 2.7% gamma-linolenic acid in injured rats. Injured rats were protein catabolic, as evidenced by a net negative nitrogen balance and loss of body mass compared with controls, but neither group showed overt signs of intolerance to the diets., Conclusions: Supplementation of parenteral nutrition with gamma-linolenic acid had the following effects: a) increased plasma gamma-linolenic acid, dihomo-gamma-linolenic acid, and bicyclo-prostaglandin E; b) increased the plasma ratio of dihomo-gamma-linolenic acid to arachidonic acid; and c) favorably reduced the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha in injured rats. These results reflect the potential capacity of gamma-linolenic acid-enriched lipid emulsions to have the following actions: a) to increase dihomo-gamma-linolenic acid, which is the fatty acid precursor of the antiaggregatory, anti-inflammatory eicosanoid, prostaglandin E1; and b) to modulate arachidonic acid-derived series-2 prostaglandins after injury.

The use of xylitol as an alternative carbohydrate calorie source in total parenteral nutrition may offer unique pharmacologic and nutritional properties in the therapy of the thermally injured. Male Sprague-Dawley rats (250 g) received a 15-second dorsal scald injury (25-30% BSA) and were parenterally fed isovolemic diets (60 ml/day) that provided 200 kcal/kg/d, 9.68 g of amino acids/kg/d, and 23.5% nonprotein calories (NPC) as fat for 3 days. The balance of NPC were provided as dextrose (Dex) or 50% xylitol:50% dextrose (Xyl/Dex). Rectus muscle and liver fractional protein synthetic rates (FSR, %/day), whole body leucine appearance (Flux), oxidation (OX), protein breakdown (PB), and synthesis (PS) were estimated using a 4-hour iv infusion of [1-14C]leucine on day 3. Mean values (+/- SE) for leucine kinetics (mumol leucine/hr/100 g), cumulative nitrogen balance (mg N) and plasma insulin concentration (Table I). (microU/mL). The partial replacement of dextrose calories with xylitol did not significantly alter whole body and tissue leucine kinetics, daily and cumulative nitrogen balance, insulin concentration, and energy expenditure (indirect calorimetry). These data indicate that xylitol may be useful as an alternative carbohydrate calorie source in parenteral nutrition to avoid possible deleterious side effects of glucose overfeeding in the critically ill but did not improve protein metabolism under the conditions of this study.

At the levels to which human beings are exposed in the workplace as well as in the general environment, lead has been shown to be a toxic element in most of its chemical forms, whether it is inhaled or ingested in water or food. The four main sources of contamination of food are soil, industrial pollution, agricultural technology and food processing. Reasonable quantities of the metal can be stored by humans in a relatively inert form in bone; lead has an affinity for bone and acts by replacing calcium. Gastrointestinal lead absorption and retention, the major pathway of lead intake, has been shown to vary widely depending on the chemical environment of the gastrointestinal lumen, age and iron stores (nutritional status of the subject). Studies in animals have shown that certain substances bind lead and increase its solubility, thus enhancing its absorption. These dietary components consist of sodium citrate, ascorbate, amino acids, vitamin D, protein and fat, and lactose. Data suggest a three-compartmental pool for lead metabolism: (1) blood; (2) soft tissue (hair, nails, sweat, salivary, gastric, pancreatic and biliary secretions); and (3) skeleton. Lead absorption occurs primarily in the duodenum where lead enters the epithelial mucosal cells. The total bodily amount of lead does not affect lead absorption; lead does not have a feedback mechanism which limits absorption. In the adult rat, lead absorption from the intestinal lumen appears to proceed by both active transport and passive diffusion. Bile is an important route of excretion in the gut.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of burn and first-pass splanchnic leucine extraction (FPE) on protein kinetics and energy expenditure were assessed by measuring O2 consumption, CO2 production, nitrogen balance, leucine kinetics, and tissue fractional protein synthetic rates (FSR-%/day) in enterally fed rats. Anesthetized male rats (200 g) were scalded on their dorsum with boiling water (25-30% body surface area) and enterally fed isovolemic diets that provided 60 kcal/day and 2.4 g of amino acids/day for 3 days. Controls were not burned. An intravenous or intragastric infusion of L-[1-14C]leucine was used to assess protein kinetics on day 3. FPE was taken as the ratio of intragastric to intravenous plasma leucine specific activity. There was a 69% reduction in cumulative nitrogen balance (P less than 0.001) and a 17-19% increase in leucine oxidation (P less than 0.05) and total energy expenditure (P less than 0.01) in burned rats. A 15% decrease in plasma leucine clearance (P less than 0.05) was accompanied by a 20% increase in plasma [leucine] (P less than 0.01) in burned rats. Burn decreased rectus muscle FSR from 5.0 +/- 0.4 to 3.5 +/- 0.5 (P less than 0.05) and increased liver FSR from 19.0 +/- 0.5 to 39.2 +/- 3.4 (P less than 0.01). First pass extraction of dietary leucine by the splanchnic bed was 8% in controls and 26% in burned rats. Leucine kinetics corrected for FPE showed increased protein degradation with burn that was not evident without FPE correction. This hypermetabolic burn model can be useful in the design of enteral diets that optimize rates of protein synthesis and degradation.

We assessed the effects of total enteral nutrition with long-chain triacylglycerides (LCT), medium-chain triacylglycerides (MCT), or two structured lipids, modified dairy fat (MDF) and modified MCT (Captex 810B, Capital City Products, Columbus, OH), on protein and energy metabolism in hypermetabolic burned rats (25% to 30% body surface area). Male Sprague-Dawley rats (200 +/- 10 g) were continuously gastrostomy-fed isovolemic diets that provided 50 kcal/d, 2 g amino acids/d and 40% nonprotein calories as lipid for three days. Changes in body weight, nitrogen balance, serum albumin, indirect calorimetry, whole body leucine kinetics, and rectus muscle and liver protein kinetics were determined. Whole body leucine kinetics and tissue fractional protein synthetic rates (FSR, percent per day) were estimated using a four-hour constant intravenous infusion of L-[1-14C]leucine on day 3. The group of rats enterally fed MDF lost less body weight than the other groups (P less than or equal to .05). MDF and Captex 810B produced a positive and significantly greater (P less than or equal to .05) daily and cumulative nitrogen balance than either LCT or MCT. Oxygen consumption (P less than or equal to .05) and total energy expenditure (P less than or equal to .05) were elevated approximately 22% with MDF as compared with LCT or MCT. Rectus muscle FSR and absolute rate of protein synthesis were increased 19% with MDF (P less than or equal to .05) as compared with LCT or MCT.(ABSTRACT TRUNCATED AT 250 WORDS)

The amino acid composition of all collagen types present in the gastrocnemius muscle of dystrophic chick embryos showed an altered profile at both day 14 and day 20 in ovo when compared with the controls. The changes observed at both day 14 and day 20 in ovo suggests that there is a removal of polar side-chains in dystrophic collagen and substitution with non-polar amino acids. The amino acid composition data between day 14 and day 20 indicated: (a) a decrease in hydroxylation (hydroxyproline and hydroxylysine) with a concurrent increase in proline and lysine and a decrease in the levels of arginine; (b) the levels of glycine and alanine did not change with age; and (c) the ratios of glycine to hydroxyproline and proline to hydroxyproline changed significantly in all dystrophic collagen types between day 14 and day 20. Contrast analysis results clearly showed that the changes in amino acid composition observed in each dystrophic type of collagen between day 14 and day 20 were not due to the effect of aging but to some other factor(s). This study provides more evidence that a problem lies in the biosynthesis of collagen present in developing muscles of dystrophic chick embryos, particularly with respect to the transcription or translation of procollagen genes and/or a failure in the processing and differentiation of collagen types.

The amino acid composition data on types I, III, IV and V collagen isolated from embryonic dystrophic skeletal muscle strongly indicate that alterations in collagen synthesis occur in intramuscular connective tissue of developing muscles in embryonic dystrophic chickens. The changes observed in the amino acid composition of dystrophic collagen were: (a) a selective removal of polar amino acids and substitution with non-polar amino acids; (b) significant decreases in basic (lysine, hydroxylysine and arginine) and hydroxylated (4-hydroxyproline and hydroxylysine) amino acids; and (c) significant increases in the amounts of glycine, proline and alanine. The amino acid substitutions suggest a genetic alteration in the collagen synthesizing process and a change in its structure. The variations in amino acid composition of collagen from dystrophic chickens could give rise to a decrease in both inter- and intramolecular cross-linking, thus decreasing the stability and functionality of newly formed collagen fibrils. The differences associated with the dystrophic collagen reported in this study are probably due to the differences in primary structure in terms of amino acid sequence rather than post-translational modifications. The structural differences noted would also lead to an alteration of the role collagen plays in regulating the differentiation of developing muscles. The changes in amino acid structure strongly suggest that the 'collagen' formed by dystrophic chickens should be considered a collagen-like protein or 'collagenoid'.

Donor pretreatment with antilymphocyte serum (ALS) effectively prevents graft-versus-host disease (GVHD) in a unidirectional (parent-to-F1 hybrid) rat small bowel transplantation model. ALS must be administered prior to or at the time of transplantation, and the intraperitoneal route is more effective than subcutaneous administration. Donor pretreatment with ALS uniformly prevents GVHD without impairing subsequent allograft function as measured by absorption of dietary energy and nitrogen, weight gain, and bowel morphology. These rodent studies suggest that ALS treatment of donors as well as recipients in small bowel transplantation may be a highly effective, simple, and easily applicable method to prevent or ameliorate GVHD in human small bowel transplantation.

There were marked differences between the levels of collagen (measured as hydroxyproline) and mucopolysaccharides (measured as hexosamine) found in embryonic chicks with genetic muscular dystrophy and their normal controls. The chief differences were that the dystrophic tissues (gastrocnemius muscle and tendon, pectoralis major and skin) had: (a) greater amounts of hexosamine early in embryonic development; (b) hydroxyproline levels that rose at a faster rate, yielding different slopes than their normal controls; (c) relatively greater amounts of hydroxyproline than hexosamine later in embryonic life (day 20). Connective tissue systems in muscles were preferentially affected. The connective tissue system associated with dystrophic tissues appeared to lag behind the normal rhythm pattern of embryological development. The changes in connective tissue metabolism observed in dystrophic chicks suggested that the collagen from dystrophic embryonic chicks may be of a different structure or composition than that found in the normals.

The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response.

The effect of total enteral nutrition with structured and conventional lipids on protein and energy metabolism was assessed in gastrostomy-fed burned rats (30% body surface area) by measuring nitrogen balance, serum albumin, energy expenditure, and rectus muscle and liver fractional synthetic rates of protein (FSRs). Male Sprague-Dawley rats weighing 200 +/- 10 g received isovolemic diets that provided 50 kcal/d, 2 g/d amino acids, and 40% nonprotein calories as lipid for 3 d. The lipid source was either long-chain triglycerides (LCTs), medium-chain triglycerides (MCTs), structured lipid (SL), or a physical mix (PM) of the oils used in SL. Burned rats enterally fed either SL (p less than 0.01) or PM (p less than 0.05) yielded significantly higher daily and cumulative nitrogen balances and rectus muscle and liver FSRs than those fed either LCTs or MCTs. Rats fed SL or MCTs maintained higher serum albumin concentrations than rats fed either PM or LCTs. This study shows that the enteral administration of a mixed fuel system containing SL or its PM improves protein anabolism and attenuates net protein catabolism after thermal injury.