Review of Infant Feeding: Key Features of Breast Milk and Infant Formula.

Mothers' own milk is the best source of nutrition for nearly all infants. Beyond somatic growth, breast milk as a biologic fluid has a variety of other benefits, including modulation of postnatal intestinal function, immune ontogeny, and brain development. Although breastfeeding is highly recommended, breastfeeding may not always be possible, suitable or solely adequate. Infant formula is an industrially produced substitute for infant consumption. Infant formula attempts to mimic the nutritional composition of breast milk as closely as possible, and is based on cow's milk or soymilk. A number of alternatives to cow's milk-based formula also exist. In this article, we review the nutritional information of breast milk and infant formulas for better understanding of the importance of breastfeeding and the uses of infant formula from birth to 12 months of age when a substitute form of nutrition is required.

Eucaloric Ketogenic Diet Reduces Hypoglycemia and Inflammation in Mice with Endotoxemia.

Dietary strategies to alter the immune response to acute inflammation have the potential to improve outcomes in critically ill patients. A eucaloric ketogenic diet (EKD), composed predominantly of fat with very small amounts of carbohydrate, can provide adequate caloric support while minimizing spikes in blood glucose and reducing oxidative stress. The purpose of this study was to evaluate the effects of an EKD on glycemic control and the inflammatory response after acute endotoxemia in mice. Mice received either an EKD or a carbohydrate-based control diet (CD) for 4 weeks. Animals subsequently underwent either a 2-h fast (postprandial) or an overnight fast (postabsorptive), and half of the animals in each diet group were randomized to receive either intraperitoneal lipopolysaccharide (1 mg/kg) or an equivalent volume of saline. Glycemic response, insulin resistance, inflammatory cytokine levels, and the expression of key inflammatory and metabolic genes were measured. After endotoxin challenge, hypoglycemia was more frequent in mice fed a CD than an EKD in the postprandial period. This was due in part to the preservation of hepatic glycogen stores despite endotoxin exposure and prolonged fasting in mice fed an EKD. Furthermore, mice fed the CD had higher levels of IL-6 and TNF-α in the postabsorptive period, with a fivefold higher expression of hepatic NFκB compared to mice fed the EKD in both fasting periods. These results suggest that the unique metabolic state induced by an EKD can alter the response to acute inflammation in mice.

Purified fish oil eliminating linoleic and alpha linolenic acid meets essential fatty acid requirements in rats.

This study examined whether purified fish oil (PFO) supplemented to an essential fatty acid deficient (EFAD) diet meets EFA needs in rats. The EFAD diet contained 10% hydrogenated coconut oil (HCO). A similar diet contained 7% HCO and 3% PFO which also provided 2.84% arachidonic acid (AA), 52.50% eicosapentaenoic acid (EPA) and 35.73% docosahexaenoic acid (DHA) but no linoleic acid (LA) or alpha linolenic acid (ALA). A 10% soybean oil control diet provided ample LA and ALA. After 4 weeks of feeding, blood glucose, plasma triglyceride and phospholipid fatty acid profiles, C-reactive protein (CRP), TNF and IL-6 were determined after saline or LPS injection. EFAD developed with the HCO diet with triene:tetraene ratios in plasma phospholipids >.20, which remained <.02 with the control and HCO+PFO diets. Mead acid levels significantly increased by a factor of 10 with the HCO diet compared to the AIN and HCO+PFO diets and were significantly lowest with the HCO+PFO diet. 18:1 n9 levels were significantly higher in plasma phospholipids and triglycerides with the HCO diet. CRP levels were significantly highest with the control diet and significantly lowest with the HCO diet. LPS significantly increased 18:1 n9 and cytokines, and decreased AA and plasma glucose in all diets and significantly increased plasma triglycerides and decreased plasma glucose in controls. Providing AA, EPA and DHA in EFAD prevents EFAD over the short-term as reflected in Mead acid production, triene:tetraene ratio, and de novo lipogenesis and may reduce the inflammatory response to LPS.

Arachidonic acid and docosahexaenoic acid supplemented to an essential fatty acid-deficient diet alters the response to endotoxin in rats.

This study examined fatty acid profiles, triene-tetraene ratios (20:3n9/20:4n6), and nutritional and inflammatory markers in rats fed an essential fatty acid-deficient (EFAD) diet provided as 2% hydrogenated coconut oil (HCO) alone for 2 weeks or with 1.3 mg of arachidonic acid (AA) and 3.3 mg of docosahexaenoic acid (DHA) (AA + DHA) added to achieve 2% fat. Healthy controls were fed an AIN 93M diet (AIN) with 2% soybean oil. The HCO and AA + DHA diets led to significant reductions of linoleic acid, α-linolenic acid, and AA (20:4n6) and increases in Mead acid (20:3n9) in plasma and liver compared with the AIN diet; but the triene-tetraene levels remained well within normal. However, levels of 20:3n9 and 20:4n6 were lower in liver phospholipids in the AA + DHA than in HCO group, suggesting reduced elongation and desaturation in ω-9 and -6 pathways. The AA + DHA group also had significantly lower levels of 18:1n9 and 16:1n7 as well as 18:1n9/18:0 and 16:1n7/16:0 than the HCO group, suggesting inhibition of stearyl-Co A desaturase-1 activity. In response to lipopolysaccharide, the levels of tumor necrosis factor and interleukin-6 were significantly lower with HCO, reflecting reduced inflammation. The AA + DHA group had higher levels of IL-6 and C-reactive protein than the HCO group but significantly lower than the AIN group. However, in response to endotoxin, interleukin-6 was higher with AA + DHA than with AIN. Feeding an EFAD diet reduces baseline inflammation and inflammatory response to endotoxin long before the development of EFAD, and added AA + DHA modifies this response.

Effects of glucose or fat calories in total parenteral nutrition on fat metabolism and systemic inflammation in rats.

This study compared the effects of total parenteral nutrition (TPN) by central vein with or without fat provided at maintenance energy requirement on fatty acid metabolism, de novo lipogenesis, and the risk of hepatic and systemic inflammation in rats. Study 1 was conducted in 2 groups: high glucose (HG), where fat-free TPN was given at maintenance levels of 180 kcal/(kg d), and low glucose (LG), where fat-free TPN containing 30% fewer calories at 126 kcal/(kg d) was provided by reducing 54 kcal/(kg d) from parenteral glucose. Study 2 contained 3 TPN groups: 1 LG group at 126 kcal/(kg d) and 2 groups at 180 kcal/(kg d) with 30% of total calories (54 kcal/[kg d]) either from soybean or fish oil emulsion. In both studies, animals fed a chow diet ad libitum were included. Plasma and hepatic triglyceride and phospholipid fatty acid profiles, enzymes indicating hepatic injury, and C-reactive protein levels (CRP) reflecting systemic injury were measured. In study 1, evidence of de novo lipogenesis was noted in LG and was more prominent in HG with elevation of CRP in HG. In study 2, de novo lipogenesis was reduced by adding either fat to LG to achieve maintenance energy levels. Moreover, adding fat as soybean oil but not fish oil significantly increased plasma and hepatic triglyceride and also elevated aspartate aminotransferase and CRP levels, reflecting inflammation. Thus, in rats, either hypocaloric feeding as glucose-based TPN or TPN provided at maintenance energy levels with the addition of fish oil limits hepatic lipid accumulation and prevents the evidence of hepatic and systemic injury found with maintenance level TPN as glucose only or glucose plus soybean oil.

A simple method of supplementation of omega-3 polyunsaturated fatty acids: use of fortified yogurt in healthy volunteers.

BACKGROUND: A relative dietary ω-3 fatty acid deficiency exists in Western diets, and this deficiency may be associated with some chronic diseases. The aim of the present study was to supplement yogurt with docosahexaenoic acid and assess whether this fatty acid could be incorporated into plasma lipids. METHODS: We developed a stable emulsion of docosahexaenoic acid that was incorporated into yogurt. Twelve healthy volunteers agreed to consume 1 serving daily that contained 600 mg of docosahexaenoic acid. RESULTS: After 3 weeks of supplementation, plasma phospholipid docosahexaenoic acid content increased significantly, by 32%, in parallel with a 16% rise in total ω-3 fatty acids. This result was associated with a significant 7% decline in phospholipid arachidonic acid. CONCLUSIONS: Fortification of ordinary foods with docosahexaenoic acid is a potentially attractive method of increasing ω-3 fatty acid content of plasma lipids, and might even lower arachidonic acid concentrations.

Effect of a fish oil-containing beverage on changes in plasma lipid fatty acids in patients with malabsorption.

BACKGROUND: The aim of this pilot study was to assess tolerance of a beverage containing ω-3 fatty acids (fish oil) in patients with malabsorption receiving chronic parenteral nutrition (PN). The authors wanted to determine whether fish oil could be absorbed and incorporated into plasma fatty acids and reduce markers of inflammation. METHODS: This was a small intervention study in home-dwelling PN-dependent patients with chronic malabsorption. Ten patients were provided a drink containing 1.5 g of fish oil per day for 12 weeks. Baseline and post-supplement serum fatty acid profiles were compared. RESULTS: Five of 10 patients withdrew from the study because of GI side effects, principally worsened diarrhea, associated with the supplement. Modest increases were found in 20:5ω-3, 22:5ω-3, and 22:6ω-3 levels in both phospholipids and triglycerides in plasma (all P < .05). In phospholipids, a reduced arachidonic acid level was seen (P = .02). These changes were not sufficient to effect improvements in serum tumor necrosis factor-alpha (TNFα), soluble TNF receptor, C-reactive protein, or interleukin-6. CONCLUSIONS: Some patients with severe malabsorption can absorb oral ω-3 fatty acid supplements and incorporate these fatty acids into serum phospholipids and triglycerides. However, side effects are very common, and no anti-inflammatory effect was found, presumably related to the modest level of fatty acid change.

Early development of essential fatty acid deficiency in rats: fat-free vs. hydrogenated coconut oil diet.

This study examined the effects of feeding an essential fatty acid deficient (EFAD) diet either without fat or with added hydrogenated coconut oil (HCO) on fatty acid profiles in rats. Both diets induced equivalent biochemical evidence of EFAD reflected by the triene/tetraene ratio in plasma phospholipids within 2 weeks. However, the HCO diet led to larger increases of 16:1n7 and 18:1n9 in muscle but smaller increases in fat tissue and plasma triglycerides than the fat-free diet, suggesting greater increases in hepatic de novo lipogenesis with the latter. In addition, the HCO diet led to larger decreases of some 18:3n3 metabolites, particularly 22:6n3, in muscle, fat and brain tissues than the fat-free diet, presumably related to lesser stimulation of elongation and desaturation. Thus, these secondary effects of an EFAD diet on fatty acid metabolism can be modified by the saturated fat in the diet while the primary impact of both diets on development of EFAD is unaffected.

Effect of a dietary intervention and n-3 fatty acid supplementation on measures of serum lipid and insulin sensitivity in persons with HIV.

BACKGROUND: Elevated serum triglyceride and low HDL-cholesterol concentrations have been reported in persons with HIV. OBJECTIVE: The effect of a dietary intervention plus n-3 (omega-3) fatty acid supplementation on serum triglycerides and markers of insulin sensitivity was investigated. DESIGN: Fifty-four persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or abnormal Quantitative Insulin Sensitivity Check Index values (<0.35 but >0.30) were recruited for a dietary intervention in which total fat, type of fat, fiber, and glycemic load were controlled along with supplementation with n-3 fatty acids to achieve an intake of 6 g/d. The subjects were randomly assigned to an intervention or control group, and serum lipids, markers of insulin sensitivity, and serum phospholipid fatty acids were measured in both groups at baseline, 3 wk, and 13 wk. RESULTS: Triglycerides in the intervention group decreased from a median of 180 mg/dL (interquartile range: 141, 396) to 114 mg/dL (interquartile range: 84, 169) from baseline to 3 wk, whereas they remained stable in the control group (P = 0.003). Serum phospholipid fatty acids indicated a decrease in de novo lipogenesis and a decrease in arachidonic acid (% nmol; P

Pharmacopeial compliance of fish oil-containing parenteral lipid emulsion mixtures: Globule size distribution (GSD) and fatty acid analyses.

Recently, the United States Pharmacopeia (USP) has established Chapter 729 with GSD limits for all lipid emulsions where the mean droplet size (MDS) must be <500 nm and the percent of fat larger than 5 microm (PFAT(5)) must be <0.05%, irrespective of the final lipid concentration. As well, the European Pharmacopeia (EP) Monograph no. 1352 specifies n3-fatty acid (FA) limits (EPA+DHA> or =45%; total n3 or T-n3> or =60%) for fish oil. We assessed compliance with USP physical and EP chemical limits of two fish oil-containing lipid emulsion mixtures. All lipid emulsions passed USP 729 limits. No samples tested had an MDS >302 nm or a PFAT(5) value >0.011%. Only one product met EP limits while the other failed. All emulsions tested were extremely fine dispersions and easily met USP 729 GSD limits. The n3-FAs profiles were lower in one, despite being labeled to contain 50% more fish oil than the other product. This latter finding suggests the n3-FA content of the fish oil source and/or the applied manufacturing processes in these products is different.

Comparison of the effects of food versus protein restriction on selected nutritional and inflammatory markers in rats.

We previously demonstrated that feeding a 2% protein AIN-76 diet ad libitum for 14 days resulted in substantial clinical and biochemical changes including weight loss, hypoglycemia, hypoalbuminemia, higher levels of plasma cytokines, oxidative stress in the liver, and activation of inflammatory signaling to interleukin (IL)-6, as compared with a 20% protein diet. In the present study, 54 rats were randomly given a standard rat chow diet ad libitum, or a 25% or 50% reduction of this intake for 14 days. The results showed that weight gain was less in the 25% food-restricted group and halted in the 50% group as compared with the control group. Unlike protein restriction, neither level of food restriction altered plasma levels of albumin and glucose, the hepatic protein abundance of signal transducers and activators of transcriptions and of mitogen-activated protein kinases, or the hepatic contents of total glutathione and malondialdehyde. The intracellular signaling in response to IL-6 stimulation was also well maintained. However, both levels of food restriction elevated IL-1 and corticosterone in plasma, did not alter ghrelin, and decreased plasma levels of free fatty acids. Because these latter 3 markers were not examined previously, 20 rats were fed an AIN-76 diet, either with 20% or 2% protein, ad libitum for 14 days. The 2% protein diet significantly decreased plasma levels of free fatty acids and increased ghrelin and corticosterone as compared with the 20% protein diet. Thus, food restriction, where all essential nutrients are reduced in proportion, is a physiologic stress that, while limiting growth, does not activate or impair the systemic inflammatory response, whereas a very low protein diet with little change in energy intake has a substantial impact on systemic inflammation, body composition, and growth.

Metabolic syndrome and serum fatty acid patterns in serum phospholipids in hypertriglyceridemic persons with human immunodeficiency virus.

BACKGROUND: HIV infection and its treatment are associated with abnormal lipid profiles. High triglyceride concentrations and low HDL-cholesterol concentrations are the most common health abnormalities and raise concerns about an increased risk of cardiovascular disease. OBJECTIVE: We compared the fatty acid patterns of serum phospholipids between persons with HIV and non-HIV controls to determine whether there are differences that explain the elevated triglyceride concentrations, insulin resistance, and inflammation that are part of the metabolic syndrome in patients with HIV. DESIGN: Thirty-nine persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or indicators of insulin resistance were recruited to examine fatty acid profiles in serum phospholipid fractions relative to those of 2 control groups without HIV (n = 31). RESULTS: Higher concentrations of 16:1 and 18:0 fatty acids in the phospholipid fraction indicated increased lipogenesis in the HIV patients and in the non-HIV controls at risk of the metabolic syndrome. However, the subjects with HIV had higher concentrations of both n-6 (omega-6) and n-3 fatty acids of higher elongation and desaturation levels, which indicated a greater promotion of these pathways in this population. The nanomolar percentage (%nmol) arachidonic acid was the same in all 3 groups. CONCLUSIONS: Persons with and without HIV, at risk of the metabolic syndrome, show indications of increased lipogenesis, more so in subjects with HIV taking medication. Higher proportions of distal elongation and desaturation fatty acid products were seen only in the phospholipids fatty acid fraction of the subjects with HIV.

Hepatic indicators of oxidative stress and tissue damage accompanied by systemic inflammation in rats following a 24-hour infusion of an unstable lipid emulsion admixture.

BACKGROUND: Use of lipid emulsions in parenteral nutrition therapy is an important source of daily energy in substitution of potentially harmful glucose calories when given in excess in the intensive care unit. When added to parenteral nutrition (PN) admixtures as a total nutrient admixture (TNA), the stability and safety of the emulsion may be compromised. Development of a rat model of a stable vs unstable lipid infusion would enable a study of the potential risk. DESIGN: Prospective, randomized, controlled study. METHODS: Surgical placement of a jugular venous catheter for the administration of TNAs was performed. Two groups were studied: a stable or s-TNA (n = 16) and an unstable or u-TNA (n = 17) as a 24-hour continuous infusion. Stability of TNAs was determined immediately before and after infusion using a laser-based method approved by the United States Pharmacopeia. RESULTS: Blood levels of aspartate aminotransferase, glutathione-S-transferase, and C-reactive protein were significantly elevated in u-TNA vs s-TNA (P < .05). Also, liver tissue concentrations of malondialdehyde were significantly higher in the u-TNA group (P < .05), and triglyceride tissue levels were also higher in u-TNA and approached statistical significance (P = .077). CONCLUSIONS: Unstable lipid infusions over 24 hours produce evidence of hepatic accumulation of fat associated with oxidative stress, liver injury, and a low-level systemic inflammatory response.

Fine vs. coarse complete all-in-one admixture infusions over 96 hours in rats: fat globule size and hepatic function.

BACKGROUND & AIMS: The United States Pharmacopeia (USP) has adopted Chapter <729> that set two globule size limits for all lipid emulsions with the mean droplet size at no >500 nm, while large-diameter fat globules as the percent fat>5 microm or PFAT(5) must be <0.05%. A quantitative risk assessment of toxicity from the intravenous infusion of all-in-one (AIO) admixtures made from a lipid emulsion that meets USP standards (fine) vs. one that does not (coarse), was conducted. METHODS: Two separate 96-h infusion studies in rats receiving nutritionally complete AIOs made from a fine (F) vs. a coarse (C) 20% starting lipid emulsion (SLE) with either 18 or 36% as fat calories were performed. The animals were equally divided in each (18% fat, n=18; 36% fat, n=22) to receive AIOs made from F or C lipids. PFAT(5) levels were measured at the outset and every 24h at the change of infusions and blood levels of liver enzymes AST and GST, and serum triglycerides (TG) were measured at the end of study. RESULTS: On average, the starting PFAT(5) values for infusions of F-AIOs were 0.018+/-0.007 (n=48) vs. C-AIOs at 0.183+/-0.026% (n=48), whereas the 24-h average was 0.234+/-0.211% (n=168) vs. 1.033+/-0.224% (n=180), respectively. No significant differences in the blood-based parameters were noted in rats between F-AIOs and C-AIOs in the studies comparing 18 or 36% of fat calories, respectively. When the data were combined into all F- vs. all C-AIOs, AST was significantly higher in C-AIOs (157+/-41) vs. F-AIOs (130+/-37), p=0.036. TG was lower in C (69+/-37) vs. F (106+/-70), nearly reaching statistical significance (p=0.056) with no differences in GST levels for C (21+/-9) vs. F (17+/-9), p=0.199. When stratified according to a PFAT(5) of 0.4%, C-AIOs were significantly higher than F-AIOs for AST (157+/-41 vs. 130+/-37, p=0.004), and TG was significantly lower in C- vs. F-AIOs (67+/-36 vs. 117+/-71, p=0.022), respectively. CONCLUSIONS: Coarse lipid emulsions that fail pharmacopeial limits produce less stable AIOs and are associated with evidence of worsened hepatic injury.

Effects of medium-chain triglycerides, long-chain triglycerides, or 2-monododecanoin on fatty acid composition in the portal vein, intestinal lymph, and systemic circulation in rats.

BACKGROUND: Fatty acid absorption patterns can have a major impact on the fatty acid composition in the portal, intestinal lymph, and systemic circulation. This study sought to determine the effects of long-chain triglycerides (LCT), medium-chain triglycerides (MCT), and 2-monododecanoin (2mono) on intestinal fatty acid composition during continuous feeding over a brief period. METHODS: The lipid sources were 100% LCT, 100% MCT, a 50:50 mixture of LCT and MCT (LCT/MCT), and a 50:50 mixture of LCT and 2mono (LCT/2mono). A total of 27 rats were randomly given 1 of the 4 diets at 200 kcal/kg/d, with 30% of total calories from lipids over 3 hours. RESULTS: MCT significantly increased each of the medium-chain fatty acids (C6:0, C8:0, and C10:0) as free fatty acids in the portal vein and about 10%/mol of C10:0 as triglycerides in the lymph compared with the other groups. There was significantly less C10:0 in lymphatic triglycerides with LCT/MCT than with MCT, but more than in the LCT and LCT/2mono diets. MCT also significantly increased the contents of C16:0, C18:0, C18:1, and C20:4 in the lymphatic triglycerides compared with all other groups including LCT/MCT. The amount of linoleic acid (C18:2) in lymphatic triglycerides followed the relative amounts of this fatty acid in the diet, with the greatest in LCT followed by LCT/MCT and LCT/2mono and least in MCT. A so-called structured lipid composed of the medium-chain fatty acid dodecanoic acid on the 2 position and long-chain fatty acids on the 1 and 3 positions appeared to be endogenously synthesized in response to the LCT/2mono diet. CONCLUSIONS: The original differences in MCT and LCT content in the diets were preserved in the fatty acid composition in the intestinal free fatty acids and triglycerides during feeding. In addition, the duration of lipid administration can play a role in altering fatty acid composition in the intestine.

Supplementation of arachidonic acid plus docosahexaenoic acid in cirrhotic patients awaiting liver transplantation: a preliminary study.

BACKGROUND: In patients with cirrhotic liver diseases, supplementation of linoleic acid and alpha-linolenic acid often does not alter the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting the necessity to directly provide these nutrients. METHODS: In a double-blind, placebo-controlled fashion, 9 cirrhotic patients listed for liver transplantation at Lahey Clinic Center were given daily supplementation with either 10 gel caps containing 500 mg of AA and 1000 mg of DHA (AA/DHA) or 250 mg of linolenic acid (LA) and 125 mg of oleic acid (OA; OA/LA) for 6 weeks. alpha-Tocopherol at 200 IU was provided daily. No other dietary prescription was made. Plasma fatty acid profiles were determined in triglyceride and phospholipids fractions. Plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin 6 (IL-6), and soluble TNF receptor II (sTNFRII) were also measured. RESULTS: Four patients receiving OA/LA and 5 patients receiving AA/DHA completed the study without evidence of any adverse effects or intolerance. The supplementation of LA, AA, and DHA effectively raised their levels in either one or both plasma lipid fractions in this limited number of subjects. DHA plus AA also lowered 22:4omega-6, 22:5omega-6, and 22:5omega-3, suggesting that DHA reduced the elongation and desaturation of AA and EPA. CONCLUSIONS: It is feasible to improve the liver disease-associated deficiency of AA or DHA with modest intakes of AA and DHA. Whether this maneuver will affect the systemic inflammatory responsiveness and ultimately clinical outcome will require a large-scale and well-controlled intervention.

Physical stability of 20% lipid injectable emulsions via simulated syringe infusion: effects of glass vs plastic product packaging.

BACKGROUND: The United States Pharmacopeia (USP) has proposed large-globule-size limits to ensure the physical stability of lipid injectable emulsions, expressed as the percent fat >5 microm, or PFAT(5), not exceeding 0.05%. Visibly obvious phase separation as free oil has been shown to occur in some samples if PFAT(5) is >0.4%. We recently found that lipids, newly packaged in plastic (P), exceed the proposed USP limits and seem to produce less stable total nutrient admixtures compared with those made from conventional glass (G), which do meet proposed USP standards. We tested the possible stability differences between 20% lipid injectable emulsions in either P or G in a simulated neonatal syringe infusion study. METHODS: Eighteen individual syringes were prepared from each 20% lipid injectable emulsion product (n = 36) and attached to a syringe pump set at an infusion rate of 0.5 mL/hour. The starting PFAT(5) levels were measured at time 0 and after 24 hours of infusion, using a laser-based light obscuration technique as described by the USP Chapter <729>. The data were assessed by a 2-way analysis of variance (ANOVA) with Container (G vs P) and Time as the independent variables and PFAT as the dependent variable. RESULTS: At time 0, the starting PFAT(5) level for lipids packaged in G was 0.006% +/- 0.001% vs 0.162% +/- 0.026% for P, whereas at the end of the infusion they were 0.013% +/- 0.003% and 0.328% +/- 0.046%, respectively. Significant differences were noted overall between groups for Container, Time, and Container-Time interaction (all p < .001). Bonferroni tests showed significant differences in PFAT(5) levels between Containers at time 0 (T-0; p < .001) and T-0 vs T-24 for P-based lipids (p < .001), whereas no such differences were noted for Time for the G-based lipids. Similar results were noted for PFAT(10) levels. CONCLUSIONS: We confirm that presently available lipid injectable emulsions packaged in newly introduced plastic containers exceed the proposed USP <729> PFAT(5) limits and subsequently become significantly less stable during a simulated syringe-based infusion. Although modest growth (p = NS) in large-diameter fat globules was observed for the glass-based lipids, they remained within proposed USP globule size limits throughout the study. Glass-based lipids seem to be a more stable dosage form and potentially a safer way to deliver lipids via syringe infusion to critically ill neonates.

Acute effects of hyperglycemia and hyperinsulinemia on hepatic oxidative stress and the systemic inflammatory response in rats.

OBJECTIVES: Intensive blood glucose control to a target value of 80-110 mg/dL has been shown to reduce morbidity and mortality in surgical intensive care unit patients. This was attributed predominantly to correction of hyperglycemia, based on multivariate regression analysis. However, the effects of glucose and insulin have not been independently evaluated. This study investigated the development of hepatic oxidative processes and systemic inflammatory response in rats with different levels of induced hyperglycemia and hyperinsulinemia. The effects of a modest increase in blood glucose following glucose infusion at a level adequate to meet energy requirements, hyperinsulinemia induced by a hyperinsulinemic euglycemic clamp with administered glucose in similar amounts, and marked hyperglycemia and hyperinsulinemia secondary to glucose infusion on hepatic oxidative stress and systemic inflammatory response in vivo were examined. DESIGN: Controlled laboratory study. SETTING: Medical school laboratory. SUBJECTS: Specific pathogen-free male Sprague-Dawley rats. INTERVENTIONS: Blood glucose was monitored over 3 hrs. At the end of study, the serum concentrations of insulin, tumor necrosis factor-alpha, interleukin-1, and alpha1 acid glycoprotein were determined. Malondialdehyde and total glutathione content were measured in the liver. MEASUREMENTS AND MAIN RESULTS: Glucose infusion adequate to provide energy requirements resulted in a modest increase in blood glucose (143+/-8 mg/dL) and hyperinsulinemia (45 microU/mL) and did not induce measurable hepatic oxidative stress or systemic inflammation. A hyperinsulinemic euglycemic clamp (insulin 112+/-9 microU/mL) resulted in evidence of increased oxidative processes in the liver but no change in hepatic antioxidant capacity or evidence of systemic inflammation. When hyperglycemia (approximately 350 mg/dL) and hyperinsulinemia (167+/-9 microU/mL) were induced by excess glucose infusion, rats manifested hepatic oxidative stress, antioxidant depletion, and a mild systemic inflammatory response. CONCLUSIONS: Hyperglycemia is a major cause of the systemic inflammatory response. Maintaining normal blood glucose, by avoiding overfeeding and providing insulin therapy when necessary, appears key to minimizing oxidative stress and systemic inflammation when intravenous nutrition is provided.

Pathological consequences to reticuloendothelial system organs following infusion of unstable all-in-one mixtures in rats.

BACKGROUND: Recent evidence of lung injury from the infusion of unstable lipid injectable emulsions as all-in-one mixtures (AIOs) was shown in a guinea pig infusion model. METHODS: We extended this research to a Sprague-Dawley rat infusion model, focusing our analyses on the dose of large-diameter fat globules (expressed as the volume-weighted percent of fat larger than 5 or 10 microm, PFAT5 or PFAT10) from the dispersed phase of emulsion mixtures of varying levels of stability, and the potential injurious effects on major tissues of the reticuloendothelial system (i.e., lungs and liver). RESULTS: Two identical infusion experiments (n=13 rats/study), involving stable (s-AIO) vs. unstable (u-AIO) mixtures were separately conducted, and differed in two respects: (1) duration of AIO infusion (24 h vs. 72 h) and, (2) starting PFAT5 levels for the u-AIO (24- vs. 72-h PFAT5: 0.682+/-0.055% vs. 0.117+/-0.024%, respectively). In both experiments, s-AIOs vs. u-AIOs were infused, and evidence of hepatic oxidative stress was noted by significantly higher tissue concentrations of malondialdehyde (MDA) during infusion of u-AIOs. The higher concentrations of MDA in the livers of animals receiving the u-AIOs were also accompanied by significantly higher plasma concentrations of AST in both infusion experiments suggesting injury. Levels of cytokines (IL-1beta, TNFalpha) in the lungs and livers in both infusion studies were variable. CONCLUSIONS: These results demonstrate the infusion of u-AIOs with starting PFAT5 levels of approximately 0.1% show evidence of pathological consequences to the liver and lungs, and therefore, such unstable AIO mixtures should probably be avoided in the clinical setting.