Nutritional management of PKU with glycomacropeptide from cheese whey.

Individuals with phenylketonuria (PKU) must follow a lifelong low-phenylalanine (Phe) diet to prevent neurological impairment. Compliance with the low-Phe diet is often poor owing to restriction in natural foods and the requirement for consumption of a Phe-free amino acid formula or medical food. Glycomacropeptide (GMP), a natural protein produced during cheese-making, is uniquely suited to a low-Phe diet because when isolated from cheese whey it contains minimal Phe (2.5-5 mg Phe/g protein). This paper reviews progress in evaluating the safety, acceptability and efficacy of GMP in the nutritional management of PKU. A variety of foods and beverages can be made with GMP to improve the taste, variety and convenience of the PKU diet. Sensory studies in individuals with PKU demonstrate that GMP foods are acceptable alternatives to amino acid medical foods. Studies in the PKU mouse model demonstrate that GMP supplemented with limiting indispensable amino acids provides a nutritionally adequate source of protein and improves the metabolic phenotype by reducing concentrations of Phe in plasma and brain. A case report in an adult with classical PKU who followed the GMP diet for 10 weeks at home indicates safety, acceptability of GMP food products, a 13-14% reduction in blood Phe levels (p<0.05) and improved distribution of dietary protein throughout the day compared with the amino acid diet. In summary, food products made with GMP that is supplemented with limiting indispensable amino acids provide a palatable alternative source of protein that may improve dietary compliance and metabolic control of PKU.

Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids.

A study was designed to examine the effects of dietary conjugated linoleic acid (CLA) on serum concentrations of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBP) and the relationship of these factors to bone metabolism. Weanling male rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 days. Treatments included 0 g/kg or 10 g/kg of CLA and soybean oil (SBO) or menhaden oil + safflower oil (MSO) following a 2 x 2 factorial design. Serum IGFBP was influenced by dietary polyunsaturated fatty acid (PUFA) type ((n-6) and (n-3)) and CLA (p = 0.01 for 38-43 kDa bands corresponding to IGFBP-3). CLA increased IGFBP level in rats fed SBO (p = 0.05) but reduced it in those fed MSO (p = 0.01). Rats fed MSO had the highest serum IGFBP-3 level. Both (n-3) fatty acids and CLA lowered ex vivo prostaglandin E2 production in bone organ culture. In tibia, rats given CLA had reduced mineral apposition rate (3.69 vs. 2.79 microm/day) and bone formation rate (BFR) (0.96 vs. 0.65 microm3/microm2/day); however, the BFR tended to be higher with MSO. Dietary lipid treatments did not affect serum intact osteocalcin or bone mineral content. These results showed that dietary PUFA type and CLA modulate local factors that regulate bone metabolism.

Investigation of insulin-like growth factor (IGF)-I and insulin receptor binding and expression in jejunum of parenterally fed rats treated with IGF-I or growth hormone.

To investigate the ability of insulin-like growth factor-I (IGF-I), but not GH, to stimulate jejunal growth, we compared indices of IGF-I and insulin receptor expression in jejunal membranes from rats maintained with total parenteral nutrition (TPN) and treated with rhIGF-I and/or rhGH. TPN without growth factor treatment (TPN control) induced jejunal atrophy, reduced serum IGF-I, increased serum insulin concentrations, and increased IGF-I receptor number, IGF-I receptor messenger RNA, and insulin-specific binding to 133% to 170% of the orally fed reference values, P < 0.01. Compared with TPN control, IGF-I or IGF-I + GH stimulated jejunal mucosal hyperplasia; IGF-I treatment increased serum IGF-I by 2- to 3-fold and decreased serum insulin concentrations by 60%, decreased IGF-I receptor number by 50% (P < 0.001), and increased insulin receptor affinity and insulin receptor protein content. Treatment with GH alone increased serum IGF-I concentration, did not alter TPN-induced jejunal atrophy, and decreased insulin-specific binding and insulin receptor protein content (39% and 59%, respectively, of the TPN control values, P < 0.01). We conclude that: 1) jejunal IGF-I receptor content reflects circulating concentration of ligand and is not limiting for jejunal growth; and 2) increased circulating concentration of IGF-I may promote jejunal growth via interaction with jejunal insulin or IGF-I receptors.

Insulin-like growth factor-I (IGF-I) responses in rats maintained with intravenous or intragastric infusion of total parenteral nutrition solutions containing medium- or long-chain triglyceride emulsions.

Our objective was to determine how intravenous or intragastric feeding affects serum concentrations of insulin-like growth factor (IGF)-I and -II and IGF binding proteins (IGFBP), and hepatic abundance of IGF-I mRNA. Male Fischer 344 rats (235-246 g) were fed for 14 d by intravenous or intragastric infusion with total parenteral nutrition (TPN) solutions providing 65% of energy from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions (MCT/LCT). Twice as much TPN solution was required per gram of weight gain with MCT/LCT compared with LCT infusion (P < 0.0003). Serum IGF-I and -II concentrations and hepatic IGF-I mRNA abundance were not significantly different. Circulating concentrations of IGFBPs with molecular weights of 38,000-43,000 (IGFBP-3) were significantly greater with intravenous MCT/LCT than with intravenous LCT infusion. Our data demonstrate that reduced growth in rats given TPN containing MCT/LCT compared with LCT emulsions is not associated with reduced serum IGF-I concentrations or hepatic abundance of IGF-I mRNA, although serum IGFBPs are elevated.

Growth hormone or insulin-like growth factor I increases fat oxidation and decreases protein oxidation without altering energy expenditure in parenterally fed rats.

We assessed whether the increased growth in parenterally fed rats treated with growth hormone (GH) or insulin-like growth factor I (IGF-I) or both is associated with alterations in energy expenditure or macronutrient oxidation or both. Surgically stressed male rats (approximately 235 g) were given total parenteral nutrition (TPN) and treated with recombinant human GH (rhGH) (800 micrograms/d), rhIGF-I (800 micrograms/d), rhGH+rhIGF-I (800 micrograms/d of each), or TPN alone for 3 d. Treatment with GH or IGF-I or both resulted in significantly greater body weight gain, nitrogen retention, and serum total IGF-I concentrations compared with TPN alone (P < 0.0001). Assessment of respiratory gas exchange and motor activity for 23 h on day 3 indicated no significant differences between groups in either total or activity-related rates of energy expenditures (kJ/kg0.75). Estimates based on the nitrogen-free respiratory quotient (RQ) revealed fat oxidation to be significantly increased by GH (P < 0.001) and IGF-I (P < 0.03), whereas protein oxidation was significantly reduced (P < 0.0001) by these growth factors. GH and IGF-I combined further enhanced fat oxidation while reducing protein catabolism. Serum insulin concentrations were significantly increased by GH but decreased by IGF-I. GH significantly decreased serum total triiodothyronine concentrations and IGF-I significantly decreased serum corticosterone concentrations. These results suggest that treatment with GH or IGF-I can increase fat oxidation and spare protein for growth without altering energy expenditure in surgically stressed rats maintained with TPN.

Medium-chain compared with long-chain triacylglycerol emulsions enhance macrophage response and increase mucosal mass in parenterally fed rats.

We tested whether infusion of medium-chain triacylglycerols (MCTs) during total parenteral nutrition (TPN) enhanced macrophage response and reduced intestinal atrophy compared with long-chain triacylglycerols (LCTs). Male Sprague-Dawley rats (230-240 g) were maintained with TPN providing 16% or 48% of nonprotein energy from MCTs plus LCTs or LCTs alone or 100% of nonprotein energy from dextrose for 6 or 12 d. Body weight gain was not significantly different among groups. Serum concentrations of beta-hydroxybutyrate were greater with MCTs plus LCTs than with LCTs alone after 6 d (P < 0.05, main effect). Triacylglycerol concentrations in liver were greater with LCTs than with MCTs plus LCTs after 6 or 12 d (P < 0.05, main effect). MCTs plus LCTs increased by 50% the percentage (P < 0.0005) and number of splenic macrophages compared with LCTs alone in conjunction with decreased triacylglycerol concentrations in spleen after 6 d (P < 0.05, main effect). In vitro tumor necrosis factor alpha secretion by splenic or circulating macrophages in response to lipopolysaccharide was increased by MCTs plus LCTs compared with LCTs alone, twofold after 6 and sevenfold after 12 d (P < 0.05, main effect). Jejunal mucosal mass was 30% greater with MCTs plus LCTs than with LCTs alone after 6 or 12 d (P < 0.01); villus height was also significantly greater after 6 d (main effect). The incidence of bacterial translocation to the mesenteric lymph nodes was not significantly different among groups. Compared with LCTs, MCTs enhanced macrophage response and decreased intestinal atrophy.

High-calorie total parenteral nutrition reduces hepatic insulin-like growth factor-I mRNA and alters serum levels of insulin-like growth factor-binding protein-1, -3, -5, and -6 in the rat.

High-calorie total parenteral nutrition (TPN) is associated with hepatic dysfunction and steatosis. Because TPN-induced steatosis might compromise hepatic expression of insulin-like growth factor-I (IGF-I) and thereby limit its potential nutritional benefit, we examined hormonal and IGF-I responses in male Sprague-Dawley rats (270 to 300 g) fed by continuous intravenous infusion with high-calorie, high-dextrose (350 kcal/kg) TPN solutions for O (control), 2, 4, and 8 days. Since IGF-binding proteins (IGFBPs) are thought to modulate the biological effects of IGFs in target tissues, we also determined serum levels of IGFBPs. Animals developed hepatic steatosis after 2 to 8 days of TPN, as reflected by a sevenfold to 15-fold increase in hepatic triacylglycerol content (P < .001 v control on each day). Serum corticosterone and insulin levels were significantly higher after 2 and 4 days of TPN, whereas serum growth hormone levels were reduced after 4 and 8 days. Serum IGF-I levels were not significantly different during TPN. However, there was a coordinate reduction in the three major hepatic IGF-I transcripts (7.0, 1.9, and 1.0 kb) after 2, 4, or 8 days of TPN, and IGF-I transcripts corresponding to multiple initiation sites within exons 1 and 2 were coordinately downregulated with TPN. Western ligand blotting indicated that serum levels of 38K to 43K, 30K to 34K, and 24K IGFBPs were increased approximately twofold after 4 and 8 days of TPN as compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone, insulin-like growth factor-1, and the insulin-like growth factor binding proteins in rats maintaining reduced body protein following lesions of the lateral hypothalamus.

Rats with lesions of the lateral hypothalamus (LH) maintain a reduced body protein mass that they effectively defend when challenged by under- or over-nutrition. The two studies reported here evaluate the potential contributions of growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the insulin-like growth factor-binding (IGFBP) to this persistent maintenance of a reduced body protein mass by LH rats. At 18 weeks postlesion, it was found that the serum levels of GH, IGF-1, total IGFBP, and IGFBP-3 of LH rats maintaining reduced body protein were not different from those of age-matched controls. However, closer to the time of surgery, at which time the lesion-induced body protein adjustments are known to occur, altered hormone and binding protein levels were observed. Specifically, at 3 weeks after lesioning, the IGF-binding proteins of LH rats were significantly elevated, whereas their GH levels were lower than those of controls. Because the GH, IGF-1, and IGF-binding proteins of LH rats were comparable to those of controls at 18 weeks after lesioning, none apparently underlie the chronically reduced body protein mass that LH rats display. Closer to the time of lesioning, however, altered GH and IGF binding protein levels may contribute to the postlesion adjustments by which the body protein mass of LH rats is lowered to its reduced level.

Effects of insulin-like growth factor-I and growth hormone in models of parenteral nutrition.

BACKGROUND: Administration of growth factors such as growth hormone (GH) and insulin-like growth factor-I (IGF-I) is being investigated as a strategy to promote nitrogen accretion in catabolic patients who may require total parenteral nutrition (TPN). IGF-I has advantages compared with GH because IGF-I enhances insulin sensitivity, is effective in conditions of GH resistance, and selectively stimulates the gastrointestinal and immune systems. METHODS: Experiments were conducted to evaluate the anabolic and metabolic effects associated with administration of recombinant human GH or IGF-I in rats subjected to clinically relevant stress and maintained with TPN. RESULTS: Administration of IGF-I, but not GH, attenuates dexamethasone-induced protein catabolism and increases insulin sensitivity. Simultaneous treatment with GH and IGF-I additively increases the serum concentration of IGF-I, whole-body anabolism, and lipid oxidation. GH or IGF-I when given alone produces similar increases in the serum concentration of IGF-I. However, GH selectively increases skeletal muscle mass whereas IGF-I selectively attenuates the intestinal atrophy and abnormal intestinal ion transport induced by TPN. These tissue-selective anabolic effects of GH and IGF-I are associated with differential increases in protein synthesis in skeletal muscle and jejunum, respectively. CONCLUSIONS: Simultaneous treatment with GH and IGF-I may offer the greatest clinical efficacy because of improved nitrogen retention in association with enhanced lipid oxidation and stimulation of protein synthesis in multiple tissue types.

Insulin-like growth factor-I enhances immune response in dexamethasone-treated or surgically stressed rats maintained with total parenteral nutrition.

BACKGROUND: New evidence suggests that insulin-like growth factor-I (IGF-I) is an important regulator of immune response. Our objective was to determine the effects of IGF-I on immune response during total parenteral nutrition (TPN) using two stress models. METHODS: Male, Sprague-Dawley rats (230 to 250 g) were given TPN with or without coinfusion of recombinant human IGF-I (800 micrograms/d for 6 days) and subjected to either dexamethasone, a synthetic glucocorticoid, or surgical stress, in the form of a midline abdominal incision. In the dexamethasone model, immune response was assessed by total cellularity of the thymus and spleen, in vitro assays of lymphocyte proliferation, and interleukin 6 (IL-6) production, and concentrations of IL-6 and tumor necrosis factor alpha (TNF-alpha) in serum. In the surgical model, flow cytometry was used to identify and quantify splenic populations of T and B lymphocytes and macrophages. RESULTS: In rats immunosuppressed by dexamethasone, IGF-I infusion increased mitogen-induced proliferation of thymocytes, but did not alter cellularity in the thymus; enhanced proliferation and IL-6 production in peripheral blood mononuclear cells following treatment with concanavalin A or lipopolysaccharide; and reduced the serum concentration of IL-6, but not TNF-alpha. In surgically stressed rats, IGF-I infusion restored the splenic populations of immature and mature B lymphocytes, which were decreased by TPN. CONCLUSIONS: our data demonstrate that IGF-1 enhances immune response during TPN in rats.

Insulin-like growth factor-I but not growth hormone attenuates dexamethasone-induced catabolism in parenterally fed rats.

BACKGROUND: We demonstrated that recombinant human insulin-like growth factor-I (rhIGF-I) or growth hormone (rhGH) produces identical body weight gain during total parenteral nutrition (TPN) in surgically-stressed rats. Our current objective was to evaluate the relative anabolic and metabolic effects associated with administration of rhIGF-I and/or rhGH during hypocaloric TPN in rats with dexamethasone (DEX)-induced catabolism. METHODS: Male Sprague-Dawley rats (approximately 270 g) given TPN and DEX were treated with IGF-I and/or GH for 6 days. Two control groups, TPN and DEX, were included. Anabolic response was assessed by change in body protein content and nitrogen balance. Metabolic response was assessed by determination of serum concentrations of IGF-I, IGF binding proteins (IGFBPs), insulin, glucose, triacylglycerol, glycerol, and free fatty acids. RESULTS: Compared with GH, IGF-I attenuated DEX-induced loss of body protein and decreased serum concentrations of glucose, free fatty acids, glycerol, and triglycerol. Treatment with IGF-I plus GH showed an anabolic response similar to IGF-I alone. IGF-I and/or GH increased serum concentrations of IGF-I and IGFBP-3. IGF-I alone increased serum level of IGFBP-5. CONCLUSION: Administration of IGF-I, but not GH, attenuates DEX-induced protein catabolism in association with increased insulin sensitivity in rats. Glucocorticoid excess may limit the response to GH therapy during TPN.

Enterotrophic effect of insulin-like growth factor-I but not growth hormone and localized expression of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and -5 mRNAs in jejunum of parenterally fed rats.

BACKGROUND: Administration of insulin-like growth factor (IGF)-I, but not growth hormone (GH), stimulates mucosal hyperplasia in surgically stressed rats with intestinal atrophy induced by hypocaloric total parenteral nutrition (TPN). Our aim was to characterize the basis for this disparity in enterotrophic action by assessing the relationships between stimulation of intestinal growth, nutritional adequacy, and localization of expression of IGF-I, insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 mRNAs in jejunum. METHODS: Rats were maintained with TPN for 8 days and treated with IGF-I or GH and adequate nutrition for 5 days after recovery from surgery. Jejunal mass, morphology, and sucrase activity were assessed. Localization of expression of IGF-I, IGFBP-3, and IGFBP-5 mRNAs in jejunum was accomplished by in situ hybridization. RESULTS: Serum IGF-I and body weight gain were significantly increased by IGF-I or GH. Jejunal mucosal dry mass, morphology, and sucrase activity were improved with IGF-I but not GH. There were no differences in IGF-I mRNA. IGFBP-3 mRNA was localized in the lamina propria of the villi. IGF-I or GH stimulated IGFBP-3 expression. IGF-I strongly stimulated IGFBP-5 expression in the lamina propria and the muscularis and induced a twofold increase in IGFBP-5 mRNA based on RNase protection assay of intact jejunum total RNA. GH induced a modest increase in IGFBP-5 expression in the muscularis with no effect on intact jejunum total RNA. CONCLUSIONS: The GH resistance observed in the jejunal mucosa of TPN rats cannot be fully explained by inadequate nutrition. The expression of IGFBP-5 in the lamina propria suggests it may modulate the enterotrophic action of exogeneous IGF-I.

Tissue manganese concentrations and antioxidant enzyme activities in rats given total parenteral nutrition with and without supplemental manganese.

BACKGROUND: Manganese is an essential but potentially toxic mineral. Parenteral administration of manganese via total parenteral nutrition (TPN) bypasses homeostatic mechanisms (intestinal absorption and presystemic hepatic elimination). Our objective in this study was to determine the effect of supplemental manganese in TPN solutions on manganese status in a rat model. METHODS: Male Sprague-Dawley rats underwent jugular catheterization and were given 61.0 +/- 0.4 g/d TPN solution providing 0.5 +/- 0.2 nmol manganese/g (Mn-; n = 6) or 16 +/- 3 nmol manganese/g (Mn+; n = 7) for 7 days. Reference rats (RF; n = 8) were fed a purified diet containing 1.3 mmol manganese/g. RESULTS: Liver manganese decreased in both TPN groups, but tibia, spleen, and pancreas manganese concentrations were greater in Mn+ rats than in Mn- or RF rats. Although no treatment differences were seen in heart or liver manganese superoxide dismutase activity, heart copper-zinc superoxide dismutase activity was lower in the Mn+ rats than in Mn- or RF rats (p < .05). Glutathione peroxidase activity was depressed in livers of both Mn- and Mn+ rats relative to RF rats (p < .0001), which was not due to selenium deficiency. CONCLUSIONS: Supplemental parenteral manganese is taken up to a greater extent by peripheral tissues than the liver. In this first report of antioxidant enzyme activities in animals maintained with TPN, we found that TPN as well as supplemental manganese can influence antioxidant enzyme activities. We conclude that it is generally unnecessary and potentially toxic to supplement TPN solutions with manganese during short-term usage.

Interrelationship of stearic acid content and triacylglycerol composition of lard, beef tallow and cocoa butter in rats.

We investigated modes whereby stearic acid (18:0) exerts a neutral or cholesterol-lowering effect using dietary fats which provided graded levels of 18:0 and distinct triacylglycerol (TAG) profiles. Male Sprague-Dawley rats (150-175 g) were fed diets containing 0.2% cholesterol and 16% fat from corn oil, or from 1% corn oil plus 15% lard (13.2% 18:0), beef tallow (19.2% 18:0) or cocoa butter (34.7% 18:0) for 3 wk, and then killed in a fasted or fed state. Chylomicron (CM) fatty acid profiles suggested reduced absorption of 18:0 with greater 18:0 intake. CM TAG profiles indicated a reduction or loss of two TAG species compared to the TAG profiles of the stearate-rich diets: 1-palmitoyl-2-oleoyl-3-stearoyl glycerol (POS) and 1,3-distearoyl-2-oleoyl glycerol (SOS). Hepatic total cholesterol concentrations were 54-77% lower (P < 0.01) in the cocoa butter-fed than the lard-and beef tallow-fed groups. The cocoa butter group showed a significantly lower ratio of high-density lipoprotein esterified/free cholesterol than all other groups. Hepatic stearoyl-CoA and oleoyl-CoA concentrations, the substrate and product for hepatic delta 9 desaturase, were not significantly different for corn oil-fed and cocoa butter-fed groups in spite of a large difference in 18:0 intake. These data suggest that the neutral or cholesterol-lowering effect of 18:0 is not due to hepatic conversion of stearic to oleic acid, and that POS and SOS are poorly absorbed from stearate-rich dietary fats.

In vivo determination of triglyceride secretion using radioactive glycerol in rats fed different dietary saturated fats.

Our objective was to determine the relative rates of in vivo triglyceride (TG) secretion and the composition of very low density lipoproteins (VLDL) in rats fed different dietary saturated fats. Male Sprague-Dawley rats (150-200 g) were fed diets containing 16% corn oil, or 14% butterfat, 14% beef tallow, 14% olive oil, or 14% coconut oil plus 2% corn oil for 5 wk. Changes in plasma TG specific radioactivity were determined in individual, unanesthetized fasted rats after injection of 100 microCi [2-3H]glycerol. Nonlinear regression analysis using a 2-compartment model was used to determine the fractional rate constant for TG turnover in plasma. The plasma TG pool was 33-40% larger with beef tallow than with corn, olive or coconut oil feeding (p less than 0.05), and 20% larger with beef tallow than with butterfat feeding. The rate of TG secretion into plasma (mg/min/100 g body weight) was 60% higher in animals fed beef tallow than corn or coconut oil (p less than 0.05) and 26-33% higher in animals fed beef tallow than olive oil or butterfat. Differences in VLDL composition (% wt) were also noted. Our data suggest that greater TG secretion is the primary factor contributing to the larger TG pool with ingestion of beef tallow relative to butterfat, corn or coconut oil. These results suggest that different dietary saturated fats have unique effects on TG metabolism in rats.

Effect of dietary fat on individual long-chain fatty acyl-CoA esters in rat liver and skeletal muscle.

The effect of dietary fat on the long-chain acyl-CoA ester profile of liver and skeletal muscle was investigated by feeding weanling rats 12%-fat diets composed of high-linoleic safflower oil (73% 18:2n-6), high-oleic safflower oil (70% 18:1n-9) or olive oil (70% 18:1n-9) for six and ten weeks. Approximately 50% of both hepatic and skeletal muscle acyl-CoA esters comprised linoleoyl-CoA or oleoyl-CoA with high-linoleic or oleic feeding, respectively. Total hepatic acyl-CoA ester concentration was 40% higher (p less than 0.05) in rats fed 12% fat compared with controls fed a 4%-fat diet. These data demonstrate that the long-chain acyl-CoA ester profile of liver and skeletal muscle reflects the dietary fatty acid profile.

A comparison of two opioid analgesics for relief of visceral pain induced by intestinal resection in rats.

While developing a rat model for human short bowel syndrome, we noted that untreated rats as well as rats administered buprenorphine after intestinal resection exhibited behavior and appearance consistent with visceral pain and distress. To provide appropriate analgesics, we developed criteria to assess pain-related behavioral changes and conducted an experiment to evaluate the effectiveness of buprenorphine versus oxymorphone to alleviate the pain induced by intestinal resection. Rats underwent either small-bowel resection or transection surgery; in addition, animals received jugular catheterization for the delivery of total parenteral nutrition (TPN). Rats treated with buprenorphine received 0.5 mg/kg every 6 h subcutaneously, and rats treated with oxymorphone received 0.03 mg/kg hourly for 32 h via continuous intravenous (i.v.) infusion with TPN solution. Rats treated with buprenorphine exhibited behavior and appearance consistent with pain and distress for as long as 32 h postoperatively, whereas animals treated with oxymorphone exhibited behavior and appearance similar to their preoperative state. Thus, oxymorphone alleviated the pain-related behavioral changes after intestinal resection far better than did buprenorphine. Of interest, we observed that the buprenorphine was associated with a decrease in the volume of urine collected, whereas oxymorphone was associated with urine volumes similar to those of nonresected rats maintained with TPN. Because oxymorphone appeared to be a superior analgesic, we also evaluated three routes for administering this drug. Pain-related behavior changes were alleviated by the administration of oxymorphone by either Alzet mini-pump, bolus i.v. injection, or continuous i.v. infusion. We conclude that compared with buprenorphine, oxymorphone is a superior analgesic for the alleviation of visceral pain due to intestinal resection.

Potential for enhancing the nutritional properties of milk fat.

Milk fat has been identified as a hypercholesterolemic fat because it contains cholesterol and is primarily saturated. However, different types of dietary saturated fats do not have equivalent effects on plasma cholesterol levels relevant to ingestion of polyunsaturated fats. Research suggests that the hypercholesterolemic effect of saturated fats in human diets is largely due to 12, 14, and 16 carbon chain length fatty acids. Evidence also suggests that stearic acid (C18:0) is as effective as oleic acid (C18:ln-9) in lowering plasma cholesterol levels when either replaces palmitic acid (C16:0) in the diet of men. Milk fat has a unique fatty acid profile with approximately 10% short- and medium-chain length saturated fatty acids (less than 12 carbons) and 35% of total fatty acids from stearic and oleic acids. The contribution of milk products to fat and cholesterol intake in the typical American diet is less than that provided by other animal products. This paper will review the recommendations of the National Cholesterol Education Program, the effects of milk fat ingestion on blood cholesterol, and the rationale and feasibility of three approaches to modifying the lipid composition of milk fat.

Corn oil, palm oil and butterfat fractions affect postprandial lipemia and lipoprotein lipase in meal-fed rats.

Our objective was to investigate the time course of postprandial lipemia and lipolytic activity in male Sprague-Dawley rats trained to eat meals containing butterfat fractions, palm oil or corn oil. Baseline and postprandial blood samples were obtained via a carotid cannula in rats fed the experimental diets for 4 wk. Rats fed saturated fats compared with corn oil showed a significantly greater peak increase in postprandial triacylglycerol concentrations. Corn oil ingestion resulted in significantly lower concentrations of cholesterol and triacylglycerol in plasma and significantly less triacylglycerol accumulation (millimoles per liter per 24 h) compared with ingestion of saturated fats. Postheparin plasma lipoprotein lipase activity and plasma insulin concentration were generally greater with ingestion of corn oil compared with palm oil or butterfat. Palm oil ingestion resulted in a biphasic plasma triacylglycerol response curve and greater postheparin plasma lipoprotein lipase activity compared with butterfat ingestion, suggesting differential effects of saturated fats on postprandial lipemia. Our results indicate that greater postprandial lipemia with ingestion of saturated fats compared with corn oil may be due in part to slower plasma triacylglycerol clearance.