Standard Total Parenteral Nutrition Solution Research Articles

GLP-2 Prevents Intestinal Mucosal Atrophy and Improves Tissue Antioxidant Capacity in a Mouse Model of Total Parenteral Nutrition.

We investigated the effects of exogenous glucagon-like peptide-2 (GLP-2) on mucosal atrophy and intestinal antioxidant capacity in a mouse model of total parenteral nutrition (TPN). Male mice (6–8 weeks old) were divided into three groups (n = 8 for each group): a control group fed a standard laboratory chow diet, and experimental TPN (received standard TPN solution) and TPN + GLP-2 groups (received TPN supplemented with 60 µg/day of GLP-2 for 5 days). Mice in the TPN group had lower body weight and reduced intestinal length, villus height, and crypt depth compared to the control group (all p < 0.05). GLP-2 supplementation increased all parameters compared to TPN only (all p < 0.05). Intestinal total superoxide dismutase activity and reduced-glutathione level in the TPN + GLP-2 group were also higher relative to the TPN group (all p < 0.05). GLP-2 administration significantly upregulated proliferating cell nuclear antigen expression and increased glucose-regulated protein (GRP78) abundance. Compared with the control and TPN + GLP-2 groups, intestinal cleaved caspase-3 was increased in the TPN group (all p < 0.05). This study shows GLP-2 reduces TPN-associated intestinal atrophy and improves tissue antioxidant capacity. This effect may be dependent on enhanced epithelial cell proliferation, reduced apoptosis, and upregulated GRP78 expression.

Effects of Branched-Chain Amino Acid Infusions on Liver Regeneration and Plasma Amino Acid Patterns in Partially Hepatectomized Rats

Even though solutions of high branched-chain amino acids (BCAAs) are known to be beneficial to patients with hepatic encephalopathy, data on the effects of BCAA on liver regeneration are limited. Two groups of young adult rats were utilized in this study: standard total parenteral nutrition solutions were administered to group SS (22.59% of BCAAs in total amino acids) and solutions high in BCAAs were given to group HS (34.44% of BCAAs). After 2 days of infusion, 70% partial hepatectomy was performed and the TPN infusions were continued for another 3 days. Liver regeneration was estimated and changes in serum amino acid patterns were determined 3 days after hepatectomy. Thymidine incorporation into liver DNA, in group HS was significantly higher than that in group SS (378±56 vs. 324±38, p=0.032). In group SS, the total concentration of BCAAs decreased (165.11±39.90mg/dL and 145.56±29.53mg/dL, p=0.014) over the experimental period, whereas that of aromatic amino acids (AAAs) increased (226.56±36.5mg/dL and 247.00±48.36mg/dL, p=0.104). However, group HS showed no changes in BCAA or AAA sums over the experimental period. After major hepatectomy, supplementation with high BCAAs helps not only to maintain a stable plasma BCAA/AAA ratio, but also promotes liver regeneration.

Glutamine: a conditionally essential nutrient or another nutritional puzzle.

Malnutrition and infection are common among patients receiving bone marrow transplant. A recent randomized, double-blind study was conducted to determine whether the addition of glutamine to standard total parenteral nutrition solutions would improve nitrogen retention and reduce hospital morbidity in a group of 45 bone marrow transplant patients. The results showed improved nitrogen balance and reduced incidence of clinical infection in the glutamine-supplemented patients.

Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: A prospective randomized double blind trial

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.

Effects of lipid administration on liver apoptotic signals in a mouse model of total parenteral nutrition (TPN).

Lipids are an important component of total parenteral nutrition (TPN), contributing the largest caloric load per volume of solution and providing essential fatty acids necessary for survival. However, lipids are known to be causative factors in oxidative stress, which are expressed via the Bcl-2 family of proteins and/or Fas-mediated apoptosis in several tissues. Interestingly, we have recently observed an increase in hepatocyte apoptosis with administration of TPN. To address the mechanism of this apoptosis, we investigated the effects of parenteral lipid administration on apoptotic signaling in a mouse model. C57BL/6J male mice received physiologic saline and standard chow (control) or standard TPN solution with (TPN+L) or without lipid (TPN-L) emulsion. After 7 days of infusion, apoptosis increased in the TPN+L at a significantly higher rate compared with control and TPN-L groups ( p<0.05). Both TPN, with and without lipids, suppressed the pro-apoptotic signals Bid and Bcl-xs ( p<0.05). In contrast, TPN with lipid increased the expression of Fas and both the pro-apoptotic factor Bad and the anti-apoptotic factor Bcl-xl ( p<0.05). These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or suppress the ability of liver hepatocytes to regenerate.

Response of glutamine metabolism to glutamine-supplemented parenteral nutrition

Increasing evidence suggests that glutamine is important for the function of many organ systems and supports the use of glutamine-enriched total parenteral nutrition (TPN) during severe illness. However, the effect of prolonged glutamine supplementation on glutamine kinetics has not been studied. We investigated the effect of 8-10 d of TPN enriched with glutamine dipeptides on glutamine kinetics. Twenty-three preoperative patients were randomly allocated to receive either TPN enriched with glutamine dipeptides (60 micromol glutamine*kg body wt(-1)*h(-1)) or isonitrogenous, isoenergetic, glutamine-free TPN. A primed, continuous, 6-h intravenous infusion of L-[5-(15)N]glutamine and L-[1-(13)C]leucine was given before (baseline) and 8-10 d after the TPN solutions were administered. Baseline measurements were performed after a 40-h administration of a standard solution of glucose and amino acids (no glutamine). Glutamine-enriched TPN increased the total appearance rate of glutamine (P: < 0.05) but did not inhibit or increase the endogenous appearance rate. The standard TPN solution also increased the glutamine appearance rate (P: < 0.05), but the change was much smaller than in the glutamine-supplemented group (P: < 0.01). The plasma glutamine concentration did not rise significantly during either treatment, suggesting increased tissue glutamine utilization, especially in the glutamine-supplemented group. In view of the enhanced glutamine requirements in response to trauma and disease by tissues such as those of the gut, the immune system, and the liver, increased glutamine availability during glutamine-enriched TPN may be beneficial preoperatively in patients with gastrointestinal disease.

Effect of glutamine or glucagon-insulin enriched total parenteral nutrition on liver and gut in 70% hepatectomized rats with colon stenosis

Background: Malnutrition of enterocytes is believed to facilitate the breakdown of the intestinal mucosal barrier, furthering a translocation of enteric bacteria with subsequent severe infection, which has been described after extensive hepatectomy. Glutamine and glucagon insulin are said to attenuate the malnutrition of enterocytes. To determine whether this was true, the effects on the remnant liver and the gut of total parenteral nutrition supplemented by admixtures of glutamine and/or glucagon insulin were investigated in rats subjected to massive hepatectomy and transient intestinal stasis. Study Design: Rats underwent a permanent cannulation of the superior caval vein without restraining their mobility, a 70% hepatectomy, and a 24 hour string-ligation stenosis of the colon. A standard total parenteral nutrition solution was infused without or with 2% glutamine and without or with glucagon-insulin supplementation, respectively. Results: Glutamine and glucagon-insulin supplemented total parenteral nutrition increased ileal mucosal DNA concentrations during and after intestinal stasis. Glutamine or glucagon-insulin alone had less pronounced effects. In the liver, the combined supplementation resulted in reduced adenosine triphosphate concentrations and increased mitochondrial adenosine triphosphate synthesis as well as in an early increase in DNA concentrations. Conclusion: Glutamine and glucagon-insulin enriched total parenteral nutrition attenuates malnutrition of enterocytes after massive abdominal stress and promotes liver regeneration after extensive hepatectomy.

Effect of glutamine or glucagon-insulin enriched total parenteral nutrition on liver and gut in 70% hepatectomized rats with colon stenosis.

Malnutrition of enterocytes is believed to facilitate the breakdown of the intestinal mucosal barrier, furthering a translocation of enteric bacteria with subsequent severe infection, which has been described after extensive hepatectomy. Glutamine and glucagon insulin are said to attenuate the malnutrition of enterocytes. To determine whether this was true, the effects on the remnant liver and the gut of total parenteral nutrition supplemented by admixtures of glutamine and/or glucagon insulin were investigated in rats subjected to massive hepatectomy and transient intestinal stasis. Rats underwent a permanent cannulation of the superior caval vein without restraining their mobility, a 70% hepatectomy, and a 24 hour string-ligation stenosis of the colon. A standard total parenteral nutrition solution was infused without or with 2% glutamine and without or with glucagon-insulin supplementation, respectively. Glutamine and glucagon-insulin supplemented total parenteral nutrition increased ileal mucosal DNA concentrations during and after intestinal stasis. Glutamine or glucagon-insulin alone had less pronounced effects. In the liver, the combined supplementation resulted in reduced adenosine triphosphate concentrations and increased mitochondrial adenosine triphosphate synthesis as well as in an early increase in DNA concentrations. Glutamine and glucagon-insulin enriched total parenteral nutrition attenuates malnutrition of enterocytes after massive abdominal stress and promotes liver regeneration after extensive hepatectomy.

A Total Parenteral Nutrition Solution Supplemented with a Nucleoside and Nucleotide Mixture Sustains Intestinal Integrity, but Does Not Stimulate Intestinal Function after Massive Bowel Resection in Rats

The effects of supplementing a total parenteral nutrition solution with a nucleoside and nucleotide mixture on mucosal adaptive processes after massive bowel resection were studied. Male Wistar rats (n = 30) underwent 80% small intestine resection, were randomized into two groups and received either standard total parenteral nutrition (TPN) or TPN supplemented with a nucleoside and nucleotide mixture (2.5 mL·kg-1·d-1). An additional five rats, fed a nonpurified diet and not resected, were used as controls. After 4 or 7 d, rats were killed and samples were collected for mucosal indices and intestinal enzymatic activities (disaccharidases and diamine oxidase). After massive small bowel resection and TPN, residual jejunal mucosal wet weights, villus heights, protein and RNA contents on d 4 and 7, and total wet weights and DNA contents on d 7 were significantly lower than in the control group. Administration of the nucleoside and nucleotide mixture resulted in significantly higher residual jejunal total and mucosal weights, protein, DNA, RNA contents, and the ratio of proliferating cell nuclear antigen positive cells per crypt than did the standard TPN solution on d 7. However, disaccharidase and diamine oxidase activities were not affected by supplementation with the nucleoside and nucleotide mixture. Our data suggest that supplementation of a nucleoside and nucleotide mixture to a TPN solution can attenuate the initial mucosal atrophy and improve intestinal cell turnover after massive bowel resection, but the supplementation has little effect on enterocyte enzymatic activities.

The enhanced effect of parenteral nutrition on hepatotoxicity

Recent studies have demonstrated that enteral feedings are associated with decreased morbidity and mortality when compared with parenteral feedings. In this study, we hypothesized that (1) route of feeding affects morbidity and mortality in a model of drug-induced hepatotoxicity and (2) glutamine and polymyxin B, which have been reported to reduce bacterial translocation, attenuate this effect when TPN is used. Male virus-free Wistar rats were divided into six groups receiving: (1) ad libitum chow infused with intravenous (IV) saline (Chow), (2) standard total parenteral nutrition solution administered via gastrostomy (Enteral), (3) standard total parenteral nutrition infused via a central catheter (TPN), (4) standard TPN containing polymyxin B (TPN-PolyB), and (5) glutamine-enriched TPN (TPN-GLN). A final group of animals was not manipulated but harvested at time 0 to serve as controls. The dose of polymyxin B used in this study has previously been shown to significantly reduce bacterial translocation. After 4 d of feeding, all rats received 5% dextrose infusion after an intraperitoneal (IP) injection of acetaminophen (ACM). Rats were sacrificed 0, 6, and 24 h after ACM administration. The TPN group had a lower liver glutathione level after 6 and 24 h, greater levels of liver enzymes after 24 h, and a lower survival rate after 24 h compared with Chow. The Enteral group had less morbidity than TPN but greater morbidity than Chow. Addition of polymyxin B or glutamine had a minimal effect on morbidity or mortality when compared to the TPN group. We conclude that rats receiving IV nutrition have greater morbidity and mortality following a standard hepatic insult than chow-fed rats. We speculate that alteration of microsomal cytochrome P-450 or drug clearance may be related to the benefits of providing nutrients by the gastrointestinal route.

Effect of methionine-deprived total parenteral nutrition on tumor protein turnover in rats.

Previous studies have shown that a methionine-lacking diet inhibited tumor growth in rats. The aim of this study was to determine how methionine free total parenteral nutrition (MTPN) can result in the inhibition of tumor growth on tumor protein metabolism in rats. On day 0, AH109A rat ascites hepatoma cells were implanted subcutaneously into male Donryu rats (n = 68, body weight, 200-225 gm). On day 10, a catheter for total parenteral nutrition (TPN) was placed and either MTPN or standard TPN solution was given for 5 days. On day 15, 1-14C-leucine was infused continuously to measure tumor protein synthesis. Tumor proteolysis was calculated from tumor regional blood flow, using the 85Sr-microsphere injection method. 1) Tumor weight was reduced with MTPN. 2) MTPN did not affect tumor protein synthesis, probably because endogenous methionine production was increased with MTPN (87.3 +/- 13.5 mumole methionine/kg/hour vs. 218.6 +/- 29.5, P < 0.01); however, MTPN caused an increase of tumor proteolysis (2.68 +/- 0.53 mumole leucine/g/hour vs. 3.79 +/- 0.73, P < 0.05). The enhanced tumor protein breakdown contributed to the inhibition of tumor growth that was found with the rats given the methionine free diet.

Effect of Glutamine Supplement and Hepatectomy on DNA and Protein Synthesis in the Remnant Liver

One of the physiological roles of glutamine is as a precursor for DNA synthesis. The aims of this study were to determine (1) whether glutamine-supplemented total parenteral nutrition (TPN) enhanced DNA and protein synthesis in the liver and (2) whether glutamine uptake was increased following partial hepatectomy in rats. Male Donryu rats ( n = 59; body weight, 250-275 g) were randomized into four groups: (1) sham operation + standard TPN solution (C-STPN); (2) C + glutamine-supplemented TPN (C-GTPN); (3) 70% partial hepatectomy + STPN (H-STPN); (4) partial hepatectomy + GTPN (H-GTPN). On Day 0, rats underwent either a sham operation or 70% partial hepatectomy and concomitantly were catheterized in the jugular vein. TPN was begun immediately after the surgery. GTPN was isocaloric and isonitrogenous with STPN and 25% of total nitrogen was given as glutamine. On Day 2, the animals were sacrificed after either a continuous infusion of 1- 14C-leucine or a bolus iv injection of bromodeoxyuridine. The rate of hepatic regeneration was enhanced with glutamine supplementation (H-STPN, 60.8 ± 1.6% vs H-GTPN, 66.3 ± 2.0, P < 0.05) due to an increase in protein synthesis in the liver (H-STPN, 134.0 ± 10.3%/day vs H-GTPN, 160.9 ± 6.9, P < 0.05) and DNA synthesis in hepatocytes (H-STPN, 23.1 ± 2.5% vs H-GTPN, 31.4 ± 2.9, P < 0.05). The uptake of glutamine by the liver was increased following hepatectomy with GTPN supplementation. In conclusion, glutamine supplement and partial hepatectomy stimulated glutamine uptake in the liver and this results in an enhancement of protein and DNA synthesis in the remnant liver.

Prevention of fatty liver and maintenance of systemic valine depletion using a newly developed dual infusion system.

Valine-depleted amino acid imbalance, while having a suppressive effect on tumor growth, may induce fatty liver. We administered a valine-depleted total parenteral nutrition (TPN) solution by the central venous route to non-tumor-bearing rats and examined the time course of the development of fatty liver. In an attempt to prevent this condition, we administered a continuous infusion of low concentrations of valine via the portal vein simultaneously with administration of central venous valine-depleted nutrition for 4 days. A marked accumulation of triglyceride was observed in the liver on day 4 of the administration of valine-depleted nutrition. It is speculated that such accumulation is the cause of fatty liver. The level of valine in the peripheral blood began to decrease soon after administration was begun and resulted in a state of systemic valine deficiency. Rats given 25% or more of the valine concentration in the standard TPN solution via the portal vein simultaneously with the administration of central venous valine-depleted nutrition, had a triglyceride level similar to that of the control group. The group given 50% or less of the valine concentration had a level of valine in the peripheral blood as low as that of the valine-depleted group, indicating the maintenance of a valine-deficient state. Administration of low concentrations of valine via the portal vein simultaneous with central venous administration of valine-depleted TPN solution may prevent fatty liver.

Glutamine Prevents the Biliary Lithogenic Effect of Total Parenteral Nutrition in Rats

Long-term total parenteral nutrition (TPN) is known to be associated with pigment gallstones. The objectives of this study were to identify the lithogenic effects of TPN and to determine whether glutamine (GLN)-enriched TPN can prevent such changes. Eighteen male Wistar rats were randomly divided into three groups of six animals. A central line was inserted via the jugular vein. The CHOW group received an infusion of saline and chow ad libitum; the TPN group received a standard TPN solution; the GLN group received TPN solution identical to the TPN group except for the addition of 2% glutamine. Diets were isonitrogenous and isocaloric and fed for 7 days. On Day 7, following laparotomy, the bile duct was cannulated, and bile flow was measured and collected for assay of total and unconjugated bilirubin (TB & UCB) and of total and ionized calcium (TCa & iCa). Caval blood was obtained for liver function studies. The results demonstrated that the hepatic bile flow was decreased in the TPN group compared with the CHOW and the GLN groups. The bilirubin concentration of bile, especially unconjugated bilirubin, in the TPN group was significantly higher when compared with the CHOW and GLN groups ( P < 0.01). The ionized calcium concentration of bile in the TPN group was also increased significantly when compared with the CHOW and GLN groups ( P < 0.05). From these data, we conclude that TPN induces lithogenic effects in hepatic bile, including increased bilirubin and calcium concentrations and decreased hepatic bile flow. Addition of glutamine to the TPN solution prevents these lithogenic changes.

Metabolic effect of parenteral nutrition in dogs with obstructive jaundice.

To assess the effect of total parenteral nutrition (TPN) on macronutrient metabolism in obstructive jaundice. Forty adult mongrel dogs were equally divided into four groups: group I (PO-control) received sham ligation of common bile duct (CBDL) and was fed dog chow and water ad libitum; group II (PO-CBDL) underwent CBDL and was fed dog chow; group III (TPN-control) received sham CBDL and TPN; and group IV (TPN-CBDL) underwent CBDL and received TPN. Blood chemistries, plasma amino acids and liver histologies were studied before (Day 1) and at the end (Day 14) of the experiment. A significant elevation of bilirubin and alkaline phosphatase was observed in dogs with CBDL. Blood glucose was not changed significantly in any group. Significant increases in triglyceride and cholesterol were present in CBDL dogs. Significant differences in the concentrations of a few plasma amino acids, including an elevation of phenylalanine, were found in TPN dogs. A significant increase in aromatic amino acids (AAA) and a noticeable depression of the molar ratio of branched-chain amino acids (BCAA) to AAA was present in TPN-CBDL dogs, as was a significant increase in blood ammonia. In the presence of obstructive jaundice, TPN does not significantly affect carbohydrate or lipid metabolism. However, a derangement in protein metabolism with the standard TPN solution in current use suggests that either a modification of amino acid composition or an increase in total energy to protein energy ratio in TPN solution may be necessary to obviate such a consequence.

Effect of glutamine-supplemented total parenteral nutrition on recovery of the small intestine after starvation atrophy.

Intestinal atrophy was induced in rats by infusion of 5% dextrose for 7 days with only oral water allowed. Compared with control animals fed standard rat chow (Purina Mills, St. Louis), the starved animals lost 30.5% of their initial body weight, 34.7% mucosal wet weight, 68.3% mucosal nitrogen content, 36.7% mucosal thickness, and 38.6% villous height and had variable losses of mucosal disaccharidase activities. Three groups of depleted rats were then refed with different regimens. One group was refed with standard Purina rodent chow (n = 15); a second group with a standard total parenteral nutrition (TPN) solution containing 16% glucose, 2.8% fat, and 4.25% standard amino acids (Travasol 8.5%, Baxter Healthcare Corporation, Deerfield, IL) (n = 15); and the third group with a TPN solution of 16% glucose, 2.8% fat, 2.75% standard amino acids, and 1.5% glutamine (n = 15). After 7 days of refeeding, rats were killed to determine the degree of intestinal recovery. Animals refed with standard TPN solution showed no significant recovery of intestinal mucosal weight, mucosal nitrogen content, villous height, mucosal thickness, or mucosal disaccharidase activities. Animals refed with glutamine-supplemented TPN solution demonstrated significant recovery of all parameters but not back to normal. Oral rodent chow completely restored intestinal anatomy and function. The addition of glutamine to TPN solutions significantly improved recovery of the intestine from starvation atrophy, and additional efforts to make it commercially available are indicated. This study again confirms the preferable use of a regular oral diet when clinically feasible and safe.

Glutamine preserves liver glutathione after lethal hepatic injury.

Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. Glutamine augments host defenses and may be important in GSH synthesis. Acetaminophen toxicity causes hepatic GSH depletion and hepatic necrosis. The authors hypothesized that glutamine-supplemented nutrition would enhance liver GSH stores and diminish hepatic injury and death after acetaminophen overdose. Wistar rats received either a standard total parenteral nutrition (TPN) solution (STD) or an isocaloric, isonitrogenous glutamine-supplemented solution (GLN). On the 5th day of feeding, animals were given acetaminophen (400 mg/kg intraperitoneally) and then killed at various time points. Standard TPN solution animals had a rapid depletion of hepatic glutathione, whereas GLN animals were resistant to this drop and rapidly repleted hepatic GSH stores. Glutamine-supplemented animals maintained higher plasma glutamine concentrations, had lesser elevations in hepatic enzymes, and sustained significantly fewer complications compared with STD animals. The authors conclude that glutamine-supplemented nutrition preserves hepatic glutathione, protects the liver, and improves survival during acetaminophen toxicity. Glutamine may augment host defenses by enhancing antioxidant protection.

The effect of glutamine-enriched TPN on gut immune cellularity

Prolonged parenteral feeding with standard nutrient solutions results in significant alteration in the structural, hormonal, and immunological composition of the intestinal tract. The purpose of the following study was to evaluate the effect of glutamine-supplemented parenteral nutrition on the immune cellularity of the gut. Twenty-one Fischer rats were randomized to three groups of seven animals each. Group I was fed rat chow and water ad lib, Group II was fed a standard solution of total parenteral nutrition (TPN) (D25/4.25% amino acids) via a central venous catheter, and Group III was fed the standard solution of TPN with 2% glutamine which was isonitrogenous and isocaloric to Group II. Animals were fed their respective diets for 1 week and bile was collected and assayed for secretory IgA (s-IgA) and IgM. The terminal ileum was stained and assayed for IgA+, IgM+, IgG+, CD4+, and CD8+ plasma cells and lymphocytes. Results indicate that the feeding of a standard parenteral diet results in a significant decrease in biliary s-IgA and IgA+ plasma cells in the gut lamina propria compared to chow-fed animals (S-IgA: chow, 858 ± 23 μg/ml; TPN, 494 ± 41 μg/ml; IgA cells: chow, 35.7 ± 1.8; TPN, 8.6 ± 0.9 cells/hpf). In addition a marked depletion of CD4+ and CD8+ lymphocytes was observed with standard solutions of parenteral nutrition compared to chow (CD4+: chow, 36.8 ± 6.6; TPN, 14.9 ± 6.0; CD8+: chow, 18.8 ± 5.6; TPN, 5.7 ± 2.7 cells/hpf). The addition of glutamine to the standard TPN solution maintained both B and T cell populations at levels similar to chow-fed animals. Glutamine may be an important nutrient for gut immune function during prolonged parenteral feeding.

Cysteine usage increases the need for acetate in neonates who receive total parenteral nutrition

The addition of cysteine (as cysteine HCl) to a total parenteral nutrition (TPN) solution enhances calcium and phosphate solubility because cysteine lowers the pH of the solution. To determine whether adding cysteine to TPN solutions affected the acid-base homeostasis of infants and increased their need for acetate to obviate acidosis, we studied two groups of neonates--those receiving TPN before (group C) and after (group NC) the addition of cysteine. Measurements were made before and during the first 2 wk of TPN administration. We measured the pH of our standard TPN solution with and without the addition of cysteine. Serum carbon dioxide was significantly lower in group C despite a significantly greater intake of acetate in group NC. In the in vitro study the addition of cysteine to the TPN solution lowered the pH from 5.5 to 5.1. Newborns who received TPN solutions to which cysteine was added had lower serum carbon dioxide values and a greater need to receive acetate than did newborns who received TPN solutions without cysteine.

Effect of Tryptophan and Cyproheptadine on Food Intake

Whether tryptophan in the usual dose found in total parenteral nutrition (TPN) solutions caused a decrease in food intake was investigated in 16 adult male Fischer 344 rats. A jugular venous catheter was placed, and patency was maintained with a continuous infusion of normal saline at 3 ml/hr. After a 10-day recovery period, eight normal saline control rats were sacrificed and the remaining eight rats were given a parenteral nutrition solution (PN-50) at 3 ml/hr, providing 50% of the rat's daily energy requirement as 5% dextrose and 2% Intralipid. On day 14, study rats were further divided into two subgroups. Subgroup A received tryptophan (180 mg/day) added to the solution for 5 days. Subgroup B received the serotonin-receptor blocker, cyproheptadine 24 mg/kg/day, continuously for 5 days, and on day 16, tryptophan (0.25% = 180 mg/kg/day) was added to the solution for 3 days. Chow and water was continuously available and spontaneous food intake was measured daily. Study rats were sacrificed on day 19. Plasma amino acids and insulin and whole brain biogenic amines were compared with those in control rats using Student's t-test. With administration of PN-50, spontaneous food intake decreased to about 60% compared with the pre-PN level. The addition of tryptophan to the continuous infusion of PN-50 did not decrease spontaneous food intake further.(ABSTRACT TRUNCATED AT 250 WORDS)