Enteral Infusion Research Articles

The Route of Administration (Enteral or Parenteral) Affects the Conversion of Isotopically Labeled L‐[2‐15N]Glutamine Into Citrulline and Arginine in Humans

Glutamine exhibits numerous beneficial effects in experimental and clinical studies. It has been suggested that these effects may be partly mediated by the conversion of glutamine into citrulline and arginine. The intestinal metabolism of glutamine appears to be crucial in this pathway. The present study was designed to establish the effect of the feeding route, enteral or parenteral, on the conversion of exogenously administered glutamine into citrulline and arginine at an organ level in humans, with a focus on gut metabolism. Sixteen patients undergoing upper gastrointestinal surgery received an IV or enteral (EN) infusion of L-[2-(15)N]glutamine. Blood was sampled from a radial artery and from the portal and right renal vein. Amino acid concentrations and enrichments were measured, and net fluxes of [(15)N]-labeled substrates across the portal drained viscera (PDV) and kidneys were calculated from arteriovenous differences and plasma flow. Arterial [(15)N]glutamine enrichments were significantly lower during enteral tracer infusion (tracer-to-tracee ratio [labeled vs unlabeled substrate, TTR%] IV: 6.66 +/- 0.35 vs EN: 3.04 +/- 0.45; p < .01), reflecting first-pass intestinal metabolism of glutamine during absorption. Compared with IV administration, enteral administration of the glutamine tracer resulted in a significantly higher intestinal fractional extraction of [(15)N]glutamine (IV: 0.15 +/- 0.03 vs EN: 0.44 +/- 0.08 micromol/kg/h; p < .01). Furthermore, enteral administration of the glutamine tracer resulted in higher arterial enrichments of [(15)N]citrulline (TTR% IV: 5.52 +/- 0.44 vs EN: 8.81 +/- 1.1; p = .02), and both routes of administration generated a significant enrichment of [(15)N]arginine (TTR% IV: 1.43 +/- 0.12 vs EN: 1.68 +/- 0.18). This was accompanied by intestinal release of [(15)N]citrulline across the PDV, which was higher with enteral glutamine (IV: 0.38 +/- 0.07 vs EN: 0.72 +/- 0.11 micromol/kg/h; p = .02), and subsequent [(15)N]arginine release in both groups. In humans, the gut preferably takes up enterally administered glutamine compared with intravenously provided glutamine. The route of administration, enteral or IV, affects the quantitative conversion of glutamine into citrulline and subsequent renal arginine synthesis in humans.

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Lack of Effect of Acute Enteral Arginine Infusion on Whole-Body and Intestinal Protein Metabolism in Humans

Arginine is a conditionally essential amino acid and exerts anabolic effects. We studied the effects of enteral arginine on whole-body and duodenal protein metabolism. Eight healthy fasted volunteers received randomly a 5-hr enteral infusion of either arginine (Arg; 20 g) or an isonitrogenous amino acid mixture (AA) and an IV infusion of [13C]leucine. Duodenal biopsies were performed. Whole-body protein turnover and duodenal protein synthesis (FSR) were calculated from GC/MS-assessed enrichment. The mRNA levels for major components of proteolytic pathways, ubiquitin, cathepsin D, and m-calpain, were evaluated by RT-PCR. Results were compared using paired Wilcoxon test. Endogenous, oxidative, and nonoxidative leucine fluxes were not different after Arg and AA infusions, respectively. Duodenal mucosal protein FSR (71% +/- 26% vs 81% +/- 30%/day) and mRNA levels of ubiquitin, cathepsin D, and m-calpain were also similar after Arg and AA infusions. We conclude that in healthy subjects, arginine infusion exerts no effect on whole-body and duodenal protein metabolism. Whether arginine might specifically affect these parameters in catabolic or inflammatory situations remains to be determined.

Enteral water for hypernatremia and intestinal morbidity in infants less than or equal to 1000 g birth weight

To evaluate the relationship between enteral water infusion for hypernatremia and significant intestinal morbidity in infants <or=1000 grams. This is a retrospective study of 321 infants <or=1000 g birth weight. Infants were grouped by the highest serum sodium (mmol/l) during the first 14 days of life as follows: <150 (normal control), >or=150 (high sodium control), >or=150 and treated with sterile water (study group). Significant intestinal morbidity was defined as probable or proven necrotizing enterocolitis or spontaneous intestinal perforation. Statistical analysis included Student's t test for continuous variables and chi(2) with Yeats correction for frequency variables. Multivariate logistic regression analysis was then performed to evaluate confounding variables among groups. The incidence of intestinal morbidity was significantly higher in the high sodium-water treated group compared to each of the other groups (13/33 (38%) for high sodium-water versus 16/100 (16%) for high sodium control and 18/188 (10%) for normal sodium control, P<0.01 chi(2)). Logistic regression analysis indicated that enteral water and hydrocortisone were risk factors for significant intestinal morbidity. Enteral sterile water for hypernatremia appears to be associated with significant intestinal morbidity in infants <or=1000 g. Hydrocortisone is also a risk factor.

First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs.

Our results in a previous study indicated that the portal absorption of intragastrically fed alpha-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net portal nutrient absorption in young pigs (n = 9) given an intraduodenal infusion of milk replacer [10 mL/(kg . h)] and either saline (control) or 930 micromol/(kg . h) AKG for 4 h. In study 2, we quantified the luminal disappearance of a duodenal AKG bolus in young pigs (n = 7). In study 3, we quantified the whole-body kinetics of (13)C-AKG metabolism when infused either enterally (n = 9) or intravenously (n = 9) in young pigs. In study 1, when compared with the control group, enteral AKG infusion increased (P < 0.01) the arterial (13.8 +/- 1.7 vs. 27.4 +/- 3.6 micromol/L) and portal (22.0 +/- 1.4 vs. 64.6 +/- 5.9 micromol/L) AKG concentrations and the net portal absorption of AKG [19.7 +/- 2.8 vs. 95.2 +/- 12.0 micromol/(kg . h)]. The mean fractional portal appearance of enterally infused AKG was 10.23 +/- 1.3%. In study 2, the luminal disappearance of AKG was 663 micromol/(kg . h), representing 63% of the intraduodenal dose. In study 3, the whole-body (13)C-AKG flux [4685 +/- 666 vs. 801 +/- 67 micromol/(kg . h)] was higher (P < 0.05) when given enterally than intravenously, but (13)CO(2) recovery was not different (37.3 +/- 1.0 vs. 36.2 +/- 0.7%dose). The first-pass splanchnic (13)C-AKG utilization was approximately 80%, of which 30% was oxidized to (13)CO(2). We conclude that the intestinal absorption of AKG is limited in young pigs largely due to substantial first-pass gastrointestinal metabolism.

Enteral levodopa/carbidopa gel infusion for the treatment of motor fluctuations and dyskinesias in advanced Parkinson’s disease

Pharmacotherapy designed to alleviate the symptoms of Parkinson’s disease is focused on the stimulation of striatal dopamine receptors. The ideal pharmacological treatment would involve continuous dopaminergic stimulation. Currently, the most effective pharmacotherapy available is levodopa delivered orally; however, its short plasma half-life in combination with erratic gastric emptying and intestinal absorption makes dopaminergic stimulation pulsatile. Motor fluctuations and dyskinesias develop with time as a consequence and can become disabling. A gel formulation of levodopa/carbidopa has been developed for enteral (duodenal or jejunal) infusion via a portable pump. The infusion provides smooth plasma levodopa levels, more continuous dopaminergic stimulation and effective treatment of motor complications.

Long-term 24-hour duodenal infusion of levodopa: Outcome and dose requirements

Short-term IV 24-hour levodopa infusion has been shown to improve motor variability and dyskinesias in patients with Parkinson disease (PD) with motor fluctuations.1 Longer-term around-the-clock enteral infusion of levodopa (n = 1) showed declining motor performance although the infusion rate was rapidly increased.2 It has been proposed that tolerance develops as a result of long continuous infusions of levodopa and dopamine agonists.3 Nighttime-only levodopa infusion has been reported in one case with immediate improvement of nocturnal akinesia.4 Duodenal/jejunal levodopa/carbidopa infusion (Duodopa) has evolved into a treatment alternative in patients with advanced PD.5 It is recommended for daytime use partly because of convenience for the patient and partly because of fear of tolerance development. Because nighttime disability and sleep disturbance are common problems for patients with advanced PD,6 oral dopaminergic medication is sometimes used during nighttime to improve sleep. We report retrospective data on five cases with continuous …

Pharmacokinetic Optimisation in the Treatment of Parkinson???s Disease

Pharmacotherapy for Parkinson's disease is focused on dopaminergic drugs, mainly the dopamine precursor levodopa and dopamine receptor agonists. The elimination half-life (t(1/2)) of levodopa from plasma (in combination with a decarboxylase inhibitor) of about 1.5 hours becomes more influential as the disease progresses. The long-duration of response to levodopa, which is evident in early Parkinson's disease, diminishes and after a few years of treatment motor performance is closely correlated to the fluctuating plasma concentrations of levodopa. Absorption of levodopa in the proximal small intestine depends on gastric emptying, which is erratic and may be slowed in Parkinson's disease. The effects of levodopa on motor function are dependent on gastric emptying in patients in the advanced stages of disease. The current treatment concept is continuous dopaminergic stimulation (CDS). Sustained-release formulations of levodopa may provide more stable plasma concentrations. Oral liquid formulations shorten the time to reach peak concentration and onset of effect but do not affect plasma levodopa variability. The t(1/2) of levodopa can be prolonged by adding a catechol-O-methyltransferase inhibitor (entacapone or tolcapone), which may reduce fluctuations in plasma concentrations, although both peak and trough concentrations are increased with frequent administration. Intravenous and enteral (duodenal/jejunal) infusions of levodopa yield stable plasma levodopa concentrations and motor performance. Enteral infusion is feasible on a long-term basis in patients with severe fluctuations. Among the dopamine receptor agonists the ergot derivatives bromocriptine, cabergoline, dihydroergocryptine and pergolide, and the non-ergot derivatives piribedil, pramipexole and ropinirole, have longer t(1/2) compared with levodopa. Thus, they stimulate dopamine receptors in a less pulsatile manner, yet pharmacokinetic studies of repeated doses of dopamine receptor agonists are few. Optimisation of these drugs is often performed with standardised titration schedules. Apomorphine and lisuride have short t(1/2) and are suitable for subcutaneous infusion, with results similar to those of levodopa infusion. Transdermal administration of dopamine receptor agonists such as rotigotine might be an alternative in the future. In general, initial dopamine receptor agonist monotherapy is associated with poorer motor performance and lower incidence of motor complications compared with levodopa. Buccal administration of the monoamine oxidase-B inhibitor selegiline (deprenyl) provides better absorption and less formation of metabolites compared with standard tablets. To conclude, several new drugs, formulations and routes of administration have been introduced in the treatment of Parkinson's disease during the last decade, mainly with CDS as the aim. CDS can be approached by optimising the use of dopaminergic drugs based on pharmacokinetic data.

Enteral Feeding Without Pancreatic Stimulation

All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result in enteral feeding without pancreatic stimulation, with particular reference to trypsin, because the avoidance of trypsin stimulation may optimize enteral feeding in acute pancreatitis. The pancreatic secretory responses to feeding were studied in 36 healthy volunteers by standard double-lumen duodenal perfusion/aspiration techniques over 6 hours. Subjects were assigned to no feeding (n = 7), duodenal feeding with a polymeric diet (n = 7) or low-fat elemental diet (n = 6), mid-distal jejunal feeding (n = 11), or intravenous feeding (n = 5). All diets provided 40 kcal/kg ideal body weight/d and 1.5 g protein/kg ideal body weight/d. Plasma gut peptide responses were monitored in 15 subjects. In comparison with basal fasting trypsin secretion rates (mean = 134 [standard error = 22] U/h), duodenal feeding with the polymeric and elemental formulae stimulated trypsin secretion (mean = 408 [standard error = 51] U/h; P < 0.001), whereas intravenous feeding (mean = 171 [standard error = 34] U/h) and mid-distal jejunal (mean = 119 [standard error = 16] U/h) did not. Stimulation was associated with an increase in plasma cholecystokinin, whereas distal jejunal feeding resulted in an increase in plasma glucagon-like peptide-1 and peptide YY concentrations. Our results suggest that enteral feeding can be given without stimulating pancreatic trypsin secretion provided it is delivered into the mid-distal jejunum. The mechanism may involve activation of the ileal brake mechanism.

Continuous L-dopa infusion

Continuous dopaminergic stimulation (CDS) is the predominant pharmacotherapeutic strategy in Parkinson's disease (PD). Levodopa is the most effective anti-PD drug but CDS is not achievable with oral formulations due to the short elimination half-life of levodopa. In advanced PD, motor performance is strongly correlated to plasma concentrations of levodopa, thus stable plasma levels are required for optimal effect. Intravenous infusion is the most reliable route of administration, but it is impractical for long-term therapy. Enteral (duodenal/jejunal) infusion of a gel formulation of levodopa/carbidopa has been studied since 1991. A pharmacokinetic trial showed that the enteral infusion provided significantly less fluctuations in plasma levodopa compared to oral sustained-release tablets. Motor performance was significantly more stable, because severe 'off' episodes could be avoided, in a trial comparing infusion as monotherapy with individualised combination therapies. Long-term follow-ups, in total more than 200 patient-years, have not shown any unexpected side-effects. Technical problems with the infusion system were rather common but may be overcome with new techniques for tubing. The infusion therapy is intended for daytime use but a few patients with severe nocturnal akinesia have successfully been treated with levodopa infusion 'around-the-clock' for up to 3 years. The 14-year-long experience suggests that enteral levodopa infusion is a safe and efficacious alternative to treat motor fluctuations and dyskinesias in advanced PD patients.

Trypsin and splanchnic protein turnover during feeding and fasting in human subjects

Knowledge of the stimulatory effects of enteral and parenteral (intravenous) feeding on the synthesis and turnover of trypsin would help in the management of acute pancreatitis, because the disease is caused by the premature activation of trypsin. To investigate this, we labeled intravenous infusions with [1-(13)C]leucine and enterals with [(2)H]leucine and measured isotope enrichment of plasma, secreted trypsin, and duodenal mucosal proteins over 6 h by duodenal perfusion/aspiration and endoscopic biopsy. Thirty healthy volunteers were studied during fasting (n = 7), intravenous feeding (n = 6), or postpyloric enteral feeding [duodenal polymeric (n = 6), elemental duodenal (n = 6), and jejunal elemental (n = 5)]. All diets provided 1.5 g x kg(-1) x day(-1) protein and 40 kcal x kg(-1) x day(-1) energy. Results demonstrated that compared with fasting, enteral feeding increased the rate of appearance (71 +/- 4 vs. 91 +/- 5 min, P = 0.01) and secretion (546 +/- 80 vs. 219 +/- 37 U/h, P = 0.01) of newly labeled trypsin and expanded zymogen stores (1,660 +/- 237 vs. 749 +/- 133 units, P = 0.03). These differences persisted whether the feedings were polymeric or elemental, duodenal, or jejunal. In contrast, intravenous feeding had no effect on basal rates. Differential labeling of the plasma amino acid pool by enteral and intravenous isotope infusions suggested that 35% of absorbed amino acids were retained within the splanchnic bed during enteral feeding and that mucosal protein turnover increased from a fasting rate of 34 +/- 6 to 108 +/- 8%/day (P < 0.05) compared with no change after intravenous feeding. In conclusion, all common forms of enteral feeding stimulate the synthesis and secretion of pancreatic trypsin, and only parenteral nutrition avoids it.

A New Swivel Model for Parenteral and Enteral Infusion in Rats

In experimentation with rats submitted to enteral and parenteral infusions for medium to long periods it is necessary to use swivels. With the objective of developing a new biocompatible, safe, efficient, and low cost swivel, the medical and engineering teams of the University of São Paulo joined forces. After defining the characteristics and criteria for the mechanical design, the new swivel was developed and bench tested for flow, rotation and sealing. Later it was evaluated on rats, after catheterization of jugular vein and stomach (by gastrostomy) for infusion of different solutions at certain concentrations and infusion rates (mean 6.73 days of infusion). The new swivel consisted of two sections of common plastic syringes for injection, together with the rubber seals, a plunger, and a hypodermic needle. The syringe with a slightly smaller diameter rotates inside the larger diameter syringe interconnected with a needle sealed by their respective rubber rings. The bench and animal tests did not reveal any functional defects. There were no blockages or leaks in the swivel and it was reused three times without losing its mechanical properties, after being hygienized and sterilized with ethylene oxide. The cost of producing this swivel is estimated to be no more than $3 US. The cooperation between the departments of medical research and mechanical engineering enabled the development of a swivel that is simple and inexpensive to make, yet fully meets the needs of parenteral and enteral infusion in rats. The authors present detailed instructions for the construction of this new swivel.

The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients

Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (P<0.05). Ala-Gln was undetectable with enteral administration, whereas Ala-Gln remained stable at a plasma concentration of 268 micromol/l throughout parenteral infusion and rapidly decreased towards zero after infusion was stopped. The highest level of glutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

Management of Blood Glucose and Diabetes in the Critically Ill Patient Receiving Enteral Feeding

Diabetes mellitus causes profound alterations in nutrient metabolism, leading to long-term systemic complications, particularly in individuals with poorly controlled disease. Nutrition support clinicians need to be aware of the effect of acute illness on stress-induced and established diabetes mellitus and the appropriate management strategies. Because enteral feeding is a vital component of critical care for many patients with diabetes mellitus, it is important to develop techniques to best manage metabolic control during enteral feeding. This article will review mechanics of blood glucose regulation, evaluation of energy sources for patients with diabetes mellitus, selection of enteral formulas and infusion routes, and glycemic control in patients receiving tube feeding. At this point, it is appropriate to use a standard formula to initiate feedings in most patients with blood glucose abnormalities. Close monitoring and judicious use of insulin are key in maintaining glucose control and avoiding complications.

Soluté de réhydratation orale (SRO) et hydratation entérale du nouveau-né dans les 15 premiers jours de vie : tolérance, efficacité et limites

We conducted a retrospective evaluation of enteral infusion with a marketed hypoosmolar oral rehydration solution (HORS), as an alternative to intravenous infusion. Premature infants, with difficult venous condition, 30 weeks or more during HORS infusion. Enteral ORS started after well-tolerated milk gastric gavage. Gradual increase of enteral feeding. January 1999 to April 2001, 105 neonates 28 weeks to 36 weeks, birth weight 1050 to 2700g, including 71.5% eutrophic newborns 30 to 34 weeks; 13.3% hypotrophic<10th P. More than 90% had a physiological weight curve: weight loss vs birth<15%, back to birth weight at day 15. No significant pathology during ORS. Failure of ORS for 7/105 children. Relative risk increased 8 fold if term was less than 30 weeks, 7 folds in the event of enteropathy before ORS. In 26.7% of the infants, gastric enteral residuals exceeded 1/3 of intake, vomiting and/or abdominal ballooning lasted less than 48 hours. There were 4 deaths during follow-up (periventricular leucomalacia, myocardial infarctus) and 1 necrotizing enterocolitis. At theoretical birth date, 25% of the neonates were hypotrophic<10th P. At one and 2 years of age, less than 5% were still hypotrophic: relative risk increased 18 fold when birth weight was<5th P. HORS is an efficient, well-tolerated, low-cost and less invasive alternative to intravenous infusion. It must be reserved for eutrophic neonates born>30 weeks gestation due to risk of failure and insufficient growth. Validation with a multicentric clinical trial is in progress.

Introduction of Enteral Food Increases Plasma GLP-2 and Decreases GLP-2 Receptor mRNA Abundance during Pig Development

Glucagon-like peptide 2 (GLP-2) may mediate in part the rapid growth effects of luminal nutrients in the small intestine of newborns. The objectives of this study were to determine plasma GLP-2 concentrations and small intestinal GLP-2 receptor (GLP-2R) mRNA abundance (measured by reverse transcription polymerase chain reaction) during pre- and postnatal development and the relationship between these variables and small intestinal growth in enterally and parenterally fed fetal and newborn pigs (premature and term-delivered, 92 and 100% gestation, respectively). Plasma GLP-2 concentrations increased before birth, peaked in suckling 1-d-old pigs (87 +/- 14 pmol/L, P < 0.05), decreased with weaning-related anorexia (34 +/- 5 pmol/L, P < 0.05) and increased when normal food intake resumed (81 +/- 9 pmol/L, P < 0.05). Plasma GLP-2 concentrations were increased 1 d after enteral infusion of colostrum in fetal pigs at 92% gestation compared with untreated controls (59 +/- 11 vs. 7 +/- 2 pmol/L, P < 0.05). In newborn pigs, plasma GLP-2 was increased 2-6 d after the enteral administration of a milk diet, compared with the parenteral infusion of elemental nutrients, but the time course of the response was delayed in premature newborn pigs. Small intestinal GLP-2R mRNA abundance was highest at birth and decreased with enteral food intake in fetal, suckling and weaned pigs (P < 0.05). In contrast, enteral feeding increased (P < 0.05) relative small intestinal weight and/or villous heights in these pigs. We conclude that the introduction of enteral feeding transiently increases plasma GLP-2 concentrations and decreases small intestinal GLP-2R mRNA levels during pig development. GLP-2 may play a role in the growth of the small intestine around birth and weaning via a response to enteral nutrition.

The relative utilization of enteral and parenteral amino acid infusions for the synthesis of whole body and trypsin proteins in humans

The relative utilization of enteral and parenteral amino acid infusions for the synthesis of whole body and trypsin proteins in humans

(+)-Catechin is a Potent Inhibitor of Intestinal Absorption of Cholesterol in Rats

Catechins exhibit a hypocholesterolemic effect in cholesterol-fed animals. The present study was conducted to examine whether (+)-catechin influences the absorption of cholesterol in rats. Male Sprague-Dawley rats were fed ad libitum an AIN-93G diet containing soybean oil for 5 wk. Rats with lymph cannulae were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion containing radiolabeled cholesterol with or without (+)-catechin. Lymph was collected hourly for 8 h. The enteral infusion of (+)-catechin significantly lowered the lymphatic absorption of (14)^C-cholesterol (21.1±3.6% dose/8 h) compared with controls infused with the lipid emulsion devoid of (+)-catechin (38.2±1.2% dose/8 h). The intestinal absorption of α-tocopherol (24.2±3.0% dose/8 h) also was significantly decreased by (+)-catechin infusion, relative to controls (32.2±2.2% dose/8 h). However, the lymphatic outputs of oleic acid, phospholipid were not affected by enteral (+)-catechin infusion. The results indicate that (+)-catechin has a profound inhibitory effect on the intestinal absorption of cholesterol, α-tocopherol without affecting the absorption of fat.

Acute Enteral Glutamine Infusion Enhances Heme Oxygenase-1 Expression in Human Duodenal Mucosa

The heat shock protein, heme oxygenase-1 (HO-1), contributes to the protection of the intestine. Some experimental models suggest that induction of HO-1 by glutamine may contribute to the preservation of intestinal mucosa. The effect of an enteral infusion of glutamine for 6 h on HO-1 expression in duodenal mucosa was studied in healthy men and women and compared with an isonitrogenous mixture of amino acids. After enteral infusion, endoscopic duodenal biopsies were performed and either fixed in formalin for immunohistochemistry or frozen for HO-1 mRNA analysis by reverse transcriptase-polymerase chain reaction. Histologic examination revealed that HO-1 was constitutively expressed in intestinal epithelial cells (IEC), and that glutamine increased the grade of HO-1 immunostaining (P </= 0.01). Glutamine also increased the percentage of HO-1 immunoreactive lamina propria cells (LPC, 10.5 vs. 7.5%, P </= 0.05). Glutamine significantly increased HO-1 mRNA expression compared with control amino acids: median (range) 156 (102-182) vs. 100 (68-179)%, P </= 0.05. The mRNA level for HO-1 was correlated with the percentage of immunoreactive LPC (r = 0.55, P = 0.017) and the grade of immunostaining in IEC (r = 0.51, P = 0.030). In conclusion, glutamine enhanced HO-1 mRNA and protein expression in human duodenal mucosa. These data support further evaluation of the effects of glutamine on intestinal HO-1 during states of intestinal inflammation.

Glutamine promotes triglyceride absorption in a dose-dependent manner.

Dietary proteins may play a role in lipid absorption. Whether amino acids are specifically involved is unknown. We hypothesized that enterally administered L-glutamine (L-Gln) given with a lipid meal increases triglyceride (TG) absorption in rats. Mesenteric lymph fistulae and gastroduodenal feeding tubes were placed in adult male Sprague-Dawley rats. The animals received an enteral bolus of Intralipid (5 ml) followed by enteral infusion of increasing concentrations of L-Gln in saline (0, 85, 170, or 340 mM) or equimolar concentrations of the inactive isomer D-Gln or an essential amino acid mixture without Gln. Lymph was collected continuously for 6 h and analyzed for TG content. Animals infused with 85 mM L-Gln had a 64% increase in total TG output vs. controls (P < 0.05) despite no difference in lymph flow rate. Total TG output for animals infused with 340 mM L-Gln declined by 43% vs. controls (P < 0.05). The effect of Gln in promoting lymphatic fat transport is specific to L-Gln and not shared by D-Gln or an equivalent amino acid mixture. L-Gln is capable of either promoting or impairing lymphatic TG transport in a dose-dependent manner.