Plasma Glutamine Concentration Research Articles

Alterations in glutamine metabolism and its conversion to citrulline in sepsis

In enterocytes, glutamine serves as the major source of energy; another metabolic fate of glutamine is conversion to citrulline. Because sepsis can affect gut function and integrity, alterations in glutamine metabolism may exist and lead to decreased citrulline production. This study aimed to investigate how sepsis affects glutamine metabolism, including its conversion to citrulline, by measuring glutamine and citrulline flux, fractional splanchnic extraction of glutamine and leucine, and the contribution of glutamine nitrogen to citrulline in septic patients and healthy controls. Eight patients with severe sepsis and 10 healthy controls were given primed, constant intravenous infusion of [(2)H2]citrulline and sequential administration of intravenous and enteral [α-(15)N]glutamine and [(13)C]leucine in the postabsorptive state. The results showed that, compared with healthy controls, septic patients had a significantly lower whole body citrulline flux and plasma concentration, higher endogenous leucine flux, and higher glutamine clearance. Fractional splanchnic extraction of leucine was higher in septic patients than in controls, but fractional extraction of glutamine was not different. The majority of the (15)N label transferred from glutamine to citrulline was found at the α-position. These results demonstrate that lower glutamine plasma concentrations in sepsis were a result of increased glutamine clearance. Despite adequate splanchnic uptake of glutamine, there is decreased production of citrulline, suggesting a defect in the metabolic conversion of glutamine to citrulline, decreased uptake of glutamine by the enterocyte but increased uptake by the liver, and/or shunting of glutamine to other metabolic pathways.

Neuronal Excitotoxicity after Carotid Angioplasty and Stent Placement Procedures

To investigate if glutamate levels also increase in carotid angioplasty and stent placement (CAS) procedures, since high plasma glutamate levels are associated with ischemic infarction and transient ischemic attacks, but the length of ischemia needed to elicit such elevation has not been assessed. All patients or their relatives signed informed consent. By using high-performance liquid chromatography, plasma glutamate concentrations were determined in 74 patients treated with CAS. Blood samples were obtained with arterial and peripheral venous catheterization before and after the procedure, and venous blood samples were obtained 24, 48, and 72 hours after CAS. Glutamate concentrations were also analyzed in two different control groups: 16 patients without carotid stenosis before and after diagnostic cerebral angiography and 20 patients treated with coronary angioplasty and stent placement. The χ(2) test, t test, and analysis of variance were used to compare glutamate concentrations among the groups. Baseline glutamate concentrations were similar between patients who underwent CAS and both control groups. In CAS patients, glutamate concentrations in venous blood increased immediately after the procedure (354.1 μmol/L ± 132.8) and returned to baseline levels at 24 hours (129.5 μmol/L ± 56.8) (P < .0001). Glutamate concentrations remained unchanged over time in both control groups. A rapid increase in plasma glutamate levels occurs after CAS procedures, unrelated to stroke.

Contribution of creatine to protein homeostasis in athletes after endurance and sprint running

Few studies have focused on the metabolic changes induced by creatine supplementation. This study investigated the effects of creatine supplementation on plasma and urinary metabolite changes of athletes after endurance and sprint running. Twelve male athletes (20.3 ± 1.4 y) performed two identical (65-70 % maximum heart rate reserved) 60 min running exercises (endurance trial) before and after creatine supplementation (12 g creatine monohydrate/day for 15 days), followed by a 5-day washout period. Subsequently, they performed two identical 100 m sprint running exercises (power trial) before and after 15 days of creatine supplementation in accordance with the supplementary protocol of the endurance trial. Body composition measurements were performed during the entire study. Plasma samples were examined for the concentrations of glucose, lactate, branched-chain amino acids (BCAAs), free-tryptophan (f-TRP), glutamine, alanine, hypoxanthine, and uric acid. Urinary samples were examined for the concentrations of hydroxyproline, 3-methylhistidine, urea nitrogen, and creatinine. Creatine supplementation significantly increased body weights of the athletes of endurance trial. Plasma lactate concentration and ratio of f-TRP/BCAAs after recovery from endurance running were significantly decreased with creatine supplementation. Plasma purine metabolites (the sum of hypoxanthine and uric acid), glutamine, urinary 3-methylhistidine, and urea nitrogen concentrations tended to decrease before running in trials with creatine supplements. After running, urinary hydroxyproline concentration significantly increased in the power trial with creatine supplements. The findings suggest that creatine supplementation tended to decrease muscle glycogen and protein degradation, especially after endurance exercise. However, creatine supplementation might induce collagen proteolysis in athletes after sprint running.

Effect of glutamine supplementation on neutrophil function in male judoists

Glutamine is an important amino acid for immune function. Though high intensity and prolonged exercise decreases plasma glutamine concentration and causes immune suppression, the relationship between neutrophil functions and glutamine has not yet been found. The purpose of this study was to investigate the impacts of glutamine supplementation on neutrophil function. Twenty-six male university judoists were recruited. Subjects were classified into glutamine and control groups. The glutamine group ingested 3000 mg of glutamine per day and the control group ingested placebo for 2 weeks. Examinations were performed at the start of preunified loading exercise (pre-ULE), then 1 and 2 weeks after ULE (post-ULE). Reactive oxygen species (ROS) production, phagocytic activity, serum opsonic activity and serum myogenic enzymes were measured. Differences between the levels obtained in pre-ULE and post-ULE for the two groups were compared. In the glutamine group, ROS production activity increased 1 week after ULE, whereas it was not observed in the control group (P < 0.001). Though myogenic enzymes increased significantly after ULE (P < 0.001), the glutamine group remained unchanged by supplementation during ULE. Glutamine supplementation has prevented excessive muscle damage and suppression of neutrophil function, especially in ROS production activity, even during an intensive training period.

Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs

Dietary intake of glutamate by postweaning pigs is markedly reduced due to low feed consumption. This study was conducted to determine the safety and efficacy of dietary supplementation with monosodium glutamate (MSG) in postweaning pigs. Piglets were weaned at 21 days of age to a corn and soybean meal-based diet supplemented with 0, 0.5, 1, 2, and 4 % MSG (n = 25/group). MSG was added to the basal diet at the expense of cornstarch. At 42 days of age (21 days after weaning), blood samples (10 mL) were obtained from the jugular vein of 25 pigs/group at 1 and 4 h after feeding for hematological and clinical chemistry tests; thereafter, pigs (n = 6/group) were euthanized to obtain tissues for histopathological examinations. Feed intake was not affected by dietary supplementation with 0-2 % MSG and was 15 % lower in pigs supplemented with 4 % MSG compared with the 0 % MSG group. Compared with the control, dietary supplementation with 1, 2 and 4 % MSG dose-dependently increased plasma concentrations of glutamate, glutamine, and other amino acids (including lysine, methionine, phenylalanine and leucine), daily weight gain, and feed efficiency in postweaning pigs. At day 7 postweaning, dietary supplementation with 1-4 % MSG also increased jejunal villus height, DNA content, and antioxidative capacity. The MSG supplementation dose-dependently reduced the incidence of diarrhea during the first week after weaning. All variables in standard hematology and clinical chemistry tests, as well as gross and microscopic structures, did not differ among the five groups of pigs. These results indicate that dietary supplementation with up to 4 % MSG is safe and improves growth performance in postweaning pigs.

Effect of glutamine on glucose metabolism in children with Duchenne muscular dystrophy

Glutamine is a potent gluconeogenic precursor and stimulates insulin secretion. Glutamine's effect on glucose metabolism in Duchenne muscular dystrophy (DMD) has never been studied. To determine plasma glucose and insulin concentrations measured during and after glutamine administration in DMD boys. We hypothesized that glutamine can modulate whole body glutamine-glucose metabolism in DMD, a genetically determined disease. As secondary endpoints of a randomized crossover trial in 30 prepubertal DMD boys, we measured fasting blood glucose, insulin and the Homeostasis Model Assessment (HOMA) index after daily oral glutamine (0.5gkg(-1) d(-1)) for 4 months versus placebo. In a separate time series trial in 6 prepubertal DMD boys, we measured the same endpoints as well as plasma glutamine and whole body glucose turnover (Ra,glc) (primed continuous i.v. infusion of d-[6,6-(2)D]glucose), while participants received acute oral glutamine (0.5gkg(-1) d(-1)) continuously for 5h. In the randomized trial, baseline measurements of HOMA correlated with age (r=0,51, p=0.007) and percent fat estimated by bioelectrical impedance analysis (BIA) (r=0.39, p=0.047). After 4 months glutamine supplementation, we observed no treatment or order effect on HOMA or insulin. During acute glutamine for 5h (time series trial), plasma glutamine doubled and was associated with increased plasma insulin concentration (10.42±2.54 vs 7.32±1.86, p=0.05) with no effect on plasma glucose, HOMA or Ra,glc. Acute glutamine transiently stimulates insulin secretion in DMD boys, which could be mediated by plasma glutamine concentrations. Fasting insulin concentration and HOMA might provide quantifiable indices of disease progression.

Dynamic changes in blood flow and oxygen consumption in the portal-drained viscera of growing pigs receiving acute administration of l-arginine

This study tested the hypothesis that an increase in arginine concentration in the portal vein may affect blood flow and oxygen consumption in the portal-drained viscera (PDV) of swine. Eight barrows (70 kg body weight) were surgically fitted with chronic catheters in the portal vein, ileal vein, and carotid artery. Thirteen days after the surgery, pigs that had been fasted for 12 h were randomly allocated to receive administration of either L-alanine (103 mg/kg body weight, isonitrogenous control) or L-arginine-HCl (61 mg/kg body weight) via the portal vein. Portal vein blood flow (PVBF) was measured with infusion of p-aminohippuric acid into the ileal vein, and blood samples were simultaneously obtained every 0.5 h for 4 h. Compared with the control, arginine infusion increased PVBF at 30-90 min after infusion but decreased PDV oxygen consumption at 60-150 min after infusion (P < 0.05). Plasma concentrations of glutamate at infusion times of 180-240 min and of arginine at infusion times of 60-240 min in arginine-infused pigs were higher than those for the control group (P < 0.05). Plasma concentrations of insulin and glucagon at the infusion times of 30-90 min were higher and of free fatty acids at the infusion times of 60-120 min were lower than those for the control pigs (P < 0.05). These results indicate that increasing arginine concentration in the portal vein enhances PDV blood flow, reduces PDV oxygen consumption, and beneficially alters the metabolic profile in swine, an established animal model for studying human nutrition and metabolism.

L-glutamine absorption is enhanced after ingestion of l-alanylglutamine compared with the free amino acid or wheat protein

Differences in plasma L-glutamine (L-Gln) concentrations from ingestion of different formulations of L-Gln were examined in 8 men (26.8 ± 4.2 years old, 181.1 ± 10.9 cm, 85.8 ± 15.4 kg). Subjects reported to the laboratory on 4 separate occasions and randomly consumed 1 of 4 drinks containing 60 mg/kg of L-Gln; 89 mg/kg of Sustamine (L-alanylglutamine [AlaGln]; Kyowa Hakko Europe GmbH, Düsseldorf, Germany), which contained an equivalent L-Gln dose as consumed in L-Gln); 200 mg/kg of an enzymatically hydrolyzed wheat protein (HWP) with an L-Gln content of 31 mg/kg; or a control that consisted only of water. It was hypothesized that the AlaGln trial would increase plasma glutamine concentrations greater than the other experimental trials. Ingestion of L-Gln, AlaGln, and HWP resulted in significant increases in the plasma L-Gln concentration, peaking at 0.5, 0.5, and 0.75 hours, respectively. The corresponding mean peak increases were 179 ± 61, 284 ± 84, and 134 ± 36 μmol/L, respectively. Concentrations returned to baseline in all subjects by 2 hours after L-Gln and HWP and by 4 hours after AlaGln. Mean areas under the plasma concentration curve, calculated between 0 and 4 hours, were 127 ± 61, 284 ± 154, and 151 ± 63 μmol∙h∙L⁻¹ for L-Gln, AlaGln, and HWP, respectively. When allowance was made for the lower L-Gln dose administered as HWP, the peak plasma concentration and area under the plasma concentration curve were approximately the same as for AlaGln. The results suggest a greater transfer from the gut to plasma of L-Gln when supplied as AlaGln and possibly also as HWP compared with when the same dose was provided as the free amino acid.

Glutamine and glutathione at ICU admission in relation to outcome

Glutamine depletion is demonstrated to be an independent predictor of hospital mortality in ICU (intensive care unit) patients. Today glutamine supplementation is recommended to ICU patients on parenteral nutrition. In addition to glutamine, glutathione may be a limiting factor in ICU patients with MOF (multiple organ failure). To study the prevalence of glutamine and glutathione depletion an observational study was performed. The results were analysed in relation to mortality and the conventional predictors of mortality outcome, APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment). Consecutive patients admitted to the ICU at Karolinska University Hospital Huddinge were studied. Patient admission scoring of APACHE II and SOFA were registered as well as mortality up to 6 months. Plasma glutamine concentration and whole blood glutathione status at admittance were analysed. The admission plasma glutamine concentrations were totally independent of the conventional risk scoring at admittance, and a subnormal concentration was an independent predictor of mortality. In addition, glutathione redox status was also an independent mortality predictor, but here a normal ratio was the risk factor. In both cases the mortality risk was mainly confined to the post-ICU period. A low plasma concentration of glutamine at ICU admission is an independent risk factor for post-ICU mortality. The possible benefit of extending glutamine supplementation post-ICU should be evaluated prospectively.

Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?

Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine. The aim of this work was to determine if glutamate, glutamine and citrulline concentrations in blood, intestine and muscle are decreased by endotoxemia, and if supplementation with glutamate or glutamine can restore normal concentrations. We induced endotoxemia in rats by an intraperitoneal injection of 0.3 mg kg(-1) lipopolysaccharide (LPS). This led to a rapid anorexia, negative nitrogen balance and a transient increase of the circulating level of IL-6 and TNF-α. When compared with the values measured in pair fed (PF) animals, almost all circulating amino acids (AA) including citrulline decreased, suggesting a decrease of intestinal function. However, at D2 after LPS injection, most circulating AA concentrations were closed to the values recorded in the PF group. At that time, among AA, only glutamate, glutamine and citrulline were decreased in gastrocnemius muscle without change in intestinal mucosa. A supplementation with 4% monosodium glutamate (MSG) or an isomolar amount of glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscle. However, MSG supplementation led to an accumulation of glutamate in the intestinal mucosa. In conclusion, endotoxemia rapidly but transiently decreased the circulating concentrations of almost all AA and more durably of glutamate, glutamine and citrulline in muscle. Supplementation with glutamate or glutamine failed to restore glutamate, glutamine and citrulline concentrations in plasma and muscles. The implication of a loss of the intestinal capacity for AA absorption and/or metabolism in endotoxemia (as judged from decreased citrulline plasma concentration) for explaining such results are discussed.

Female distance runners show a different response to post-workout consumption of wheat gluten hydrolysate compared to their male counterparts

Wheat gluten hydrolysate (WGH) is rich in glutamyl residue; glutamine is considered a conditionally essential amino acid under physical stress. WGH has been reported to suppress post-exercise rises in serum creatine kinase in male distance runners. This study aimed to reproduce the effects in female distance runners under similar conditions. The study was conducted in a double-blinded crossover manner. Six female collegiate distance runners ingested WGH or a placebo after a 2-h run at an intensity estimated as 60-70% of their maximum oxygen uptake. Blood was sampled before, immediately after, and at 10 and 24 h after the run. Unlike those in male runners, serum creatine kinase (CK) increased slightly, with a peak at 10 h after the run, while plasma glutamine kept declining. The anti-inflammatory effect of WGH was not evident since the post-exercise elevation of CK was ambiguous. Plasma glutamine concentrations also showed a different kinetics from that in men.

Enteral nutrition supplemented with l-glutamine in patients with systemic inflammatory response syndrome due to pulmonary infection

ObjectiveTo evaluate the effect of enteral nutrition (EN) supplemented with l-glutamine on glycolytic parameters, inflammation, immune function, and oxidative stress in moderately ill intensive care patients with sepsis. MethodsThirty patients received EN. Fifteen patients received EN supplemented with glutamine (30 g; GLN group) for 2 d followed by EN supplemented with calcium caseinate (30 g, CAS group), also over 2 d. The other 15 patients received EN with calcium caseinate (30 g; CAS group) for 2 d followed by EN with glutamine (30 g; GLN group), also over 2 days. One washout day with only EN was provided between every 2-d period of EN plus supplementation to all patients. Blood samples were taken before and after supplementation. ResultsThere were no changes in glycolytic parameters in either group. Leukocytes decreased in the two groups (from 13 650 to 11 500 in the CAS group, P = 0.019; from 12.850 to 11.000 in the GLN group, P = 0.046). Lymphocytes increased in the GLN group (from 954 to 1916, P < 0.0001) and were more numerous after glutamine supplementation (from 1916 to 1085, P < 0.0001, GLN versus CAS). No significant changes were observed in interleukin levels, but urea levels were higher in the GLN compared with the CAS group (50.0–47.0, P = 0.030). Glutathione plasma concentrations did not differ significantly between the groups. No significant changes were observed in the plasma glutamine and glutamate concentrations. ConclusionsThe EN supplemented with glutamine increased the lymphocyte count and helped to decrease lipid peroxidation but presented no effect on the antioxidant glutathione capacity and on cytokine concentrations or glycolytic parameters.

Improvements of immune status, intestinal integrity and gain performance in the early-weaned calves parenterally supplemented with l-alanyl-l-glutamine dipeptide

Glutamine (Gln) is an important substrate for the innate immune cells including lymphocytes and macrophages. In this report, the effects of alanyl-glutamine dipeptide (Ala-Gln) on the naïve immune system, intestinal integrity and gain performance of early-weaned calves were investigated. Early-weaned Chinese Holstein calves were intravenously administered different dosages of Ala-Gln. The effects of Ala-Gln administration were ascertained by evaluating the blood for naïve T lymphocyte subpopulations, the concentrations of serum IgG, serum IgA and intestinal mucosal secretory IgA (s-IgA), the intestinal integrity, as well as the gain performance. Results demonstrated that intravenous administration of Ala-Gln dipeptide (1.01g/kg×d−1) for 7 days had a positive effect on gain performance, intestinal integrity and the immune system. Calves administered doses of Ala-Gln displayed an improvement in gain performance and health status concurrent with increases in blood CD2+ and CD4+ lymphocytes, the ratio of CD4+/CD8+, serum IgA and IgG, intestinal mucosal s-IgA while decreasing the occurrence of diarrhea. Moreover, we found that animals given the effective dose (1.01g/kg×d−1) of Ala-Gln resulted in improved immune status and intestinal integrity relative to those given a lower (0.49g/kg×d−1) or higher dose (1.99g/kg×d−1) of Ala-Gln. These findings suggest that maintaining a certain concentration of plasma and/or tissue glutamine in the early stages of weaning is an effective alternative approach for improvement of growth performance in early-wean calves.

Glutamine and α‐ketoglutarate as glutamate sources for glutathione synthesis in human erythrocytes

Glutathione (GSH) is an intracellular antioxidant synthesized from glutamate, cysteine and glycine. The human erythrocyte (red blood cell, RBC) requires a continuous supply of glutamate to prevent the limitation of GSH synthesis in the presence of sufficient cysteine, but the RBC membrane is almost impermeable to glutamate. As optimal GSH synthesis is important in diseases associated with oxidative stress, we compared the rate of synthesis using two potential glutamate substrates, α-ketoglutarate and glutamine. Both substrates traverse the RBC membrane rapidly relative to many other metabolites. In whole RBCs partially depleted of intracellular GSH and glutamate, 10 mm extracellular α-ketoglutarate, but not 10 mm glutamine, significantly increased the rate of GSH synthesis (0.85 ± 0.09 and 0.61 ± 0.18 μmol·(L RBC)(-1) ·min(-1), respectively) compared with 0.52 ± 0.09 μmol·(L RBC)(-1) ·min(-1) for RBCs without an external glutamate source. Mathematical modelling of the situation with 0.8 mm extracellular glutamine returned a rate of glutamate production of 0.36 μmol·(L RBC)(-1) ·min(-1), while the initial rate for 0.8 mM α-ketoglutarate was 0.97 μmol·(L RBC)(-1) ·min(-1). However, with normal plasma concentrations, the calculated rate of GSH synthesis was higher with glutamine than with α-ketoglutarate (0.31 and 0.25 μmol·(L RBC)(-1) ·min(-1), respectively), due to the substantially higher plasma concentration of glutamine. Thus, a potential protocol to maximize the rate of GSH synthesis would be to administer a cysteine precursor plus a source of α-ketoglutarate and/or glutamine.

Glutamine supplementation

Intravenous glutamine supplementation is standard care when parenteral nutrition is given for critical illness. There are data of a reduced mortality when glutamine supplementation is given. In addition, standard commercial products for parenteral nutrition do not contain any glutamine due to glutamine instability in aqueous solutions. For the majority of critical ill patients who are fed enterally, the available evidence is insufficient to recommend glutamine supplementation. Standard formulation of enteral nutrition contains some glutamine: 2-4 g/L. However, this dose is insufficient to normalize glutamine plasma concentration.Plasma concentration of glutamine is low in many patients with critical illness and a low level is an independent risk factor for mortality. A low plasma glutamine concentration is the best indicator of glutamine depletion. Data are emerging about how the endogenous production of glutamine is regulated. We know that skeletal muscle is the major producer of glutamine and that a part of the profound depletion of skeletal muscle seen in critical illness is a reflection of the need to produce glutamine.Glutamine is utilized in rapidly dividing cells in the splanchnic area. Quantitatively most glutamine is oxidized, but the availability of glutamine in surplus is important for the de novo synthesis of nucleotides and necessary for cell division and protein synthesis. More knowledge about the regulation of the endogenous production of glutamine is needed to outline better guidelines for glutamine supplementation in the future.

Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients

Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi-centric, double-blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation. Patients (n=413) given nutrition by an enteral and/or a parenteral route with the aim of providing full nutrition were included within 72 h after ICU admission. Glutamine was supplemented as i.v. l-alanyl-l-glutamine, 0.283 g glutamine/kg body weight/24 h for the entire ICU stay. Placebo was saline in identical bottles. All included patients were considered as intention-to-treat patients. Patients given supplementation for >3 days were considered as predetermined per protocol (PP) patients. There was a lower ICU mortality in the treatment arm as compared with the controls in the PP group, but not at 6 months. For change in the SOFA scores, no differences were seen, 1 (0,3) vs. 2 (0.4), P=0.792, for the glutamine group and the controls, respectively. In summary, a reduced ICU mortality was observed during i.v. glutamine supplementation in the PP group. The pragmatic design of the study makes the results representative for a broad range of ICU patients.

Assessment of plasma ammonia and glutamine concentrations in urea cycle disorders

Objectives To analyze the association between ammonia and glutamine used for metabolic control in inherited urea cycle disorders (UCD) in a large series of patients. Design and methods Paired plasma amino acid-ammonia data from 26 UCD patients were analyzed ( n = 921). Results Increased plasma glutamine values were consistently observed in UCD patients, despite normal plasma ammonia concentrations, especially for mitochondrial UCD. Conclusions Further therapeutic efforts are probably needed to control increased glutamine values, considering their potentially neurotoxic effect.

Minimal Enteral Glutamate Slows Gastric Emptying in Preterm Pigs

Glutamate (GLU) is the major excitatory neurotransmitter in the body. GLU receptors and transporters are present in the gut. Emerging evidence suggests that GLU may play a functional role in promoting gastric emptying and digestion. We hypothesized that dietary GLU stimulates gastric emptying in the developing gut. 10‐d preterm, parenterally‐fed pigs received partial enteral nutrition (25%) as milk‐based formula supplemented with monosodium glutamate (MSG) at 0, 2, 4 and 6 times the basal GLU intake (n=5–8 pigs/group) for 7 d. Calorimetry and 13C‐octanoic acid breath test were performed on d 3, 5, 7 and 9 of life. We found no differences in body weight gain, organ weight and arterial plasma GLU and glutamine concentrations between the treatment groups. However, portal GLU concentration was significantly higher in pigs fed the MSG 4 and 6 doses. There was no treatment effect on VO2 uptake, VCO2 production, respiratory exchange ratio and heat production. The average lag time (Tlag) and gastric half emptying time (T1/2) between all treatment groups were 121 and 188 min, respectively. Tlag and T1/2 tended to increase with MSG supplementation in a dose dependent manner. At d 9, the cumulative % recovery of 13C‐octanoic acid was lower in MSG‐4 and MSG‐6 groups. Our results suggest that enteral MSG supplementation slows gastric emptying in the developing gut. (Funded by Ajinomoto)

Acute metabolic encephalopathy in two patients treated with asparaginase and ondasetron

L-asparaginase has been an important agent of acute lymphoblastic leukemia (ALL) therapy for more than 40 years. The major adverse events of L-asparaginase are immunoallergic reaction, pancreatitis, liver cytolysis (increased ASAT, ALAT, and bilirubin), and cerebral haemorrhage or thrombosis. Hyperammonemia has already been described with L -asparaginase treatment [1]. In the present article, we report acute metabolic encephalopathy in two young boys receiving asparaginase for B ALL relapse. We discuss the pathophysiology of this metabolic encephalopathy with hyperammonemia and its medical management.

Effects of Glutamine on Gastrointestinal Motor Activity in Patients following Gastric Surgery

Postoperative ileus (POI) is one of the most common complications of gastrointestinal surgery. The present study was performed to evaluate the effects of glutamine administration on POI after gastric surgery in humans. The subjects were 31 patients who underwent partial distal gastrectomy for gastric cancer and who were randomly assigned to one of two groups based on postoperative treatment: the glutamine group (3 g/day) and the control group. Manometric recording was done 12 days after surgery, and plasma glutamine concentrations were measured preoperatively and on postoperative day 12. Motor activities of the duodenum in the glutamine group were significantly greater than those of the control group in the interdigestive state. The incidence of phase III motor activity (interdigestive migrating motor contractions) in the glutamine group was significantly higher than that in the control group (60 versus 19%). The glutamine group showed a significantly smaller decrease of plasma glutamine levels compared with the control group. Glutamine could act as a motility-recovery agent after gastrectomy in humans.