L-Glutamine and Survival of Patients with Locally Advanced Head and Neck Cancer Receiving Chemoradiotherapy.

We previously reported that L-glutamine reduces the severity of mucositis caused by chemoradiotherapy in patients with head and neck cancer. However, the impact of glutamine on the anti-tumor effect of chemoradiotherapy remains controversial. This study, which included 40 patients, investigated whether L-glutamine influences survival. Radiation therapy (total: 66 or 70 Gy), cisplatin, and docetaxel were co-administered for a period of 6 weeks. Patients were randomly assigned to receive either glutamine (glutamine group, n = 20) or placebo (placebo group, n = 20) during the entire course of chemoradiotherapy. We compared the overall survival and progression-free survival rates between the two groups. At 5-year follow-up, 16 (80%) and 13 (72%) patients in the glutamine and placebo groups, respectively, survived (with no significant difference in overall survival [glutamine group: 55.2 ± 12.7 months vs. placebo group: 48.3 ± 21.3 months]). A total of 14 (70%) and 12 (67%) patients in the glutamine and placebo groups, respectively, did not experience disease progression (with no significant difference in progression-free survival [glutamine group: 46.7 ± 19.5 months vs. placebo group: 43.6 ± 25.2 months]). These findings indicate that L-glutamine does not influence the survival of patients with locally advanced head and neck cancer receiving chemoradiotherapy.

Both high and low plasma glutamine levels predict mortality in critically ill patients.

PURPOSE: Plasma amino acids are important indicators for understanding human kinetics and amino acid dynamics. We aimed to investigate the association between the plasma glutamine levels and the mortality rates and determine whether plasma glutamine can predict the prognosis of critically ill patients. METHODS: The clinical records of adult patients who were admitted to an ICU were retrospectively evaluated to investigate the plasma levels of amino acids, including glutamine. RESULTS: Two hundred fourteen patients were included in this study (male, 62%; median age, 64 years; range 20-97 years). The patients' diagnoses included sepsis (45%), trauma (14%), cardiovascular disease (9%), fulminant hepatitis (9%), burns (4%), and others (19%). The mortality rates in patients with plasma glutamine <400 nmol/mL (group L; 39%, 28/71) or ≥700 nmol/mL (group H; 50%, 15/30) were significantly higher (p < 0.05 and p < 0.01, respectively) than those in patients with plasma glutamine levels of 400-700 nmol/mL (group M; 21%, 24/113). Among patients with sepsis, the mortality rates of group L (46%) and group H (67%) were significantly higher (p < 0.05 or p < 0.01, respectively) in comparison with group M (26%). CONCLUSION: Both lower and higher plasma glutamine levels were risk factors for mortality in critically ill patients.

Cardiogenic shock caused by a left midventricular obstruction during refeeding in a patient with anorexia nervosa.

OBJECTIVE: Refeeding syndrome occurs when reinstating nutrition to severely malnourished patients. It can sometimes be fatal, particularly as a result of cardiac involvement such as congestive heart failure and arrhythmias. The aim of this study was to report a case of cardiogenic shock that occurred during refeeding in a patient with anorexia nervosa (AN). The cardiogenic shock was due to a previously unrecognized mechanism, namely a transient left midventricular obstruction that completely disappeared after treatment. METHODS: A 46-y-old woman with AN who had followed a carbohydrate- and a fat-deficient diet for >10 y was hospitalized for dyspnea on exertion. She had severely impaired cardiac systolic function on admission and was considered high risk for refeeding syndrome. During a stepwise increase of calories, she showed no electrolyte or mineral abnormalities characteristic of refeeding syndrome. RESULTS: After intravenous administration of a fat emulsion, the patient suffered from cardiogenic shock due to an unexpected mechanism, namely a left midventricular obstruction caused by cardiac hypercontraction, a thickened left ventricular wall, and intravascular volume depletion. With cessation of the fat emulsion and initiation of volume repletion she recovered from shock immediately and her echocardiogram returned to normal by discharge. CONCLUSIONS: This case illustrated a novel cause of cardiogenic shock during refeeding and the need for caution during the intravenous administration of a fat emulsion in patients with initial left ventricular systolic dysfunction.

[ROLE OF A NUTRITION SUPPORT TEAM FOR SURGICAL PATIENTS].

A number of studies have reported that malnutrition is documented in up to 50％ of hospitalized patients, and malnutrition is closely correlated with the incidence of postoperative complications in surgical patients. The concept of a nutrition support team (NST) is to use its expertise for the entire spectrum of nutritional and metabolic support and to reduce the incidence of complications in hospitalized patients. It is widely recommended that the NST include a physician, dietitian, nurse, pharmacist, and other medical staff, and the physician should play the leading role in maintaining the activity of the NST. The clinical goals of the NST are defined as the identification of nutritionally impaired patients, making nutritional assessments that can lead to precise dietary therapy, and the provision of effective nutritional support. Educating medical students, residents, and other clinical staff in clinical nutrition will be an important role for NSTs in the near future.

Influence of nutritional status on the therapeutic effect of infliximab in patients with Crohn's disease.

PURPOSE: Crohn's disease (CD) is a refractory inflammatory bowel disease of unknown etiology, frequently complicated by malnutrition. It is thought that the delayed wound healing associated with this malnutrition in CD patients might adversely affect the therapeutic benefits of infliximab (IFX). Therefore, we investigated the effects of nutritional status on IFX treatment. METHODS: We assessed nutritional status and CD activity when IFX therapy was initiated and following the third dose, 6 weeks later. Nutritional status was assessed using the body mass index (BMI) and nutritional risk index (NRI), whereas CD activity was assessed using the CD activity index (CDAI). RESULTS: All patients with a BMI ≥ 18.5 kg/m(2) at the time of IFX therapy met the effective criteria for the CDAI, and IFX treatment was considered responsive in these patients. Furthermore, IFX treatment was responsive, with a high level of effectiveness, in all five subjects (31.3 %) with NRI scores of 97.5 and above with no risk of malnutrition (p = 0.037). CONCLUSIONS: Our results suggest that nutritional status does influence the therapeutic effect of IFX in CD patients. The response rate to IFX treatment thus could be improved by optimizing the nutritional status. We recommend comprehensive nutritional assessment and intervention prior to IFX treatment schedules.

L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer: a double-blind, randomized, placebo-controlled trial.

The incidence of severe mucositis in the oral cavity, pharynx and larynx is high among patients with head and neck cancer (HNC) receiving chemoradiotherapy (CRT), resulting in significant pain and impairment of quality of life. The present study investigated whether L-glutamine (glutamine) decreases the severity of mucositis in the oral cavity, pharynx and larynx induced by CRT. This double-blind, randomized, placebo-controlled trial included 40 untreated patients with squamous cell carcinoma of the nasopharynx, oropharynx, hypopharynx or larynx. Patients received 66 or 70 Gy of total radiation at the rate of 2 Gy/fraction daily and 5 fractions/week. Cisplatin (20 mg/m2) and docetaxel (10 mg/m2) were intravenously co-administered once a week for 6 weeks. Patients were randomized to orally receive either glutamine (group G) or placebo (group P) at a dose of 10 g 3 times a day throughout the CRT course. Mucositis was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The primary end point was mucositis severity. Mucositis developed in all patients. A maximal mucositis grade of G4 was observed in 0 and 25% group G and P patients, respectively, while that of G2 was observed in 10 and 0% group G and P patients, respectively (p=0.023). Glutamine significantly decreased the maximal mucositis grade (group G, 2.9±0.3; group P, 3.3±0.4; p=0.005) and pain score at weeks 4, 5 and 6. Glutamine significantly decreased mucositis severity in the oral cavity, pharynx and larynx induced by CRT in patients with HNC.

Refractory hypoglycemia and subsequent cardiogenic shock in starvation and refeeding: report of three cases.

OBJECTIVE: Although starvation is associated with high in-hospital mortality, its related cardiac complications are not sufficiently understood. The aim of this study was to determine the clinical course and pathogenesis of cardiac complications in malnourished patients. METHODS: We reviewed three cases of hypoglycemia and hypotriglyceridemia with cardiac complications in starvation. RESULTS: This report concerns three patients, respectively suffering from anorexia nervosa, esophageal carcinoma, and Parkinson's disease. Their ages ranged from 18 to 70 y, body mass index was 11.5 ± 1.5 kg/m2 (mean ± SD), and the main symptom was coma. The average blood glucose level was 15.7 ± 7.8 mg/dL without any history of insulin use or diabetes mellitus. In all cases, hypoglycemia was refractory and repetitive so that continuous glucose administration was required to maintain euglycemia. Serum triglyceride and non-esterified fatty acid levels were also very low (7 ± 4 mg/dL and 10 ± 9.1 µEq/L, respectively). Levels of serum potassium, phosphate, and magnesium were almost normal at admission. The main cardiac complications included Takotsubo cardiomyopathy and cardiac arrest. All patients survived as a result of intensive treatment. CONCLUSIONS: Repetitive severe hypoglycemia without known background causes should be viewed as an important sign. Once this occurs, the administration of a much higher caloric input than usual accompanied by intensive monitoring will be required to maintain appropriate glucose levels. The early identification of such patients seems to be essential to reduce the high risk for cardiac complications during starvation and refeeding.

Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats.

PURPOSE: High doses of anticancer drugs often damage the intestinal mucosa. The purpose of the present study was to examine the effect of glutamine on mucosal damage induced by cyclophosphamide in a rat model, and to elucidate the mechanisms responsible for its protective effects. METHOD: Rats were randomly assigned to one of the three experimental groups. Group A (control) (n = 8): intraperitoneal injection of saline, group B (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg), group C (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg) and oral glutamine (1.0 g/kg). After 3 days, the ileal segment was removed for morphological and the biochemical analyses. We also evaluated the level of mucosal apoptosis by the TUNEL method and enterocyte proliferation using bromodeoxyuridine (BrdU). RESULTS: Mucosal atrophy was observed in group B but not in groups A or C. The mucosal wet weight, protein and glutathione levels were significantly decreased in group B compared with group A, and were increased significantly in group C compared with group B. While enterocyte proliferation significantly decreased and the apoptotic index significantly increased in group B compared with group A, a significant increase in the enterocyte proliferation and a significant decrease in apoptosis were observed in group C compared with group B. CONCLUSIONS: Glutamine prevented intestinal mucosal injury induced by cyclophosphamide via increased glutathione, decreased apoptosis and increased proliferation of intestinal epithelial cells.

Parenteral nutrition administration leads to specific alterations in the expression of adipocytokines and peroxisome proliferator-activated receptors in a rat model.

BACKGROUND: Similar to metabolic syndrome, parenteral nutrition (PN) administration has also been associated with biologic abnormalities of glucose and lipids. Such complications include hyperglycemia, hypertriglyceridemia, liver dysfunction, and hepatobiliary complications. Because metabolic syndrome has been associated with altered expression of adipocytokines, and peroxisome proliferator-activated receptors (PPARs), the present study hypothesized that PN would also lead to alterations in adipocytokines and related gene abundances. METHODS: Male Wister rats received either intravenous (IV) saline and chow (control) or PN. To determine the contribution of lipids to metabolic changes, the following 2 PN groups were studied: PN with IV lipid (PN+L) and PN without lipid (PN-L). Rats were studied after 7 days. RESULTS: A marked increase in hepatic glycogen staining was found in the PN-L group, and conversely, a marked increase in hepatic lipid staining was observed in the PN+L group. Both PN groups demonstrated a 30% increase in serum adiponectin levels in comparison to controls. In the liver, ACDC mRNA expression significantly increased (10%-20%), while ADIPOR1 expression significantly declined in the PN groups compared with controls. PPAR expression significantly declined (10%-30%) in the PN+L group compared with controls. In contrast to metabolic syndrome, PN+L led to a decrease in tumor necrosis factor α and interleukin 6 levels in the liver. CONCLUSIONS: The study shows that PN led to specific alterations in the abundance of adipocytokines and PPARs. These changes give critical insight into many of the metabolic derangements in lipid metabolism, which patients may experience with PN.

Protective mechanism of glutamine on the expression of proliferating cell nuclear antigen after cisplatin-induced intestinal mucosal injury.

BACKGROUND: Glutamine prevents the intestinal mucosal injury induced by chemotherapy. However, the mechanism has not yet been elucidated. Proliferating cell nuclear antigen (PCNA) is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle, and PCNA is also involved in the DNA damage tolerance pathway known as post-replication repair. We hypothesized that glutamine supplementation might stimulate the intestinal epithelial cell cycle interruption induced by chemotherapy. The effect of supplemental glutamine after cisplatin-induced intestinal mucosal injury on the expression of PCNA was investigated. MATERIALS AND METHODS: The male Wister rats were divided into three groups; a control group (control n = 5), which received standard rat diet; the Cis group (cisplatin 6 mg/kg i.p., n = 5), and the Cis + Gln group [cisplatin + Ala-Glutamine (0.5 g/day × 3 days p.o., n = 5)]. After 1, 3, and 7 days of chemotherapy, PCNA, and glutamine transporter (ASCT2) expression in the small intestine (jejunum and ileum) was investigated. RESULTS: The expression of PCNA in the crypt of the small intestine (jejunum and ileum) decreased after chemotherapy, while the expression strongly increased by glutamine administration, even if it was after chemotherapy. On day 1, both the mRNA expression of the glutamine transporter (ASCT2) and PCNA expression in crypt cells were significantly increased by administration of glutamine (Cis + Gln group). The increased expression of ACST2 appeared earlier than in the Cis group. In the Cis + Gln group, the PCNA expression was normalized on day 3, and the expression was same as that in the control group on day 3. CONCLUSION: Glutamine supplementation rapidly improved the expression of PCNA after cisplatin-induced intestinal mucosal injury. The effects of glutamine may be due to an anti-oxidant effect, but the amino acid might also attenuate the initial mucosal injury and improve intestinal cell turnover.

Cisplatin upregulates glutamine transport in human intestinal epithelial cells: the protective mechanism of glutamine on intestinal mucosa after chemotherapy.

BACKGROUND: Glutamine (GLN) prevents the intestinal mucosal injury induced by chemotherapy, although the mechanism of this protective action has not yet been elucidated. Amino acid transport across the plasma membrane is essential for supplying enterocytes with amino acids for cellular metabolism. It was hypothesized that chemotherapy stimulates GLN transport, which enables GLN to be used more efficiently as a metabolic fuel. METHODS: A rat model was used to examine the effect of enteral GLN on intestinal mucosal injury induced by intraperitoneal injection of cisplatin (7.0 mg/kg of body weight). The effects of cisplatin on amino acid transport and the expression of messenger RNA and protein were evaluated by real-time polymerase chain reaction and Western blot analysis, respectively, in the human intestinal epithelial cell line Caco-2. The effects of cisplatin on glutaminase activity and intracellular glutathione were also studied. RESULTS: GLN prevented mucosal atrophy induced by cisplatin in rats. In Caco-2 cells, cisplatin significantly increased GLN transport and the expression of GLN transporter ASCT2 messenger RNA and protein. Leucine, but not glutamate, transport significantly increased in the cisplatin-treated group due to the increase in LAT1 (leucine transporter) protein expression. Glutaminase activity and intracellular glutathione increased significantly in the cisplatin-treated group. CONCLUSIONS: Bolus enteral GLN prevents intestinal mucosal injury induced by cisplatin in rats, as demonstrated by increased GLN transport and increased GLN transporter expression after cisplatin administration.

Hypoxia upregulates amino acid transport in a human neuroblastoma cell line.

BACKGROUND/PURPOSE: Some tumor cells survive and even grow in hypoxic conditions. We examined the effect of hypoxia on amino acid transport in a human neuroblastoma cell line SK-N-SH. METHODS: Cells were incubated under hypoxic conditions (1% O2-5% CO2-94% N2). After 0, 8, 16, and 24 hours, the transport of 3H-glutamine, 3H-glutamate, and 3H-leucine was assayed. 3H-Thymidine and 3H-leucine incorporation was measured for the determination of DNA and protein synthesis, respectively. RESULTS: Hypoxia increased Na+-dependent glutamine and Na+-independent leucine transport significantly at 16 and 24 hours compared with control (P < .01) by a mechanism that increased Vmax without affecting Km. These increases were completely blocked by actinomycin D and cycloheximide. There was no significant difference in Na+-dependent glutamate transport between control and hypoxic groups. DNA and protein synthesis significantly decreased in the hypoxic condition compared with control (P < .01). CONCLUSIONS: This study demonstrated that hypoxia upregulates amino acid transport in a human neuroblastoma cell line. This mechanism may allow cells to survive and even grow under hypoxic conditions.

Glutamine stimulates amino acid transport during ischemia-reperfusion in human intestinal epithelial cells.

BACKGROUND: The potential mechanism of intestinal ischemia-reperfusion (I/R) injury includes oxygen-derived toxic free radicals. We tested the hypothesis that glutamine increases intracellular glutathione, a protective substrate against oxidative stress, by stimulating membrane amino acid transport during I/R using human intestinal epithelial cell line Caco-2. METHODS: Ischemic conditions were obtained by combining both hypoxic (1%O2-5%CO2-94% N2) and nutrient-deprived (Phosphate-Buffered Saline; PBS) conditions. After 2 h of ischemia, re-oxygenation (5%CO2-95% air) was initiated and the culture medium was changed to PBS, PBS supplemented with amino acids (A.A.), and PBS supplemented with 2 mm glutamine plus amino acids (Gln) (reperfusion). After 4 h of reperfusion, the transport of 3H-glutamine, 3H-glutamate, and 3H-leucine was assayed and intracellular glutathione was measured. 3H-thymidine incorporation was measured for the determination of DNA synthesis. Data (mean +/- SD) were analyzed by ANOVA. RESULTS: Ischemia decreased Na+-dependent glutamine, Na+-dependent glutamate, and Na+-independent leucine transport compared with control (P < 0.01). After reperfusion, glutamine and glutamate transport in the PBS and A.A. groups decreased significantly compared with control (P < 0.01), whereas glutamine supplementation increased glutamine transport to the levels in control (P < 0.01) and partially increased glutamate transport (P < 0.01). Leucine transport significantly increased in the A.A. and Gln groups compared with the PBS group. Glutamine significantly increased intracellular glutathione and DNA synthesis compared with the PBS and A.A. groups (P < 0.01). CONCLUSIONS: This study demonstrated that glutamine up-regulates amino acid transport during I/R in human intestinal epithelial cells, possibly resulting in increased intracellular glutathione and DNA synthesis.

Glutamine regulates amino acid transport and glutathione levels in a human neuroblastoma cell line.

Both amino acid transport and glutathione play a key role in regulating cancer cell growth. Glutamine can serve as an important ATP source for cancer cells, and it can supply glutamate, a precursor for the synthesis of glutathione, by the hydrolysis of glutamine. We examined the effects of glutamine concentrations [2 mM (control), 400 microM, 200 microM, and 0 microM] on cell growth, amino acid transport, and glutathione levels in a human neuroblastoma cell line, SK-N-SH, by using cell culture technique. Cell growth rates were dependent on glutamine concentrations in culture media. Glutamate transport significantly increased in glutamine-deprived groups, and this increase was remarkable in lower glutamine groups (200 microM and 0 microM glutamine). Glutamine deprivation resulted in a significant decrease in glutathione levels by 20% compared with control, but glutathione in 0 microM glutamine was maintained with the same levels found in 400 microM and 200 microM glutamine. DNA and protein synthesis correlated directly with glutamine concentrations in culture media. Our results suggest that glutamine mediates neuroblastoma cell proliferation by regulating amino acid transport and glutathione synthesis, both when sufficient nutrients are present and when key nutrients such as glutamine are in limited supply.

Laparoscopic left-sided Nissen fundoplication in children.

It is sometimes difficult or inappropriate to adopt the standard surgical steps of adult laparoscopic procedures in pediatric patients because of the inevitably smaller anatomical structures and confined intra-abdominal working space. During laparoscopic Nissen fundoplication difficulties are usually encountered, especially when dissecting the diaphragmatic crura, creating the retroesophageal window, and repairing the crura. Thus, we devised a technique to accomplish these steps in pediatric patients. Both crural dissection and repair are approached from the left side of the esophagus and the port configuration for the laparoscope and other instruments is altered, providing better surgical exposure and easier handing of the instruments, even in very small patients. We describe this technique in detail and our results.

Amino acid transport is down-regulated in ischemic human intestinal epithelial cells.

Amino acid transport across the plasma membrane is essential for supplying enterocytes with amino acids for cellular metabolism. We studied amino acid transport during ischemic conditions using human intestinal epithelial cell line Caco-2. Cells were incubated under nutrient-deprived (phosphate-buffered saline, PBS), hypoxic, and ischemic (PBS+hypoxia) conditions. Ischemia resulted in a significant decrease in glutamine transport by a mechanism that decreased V(max) without affecting K(m). The expression of system ATB degrees (glutamine transporter) mRNA decreased in the ischemic and nutrient-deprived groups, suggesting that the down-regulation of glutamine transport is due to modification of expression of the ATB degrees gene. The transport of glutamate and leucine, DNA synthesis, and intracellular glutathione also decreased in the ischemic group. These findings throw some light on the mechanism of intestinal epithelial damage during ischemia.

Laparoscopic liver biopsy performed safely in a child with hepatic dysfunction: report of a case.

We performed laparoscopic liver biopsy in a 10-year-old girl with acute myelocytic leukemia and coagulopathy. Each biopsy was taken under laparoscopic ultrasound (LUS) guidance, and hemostasis was achieved with an argon beam coagulator (ABC). These instruments were introduced through one 10/12-mm port, which also allowed the insertion of surgical gauze for direct compression. By using LUS, ABC, and one full-sized working port, laparoscopic liver biopsy becomes a viable and safer alternative, even for children with coagulopathy.

Beneficial effects of n-9 eicosatrienoic acid on experimental bowel lesions.

PURPOSE: Dietary fortification of n-9 polyunsaturated fatty acids (PUFA) or 5,8,11-eicosatrienoic acid (ETrA) as well as n-3 PUFA might contribute to the suppression of leukotriene B4 (LTB4) synthesis and thereby reduce inflammatory bowel lesions. As a result, the effect of an ETrA-enriched diet on experimental bowel lesions was examined in this study. METHODS: In Expt. 1, rats were freely fed either an ETrA-enriched or a standard diet. After 7 days of feeding, acute bowel lesions were induced by the subcutaneous injection of 10 mg/kg indomethacin. In Expt. 2, chronic bowel lesions were made by performing subcutaneous injections of 7.5 mg/kg indomethacin twice. After the first injection, the rats were freely fed either an ETrA-enriched or a standard diet for 7 days. RESULTS: In both experiments, the rats fed an ETrA-enriched diet showed increased levels of ETrA in the plasma and intestinal mucosa, and a decreased inflammation score. However, there was no significant decrease in plasma and intestinal mucosal LTB4 in the ETrA-enriched diet-fed rats. CONCLUSION: These results suggest that the dietary supplementation of ETrA may have both prophylactic and therapeutic effects on experimentally produced bowel lesions. Further investigations are necessary to clarify the effects of ETrA on bowel lesions and its mechanisms.

A modular laparoscopic training program for pediatric surgeons.

OBJECTIVES: A structured endoscopic training program for pediatric surgeons has not yet been established. This study was conducted to develop a modular training program (MTP) for pediatric surgeons and to evaluate its effectiveness for surgeons with and without previous experience in laparoscopic surgery. METHODS: Nine pediatric surgeons participated in the study. They were divided into 2 groups: group A (n=4), surgeons who had experienced more than 10 cases of laparoscopic surgery prior to MTP; group B (n=5), those who had experienced fewer than 10 cases. They participated in a standardized MTP workshop, which consisted of 2 "see-through" and 3 "laparoscopic" tasks. Each participant's psychomotor skills were evaluated objectively before and after MTP with a computer-generated virtual simulator and were evaluated for precision, efficiency, and speed. RESULTS: In participants, speed was significantly enhanced after MTP. In group A, no differences were observed after MTP, whereas significant improvements were noted in efficiency and speed after MTP in group B. Before MTP, efficiency was significantly higher in group A than in group B; however, no difference remained between the 2 groups after MTP. CONCLUSIONS: MTP is effective for nonlaparoscopic pediatric surgeons to become familiar with basic endoscopic skills.

Alanyl-glutamine-supplemented parenteral nutrition prevents intestinal ischemia-reperfusion injury in rats.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury plays an important role in the pathogenesis of systemic inflammation and multiple-organ failure. We studied whether glutamine, the primary fuel of the small intestine, prevents intestinal mucosal damage after intestinal I/R in rats. METHODS: Rats were randomly divided into 4 groups: a sham-standard amino acid (SAA) group (n = 8); a sham-glutamine (Gln) group (n = 8); an I/R-SAA group (n = 10); and an I/R-Gln group (n = 9). Alanyl-glutamine solution was produced by replacing 36% of the total amino acid nitrogen with Gln. The superior mesenteric artery was ligated. After 60 minutes of ischemia, reperfusion was initiated and infusion was started. After 24-hour reperfusion, the intestinal segment was removed for morphological and biochemical analysis, and blood samples were drawn from the portal vein. Fluorescein isothiocyanate-conjugated dextran 70,000 (FITC-dextran) was infused into the duodenum 2 hours before animal death. RESULTS: In the I/R-SAA group, extensive epithelial sloughing and mucosal ulceration of villous tips were observed, whereas these findings did not occur in the I/R-Gln group. Mucosal wet weight, DNA, and protein content decreased significantly in the I/R-SAA group compared with the sham-SAA group and increased significantly in the I/R-Gln group compared with the I/R-SAA group. Plasma FITC-dextran significantly increased in the I/R-SAA group compared with the sham-SAA group, but the plasma level in the I/R-Gln group was comparable with that of each sham group. Mucosal glutaminase activity significantly increased in both the I/R-SAA and I/R-Gln groups compared with the sham-SAA and sham-Gln groups, respectively. CONCLUSIONS: Alanyl-glutamine protects against morphologic and functional mucosal injury after intestinal I/R in rats.