1.Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model.
Yingqian ZHAO ; Qiang WANG ; Yuan WANG ; Jie LI ; Gang LU ; Zhibin LIU
Environmental Health and Preventive Medicine 2019;24(1):4-4
BACKGROUND:
Parkinson's disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson's disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP)-induced Parkinson's disease cell model.
METHODS:
MPP was used to induce PD models in PC12 cells and classified into control, M0 (MPP), G0 (glutamine), and M0+G0 groups. CCK-8 and AO/EB staining assays were used to examine cell proliferation and apoptosis, respectively. Western blotting was applied to examine the protein expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR.
RESULTS:
We showed that glutamine suppressed cytotoxicity induced by MPP in PC12 cells. MPP decreased the superoxide dismutase and glutathione peroxidase activity and increased the malondialdehyde content, which were restored by glutamine. Moreover, MPP increased the expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR, which were inhibited by glutamine. And the antioxidant capacity of glutamine on PC12 cells could be improved by LY294002 and inhibited by IGF-1.
CONCLUSION
These results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP through inhibiting the activation of the PI3K/Akt signaling pathway. The effects of glutamine should be investigated and the protective mechanism of glutamine in PD must be explored in future studies.
1-Methyl-4-phenylpyridinium
;
administration & dosage
;
Analysis of Variance
;
Animals
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Cell Culture Techniques
;
Disease Models, Animal
;
Glutamine
;
pharmacology
;
Oxidative Stress
;
drug effects
;
Parkinson Disease
;
Phosphatidylinositol 3-Kinases
;
metabolism
;
Protective Agents
;
pharmacology
;
Proto-Oncogene Proteins c-akt
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metabolism
;
Rats
2.Effects of early oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury.
Kedai SUN ; Zhiwei DONG ; Jing CHEN ; Pan LIU ; Yali GONG ; Yizhi PENG
Chinese Journal of Burns 2015;31(1):25-29
OBJECTIVETo explore the effects of oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury at early stage.
METHODSTwenty-four patients with severe burn injury admitted to our burn ward from August 2013 to September 2014, conforming to the study criteria, were divided into conventional therapy group (n = 12) and early enteral feeding group (n = 12) according to the random number table. Patients in conventional therapy group received conventional treatment immediately after admission, while those in early enteral feeding group were orally given 100 mL of a mixture of glutamine, probiotics, and prebiotics once a day besides conventional treatment for 7 days. Serum levels of diamine oxidase (DAO) and procalcitonin (PCT) and plasma level of LPS were determined by ELISA before treatment and on treatment day (TD) 1, 3, 7, 14, and 21. Wound secretion and blood samples were collected for bacterial culture within the 21 TD. The incidence of MODS within the 21 TD was observed. Data were processed with Fisher's exact test, rank sum test, analysis of variance for repeated measurement, and LSD-t test.
RESULTS(1) Serum levels of DAO in patients of early enteral feeding group on TD 7, 14, and 21 were respectively (14.9 ± 3.7), (12.4 ± 3.1), and (9.5 ± 0.7) ng/mL, which were significantly lower than those of conventional therapy group [(17.5 ± 4.0), (16.3 ± 3.3), and (13.0 ± 1.1) ng/mL, with t values from 2.913 to 15.304, P values below 0.01]. Serum levels of DAO at the other time points were close between the two groups (with t values from -0.598 to 0.139, P values above 0.05). (2) Compared with serum levels of PCT in patients of conventional therapy group [(11.7 ± 20.9) and (12.9 ± 23.9) ng/mL], those of early enteral feeding group were significantly lower on TD 7 and 14 [(2.7 ± 8.1) and (2.0 ± 5.6) ng/mL, with Z values respectively -2.919 and -2.139, P < 0.05 or P < 0.01]. Serum levels of PCT at the other time points were close between the two groups (with Z values from -1.833 to -0.346, P values above 0.05). (3) Plasma level of LPS in patients of early enteral feeding group on TD 7 was (33 ± 56) pg/mL, which was significantly lower than that of conventional therapy group [(102 ± 108) pg/mL, Z = -2.046, P < 0.05]. Plasma levels of LPS at the other time points between the two groups showed no significant difference (with Z values from -2.003~-0.526, P values above 0.05). (4) Positive results in bacterial culture of wound secretion were approximately the same between the two groups (P > 0.05). Bacterial culture of blood was positive in 7 patients of conventional therapy group and 1 patient of early enteral feeding group, showing significantly statistical difference (P < 0.05). MODS was observed in 1 patient of conventional therapy group, showing no significantly statistical difference with that of early enteral feeding group (no patient, P > 0.05).
CONCLUSIONSEarly intestinal feeding of mixed enteral nutritional agent in addition to conventional therapy can effectively promote repair of the impairment of intestinal mucosal barrier, protect integrity of intestinal mucosa, reduce damage to intestines, and alleviate inflammatory response in patients suffering from severe burn injury.
Administration, Oral ; Amine Oxidase (Copper-Containing) ; blood ; Burns ; metabolism ; therapy ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Enteral Nutrition ; methods ; Female ; Glutamine ; administration & dosage ; pharmacology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; Protein Precursors ; blood ; Treatment Outcome ; Wound Healing
3.Glutamine-Supplemented Parenteral Nutrition and Probiotics in Four Adult Autoimmune Enteropathy Patients.
Ren Ying XU ; Yan Ping WAN ; Yi Quan ZHOU ; Li Ping LU ; Zhi Qi CHEN ; Ying Jie WU ; Wei CAI
Gut and Liver 2014;8(3):324-328
To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients' medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5x10(8) colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition.
Adult
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Bifidobacterium
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Enterococcus faecalis
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Female
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Glutamine/*administration & dosage
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Humans
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Lactobacillus acidophilus
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Length of Stay
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Male
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Malnutrition/therapy
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Parenteral Nutrition/*methods
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Polyendocrinopathies, Autoimmune/*therapy
;
Probiotics/*administration & dosage
;
Young Adult
4.Effect of early enteral nutrition supplemented with glutamine on postoperative intestinal mucosal barrier function in patients with gastric carcinoma.
Xiao-dong XU ; Yuan-shui SUN ; Qin-shu SHAO ; Jun-feng HU ; Zhen-yuan QIAN ; Yong-lie ZHOU ; Zai-yuan YE
Chinese Journal of Gastrointestinal Surgery 2011;14(6):436-439
OBJECTIVETo investigate the effect of early enteral nutrition (EEN) supplemented with glutamine on postoperative intestinal mucosal barrier function of patients with gastric carcinoma.
METHODSEighty patients with gastric carcinoma who underwent intraoperative peritoneal hyperthermic chemotherapy(IPHC) were randomized into two groups: EEN+glutamine (EEN+Gln) group(n=40) and EEN group(n=40). Intestinal mucosal barrier function was evaluated by serum diamine oxidase (DAO), ratio of lactulose to mannitol(L/M), endotoxin lipopolysaccharides(LPS), and tumor necrosis factor-α(TNF-α) at 1 day before operation, 1 day, 7 days, 12 days after operation. Time to first flatus and tolerance to EEN were recorded as well.
RESULTSThere were no significant differences in the two groups in demographics(all P>0.05). Two cases(5%) in the EEN+Gln group and 1 case (2.5%) in the EEN group could not tolerate well(P>0.05). On postoperative day 1, there were no differences in serum DAO, L/M ratio, LPS, TNF-α between the two groups (P>0.05). On postoperative day 7, all the parameters for mucosal barrier function were significantly lower in the EEN+Gln group. On postoperative day 12, the urinary L/M and DAO, LPS, and TNF-α were still significantly lower in the EEN+Gln group, however, urinary L/M was comparable between the two groups. There were no differences between the two groups in the time to first flatus (P>0.05).
CONCLUSIONThe immunologic tolerance of enteral nutrition supplemented with glutamine is favorable, which provides protective effect on intestinal mucosal barrier in patients with gastric carcinoma undergoing IPHC.
Aged ; Enteral Nutrition ; methods ; Female ; Glutamine ; administration & dosage ; therapeutic use ; Humans ; Intestinal Mucosa ; drug effects ; physiopathology ; Male ; Middle Aged ; Postoperative Care ; Prospective Studies ; Stomach Neoplasms ; physiopathology ; therapy
5.Effect of oral glutamine on intestinal barrier function in young rats with endotoxemia.
Xiao CHANG ; Lin-Lin WANG ; Shu-Jun LIAN ; Qing TANG ; Ping CHEN ; Hua WANG
Chinese Journal of Contemporary Pediatrics 2010;12(10):809-811
OBJECTIVETo study the effect of glutamine on intestinal barrier function by examining the changes of plasma D-lactic levels and diamine oxidase (DAO) levels in plasma and intestinal tissue after glutamine intervention in young rats with endotoxemia.
METHODSEighty 18-day-old rats were randomly divided into endotoxemia and glutamine intervention groups (n=40 each). Endotoxemia was induced by lipopolysaccharide (LPS) injection. Plasma and small intestine homogenate were collected 1.5, 6, 24 and 72 hrs and 7 days after LPS injection. The glutamine intervention group was immediately administered with oral glutamine (2 g/kg) after LPS injection. Afterwards, glutamine was administered once daily. Plasma D-lactic and DAO levels and intestinal DAO levels were measured.
RESULTSPlasma DAO activity in the glutamine intervention group was significantly lower than that in the endotoxemia group 6 and 72 hrs after LPS injection (P<0.05). In contrast, the intestinal DAO activity in the glutamine intervention group was significantly higher than that in the endotoxemia group 6, 24 and 72 hrs and 7 days after LPS injection (P<0.05 or 0.01). Plasma D-lactic levels in the glutamine intervention group were significantly lower than those in the endotoxemia group 6, 24 and 72 hrs and 7 days after LPS injection (P<0.01).
CONCLUSIONSGlutamine may reduce the permeability of intestinal mucosa, and thus provides protective effects on intestinal barrier function in rats with endotoxemia.
Administration, Oral ; Amine Oxidase (Copper-Containing) ; metabolism ; Animals ; Behavior, Animal ; Endotoxemia ; metabolism ; Female ; Glutamine ; administration & dosage ; pharmacology ; Intestines ; drug effects ; metabolism ; Lactic Acid ; blood ; Male ; Rats ; Rats, Wistar
6.Effects of glutamine supplementation on patients undergoing abdominal surgery.
Yue-ping FAN ; Jian-chun YU ; Wei-ming KANG ; Qun ZHANG
Chinese Medical Sciences Journal 2009;24(1):55-59
OBJECTIVETo evaluate the effects of supplementation of glutamine (GLN) on maintaining glutathione (GSH) level, immune system function, liver function, and clinical outcome of patients receiving abdominal operation.
METHODSForty patients undergoing elective abdominal surgical treatment were randomly divided into 2 groups: study group (n = 20) and control group (n = 20). All patients received total parenteral nutrition (TPN) for up to 7 days during perioperative period. The study group received TPN supplemented with GLN dipeptide while the control group received TPN without GLN dipeptide. Patients in both groups received equivalent nitrogen and caloric intake. Blood sample was taken on preoperative day, and the 1st, 3rd, 6th postoperative day to measure GSH level, immune indexes, and liver function indexes.
RESULTSThe decrease of GSH level in plasma and red blood cell (RBC) in study group was less than that in control group during postoperative period. Ratio of GSH/glutathione disulfide (GSSG) in plasma in study group was higher than that in control group on the 3rd postoperative day (52.53 +/- 11.46 vs. 31.43 +/- 7.27, P = 0.001). Albumin level in study group was higher than that in control group on the 3rd postoperative day (37.7 +/- 3.8 g/L vs. 33.8 +/- 4.2 g/L, P = 0.02). There was no significant difference in the levels of immunoglobin (IgG, IgM, IgA) or T lymphocyte subgroup (CD4, CD8, CD4/CD8) in both groups during postoperative period. There was one case with infectious complication in control group, while none in study group. A trend of shortened hospital stay was observed in study group compared with control group (22.3 +/- 2.1 d vs. 24.9 +/- 1.7 d, P = 0.32).
CONCLUSIONSSupplementation of GLN-enriched TPN has beneficial effects on maintaining GSH levels in plasma and RBC, sustaining GSH/GSSG ratio and albumin level, and keeping antioxidant abilities during postoperative period in patients with abdominal operation, with the trends of decreasing incidence of infectious complication and shortening hospital stay.
Abdomen ; surgery ; Adolescent ; Adult ; Aged ; Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Dietary Supplements ; Female ; Glutamine ; administration & dosage ; therapeutic use ; Glutathione ; blood ; Glutathione Disulfide ; blood ; Humans ; Immunoglobulins ; blood ; Length of Stay ; statistics & numerical data ; Lymphocyte Count ; Male ; Middle Aged ; Parenteral Nutrition ; Postoperative Complications ; prevention & control ; Serum Albumin ; metabolism ; Treatment Outcome ; Young Adult ; gamma-Glutamyltransferase ; blood
7.Safety and efficacy of Qingre Buyi Decoction in the treatment of acute radiation proctitis: a prospective, randomized and controlled trial.
Lie WANG ; Zai-zhong ZHANG ; Xiao-huang TU ; Zhong-dong ZOU ; Jian-hua LIU ; Yu WANG
Chinese journal of integrative medicine 2009;15(4):272-278
OBJECTIVETo investigate the efficiency, safety, and possible mechanisms of Qingre Buyi Decoction (QBD) in the treatment of acute radiation proctitis (ARP).
METHODSThis study was a single center, prospective, single blind, randomized, and placebo-controlled clinical trial. A total of 60 patients with ARP was equally and randomly distributed into the control group (conventional treatment) and the combination group (conventional treatment plus QBD). The changes of main Chinese medicine clinical symptoms and signs, including stomachache, diarrhea, mucous or bloody stool before and after treatment, and their adverse reactions were observed after the two-week treatment. Also, D-lactate and diamine oxidase (DAO) levels, hepatic and renal function were measured. Cure rates, effective rates, and recurrence rates were compared between the two groups.
RESULTSThe blood levels of both DAO and D-lactate were significantly decreased in the combination group as compared with those in the control group (P<0.05 or P<0.01). All main clinical symptoms and signs were alleviated more significantly in the combination group (P<0.01). The main symptom scores also were significantly decreased after treatment in the control group (P<0.01), except those for mucous or bloody stool (P>0.05). Compared to the control group, the improvements of stomachache, diarrhea, defecation dysfunction, and stool blood in the combination group were significantly better (P<0.05 or P<0.01). For the combination group, the curative rate, effective rate, and recurrence rate was 76.67%, 16.67%, and 6.67%, respectively. On the other hand, for the control group, the rate was 53.33%, 16.67%, and 30.00%, respectively. The total curative effect was significantly better in the combination group than in the control group (P<0.05). However, the recurrence rate was similar between the two groups (P>0.05). The hepatic and renal function remained normal in both groups (P>0.05). In addition, no severe adverse event was found in both groups.
CONCLUSIONSAddition of QBD to the conventional treatment can effectively alleviate the damage of intestinal mucosal barrier function and improve all main clinical symptoms and signs of the ARP. The combination of conventional treatment with Chinese herbal medicine QBD is effective and safe for ARP.
Acute Disease ; Adult ; Aged ; Anti-Inflammatory Agents ; administration & dosage ; Azulenes ; administration & dosage ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Gastrointestinal Agents ; administration & dosage ; Glutamine ; administration & dosage ; Humans ; Integrative Medicine ; methods ; Male ; Middle Aged ; Norfloxacin ; administration & dosage ; Pain ; complications ; Proctitis ; complications ; drug therapy ; Sesquiterpenes ; administration & dosage ; Silicates ; administration & dosage ; Single-Blind Method ; Treatment Outcome
8.The change of intestinal mucosa barrier in chronic severe hepatitis B patients and clinical intervention.
Huai-Yu SONG ; Chun-Hua JIANG ; Jian-Rong YANG ; Qiu-Hong CHEN ; Jun HUANG ; Yun-Hua HUANG ; Lie-Xin LIANG
Chinese Journal of Hepatology 2009;17(10):754-758
OBJECTIVETo study the change of intestinal mucosa barrier in chronic severe hepatitis B patients and clinical intervention.
METHOD(1) 30 normal healthy controls and 60 chronic severe hepatitis B patients were enrolled in this study. The change of intestinal permeability was determined by urine lactulose/ mannitol ratio (L/M), and the serum diamine oxidase (DAO) was measured. (2) 60 chronic severe hepatitis B patients were randomly divided into two groups: the control group and the treated group, each group has 30 cases. Patients in the control group received standard treatment for 2 weeks, however, in addition to standard treatment, patients in the treated group also received glutamine 10g tid. Endotoxin (ET), DAO and L/M were compared between the two group.
RESULTS(1) Compared to healthy controls, the level of L/M and DAO was significantly increased in chronic severe hepatitis B patients (t = 2.762, P less than 0.01 or t = 6.326, P less than 0.01). (2) Compared to the control group, ET, DAO and L/M were significantly lower 2 weeks after treatment (F = 11.662, P less than 0.01; F = 12.699, P less than 0.01; F = 19.981, P less than 0.01).
CONCLUSION(1) There is an early intestinal mucosa barrier damage in chronic severe hepatitis B patients. (2) Compared to standard treatment, adding glutamine can reverse intestinal mucosa barrier damage.
Administration, Oral ; Adolescent ; Adult ; Amine Oxidase (Copper-Containing) ; blood ; Antiviral Agents ; pharmacology ; therapeutic use ; Child ; Endotoxins ; blood ; Female ; Glutamine ; pharmacology ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; metabolism ; physiopathology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; physiopathology ; Intestine, Small ; Lactulose ; urine ; Male ; Mannitol ; urine ; Middle Aged ; Permeability ; Treatment Outcome ; Young Adult
9.Effect of parenteral glutamine supplementation in premature infants.
Zheng-hong LI ; Dan-hua WANG ; Mei DONG
Chinese Medical Journal 2007;120(2):140-144
BACKGROUNDGlutamine, proposed to be conditionally essential for critically ill patients, is not added routinely to parenteral amino acid formulations for premature infants and is provided in only small quantities by the enteral route when enteral feeding is low. Parenteral feeding is the basic way of nutrition in the first days of life of premature infants. In this study, we evaluated the effects of glutamine supplemented parenteral nutrition for premature infants on growth and development, feeding toleration, and infective episodes.
METHODSFrom December 2002 to July 2006, 53 premature infants were given either standard or glutamine supplemented parenteral nutrition for more than 2 weeks. Twenty-eight infants were in glutamine supplemented group, whose gestational age (31.4 +/- 2.0) weeks, birth weight range (1386 +/- 251) g; twenty-five infants were in control group, gestational age (31.1 +/- 1.7) weeks, with birth weight range (1346 +/- 199) g. There were no differences between the two groups. Various growth and biochemical indices were monitored throughout the duration of hospital stay. Data between groups were analyzed with Student's t test. Nonparametric data were analyzed using a Chi-square test. A two-tailed P value < 0.05 was considered statistically significant.
RESULTSThe level of serum albumin was lower in the glutamine groups on the second week (3.0 vs 3.2 g/dl, P = 0.028), and blood urea nitrogen was higher in glutamine groups on the fourth week (8.1 vs 4.9 mg/dl, P = 0.014), but normal. Glutamine group infants took fewer days to regain birth weight (8.1 vs 10.4 days, P = 0.017), required fewer days on parenteral nutrition (24.8 vs 30.8 days, P = 0.035), with shorter stays in hospital (32.1 vs 38.6 days, P = 0.047). Episodes of hospital acquired infection in glutamine supplemented infants were lower than that in control group (0.96 vs 1.84 times, P = 0.000).
CONCLUSIONParenteral glutamine supplementation in premature infants can shorten days on parenteral nutrition and length of stay in hospital, and decrease hospital acquired infection episodes.
Blood Urea Nitrogen ; Child Development ; Cross Infection ; epidemiology ; Glutamine ; administration & dosage ; Growth ; Humans ; Infant, Newborn ; Infant, Premature ; Parenteral Nutrition
10.Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy.
Chinese Journal of Gastrointestinal Surgery 2006;9(1):59-61
OBJECTIVETo study the protective effect of glutamine (Gln) on intestinal permeability in patients receiving chemotherapy.
METHODSThirty-nine patients with gastrointestinal cancer after operation were randomly divided into Gln and control groups, and received oral administration of glutamine (30 g/d) for 7 days (n=22) or not (n=17). All patients received CF+ 5-FU chemotherapy for 5 days. Serum concentration of glutamine and urinary lactulose/mannitol (L/M) ratio were measured before and 1 day after chemotherapy.
RESULTSAfter chemotherapy, the serum Gln concentration was significantly decreased to (535.42+/- 53.75) micromol/L in the control group and increased to (54.44+/- 81.26) micromol/L in the Gln group, and there was significant difference between the two groups (P< 0.01). Urine L/M ratio was significantly increased to (0.0453+/- 0.0078) in the control group and decreased to (0.0331+/- 0.0061) in the Gln group, and there was significant difference between the two groups after chemotherapy (P< 0.01).
CONCLUSIONOral administration of glutamine granules can increase serum concentration of glutamine in chemotherapy patients with gastrointestinal cancer and can decrease intestinal permeability, maintain intestinal barrier.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Female ; Gastrointestinal Neoplasms ; drug therapy ; therapy ; Glutamine ; administration & dosage ; therapeutic use ; Humans ; Intestinal Mucosa ; drug effects ; Male ; Middle Aged ; Postoperative Period

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