[Protective effects of glycyl-glutamine dipeptide supplement on the heart function in burn rats].

OBJECTIVE: To investigate the protective effects of glycyl-glutamine dipeptide supplement on the function of myocardial dynamics in severely burned rats, and to explore its mechanism. METHODS: One hundred and thirty-six Wistar rats were randomly divided into five groups: i. e, control group (C, n = 8, without burns), burn group (B, n = 32), Gln group (Gln, n = 32), Gly group (Gly, n = 32) and Gly-Gln group (Gly-Gln, n = 32). The rats in the latter four groups were respectively treated with tyrosine (1.5 g x kg(-1) x d(-1)), glutamine (1.0 g x kg(-1) x d(-1)) and tyrosine (0.5 g x kg(-1) x d(-1)), glycine (0.5 g x kg(-1) x d(-1)) and tyrosine (1.0 g x kg(-1) x d(-1)), and Glycyl-glutamine dipeptide (1.5 g x kg(-1) x d(-1)) after receiving a 30% TBSA full-thickness burn on the back. Glutathione (GSH), adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), cell energy charge (EC) and the index of myocardial dynamics (ASOP, AODP, LVSP, + dp/dtmax) were measured at 12, 24, 48, 72 post-burn hours (PBH). RESULTS: The content of GSH, ATP, EC and the level of aortic systolic pressure (ASOP), aortic diastolic blood pressure (AODP), left ventricular end diastolic pressure (LVEDP) and maximum rate of intraventricular pressure rise/down (+ dp/dtmax) in B, Gln, Gly, Gly-Gln groups were obviously lower than those in C group (P < 0.01), while the levels of AMP and ADP showed an opposite tendency. Compared with B group, the above indices were ameliorated. The content of GSH (72.7 +/- 1.7) micromol/g in Gly-Gln group at 12 PBH was obviously higher than that in Gln group (67.8 +/- 3.8) micromol/g (P < 0.01). The levels of EC and AOSP were obviously higher in Gly-Gln group than that in Gln group (P < 0.01). The level of GSH, EC, AOSP in Gly-Gln groups were obviously higher than those in Gly group at 48 PBH. CONCLUSION: Glycyl-glutamine dipeptide, Gly and Gln supplementation after burns can improve the content of GSH and high energy phosphate compound, and suppress the decline of myocardial dynamics function. The effects of Glycyl-glutamine dipeptide is better than single Gly or Gln, indicating that the protective effect on myocardial function after severe burns by Gln and Gly is synergistic.

[Analysis of the influence on the prognosis and safety of arginine in patients with severe trauma and burns--a multi-center randomized double blinded, placebo controlled, clinical trail in 86 patients].

OBJECTIVE: To observe the influence on prognosis and possible side-effects of arginine in METHODS: Multi-center clinical trial, randomized double blinded patients with severe trauma and burns. and placebo control methods were employed in the study. Eighty-six patients with severe trauma and burns were randomly divided into control (C, n = 45) and arginine treatment (Arg, n = 41) groups. The patients in Arg group received arginine in dose of 0. 4 g x kg(-1) x d(-1) orally, while those in C group received same dose of placebo (tyrosine) for 7 days. All the patients in both groups were given diet with equal calories and equal nitrogen content. The changes in the wound healing time, hospital stay, and the incidence of side-effects of the medication in both groups of patients were observed and compared before and after the supplementation of arginine. RESULTS: The wound healing time and hospital stay days of severe trauma patient in Arg group (n = 29) were 11. 1+/-2. 8 d and 19+/-6 d, which were all obviously shorter than those in C group (13. 2+/-5. 5 d, 22 +/-6 d, n =33, P <0.05). On the other hand, in severe burn patients there were no significant difference of the wound healing time (20+/-5 d vs 22+/-8 d, n = 12, P > 0. 05) and hospital stay days (28+/-6 d vs 29+/-8 d, n = 12, P >0. 05) between the Arg and C groups. In addition, in C and Arg groups, the occurrence of the side-effects were seldom (2. 44% vs 2. 22% , P = 1. 000) and it disappeared when the supplementation of drugs was stopped. CONCLUSION: Oral feeding of arginine is beneficial in enhancing wound healing, reduction of hospital stay days in severe trauma patients and with little side-effects, but it is not beneficial to improve the prognosis of severe burn patients. Maybe this is due to inadequate number of case involved in the study.

[Effects of glutamine given through different avenues on intestine mucosal barrier function in burned rats].

OBJECTIVE: To observe the effect of glutamine given through different avenues on intestine mucosal barrier damage induced by severe burn injury. METHODS: One hundred and sixty Wistar rats were randomly divided into four groups: namely normal control (C group), burned control (B group), parenteral nutrition with glutamine (PN+GLN group) and enteral nutrition with glutamine (EN+GLN group). Rats in B group, PN+GLN group, and EN+GLN group were subjected to 30% total body surface area (TBSA) full-thickness burn injury. In the latter three groups, nutritional intake was isonitrogenous and isocaloric. In PN+GLN group and EN+GLN group the nutrition were supplemented with glutamine 1.0 g.kg(-1).d(-1), and in B group tyrosine 1.0 g.kg(-1).d(-1). Indexes relevant to injury to the intestine were determined on postburn day (PBD) 1, 3, 5, 7 and 10. RESULTS: After burn injury, the index of intestinal mucosal injury, intestine mucosal permeability and the activity of plasma diamine oxidase (DAO) were significant increased compared with C group (all P<0.01). On the other hand, the intestine mucosal blood flow (IMBF), mucosa thickness, villous height, crypt depth and intestinal epithelial proliferation index were significantly decreased (P<0.05 or P<0.01). Compared with B group, the extent of changes in these indices were lowered in PN+GLN group and EN+GLN group (P<0.05 or P<0.01), and the effects were more marked in EN+GLN group than those in PN+GLN group. CONCLUSION: GLN is beneficial in minimizing intestinal injury, promoting intestinal mucosal repair. Enteral supplementation of GLN is a better way of administration.

[Effects of glutamine granules on immunofunction in trauma patients: a double-blind randomized controlled, multi-center clinical trail with 120 patients].

OBJECTIVE: To evaluate the effect of glutamine granules on immunofunction in severe burns and trauma patients. METHODS: One hundred and twenty patients with severe burns, multiple trauma and post operation who met the requirements of the protocol joined this double-blind randomized controlled, multi-center clinical trail. Patients were randomly divided into two groups: placebo control group (P group, 60 patients) and glutamine granules treatment group (GLN group, 60 patients). There was isonitrogenous and isocaloric intake in both groups. GLN and P group patients had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(-1) for 7 days, respectively. The level of plasma glutamine and some index of immunofunction were determined, and the complication and side effect were also observed. RESULTS: After 7 days of taking glutamine granules orally, plasma GLN concentration was significantly higher than that in P group [(593 +/- 185) micromol/L vs (407 +/- 190) micromol/L)] (P < 0.01). IL-2 level, CD(4)/CD(8) ratio, PMN swallow ratio in GLN group were significantly higher than those in P group (P < 0.05-0.01), but the concentration of IgG, IgM, C(3)/C(4) were not significantly different when compared with P group (P > 0.05). In addition, the occurrence of side effect in both groups was seldom. CONCLUSION: Taking glutamine granules could increase plasma GLN concentration, enhance body immunofunction, and using glutamine granules is safe.

[Comparative study on the influence of arginine hydrochloride and arginine acetate on the immune function and acid-base balance in rabbits with severe burns].

OBJECTIVE: To investigate the influence of arginine hydrochloride and arginine acetate on the immune function and acid-base balance in rabbits with severe burns. METHODS: One hundred and ten flap-eared rabbits were used in the study, in which 8 served as normal control, while the rest were inflicted with 30% TBSA full thickness burn. All the rabbits were divided into 10 groups, i.e. normal control (C, n = 14), burn control (B, n = 14, with intravenous infusion of Ringer's solution), 0.3 g/kg arginine hydrochloride (AH, n = 12), 0.3 g/kg arginine acetate (AA, n = 10), 0.6 g/kg AH (n = 10), and 0.6g/kg AA (n = 10) groups, 1.2 g/kg AH (n = 10), 1.2 g/kg AA (n = 10), 2.4 g/kg AA (n = 14) and 2.4 g/kg AH (n = 12) groups. AA and AH in different doses were fed to rabbits in corresponding groups 2 times a day for 7 days. The changes in the immune function, acid-base balance, chloride ion metabolism, and mortality were determined. RESULTS: Disorder in immune system was found after severe burns, with enhanced immune function at the beginning and weakening afterwards. The lymphocytic transformation rate, the CD4/CD8 ratio, the phagocytosis rate and the chemotactic index of white blood cells on 7 post burn day (PBD) were obviously lower in B group compared with C group (P < 0.05 or 0.01). These indices were obviously higher in 1.2, 2.4 g/kg AA and AH groups than those in B group on 7 PBD (P < 0.05 or 0.01). There was no difference in improvement of immune functions between 0.3, 0.6g/kg AH, AA group and B group. The values of blood pH, base excess (BE), buffer base (BB), HCO(3)(-) level in AH group were significantly lower than those in C group on 7 PBD (P < 0.05 or 0.01), while there were no obvious changes in AA group, they were obviously higher than those in AH group (P < 0.05 or 0.01). The contents of chloride ion in but 2.4 g/kg AH group during 5 to 7 PBD were obviously higher than those in C group and 2.4 g/kg AA group (P < 0.05 or 0.01), while no difference was found between 2.4 g/kg AA and C groups. The mortality in B group was obviously higher than that in 0.3, 0.6, 1.2 g/kg AH and AA groups (P < 0.05 or 0.01), but significantly lower than that in 2.4 g/kg AA and AH groups (P < 0.05). CONCLUSION: Disorders in immune functions were observed in severely burned rabbits. Administration of arginine acetate as well as arginine hydrochloride could enhance the immune function, but arginine acetate seemed to be safer than arginine hydrochloride. Excessive dosage should be avoided to prevent a rise of the mortality.

[Analysis of the therapeutic effect and the safety of glutamine granules per os in patients with severe burns and trauma].

OBJECTIVE: To observe the therapeutic effect and possible side effects of glutamine granules per os in patients with trauma, burns and major operations. METHODS: Patients inflicted with severe burns, trauma and major operations were enrolled in the study. One hundred and twenty patients were randomly divided into two groups, 60 in control group (C) and 60 in glutamine group (Gln). Randomized double blind and placebo control methods were employed in the study. All the patients in both groups were given diet with equal calories and equal nitrogen content. The patients in Gln group received glutamine granules in dose of 0.5 g.kg(-1).d(-1) orally or by gavage, while those in C group received same dose of placebo (glycine) for 7 days. The changes in the intestinal mucosal barrier function, the protein metabolism, the immune function, hepatic and renal functions, and the incidence of side effects of the medication in both groups of patients were observed and compared before and after the supplementation of glutamine or glycine. RESULTS: The plasma contents of glutamine, proteins and interleukin 2 in both groups were all lower than normal values. But the plasma diamine oxidase (DAO) activity, endotoxin content, intestinal mucosal permeability (urine lactose/mannitol, L/M) and urine excretion of nitrogen increased obviously in both groups. The plasma glutamine concentration in Gln group increased by 38.04% after the administration of Gln for 7 days (P < 0.01). The plasma contents of pro-albumin, transferrin, and IL-2 were obviously higher than those in the C group (the increase rates were 21.19%, 51.11%, 57.54%, respectively, P < 0.01). The plasma DAO activity, L/M ratio, endotoxin content and urine nitrogen excretion in Gln group were evidently lower than those in C group (the decrease rates were 47.26%, 52.18, 22.22% and 27.78%, respectively, P < 0.05 or 0.01). There was no obvious difference in the plasma levels of total protein and albumin, the indices in blood and urine test, or the hepatic and renal functions between the two groups before and after the amino acid supplementation. Mild side effects such as nausea, diarrhea, constipation occurred in both groups, but all of them disappeared spontaneously afterwards (P > 0.05). CONCLUSION: Oral administration of glutamine could be helpful to increase plasma concentration of glutamine and to ameliorate obviously the intestinal mucosal injury, to promote systemic protein synthesis and to inhibit protein catabolism and to upgrade systemic immune function with little side effect in patients with severe injury.

[Effects of glutamine granules on protein metabolism in trauma patients].

OBJECTIVE: To evaluate the effect of glutamine granules on protein metabolism in severe burns and trauma patients. METHODS: 120 patients with severe burns, multiple trauma and post operation who met the requirements of the protocol joined this double-blind randomized controlled, multi-center clinical trail. Patients were randomly divided into two groups: placebo control group (P group, 60 patients) and glutamine granules treatment group (GLN group, 60 patients). There was isonitrogenous and isocaloric intake in both groups, GLN and P group patents had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(-1) for 7 days, respectively. The level of plasma glutamine, protein and urine nitrogen exclude were determined, wound healing rate of burn area and hospital stay were recorded, and then observed the complication and side effect. RESULTS: After 7 days of taking glutamine granules orally, plasma GLN concentration was significant higher than that in P group (592.50 +/- 185.23 micro mol/L vs. 407.41 +/- 190.22 micro mol/L) (P < 0.01). Plasma prealbumin and transferrin in GLN group were significant higher than those in P group (P < 0.01), but the concentration of total protein and albumin were no marked changes compare with P group (P > 0.05). The capacity of urine nitrogen exclude in GLN group were significant lower than that in P group. Additional, the wound healing rate was faster and hospital stay days was shorter than P group (P < 0.05), and the occurrence of glutamine granules side effect was seldom. CONCLUSION: Taking glutamine could promote protein synthesis, abate protein decompose, ameliorate wound healing rate and reduce hospital stay obviously.

[Effects of enteral supplementation with glutamine on mitochondria respiratory function of intestinal epithelium in burned rats].

OBJECTIVE: To investigate the effects of enteral supplementation with glutamine on mitochondria respiratory function of intestinal epithelium in burned rats. METHODS: Wistar rats inflicted with 30% total body surface area (TBSA) full thickness thermal injury were randomly divided into three groups, i.e. burn with enteral nutrition (EN), burn with glutamine treatment (GLN), and normal control (C) groups. Burned rats were infused 732.2 kJ.kg-1.d-1 solution for intravenous nutrition and oral administration, in which the supply energy ratio of glucose, fat and protein was 55:30:15 respectively, glucose was 15.3% and the proportion of calorie to nitrogen was 183:1. The following indices including respiratory control rate (RCR), oxygen extraction (Oext), P/O ratio and intestine mucosal blood flow (IMBF) were measured on postburn days 1, 3, 5, 7, 10. RESULTS: After burn injury, the RCR, Oext, P/O ratio, and IMBF were significant decreased in both EN and GLN groups, but all above indices were markedly increased in GLN group compared to those in EN group. CONCLUSION: After burn injury, the IMBF and Oext were declined, resulting in mitochondria respiratory oxidative dysfunction and phosphorylation discoupling in intestinal epithelium. GLN supplementation appears to be beneficial to improving IMBF, increasing Oext, abating the extent of mitochondria respiration dysfunction, and promoting oxidative phosphorylation.

[Experimental study on the effects of intestinal trefoil factor on intestinal epithelial proliferation and its signal transduction mechanism].

OBJECTIVE: To explore the effects of intestinal trefoil factor (ITF) on intestinal epithelial proliferation and its possible signal transduction mechanism. METHODS: 1). The intestinal epithelial cytoplasmic membrane was isolated and harvested from Wistar rats, and it was treated with various doses of ITF in the concentration of 0.01, 0.10, 1.00 and 10.00 micro g/ml. The tyrosine protein kinase (TPK) activity from cytoplasmic membrane ITF receptor was determined by membrane-bound method. 2). The intestinal epithelial cells 6 (IEC-6) cultured in vitro were employed in the study. Some of the cells were used as normal control, while a group of cells were stimulated by 1 micro g/ml ITF, and others were treated by PD098059, SB202190 and SB202474, respectively. The last three agents were inhibitors of three members of mitogen-activated protein kinase family (MAPKs), i.e. extracellular signal regulated protein kinases (ERKs), protein kinase p38 (p38), and stress-activated protein kinase (SAPK). They were used before the addition of 1 micro g/ml of ITF. The changes in DNA synthetic rate and the MAPK activity of IEC-6 after being treated by above agents were assessed by (3)H-TdR incorporation method. RESULTS: ITF receptor possessed TPK activity. TPK activity of ITF receptor, MAPKs activity and DNA synthetic rate of IEC-6 were increased obviously under the stimulation of ITF (P < 0.01). The above ITF effects could be evidently blocked by PD098059 and partially attenuated by SB202474. But SB202190 showed no effect in this respect. CONCLUSION: ITF could promote intestinal epithelial proliferation and transmit extracellular signals mainly by means of ERKs signalling pathway.

[Influence of glucagon-like peptide-2 on the proliferation of the intestinal mucosal cells in scalded rats].

OBJECTIVE: To explore the influence of glucagon-like peptide-2 (GLP-2) on the proliferation of the intestinal mucosal cells in scalded rats. METHODS: Fifty-five Wistar rats were employed in the study and were randomly divided into normal control (C), simple scald (S) and scald with GLP-2 treatment (G) groups. The rats in G group received GLP-2 introperitoneally in a dose of 200 micro g/kg two times a day. The rats in S and G groups were sacrificed at 6 postburn hours (PBHs), 12 PBHs, 1 postburn day (PBD1), PBD3 and PBD5 and the rats in C group were also sacrificed. Plasma diamine oxidase (DAO) activity, cell cycle protein cyclin D expression and the proliferating cell nuclear antigen (PCNA) in all groups were determined. And the histological change in the intestinal mucosal tissue was observed simultaneously. with all the above determinations. RESULTS: Compared with those in C group, the PCNA expression at 6 and 12 PBHs in S group was enhanced slightly and weakened at PBD1, reaching the lowest level at PBD3 and it was still lower than that in C group at PBD5. Changes in PCNA in G group were similar to that in S group, except that the expression at PBD3 and PBD5 was stronger than that in S group. The intestinal mucosal cyclin D protein expression was increased at 6 and 12 PBHs in S group, but decreased by 40% before injury at PBD1. Nevertheless, the cyclin D protein expression in G group was much higher than that in S group at PBD1, PBD3 and PBD5. The plasma DAO activity increased significantly in rats after burn injury. But the activity decreased obviously after GLP-2 treatment for 5 days (P < 0.01). It was observed histologically in G group that the lining of Exogenous intestinal villi was regular and well arranged without evident epithelial exfoliation. CONCLUSION: Exogenous GLP-2 might ameliorate intestinal mucosal injury in scalded rats, and promotion of the expression of PCNA and cyclin D, resulting in proliferation of injured intestinal mucosal cells, might be the underlying mechanisms.