Expert consensus on clinical application of intravenous alanyl-glutamine dipeptide / 中华临床营养杂志

Alanyl-glutamine dipeptide is an important component in parenteral nutrition, which can be decomposed into alanine and L-glutamine in vivo. It plays multiple functions including maintaining intestinal barrier, improving immunity, promoting protein synthesis, and regulating the production and release of inflammatory mediators. Substantial clinical evidences have demonstrated its favorable effectiveness and safety. Rational application of alanyl-glutamine dipeptide can reduce postoperative complications, shorten hospital stay and save medical costs. There are still controversies at home and abroad on the applicable population and dosage of alanyl-glutamine dipeptide. Chinese Society of Parenteral and Enteral Nutrition organized China's experts of related disciplines to compile international standards in accordance with the latest guidelines and consensus, so as to achieve the goal of standardized application and patient benefits.

Heat shock response in noise-induced hearing loss: effects of alanyl-glutamine dipeptide supplementation on heat shock proteins status / Resposta de choque térmico em perda auditiva induzida por ruído: efeitos da suplementação com dipeptídeos de alanil-glutamina sobre o estado das proteínas de choque térmico

Abstract Introduction: The 72 kDa heat shock protein, HSP72, located intracellularly provides cochlear cytoprotective and anti-inflammatory roles in the inner ear during stressful noise challenges. The expression of intracellular HSP72 (iHSP72) can be potentiated by alanyl-glutamine dipeptide supplementation. Conversely, these proteins act as pro-inflammatory signals in the extracellular milieu (eHSP72). Objective: We explore whether noise-induced hearing loss promotes both intracellular and extracellular HSP72 heat shock response alterations, and if alanyl-glutamine dipeptide supplementation could modify heat shock response and prevent hearing loss. Methods: Female 90 day-old Wistar rats (n = 32) were randomly divided into four groups: control, noise-induced hearing loss, treated with alanyl-glutamine dipeptide and noise-induced hearing loss plus alanyl-glutamine dipeptide. Auditory brainstem responses were evaluated before noise exposure (124 dB SPL for 2 h) and 14 days after. Cochlea, nuclear cochlear complex and plasma samples were collected for the measurement of intracellular HSP72 and extracellular HSP72 by a high-sensitivity ELISA kit. Results: We found an increase in both iHSP72 and eHSP72 levels in the noise-induced hearing loss group, which was alleviated by alanyl-glutamine dipeptide treatment. Furthermore, H-index of HSP72 (plasma/cochlea eHSP72/iHSP72 ratio) was increased in the noise-induced hearing loss group, but prevented by alanyl-glutamine dipeptide treatment, although alanyl-glutamine dipeptide had no effect on auditory threshold. Conclusions: Our data indicates that cochlear damage induced by noise exposure is accompanied by local and systemic heat shock response markers. Also, alanyl-glutamine reduced stress markers even though it had no effect on noise-induced hearing loss. Finally, plasma levels of 72 kDa heat shock proteins can be used as a biomarker of auditory stress after noise exposure.

Resumo Introdução: A proteína de choque térmico de 72 kDa, HSP72 localizada intracelularmente, tem papéis citoprotetores e anti-inflamatórios cocleares na orelha interna durante situações de ruído estressantes. A expressão dessa proteína pode ser potencializada pela suplementação com dipeptídeo de alanil-glutamina. Por outro lado, essas proteínas atuam como sinais pró-inflamatórios no meio extracelular. Objetivo: Investigar se a perda auditiva induzida por ruído promove alterações tanto das proteínas HSP72 intracelulares quanto extracelulares na resposta de choque térmico e se a suplementação com alanil-glutamina pode modificar a resposta de choque térmico e evitar a perda auditiva. Método: Ratos Wistar fêmeas, com 90 dias de idade (n = 32), foram divididos aleatoriamente em quatro grupos: controle, perda auditiva induzida por ruído, tratados com alanil-glutamina e perda auditiva induzida por ruído mais alanil-glutamina. Os potenciais evocados auditivos do tronco encefálico foram avaliados antes da exposição ao ruído (124 dB NPS por 2 h) e 14 dias após. A cóclea, o complexo nuclear coclear e amostras de plasma foram coletadas para mensuração de HSP72 intra e extracelular com um kit Elisa de alta sensibilidade. Resultados: Houve um aumento nos níveis de HSP72 intra e extracelular no grupo perda auditiva induzida por ruído, que foi minimizado pelo tratamento com alanil-glutamina. Além disso, o índice H das HSP72 (razão HSP72 extracelular/HSP72intracelular plasma/cóclea) aumentou no grupo perda auditiva induzida por ruído, mas foi limitado pelo tratamento com alanil-glutamina, embora o alanil-glutamina não tenha efeito no limiar auditivo. Conclusões: Nossos dados indicam que o dano coclear induzido pela exposição ao ruído é acompanhado por marcadores da resposta de choque térmico locais e sistêmicos. Além disso, alanil-glutamina reduziu os marcadores de estresse, mesmo não tendo efeito sobre a perda auditiva induzida por ruído. Finalmente, os níveis plasmáticos de proteínas de choque térmico de 72 kDa podem ser usados como biomarcador do estresse auditivo, após a exposição ao ruído.

Clinical Study on the Application of Alanyl-glutamine Dipeptide-intensified Early Enteral Nutrition Sup-port in Sepsis Patients / 中国药房

OBJECTIVE:To investigate the effects of alanyl-glutamine dipeptide-intensified early enteral nutrition (EN) sup-port on nutritional indexes,immune indexes,renal indexes and complications of sepsis patients. METHODS:A total of 112 cases of sepsis admitted into our hospital during May 2013-Jan. 2015 were selected and divided into observation group and control group according to random number table,with 56 cases in each group. Both groups received routine antibiotic therapy and early EN support(48 h)with nitrogen supplement 0.2 g/kg,calories 25 kcal/kg and nonprotein calories 19-21 kcal/kg each day. Observation group was additionally given Alanyl-glutamine for injection 0.5 g/kg with 0.9% sodium chloride injection 100 mL,continuous pump within 24 h,for 4 d. The levels of nutritional indexes (ALB,PAB,Hb),immune indexes (CRP,IgG,IgA and IgM), APACHEⅡ scores,SOFA scores,liver and renal function indexes (the levels of ALT,AST,Cr and BUN) were compared be-tween 2 groups before and after treatment. The prognosis and the occurrence of complication were also observed in 2 groups. RE-SULTS:Before treatment,there was no statistical significance in the levels of ALB,PAB,Hb,CRP,IgG,IgA,IgM,ALT, AST,Cr,BUN and APACHEⅡ scores,SOFA scores between 2 groups(P>0.05). After treatment,the levels of ALB and PAB in observation group were increased significantly compared to before treatment,and the observation groups was significantly higher than control group,with statistical significance(P<0.05). APACHEⅡ score and SOFA score of 2 groups were decreased significantly compared to before treatment,and the observation group was significantly lower than the control group,with statis-tical significance(P<0.05). CRP of 2 groups were decreased significantly while IgG were increased significantly;the observa-tion group was significantly better than the control group,with statistical significance (P<0.05). Cr and BUN levels of 2 groups were decreased significantly compared to before treatment,and the level of Cr in observation group was significantly con-trol group,with statistical significance (P<0.05). The time of ICU stay,ventilator supporting time and antibiotics application time in observation group were significantly shorter than control group,and the incidence of diarrhea and gastric retention were significantly lower than control group,with statistical significance (P<0.05). CONCLUSIONS:Alanyl-glutamine dipeptide-in-tensified early EN support can significantly improve immune function and liver and renal function of sepsis patients and reduce the occurrence of complications.

Clinical Effect of Alanyl Glutamine Combined with Octreotide on Severe Acute Pancreatitis / 现代生物医学进展

Objective:To explore the clinical efficacy of alanyl glutamine (Ala-Gln) combined with octreotide in the treatment of severe acute pancreatitis (SAP) and its effects on the serum interleukin-6 (IL-6),C reactive protein (CRP) levels and related biochemical parameters.Methods:100 cases of patients with SAP in our hospital from January 2013 to December 2016 were selected and randomly divided into two groups.The control group was treated by octreotide,while the observation group was treated by Ala-Gln combined with octreotide.The clinical effect,changes of serum IL-6,CRP,amylase (AMY),lactate dehydrogenase (LDH),prealbumin (PA) and albumin (ALB) levels before and after therapy were compared between two groups.Results:On the 10th day after treatment,the overall effective rate of observation group was 88.0％ which was significantly higher than that of the control group (64.0％,P＜0.05).The serum IL-6,CRP,AMY and LDH levels of both groups on the 10th day after treatment were significantly lower than those before treatment (P＜0.01).Compared with the control group,the improvement of serum IL-6,CRP,AMY,LDH levels of observation group were more significant(P＜0.01).Compared with those before treatment,the serum PA and ALB levels of both groups were significantly increased on the 10th day after treatment(P＜0.05),and the improvement of serum PA and ALB levels of observation group on the 10th day after treatment were significantly better than those of the control group(P＜0.01).Conclusion:Alanyl glutamine combined with octreotide could effectively eliminate or alleviate the symptoms and signs of patients with severe acute pancreatitis,control the inflammatory reaction,improve the level of metabolism,improve the prognosis.

Clinical effect of alanyl glutamine in the treatment of patients with gastrointestinal function obstacle caused by severe phorate poisoning / 中华劳动卫生职业病杂志

Objective@#To observe the therapeutic efficacy of alanyl glutamine injection on patients with gastrointestinal function obstacle caused by severe phorate poisoning.@*Methods@#A total of 80 eligible patients with gastrointestinal function obstacle caused by severe phorate poisoning were randomly divided into the control group (n=40) and treatment group (n=40) . The control group was treated with the conventional therapy, which included forbidden diet, atropine, pralidoxime iodide, anti-inflammatory, albumin infusion, ω-3 fish oil fat emulsion, protection of organs function, blood perfusion, and Fat Emulsion, Amino Acids (17) and Glucose Injection. The treatment group was treated with alanyl glutamine injection plus the conventional therapy. To observe the time of recovering to normal of gastrointestinal function between the two groups, compared the AChE activity and changes of prealbumin, albumin and total protein of the two groups respectively. Furthermore, the total atropine dosage, the total pralidoxime iodide dosage and ICU stay time between the two groups were also compared.@*Results@#The gastrointestinal function recovery time of patients in the treatment group was less than the control group, the difference was statistically significant (P<0.05) . From the third day of treatment, the serum cholinesterase activity of the treatment group was higher than the control group, the difference was statistically significant (P<0.05) . On the 5th day and 10th day of the treatment, the prealbumin, albumin and total protein of the treatment group were significantly higher than these indexes of the control group in the same period, the difference were statistically significant (P<0.05) . The total atropine dosage, the total pralidoxime iodide dosage and ICU stay time in the treatment group were lower than the control group, the difference were statistically significant (P<0.05) .@*Conclusion@#Alanyl glutamine injection has a great therapeutic effect for gastrointestinal function obstacle patients caused by severe phorate poisoning.

Formulation and Intervention Effect Analysis of Evaluation Criteria for Alanyl-glutamine Rational Use in Our Hospital / 中国药房

OBJECTIVE:To explore the effect of clinical pharmacist intervention on the rational use of Alanyl-glutamine injection.METHODS:Referring to package inserts of Alanyl-glutamine injection,Clinical Pharmacy Consensus of Parenteral Nutrition,ASPEN Nutrition Therapy Guidelines for Critically Ill Patients,related domestic and foreign literatures,evaluation criteria for Alanyl-glutamine injection rational use was formulated.After collecting Alanyl-glutamine injection cases (497 cases) in the second quarter of 2015 and those cases (385 cases) in the second quarter of 2016,rational use of Alanyl-glutamine injection were analyzed comparatively before and after intervention.RESULTS:The utilization rate and irrational rate of Alanyl-glutamine injection were 4.6％ and 52.9％ before intervention as well as 2.9％ and 10.9％ after intervention,with statistical significance (P＜0.05).There was statistical significance in hyper-indication,excessive concentration of drug liquid,excessive supply of amino acid,irrational compatibility and solvent selection,long treatment course before and after intervention (P＜0.05).CONCLUSIONS:Clinical pharmacists reduce irrational rate of drug use and guarantee safe and effective drug use through formulating evaluation criteria for Alanyl-glutamine injection rational use and providing pharmaceutical intervention on rational use of Alanyl-glutamine injection.

Effect of pharmaceutical intervention on rational use of alanyl-glutamine / 中国基层医药

Objective To explore the effect of clinical pharmacist intervention on the rational use of alanyl-glutamine injection.Methods Refer to the second quarter of 2015 and the second quarter of 2016 in the General Hospital of Shanxi Datong Coal Group using alanyl-glutamine injection discharge instructions for special comment, compared and analyzed the changes in the use of the drug before and after the intervention.Results Before intervention, the usage rate and the irrational rate of alanyl-glutamine injection were 4.6% and 52.9%,those were 2.9% and 10.9% after intervention.The differences were statistically significant(χ2 =49.209,169.200,all P<0.05).There were significant differences before and after intervention compared in the choice of drug suitability,the high concentration of the medicine liquid,the excessive supply of amino acid and the incompatibility of the compatibility (χ2 =38.882, 31.348,26.242,4.286,all P<0.05 ).Conclusion The pharmacy intervention is feasible and effective for the rational use of alanyl-glutamine injection,and it can reduce irrational using rate.

Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

The effects of pretreatment with alanyl-glutamine dipeptide on intestinal barrier function in rats after cardiopulmonary bypass / 中华胸心血管外科杂志

Objective To explore the protective effects of pretreatment with alanyl-glutamine dipeptide on intestinal barrier function in rats after cardiopulmonary bypass.Methods CPB model in rats was established.60 SD rats were randomly divided into group G(pretreatment with alanyl-glutamine before CPB for 3 days and primed with it during CPB,n =20),group CPB(n =20) and sham-operation(SH) group(n =20).The diamine oxidase(DAO) activity of plasma and tissue homogenate of intestinal mucosa were measured by spectrophotometry,and the concentration of plasma D-lactate was also detected by spectrophotometry.The levels of plasma lipopolysaccharide(LPS) was measured by tachypleus amebocyte lysate development process.And software SPSS 16.0 was used for statistics analysis.Results The plasma DAO activity in group G was significantly lower than that in group CPB(P ＜0.05),even though compared with group SH,the DAO activity in group G and CPB were significantly increased (P ＜ 0.05).The activity of DAO in tissue homogenate in group G and CPB were decreased more significantly than that in group SH(P ＜ 0.05),but there was no difference between group G and CPB (P =0.065).The plasma concentrations of D-lactate and LPS in group G were significantly lower than that in group CPB (P ＜ 0.05),and the plasma concentration of D-lactate and LPS in both group G and CPB were markedly enhanced compared with group SH(P ＜ 0.05).Conclusion Precondition with alanyl-gluamine dipeptide can decrease the permeability of gut mucosa,and might be a new way to protect the intestinal barrier function during cardiopulmonary bypass.

Study on intestinal mucosal barrier dysfunction induced by postthoracotomyand and protection of alanyl-glutamine dipeptide in aged patients / 中国综合临床

Objective To investigate the changes of intestinal mucosal barrier function and protection of alanyl-glutamine(Alm-Gln) dipeptide during early stage of postthoracotomy in aged patients.Methods A prospective,randomized and controlled trial was conducted and 20 aged patients who underwent non-digestive thoracotomy were randomized into two groups,experimental group (intravenous administration of Aln-Gln dipeptide,0.5 g/(kg · d),for 4 days,n =10) and control group(equal amount saline as placebo,for 4 days,n =10).The indices of boby temperatures,heart rates,respiration and white blood cell count of all patients were daily recorded during administration.Serum concentrations of glutamine (Gln),D-lactate,diamine oxidase (DAO) and tumor necrosis factor-α(TNF-α) were measured before and after operation.Results There were no statistically significant differences in the patients' general information between experimental group and control group including age,gender and body weight.Plasma Gln concentration in postoperative 5 days was higher than that of pre-operation of experiment group ((478.32 ± 47.42) μmol/L vs.(372.67 ± 29.14) μmol/L,P =0.021).The plasma Gln level of control group at 5th day after operation was higher than that in pre-operation ((431.12 ± 42.27) μmol/L vs.(386.29 ± 19.73) μmol/L,P =0.017).The plasma level of Gln in experimental group was significantly higher than that in control group after operation((478.32±47.42) μmol/L vs.(386.29 ± 19.73) μmol/L,P =0.012).There were no significantly differences between the two groups in terms of the plasma level of DAO and D-lactate before operation (P ＞ 0.05).Meanwhile the levels of DAO and D-lactate in both group at 5th day after operation were significantly higher than that at before operation(DAO:(2.53 ±0.47) U/ml vs.(1.66±0.32) U/ml,P =0.003;D-lactate:(6.82 ±1.91) mg/L vs.(4.92 ±1.57) mg/L,P =0.024),and the levels of them in experimental group were significantly lower than that in control group(DAO:(1.10 ± 0.23) U/ml vs.(2.53 ± 0.47) U/ml,P =0.013 ; D-lactate:(4.87 ± 1.33) mg/L vs.(6.82 ± 1.91) mg/L,P =0.019).The concentration of TNF-α was significant increase in both two groups at first day after operation,but decreased at the third day.The concentration of TNF-α in experimental group at 5th day after operation was lower than that in control group ((6.89 ± 5.21) pg/L vs.(13.04 ± 4.46) pg,/L,P =0.003).The morbidity of systemic inflammatory response syndrome (SIRS) was significantly decreased in experimental group and the rate of SIRS was also lower than that in the control group(P ＜ 0.01).Conclusion Intestinal mucosal barrier function was damaged after thoracotomy in aged patients.Administration of Aln-Gln dipeptide could increase the level of serum Gln,protect the intestinal barrier and attenuate the systemic inflammatory response.Aln-Gln dipeptide can be used to help aged patients recover rapidly.

Effect of alanyl-glutamine dipeptide on the short-term outcomes of critically ill patients: a retrospective study of 617 cases / 中华临床营养杂志

Objective To explore the effects of alanyl-glutamine (Ala-Gln) dipeptide supplemented parenteral nutrition (PN) on the short-term outcomes in critically ill adult patients.Methods In this retrospective study,we reviewed the clinical data of critically ill adult patients who were treated by standard PN from January 2006 to December 2011.The length of stay in intensive care unit (ICU-LOS),incidences of infections and multiple organ dysfunction syndrome (MODS),and mortality were compared between the group of Ala-Gln dipeptide supplemented PN (intervention group) and the group of PN without Ala-Gln dipeptide (control group).Results Finially,617 cases were enrolled in the study,including 312 cases in the control group and 305 cases in the intervention group.The ICU-LOS was significantly shorter in the intervention group than that in the control group [(17.2 ± 6.5) d vs.(16.1 ± 5.3) d,P =0.011).Compared with the control group,the incidences of infection (42.9％ vs.33.1％,P =0.011) and MODS (46.5％ vs.38.0％,P =0.030) and the mortality (34.9％vs.25.9％,P =0.014) in the intervention group patients were significantly lower.Conclusion Ala-Gln dipeptide supplemented PN can improve the short-term outcomes of critically ill adult patients.

Effects of alanyl-glutamine dipeptide administration on postoperative intestinal permeability and systemic inflammatory response / 肠外与肠内营养

Objective: The study was designed to observe the effects of alanyl-glutamine (Aln-Gln) dipeptide on postoperative intestinal permeability and systemic inflammatory response.Methods: A prospective,randomized and controlled trial was taken.20 patients who underwent abdominal surgery were randomized into two groups: study group (intravenous administration of Aln-Gln dipeptide,0.5 g /(kg·d),for 4 days,n=10) and control group (equal normal saline as placebo,for 4 days,n=10).Temperatures,heart rates and respiration rates of all patients were daily recorded during administration.The white blood cell counts ,serum concentrations of glutamine (Gln),diamine oxidase (DAO) and interleukin-6(IL-6) and urine lactulose/mannito (L/M) ratio were measured before and after operation.Results: Serum Gln concentration was significantly decreased in control group and increased in study group on postoperative day 5.Urine L/M ratio,serum concentrations of DAO and IL-6 were significantly increased in control group and decreased in study group.The morbidity of SIRS was significantly decreased in the study group and the score of SIRS was also lower than in the control group.Conclusions: Administration of Aln-Gln dipeptide can increase the level of serum Gln,decrease the intestinal permeability,maintain the intestinal barrier and attenuate the systemic inflammatory response in the early period of postoperative patients.Aln-Gln dipeptide can be used in the fast track surgery to help patients recover rapidly.

Protective effect of alanyl-glutamine dipeptide on acute gastric ulcer in rats / 国际药学研究杂志

Objective: To evaluate the protective effect of alanyl-glutamine dipeptide (Ala-Gin) on different acute gastric ulcer models in rats and investigate its possible mechanisms. Methods: The gastric ulcer in rats was induced by waterimmersion restraint stress, ethanol and pylorus ligation. On each gastric ulcer model, sixty SD rats were randomly divided into six groups including the gastric ulcer control group, cimetidine (0.1 g/kg) and marzulene-S (1.0 g/kg) treatment groups,as well as 0.5, 1.0 and 1.5 g/kg Ala-Gin treatment groups. Before the gastric ulcer, different doses of drugs were administered intragastrically,once a day for 3 days. Ulcer index, gastric acid, gastric juice value, gastric acid, free acid, total acid and pepsin activity were used to evaluate and compare the protective effect of Ala-Gin and other anti-ulcer drugs. Results: Ala-Gin significantly reduced the gastric ulcer index in all giving dose (P<0.01) and its protective effect increased significantly with the climbing dose. In all three gastric ulcer models,the anti-ulcer effects of 1.0 and 1.5 g/kg Ala-Gin treatment groups were equal to that of marzulene-S. In addition, Ala-Gin also markedly inhibited the secretion of free acid (P<0.01)and decreased the activity of pepsin (P<0.05) on pylorus ligation gastric ulcer rats. Conclusion: Ala-Gin has obviously anti-ulcer effect on different experimental gastric ulcer models. Except for the known protective effect on gastric mucosa, its anti-ulcer mechanisms may be related to its inhibitory effect on gastric acid and pepsin.

Protective effects of alanyl-glutamine on acute lung injury induced by lipopolysaccharide in rats / 中南大学学报(医学版)

Objective To investigate the effect of alanyl-glutamine (Ala-Gln) on acute lung injury (ALI) in rats induced by sepsis and its mechanisms. Methods Forty healthy adult Wistar rats were randomly divided into a control group, a lipopolysaccharide (LPS)-induced shock group, an Ala-Gln treated group, and a glutamine (Gin) treated group. The control group received an intravenous infusion of 28 mL/kg lactated Ringer's solution(LR). The LPS-induced shock group received an intravenous administration of 25 mL/kg LR, and then 3 mL/kg (6 mg/kg) LPS (L-2880, Sigma, America). The AlaGin treated group received 4.5% Dipeptiven (25 mL/kg, equaling 0.75 g/kg Gin) immediately before 3 mL/kg (6 mg/kg) LPS. The Gin treated group received 3% glutamine (25 mL/kg, 0.75g/kg) immediately before 3 mL/kg (6 mg/kg) LPS. Serum (1 mL) was drawn via the femoral vein or cardiac puncture before LPS injection (T0) and 6 h after the administration of LPS (T1), respectively. All rats were killed 6 h after LPS infusion. The samples of pulmonary tissue and lung lavage fluid were collected after experiments. Tumor necrosis factor-α (TNF-α), interleukin-1β( IL-1β), and interleukin-8(IL-8) in the serum at T0 and T1 were detected by ELISA. Apoptosis in the lung epithelial cells was detected with TUNEL assays. The lung wet/dry(W/D) weight ratio and total protein in the bronchoalveolar lavage fluid (BALF) were measured. Results Six hours after the infusion of LPS (T1), the plasma concentrations of TNF-α, IL-1β, and IL-8 were much lower in the Ah-Gln treated group and the Gin treated group than those in the LPS-induced shock group (P < 0.05). Compared with the LPS-induced shock group, AlaGin and Gin significantly reduced the increase in the lung wet/dry weight ratio (P<0.05) and attenuated the morphological lung damage. Conclusion Intravenous administration of Ala-Gha can effectively protect the lung from sepsis induced injury.

Alanyl- glutamine down- regulates iNOS and TNF-α expression in injured intestinal mucosa induced by oral FK506 / 中国病理生理杂志

AIM: To investigate the effects of alanyl - glutamine ( Ala -Gln) on expression of iNOS and TNF- α in injured intestinal mucosa induced by oral tacrolimus (FK506). METHODS: Twenty -four BALB/c mice were randomized to receive orally 0.2 mL of normal saline solution ( group Ⅰ ), 0.2 mL of FK506 in a dose of 0.1 mg/kg ( group Ⅱ ) or 1.0 mg/kg (group Ⅲ), and orally high -dose FK506 (0.2 mL, 1.0 mg/kg) plus intraperitoneal injection of Ala -Gln (0.5 g/kg )(group Ⅳ ),respectively. Damages of intestinal mucosa were determined by pathological examination.Intestinal mucosal permeability was analysed by FITC - dextran fluorescence assay. Expression of iNOS and TNF - α in intestine was detected by RT - PCR and Western blotting. RESULTS: Severe damage on the villi and increased intestinal permeability were observed in high - dose FK506 treated mice according to scanning electron microscopy and FITC - dextran flux respectively. The erosion and increased intestinal permeability were significantly alleviated by Ala - Gln treatment. Transcription of iNOS mRNA and TNF - α mRNA, which was up - regulated in high - dose FK506 treated group,was also markedly down- regulated in mice combined with Ala- Gln- treatment. A significantly increased expression of iNOS and TNF - α protein was found in the high - dose FK506 treated mice, while small amounts of these proteins were identified in the Ala - Gln - treated group. CONCLUSION: FK506 could induce a significant impairment of intestinal mucosa morphologically, which might be associated with up - regulated expression of iNOS and TNF - α in small intestinal mucosa. Subsequently, the intestinal permeability is increased. Ala - Gln has a strong protective effect on FK506 - induced intestinal barrier dysfunction, probably relates to the down - regulation of iNOS and TNF - α expression.

Effect of Alanyl-glutamine on Aged Patients with Severe Pneumonia / 药物流行病学杂志

Objective:To study the effect of alanyl-glutamine(Ala-Gln) on aged patients with severe pneumonia. Methods:The hospital acquired 56 cases of patients with severe pneumonia,who were randomized in two groups:Ala-Gln group in 30 cases and controlled group in 26 cases Both groups were cared with anti-infection,nutrition support and symptomatic treatment,during which Ala-Gln group was supplemented with 10g alanyl-glutamine amid 250ml amino acid intravenous drip in 14 days,two times each.Before and after the treatment,both groups were monitored over their intestinal functions and measured over their Alb,IgG,total lymphocytes count,C-reactive protein,nitrogen balance,blood routine,liver and kidney function examinations.Result:There were statistical differences between the groups involving intestinal function monitoring(P

Observation on the Safety and Efficacy of Alanyl-glutamine Dipeptide in Patients after Gastrointestinal Operation / 中国药房

OBJECTIVE:To investigate the safety and efficacy of alanyl-glutamine dipeptide administered via peripheral vein total parenteral nutrition(TPN)in patients after gastrointestinal operation.METHODS:64cases after gastrointestinal operations were randomly divided into routine TPN group(control group)and TPN plus alanyl-glutamine dipeptide group(therapeautic group),all of which were treated with the corresponding medicines from the first day to the7th day after oper?ation.RESULTS:The levels of both seralbumin and prealbumin rebounded on the8th day after operation with those of the control group rebound more slowly,significant differences were noted between the2groups(P

Effect of alanyl-glutamine on immune function of patients with gastric cancer / 中国康复理论与实践

@#ObjectiveTo investigate the effect of alanyl-glutamine supplemented total parenteral nutrition (TPN) on immune function of patients with gastric cancer.MethodsFifty gastric cancer patients with radical gastrectomy were randomly divided into the control group (n=25) and experiment group (n=25). Patients in the control group received conventional TPN support, and patients in the experiment group received TPN support and alanyl-glutamine (0.34 g/kg). All patients were observed for 7 days. The levels of IgG, IgA, IgM, CD3, CD4, CD8 and CD4/CD8 were measured before operation and on first and eighth day after operation.ResultsAll the levels of immune function were decreased on first day after operation in two groups. But the levels of IgG, IgA, IgM, CD3, CD4 and CD4/CD8 were significantly different between two groups on eighth day after operation (P<0.05). No serious infectious complication occurred in both groups.ConclusionTPN supplemented with alanyl-glutamine can improve the immune function of patients with gastric cancer radical gastrectomy.

Effect of alanyl-glutamine on metabolism of protein and nutrition states after liver transplantation / 肠外与肠内营养

Objective:To observe the effect of dipeptide-supplemented TPN on post-transplantational metabolism of protein and nutrition state.Methods:24 patients were randomly divided into two groups: group one being TPN without Ala-Gln(traditional TPN) and group two being TPN with Ala-gln(dipeptide group).Patients received isocaloric(104.6 kJ/kg?d~(-1)) and isonitrogenous(0.16 g/kg?d~(-1))TPN for seven days.Anthropometric parameter,prognostic nutritional index(PNI)、tatal protein((TP)、)albumin(A)、prealbumin(PAB)、 transferrin(TF) were monitored on the second day and on the ninth day after transplantation.Results:The anthropometric parameter of traditional group decreased significantly(P

Application of total parenteral nutrition with alanyl-glutamine dipeptide in postoperative patients of gastrointestinal neoplasms / 第三军医大学学报

Objective To investigate the application of total parenteral nutrition with alanyl-glutamine dipeptide in postoperative patients of gastrointestinal neoplasms.Methods Sixty-four postoperative patients of gastrointestinal neoplasms were randomly divided into study group and control group.The patients in the two groups all received isocaloric(96.0 kJ?kg-1?d-1)and isonitrogen(0.25 g?kg-1?d-1)parenteral nutrition from postoperative day 1 to day 7,and the study group received additional alanyl-glutamine.The serum levels of albumin,pre-albumin,IgG,IgA,IgM,C3,C4 were measured before operation and on postoperative day 1 and 8.Nitrogen balance was calculated on postoperative day 1,4 and 8.Results Compared with preoperation,the serum levels of albumin and pre-albumin were both significantly decreased in two groups(P