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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.
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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.
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Animals , Female , Rats , Hearing Loss, Noise-Induced/prevention & control , Hearing Loss, Noise-Induced/drug therapy , Rats, Wistar , Heat-Shock Response , Dietary Supplements , Dipeptides , Heat-Shock ProteinsABSTRACT
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.
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Objective To assess the short-time economics of various glutamine dipeptide-enriched parenteral nutrition (PN) for patients undergoing elective surgery for gastrointestinal tumors, with an attempt to provide evidence for decision makers on clinical nutrition support.Methods A prospective cohort study was designed.From payer/disburser''s perspective, a cost-effectiveness decision-tree model was developed to assess the clinical outcomes and short-time economic effects of glutamine dipeptide-enriched PN that used in different time points (early postoperative or perioperative).Cost-effectiveness analysis, cost-utility analysis, and incremental cost-effectiveness analysis were adopted in the decision-tree model.One-way sensitivity analysis was performed to determine the robustness of the results.Results Totally 107 patients were included.There was no significant difference between the perioperative alanine(Ala) glutamine(Gln) nutrition support (group A) and early postoperative Ala-Gln nutrition support (group B) in the ratio of 5％ weight declines on the 8th day after surgery and infection-related postoperative complications (72.1％ vs.78.1％, χ2=0.509, P=0.498 and 2.32％ vs.4.69％, χ2=0.060, P=0.806).The levels of prealbumin (PA) and albumin(Alb) and the level of total lymphocyte count(TLC) also the time of recovering gastrointestinal function, length of stay nutritional discharge index(LOSNDI), and direct costs were significantly different [PA:(208.19±56.92)mg/L vs.(187.97±62.05)mg/L, t=2.283,P=0.039;Alb:(33.82±3.91)×109 vs.(31.96±4.57)×109, t=2.184, P=0.036;TLC:(1.19±0.55)×109 vs.(0.89±0.66)×109, t=2.461, P=0.015;the time of recovering gastrointestinal function(3.06±0.28)d vs.(3.39 ± 0.34)d, t=-3.675, P=0.000;LOSNDI:(16.84±2.92)d vs.(18.52 ±3.47)d, t=-2.613, P=0.011;direct costs:￥(17 029.05±317.28) vs.￥(15 610.64±292.56), t=23.764, P=0.000].When LOSNDI and quality-adjusted life years (QALYs) were estimated as indicators of effectiveness, the incremental cost-effectiveness ratios and incremental cost-utility ratios of group A were ￥844.3 and ￥70 920.5, respectively.Net monetary benefit of group B was more than that of group A.One-way sensitivity analysis showed that parameters had no significant effect on the model.Conclusion When using local per capita gross domestic product as threshold, early postoperative Ala-Gln PN was more economical than perioperative Ala-Gln PN strategy evaluation.
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OBJECTIVE:To investigate the effects of glutamine on neurological and gastrointestinal function of severe organo-phosphate poisoning patients. METHODS:46 patients with severe organic phosphorus poisoning in our hospital were enrolled and ran-domly divided into control group and observation group,with 23 cases in each group. Control group was given antidote atropine,en-ergy recovery agent pralidoxime chloride,blood perfusion and other symptomatic treatment. Observation group was additionally given Glutamine dipeptide injection 0.5 g/kg,ivgtt,qd,on the basis of control group. Both groups received the treatment for consecutive 3 d. The time of poisoning symptom disappearance,the time of blood cholinesterase recovery,hospitalization time,neurological and gastrointestinal function indexes were compared between 2 groups. RESULTS:The time of poisoning symptom disappearance,the time of blood cholinesterase recovery and hospitalization time of observation group were significantly shorter than those of control group,with statistical significance (P<0.05). After treatment,serum diamine oxidase and lactulose/mannitol of observation group were significantly lower than those of control group,while the serum content of citrulline was higher than in control group,with sta-tistical significance (P<0.05). After treatment,MCV and SCV of observation group were significantly higher than those of control group,while F wave latency was significantly shorter than control group,with statistical significance(P<0.05). CONCLUSIONS:Glutamine dipeptide is helpful to promote remission,improve gastrointestinal and neurological function.
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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.
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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.
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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.
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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
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0.05).The data of nitrogenous retention rate,net nitrogenous utililizing rate and cumulative nitrogen balance showed that there was significant difference in Group G comparing with Group N and Group V respectively( P
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Objective: The study was designed to observe the effects of alanyl-glutamine(Aln-Gln) dipeptide on postoperative intestinal permeability and immmunologic function in abdominal patients. Methods: A prospective,randomized and controlled trial was taken.20 patients who underwent abdominal operation were divided 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).Serum concentrations of glutamine(Gln) and diamine oxidase(DAO),blood total lymphocyte count(TLC) and human leukocyte antigen(HLA)-DR 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 and serum DAO level were significantly increased in control group and decreased in study group after operation.Blood TLC and HLA-DR expression in the study group were significantly higher than those in control group on postoperative day 5. Conclusion: Intravenous administration of Aln-Gln dipeptide can increase the serum Gln level,decrease the intestinal permeability,maintain the intestinal barrier and improve the immmunologic function in the early period of postoperative patients.Aln-Gln dipeptide can be used in the fast track surgery to help patients recover rapidly.
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Objectives: To study the value of glutamine dipeptide supplemented lower caloric parenteral nutrition in elder abdominal surgical patients. Methods:Forty patients were randomly allocated into study group and control group, receiving isocaloric (83.6 kJ/kg?d -1 ) and isonitrogenous (0.16 g/kg?d -1 ) PN from post operation day1 to post operation day 6. The study group received 0.3 g of alanyl glutamine/(kg?d)? Plasma albumin, pre albumin, IgG, IgA and IgM level were measured and lymphocyte was counted before surgery and on days 1 and 7 after surgery. Nitrogen balances were calculated postoperatively on day 1, 4 and 7. Results:Compared with preoperation, plasma albumin and pre albumin levels were both decreased in two groups and was markedly decreased in the control group ( P