AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobari...AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.展开更多
AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Para...AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.展开更多
Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictabl...Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders,such as genetic(private mutations and lyonization) and external factors;however,the outcomes of these conditions may differ.We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth.Hyperammonemia after parturition in a female patient with OTCD can be fatal,and this type of hyperammonemia persists for an extended period of time.Here,we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition.Once hyperammonemia crisis occurs after giving birth,it is difficult to improve the metabolic state.Therefore,it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.展开更多
AIM To evaluate the protective effects of glutamine in a model of portal hypertension(PH) induced by partial portal vein ligation(PPVL).METHODS Male Wistar rats were housed in a controlled environment and were allowed...AIM To evaluate the protective effects of glutamine in a model of portal hypertension(PH) induced by partial portal vein ligation(PPVL).METHODS Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum. Twenty-four male Wistar rats were divided into four experimental groups:(1) control group(SO)-rats underwent exploratory laparotomy;(2) control + glutamine group(SO + G)-rats were subjected to laparotomy and were treated intraperitoneally with glutamine;(3) portal hypertension group(PPVL)-rats were subjected to PPVL; and(4) PPVL + glutamine group(PPVL + G)-rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase(GPx), endothelial nitric oxide synthase(e NOS) and inducible nitric oxide synthase(i NOS) after PPVL.RESULTS Lipid peroxidation of the membrane was increased in the animals subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups(P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH(P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification(44 pixel = 1 μm) were captured. The sum means of all áreas, of each group were calculated. The mean areas of e NOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for e NOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group(P < 0.01). For i NOS, the control(SO) and control + G(SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of i NOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine(P < 0.01).CONCLUSION Treatment with glutamine prevents gut mucosal injury after PH in rats.展开更多
A novel metabolomic method based on gas chromatography/mass spectrometry(GC-MS)was applied to determine the metabolites in the serum of piglets in response to weaning and dietary L-glutamine(Gln)supplementation.Thirty...A novel metabolomic method based on gas chromatography/mass spectrometry(GC-MS)was applied to determine the metabolites in the serum of piglets in response to weaning and dietary L-glutamine(Gln)supplementation.Thirty-six 21-d-old piglets were randomly assigned into three groups.One group continued to suckle from the sows(suckling group),whereas the other two groups were weaned and their diets were supplemented with 1%(w/w)Gln or isonitrogenous L-alanine,respectively,representing Gln group or control group.Serum samples were collected to characterize metabolites after a 7-d treatment.Results showed that twenty metabolites were down-regulated significantly(P<0.05)in control piglets compared with suckling ones.These data demonstrated that early weaning causes a wide range of metabolic changes across arginine and proline metabolism,aminosugar and nucleotide metabolism,galactose metabolism,glycerophospholipid metabolism,biosynthesis of unsaturated fatty acid,and fatty acid metabolism.Dietary Gln supplementation increased the levels of creatinine,D-xylose,2-hydroxybutyric acid,palmitelaidic acid,andα-L-galactofuranose(P<0.05)in early weaned piglets,and were involved in the arginine and proline metabolism,carbohydrate metabolism,and fatty acid metabolism.A leave-one-out cross-validation of random forest analysis indicated that creatinine was the most important metabolite among the three groups.Notably,the concentration of creatinine in control piglets was decreased(P=0.00001)compared to the suckling piglets,and increased(P=0.0003)in Gln-supplemented piglets.A correlation network for weaned and suckling piglets revealed that early weaning changed the metabolic pathways,leading to the abnormality of carbohydrate metabolism,amino acid metabolism,and lipid metabolism,which could be partially improved by dietary Gln supplementation.These findings provide fresh insight into the complex metabolic changes in response to early weaning and dietary Gln supplementation in piglets.展开更多
基金Supported by Scientific and Technical Research Funds from Chinese PLA during the Eleventh Five-Year Plan Period,No. 2008G093National Natural Science Foundation of China,No. 30900715National Science and Technology Ministry,No. 2009BAI85B03
文摘AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.
基金Supported by VU University Medical Center,Amsterdam,The Netherlands
文摘AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.
基金Supported by A Grant-in-Aid for Guidelines and Lifetime Medical Support Systems for inborn errors of metabolism found by newborn screeninga Grant-in-Aid for the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development,AMED
文摘Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders,such as genetic(private mutations and lyonization) and external factors;however,the outcomes of these conditions may differ.We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth.Hyperammonemia after parturition in a female patient with OTCD can be fatal,and this type of hyperammonemia persists for an extended period of time.Here,we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition.Once hyperammonemia crisis occurs after giving birth,it is difficult to improve the metabolic state.Therefore,it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.
文摘AIM To evaluate the protective effects of glutamine in a model of portal hypertension(PH) induced by partial portal vein ligation(PPVL).METHODS Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum. Twenty-four male Wistar rats were divided into four experimental groups:(1) control group(SO)-rats underwent exploratory laparotomy;(2) control + glutamine group(SO + G)-rats were subjected to laparotomy and were treated intraperitoneally with glutamine;(3) portal hypertension group(PPVL)-rats were subjected to PPVL; and(4) PPVL + glutamine group(PPVL + G)-rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase(GPx), endothelial nitric oxide synthase(e NOS) and inducible nitric oxide synthase(i NOS) after PPVL.RESULTS Lipid peroxidation of the membrane was increased in the animals subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups(P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH(P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH(P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification(44 pixel = 1 μm) were captured. The sum means of all áreas, of each group were calculated. The mean areas of e NOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for e NOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group(P < 0.01). For i NOS, the control(SO) and control + G(SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of i NOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine(P < 0.01).CONCLUSION Treatment with glutamine prevents gut mucosal injury after PH in rats.
基金Project supported by the National Natural Science Foundation of China(No.30700578)the Local Cooperative Enterprises of Zhejiang Province,China(Nos.H20080692 and H20020883)
文摘A novel metabolomic method based on gas chromatography/mass spectrometry(GC-MS)was applied to determine the metabolites in the serum of piglets in response to weaning and dietary L-glutamine(Gln)supplementation.Thirty-six 21-d-old piglets were randomly assigned into three groups.One group continued to suckle from the sows(suckling group),whereas the other two groups were weaned and their diets were supplemented with 1%(w/w)Gln or isonitrogenous L-alanine,respectively,representing Gln group or control group.Serum samples were collected to characterize metabolites after a 7-d treatment.Results showed that twenty metabolites were down-regulated significantly(P<0.05)in control piglets compared with suckling ones.These data demonstrated that early weaning causes a wide range of metabolic changes across arginine and proline metabolism,aminosugar and nucleotide metabolism,galactose metabolism,glycerophospholipid metabolism,biosynthesis of unsaturated fatty acid,and fatty acid metabolism.Dietary Gln supplementation increased the levels of creatinine,D-xylose,2-hydroxybutyric acid,palmitelaidic acid,andα-L-galactofuranose(P<0.05)in early weaned piglets,and were involved in the arginine and proline metabolism,carbohydrate metabolism,and fatty acid metabolism.A leave-one-out cross-validation of random forest analysis indicated that creatinine was the most important metabolite among the three groups.Notably,the concentration of creatinine in control piglets was decreased(P=0.00001)compared to the suckling piglets,and increased(P=0.0003)in Gln-supplemented piglets.A correlation network for weaned and suckling piglets revealed that early weaning changed the metabolic pathways,leading to the abnormality of carbohydrate metabolism,amino acid metabolism,and lipid metabolism,which could be partially improved by dietary Gln supplementation.These findings provide fresh insight into the complex metabolic changes in response to early weaning and dietary Gln supplementation in piglets.
