Biochemical studies on the cardioprotective effect of glutamine on tissue antioxidant defense system in isoprenaline-induced myocardial infarction in rats

Oxidative stress is one of the mechanisms with a central role involved in the pathogenesis of myocardial infarction. The protective effect of glutamine on myocardial antioxidant defense system was investigated during isoprenaline-induced myocardial infarction, an animal model of myocardial infarction of human beings. Levels of diagnostic marker enzymes in plasma, reduced glutathione (GSH) and lipid peroxides and the activities of glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase in heart tissue were determined. Injection of isoprenaline caused significant increases in the levels of diagnostic marker enzymes in plasma and lipid peroxidation in heart tissue. A parallel decline in the levels of ATP (Adenosine triphosphate) and GSH and the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes in heart tissue was also observed. Prior oral administration of glutamine significantly prevented isoprenaline-induced adverse effects and maintained myocardial antioxidant status at near normal status. The cardioprotective effect of glutamine is probably related to a strengthening of the myocardial membrane by its membrane stabilizing action, or to a counteraction of free radicals by its antioxidant property, or to its ability to maintain near to normal status the activities of free radical scavenging enzymes and the level of GSH, which protect myocardial membrane against oxidative damage by decreasing lipid peroxidation.     

Free amino acids in plasma and muscle during 24 hours post-operatively – a descriptive study

Summary. Intracellular amino acids in skeletal muscle show a specific concentration pattern on the third post-operative day. The temporal development of these changes has not been clarified. Here the amino acid concentrations in skeletal muscle were studied during the first post-operative day in fourteen patients undergoing elective abdominal surgery. Muscle amino acids were determined pre-operatively, as well as at 12 and 24 h post-operatively. In muscle the concentrations of glutamine and the basic amino acids decreased gradually during the first 24 h after surgery to 79% (P< 0 001) and 67% (P< 001) respectively. The sum of the essential amino acids decreased to 73% (P<0 001) at 12 h, but thereafter rose to 91% (P<0 05) at 24 h. The sum of the BCAA decreased to 84% (P<0.05) at 12 h but then increased to 116% (P<0 05) at 24 h. The alanine concentration increased to 122% (P<0 001) during the first postoperative day. In plasma the alanine concentration increased at 12 h while most other amino acids declined. At 24 h post-operatively the plasma concentrations of all amino acids had returned to normal or showed a tendency towards normalization except for phenylalanine, which increased. At the end of the first post-operative day the concentrations of amino acids in muscle were consistent with the alterations previously observed three days after surgery. The changes in plasma amino acid concentrations only partly reflected those in muscle.     

复方谷氨酰胺肠溶胶囊治疗肠易激综合征的疗效及对胃肠激素的影响

目的分析复方谷氨酰胺肠溶胶囊治疗肠易激综合征的疗效及对患者胃肠激素的影响。方法 72例肠易激综合征患者随机分为观察组和对照组。对照组患者给予肠易激综合征常规治疗,观察组患者在常规治疗基础上使用复方谷氨酰胺肠溶胶囊治疗。结果观察组患者治疗总有效率为94.45%,显著高于对照组的77.78%(P0.05)。观察组患者排便异常、腹胀、腹痛、胃肠不适、焦虑、抑郁及头痛改善率显著高于对照组(P0.05)。观察组患者VIP及SS水平显著低于对照组患者(P0.01)。结论复方谷氨酰胺肠溶胶囊能有效改善肠易激综合征患者症状,增强胃肠免疫力,调节胃肠激素分泌。     

Manganese‐induced downregulation of astroglial glutamine transporter SNAT3 involves ubiquitin‐mediated proteolytic system

SNAT3 is a major facilitator of glutamine (Gln) efflux from astrocytes, supplying Gln to neurons for neurotransmitter synthesis. Our previous investigations have shown that, in primary cortical astrocyte cultures, SNAT3 protein is degraded after exposure to manganese (Mn²⁺). The present studies were performed to identify the processes responsible for this effect. One of the well‐established mechanisms for protein‐level regulation is posttranslational modification via ubiquitination, which leads to the rapid degradation of proteins by the 26S proteasome pathway. Here, we show that astrocytic SNAT3 directly interacts with the ubiquitin ligase, Nedd4‐2 (neural precursor cells expressed developmentally downregulated 4‐2), and that Mn²⁺ increases both Nedd4‐2 mRNA and protein levels. Additionally, we have found that Mn²⁺ exposure elevates astrocytic ubiquitin B mRNA expression, free ubiquitin protein levels, and total protein ubiquitination. Furthermore, Mn²⁺ effectively decreases astrocytic mRNA expression and the phosphorylation of serum and glucocorticoid‐inducible kinase, a regulatory protein, which, in the active phosphorylated form, is responsible for the phosphorylation and subsequent inactivation of Nedd4‐2. Additional findings establish that Mn²⁺ increases astrocytic caspase‐like proteolytic proteasome activity and that the Mn²⁺‐dependent degradation of SNAT3 protein is blocked by the proteasome inhibitors, N‐acetyl‐leu‐leu‐norleucinal and lactacystin. Combined, these results demonstrate that Mn²⁺‐induced SNAT3 protein degradation and the dysregulation of Gln homeostasis in primary astrocyte cultures proceeds through the ubiquitin‐mediated proteolytic system. © 2010 Wiley‐Liss, Inc.     

前体氨基酸对维生素B12发酵合成的影响

谷氨酸、苏氨酸、甘氨酸和甲硫氨酸是维生素B12合成的重要前体。在脱氮假单胞菌（Pseudomonas denitrifican）发酵的产物合成期以补加的方式考察了这4种氨基酸对维生素B12合成的影响。在合成培养基的基础上,通过单因素添加试验分别考察了这些氨基酸对维生素B12合成的影响,发现谷氨酸、甘氨酸和苏氨酸影响显著;并进一步利用三因素三水平的正交试验设计考察了氨基酸混合添加对菌体生长和维生素B12合成的影响,结果表明谷氨酸是最主要的影响因素,并且发现同时添加多种氨基酸更有利。当添加量为谷氨酸0.45 g/L、苏氨酸0.20 g/L、甘氨酸0.15 g/L时,得到的菌体量和维生素B12产量分别比对照组提高了13.1%和46.0%。     

Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy

Substitution of amino acid (aa) 70 and/or 91 in the core region of HCV genotype 1b (HCV‐1b) is an important predictor of hepatocarcinogenesis, but its impact on the development of hepatocellular carcinoma (HCC) following eradication of HCV RNA by antiviral therapy is not clear. 1,273 patients with HCV‐related chronic liver disease, with sustained virological response, defined as negative HCV RNA at 24 weeks after cessation of interferon monotherapy or interferon plus ribavirin combination therapy, were included in a follow‐up study to evaluate the impact of aa substitution in the core region on hepatocarcinogenesis. Twenty six patients developed HCC during the follow‐up. The cumulative rates of new HCC were 3.2%, 4.8%, and 8.6% at the end of 5, 10, and 15 years, respectively. The rates in patients infected with HCV‐1b/Gln70(His70) [glutamine (histidine) at aa 70] were significantly higher than in patients infected with HCV‐1b/Arg70 (arginine at aa 70) (P = 0.007; log‐rank test) and HCV‐2a/2b (P < 0.001; log‐rank test). The rates in patients infected with HCV‐1b/Arg70 were not significantly higher than in those infected with HCV‐2a/2b (P = 0.617; log‐rank test). Multivariate analysis identified HCV‐1b/Gln70(His70) (HR 10.5, P < 0.001), advanced fibrosis (HR 9.03, P = 0.002), and old age (HR 3.09, P = 0.066) as determinants of hepatocarcinogenesis. In conclusion, aa substitution in the core region of HCV‐1b at the start of antiviral therapy is an important predictor of HCC following eradication of HCV RNA. This study emphasizes the importance of detection of aa substitutions in the core region before antiviral therapy. J. Med. Virol. 83:1016–1022, 2011. © 2011 Wiley‐Liss, Inc.     

谷胺酰胺预处理对兔脊髓缺血再灌注损伤后血小板聚集及活化功能的影响

目的：探讨血小板聚集及活化功能在脊髓缺血再灌注损伤（SCIRI）中的变化及谷氨酰胺预处理对其的影响．方法：利用Zivin法建立家兔SCIRI模型,动态监测SCIRI及谷氨酰胺预处理时血小板聚集试验（PAgT）及活化功能特异指标血浆GMP-140浓度的变化．结果：PAgT及GMP-140浓度在缺血45min逐渐升高,持续至再灌注6h,与Sham组相比差异显著（P〈0．01）,于再灌注12h下降到缺血前水平（P〉0．05）;谷氨酰胺预处理后血小板进一步活化,高峰期延迟．结论：血小板处于过度活化状态,聚集功能增强,引起凝血功能亢进,可能是参与了脊髓缺血再灌注后神经元损伤与修复过程,谷氨酰胺预处理后血小板进一步活化．     

兔脊髓缺血再灌注损伤时凝血功能的变化及谷氨酰胺预处理的影响

目的：探讨兔脊髓缺血再灌注损伤（SCIRI）时凝血功能的变化、意义及谷氨酰胺预处理对其影响．方法：采用Zivin法建立SCIRI模型,动态观察SCIRI及谷氨酰胺预处理时血液胛（凝血酶原时间）,AVIT（部分凝血活酶时间）,TT（凝血酶时间）和FIB（纤维蛋白原）的变化．结果：假手术组PT,APTT,FIB逐渐升高（P〉0．05）,TT逐渐降低至缺血45min时显著降低然后逐渐升高（P〈0．01）;缺血再灌注组（I／R）凝血四项各项指标逐渐升高,2h达到最高峰后逐渐下降,12h降到缺血前水平,在这一过程中,除门外,45min,2h,6h时间点与缺血前比较均有显著差异（P〈0．01）;谷氨酰胺预处理组凝血4项各项指标与I／R组比较仅有下降趋势（P〉0．05）．结论：SCIRI引起凝血状态显著改变,可能为凝血因子水平、活性及功能改变导致,谷氨酰胺预处理没有改善SCI-RI引起凝血状态改变．     

Mechanisms underlying Li+ effects in glutamatergic and GABAergic neurotransmissions in the adult rat brain and in primary cultures of neural cells as revealed by 13C NMR

We investigated by (13)C nuclear magnetic resonance (NMR) the mechanisms underlying Li(+) effects on glutamatergic and GABAergic neurotransmission systems in the adult rat brain and in primary cultures of cortical neurons and astrocytes during the metabolism of (1-(13)C) glucose or (2-(13)C) acetate. Adult male rats receiving a single dose of Li(+) intraperitoneally (7 mmol/kg) were infused 2 hr later, for 60 min, with (1-(13)C) glucose (80 mumol/min/kg) or (2-(13)C) acetate (240 micromol/min/kg). High-resolution (13)C NMR spectra of brain extracts prepared after the infusion revealed that Li(+) significantly decreased the incorporation of (13)C in glutamate and GABA (gamma-aminobutyric acid) carbons from (1-(13)C) glucose, but not from (2-(13)C) acetate. To complement the in vivo approach, primary cultures of cortical neurons or astrocytes were incubated with 1 mM uniformly (13)C-labeled glucose or 5 mM (2-(13)C) acetate, in the absence and presence of increasing Li(+) concentrations up to 15 mM. Under these conditions, Li(+) significantly decreased neuronal glucose uptake in a concentration-dependent manner without apparent effects on astrocytic acetate uptake. Extracts prepared at the end of the incubations showed that Li(+) significantly decreased the incorporation of (13)C labeling into GABA carbons from its precursor glutamate in neurons, but such a decrease into glutamine carbons in astrocytes was not statistically significant. Our results indicate that the effects of Li(+) are mediated through a reduction of neuronal glucose uptake, resulting in a decrease of glutamatergic and GABAergic neurotransmission without apparent effects on astrocytic metabolism.