GABA_B受体对牛磺酸调节突触体氨基酸释放的影响

目的　牛磺酸 (Tau)调节大鼠大脑皮层突触体Asp、Glu、GABA的释放的机制尚不清楚 ,本研究从GABA受体的角度进行探讨。方法　将 phaclofen、biculline、baclofen加入悬浮有突触体的KRB液中 ,氨基酸测定采用Dans Cl柱前衍生 ,高效液相测定。结果　Tau对GABA释放的抑制作用能有效被Phaclofen所拮抗 ,而它们对GluAsp的释放均无影响。结论　Tau抑制去极化引发GABA的释放是通过激发突触体前膜GABAB 受体而起作用的 ,同时还作用于Asp、Glu神经末梢的突触体前膜 ,从而抑制去极化引发的Asp、Glu的释放。     

虎杖苷对大鼠脑出血性损伤脑脊液中兴奋性氨基酸动态变化的影响

目的:观察虎杖苷对大鼠脑出血损伤后脑脊液中兴奋性氨基酸动态变化和脑组织含水量的影响,探讨虎杖苷对脑出血损伤的治疗作用及其作用机制。方法:采用微透析-高效液相色谱法建立天门冬氨酸(Asp)、谷氨酸(G lu)的测定方法;用Ⅶ型胶原酶诱导建立大鼠脑出血模型,观察虎杖苷对大鼠脑出血后0,6,12,24,36,48,60,72,84,96,108 h脑脊液内天门冬氨酸、谷氨酸含量的动态变化,并断头取脑检测脑组织含水量。结果:天门冬氨酸和谷氨酸含量在大鼠脑出血后24 h内迅速升高,并于24 h达到最高,随后逐渐开始降低。虎杖苷治疗后,天门冬氨酸和谷氨酸含量均上升缓慢,分别在12~72,6~84 h与同时段模型组比较有显著性差异(P0.01或P0.05),84,96 h后与同时段模型组相比无显著性差异。与假手术组比较,模型组脑含水量明显较高,虎杖苷组则明显降低(P0.01)。结论:虎杖苷能抑制脑出血后脑脊液中ASP,G lu含量升高,能明显抑制脑出血造成的脑水肿,表明虎杖苷抗脑出血损伤的作用机制可能与其抗脑出血后兴奋性氨基酸含量的升高有关。     

Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier

Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (W_hPAMAM/W_DNA). The resulting HPAMAM–Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2?h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM–Glu20 represented much higher (p?<?0.05) than that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells. Cellular uptake of the hPAMAM–Glu20 in MDA-MB231 cells, 173.56?±?1.37%, was significantly higher than that of MCF7 cells, 65.00?±?1.73% (p?<?0.05). The results indicated that hPAMAM–Glu20-mediated gene delivery to breast cancer cells is a feasible and effective strategy that may provide a new therapeutic avenue as a non-viral gene delivery carrier. In addition, it was found that hPAMAM–glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.     

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.     

Association between Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism and Diabetic Nephropathy Susceptibility

The association between endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphism and diabetic nephropathy (DN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS Glu298Asp gene polymorphism and DN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Eight articles were identified for the analysis of association between eNOS Glu298Asp gene polymorphism and DN risk. T allele was associated with DN susceptibility in overall populations, in Asians, and for Caucasians (overall populations, p = 0.005; Asians, p = 0.004; Caucasians, p = 0.002). Furthermore, GG genotype might play a protective role against DN onset for overall populations, Asians, Caucasians, and Africans. However, a link between eNOS Glu298Asp gene polymorphism and DN risk was not found in overall populations, Asians, Caucasians, and Brazil population. In conclusion, T allele might become a significant genetic molecular marker for the onset of DN in overall populations, in Asians, and for Caucasians. However, more studies should be performed in the future.     

Coffee polyphenols improve peripheral endothelial function after glucose loading in healthy male adults

Brewed coffee is a widely consumed beverage, and many studies have examined its effects on human health. We investigated the vascular effects of coffee polyphenols (CPPs), hypothesizing that a single ingestion of CPP during glucose loading would improve endothelial function. To test this hypothesis, we conducted a randomized acute clinical intervention study with crossover design and measured reactive hyperemia index (RHI) to assess the acute effects of a 75-g glucose load with CPP in healthy, nondiabetic adult men. Blood glucose and insulin levels were elevated after glucose loading with and without CPP, with no significant differences between treatments. The RHI did not significantly decrease after glucose loading without CPP. With CPP, however, RHI significantly (P < .05) increased over baseline after glucose loading. The difference between treatments was statistically significant (P < .05). No significant changes were observed in an oxidative stress marker after glucose loading with or without CPP. These findings suggest that a single ingestion of CPP improves peripheral endothelial function after glucose loading in healthy subjects.     

Ammonium accumulation and chemokine decrease in culture media of Gcdh−/− 3D reaggregated brain cell cultures

Glutaric Aciduria type I (GA-I) is caused by mutations in the GCDH gene. Its deficiency results in accumulation of the key metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body tissues and fluids. Present knowledge on the neuropathogenesis of GA-I suggests that GA and 3-OHGA have toxic properties on the developing brain.We analyzed morphological and biochemical features of 3D brain cell aggregates issued from Gcdh^?/? mice at two different developmental stages, day-in-vitro (DIV) 8 and 14, corresponding to the neonatal period and early childhood. We also induced a metabolic stress by exposing the aggregates to 10 mM l-lysine (Lys).Significant amounts of GA and 3-OHGA were detected in Gcdh^?/? aggregates and their culture media. Ammonium was significantly increased in culture media of Gcdh^?/? aggregates at the early developmental stage. Concentrations of GA, 3-OHGA and ammonium increased significantly after exposure to Lys. Gcdh^?/? aggregates manifested morphological alterations of all brain cell types at DIV 8 while at DIV 14 they were only visible after exposure to Lys. Several chemokine levels were significantly decreased in culture media of Gcdh^?/? aggregates at DIV 14 and after exposure to Lys at DIV 8.This new in vitro model for brain damage in GA-I mimics well in vivo conditions. As seen previously in WT aggregates exposed to 3-OHGA, we confirmed a significant ammonium production by immature Gcdh^?/? brain cells. We described for the first time a decrease of chemokines in Gcdh^?/? culture media which might contribute to brain cell injury in GA-I.     

滋肾通络方对MCAO大鼠脑组织氨基酸递质含量的影响

目的:观察滋肾通络方对大脑中动脉闭塞MCAO大鼠脑组织氨基酸递质含量的影响.方法:例作MCAO大鼠模型,随机分为假手术组、模型组、中药高剂量组、中药低剂量组和西药组.灌胃20天后,取大鼠脑组织,匀浆,取上清液,用氨基酸分析仪检测各组Asp、Glu、Gly的含量.结果:模型组Asp、Glu、Cly的含量均升高,用药组的Asp、Glu、Gly的含量均降低.且中药组的下降趋势优于西药组.结论:滋肾通络方可降低兴奋性氨基酸的含量,从而对脑缺血损伤具有保护作用.     

Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

TM与PET/CT联合诊断肺结节的临床意义

目的：探讨分子生物学（TM）与PET/CT联合诊断肺结节的临床意义。方法经PET/CT检查可疑肺部肿瘤及结节患者98例,并行同期血清肿瘤标记物检测。所有患者均经纤维支气管镜、穿刺、手术等组织病理学检查、多种影像学检查及临床随访确诊。结果肿瘤标记物的灵敏度、特异度、准确度为70.5%、75.6%、73.5%,PET/CT为86.8%、86.5%、87.7%,二者联合检测为95.1%、81.1%、93.9%。结论TM与18F-FDG PET/CT联合检测,对肺部病灶良、恶性诊断的准确率高于单独一种检测方法,具有一定的互补性,可为临床的诊断与治疗提供更多信息。