Glutathione metabolism in red cell aging

Normal human red cells were centrifugally separated according to age by discontinuous density gradient of Percoll. Reduced glutathione (GSH), GSH stability and glucose-6-phosphate dehydrogenase (G6PD) activity in fractionated red cells decreased with age, while oxidized glutathione (GSSG) and methemoglobin (MetHb) increased with age.     

Inverted tandem (“mirror”) duplications in human chromosomes: Inv dup 8p, 4q, 22q

We have studied 4 patients with inverted tandem duplications of parts of chromosomes, a hitherto rarely identified from of a structural rearrangement involving a single chromosome in man. In Patients 1 and 2, the duplication involved parts of the short arm of chromosome 8 (regions 8p 12→8p23 and 8p21→8p23, respectively). Both patients manifested certain characteristics of the mosaic trisomy 8 syndrome. Elevated levels of glutathione reductase (GSR) in their erythrocytes supported the interpretation of a partial duplication of chromosome 8 and indicated a regional localization for the GSR gene locus. In Patient 3, the distal half of the long arm of chromosome 4 was duplicated (region4q26→4q35). Clinical evidence supported this interpretation, as Patient 3 resembled phenotypically the 13 reported cases with duplication of the distal 4q. The cytogenetic findings in Patient 4 suggested a possibly inverted duplication of 22q. The clinical correlation was less convincing due to the lack of a well-defined phenotype for trisomy 22. These chromosome aberrations had occurred de novo in all 4 cases. Although they involved different chromosomal regions, they might well have arisen by the same mechanism. Possible modes of origin that are discussed in detail include unequal exchange between homologous chromosomes, between chromatids of 1 chromosome or between strands of 1 DNA duplex.     

Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease

Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH(*)) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H(2)O(2) is hampered in these cells, thereby increasing not only the risk of detrimental effects of H(2)O(2) directly, but also those of its extremely reactive derivatives such as OH(*). Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes.     

一氧化氮及相关物质在卵巢肿瘤组织中的检测

目的探讨一氧化氮（nitricoxide,NO）及其代谢中的相关物质谷胱甘肽(glutathione,GSH)的含量及超氧化物歧化酶(superoxidedismutase,SOD)的活性在卵巢肿瘤组织中的变化。方法应用改良的镀铜镉还原法测定NO     

还原型谷胱甘肽治疗尿毒症贫血的初步探讨

目的　观察外源性还原型谷胱甘肽对尿毒症贫血的治疗效果。方法　将 42例尿毒症贫血患者随机分为两组。两组患者均给予重组人红细胞生成素 (r- Hu EPO) 30 0 0 U,每周两次皮下注射 ,疗程 12周。治疗组患者同时静脉给予外源性还原型谷胱甘肽 (GSH) 12 0 0 mg,每周两次 ,疗程 12周。于治疗前和治疗后抽静脉血测定血红蛋白 (Hb) ,红细胞 (RBC)和红细胞压积 (HCT)水平。结果　 r- Hu EPO治疗后两组患者 HB,RBC和 HCT水平均显著上升 (P<0 .0 1)。 GSH治疗组 Hb,RBC和 HCT水平与对照组比较上升明显 (P<0 .0 5 ) ,治疗组 Hb,RBC和HCT的上升幅度高于对照组 (P<0 .0 5 )。结论　外源性还原型谷胱甘肽能显著提高 r- Hu EPO治疗肾性贫血的疗效 ,GSH可能是治疗尿毒症贫血的有效药物。     

胃癌患者血清及组织中组织蛋白酶-D、谷胱甘肽-S-转移酶活性测定的临床意义

目的　探讨组织蛋白酶 - D(Cath- D)、谷胱甘肽 - S-转移酶 (GST)活性变化与胃癌发生、发展及预后的关系。　方法　检测胃癌、单纯性胃炎、胃炎伴癌前病变患者血清、癌组织、癌旁组织、胃窦粘膜中 Cath- D、GST的活性和手术前后血清 GST活性。　结果　 (1)胃癌组的 Cath- D、GST的活性显著高于单纯性胃炎组及胃炎伴癌前病变组 (P<0 .0 1) ,胃炎伴癌前病变组 GST的活性显著高于单纯性胃炎组 (P<0 .0 5 ) ,Cath- D活性与单纯性胃炎组比较差异无显著性 (P>0 .0 5 )。 (2 )胃癌组织 Cath- D、GST的活性显著高于癌旁组织 (P<0 .0 5 )、癌旁组织中Cath- D、GST的活性显著高于对照组织 (P<0 .0 5 )。 (3)伴有淋巴结转移的胃癌组织中 Cath- D活性显著高于不伴有淋巴结转移的 (P<0 .0 5 ) ,GST的活性在伴有与不伴有淋巴结转移者中差异无显著性 (P>0 .0 5 )。 (4) Cath- D的活性与按预后好坏的组织学分型 (P<0 .0 1)、按 TNM的分期 (P<0 .0 1)等病理指标有密切相关 ,而 GST的活性与病理指标无显著相关 (P>0 .0 5 )。 (5 )胃癌手术后 10天血清中 GST的活性明显低于手术前 (P<0 .0 1)。　结论　Cath- D、GST活性联合检测可用于胃癌高危人群筛选、监测癌前病变进展及预测肿瘤复发     

猪带绦虫囊尾蚴囊液谷胱甘肽S转换酶活性测定

目的：探讨猪带绦虫囊尾蚴囊液内谷胱甘肽Ｓ转换酶（ＧＳＴ）的活性。方法：测定酶催化反应后底物浓度的变化,计算ＧＳＴ活力单位。结果：囊液经１：２０稀释,重复４次测定酶促管与非酶促管吸光值,测得平均ＧＳＴ活性为６１．８４活力单位;囊液冻干品则几无ＧＳＴ活性。结论：囊液中存在游离形式的ＧＳＴ活性,对筛选保护性抗原和可能的化疗靶分子具有潜在意义。     

肝脏缺血再灌注损伤时大鼠血清谷胱甘肽及其相关酶活性的变化

目的 还原型谷胱甘肽（GSH）是体内重要的氧自由基的清除剂。本实验意在研究缺血肝脏复流后血清谷胱甘肽及其相关酶水平变化,及L－精氨酸对其水平的影响。方法 雄性SD大鼠90只随机分为3组;左中肝叶先行缺血70min,后恢复血流,于复流前静脉给予生理盐水（损伤组）,或复流前静脉给与L－精氨酸（200mg/kg)（处理组）;假手术组只给与暴露左中肝叶之肝蒂。各组动物在复流后0、1、3、6、12h取血清标本,用以检测丙氨酸氨基转移酶（ALT）、MDA、 还原型谷胱甘肽（GSH）,谷胱甘肽过氧化物酶（GSH－PX）和谷胱甘肽－S转移酶（GSH－ST）。并取肝组织标本做光镜和电镜观察,了解组织病变特点。结果 损伤组血清ALT、MDA、GSH－ST和GSH－PX含量较假手术组有明显的提高（P＜0．05）,而在复流后3h血清GSH水平明显降低（P＜0．05）。给与L－精氨酸处理可以明显减轻这种变化（P＜0．05）。结论 L－精氨酸对大鼠肝脏缺血再灌注损伤的保护作用可能与上调还原型谷胱甘肽水平有关。血清GSH－PT、GSH－ST活性受到肝细胞损伤后释放增加的影响,与肝脏损伤程度有关。     

谷胱甘肽对高糖时人内皮细胞分泌前列环素和内皮素-1的影响

了解谷胱甘肽（ＧＳＨ）对高糖时人内皮细胞分泌前列环素（ＰＧＩ２）和内皮素－１（ＥＴ－１）的影响。方法： 原代培养人脐静脉内皮细胞,分别加入正常对照组,高糖组,正常＋ＧＳＨ组,高糖＋ＧＳＨ组培养基,放免法测定培养 ２４ｈ,４８ｈ,７２ｈ时培养基中的ＰＧＩ２和ＥＴ－１含量。结果：①高糖组较正常对照组ＰＧＩ２显著下降（Ｐ＜０．０１）,ＥＴ－１显 著升高（Ｐ＜０．０１）;②高糖＋ＧＳＨ组较高糖组ＰＧＩ２升高（Ｐ＜０．０１）,ＥＴ－１显著下降（Ｐ＜０．０１）。结论：ＧＳＨ在调节高 糖时人血管内皮细胞分泌 ＰＧＩ２／ＥＴ－１的平衡方面起一定作用。