胃癌及癌旁黏膜组织胎盘型谷胱甘肽S-转移酶的表达

①目的 探讨胎盘型谷胱甘肽Ｓ－转移酶（ＧＳＴπ）在胃癌中表达的意义。②方法 应用ＬＳＡＢ免疫组化方法检测了胃癌及癌帝黏膜组织ＣＳＴπ的表达。③结果 正常胃黏膜组织ＧＳＴπ阳性表达率为１６．７％,肠上皮化生和不典型增生腺体ＧＳＴπ阳性表达率分别为７１．４％和１００．０％,显著高于正常胃黏膜（Ｘ＾２＝８．４,１９．４,Ｐ〈０．０１）。胃癌组织中ＧＳＴπ阳性表达率为８０．３％,高分化腺癌和低分化腺癌ＧＳ     

愈肝汤对慢性乙肝患者脂质过氧化的影响

目的　探讨愈肝汤对慢性乙肝患者的脂质过氧化作用。方法　 43例慢性乙肝患者服愈肝汤治疗 3mo ,观察其治疗前后超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH -Px)活力和过氧化脂质(LPO)水平的变化 ,并与 38例健康对照组比较。结果　慢性乙肝患者SOD、GSH -Px活力降低 (P <0 .0 5 ) ,LPO水平升高 (P <0 .0 5 ) ;愈肝汤可升高SOD和GSH -Px酶活性 (P <0 .0 1) ,降低LPO水平 (P <0 .0 5 )。结论　愈肝汤对慢性乙肝患者有明显的抗脂质过氧化作用 ,这是其治疗慢性乙型肝炎、减轻肝细胞损伤的重要机理之一。     

HepG2 细胞谷胱甘肽含量和谷胱甘肽转移酶活力的诱导

目的：建立一种具有较高ＧＳＨ含量和ＧＳＴ活力的肝细胞系。方法：将ＨｅｐＧ２细胞在０．１,０．３,０．５ｍｇ／Ｌ浓度的ＣＤＤＰ间歇作用下传代１２个月后得到三种稳定的ＣＤＤＰ耐药细胞系ＨｅｐＧ２／ＣＤＤＰ０．１,ＨｅｐＧ２／ＣＤＤＰ０．３,ＨｅｐＧ２／ＣＤＤＰ０．５细胞的ＧＳＨ含量和ＧＳＴ活力,结果用显著性ｔ检验方法作统计学处理。结果：诱导刺激后的子代ＨｅｐＧ２／ＣＤＤＰ０．１,ＨｅｐＧ２／ＣＤＤＰ０     

Glutathione S-transferase activity in epithelial ovarian cancer: Association with response to chemotherapy and disease outcome

Background: Conflicting data have been reported about the associationbetween glutathione S-transferase (GST), a family of proteins implicated indetoxification of cytotoxic drugs in human ovarian in vitro models, andresponse to chemotherapy and prognosis in ovarian cancer patients. The aim ofthis study was to analyze the possible clinical role of GST activity in alarge series of primary ovarian cancer patients.Patients and methods: The study included a large series of primaryuntreated ovarian cancer patients who underwent cytoreductive surgery andchemotherapy and who were followed up in a single institution. GST activitylevels were assessed in tumor extracts by using a biochemical assay. A cut-offof 250 units of enzymatic activity was chosen according to the receiveroperating characteristics (ROC) curve.Results: GST activity levels were distributed in an asymmetrical manner(median: 266 units; range: 4–918 units) and did not seem to beassociated with stage, histopathological grading, ascites, or residual tumorafter surgery. Higher GST activity levels were found in patients who respondedto chemotherapy (median: 298 units, range: 50–691) than in those whoresponded only partially (median: 227 units, range: 19–747) or not atall to chemotherapy (median: 246 units, range: 4–811) (H = 7.02, P =0.029). Moreover, the percentage of cases with >250 units was significantlyhigher among complete responders (66%) than partial responders(37%) or non-responders (48%) (² = 7.32;P = 0.025). When multivariate analysis, including clinico-pathologicalparameters and GST activity status as predictors of response to chemotherapy,was carried out, residual tumor, stage and GST status retained independentpredictive value. Patients with high GST activity had more favourableprognosis than those with low GST activity. The median PFS was 42 months forpatients with high GST activity compared to 17 months for those with low GSTactivity (P = 0.037). The median overall survival was 72 months forhigh-GST-activity and42 months for low-GST-activity patients (P = 0.043). Substantially similarresults were obtained in the subgroup of stage II–III–IV ovariancancer patients. Multivariate analysis including the clinico-pathologicalparameters and GST activity status was performed in stage III–IV ovariancancer patients: Stage IV disease, residual tumor >2 cm, the presence ofascites and low GST activity status retained independent negative prognosticroles.Conclusion: A direct association between high GST activity and a betterclinical outcome in terms of response to chemotherapy and survival has beenobserved in a large series of primary untreated ovarian cancer patients. Theseresults, which are contrary to the expectations raised by in vitro studies,emphasize the need for caution when translating in vitro-generated hypothesesto the clinical setting.     

Role of calcium in thromboxane B2-mediated injury to rabbit gastric mucosal cells

A sustained increase in cytosolic Ca²⁺ can damage gastric mucosal cells. The present study has examined the role of Ca²⁺ in thromboxane B₂ (TXB₂)-mediated damage of rabbit isolated gastric mucosal cells. Cells were isolated from rabbit oxyntic mucosa by collagenase-EDTA digestion. Cell metabolic activity and cell damage were estimated by alamar blue dye absorbance and trypan blue uptake, respectively. Cellular Ca²⁺ was monitored by indo-1 dye fluorescence. Addition of TXB₂ (10^–6 and 10^–8 M) to the cell suspension resulted in a decrease in metabolic activity, and this effect was reduced when Ca²⁺ was removed from the incubation Ca²⁺ and incubation of cells with the intracellular Ca²⁺ chelator, BAPTA-AM (20 M), reduced cell injury in response to TXB₂. Incubation of cells with the Ca²⁺ ionophore A23187 (1–25 M) resulted in a dose-dependent increase in trypan blue uptake and a reduction in cell metabolism. Cell unjury in response to A23187 were exacerbated by addition of TXB₂ (10^–8 M) to the cell suspension. TXB₂ treatment reduced cellular content of reduced glutathione (GSH), while exogenous GSH addition (10 mM) reduced TXB₂-mediated cell injury. These data demonstrate that TXB₂ can directly injure gastric mucosal cells. Gastric mucosal cellular damage in response to TXB₂ is mediated in part by a disruption of Ca²⁺ homeostasis as well as a reduction in cellular GSH content.This work was supported by a grant from the Medical Research Council of Canada MT6426.     

Observations on the human cornea in vitro

Human corneas seem to have a vegetative physiology similar to the rabbits. The swelling-hydration characteristics of the stromas are similar and there is a pump in the endothelium which continuously pumps fluid out of the stroma. An electrical potential is found across the endothelium which is stimulated and stabilised in the presence of 0·5 mm reduced glutathione. Both fluid flow across the endothelium and trans-endothelial electrical potential are reversibly abolished in the absence of exogenous bicarbonate and CO₂ which suggests that the two phenomena are manifestations of a common underlying mechanism.Difficulties in using the specular microscope on human cornea in vitro are illustrated. It is suggested that results from such experiments usually cannot be interpreted.     

谷胱甘肽治疗帕金森病30例临床观察

目的 探讨还原型谷胱甘肽(古拉定，GLT)对帕金森病人治疗效果，观察GLT治疗后病人血超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH—Px)、丙二醛(MDA)水平的变化。方法 选择30例临床未治疗或服用美多巴因副反应被迫减药病人，应用GLT进行治疗，治疗前后行血SOD、GSH—PX、MDA测定，并设立对照组、正常人组比较；治疗、Px对照组进行了治疗前后H—Y分级及Webster评分。结果 治疗组和正常人组比较，血SOD、GSH—Px显减低(P＜o．01)，MDA显增高(P＜o．01)；GLT治疗后，SOD、GSH—Px值较治疗前明显升高(P＜o．05、P＜o．01)，MDA值下降(P＜o．05)，而对照组改变不明显。治疗前后评分，治疗后临床症状有显改善(P＜o．01)，与对照组比较，两组有显差异(P＜o．01)。结论 GLT对PD病人有较显治疗作用。     

古拉定在肝硬化亚临床肝性脑病治疗中的临床意义

目的　探讨古拉定 (GLT)在肝硬化亚临床性肝性脑病 (SHE)治疗中的临床意义。方法　以古拉定联合乳果糖治疗 4 7例SHE ,在 1mon治疗结束后随访 6mon ,并以单用乳果糖治疗的 5 0例SHE作对照 ,观察智力测验好转情况及肝功能改变情况。结果　数字连接试验 (NCT)及数字符合试验 (DST)在治疗结束及随访 6mon时的好转率分别为 69 0 %、5 2 6%和 4 7 6%、5 0 % ,而对照则分别为 4 0 8%、4 5 0 %和 17 4 % ,除DST治疗 1mon时两组差异无显著性外 ,两组其余各项比较差异均有显著性 (P <0 0 5或P <0 0 1) ;治疗组肝功能Child Pugh计分在治疗前为 8 92± 1 16,治疗 1mon时降为 7 73± 1 3 1(P <0 0 1) ,随访 6mon时为 8 0 2± 1 17(P <0 0 5 ) ,而对照组在治疗前为 8 65± 2 4 1,1mon时为 7 86± 1 4 6(P <0 0 5 ) ,至 6mon时为 8 4 4± 1 87,与治疗前差异无显著性。结论　古拉定能提高乳果糖对肝硬化SHE治疗的近期疗效及远期疗效 ,机制可能是通过改善肝功能状态而起作用     

谷胱甘肽治疗急性酒精中毒

目的 :探讨谷胱甘肽注射液治疗急性酒精中毒的疗效及安全性。方法 :5 0例急性酒精中毒昏睡期病人随机分为 2组 :谷胱甘肽组 2 8例 [男性 2 3例 ,女性 5例 ,年龄 (33±s 11)a],给予谷胱甘肽注射液 1.8g加入 5 %葡萄糖注射液 2 5 0mL中静脉滴注。促进乙醇氧化组 2 2例 [男性 18例 ,女性 4例 ,年龄 (35± 9)a],给予 5 %葡萄糖注射液 2 5 0mL +2 0U正规胰岛素注射液静脉滴注 ,同时给予维生素C、维生素B6 静脉注射。 2组病人均给予温水洗胃 ,并给予静脉注射呋塞米、西咪替丁及补液治疗。结果 :在清醒时间及给药后 3h清醒例数方面 ,治疗组明显优于对照组 ,治疗组病人苏醒时间为 (76± 4 4 )min ;对照组为 (133± 5 9)min(P <0 .0 1)。给药后 3h治疗组清醒 2 5例 (89% ) ,对照组清醒 7例(32 % ) (P <0 .0 1)。结论 :谷胱甘肽注射液治疗急性酒精中毒昏睡期病人的苏醒时间明显短于传统的促进乙醇氧化疗法 ,对急性酒精中毒具有可靠的治疗效果     

亚硝基谷胱甘肽对大鼠肝微粒体谷胱甘肽转移酶的激活及机制

目的　探索一氧化氮供体亚硝基谷胱甘肽(GSNO)能否在体外通过S 亚硝酰化机制激活大鼠肝微粒体谷胱甘肽转移酶 (mGST)。方法　微粒体粗提物与GSNO体外共孵育 ,测定mGST催化动力学改变 ,结合N 乙基马来酰亚胺 (NEM )再激活实验和二巯基苏醇 (DTT)逆转实验 ,以及酶蛋白游离巯基和酶S 亚硝酰化蛋白的改变 ,研究酶的激活机制。结果　GSNO在 0 .12 5～ 2mmol·L- 1浓度范围内呈浓度和时间 (3～ 15min)依赖性地激活mGST ,NEM对酶的再激活效应消失 ,DTT可以逆转上述激活作用 ,同时酶蛋白游离巯基浓度依赖性减少 ,而S 亚硝酰化蛋白浓度依赖性增多。结论　GSNO体外可激活大鼠肝mGST ,激活机制可能与mGST第 4 9位半胱氨酸 (Cys4 9)的巯基被亚硝酰化形成S 亚硝基硫醇结构有关。