Thrombin regulates components of the fibrinolytic system in human mesangial cells

Besides its procoagulant activity, thrombin has been shown to stimulate cell proliferation and to regulate the fibrinolytic pathway. We report here the effect of purified human alpha thrombin on the synthesis of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by cultured human mesangial cells. Thrombin (0 to 2.5 U/ml) increased in a time- and dose-dependent manner the production of t-PA and PAI-1 (2- to 3-fold increase of secreted t-PA and PAI-1 release during a 24 hour incubation). This effect was associated with a twofold increase in DNA synthesis measured by 3H-thymidine incorporation. Zymographic analysis and reverse fibrin autography showed that thrombin also increased the level of the 110 Kd t-PA-PAI-1 complex, whereas PAI-1 was present as a free 50 Kd form in the culture medium conditioned by unstimulated and thrombin-stimulated cells. Free t-PA was never observed. Both membrane binding and catalytic activity of thrombin were required since the effects of 1 U/ml thrombin were inhibited by addition 2 U/ml hirudin, which inhibits the membrane binding and catalytic activity of thrombin, and since DFP-inactivated thrombin, which has the ability to bind but which has no enzymatic activity, did not induce t-PA or PAI-1. Gamma thrombin, which does not bind to thrombin receptor, did not increase t-PA and PAI-1 releases. The effects of thrombin were probably mediated by protein kinase C activation since H7, an inhibitor of protein kinases, inhibited significantly thrombin effects on t-PA and PAI-1 production, and since addition of an activator of protein kinase A, 8-bromocyclic AMP (100 microM), induced a significant inhibition of the thrombin effect. The effects of thrombin were also suppressed by 1.25 micrograms/ml alpha amanitin, suggesting a requirement of de novo RNA synthesis. Northern blot analysis indicated that thrombin induced an increase in the mRNA levels of t-PA and of PAI-1. We conclude that thrombin increases DNA synthesis in human mesangial cells and enhances the synthesis of both t-PA and PAI-1. The latter is released in a large excess as compared to t-PA. Hence, thrombin may have a role in provoking a localized hypofibrinolytic state and may contribute to the persistence of glomerular fibrin deposits during proliferative glomerulonephritis.     

化学中毒与急性缺氧的双因素联合效应的实验研究

目的 研究化学中毒与急性缺氧两因素的联合效应。方法 建立常压常氧、常压缺氧和低压缺氧3种模型，以梭曼(Soman)、氰化钠(NaCN)和4-DMAP(4-dimethylaminophenol)为代表，测定大鼠、小鼠、家猫、PC12细胞、兔血红细胞等在3种模型条件下对毒物药物的行为、生化和生理指标变化。结果梭曼单独作用可导致动物协调运动下降、脑等组织含水率增加、脑组织AChE活性降低、MR下调、NE和cAMP含量增加。急性缺氧单独作用也可引起动物协调运动及自主活动的降低、脑等组织含水率的增加、外周血和脑组织AChE活性升高、MR受体上调、NE和cAMP含量增加、4-DMAP药效升高。化学中毒与急性缺氧同时作用，上述变化更加复杂。结论 化学中毒与急性缺氧两种因素同时作用于机体，对机体产生广泛而复杂的损伤作用。此种作用为两因素的联合效应。缺氧引起的机体功能下降对联合效应的增加部分贡献较大。急性缺氧既可使重要的组织成分发生质或量的变化，也会影响某些抗毒剂的作用强度。     

Sideropenic Dysphagia综合征膜性蹼26例分析

目的 :研究SideropenicDysphagla (S -D)综合征膜性蹼产生的机制。方法 :回顾分析S -D综合征2 6例的临床资料。结果 :影像学检查显示膜性蹼在颈段食道前壁呈 2mm深的模样陷凹。血液学检查为缺铁性低血红蛋白性贫血改变。结论 :缺铁性贫血是S -D综合征的原因 ,铁剂治疗有效     

Deletion of aldose reductase leads to protection against cerebral ischemic injury.

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR(-/-) brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR(-/-) brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.     

经皮椎体成形术治疗脊柱疾病

目的评价经皮椎体成形术治疗脊柱疾病的临床应用价值.方法 56例多发骨髓瘤、溶骨性脊柱转移瘤、骨质疏松性椎体压缩性骨折患者应用经皮椎体成形术后,分24 h、3个月两阶段评估患者疼痛、术后X线片检查结果、椎体高度等指标.结果术后止痛效果良好,尤以骨质疏松性椎体压缩性骨折患者的止痛效果最好.无严重并发症. 结论经皮椎体成形术对骨质疏松性椎体压缩性骨折等脊柱疾病的止痛、稳固椎体等效果明显,可以谨慎开展.     

老年人肱骨近端二部分和三部分移位骨折19例临床分析

目的 探讨老年人肱骨近端二部分和三部分移位骨折的手术治疗方法。方法 回顾性分析19例老年肱骨近端二部分和三部分移位骨折患者的临床资料，其中二部分骨折13例、三部分骨折6例，采用切开复位，肱骨近端解剖钢板固定治疗。结果 二部分骨折术后优良率为76．9％，未出现骨折不愈合及肱骨头坏死；三部分骨折术后优良率为66．7％，肱骨头坏死率16．7％。结论 老年人肱骨近端二部分和三部分骨折应尽量采用有限切开复位，选择肱骨近端解剖钢板固定。     

夜来香根茎水提取液局部麻醉作用的研究

目的：研究夜来香(CN)根茎水提取液的局部麻醉作用及其作用机制。方法：采用蟾蜍离体坐骨神经动作电位法、豚鼠皮丘法、椎管麻醉法、表面麻醉法。结果：20％的CN水提取液对蟾蜍离体坐骨神经动作电位可完全消失，但较1％的普鲁卡因稍弱。豚鼠皮丘实验表明，20％CN提取液有浸润麻醉作用，其浸润麻醉效果与1％的普鲁卡因相似，而且盐酸肾上腺素可增强其麻醉强度和明显延长局麻作用时间；家兔椎管麻醉实验表明CN提取液有明显的椎管麻醉作用；CN提取液对家兔角膜也有一定的表麻作用，只是作用强度及持续时间比1％的普鲁卡因稍弱或稍短。结论：CN提取液有明显的局部麻醉作用。     

自身免疫性白内障的晶状体代谢与生理改变研究

目的 :探讨自身免疫性白内障 (AIC)的病理生理学机制。　方法 :采用酶组织化学方法以及晶状体生理功能检查 ,观察AIC模型动物晶状体生理功能与组织内主要酶活性的变化。　结果 :晶状体组织内Na K ATP酶活性降低与晶状体调节力下降、裂隙灯下显微镜混浊改变之间存在着相关性。　结论 :自身免疫性晶状体损伤 ,进而造成晶状体组织内相关酶代谢异常是AIC的病理基础     

口服谷氨酰胺颗粒对烧创伤患者的疗效及安全性分析

目的观察口服谷氨酰胺(Gln)颗粒对烧(创)伤及大手术患者的疗效及可能发生的不良反应.方法采用随机双盲、安慰剂对照法,将受试患者分为Gln组和对照组,每组60例,两组患者采用等氮、等热量的营养支持.Gln组口服或管饲Gln 0.5 g·kg-1·d-1,对照组使用同等剂量的安慰剂甘氨酸,疗程均为7 d.比较用药前后两组患者肠黏膜屏障功能、蛋白代谢、免疫功能、肝和肾功能的变化及不良反应等. 结果伤后两组患者血浆Gln浓度明显低于正常值,而血浆二胺氧化酶(DAO)活性、内毒素含量、肠黏膜通透性[尿乳果糖/甘露醇(L/M)]及尿氮排量均明显增高;但Gln组用药7 d后血浆Gln浓度与用药前比较增加38.04%(P＜0.01).Gln组血浆前白蛋白、转铁蛋白及白细胞介素2(IL-2)含量均显著高于对照组(P＜0.01),升幅分别为21.19%、51.11%、57.54%.血浆DAO活性、L/M比值、内毒素含量及尿氮排量明显低于对照组,降幅分别为47.26%、52.18%、22.22%、27.78%(P＜0.05或0.01).两组患者的血浆总蛋白、白蛋白、血尿常规及肝、肾功能在用约前后变化不明显(P＞0.05).用药后有少数患者出现轻微不良反应如恶心、腹泻和便秘等,2～3 d后自行缓解,两组间比较,差异无显著性意义(P＞0.05).结论口服Gln能显著提高患者血浆Gln浓度,明显减轻伤后肠黏膜受损程度,并能促进机体蛋白合成,降低蛋白分解,提高机体免疫功能,且临床应用无明显不良反应.     

形状记忆合金环抱接骨板治疗锁骨骨折

目的 探讨形状记忆合金环抱接骨板治疗锁骨骨折的手术方法及疗效。方法 采用西脉记忆合金环抱接骨板治疗锁骨骨折54例。结果 54例病人全部获得随访，优良率96.3％。结论 形状记忆合金环抱接骨板治疗锁骨骨折是一种方便有效的方法，具有手术操作简便、内固定确实等优点，但应加强术后管理。