Thrombin Inhibition in discordant xenograft rejection

Abstract: Microvascular thrombosis and the associated platelet and endothelial cell activation are prominent observations in xenograft rejection. This pathological picture could be related to the excessive generation of thrombin in the context of either inflammation or putative inter-species molecular incompatibilities between activated coagulation factors and their natural anticoagulants. Relatively selective thrombin Inhibition with the serine protease inhibitor SDZ MTH 958 (MTH-958) are independent of heparinoids and anti-thrombin III. MTH-958 has been shown to significantly prolong porcine cardiac function during perfusion with human blood in an ex vivo model. The aim of this study was to validate the role of thrombin generation in a rodent model of discordant xenograft rejection in vivo. The effect of thrombin inhibition with MTH-958 was tested in both hyperacute rejection (HAR) and delayed xenograft rejection (DXR) after decomplementation with cobra venom factor (CVF) in normal Lewis (Lew) rats and Intrinsic C6 deficiency In PVG (C6-/PVG) recipient rats. Recipient rats received heterotopic guinea pig cardiac xenografts and were treated with titrated doses of MTH-958 until the time of graft rejection. Plasma samples at selected time points were examined to confirm effective thrombin inhibition, and rejected grafts were analyzed by immunohistology. MTH-958 significantly improved graft survival in HAR albeit the extent of prolongation was not marked, but the agent failed to prolong survival In CVF-treated Lew rats. In C6-/PVG rats receiving MTH-958, a significantly reduced graft survival time was observed when compared with C6-/PVG controls. The grafts from MTH-958-treated animals showed dense deposits of C3, IgM, and IgG with fibrin levels similar to controls. The thrombin antagonist tested could prolong xenograft survival during HAR but had no benefit in DXR. The relative non-specificity of the serine protease inhibitor MTH-958 with the potential activation of alternative pathway of complement via the inhibition of factor I could account for the failure to prolong xenograft survival in DXR. The pathogenetic significance of thrombin generation in this situation remains to be determined by the use of more selective and pharmacologically acceptable I anti-thrombin agents.     

大鼠局灶性脑缺血再灌注模型的建立及其组织形态改变

目的：建立大鼠脑缺血2h再灌注不同时程实验动物模型，探讨其病理形态学HE染色特点。方法：线栓法行大鼠大脑中动脉闭塞(MCAo)造成局灶性脑缺血2h再灌注模型，假手术组不插入线栓。HE染色观察病理组织形态学特点。结果：所有局灶性脑缺血再灌注模型在麻醉苏醒后均表现为局灶性神经功能缺陷。再灌注后3h，神经功能缺陷部分恢复。这些表现与临床局灶性脑缺血再灌注溶栓治疗的病人相似。HE染色可见胞浆均质红染、细胞核固缩以及细胞膜和细胞结构破坏的嗜伊红的死亡神经元。结论：Wistar大鼠局灶性脑缺血再灌注模型的神经功能缺损与人类缺血性脑血管病相近，是研究脑缺血再灌注损伤的病理形态学机制的良好模型。     

心痛灵喷雾剂抗心肌缺血的实验观察

①目的　观察心痛灵喷雾剂对心肌缺血大鼠的药理作用。②方法　通过结扎大鼠冠状动脉前降支制备大鼠心肌缺血模型 ,观察心痛灵喷雾剂对心肌缺血面积和血清磷酸肌酸激酶 (CK)、乳酸脱氢酶 (LDH)、谷草转氨酶 (GOT)的影响 ;静脉注射垂体后叶素制备大鼠心肌缺血模型 ,观察心痛灵喷雾剂对心电图改变的影响。③结果　心痛灵喷雾剂可减少心肌缺血大鼠心肌梗死面积 ,降低血清CK、LDH、GOT活性 ,并减轻静脉注射垂体后叶素引起的缺血性心电图改变 (tD=1.2 2 3～ 13.890 ,P <0 .0 5、0 .0 1)。④结论　心痛灵喷雾剂具有抗心肌缺血的作用     

大鼠壁细胞的黏膜刮取式分离方法

采用黏膜刮取式方法，分离大鼠胃黏膜细胞。用相差显微镜、HE染色、电镜、荧光显微镜、免疫细胞化学染色等方法，对壁细胞进行观察和鉴定，并测定了壁细胞直径。结果成功地分离了大鼠胃黏膜细胞，同时证实，壁细胞在所分离的细胞中直径最大。     

玉郎伞提取物对大鼠自发性高血压的影响

目的：研究玉郎伞提取物(YLS)对自发性高血压大鼠(SHR)及正常大鼠血压(BP)的影响。方法：应用颈动脉插管测压法，连接MS2000多媒体生物信号记录系统测定静注YLS前及药后20s、30s、lmin、2min、5min时的收缩压(SP)、舒张压(DP)、平均动脉压(MP)。结果：YLS使SHR及正常大鼠血压明显降低(P＜0．01)，降压作用维持时间较短，给药后5min血压基本恢复正常；YLS对去甲肾上腺素(NA)和异丙肾上腺素（ISO)的作用无明显影响。结论：YLS对正常大鼠及SHR血压有明显的降低作用。     

二氧化硅对大鼠血浆中微量元素含量的影响

给大鼠经气管分别注入４、１６、６４ｍｇ石英粉尘生理盐水混悬液。在染尘后第７，１５和３０天解剖动物，测定血浆中Ｃｕ、Ｚｎ，Ｍｎ、Ｍｏ、Ｓｉ、Ｒｂ和Ｓｒ等７种微量元素的含量。实验结果表明，随着染尘剂量的增加，血浆中铜的含量明显增高，呈正相关，相关系数为０．９９９。而血浆锌的含量随着染尘剂量的增加而明显的降低，呈负相关，相关系数为－０．９９８。血浆中Ｍｏ、Ｍｎ、Ｓｉ、Ｒｂ和Ｓｒ含量与对照组比无明显差异。     

简易定向锥颅脑内血肿碎吸术治疗高血压脑出血——介绍一种简易脑内血肿碎吸器的研制及临床应用

本文介绍一种高血压脑出血外科治疗的新方法,即简易定向锥颅脑内血肿碎吸术。截至1988年10月临床应用19例,年龄41～79岁,出血量平均为48.1ml,一次吸除量为总量的79％(38ml),术后立即清醒者8/19例,偏瘫好转者4/19例,死亡4例。实践证明本法简单,安全有效,病人负担轻。     

3-氯丙二醇和2,3-氧丙醇合并灌喂九个疗程和停药120天后对大白鼠性腺器官的生化观察

本实验以合并3-氯丙二醇和2,3-氧丙醇(5+75mg/kg/d×2)给大鼠9个疗程,停药120天,共历程210天。观察其睾丸及附睾头、精囊某些生化成份的影响,其结果表明实验组之糖蛋白、RNA、DNA,含量有不同变化,停药120天未能完全恢复。停药120天后,乳酸脱氢酶活性及其同功酶酶谱的分析表明,能量的供能未能恢复到对照组的水平。从酶谱来看,药物所致的供能方式受损伤,因器官不同而有不同,并讨论了药物所致的不育,可能与能量供给有关。     

老年大鼠脑内肾上腺素能神经递质系统的变化

本文从下丘脑、大脑皮层、海马等脑区去甲肾上腺素(NA)的含量,其合成酶与降解酶的活性、NA受体数目等多环节的测定来分析肾上腺素能神经递质系统在老化脑中的变化。实验结果表明衰老过程下丘脑、大脑皮层内NA合成酶活性没变化,NA含量明显增高,下丘脑内α_1受体数目显著减少。上述结果提示这些脑区肾上腺素能神经的活动有可能减弱。同时,海马内单胺氧化酶B(MAO B)活性明显增加,说明海马神经元外组织有增生的可能。泰文并讨论了这些变化与老年记忆、行为与神经内分泌等脑功能衰退的关系。