超抗原SEA抗肿瘤研究进展

超抗原是指一些细菌或病毒编码的蛋白分子，只需极低浓度即可激活大量的淋巴细胞克隆．作为一种强大的T细胞激活剂，超抗原成为肿瘤免疫治疗研究的热点之一．本文对其特性及目前的研究进展作一综述．     

Synthesis of substituted 7,12-dihydropyrido[3,2-b:5,4-b']diindoles: rigid planar benzodiazepine receptor ligands with inverse agonist/antagonist properties

A series of 1-, 2-, 3-, 4-, 5-, 6-, 7-, 10-, and 12-substituted pyridodiindoles were synthesized and screened in vitro against [3H]diazepam for activity at the benzodiazepine receptor (BzR). In vitro, the 2-substituted pyridodiindoles were found to be the most potent (IC50 less than 10 nM) of this new class of BzR ligands. In vivo, 2-methoxypyridodiindole 19a (IC50 = 8 nM) was found to be the most potent partial inverse agonist (proconvulsant) of the series. The parent compound 2 (IC50 = 4 nM) was only slightly less potent. In addition, 2-hydroxypyridodiindole 21a (IC50 = 6 nM) was found to exhibit potent proconvulsant activity when administered as a prodrug derivative, pivaloyl ester 22. 2-Chloropyridodiindole 16a (IC50 = 10 nM) was devoid of preconvulsant activity; however, 16a was found to be the most potent antagonist of the anticonvulsant effects of diazepam in this class of BzR ligands. From the in vivo data available, substitution on ring E of 2 with electron-withdrawing groups results in antagonists at BzR, while replacement of hydrogen at C-2 with electron-releasing groups provides enhanced inverse agonist activity. The pyridodiindoles were used as "templates" for the formulation of a model of the inverse agonist/antagonist active site of the BzR. The proposed model consists of a hydrogen bond acceptor site (A1) and a hydrogen bond donor site (D2) disposed 6.0-8.5 A from each other on the receptor protein. The hydrogen-bonding sites are believed to be located at the base of a narrow cleft. A large lipophilic pocket at the mouth of the narrow cleft serves to direct molecules into the binding site, while the presence of a small lipophilic pocket permits substitution only at position 2 of the pyridodiindole nucleus for maximum binding potency.     

绝经后骨质疏松大鼠模型的综合评价

利用双能X线骨密度仪、扫描电镜和骨生物力学试验综合评价大鼠去卵巢后的骨骼状况。结果显示：①大鼠卵巢切除后,活体、离体腰椎以及股骨（除R3区）、胫骨近端干骺端（R1区）的离体骨密度显著下降（P＜0.01),离体L5和L6的骨丢失率最大,达13%;②骨小梁减少、变细,连接中断,骨小梁表面有吸收陷窝;③腰椎压缩强度和股骨力学性均下降,前者更明显,腰椎最大压缩力下降率达33.32%。提示：①类似于绝经后妇女,6月龄大鼠在卵巢切除4个月后骨量和骨质量均下降,特别在富含松质骨的部位,如腰椎、股骨远端等;②利用绝经后骨质疏松大鼠模型评价骨质疏松新药的有效性,应包括该新药对骨量、骨结构和骨强度的作用。     

老年人低位硬膜外麻醉围术期自主神经功能的变化

目的：应用心率变异性（HRV）分析仪监测评估低位硬膜外麻醉围术期自主神经的改变。方法：选择低位硬膜外麻醉下择期手术患者20例,ASAⅠ-Ⅱ级,按年龄分为老年组和年轻组,每组10例,观察术前1d、麻醉完善后切皮前、切皮后30min、术后2h,1d,3d,7d处时相点的心率（HR）、平均动脉压（MAP）以及HRV分析各成分变化。结果：围术期老年组HRV显示RMSSD（相邻RR间期差值均方根）、总频（TP）、低频（LF）、代频标化（LFnorm)均呈显著性下降,同时伴有心率减慢、平均动脉下降。年轻组TP和LF在麻醉完善后切皮前、术后2h,1d下降显著,于术后3d恢复,而R和MAP在围术期无显著改变。两组两比较,老年组TP和LF在麻醉后各时相占 明显低于年轻组（P＜0．01）。老年组高频（HF）及高频标化（HFnorm)在麻醉给药后切皮瓣均无明显变化,但在术中和术后各时相点的下降,而年轻组仅切皮后30min,出现一过性下降。结论HRV可较好地评估围术期机体自神经变化;术期麻醉和手术创伤均可使机体自主神系统调节受损,尤其老年人受损程度大,恢复慢,恢复慢,术后1周仍不能完全恢复。     

血液分离胶的制备研究

目的 :对血液分离胶的制备进行研究。方法 :用天然橡胶和特效触变剂等原料制备具有触变性的凝胶 ,研究该凝胶分离血清的较优组成。结果 :血液分离胶的较优组成是天然橡胶 12 .8%、特效触变剂 2 8.0 %和溶剂汽油 5 8.2 %。结论 :所制备的血液分离胶具有制备容易、分离效果好和成本较低等优点。     

成都地区汉族人群ACE基因多态性与血清ACE活性的相关性

为调查中国汉族人群血管紧张素转换酶(ACE) 基因多态性分布及与血清ACE(SA CE)活性的相关性.采用比色法和PCR技术,对90例健康汉族人群进行SACE活性和ACE基因插入/缺失(I/D)多态性的检测.结果显示:中国汉族人群ACE基因DD型占18%,DI型占44%,II 型占38%, D和I等位基因频率分别为0.40和0.60.ACE基因多态性与SACE活性密切相关,提示不同种族间ACE基因分布存在着差异,中国汉族人群ACE基因多态性以II型和I等位基因占优势;SACE活性受ACE基因I/D多态性的影响.     

99mTc-DTPA气溶胶显像测定呼吸道粘液纤毛清除功能

为进一步研究呼吸道疾病时的粘液纤毛清除功能,采用99mTc-DTPA气溶胶吸入显像,通过电影显示定性和定量指标分析.对18 例健康受试者和患者进行了显像研究,得到气道清除率和粘液纤毛清除率的正常值,并观察了32例慢性阻塞性肺病(COPD)患者气管-支气管纤毛清除功能的改变.结果显示,健康受试者与COPD患者粘液纤毛清除率(mm/min)分别为3.89±0.92和1.32±0.59,两者比较有显著性差异(P＜0.01),COPD患者不同时间气道清除率和粘液纤毛清除率均明显低于健康受试者(P＜0.01).本研究方法简便客观,具有定性观察和定量分析的优点,对于呼吸系统其它疾病(如支气管扩张、原发性纤毛无运动)的研究及药物疗效的评价具有重要的临床实用价值.     

2型糖尿病及其血管并发症患者血清ACE活性的变化

为了解2型糖尿病及其血管并发症患者血清ACE(SACE)活性的变化, 采用比色法对1 27例2型糖尿病患者和90例正常人进行SACE活性的检测。结果显示：糖尿病患者SACE活性(45 9. 51±175.85U)明显高于正常人(321.14±121.27U);糖尿病肾病组SACE活性(548.27±166.60 U)明显高于非肾病组(383.20±139-00U),但微量蛋白尿组(528.10±190.70U)与大量蛋白 尿 组(545.83±138.60U)SACE活性比较无统计学意义(P＞005);糖尿病视网膜病变 组SACE活性(465.64±178.93 U)与无视网膜病变组(449.07±170.04U)比较也无统计学意义;糖尿病患者SACE活性与病程 、 血压、血脂和血糖无关。提示ACE可能仅参与了糖尿病和糖尿病肾病的发病,而与糖尿病肾 病进行性发展、糖尿病视网膜病变和高血压发病无关。     

颅脑肿瘤手术行急性等容血液稀释的临床研究

目的：研究急性等容血液稀释对颅脑肿瘤病人血流动力学、氧转运及凝血纤溶方面的影响,探讨该方法的安全性。方法：选择颅脑肿瘤手术病人12例,麻醉后从右颈内静脉放置Swan～Ganz导管,从桡动脉放血8ml/kg,同时等速从静脉输入等量的海脉素。分别测定血液稀释前后的血流动力学,氧转运及凝血纤溶方面的指标。结果：CO、SV、DO2显著增加(P＜0.05);PT延长(P＜0.05);PLT较血液稀释前减少,其余指标无明显改变。结论：急性等容血液稀释对颅脑肿瘤病人的血流动力学及凝血纤溶功能影响小,而氧供增加,是一安全有效的血液保护方法。     

Polymorphism of ACE gene and its relationship with serum ACE activity in the Hans in Chengdu region]

This study was aimed at the angiotensin converting enzyme (ACE) gene insertion/deletion(I/D) polymorphism distribution in Chinese and its relationship with serum ACE activity(SACE). SACE activity and ACE gene polymorphism in 90 healthy persons in Chengdu region were investigated using a spectrophotometric assay and the PCR technique, respectively. The results showed that, in the Hans, DD genotype of ACE gene was 18%, DI genotype 44%, and II genotype 38%. Allele frequencies were 0.40 for the D allele and 0.60 for the I allele. There were significant relationships between ACE I/D polymorphism and SACE activity. The results suggest that ACE genotype distribution be different between races, that II genotype and I allele be more frequent in Chinese, and that SACE activity be under the influence of a genetic polymorphism of ACE in Chinese.