Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones

Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.     

Analysis of differential effects of Pb2+ on protein kinase C isozymes

Protein kinase C has been implicated as a cellular target for Pb2+ toxicity. We have previously proposed that Pb2+ modulates PKC activity by interacting with multiple sites within the enzyme. In order to further characterize the Pb-PKC interactions we compared the effects of Pb2+ on the CA-dependent and -independent protein kinase C isozymes using recombinant human PKC-alpha, PKC-epsilon, and PKC-zeta as well as the catalytic fragment of bovine brain protein kinase C, the PKC-M. The results demonstrate that, whereas at pM concentrations Pb2+ activates PKC-alpha half maximally (KAct approximately 2 pM), it has no effect on PKC-epsilon, PKC-zeta, or PKC-M activities. The activation of PKC-alpha by Pb2+ is additive with Ca2+ in a manner indicating interaction with half of the calcium activation sites. In the micromolar range of concentrations, Pb2+ inhibits all PKCs with estimated K0.5 of 1.0, 2.3, 28, and 93 microM for PKC-M, PKC-alpha, PKC-epsilon, and PKC-zeta, respectively. Examination of Pb2+ effects on PKC-M kinetics indicates a mixed type inhibition with respect to ATP and noncompetitive inhibition with respect to histone. Taken together with the results of our previous study (Tomsig and Suszkiw, J. Neurochem. 64, 2667-2673, 1995) and the evidence for the existence of two Ca2+ coordination sites Ca1 and Ca2 within the C2 domain (Shao et al., Science [Washington, D.C.] 273, 248-251, 1996), the results of the current study provide further support for a multisite Pb-PKC interaction scheme wherein lead (1) partially activates the enzyme through pM-affinity interactions with the Ca1 site and inhibits the divalent cation-dependent activity through nM-affinity interactions with Ca2 site in the C2 domain and (2) inhibits the constitutive kinase activity through microM-affinity interactions with the catalytic domain. The concentration dependence of the differential effects of Pb2+ on the calcium-dependent and -independent PKCs underscores the importance of the C2 motif as a high affinity molecular target for Pb2+.     

53所托幼园所卫生保健状况调查

为对我区托幼园所卫生保健工作的进一步开展提供参考,本文对和平区53所托幼园所的卫生保健工作状况进行了调查。结果表明,和平区集体托幼卫生保健工作较好地达到了卫生部颁布的“托儿所、幼儿园卫生保健制度“规定的标准。总结出坚持“五化”管理,抓好全区集体托幼卫生保健工作的经验,同时找出了存在的问题,提出了加强基础管理的对策。     

Mucinous pancreatic ductal ectasia of latent malignancy: an emerging clinicopathologic entity.

The natural history of classic mucinous cystic neoplasms of the pancreas has been previously defined. In this report, an unusual variant of a pancreatic mucinous cystic neoplasm, termed "mucinous pancreatic duct ectasia of latent malignancy," is described. The lesion is characterized by massive dilatation of the main pancreatic duct and its tributaries. Histologically, the ducts are lined by epithelium, which is indistinguishable from the classic mucinous cystic neoplasms. Until the natural history of classic mucinous cystic neoplasm is better documented, resection appears to be the treatment of choice.     

当归对大鼠免疫性肝损伤的保护作用

目的 研究当归对免疫性肝损伤大鼠的保护作用。方法 采用牛血清白蛋白(BSA)致大鼠免疫肝损伤模型,观察当归大、小剂量对其肝功能、超氧化物歧化酶(SOD)、丙二醛(MDA)及肝细胞膜功能的影响。结果当归尤其是小刘量当归具有明显提高肝细胞SOD、降低MDA(P<0.05).并提高肝细胞膜ATP酶(ATPase)活性(P<0.05)的作用。结论提示当归具有明显的抗肝损伤作用.机制可能与其抗脂质过氧化作用及改善肝细胞功能有关。     

醒脑启智胶囊对血管性痴呆小鼠学习记忆障碍的影响

目的：观察醒脑启智胶囊对血管性痴呆学习记忆障碍小鼠的影响。方法：复制脑缺血再灌注血管性痴呆小鼠模型，分别于术后7天、15天、30天采用跳台法检测各组小鼠行为学变化。结果：造模小鼠学习与记忆能力下降，表现为学习反应时间延长，记忆潜伏时间缩短，错误次数增加。醒脑启智胶囊可使模型小鼠学习反应时间缩短，记忆潜伏时间延长，错误次数减少。结论：醒脑启智胶囊对模型小鼠学习与记忆能力下降有显改善作用。     

心宁美治疗病毒性心肌炎的临床研究

目的:探讨心宁美治疗病毒性心肌炎的临床疗效。方法:将180例入选病例按随机原则分为治疗组120例、对照组60例,分别给与心宁美(冲剂)、常规西药治疗,并观察其主要症状、心肌酶谱及心电图的改变。结果:治疗组对主要症状、心肌酶谱及心电图的改善均明显优于对照组(P<0.05或P<0.01)。结论:心宁美治疗病毒性心肌炎具有较好疗效。     

利咽口服液对实验性慢性咽炎病理形态学的影响

目的：观察利咽口服液对慢性咽炎动物模型咽部病理形态的影响。方法：采用光镜对利咽口服液高、中、低治疗组及模型组、阳性对照组动物的咽部组织进行了观察。结果：模型动物咽部上皮内可见灶性或弥漫性炎细胞浸润(主要为淋巴细胞、单核细胞)；上皮层轻度增厚，钉突延长，血管明显扩张、充血、纤维组织增生；经利咽口服液治疗，动物咽部的慢性炎症明显减轻或趋于正常，且以中、高剂量组为明显。结论：利咽口服液对慢性咽炎有较好的治疗作用。其作用可能是通过抗炎、改善咽部血管通透性、减轻炎性渗出、抑制组织增生等多途径来实现的。     

老年斑、神经元纤维缠结与硫酸多糖

老年斑 (senileplaques ,SP)、神经元纤维缠结 (neurofib rillarytangles,NFTs)是老年性痴呆最典型的病理特征 ,其中SP的主要成分为 β样淀粉蛋白 (Aβ) ,NFTs主要由异常修饰的tau蛋白组成。许多研究发现硫酸多糖与SP、NFTs的形成密切相关。大量文献报道硫酸多糖与淀粉样前体蛋白(APP)、Aβ以及tau蛋白具有高度亲和性 ,它不仅可以促进APP的异常代谢 ,导致Aβ的大量产生 ,诱导其形成纤丝并聚集、沉积于细胞外 ,而且还可促进tau蛋白发生高度磷酸化 ,形成成对螺旋丝 (PHF)并聚集成NFTs。但也有文献报道外源性硫酸多糖具有促进APP的神经营养作用 ,抑制Aβ纤丝的形成 ,并增强磷酸酯酶PP2B的活性 ,从而减少tau蛋白的磷酸化修饰。并且硫酸多糖的糖基组成、糖链长度、硫酸基的数目及位置不同 ,它在SP、NFTs的形成过程中扮演的作用也不同 ,所以可通过分子结构改造而使硫酸多糖表现抑制SP、NFTs形成的活性 ,从而达到抗老年性痴呆的作用     

头孢替唑钠与头孢唑啉钠对照治疗急性细菌性感染130例

目的：观察头孢替唑钠治疗急性细菌性感染的疗效及安全性。方法：130例急性呼吸道及泌尿道感染患者，随机分成试验组和对照组。分别接受头孢替唑钠和头孢唑啉钠，均用2g溶于5％葡萄糖溶液或生理氯化钠溶液中静滴，bid，疗程7-14d。结果：试验组痊愈率66．7％，明显优于对照组（P＜0．01），总有效率试验组97．0，优照组无明显差异（P＞0．05）。头孢替唑钠对106株致病菌的敏感率96％（102／106株高敏），对金葡球菌MIC值为0.06-0.5mg.L^-1，低于头孢唑啉、头孢氨苄，头孢呋辛及头孢他啶的MIC值。结论：头孢替唑钠是治疗急性呼吸道及泌尿道感染安全有效的抗生素。