Problems in the design of anticancer agents

Theoretically, two predominant paths for obtaining more selective anticancer agents may be envisaged. These are: (a) to make compounds which distribute only or preferentially in cancer cells; (b) to make compounds that are able selectively to kill or to differentiate cancer cells. Although in the last two decades research into new anticancer drugs has not produced satisfactory results, there is solid ground on which novel strategies can be developed, mainly based on a much greater biological knowledge of human tumours. This article does not review all the possible approaches that may be followed, but simply discusses some ideas and problems mainly taken from the current research of our laboratory.     

台湾产奇特长唇瓢虫雄性外生殖器与两新种描述：...

本文描述了奇特长唇瓢虫Shiro(?)lla mirol(?)ilis Sasaji的雄性外生殖器与本属两新种:附肢长唇瓢虫Sh.oppe(?)nd(?)a sp.n.,阿里山长唇瓢虫Sh.(?) sp.n.,均产于台湾.种类检索如下:1(2).后基线伸达第一腹板1/2略强:阳基侧叶长,无触须状附肢;鞘翅淡黄棕色,具七个黑色斑纹;体 长1.82 mm………………………………………………………阿里山长唇瓢虫Sh.(?)sp.n.2(1).后基线后缘远超第一腹板长度的1/2;阳基侧叶短,具触须状附肢:3(4).前胸背板棕色,具两个暗棕色模糊斑点;鞘翅棕色,具九个黑斑;体长2.12～2.59 m………… …………………………………………………………………………附肢长唇瓢虫Sh.(?)sp.n.4(3).前胸背板淡黄棕色,无斑点;鞘翅淡黄棕色,具六个黑斑,侧面的一对长形;体长2.00～2.26mm …………………………………………………………………………奇特长唇瓢虫Sh.(?)sasaji     

Vascular pharmacology of methylene blue in vitro and in vivo: a comparison with NG-nitro-L-arginine and diphenyleneiodonium.

1. The vascular effects of the soluble guanylyl cyclase inhibitor, methylene blue as well as the nitric oxide (NO) synthase inhibitors, NG-nitro-L-arginine (L-NOARG) and diphenyleneiodonium (DPI) were studied in rat isolated aortic rings and conscious, unrestrained rats. 2. Acetylcholine (ACh) and sodium nitroprusside (SNP) caused concentration-dependent relaxation of preconstricted aortic rings. Both methylene blue (1 x 10(-5) M) and L-NOARG (3 x 10(-5) M) abolished ACh-induced relaxation; however, methylene blue but not L-NOARG shifted the concentration-response curve of SNP to the right. 3. In conscious rats, i.v. infusion of methylene blue (1.1 x 10(-5) mol kg-1 min-1), at a concentration which reduced the aortic tissue level of cyclic GMP by 50%, did not significantly alter mean arterial pressure (MAP) and heart rate (HR). In contrast, i.v. bolus injection of L-NOARG (1.5 x 10(-4) mol kg-1) markedly increased MAP and decreased HR. 4. Both ACh and SNP dose-dependently decreased MAP in conscious rats. Methylene blue did not alter the magnitude or duration of ACh- or SNP-induced depressor responses. L-NOARG, on the other hand, significantly though incompletely, reduced the magnitude and duration of the depressor response to ACh but not SNP. The depressor response to ACh or SNP was not altered by pretreatment with indomethacin (1.4 x 10(-5) mol kg-1) or capsaicin (3.3 x 10(-4) mol kg-1). 5. NG-nitro-L-arginine methyl ester (L-NAME) also caused dose-dependent increases in MAP in conscious rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

经皮顺行交锁钉治疗股骨干骨折

目的:评价经皮顺行交锁钉治疗股骨干骨折的临床疗效.方法:对79例82处股骨干骨折采用髋部小切口经皮顺行交锁钉治疗,观察疗效.结果:75例(92%)获得了良好的解剖对位并达到一期愈合,6例(8%)迟缓愈合.另外,由于再次手术1例(1%)发生了深部感染.失血量较少(平均小于100 mL),切口平均长25 mm.1年后随访只有10%髋部疼痛.结论:与传统手术方式相比,经皮技术术中出血少、对周围组织创伤少,是一个安全又有效的方法.     

Adrenalectomy abolishes antagonism of alpha-adrenoceptor-mediated hypotension by a beta-blocker in conscious rats.

1. The effects of a single bolus injection of propranolol, atenolol or ICI 118,551, non-selective beta-, selective beta 1- and selective beta 2-adrenoceptor antagonists, respectively, on mean arterial pressure (MAP) and plasma catecholamine concentrations were examined in seven groups of conscious and unrestrained adrenalectomized rats receiving a continuous infusion of the alpha-adrenoceptor antagonist phentolamine. In all rats adrenaline was undetectable in the plasma four days after adrenalectomy. 2. In the first three groups, phentolamine significantly decreased MAP and increased the plasma concentrations of noradrenaline. The injection of propranolol, atenolol or ICI 118,551 in Groups I, II and III, respectively, caused a small increase in MAP and a small, but not significant, decrease in plasma noradrenaline concentrations. 3. Groups IV, V and VI were given a continuous infusion of adrenaline for 1 h prior to the infusion of phentolamine, followed by a bolus injection of propranolol, atenolol or ICI 118,551, respectively. Group VII was treated similarly to IV, but was also given daily cortisone replacement after adrenalectomy. Adrenaline slightly, but not significantly, decreased MAP while phentolamine significantly decreased MAP and increased plasma noradrenaline concentrations in all groups. A subsequent injection of a beta-blocker caused a significant increase in MAP in each group and a slight decrease in the plasma level of noradrenaline which reached statistical significance in group VII. The pressor effect of propranolol was significantly greater in the cortisone-treated rats (Group VII) than in Group IV. 5. The results suggest that adrenaline and adrenocortical steroids are both involved in the antagonism of alpha-adrenoceptor-induced hypotension by a beta-blocker.     

Factors affecting penetration of zona-free hamster ova

The sperm penetration assay is an expensive, time-consuming test to assess male fertility in vitro. Although some investigators are enthusiastic in its application, others feel that it is not sensitive or specific enough to be used as part of the routine infertility evaluation. Indeed, this bioassay is not a faithful reproduction of in vivo conditions. However, if the SPA is abnormal, it is unlikely that sperm will fertilize a human ovum in vivo. Conversely, a normal SPA does not guarantee successful in vivo fertilization. No bioassay can be absolute in its predictive value, but false-negative results must be kept to a minimum for this bioassay to be of any clinical significance. Each laboratory performing the SPA should optimize the assay for sensitivity, reproducibility, and minimization of false-negative results and then establish normal and abnormal ranges of its own. If the limitations of the SPA are kept in mind, and if we employ it very selectively, it may still be useful.     

Empty sella syndrome in childhood

The empty sella syndrome is common in middle-aged women, usually presenting with headache, and only occasionally associated with endocrine or visual abnormalities. It is rare in childhood. Childhood cases tend to present either with endocrine disturbances, visual symptoms, or with craniofacial syndromes. We present three cases of complete empty sella with childhood onset, each discovered unexpectedly during evaluation of endocrine or visual dysfunction.     

献血者档案的管理

本文探讨了当前在采供血机构(血站)的管理工作中,加强献血者档案管理的规范化、系统化、网络化运作方面的研究,构建以计算机管理系统为基础,人机结合为手段,信息共享为目的的新型档案管理模式,其目的是为了准确、快速查询、利用血源档案信息,以确保临床安全输血,充分满足临床用血需求提供良好的服务。