Therapeutic effect of antimicrobial drugs against experimental infections due toYersinia pestis in mice

Although there are effective antibacterial agents against plague, newer antibacterial agents have been developed which show more potent activity against other bacterial organisms, but have not been tested againstYersinia pestis. A strain ofYersinia pestis was selected (no. 22; National Institute of Infectious Diseases, Tokyo, Japan) that caused a systemic infection in mice.Y. pestis no. 22 was intraperitoneally inoculated into DDY-strain mice, and 13 oral or 6 injectable antibacterial drugs given to the infected mice at varying doses 1 and 24 hours after infection. Levofloxacin, sparfloxacin and ofloxacin were the most effective oral agents against the infection, and prulifloxacin and pazufloxacin were also effective but to a lesser extent. Also, gentamicin and arbekacin were the most potent injectable antibacterial agents againstY. pestis. These results suggest that there are several new drugs, both oral and injectable, which exert excellent in vivo antibacterial activity against a mouse infection model and may be useful for the clinical treatment of plague.     

亚硒酸钠对顺铂致人体淋巴细胞增殖抑制的拮抗作用

目的 检测亚硒酸钠是否能够削弱或解除顺铂对植物血球凝激素(PHA)刺激的人体外周血淋巴细胞的增殖抑制。方法 用顺铂和亚硒酸钠单独或联合处理PHA刺激的人体外周血淋巴细胞，顺铂(0．05，0．20，0．50mg／L)在细胞培养24h时加入，亚硒酸钠(0．05mg／L)在不同处理中分别在细胞培养开始时加入或与顺铂同时加入；培养72h后检测转化淋巴细胞的有丝分裂指数。结果0．05mg/L亚硒酸钠在培养开始时加入，PHA刺激转化的淋巴细胞有丝分裂指数较对照增长42．8％(P＜0．05)，与顺铂同时加入，有丝分裂指数增长13．7％(P＞0．05)。0．05与0．20mg/L顺铂处理细胞，有丝分裂指数未发生显性改变，当顺铂剂量为0．50mg/L时，细胞有丝分裂指数较对照降低54．5％(P＜0．001)。亚硒酸钠预处理细胞可以解除0．50mg/L顺铂所致的细胞增殖抑制，使有丝分裂指数恢复正常，但亚硒酸钠与顺铂同时加入时，被顺铂抑制的有丝分裂指数只能部分提高。结论0．05mg/L亚硒酸钠单独作用于淋巴细胞可直接促进细胞增殖，与顺铂联合处理细胞时，可降低顺铂毒性，拮抗顺铂的抗增殖作用。亚硒酸钠在细胞培养开始时加入培养体系效果更佳。     

Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264

The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca²⁺-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca²⁺-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC₅₀ of Ca²⁺ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to 113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component I_Kr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define I_Kr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca²⁺-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the I_Kr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions are clearly independent of sterical configuration. The combination of Ca²⁺-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic use. Received: 7 January 1997 / Accepted: 25 February 1997     

New peritoneal dialysis solutions

Summary: Current peritoneal dialysis solutions are not biocompatible, particularly in respect to low pH, high osmolality and use of lactate. In addition, glucose is not an ideal osmotic agent. Recent advances in the formulation of peritoneal dialysis fluids aim to provide a more physiological environment to preserve membrane integrity. the effects of pH and lactate have been overcome by the use of bicarbonate based solutions whilst icodextrin (glucose polymers) often prolonged ultrafiltration in spite of being isomotic to uraemic plasma. Future formulations will see a combination of osmotic agents (including amino acids) and bicarbonate to achieve a more biocompatible solution whilst still meeting the ultrafiltration needs of the patients. Additives (glycosaminoglycans, procysteine) may protect the peritoneum from free radical injury.     

透明质酸钠玻璃体腔内充填在严重开放性眼球损伤治疗中的应用

目的 研究透明质酸钠玻璃体腔内充填对严重开放性眼球损伤预后的影响。方法 在严重开放性眼球损伤一期手术缝合后玻璃体腔内充填透明质酸钠至眼压Tn。结果 用透明质酸钠在玻璃体腔内充填，眼球萎缩的发生率（6．67％）明显低于用BSS液充填的发生率（70．58％）。结论 透明质酸钠玻璃体腔内充填在严重开放性眼球损伤治疗中的应用对眼球外形维持和视功能恢复有重要作用。     

复方华蟾胶囊抗小鼠肿中瘤作用的实验研究

目的了解复方华蟾胶囊抗小鼠移植性肿瘤的作用.方法以小鼠肝癌22(H22)、小鼠肉瘤180(S180)为瘤株,应用动物移植性肿瘤的体内试验法对药物进行抗癌药效学试验.结果复方华蟾胶囊灌胃4,2 g/kg@d,连续14 d,对小鼠移植性肝癌实体型生长有明显的抑制作用,抑瘤率分别为38.09%,30.95%.对小鼠移植性S180实体型生长有明显的抑制作用,抑瘤率分别为34.7%,30.08%.复方华蟾胶囊对荷瘤小鼠的胸腺和脾脏重量无影响.结论复方华蟾胶囊在试验条件下有一定抗肿瘤作用.     

苦碟子抗肿瘤作用的实验性研究

目的 研究苦碟子对动物移植性肿瘤的作用。方法 以小鼠移植性肉瘤180（S180)和艾氏腹水瘤（EAC）为模型，观察苦碟子的抗肿瘤作用，并分别计算出抑瘤率和生命延长率。结果 不同剂量的苦碟子对小鼠肉瘤S180的抑制率分别为39．86％，38．14％和35．73％（与对照组相比差异有显著性，P＜0．01），苦碟子也能延长荷艾氏腹水瘤（EAC）小鼠的存活期，生命的延长率分别为41．27％、29．79％和17．88％（高剂量组和中等剂量组与对照组相比差异有显著性，P＜0．01）。结论 苦碟子在动物体内可能具有抗肿瘤作用，可作为一种有前途的抗肿瘤药物进行研究。     

调整给药时间减轻顺铂肾毒性的研究

目的　观察不同给药时间对顺铂肾毒性的影响。　方法　 1 6例癌症患者分为两组各 8例 ,分别在上午 1 0时或下午 8时静滴 6 0mg m2 顺铂 ,3～ 4周后作第 2周期化疗时交换给药时间 ,以尿 β2 微球蛋白浓度作为肾小管功能改变的指标。　结果　治疗前两组的尿 β2 微球蛋白浓度均在 2 0 0 μg L以下。治疗后 ,上午 1 0时给药组的尿β2 微球蛋白浓度在第 1周期为 4 96± 6 6 μg L ,第 2周期为 5 0 4± 74 μg L ,下午 8时给药组分别为 2 77± 4 3μg L(t=3.6 6 ,P <0 .0 1 )和 2 83± 39μg L(t=3.6 3,P <0 .0 1 )。 　结论　不同时间给药对顺铂的肾毒性有显著影响 ,下午 8时给药可明显减轻顺铂的肾毒性。     

头孢西丁钠中甲醇残留量的顶空毛细管GC法测定

建立了顶空毛细管GC法测定头孢西丁钠中甲醇残留量，并探讨了药物结构中甲氧基对测定的影响。采用DM-624石英毛细管柱，检测器为FID。甲醇在0．02～5mg／ml浓度范围内，与峰面积线性关系良好（r=0．9999）。方法平均回收率为97．7％，RSD为1．8％。