L-2000,L-1600和HI-6抗小鼠梭曼中毒效能比较

目的　在小鼠上进行L 2 0 0 0 ,L 16 0 0及HI 6抗梭曼中毒效能 (PR)比较 ,为全面评价L 2 0 0 0的抗毒作用提供实验依据。方法　药物预防和急救小鼠梭曼中毒ED50 测定 ;药物急救小鼠梭曼中毒PR值测定 ;药物小鼠急性毒性测定。结果　①L 2 0 0 0预防小鼠梭曼中毒强度比L 16 0 0强 5 .2倍 ,比HI 6强2 .9倍。②L 2 0 0 0和L 16 0 0等剂量 (10mg·kg- 1)预防或急救小鼠梭曼中毒PR比较 ,两者差别均不显著。在等毒性剂量 (1/5LD50 )条件下 ,L 2 0 0 0比L 16 0 0强 ,两者差别显著 (P <0 .0 1) ,L 2 0 0 0不如HI 6强 ,两者差别显著 (P <0 .0 1)。③L 2 0 0 0 ,L 16 0 0和HI 6伍用抗胆碱能药L 16 0 2 +L 16 0 3,急救小鼠梭曼中毒 ,均有明显的协同作用 ,HI 6无论是等剂量(10mg·kg- 1)或等毒性 (1/5LD50 ) ,其抗毒效能大于L 2 0 0 0和L 16 0 0 (P <0 .0 1) ,L 2 0 0 0和L 16 0 0差别不显著。④以L 16 0 2 +L 16 0 3为底药 ,HI 6与L 2 0 0 0合用均比单独使用好 ,差别显著 (P <0 .0 5 ) ,说明两者有协同作用。⑤L 2 0 0 0预防或急救小鼠梭曼中毒时其治疗指数和安全系数均大于HI 6和L 16 0 0 ,其大小顺序是L 2 0 0 0 >HI 6 >L 16 0 0。结论L 2 0 0 0预防和治疗小鼠梭曼中毒效价强度比L 16 0 0和HI 6强 ,其治疗指数和安     

顺铂及注射用顺铂含量测定方法研究

顺铂为抗肿瘤药物 ,临床上主要用于治疗睾丸肿瘤及头颈部肿瘤等。中国药典采用炽灼重量法测定其含量。本文参照BP及USP色谱条件 ,采用HPLC法测定含量 ,结果满意。1 仪器与试药美国TSP高效液相色谱仪 ,附 :32 0 0泵 ,6 0 0 0LP检测器 ,PC10 0 0工作站。顺铂对照品由齐鲁制药厂提供 ;样品由德州制药厂提供 (0 2 0 4 0 1、0 2 0 4 0 2、0 2 0 4 0 3为顺铂 ,0 2 0 4 0 11、0 2 0 5 0 11、0 2 0 6 0 11为注射用顺铂 )。甲醇为色谱纯 ,其他均为分析纯。2 试验与结果2 1　色谱条件　色谱柱 ,NH2 柱 (30 0×4 6mm ,10 μm) ;流动相 :醋酸…     

醋酸铅对大鼠脑组织神经生长因子表达的影响

目的　研究醋酸铅对大鼠脑组织神经生长因子表达的影响。方法　对SD大鼠用 2 5、5 0、10 0mg/kg体重醋酸铅腹腔注射 5d ,石墨炉原子吸收法测定血清和脑组织中铅的含量 ;RT PCR和免疫组化方法分别观测脑组织中神经生长因子 (NGF)mRNA和蛋白含量的表达。结果　醋酸铅染毒后 ,血清和脑组织中铅含量迅速升高 ,与对照组相比 ,差异有显著性 (P <0 0 1,P <0 0 5 ) ;NGFmRNA表达在皮层中、高剂量组 (0 65± 0 0 9,0 744± 0 0 7)和海马各剂量组 (0 76± 0 13 ,0 80± 0 0 6,1 0 0± 0 0 4)显著高于对照组 (0 3 9± 0 10 ,0 3 9± 0 0 4) (P <0 0 5 ) ;中、高剂量组皮层组织NGF平均灰度(180 49± 10 3 3 ,169 72± 19 75 )与对照组 (2 0 0 75± 3 2 7)相比 ,差异有显著性 (P <0 0 5 ) ;各剂量组海马组织NGF面密度(0 0 9± 0 0 1,0 12± 0 0 2 ,0 13± 0 0 4)与对照组 (0 0 3± 0 0 1)相比 ,差异有显著性 (P <0 0 1)。结论　醋酸铅可以诱导大鼠脑组织中NGFmRNA的表达 ,并使NGF蛋白含量增加。     

奥硝唑葡萄糖注射液内毒素检测法实验研究

细菌内毒素检查法是近年来检测发热物质比较灵敏、准确的一种方法。本文就奥硝唑葡萄糖注射液用细菌内毒素检查法控制热原的可行性进行了试验研究 ,现报道如下。1　试验材料奥硝唑葡萄糖注射液 2 5 0 m L∶ 5 0 0 mg(批号0 0 0 70 5 ,0 0 0 71 4 ,0 0 0 72 7,陕西博华制药有限公司 )。细菌内毒素检查用水 (批号 W98- 1 ,中国药品生物制品厂 )。鲎试剂 (批号 0 0 0 90 9,0 .5 EU· m L-1 ,批号0 0 0 71 5 ,0 .2 5 EU·m L-1 ,批号 0 0 0 2 1 4 ,0 .1 2 5 EU·m L-1湛江海洋生物制药厂 )。鲎试剂 (批号 0 0 0 90 7,0 .2 5EU·m L-1 新北…     

颈椎安的制备、质量标准及临床应用

颈椎病是因椎间盘变性、颈椎骨质增生所引起的综合征。以颈肩疼痛、上肢麻木、肌肉无力、眩晕、猝倒、步履蹒跚 ,甚至四肢瘫痪为特征 ,属常见病、多发病。自 2 0 0 0年 1月至 2 0 0 2年 3月 ,我们用自制的颈椎安治疗该病 ,取得良好效果。现报告如下。1　处方与制备方法1 1　处方　当归 6 0g,川芎 5 0 g,三七参 4 0 g ,威灵仙 10 0g ,土鳖虫 5 0 g,蜈蚣 30条 ,桃仁 5 0g ,忍冬藤 6 0 g ,葛根 6 0 g ,羌活 6 0g ,煅自然铜 5 0 g ,昆布 5 0 g ,海藻 5 0 g ,乌药 5 0g ,丹参6 0 g ,苏木 5 0 g ,黄芪 6 0g ,蒲公英 10 0 g ,地丁 10 0 g ,野菊花15…     

对《中国药典》(2000年版)盐酸赖氨酸含量测定方法的改进

盐酸赖氨酸是氨基酸类药。《中国药典》 2 0 0 0年版收载的含量测定方法为非水滴定法 ,盐酸赖氨酸不易溶解 ,需要加热至 6 0～ 70℃ ,操作费时 ,而且导致结果偏低。本文采用醋酸汞试液溶解样品 ,操作简便 ,结果满意。1　仪器和试药ＰＨＳ - 3Ｃ数字酸度计 (上海雷磁仪器厂 ) ;醋酸汞、冰醋酸、高氯酸、醋酐均为分析纯 ;盐酸赖氨酸 ,批号 0 0 0 6 0 1、0 0 0 6 0 2、 0 0 0 6 0 3(南宁邕江制药厂提供 ) ;批号 0 0 0 5 10、0 0 0 5 11、 0 0 0 5 12 (南宁安力泰药业有限责任公司提供 )。2　方法与结果取本品约 80ｍｇ ,磨细 ,精密称定 ,加醋酸…     

异丙酚静脉麻醉用于人工流产镇痛500例观察

我院自 2 0 0 0年 9月至 2 0 0 1年 6月以异丙酚静脉麻醉用于人工流产术 (人流 )镇痛 ,取得良好效果 ,现报告如下。对象与方法一、对象 :自 2 0 0 0年 9月至 2 0 0 1年 6月对来我院要求人流而无禁忌证的孕妇 10 0 0例 ,随机分为两组。观察组5 0 0例采用异丙酚静脉麻醉行人流术 ,对照组 5 0 0例不用麻醉行人流术。观察组中初孕妇占 5 1 2 % (2 5 6 / 5 0 0 ) ,经产妇占 4 8 8% (2 4 4 / 5 0 0 )。对照组初孕妇占 5 0 4 % (2 5 2 / 5 0 0 ) ,经产妇占 4 9 6 % (2 4 8/ 5 0 0 )。两组年龄 18～ 4 5岁 ,孕 6～ 12周 ,一般资料无显著性差异 (χ2…     

我科1998—2000年废片原因分析

X线检查是临床辅助诊断不可缺少的手段 ,如何保证质量 ,减少受检者不必要的辐射 ,已成为放射工作的重要任务。为此 ,笔者对我科 1998～ 2 0 0 0年引起废片的原因进行分析。1　基本情况我科 1998～ 2 0 0 0年总共摄片数为 46 72 0张 ,废片 44 6张 ,废片率为 0 .95 % ;1998年废片率为 1.36 % ,1999年为 0 .98% ,2 0 0 0年为 0 .6 3% ;废片所占比重 ,1998年为 0 .38% ,1999年为 0 .34% ,2 0 0 0年为 0 .2 3%。随时间推移有下降趋势。2　废片原因分析见附表。附表　 1998～ 2 0 0 0年废片原因分析原因1998年 1999年 2 0 0 0年废片数 %废片数 %…     

注射用阿莫西林钠细菌内毒素检查方法探讨

注射用阿莫西林钠为《中国药典》2 0 0 0年版收载品种 ,热原检查方法为家兔法 ,笔者对该品进行了细菌内毒素检查方法探讨。1　材料注射用阿莫西林钠 (5 0 0 mg·瓶 -1,批号 :C2 0 0 1 0 4 3 6 ,C2 0 0 1 0 83 5 ,C2 0 0 1 1 0 0 2 ,哈尔滨制药总厂 ) ;鲎试剂 (灵敏度为 0 .5 EU· m L-1,批号为0 1 0 72 6 ;灵敏度为 0 .2 5 EU· m L-1,批号为 0 1 0 70 9,湛江海洋生物制品厂 ) ;细菌内毒素工作标准品 (1 0 0EU·支-1,批号 :2 0 0 0 - 7,中国药品生物制品检定所 ) ;细菌内毒素检查用水 (批号 0 0 0 3 2 0 ,湛江海洋生物制品厂 )。2　方…     

美沙酮合用氯硝西泮致严重中毒一例

患者 ,男 ,2 0a ,无业 ,初中文化。患者于 2 0 0 0年 4月开始烫吸海洛因 ,近 1a来改为静脉注射 1 0g·d- 1 ,入所体检无特殊 ,尿检吗啡 (+)。给予美沙酮替代递减治疗 ,每日 8:0 0和16 :0 0分 2次口服 ,d15 0mg ,d2 4 0mg,d335mg ,d 311∶0 0患者自诉头痛、畏寒、竖毛等不适 ,至 14∶0 0诉上述症状仍未缓解 ,当即予氯硝西泮注射液 2mg +5 %葡萄糖溶液 5 0 0ml静脉点滴 ,将 16 :0 0的美沙酮提前口服 ,约 0 .5h后入睡。 16∶0 0发现患者呼吸浅表 ,每分钟 4 - 6次 ,呼之不应 ,压眶反应消失 ,瞳孔直径 1 5mm。急予iv纳洛酮 0 .4mg,2min后呼吸增至…     

Application of data mining and visualization techniques for the prediction of drug-induced nausea in man

The therapeutic value of many drugs can be limited by gastrointestinal (GI) adverse effects such as nausea and vomiting. Nausea is a subjective human sensation, hence little is known about preclinical biomarkers that may accurately and effectively predict its presence in man. The aim of this analysis was to use informatics and data-mining tools to identify plausible preclinical GI effects that may be associated with nausea and that could be of potential use in its prediction. A total of 86 marketed drugs were used in this analysis, and the main outcome was a confirmation that nausogenic and non-nausogenic drugs can be clearly separated based on their preclinical GI observations. Specifically, combinations of common preclinical GI effects (vomiting, diarrhea, and salivary hypersecretion) proved to be strong predictors. The model was subsequently validated with a subset of 20 blinded proprietary small molecules and successfully predicted clinical outcome in 90% of cases. This investigation demonstrated the feasibility of data-mining approaches to facilitate discovery of novel, plausible associations that can be used to understand drug-induced adverse effects.     

Interaction of apomorphine and haloperidol: Effects on locomotion and other behaviour in the marmoset

The behavioural effects of increasing doses of apomorphine and haloperidol were observed in a group of six marmosets. Behaviour was classified quantitatively into categories: Locomotion, inactivity, checking (small head movements), social interaction and purposeful activities. Statistical analysis revealed that apomorphine had a stimulant effect on checking and locomotion which could be antagonized by haloperidol. Activities and social contact were severely reduced by both apomorphine and haloperidol. Inactivity was increased by the lowest dose of apomorphine in otherwise untreated animals. It is suggested that haloperidol antagonizes the stimulant effects of apomorphine but is synergistic to its suppressant effects, and that the low dose effect of apomorphine on inactivity is mediated by a mechanism which may be different from that acted upon by haloperidol.     

On the issue of drug washout prior to polysomnographic studies in depressed patients.

In psychoneurobiological studies it is a point of controversy how long psychoactive medication has to be withdrawn to exclude drug effects on the variables to be investigated. In order to answer the question of whether the generally assumed two-week washout of psychoactive medication is sufficient for polysomnographic studies, we computed a post hoc analysis of EEG sleep recordings in 61 newly admitted depressed patients. The results indicate that after a 2-week withdrawal of tricyclic antidepressants and/or benzodiazepines there are no major drug effects on visually scored polysomnograms. In addition, the observations raise the question of whether even a 1-week drug washout may be sufficient to exclude confounding effects of prior psychoactive medication on EEG sleep.     

Flavonoid content assay: influence of the reagent concentration and reaction time on the spectrophotometric behavior of the aluminium chloride--flavonoid complex.

The spectrophotometric assay based on aluminum chloride complex formation is one of the most commonly analytical procedures applied to flavonoid content determination. However, only a few optimization studies on the reaction conditions were done so far. The present work aims to the investigation of aluminum chloride concentration and reaction time effects on the spectrophotometric behavior of different flavonoids. The effects of both variation factors were studied by Central Composite Design and Response Surface Analysis methodology. The absorption data analysis showed that the effects of reaction time and reagent concentration on the absorption maximum are intricate and specific. A clear relationship between spectrophotometric behavior and flavonoid type or particular structure patterns could not be established.     

Comparison of the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat

Some of the dioxolanes produce pharmacological effects that have much in common with phencyclidine and phencyclidine-like drugs. Dioxadrol can be resolved into two enantiomers, dexoxadrol and levoxadrol. Dexoxadrol has an affinity for phencyclidine receptors that is much greater than that of levoxadrol, but dexoxadrol and levoxadrol have nearly equal affinities for sigma receptors. The systematic analysis of the relative potencies of dexoxadrol and levoxadrol can be used as an approach to define effects mediated by phencyclidine vs sigma receptors. Compounds that act on phencyclidine receptors, as well as affecting behavior, alter body temperature in the rat. The purpose of the present study was to compare and contrast the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat. Dexoxadrol and levoxadrol (5.0, 10.0, 20.0 or 40.0 mg/kg), MK-801 (0.12, 0.6 or 1.2 mg/kg) or phencyclidine (5.0, 10.0 or 20.0 mg/kg) were administered subcutaneously and body temperature was measured. Both dexoxadrol and MK-801 produced hyperthermia but levoxadrol did not affect body temperature. In contrast to the hyperthermic effects of dexoxadrol and MK-801, phencyclidine produced hypothermia. These findings indicate that hypothermia induced by phencyclidine is not due to interactions with phencyclidine receptors and, while dexoxadrol, MK-801 and phencyclidine may share some similar receptor binding and behavioral characteristics, they can be differentiated on the basis of their effects on body temperature.     

法匹拉韦治疗新型冠状病毒肺炎的可行性分析

目的 探讨法匹拉韦治疗新型冠状病毒肺炎(COVID-19)的临床可行性。方法 针对从已上市/已进入临床研究的药物中挖掘出的、可能具有抗新型冠状病毒(SARS-CoV-2)作用的药物之一法匹拉韦,结合其作用机制、临床应用史和临床疗效及安全性试验进行可行性分析。结果 与结论法匹拉韦为国内首个在疫情期间批准上市的抗病毒药物,适应证为成人新型或再次流行的流感。经可行性分析,其对多种RNA病毒疗效显著,且不良反应也较少,从理论上对SARS-CoV-2也有作用,但有待更大规模的临床试验进行验证。     

吸入麻醉药“浓度效应”的定量分析

目的:对吸入麻醉药的浓度效应做出定量分析。方法:利用热力学的宏观理论和高等数学的思维方法,分三个层面讨论浓度效应:肺泡内麻醉药的浓度与吸入浓度的关系;肺泡内麻醉药的分压与吸入浓度的关系;血液中麻醉药的分压与吸入浓度的关系。结果:吸入浓度越高,肺泡内麻醉药的浓度升高越快,肺泡内麻醉药的分压和血中麻醉药的分压也上升的越快。结论:浓度效应的存在能用数学物理的方法给予证明。     

Statistical analysis of the effects of common chemical substituents on ligand potency

The results of a statistical analysis of more than 84,000 compounds from lead optimization programs against 30 different protein targets is presented, with a focus on the effects that different chemical substituents have on compound potency. It is observed that the potency changes induced by most chemical groups follows a nearly normal distribution centered near zero (i.e., no effect on potency). However, the widths of the distributions vary significantly between different substituents, and these effects cannot be rationalized by simple physicochemical parameters. In addition, certain substituents consistently bias the distribution toward higher or lower potency, suggesting the existence of preferred and nonpreferred chemical groups for lead optimization. The implications of these results for understanding protein-ligand recognition and for enhancing the efficiency and speed of lead optimization will be discussed.     

Relative quantification of the proteomic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model

Zearalenone (ZEN) is a mycotoxin with endocrine disrupting effects having vast economic implications in e.g. pig farming. Structurally, ZEN resembles 17β-estradiol, and thus is able to bind to estrogen receptors (ER) in target cells. Because of this, it is also classified as a non-steroidal estrogen, a phytoestrogen, a mycoestrogen, and a growth promoter. Quantitative proteomic analysis was undertaken using stable-isotope labeling by amino acids in cell culture (SILAC) upon exposure of the steroidogenesis cell model H295R with ZEN to elucidate its effect on protein regulation. ZEN significantly regulated 21 proteins, including proteins with known endocrine disrupting effects and several oncogenes. In addition, network analysis using Ingenuity Pathway Analysis showed that ZEN affected the oxidative phosphorylation pathway and the mitochondrial dysfunction pathway, both previously reported to be involved in endocrine dysfunction.