原发性高血压合理用药类别筛选模型的建立和检验

目的:建立原发性高血压合理用药类别筛选模型并检验其在实践中的应用。方法:抽取大连医科大学附属第二医院2017年3月至2018年12月心内科门诊和住院的原发性高血压患者的医嘱记录,共计4 597条,再从以上记录中筛选出满足纳入标准的549条记录。医嘱记录均为高血压治疗达标患者,且为单药治疗,患者信息完整。判别分析模型建立过程中,分组变量的选择是根据管理学80/20法则找出占比例80%以上的药物分类,自变量的选择是采用单变量分析的方法筛选。用549条记录中的384条(70%)建立模型,求解判别函数,剩余165条(30%)用于训练模型,以验证模型的预测效果。结果:分析得出,纳入病例中血管紧张素类、β受体阻滞剂类、钙拮抗类三类药品的应用合占所有用药类别的94%,将它们作为判别分析的分组变量,然后从10个自变量中采用单变量分析方法筛选出对用药分类筛选具有显著统计学意义的自变量,结果年龄、就诊时情况、既往用药和主要合并疾病被选为自变量(P<0.05),用于建模,模型拟合良好,可以进行原发性高血压合理用药类别筛选。通过验证,该模型的准确率在50%左右。结论:原发性高血压合理用药类别筛选模型可提高原发性高血压治疗中的合理用药水平。

Application of Microcalorimetric Technique for the Screening and Examination of Medicines

According to the heating effect caused by interaction between matters,a series of experiments on the interaction between drugs and cells from human bodies,DNA and physiological saline have been carried out with a MS-80 standard Calvet microcalorimeter.The experiments include: (1) Thermokinetic studies of the effect of anticancer drugs [sodium norcantharidate (ASN),the bioac- tire materials (Sp.P and Sp.S) from algae etc.]on the cancer cells [Hela,human breast carcinoma (Bcap-37),human adenocarcinoma gastric cells (SGc-7901 and MCF-7) etc.] and the normal cells from human bodies [diploid fibroblasts from human fetal lung (2BS) etc.] at 310.15 K:(2) Studies of the in- tercalation binding of some alkaloidal drugs with the bioactivity to inhibit monoamine oxidase (harmalinc and harmine etc.) to call thymus DNA in neutral aqueous solution at 298.15 K:(3) Studies of the interaction between long acting drugs (long acting oral contraceptive-norgestrel etc.) and slow- releasing drug (Contac) and aqueous solution of 0.9% NaCI at 310.15 K.All the experimental results have given their characteristic thermograms and the interaction enthalpy changes.On the analysis of all the results,the authors put forward a method on application of microcalorimetric technique for screen- ing and examination of medicines.The principle of application and the experimental operation of this method have been expounded,and some results of the above experiments have been discussed.As one of the methods for screening and examining medicines,the microcalorimctric method has some distin- guished features and advantages over other methods.

荧光定量PCR法与培养法检测女性不育症解脲支原体的比较评价

目的评价荧光定量PCR与培养法检测女性不育症解脲支原体方法,并筛选解脲支原体感染的治疗药物。方法应用PCR法和培养法检测351例女性不育症患者和201例正常生育妇女的解脲支原体,同时对11种抗菌药物作药敏试验。结果在不育症患者中荧光定量PCR和培养法检测UU阳性率分别为55.3%和42.7%,已生育妇女的UU阳性率分别为30.3%和24.9%。PCR法检出率明显高于培养法,P<0.01,11种药物敏感试验结果UU培养法阳性者对大环内酯类克拉霉素最敏感为96.4%,对喹诺酮类环丙沙星耐药性最高为60.1%。结论荧光定量PCR对UU检出率高且快,培养法检测虽慢,可同时作药敏试验为临床指导选择用药。

INTRODUCTION OF THE HIGH THROUGHPUT SCREENING SYSTEM

In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised.

Antibacterial Screening of Fifteen Cameroonian Medicinal Plants against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi

Multi-drug resistant microbial infections caused by Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi represent a critical public health issue worldwide. Plant-derived agents are credible sources for search and development of alternative antimicrobials to fight these infections. This study describes the in-vitro antibacterial activity of plants extracts from 15 medicinal plants of the Cameroonian pharmacopeia against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. Plants selected based on their ethnopharmacological uses were extracted by either maceration or decoction using distilled water, ethanol, methanol and ethylacetate. The afforded extracts were phytochemically screened for bioactive secondary metabolites. The microdilution method was used to assess the antibacterial activity. The two promising extracts were tested in combination using the cbeckboard technique. Eighty one extracts showed antibacterial activity with eight having minimum inhibitory concentrations below 2.5 mg/mL. Results from combination assays with extracts from Terminalia catappa and Gnidia glauca leaves showed synergistic effect against Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi and additive effect against Staphylococcus aureus. These extracts mainly contained saponins, tannins, glucosides, phenols, triterpenes and anthraquinones. These results support the ethnobotanical claims and indicate further directions for the investigation of plants extracts to develop alternative drugs against multi-resistant bacteria.

A new method of immobilizing HEK293 cells on the inner wall of a capillary column as stationary phase for drug screening

It is a new strategy to immobilize cells on the inner wall of a capillary column and use affinity capillary electrophoresis（ACE） to study receptor-ligand interactions or to screen natural products and compounds synthesized by combinatorial chemistry. In this paper, we developed a new method of immobilizing HEK293 cells on the inner wall of a capillary column. Four important experimental conditions were optimized, including cell injection density, PLL concentration, cell culturing time and sterile processing method. Immobilized cell-coated capillary columns prepared under the optimized experimental conditions exhibited good uniformity, stability and durability, which were suitable for capillary electrophoresis. The method could also be used to immobilize HEK293 cells over-expressing certain membrane receptors on the inner wall of a capillary. In this way, cell-coated capillary columns could be applied to ACE drug screening targeting certain membrane proteins.

Study of parameters affecting infection risk from contaminated injectable products using multiple spot contamination model: a case study of insulin vials

Infections of patients from consumption of contaminated pharmaceutical products constituted major health risk problems. Medicinal products are liable to microbial intrusion during in-use application. The current study focused on repeated contamination with constant level of microbiological burden by two bacteria viz. Staphylococcus aureus and Pseudomonas aeruginosa were used as dose-response models for infection through two different routes of administration. Nine different forms of insulin vials were subjected to this type of simulation study at constant assumed level of contaminations, preservative efficacy test(PET) and dose potency. Multi-spot contamination imitation study showed that initial fast rise in contamination, followed shortly by longer but steeper slope which finally turned into higher rate of contamination during the few last doses of the unit dosage forms, where the volume of the product became increasingly and progressively very small. When the probability of infection curves was constructed, both S. aureus and P. aeruginosa showed same pattern, with notably higher risk from septicemia route of the latter rather than subcutaneous route of the former. The present simulation study showed that continuous use of the same contaminated syringe progressively increased the risk of infection, especially at final few doses(between 3th and 10 th last doses depending on the dosage form sizes in the vials and the administration volumes) of the product. Small volume parenterals(SVP) are especially products at higher risk than the larger volume ones.