常用抗生素对部分致病大肠埃希菌的抗菌活性检测

目的 通过检测21种常用抗生素对部分致病大肠埃希菌的体外抗菌活性及细菌产β-内酰胺酶情况,以协助临床医生正确选用抗生素治疗大肠埃希菌感染。结果 多数菌株属于多重高度耐药株且产β一内酰胺酶。大部分菌株均耐受青霉素类药物;复方哌拉西林/舒巴坦的抗菌活性则明显提高;舒巴哌酮、第三代头孢菌素的抗菌活性都较高;所有菌株均对碳青霉烯类美罗培南敏感;妥布霉素、新的第三代喹诺酮类中的氟罗沙星和第四代喹诺酮类妥舒沙星、司帕沙星的抗菌活性都较高。结论 使用青霉素类或头抱菌素类时合用酶抑制剂可明显提高疗效;美罗培南的疗效最佳;新的第三代和第四代喹诺酮类的疗效较好。临床医生最好先获得细菌的药敏报告,再选用适当的抗生素进行治疗。     

The effects of compounds related to γ-aminobutyrate and benzodiazepine receptors on behavioural responses to anxiogenic stimuli in the rat: Extinction and successive discrimination

In a first set of experiments rats were trained to run in a straight alley for food reward on a continuous reinforcement schedule and the running response was then extinguished. On the last 2 days of training and daily throughout extinction different groups of animals were injected IP with saline, 5 mg/kg chlordiazepoxide, 0.75 mg/kg picrotoxin, chlordiazepoxide + picrotoxin, chlordiazepoxide +1.5 mg/kg bicuculline, 0.00125 or 0.25 mg/kg muscimol, 1 mg/kg baclofen, chlordiazepoxide + baclofen, or 0.00125 mg/kg muscimol + baclofen. Chlordiazepoxide increased resistance to extinction, a well-known anxiolytic effect. This effect was blocked by both picrotoxin and bicuculline. Picrotoxin on its own reduced resistance to extinction (an anxiogenic-like effect). Whether given alone or in combination with other drugs, muscimol and baclofen had no effect.In a second set of experiments rats were trained in a successive operant discrimination (signalled by a flashing or steady light) between components in which sucrose reward was available on a variable-interval schedule for barpressing and components in which no reward was given. Chlordiazepoxide at 10 mg/kg increased responding in both rewarded and nonrewarded components, but more in the latter than could be accounted for by change in the former. This effect is as expected with an anxiolytic drug. It was not altered by administration of bicuculline at 1.5 or 1.75 mg/kg; at 2 mg/kg bicuculline acted synergistically with chlordiazepoxide. Picrotoxin (1 and 1.5 mg/kg) also acted synergistically with chloridazepoxide, enhancing the latter's rate-increasing effects, but only during rewarded components. Neither muscimol (0.00125 and 0.25 mg/kg) nor baclofen (0.01 mg/kg) affected response rates, whether given alone or in combination. However, baclofen in a dose of 1 mg/kg, provided it was given to rats also injected with muscimol (0.00125 or 0.25 mg/kg) at other times, significantly reduced responding during nonrewarded components (an apparently anxiogenic effect).The results of the two sets of experiments are discussed in relation to the hypothesis that anxiolytic drugs affect behaviour by increasing GABAergic inhibition. Offprint requests to: C. Buckland     

聚碳酸酯聚氨酯弹性体的模拟生物老化性能的研究

研究了聚碳酸酯聚氨酯的水解剂，氧化，钙化等生物老化性能，并与聚醚聚氨酯样品做了比较，结果表明，胺扩链样品具有较好的耐水解性能，聚碳酸酯氨酯的抗氧化性能优于聚醚聚氨酯，同了聚醚氨酯一样，聚碳酸酯聚氨酯同样受钙的影响，含水氯化钙对聚碳酸酯聚氨酯的相结构产生影响，并对弹性具有增强作用。     

The Interaction Between the Indirect Anticoagulant Coumatetralyl and Calciferol (Vitamin D3) in Warfarin-resistant Rats (Rattus norvegicus)

Resistance to 4-hydroxycoumarin anticoagulant rodenticides has been a problem in some local foci for a number of years. One method of managing resistance could be to use synergists in conjunction with anticoagulants. We investigated the effect of administering cholecalciferol and coumatetralyl alone and in a synergistic mixture to anticoagulant-resistant rats by monitoring plasma factor X concentrations. The study showed that the efficacy of the compounds was significantly improved when they were used together. This synergistic effect led to an increased mortality in female rats that had been treated with both compounds compared to both a control group and groups of rats that had received the compounds singly. An unexpected result from this work was that cholecalciferol when given on its own to rats caused a decrease in plasma factor X concentration. We hypothesise that this effect was due to a vitamin D-induced increase in production of vitamin K-dependent proteins leading to a saturation of the carboxylation process and hence to a significant number of factor X molecules being under-carboxylated and therefore dysfunctional. It is suggested that the reduction in factor X levels is a major component of the increased efficacy of the anticoagulant/calciferol mixture and also that effects on other vitamin K-dependent proteins, e.g. matrix GLA protein, may play a role in the increased mortality seen in female rats.  This work illustrates that synergists could be utilised in managing anticoagulant resistance. There are also possible implications for human patients on anticoagulant therapy who may be receiving increased amounts of vitamin D analogues through, for example, dietary supplements.     

Resistant mechanisms of cisplatin in human lung adenocarcinoma cell line A549DDP

To study the resistant mechanisms of cisplatin in human lung adenocarcinoma cell line A₅₄₉DDP. A₅₄₉DDP cells was established by stepwise increasing concentration of cisplatin (CDDP) in medium. Interstrand cross-linked DNA (ICL) was measured by ethidium bromide fluorescence assay. The intracellular and intranuclear accumulation of cisplatin was measured by atomic absorption spectrometry. The removal of GS-X was determined by FCM and fluorescence microscopy. Results: The A₅₄₉DDP cell line was 8.9-fold resistance relative to the parental A₅₄₉ cell line. The formation of ICL in A₅₄₉ was 6.28 times higher than that in A₅₄₉DDP cells. The intracellular and intranuclear accumulation of cisplatin in A₅₄₉ cells was 5.9 times and 4.1 times higher than that in A₅₄₉DDP cells, respectively. The ability of GS-X pump pumped GS-X complex (GS-Pt) in A₅₄₉DDP cells was higher than that in A₅₄₉. The repair rate in A₅₄₉DDP cells was 2 times higher than that in A₅₄₉. Conclusions: Decreased accumulation and increased export of cisplatin might be the main mechanism of cisplatin resistant A₅₄₉DDP cells while the enhanced repair capacity of DNA may play a role in CDDP resistance.     

肺动脉血流指数及肺表面活性蛋白水平对重度子痫前期合并妊娠期糖尿病孕妇围生儿肺成熟度的临床应用价值

目的探讨胎儿肺动脉血流指数,如肺动脉搏动指数(PI)及阻力指数(RI),以及新生儿脐血中肺表面活性蛋白(SP)-A、-B水平,对重度子痫前期(sPE)合并妊娠期糖尿病(GDM)孕妇的围生儿肺成熟度的评估价值。 方法选择2018年1月至2019年10月,于吉林大学第二医院分娩的sPE合并GDM孕妇的60例围生儿为研究对象。根据新生儿出生胎龄,将其分为A组(n＝22,出生胎龄≥37周),B组(n＝20,35周≤出生胎龄<37周)和C组(n＝18,出生胎龄<35周)。采用Kruskal Wallis H秩和检验及Mann-Whitney U检验,对3组胎儿肺动脉PI及RI,新生儿脐血中肺SP-A、-B水平,以及新生儿生后1 min Apgar评分及出生体重,分别进行总体比较及两两比较;采用χ²检验,对3组新生儿呼吸窘迫综合征(NRDS)发生率,进行总体比较及两两比较;采用Spearman秩相关分析法,对3组受试儿PI、RI、SP-A、SP-B、生后1 min Apgar评分及出生体重分别与出生胎龄进行相关性分析。本研究经吉林大学第二医院伦理委员会批准[审批文号：2019年研审第(111)号],并与所有受试儿监护人签署临床研究知情同意书。 结果① A、B、C组胎儿肺动脉PI及RI、新生儿脐血肺SP-A及SP-B水平总体比较,差异均有统计学意义(P<0.05);其任意2组的两两比较,差异亦均有统计学意义(P<0.05),并且随着出生胎龄增加,胎儿肺动脉PI及RI降低,新生儿脐血中肺SP-A、-B水平增高。②A组与B组新生儿的生后1 min Apgar评分及出生体重[9分(9~9分)、3 010 g(2 777~3 802 g)与9分(8~9分)、2 680 g(2 000~3 427 g)],均分别高于C组的8分(8~8分)、1 660 g(1 500~2 005 g),而NRDS发生率(4.5%、20.0%),则均分别低于C组的66.7%,并且差异均有统计学意义(A组vs C组：Z＝28.242、30.202,χ²＝17.415;B组vs C组：Z＝19.433、21.111,χ²＝8.464;P均<0.001)。A组与B组上述3项指标比较,差异均无统计学意义(P>0.05)。③胎儿肺动脉PI及RI均与出生胎龄呈负相关关系(r_s＝—0.780、—0.856,P均<0.001);新生儿脐血中肺SP-A、-B水平,生后1 min Apgar评分及出生体重,均与出生胎龄呈正相关关系(r_s＝0.842、0.872、0.689、0.820,P均<0.001)。 结论胎儿肺动脉PI及RI,以及新生儿脐血中肺SP-A、-B水平,可作为评估sPE合并GDM孕妇的围生儿肺成熟度的指标。     

Micro-RNA149 confers taxane resistance to malignant mesothelioma cells via regulation of P-glycoprotein expression

Multidrug resistance (MDR) represents a major hindrance to the efficacy of cancer chemotherapeutics. While surgical resection, radiation, and chemotherapy can be used to reduce tumor size, the subsequent appearance of drug resistant cells is a frequent problem. One of the main contributors to the development of MDR is increased expression of multi-drug resistant protein 1 (MDR1), also known as P-glycoprotein (P-gp). P-gp is a membrane-associated efflux pump that can efficiently remove internalized taxane-base chemotherapeutics thus preventing drug accumulation and maintaining cellular viability. Consequently, investigation into the molecular mechanisms responsible for regulation of P-gp expression is necessary to facilitate treatment of MDR tumors. Using molecular and biochemical approaches, we identified that the micro-RNA, miRNA149, contributes to the development of MDR within malignant mesothelioma cells by regulating the expression of MDR1.     

'In vitro' development of metronidazole, erythromycin, amoxicillin and gentamicin resistance in Helicobacter pylori

Serial passage of 37 Helicobacter pylori clinical isolates on increasing concentrations of metronidazole rapidly produced five strains with MICs up to 512 fold higher than those for the original strains. For these five metronidazole-resistant strains the MICs of erythromycin, gentamicin and amoxicillin were unchanged. When they were submitted to the same technique for these last antimicrobial agents, only one strain developed high level resistance to erythromycin and gentamicin having MIC values respectively up to 32 and 64-fold increased. Finally, no amoxicillin-resistant Helicobacter pylori could be obtained.