In Vitro Antibacterial Activity of the New Quinolone Bay y3118 against Clinical Isolates

Summary

The in vitro antibacterial activity of the new fluoroquinolone Bay y3118 against 609 clinical isolates was evaluated. Bay y3118 exhibited activity against a broad spectrum of organisms, including Gram-negative bacilli, Gram-positive cocci, mycobacteria. The activity of Bay y3118 was often superior to that of other quinolones. Against Gram-negative bacilli its activity was similar to that of ceftriaxone, cefotaxime, ceftazidime and imipenem except for Serratia marcescens, Klebsiella pneumoniae, Enterobacter spp. and Xanthomonas maltophilia, where its activity was superior. Gentamicin and piperacillin sometimes were less active. Bay y3118 was active against a large number of Gram-positive cocci. The fluoroquinolones tested were active against all the strains of Mycobacterium tuberculosis, but only Bay y3118 was effective against Mycobacterium avium.     

Comparative Study of the In Vitro Antibacterial Activity of Ciprofloxacin and Thirteen other Antimicrobial Drugs with Respect to Recently Isolated Pathogens

Summary

The in vitro antibacterial activity of ciprofloxacin and 13 other antimicrobial drugs was evaluated with respect to 569 pathogens, mainly isolated from urine. Ciprofloxacin was found active in 96.1% of all of the Gram-positive and Gram-negative strains tested, amikacin in 90.6%, ceftazidime in 89.8%, ceftriaxone in 85.3%, piperacillin in 82.7%, tobramycin in 82.6%, gentamicin in 81.5%, aztreonam in 78.3%, nitrofurantoin in 72.6%, cotrimoxazole in 71.6%, cinoxacin in 71.0%, pipemidic acid in 70.6%, nalidixic acid in 66.7%, ampicillin in 50.1%. Ciprofloxacin was found to be the most active of the drugs studied against the bacterial strains which cause urinary, respiratory and other infections.     

In Vitro Activity of Vinorelbine on Human Leukemia Cells

Abstract

Vinorelbine (VNR) is a semi-synthetic Vinca rosea alkaloid that has been employed both as a single agent and in combination, and has shown significant antitumor activity. As little is known about VNR activity on human leukemia, we studied its In Vitro cytotoxic effect on human leukemia cell lines (FLG 29.1, HL60, K562, Balm 4, CEM and Daudi) and on fresh leukemia cells from 28 patients: 2 acute myeloid leukemia (AML); 3 chronic myeloid leukemia in blas-tic phase (CML-BP); 5 acute lymphoblastic leukemia (ALL); 18 B-chronic lymphatic leukemia (B-CLL), employing the colorimetric INT assay and determining the IC₅₀.

We observed that VNR exerts its cytotoxic activity on leukemic cell lines in a dose-dependent fashion. The lymphoid cell lines appear more sensitive than the myeloid ones to the VNR-dependent growth inhibition.

A similar pattern was noticed for leukemia cells in primary cultures. VNR is not effective on CML-BP cells, shows variable activity on the AML and ALL cells and is very effective against B-CLL cells. VNR inhibited the growth of fresh B-CLL cells from 15 of 18 patients, the IC₅₀ doses ranging from 4 ng/ml to 83 μg/ml (doses coinciding with the plasma levels obtained in clinics). These observations strongly suggest that VNR could be useful in clinics for the treatment of B-CLL.     

Comparative In- Vitro Activity of Piperacillin and Piperacillin Plus Tazobactam Towards Beta-Lactamase Producing Clinical Isolates

Summary

The authors evaluated the in-vitro antibacterial activity of piperacillin alone and of piperacillin combined with tazobactam, a new beta-lactamase inhibitor, on 398 clinical isolates, both Gram-positive and Gram-negative. The piperacillin/tazobactam combination was evaluated in the fixed ratio 8:1. The vast majority of the microorganisms tested had reduced susceptibility to piperacillin (minimum inhibitory concentration (MIC) range 0.12— > 256 mg/1) due to beta-lactamase production.

The following results were obtained: against Haemophilus influenzae, tazobactam was effective in reducing the MICs of piperacillin by 512 fold. The activity of piperacillin/tazobactam was lower against Pseudomonas sp., while some activity was demonstrated against some strains of Klebsiella. Good activity was seen not only against methicillin-susceptible (MS) staphylococci but also against some methicillin-resistant (MR) strains. In the latter, the combination of piperacillin/tazobactam was active only if the strains showed beta-lactamase production. These findings are interesting above all in regard to the synergistic effect demonstrated against MR beta-lactamase producing staphylococci and the Klebsiella-Enterobacter-Serratia (KES) group.     

The Antitumor Activity of Meisoindigo against Human Colorectal Cancer HT-29 Cells In Vitro and In Vivo

Abstract

The study was conducted to examine the antitumor activity of meisoindigo on HT-29 cells In Vitro and In Vivo. The cytotoxicity of meisoindigo was evaluated by MTT assay. The related genes and proteins were inspected with RT-PCR and western blot assay respectively, and the effects of meisoindigo on the cell cycle were analyzed by flow cytometry. The efficacy of meisoindigo In Vivo was evaluated in an HT-29 cell xenograft nude mice model. The results show that meisoindigo effectively inhibits HT- 29 cell proliferation (IC₅₀ 4.3 mmol/L), arrests HT-29 cells in G2/ M phase and induces HT-29 cell apoptosis. The downstream genes and proteins of GSK-3β(ser⁹) expression level decrease. Meisoindigo significantly inhibits the HT-29 xenograft tumors growth at the dose of 100 mg/kg. The mechanism of meisoindigo activity against HT-29 cells may be related to its inhibition of glycogen synthase kinase-3β, GSK-3β(ser⁹) phosphorylation in Wnt signaling pathway. These findings indicate the potential value of meisoindigo for the treatment of colorectal cancer.     

Evaluation of Moxifloxacin Activity In Vitro Against Mycobacterium tuberculosis,Including Resistant and Multidrug-Resistant Strains

Abstract

The new quinolone moxifloxacin was tested against 86 strains of Mycobacterium tuberculosis including 13 resistant and 4 multiresistant strains. The antimicrobial susceptibility was tested, in parallel, using two different liquid media, the radiometric Bactec 12B and the Mycobacteria Growth Indicator Tube (Becton Dickinson, USA). All strains but two were susceptible at 0.5 μg/ml of moxifloxacin; for the remaining two strains, both multidrugresistant, the minimal inhibitory concentrations (MIC) were =2 and >4 >g/ml respectively. Our data confirm the high antitubercular in vitro activity of moxifloxacin.     

Antibacterial Activity of the Dialysates and Sera during Treatment with Chemotherapeutic Combinations in Continuous Ambulatory Peritoneal Dialysis (CAPD)

Summary

In everyday clinical practice, different chemotherapeutics are mostly applied intraperitoneally in treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Antibacterial activity of the dialysates and sera were studied, according to their bacteriostatic effect after the intraperitoneal and/or peroral administration of chemotherapy. All samples were tested by the two-fold dilution method. We found that the best therapeutical effect is obtained by applying the combination of two compatible chemotherapeutics, in which the first acts in the peritoneal cavity, and the other represents the «pool» of chemotherapeutics forming a barrier to the spreading of bacteria into other distant parts of the body.     

CEA和MGAgs联合检测对腹水鉴别诊断的价值

为探讨 CEA和 MGAgs对良恶性腹水的鉴别诊断价值 ,同期检测 30例良性腹水和2 7例恶性腹水中 CEA和 MGAgs的含量。结果显示 ,CEA和 MGAgs诊断恶性腹水的敏感性分别为 5 5 .6 %和 5 9.7% ,特异性为 10 0 %和 96 .7% ,准确度为 78.9%和 78.9%。联合检测的敏感性、特异性和准确度分别为 77.8%、96 .7%和 87.7%。 CEA和 MGAgs联合检测对良恶性腹水有较高鉴别诊断价值。     

重组人canstatin表达产物的抗肿瘤活性鉴定

 目的　正确构建人canstatin原核表达载体 ,诱导表达重组人canstatin融合蛋白 ,并对其活性鉴定。方法　将人canstatincDNA亚克隆入 pQE30 ,构建重组质粒 pQE30 canstatin ;转化M 15 [pREP4] 中 ,IPTG诱导表达 ,纯化回收表达产物 ,复性后用Lewis肺癌移植瘤模型对其活性鉴定。结果　成功构建人canstatincDNA表达载体 ,纯化回收 ,获得高纯度canstatin重组蛋白。纯化产物在体内能抑制Lewis肺癌移植瘤血管的生成 ,从而抑制肿瘤生长和转移 ,抑瘤率 (% )为 6 0 .0 % ,转移抑制率 (% )为 74 .3%。结论　 (1)成功构建了原核表达载体 pQE30 canstatin。 (2 )重组人canstatin融合蛋白在原核表达系统中高水平表达 ,并获得高纯度canstatin重组蛋白。 (3)重组canstatin融合蛋白可抑制Lewis肺癌移植瘤血管的生成 ,从而抑制肿瘤生长和转移活性。     

In vitro and In vivo Antitumor Activity of Tiliacorinine in Human Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with IC50 4.5-7 μM by inducing apoptosis through caspase activation, upregulation of BAX, and down-regulation of BclxL and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment.     

放射线照射后NK-92 细胞对人宫颈癌细胞体外杀伤活性的研究

 目的 研究放射线照射后NK-92细胞对人宫颈癌细胞的体外杀伤活性。方法 应用医用电子直线加速器对NK-92细胞进行照射处理(0、400cGy)后，以体外培养人宫颈癌细胞系Hela为靶细胞，以NK-92的敏感细胞株K562作为对照，应用4h^51Cr释放法检测不同效靶比情况下NK-92细胞的杀伤活性。结果 NK-92细胞0cGy照射组，效靶比较低时(1：1、5：1)对Hela细胞杀伤率为15％～33％，随效靶比升高，杀伤率随之上升，10：1时杀伤率显著上升为47％，20：1时杀伤率仅上升了3％；对于K562细胞，杀伤率为33％～69％。400cGy组照射后2d，NK-92细胞对Hela细胞不同效靶比的杀伤率与0cGy组相比稍有降低，其总体杀伤率为14％～47％，对K562细胞杀伤范围在30％～60％之间。结论 放射线照射后的NK-92细胞对人宫颈癌Hela细胞系具有一定的杀伤活性。     

In Vitro Activity of Lomefloxacin (SC-47111) Against Enterobacteriaceae,Enterococci and Staphylococci

Summary

The activity of lomefloxacin, a new difluorinated quinolone, was tested against 190 Enterobacteriaceae strains (belonging to 23 different species), 70 enterococci and 70 staphylococci. As regards Enterobacteriaceae, the activity of lomefloxacin was the same as that of norfloxacin in 9 out of the 23 species tested, and only slightly lower in further 8 species. Minimum inhibitory concentrations (MIC) values for 90% of strains were 0.5 μg/ml in 2 species, 0.25 μg/ml in 6, 0.125 μg/ml in 4, and lower than 0.125 μg/ml in 8. Slightly higher values were obtained for Serratia marcescens (2 μg/ml), whilst, as already reported for the other new quinolones, the susceptibility of the Providencia genus was very poor, with MIC values up to 128 μg/ml for the vast majority of strains. Lomefloxacin proved bactericidal at the MIC in all the Enterobacteriaceae strains tested but 20. In the latter strains, however, bactericidal activity could be appreciated at values slightly exceeding MIC. As regards enterococci, the MIC for 90% of strains was 32 μg/ml. Minimum bactericidal concentration (MBC) was the same as the MIC for 78% of the strains tested and was only twofold higher in all the others. The new drug was also active against staphylococci having an MIC50 and MIC₉₀ of 0.5 and 2 μg/ml, respectively. It was bactericidal at the MIC for 62% of the strains and at twofold the MIC for all the others.     

三种药物对人乳腺癌细胞体外杀伤作用比较

目的 :比较吡柔比星(THP)和阿霉素(ADM)、表阿霉素(EPI)对人乳腺癌细胞的体外抑制及凋亡诱导作用,以及药物杀伤的时效关系。 方法 :采用ATP生物荧光肿瘤体外药敏检测技术(ATP-TCA),比较吡柔比星和阿霉素、表阿霉素对人乳腺癌细胞系MCF-7、T-47D和Bcap-37的生长抑制作用,并绘制细胞存活率-时间曲线;用Annexin V凋亡检测技术检测药物诱导细胞凋亡的情况。 结果 :3种药物对乳腺癌细胞系MCF-7、T-47D和Bcap-37的生长抑制作用呈现明显的剂量依赖性;吡柔比星对其生长抑制作用明显高于阿霉素和表阿霉素,其IC₅₀仅相当于阿霉素和表阿霉素的1/3-1/6,与后两者的差异均具有显著意义(P<0.01);阿霉素和表阿霉素的抑制作用相当,两者IC₅₀无显著性差异(P>0.05)。三种药物对乳腺癌细胞的抑制作用均呈时间依赖关系,低浓度的吡柔比星在短时间内(12h)即具有生长抑制作用,而阿霉素和表阿霉素的起效时间较为迟缓(24-36h),72h后肿瘤细胞的存活率较吡柔比星高10%-20%。3种乳腺癌细胞分别经低浓度的吡柔比星、阿霉素和表阿霉素处理后均可诱导凋亡,其中吡柔比星组的细胞凋亡比例较其它两组为高。 结论 :吡柔比星对乳腺癌细胞具有较好的生长抑制和凋亡诱导作用,其起效时间明显早于阿霉素和表阿霉素。该药良好的抑瘤效果和迅速的起效时间对于提高乳腺癌临床疗效,减轻不良反应有重要的参考和临床应用价值。     

重组人纽表位肽12生物学活性测定方法的研究

目的：建立适用于重组人纽表位肽12体外质量控制的生物学活性测定方法，用于该制品的生物学活性评价。方法：采用小鼠，比较不同品系、给药浓度、给药周期等条件下应用ELISA方法检测出的小鼠相应抗体水平，确定最佳实验条件，以建立相应的体外活性测定方法。结果：FVB／N转neu基因小鼠(TgN MMTVneu202 Mul，Jackson Lab．，USA)对重组人纽表位肽12的反应存在量——效关系，并确定了最佳测定条件和给药剂量，用抗体阳转百分率作为评价指标，样品测定重复性较好，CV％值为6．7％(H=4)，结果可靠。结论：已建立的FVB／N转neu基因小鼠测定重组人纽表位肽12生物学活性的方法可用于重组人纽表位肽12生物学活性的常规评价。     

In Vitro Antibacterial Activity of DX-619, a Novel Des-F (6)-Quinolone Against Clinical Isolates in China

Abstract

The aim of the study was to investigate In Vitro antibacterial activity and bactericidal effect of DX-619 and other nine comparators against 1,101 recently collected clinical bacterial isolates in China. The minimum inhibitory concentrations (MICs) of antimicrobials were determined by a CLSI recommended standard agar dilution method and the minimum bactericidal concentrations (MBCs) were examined by the broth dilution method. Time-kill curves against representative isolates of Staphylococcus aureus, enterococci, and Klebsiellia pneumoniae were also conducted.

DX-619 exhibited excellent antibacterial activity against 1,101 clinical isolates, especially to multi-drug resistant Gram-positive cocci. The MIC₉₀s of DX-619 were ≤0.016 and 0.125 mg/L against methicillin-sensitive and -resistant S. aureus, 0.062 and 0.125 mg/L against methicillin-sensitive and -resistant S. epidermidis, respectively, which were 8-512 and 64-128 fold lower than those of comparative fluoroquinolones. The MIC₉₀s of DX-619 for penicillin-sensitive and -non-sensitive Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium were 0.016, 0.062, 0.25 and 0.5 mg/L, respectively. The MIC₉₀s of DX-619 against Enterobacteriaceae (except for Escherichia coli) and glucose-nonfermenting bacilli were ≤4 mg/L, which were comparable to other comparators. MBCs and time-kill curves showed that DX-619 was a potent bactericidal agent. There was no significant inoculum effect on MICs. But the activities of DX-619 against S. aureus, K. pneumoniae and Pseudomonas aeruginosa were decreased by acidic pH and human serum. DX-619 was a potent antibacterial compound against multi-drug resistant bacteria including Gram-positive cocci, such as S. aureus and enterococci, which may warrant further exploration.     

The Influence of Some Antifungal Drugs on In Vitro Adherence of Candida albicans to Human Buccal Epithelial Cells

Summary:  An in vitro adherence test with 10 Candida albicans strains to buccal epithelial cells (BEC) was performed in a medium with the following antifungal drugs: nystatin, amphotericin B, 5-fluorocytosine, clotrimazole and ketoconazole. Simultaneously, an in vitro adherence test was made without drugs added, but the fungal cells had been previously treated with the same drugs. All antifungal drugs applied significantly inhibited the adherence of C. albicans to BEC (p < 0.01). Pretreatment of the fungi with drugs inhibited their adherence to BEC stronger than the addition of the drugs to the test medium. Subinhibitory doses of the drugs were less effective than therapeutic ones. The most effective inhibition of the adherence was obtained with 5-fluorocytosine and ketoconazole, while nystatin turned out to be the least effective.
Zusammenfassung:  Mit 10 Candida albicans- Stämmen wurden Adhärenzteste in vitro mit Epithelzellen der Mundschleimhaut (BEC) unter Zusatz folgender Antimyzetika durchgeführt: Nystatin, Amphotericin B, 5-Fluorcytosin, Clotrimazol und Ketoconazol. Parallel dazu wurden Adhärenzteste ohne Antimyzetika-Zusatz, jedoch nach antimyzetischer Vorbehandlung der Pilzzellen durchgeführt. Alle verwendeten Antimyzetika hemmten signifikant die Adhärenz von C. albicans an BEC (p < 0.01). Die antimyzetische Vorbehandlung hemmte die Adhärenz stärker als der Antimyzetika-Zusatz während des Adhärenzversuches. Subinhibitorische Dosen waren weniger wirksam als therapeutische Dosen. Die stärkste Adherenzhemmung wurde bei 5-FC und Ketoconazol, die schwächste bei Nystatin beobachtet.     

新型铂（Ⅱ）类配合物对结肠癌SW620 细胞系的体外抗癌活性研究*

目的：本实验研究了两种新型铂（Ⅱ）类配合物（2,3- 吡啶二羧酸二水合铂、2,3- 吡嗪二羧酸二水合铂）对结肠癌SW620 细胞系的体外抗癌活性及其对细胞凋亡的影响。同时与奥沙利铂作一对照,以明确该两种新型铂（Ⅱ）类配合物是否具有更好的体外抑瘤效果。方法：采用人结肠癌细胞系SW620 作为研究对象,三种药物分别以不同浓度作用于对数生长期的SW620细胞24h、48h 后,应用软琼脂糖集落形成试验检测集落形成抑制率,以AnnexinV/PI双染法测定细胞凋亡率,以扫描电镜观测三种
药物作用后细胞形态和超微结构的改变。结果：软琼脂糖细胞集落形成抑制率实验显示出奥沙利铂、吡嗪、吡啶三种药物做用24h 后对 SW620 细胞系的半数抑制浓度（IC 50）分别为 266.51,176.18,159.25μ mol/L,48h 的IC 50分别为 158.84,161.27,125.67μ mol/L,其药物作用强度为吡啶>吡嗪>Oxa,有显著性差异（P<0.01）。AnnexinV/PI双染法显示出三种药物均可诱导SW620 细胞产生凋亡,其作用呈浓度和时间依赖性,并且随药物作用浓度及时间延长死亡细胞增多,作用强度为吡啶> 吡嗪>Oxa,有显著性差异（P<0.01）。电镜下可见细胞典型早晚期细胞凋亡特征。结论：这两种新型铂（Ⅱ）配合物对结肠癌SW620 细胞系显示出良好的体外抑瘤效果,该作用呈浓度和时间依赖性,并且强于奥沙利铂。药物作用靶点之一在于诱导细胞产生凋亡。     

蛋白酶体抑制剂Z-LLL-CHO对人骨肉瘤细胞株MG-63作用的体外研究

目的　探讨蛋白酶体抑制剂Z LLL CHO对人骨肉瘤细胞株MG 63的作用 ,并探讨其作用机制。方法　将不同浓度的Z LLL CHO作用于骨肉瘤细胞株MG 63 ,采用荧光显微镜观察细胞形态改变、电镜观察细胞超微结构变化、MTT法检测细胞增殖活力、琼脂糖凝胶电泳检测细胞凋亡、流式细胞仪分析细胞凋亡率及细胞周期改变。结果　Z LLL CHO可有效抑制MG 63细胞株的生长 ,并诱导细胞发生凋亡。凋亡细胞表现为浓染致密的颗粒块状荧光 ,胞核固缩、染色质凝聚并边缘化 ,DNA呈“阶梯状”排列的条带。流式细胞仪分析显示 ,Z LLL CHO在 1.0 μmol/L作用 2 4h、3 6h、48h后 ,细胞凋亡率分别为 5 .4%、2 0 .5 %、5 2 .7%。随药物浓度增高及作用时间延长 ,细胞周期被阻滞于G2 /M期。结论　蛋白酶体抑制剂Z LLL CHO可有效抑制人骨肉瘤MG 63细胞株的生长增殖 ,阻滞细胞周期及诱导细胞凋亡可能起重要作用。     

蛇毒制剂抗肿瘤体外实验研究

作者应用蛇毒提纯成份（蛇毒Ａ、Ｂ、Ｃ）及蛇毒混合品，对４株人类肿瘤细胞进行体外抗癌实验并进行比较。结果表明，蛇毒－Ａ对细胞增殖的抑制率高于蛇毒混合品（Ｐ＜０．０５）。蛇毒－Ａ１０００μｇ／ｍｌ对ＳＧＣ－７９０１细胞的抑制率为６２．７％，高于蛇毒－Ｂ、Ｃ及蛇毒混合品。用蛇毒－Ａ处理后，４株细胞均有形态学的改变，以ＳＧＣ及ＳＭＭＣ细胞最为明显。