BACKGROUND & AIMS: :Two novel series of quinoxalines derived from 3-phenylquinoxalin-2(1H)-one and 2-hydrazino-3-phenylquinoxaline, namely 1-substituted-3-phenylquinoxaline-2(1H)-ones, 2a-c, 3a-d, and 4; 2-(3-oxo-3,3a,4,5,6,7-hexahydroindazol-2-yl)-3-phenylquinoxaline 6; N- cyclopentylidene or benzylidene-N'-(3-phenylquinoxaline-2-yl)hydrazines, 7 and 18; 1-substituted-4-phenyl-1,2,4-triazolo[4,3-a]quinoxalines, 9, 10, 12, 13, 14, and 16 have been synthesized in order to evaluate their antitumor and antimicrobial activities. Preliminary screening at NCI showed that compounds 2b, 2c, 3b, 3c, and 9 exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10(-6) to 10(-5) molar concentrations. Compound 3b was the most active with a broad spectrum of activity. Compound 3c showed selectivity towards CNS-cancer SF-639, leukemia CCRF-CEM, and melanoma SK-MEL-5 (GI(50) = 4.03, 6.46, and 4.17 microM, respectively). On the other hand, the in vitro microbiological data revealed that the prepared compounds showed mild antimicrobial activity.

背景与目标： : 衍生自3-苯基喹喔啉-2(1H)-酮和2-肼基-3-苯基喹喔啉的两个新系列喹喔啉，即1-取代-3-苯基喹喔啉-2(1H)-酮，2a-c，3a-d和4; 2-(3-氧代-3,3a，4,5，6,7-六氢吲哚-2-基)-3-苯基喹喔啉6; N-环戊基或亚苄基-N'-(3-苯基喹喔啉-2-基) 肼，7和18; 1-取代-4-苯基-1,2，4-三唑并 [4,3-a] 喹喔啉，9,10，12,13，14，合成了16个化合物，以评估其抗肿瘤和抗菌活性。NCI的初步筛选表明，化合物2b，2c，3b，3c，和9在10(-6) 至10(-5) 摩尔浓度之间的各种肿瘤细胞株上表现出中等至强的生长抑制活性。化合物3b是活性最强的，具有广泛的活性。化合物3c显示出对CNS-癌症SF-639，白血病CCRF-CEM的选择性，和黑色素瘤SK-MEL-5 (GI(50) 分别为4.03、6.46和4.17 microM)。另一方面，体外微生物数据显示制备的化合物显示出温和的抗菌活性。

BACKGROUND & AIMS: :Bacteria utilize quorum-sensing systems to modulate environmental stress responses. The quorum-sensing system of Streptococcus mutans is mediated by the competence-stimulating peptide (CSP), whose precursor is encoded by the comC gene. A comC mutant of strain GS5 exhibited enhanced antimicrobial sensitivity to a wide variety of different agents. Since the addition of exogenous CSP did not complement this phenotype, it was determined that the increased tetracycline, penicillin, and triclosan sensitivities resulted from repression of the putative bacteriocin immunity protein gene, bip, which is located immediately upstream from comC. We further demonstrated that the inactivation of bip or smbG, another bacteriocin immunity protein gene present within the smb operon in S. mutans GS5, affected sensitivity to a variety of antimicrobial agents. Furthermore, both the bip and smbG genes were upregulated in the presence of low concentrations of antibiotics and were induced during biofilm formation relative to in planktonic cells. These results suggest, for the first time, that the antimicrobial sensitivity of a bacterium can be modulated by some of the putative bacteriocin immunity proteins expressed by the organism. The implications of these observations for the evolution of bacteriocin immunity protein genes as well as for potential new chemotherapeutic strategies are discussed.

背景与目标： 细菌利用群体感应系统来调节环境应激反应。变形链球菌的群体感应系统由能力刺激肽 (CSP) 介导，其前体由comC基因编码。菌株GS5的comC突变体对多种不同药物表现出增强的抗菌敏感性。由于添加外源CSP并不能补充该表型，因此可以确定四环素，青霉素和三氯生敏感性的增加是由于抑制了推定的细菌素免疫蛋白基因bip引起的，该基因位于comC的上游。我们进一步证明，变形链球菌GS5中smb操纵子中存在的另一种细菌素免疫蛋白基因bip或smbG的失活会影响对多种抗菌剂的敏感性。此外，bip和smbG基因在低浓度抗生素的存在下均被上调，并且相对于浮游细胞而言，在生物膜形成过程中被诱导。这些结果首次表明，细菌的抗菌敏感性可以通过生物体表达的某些推定的细菌素免疫蛋白来调节。讨论了这些观察结果对细菌素免疫蛋白基因进化以及潜在的新化学治疗策略的影响。

BACKGROUND & AIMS: :We compared the in vitro activities of tigecycline to those of other agents against 300 nonduplicate isolates of Streptococcus pneumoniae (194 isolates), Haemophilus influenzae (60 isolates), and Moraxella catarrhalis (46 isolates) recovered from patients treated in three major hospitals in Taiwan from August through December, 2003. All of these isolates were inhibited at 0.5 mg/L of tigecycline. For S. pneumoniae isolates, 72% were not susceptible to penicillin (69% intermediate and 3% resistant) and 96% were not susceptible to azithromycin. Among the 178 isolates resistant to azithromycin, 53 isolates (30%) had the M phenotype and 70% had the cMLSB phenotype. The rate of nonsusceptibility to ertapenem, telithromycin, moxifloxacin, and quinupristindalfopristin in S. pneumoniae was 3%, 2%, 1%, and 57%, respectively. For H. influenzae, 36 (60%) were not susceptible to ampicillin, among which 31 possessed beta-lactamase. A high rate (8.3%) of H. influenzae isolates with beta-lactamase-negative and ampicillin-resistant phenotype was found. All H. influenzae isolates were susceptible to azithromycin, but 40% of them were not susceptible to clarithromycin. Ninety-eight percent (44 isolates) of M. catarrhalis possessed beta-lactamase. All three fluoroquinolones tested were highly active (MIC90 < or =0.12 mg/L) against H. influenzae and M. catarrhalis.

背景与目标： : 我们比较了替加环素与其他药物对300种非重复肺炎链球菌分离株 (194株)，流感嗜血杆菌 (60株) 和卡他莫拉菌 (46株) 的体外活性，这些分离株是从8月到2003年12月在台湾的三家主要医院中康复的。在0.5 mg/L替加环素的浓度下，所有这些分离株均被抑制。对于肺炎链球菌分离株，72% 对青霉素不敏感 (69% 中间体和3% 耐药)，96% 对阿奇霉素不敏感。在对阿奇霉素耐药的178株中，53株 (30% 株) 具有M表型，70% 株具有cMLSB表型。肺炎链球菌对厄他培南，泰利霉素，莫西沙星和奎奴普汀的不敏感性分别为3%，2%，1% 和57%。对于流感嗜血杆菌，36 (60%) 对氨苄青霉素不敏感，其中31具有 β-内酰胺酶。发现具有 β-内酰胺酶阴性和氨苄青霉素抗性表型的流感嗜血杆菌分离株率高 (8.3%)。所有流感嗜血杆菌分离株对阿奇霉素敏感，但其中40% 对克拉霉素不敏感。卡他氏杆菌的百分之九十八 (44个分离株) 具有 β-内酰胺酶。测试的所有三种氟喹诺酮类药物对流感嗜血杆菌和卡他氏杆菌具有高度活性 (MIC90 <或 = 0.12 mg/L)。

BACKGROUND & AIMS: :The strategic use of fluorine substitution in drug discovery and drug development is well documented. The small size and high electronegativity of fluorine are among properties of this element that lend special advantages. Applications in drugs targeted to the central nervous system (CNS) have been particularly fruitful in addition to favorable properties seen in many peripherally acting drugs. Fluorine substitution can be used to solve problems unique to the CNS, such as blood brain barrier (BBB) penetration. Likewise, use of the positron emitting isotope, (18)F, provides a unique tool for non-invasive imaging and diagnoses in the CNS. In this review, fluorine in CNS drugs and drug discovery are discussed.

背景与目标： : 氟替代在药物发现和药物开发中的战略用途已得到充分证明。氟的小尺寸和高电负性是该元素的特殊优点之一。除了在许多外周作用药物中看到的有利特性外，针对中枢神经系统 (CNS) 的药物中的应用特别富有成效。氟替代可用于解决CNS特有的问题，例如血脑屏障 (BBB) 渗透。同样，使用正电子发射同位素 (18)F为CNS中的非侵入性成像和诊断提供了独特的工具。本文对中枢神经系统药物中的氟和药物发现进行了讨论。

BACKGROUND & AIMS: :New hydrazone derivatives were synthesized via the nucleophilic addition-elimination reaction of 2-[(1-methyl-1H-tetrazol-5-yl)thio)]acetohydrazide with aromatic aldehydes/ketones. The compounds were tested in vitro against various Candida species and compared with ketoconazole. Genotoxicity of the most effective anticandidal compounds was evaluated by umuC and Ames assays. All compounds were also investigated for their cytotoxic effects on NIH3T3 and A549 cell lines. Compound 8 was the most effective antifungal derivative against C. albicans (ATCC-90028) with a MIC value of 0.05 mg/mL. Compound 5 can be identified as the most promising anticancer agent against A549 cancer cell lines due to its inhibitory effect on A549 cell lines and low toxicity to NIH3T3 cells.

背景与目标： : 通过2-[(1-甲基-1h-四唑-5-基) 硫代)] 乙酰酰肼与芳族醛/酮的亲核加成消除反应合成了新的腙衍生物。对化合物进行了针对各种念珠菌的体外测试，并与酮康唑进行了比较。通过umuC和Ames分析评估了最有效的抗癌症化合物的遗传毒性。还研究了所有化合物对NIH3T3和A549细胞系的细胞毒性作用。化合物8是对白色念珠菌 (ATCC-90028) 最有效的抗真菌衍生物，MIC值为0.05 mg/ml。化合物5由于对A549细胞系的抑制作用和对NIH3T3细胞的低毒性，可被确定为最有前途的抗A549癌细胞系的抗癌剂。

BACKGROUND & AIMS: :Aurelin is a 40-residue cationic antimicrobial peptide isolated from the mezoglea of a scyphoid jellyfish Aurelia aurita. Aurelin and its (15)N-labeled analogue were overexpressed in Escherichia coli and purified. Antimicrobial activity of the recombinant peptide was examined, and its spatial structure was studied by NMR spectroscopy. Aurelin represents a compact globule, enclosing one 3(10)-helix and two α-helical regions cross-linked by three disulfide bonds. The peptide binds to anionic lipid (POPC/DOPG, 3:1) vesicles even at physiological salt concentration, it does not interact with zwitterionic (POPC) vesicles and interacts with the DPC micelle surface with moderate affinity via two α-helical regions. Although aurelin shows structural homology to the BgK and ShK toxins of sea anemones, its surface does not possess the "functional dyad" required for the high-affinity interaction with the K(+)-channels. The obtained data permit to correlate the modest antibacterial properties and membrane activity of aurelin.

背景与目标： : Aurelin是从scyphoid水母Aurelia aurita的mezoglea中分离出的40残基阳离子抗菌肽。Aurelin及其 (15)N标记的类似物在大肠杆菌中过表达并纯化。研究了重组肽的抗菌活性，并通过NMR光谱研究了其空间结构。Aurelin代表紧凑的小球，包含一个3(10)-螺旋和两个由三个二硫键交联的 α-螺旋区域。该肽即使在生理盐浓度下也与阴离子脂质 (POPC/DOPG，3:1) 囊泡结合，它不与两性离子 (POPC) 囊泡相互作用，并且通过两个 α 螺旋区域以中等亲和力与DPC胶束表面相互作用。尽管aurelin显示出与海葵的BgK和ShK毒素的结构同源性，但其表面不具有与K ()-通道高亲和力相互作用所需的 “功能性二体”。获得的数据允许将aurelin的适度抗菌特性和膜活性相关联。

BACKGROUND & AIMS: :Alkenylboronic acids have shown important biological activities that contribute to neuroprotection. We have determined their influence on the β-amyloid (βA) aggregation process, β-secretase and acethylcholinesterase activities on cell-free systems, on the redox and lipid peroxidation status, and on the vulnerability to apoptotic death in an APPswe neuroblastoma cell line, before and after hydrogen peroxide treatment. We have discovered that 2-arylvinylboronic acids and some of their esters possess a set of properties which makes them highly useful as neuroprotective agents affecting multiple biological targets involved in AD. These properties are not paralleled by the related 2-arylboronic acids.

背景与目标： : 烯基硼酸显示出重要的生物活性，有助于神经保护。我们已经确定了它们对 β-淀粉样蛋白 (β a) 聚集过程，β-分泌酶和乙胆碱酯酶在无细胞系统上的活性，对氧化还原和脂质过氧化状态以及对APPswe神经母细胞瘤细胞凋亡死亡的脆弱性的影响过氧化氢治疗之前和之后。我们发现2-芳基乙烯基硼酸及其某些酯具有一系列特性，这使它们作为影响AD中涉及的多个生物靶标的神经保护剂非常有用。这些性质与相关的2-芳基硼酸不平行。

BACKGROUND & AIMS: :A series of novel resveratrol derivatives were designed, synthesised and evaluated as potential therapeutic agents for the treatment of Alzheimer's disease. Among these compounds, compound 7l, (E)-5-(4-(isopropylamino)styryl)benzene-1,3-diol, exhibited potent ß-amyloid aggregation inhibition activity, which was confirmed by a ThT fluorescence assay (71.65% at 20 μM) and transmission electron microscopy (TEM). Compound 7l also exhibited good antioxidant activity (4.12 Trolox equivalents in an oxygen radical absorbance capacity assay and a 37% reduction in reactive oxygen species in cells at 10 μM). The cytotoxicity analysis of compounds 7f, 7i, 7j and 7l indicated that these compounds have lower toxicities than resveratrol at 60 μM.

背景与目标： : 设计，合成和评估了一系列新型白藜芦醇衍生物，可作为治疗阿尔茨海默氏病的潜在治疗剂。在这些化合物中，化合物7l，(E)-5-(4-(异丙基氨基) 苯乙烯基) 苯-1,3-二醇表现出有效的 β-淀粉样蛋白聚集抑制活性，通过ThT荧光分析 (71.65% 在20μm) 和透射电子显微镜 (TEM) 证实了这一点。化合物7l也显示出良好的抗氧化活性 (在氧自由基吸收能力分析中4.12的Trolox当量和10μm细胞中活性氧的37% 减少)。化合物的细胞毒性分析7f，7i，7j和7l表明这些化合物在60μm时的毒性比白藜芦醇低。

BACKGROUND & AIMS: :In this study, we evaluated the cytotoxic activity and antiproliferative potency of novel octahydropyrazin[2,1-a:5,4-a']diisoquinoline derivatives (1-7) in MCF-7 and MDA-MB-231 breast cancer cell lines. Annexin V binding assay and disruption of the mitochondrial potential were performed to determine apoptosis. The activity of caspases 3, 8, 9, and 10 was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The results from experiments were compared with effects obtained after incubation in the presence of camptothecin and etoposide. Our study demonstrated that the most active compounds in both analyzed breast cancer cell lines were compounds 3 and 4. We also observed that all compounds induced apoptosis. We demonstrated the higher activity of caspases 3, 8, 9, and 10, which confirmed that induction of apoptosis is associated with external and internal cell death pathway. Our study revealed that the novel compounds in group of diisoquinoline derivatives are promising candidates in anticancer treatment by activation of both extrinsic and intrinsic apoptotic pathways.

背景与目标： : 在这项研究中，我们评估了新型八氢吡嗪 [2,1-a:5,4-a '] 二异喹啉衍生物 (1-7) 在MCF-7和MDA-MB-231乳腺癌细胞系中的细胞毒性和抗增殖能力。进行膜联蛋白V结合测定和线粒体电位破坏以确定细胞凋亡。与测试化合物孵育24小时后，测量了胱天蛋白酶3、8、9和10的活性，以解释诱导凋亡的详细分子机制。将实验结果与在喜树碱和依托泊苷存在下孵育后获得的效果进行了比较。我们的研究表明，在两种分析的乳腺癌细胞系中最具活性的化合物是化合物3和4。我们还观察到所有化合物均诱导细胞凋亡。我们证明了caspases 3、8、9和10的较高活性，这证实了凋亡的诱导与外部和内部细胞死亡途径有关。我们的研究表明，二异喹啉衍生物组中的新型化合物通过激活外在和内在凋亡途径在抗癌治疗中是有希望的候选者。

BACKGROUND & AIMS: :Antitumor agents that bind to tubulin and disrupt microtubule dynamics have attracted considerable attention in the last few years. To extend our knowledge of the thiazole ring as a suitable mimic for the cis-olefin present in combretastatin A-4, we fixed the 3,4,5-trimethoxyphenyl at the C4-position of the thiazole core. We found that the substituents at the C2- and C5-positions had a profound effect on antiproliferative activity. Comparing compounds with the same substituents at the C5-position of the thiazole ring, the moiety at the C2-position influenced antiproliferative activities, with the order of potency being NHCH(3) > Me > N(CH(3))(2). The N-methylamino substituent significantly improved antiproliferative activity on MCF-7 cells with respect to C2-amino counterparts. Increasing steric bulk at the C2-position from N-methylamino to N,N-dimethylamino caused a 1-2 log decrease in activity. The 2-N-methylamino thiazole derivatives 3b, 3d and 3e were the most active compounds as antiproliferative agents, with IC(50) values from low micromolar to single digit nanomolar, and, in addition, they are also active on multidrug-resistant cell lines over-expressing P-glycoprotein. Antiproliferative activity was probably caused by the compounds binding to the colchicines site of tubulin polymerization and disrupting microtubule dynamics. Moreover, the most active compound 3e induced apoptosis through the activation of caspase-2, -3 and -8, but 3e did not cause mitochondrial depolarization.

背景与目标： : 与微管蛋白结合并破坏微管动力学的抗肿瘤剂在过去几年中引起了极大的关注。为了扩展我们对噻唑环作为combretastatin A-4中存在的顺式烯烃的合适模拟物的了解，我们将3,4，5-三甲氧基苯基固定在噻唑核的C4-position。我们发现C2-和C5-positions的取代基对抗增殖活性具有深远的影响。比较噻唑环C5-position具有相同取代基的化合物，C2-position部分影响抗增殖活性，效力顺序为NHCH(3)> Me> N(CH(3))(2)。相对于C2-amino对应物，N-甲基氨基取代基显着提高了MCF-7细胞的抗增殖活性。从N-甲基氨基到N，N-二甲基氨基C2-position的空间体积增加导致活性降低1-2对数。2-n-甲基氨基噻唑衍生物3b，3d和3e是作为抗增殖剂的最具活性的化合物，其IC(50) 值从低微摩尔到个位数纳摩尔，此外，它们在多药耐药细胞系中也具有活性过表达P-糖蛋白。抗增殖活性可能是由化合物与微管蛋白聚合的秋水仙碱位点结合并破坏微管动力学引起的。此外，活性最高的化合物3e通过激活caspase-2，-3和-8诱导细胞凋亡，但3e并未引起线粒体去极化。

BACKGROUND & AIMS: :Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens.

背景与目标： : 检查了24种抗菌药物对选定的产气荚膜梭菌菌株的起效速度和杀菌活性。头孢曲松，亚胺培南，甲硝唑，美洛西林，青霉素g，哌拉西林和替考拉宁在暴露后2-4小时内将菌落计数减少至少3 log10单位。克林霉素，氟喹诺酮类，交沙霉素和四环素引起延迟杀伤 (暴露后4-22小时活菌计数大于或等于99.9% 减少)。氯霉素和利福平对4株菌株中的2株缺乏杀菌活性，而红霉素，夫西地酸和磷霉素 (添加了6-磷酸葡萄糖) 仅对所有4株菌株具有抑制作用。亚胺培南和青霉素g分别与9种和12种抗菌药物联合使用。基本上所有的药物组合都产生不同的效果; 只有青霉素g加强力霉素导致对产气荚膜炎的拮抗作用。

BACKGROUND & AIMS: AIMS:To evaluate the prevalence and antimicrobial resistance of Enterococcus species from chickens and pigs in Beijing and Shandong Province, China. METHODS AND RESULTS:Swab samples were collected from four farms in Beijing and two in Shandong Province in 2009 and tested for Enterococcus. Minimum inhibitory concentrations of antimicrobial agents were determined using broth microdilution or agar screening methods. A total of 453 Enterococcus isolates were recovered, belonging to six different Enterococcus species. All isolates were sensitive to vancomycin. Resistance to tetracycline (92.5%), amikacin (89.4%), erythromycin (72.8%) and rifampin (58.1%), and high-level streptomycin resistance (HLSR, 50.3%) were prevalent, while resistance to penicillins (7.9% to penicillin and 4.2% to ampicillin) was rare. The resistance rates to phenicols (chloramphenicol and florfenicol) and enrofloxacin, and high-level gentamicin resistance (HLGR) were approximately 30%. The vast majority of the Enterococcus isolates were classified as multidrug-resistant organisms. CONCLUSIONS:Resistance of Enterococcus sp. to most antimicrobials was more prevalent in China than in European or other Asian countries. SIGNIFICANCE AND IMPACT OF THE STUDY:Our findings reveal a high level of antimicrobial resistance in Enterococcus isolates from food animals in China and underline the need for prudent use of antibiotics in chicken and pig production to minimize the spread of antibiotic-resistant enterococci.

背景与目标：

BACKGROUND & AIMS: :Phyto-psychopharmacological agents are extracts of plants with stimulating or calming effects on the central nervous system. Phyto-psycho-pharmacological agents are among the most commonly prescribed herbal medicines in Germany. The efficacy and harmlessness of some of the preparations have been established by high quality clinical trials. Between 1975 and 1992, a total of 34 clinical studies involving some 2326 patients were published on the effects of Ginkgo special extract EGb 761 and LI 1370; to date, 28 clinical trials in 2120 patients have been under-taken with alcoholic extracts of St. John's Wort. The therapeutic efficacy of kava and valerian extracts has been investigated in six and four controlled studies, respectively. In general, a high placebo effect is likely, which is why it is essential to include control groups in these studies. A considerable advantage over synthetic psychopharmacological agents is the low incidence of side effects, which in safety assessment studies is below 3%. The sharp increase in quality standards for clinical trials has meant that only a few preparations have undergone large scale testing programs in accordance with international guidelines. For other phyto-psychopharmacological agents, there is the danger that no further clinical trials will be undertaken due to the excessively high standards now demanded.

背景与目标： : 植物心理药物是对中枢神经系统具有刺激或镇静作用的植物提取物。植物心理药物是德国最常用的草药之一。一些制剂的疗效和无害化已通过高质量的临床试验确定。在1975年至1992年之间，共发表了34项临床研究，涉及约2326名患者，涉及银杏特殊提取物EGb 761和LI 1370的影响; 迄今为止，已对2120名患者进行了28项临床试验，其中包括圣约翰草的酒精提取物。卡瓦和缬草提取物的治疗功效已分别在六个和四个对照研究中进行了研究。一般来说，安慰剂效应可能很高，这就是为什么在这些研究中包括对照组是必不可少的。与合成精神药物相比，相当大的优势是副作用的发生率低，在安全性评估研究中，副作用的发生率低于3%。临床试验质量标准的急剧提高意味着只有少数制剂按照国际指南进行了大规模的测试计划。对于其他植物心理药物，由于现在要求的标准过高，因此存在无法进行进一步临床试验的危险。

BACKGROUND & AIMS: OBJECTIVES:The precise role for intraventricular (IVT) antimicrobials in combination with systemic antibiotics in management of cerebrospinal fluid (CSF) diversion device-associated infections is uncertain. We evaluated our current practice, comparing dual therapy against systemic antimicrobials alone. METHODS:All adult patients with at least two consecutive CSF isolates who were treated for CSF diversion device-related infection over a 5-year period (2005-2010) were identified retrospectively. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were analysed. RESULTS:Forty-eight patients were identified - 25 received IVT and systemic antibiotics (group A), and 23 systemic antibiotics alone (group B). Clinical features were similar between groups, as were causative organisms. CSF leucocyte counts differed slightly (A > B, p = 0.067) but no laboratory parameters differed significantly. Infected devices were generally revised (A = 92%, B = 91%). Mean times to CSF sterilisation and normalisation of CSF microscopy were significantly shorter for group A (p < 0.05 and p < 0.005 respectively), as was duration of hospital stay (p < 0.002) and required length of systemic antimicrobial therapy (p < 0.001). CONCLUSIONS:Our findings indicate that IVT antibiotics enhance clinical and microbiological recovery and should therefore be considered for patients with CSF infection associated with a CSF diversion device. We recommend further evaluation of this approach in a prospective, randomised, controlled trial.

背景与目标：

BACKGROUND & AIMS: :Since there are no systematic studies available on the effects of anti-microtubule agents on ciliated protozoa, we screened a wide variety of such compounds for their effects on the growth of Paramecium tetraurelia cell cultures. Compounds tested include agents of widely different chemical composition and with reported effects on widely different cell types. We can differentiate between different drug effects: (a) Rotenone is the only agent without any recognisable effect, (b) Another group of compounds (including colchicine) requires very high concentrations, as compared to higher animal cells, i.e., rather close to a cytotoxic level; this group also includes tubulozole (unexpectedly without any difference between the cis- and the trans-stereoisomer). (c) A third group of drugs inhibits cell culture growth without any lethal effects (benzimidazoles, nocodazole, parbendazole; the [anti-]fungal antibiotic, griseofulvin; the herbicide, trifluralin). (d) Finally a group of agents are active in a concentration range also reported for plants (the herbicide, APM) or for higher animal cells (including the microtubule stabiliser, taxol) or for both (vinblastine, vincristine, triethyl lead), although they are cytotoxic at higher concentrations (like compounds of group [b]). Therefore, in particular compounds of group (c) and possibly of group (d) might be considered further on for a more detailed analysis of a possibly genuine anti-microtubular effect in Paramecium cells. Of particular interest may be nocodazole, parbendazole and trifluralin, since they can inhibit cell culture growth (over 24 h tested) in relatively low concentrations (comparable to other cell types) without any impairment of cell viability.

背景与目标： : 由于尚无关于抗微管剂对纤毛原生动物的影响的系统研究，因此我们筛选了各种此类化合物对草履虫四重草细胞培养物生长的影响。测试的化合物包括化学成分广泛不同的试剂，据报道对细胞类型广泛不同的影响。我们可以区分不同的药物作用 :( a) 鱼藤酮是唯一没有任何可识别作用的药物，(b) 与较高的动物细胞相比，另一组化合物 (包括秋水仙碱) 需要非常高的浓度，即相当接近细胞毒性水平; 该组还包括小管 (出乎意料的是，顺式和反式立体异构体之间没有任何区别)。(c) 第三组药物抑制细胞培养物的生长，而没有任何致死作用 (苯并咪唑，诺考达唑，帕苯达唑; [抗] 真菌抗生素灰黄霉素; 除草剂，氟拉林)。(d) 最后，一组试剂在植物 (除草剂，APM) 或高等动物细胞 (包括微管稳定剂，紫杉醇) 或两者 (长春碱，长春新碱，三乙基铅) 的浓度范围内具有活性，尽管它们在较高浓度下具有细胞毒性 (如 [b] 组的化合物)。因此，特别是可以进一步考虑 (c) 组和 (d) 组的化合物，以更详细地分析草履虫细胞中可能真正的抗微管作用。特别令人感兴趣的可能是诺考达唑，帕苯达唑和三氟拉林，因为它们可以在相对较低的浓度 (与其他细胞类型相当) 下抑制细胞培养物生长 (测试超过24小时)，而不会损害细胞活力。