• 【结直肠腺癌和其他大肠疾病中的雌激素受体。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Sciascia C,Olivero G,Comandone A,Festa T,Fiori MG,Enrichens F
    BACKGROUND & AIMS: :Seventy-two patients with tumor and ten with non-neoplastic colon disease were studied for the presence of estrogen receptors (ER) by three different methods. Only seven specimens (six primary adenocarcinomas and one recurrent cancer) had an ER concentration above 3 fm/mg of cytosolic protein, with no sex, age and tumor stage correlation. Our results suggest that the large bowel does not contain a cytosolic receptor for estradiol.
    背景与目标: : 通过三种不同的方法研究了72例肿瘤患者和10例非肿瘤性结肠疾病的雌激素受体 (ER) 的存在。只有7个标本 (6个原发性腺癌和1个复发性癌症) 的ER浓度高于3 fm/mg的胞质蛋白,没有性别,年龄和肿瘤分期的相关性。我们的结果表明,大肠不含雌二醇的胞质受体。
  • 【在台湾,替加环素与其他抗菌剂对肺炎链球菌,流感嗜血杆菌和卡他莫拉菌的体外活性比较。】 复制标题 收藏 收藏
    DOI:10.1089/mdr.2006.12.130 复制DOI
    作者列表:Lau YJ,Hsueh PR,Liu YC,Shyr JM,Huang WK,Teng LJ,Liu CY,Luh KT
    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)。
  • 【雌激素过量引起的缺乏1型5α-还原酶的小鼠的胎儿死亡。】 复制标题 收藏 收藏
    DOI:10.1210/mend.11.7.9933 复制DOI
    作者列表:Mahendroo MS,Cala KM,Landrum DP,Russell DW
    BACKGROUND & AIMS: :Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5alpha-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5alpha-reduce androgens leads to their conversion to estrogens, which in turn causes fetal death in midgestation. These findings indicate that the 5alpha-reduction of androgens in female animals plays a crucial role in guarding against estrogen toxicity during pregnancy.
    背景与目标: : 缺乏类固醇5α-还原酶1型的雌性小鼠的产仔数减少。纯合缺陷雌性的平均产仔为2.7幼仔,而野生型对照为8.0幼仔。在突变动物中,卵子发生,受精,植入和胎盘形态似乎正常。胎儿损失发生在妊娠10.75和11.0之间,与妊娠中期胎盘雄激素产生激增和野生型小鼠蜕膜中5α-还原酶1型表达的诱导相称。在妊娠第9天,雄烯二酮和睾丸激素的血浆水平高2至3倍,在整个妊娠早期和中期,敲除小鼠的雌二醇水平长期升高2至3倍。施用雌激素受体拮抗剂或芳香化酶抑制剂可逆转突变小鼠的高胎儿死亡率,而雌二醇处理野生型妊娠小鼠会导致胎儿浪费。结果表明,在缺陷小鼠中,未能减少5α-雄激素会导致其转化为雌激素,进而导致妊娠中期胎儿死亡。这些发现表明,雌性动物中雄激素的5α 减少在预防怀孕期间的雌激素毒性中起着至关重要的作用。
  • 【关系质量,激素避孕选择和青少年妇女不使用避孕套的发展关联。】 复制标题 收藏 收藏
    DOI:10.1016/j.jadohealth.2005.12.027 复制DOI
    作者列表:Sayegh MA,Fortenberry JD,Shew M,Orr DP
    BACKGROUND & AIMS: PURPOSE:Consistent condom use is critical to efforts to prevent sexually transmitted infections among adolescents, but condom use may decline as relationships and contraceptive needs change. The purpose of this research is to assess changes in condom non-use longitudinally in the context of changes in relationship quality, coital frequency and hormonal contraceptive choice. METHODS:Participants were women (aged 14-17 years at enrollment) recruited from three urban adolescent medicine clinics. Data were collected at three-month intervals using a face-to-face structured interview. Participants were able to contribute up to 10 interviews, but on average contributed 4.2 interviews over the 27-month period. Independent variables assessed partner-specific relationship quality (five items; scale range 5-25; alpha = .92, e.g., this partner is a very important person to me); and, number of coital events with a specific partner. Additional items assessed experience with oral contraceptive pills (OCP) use and injected depo medroxy-progesterone acetate (DMPA). The outcome variable was number of coital events without condom use during the past three months. Analyses were conducted as a three-level hierarchical linear growth curve model using HLM 6. The Level 1 predictor was time, to test the hypothesis that condom non-use increases over time. Level 2 predictors assessed relationship quality and coital frequency across all partners to assess hypotheses that participants' condom non-use increases over time as a function of relationship quality and coital frequency. Level 3 predictors assessed the participant-level influence of OCP or DMPA experience on time-related changes in condom non-use. RESULTS:A total of 176 women reported 279 sex partners and contributed 478 visits. Both average coital frequency and average condom non-use linearly increased during the 27-month follow-up. At any given follow-up, about 35% reported recent OCP use, and 65% reported DMPA use. HLM analyses showed that condom non-use increased as a function of time (beta = .12; p = .03, Level 1 analysis). Increased condom non-use over time was primarily a function of increased coital frequency (beta = .01; p = .00), although higher levels of relationship quality were associated with increased condom non-use at enrollment (beta = .44; p = .00, Level 2 analysis). The temporal rise in condom non-use significantly increased among DMPA users (beta = .06; p = .00) but not OCP users (Level 3 analysis) (beta = -.04; p = .06). CONCLUSIONS:Developmentally, relationship characteristics and coital frequency appear to have increasing weight in decisions about condom use. Hormonal contraceptive methods are not equivalently associated with the overall temporal decline in condom use. Future research associated with dual contraceptive/condom use should address differential factors associated condom use in combination with different hormonal methods.
    背景与目标:
  • 【氟化分子作为中枢神经系统中的药物和显像剂。】 复制标题 收藏 收藏
    DOI:10.2174/156802606777951046 复制DOI
    作者列表:Sun S,Adejare A
    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。
  • 【一些腙衍生物作为新型抗癌剂和抗癌剂的合成和生物学评价。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejmech.2012.10.011 复制DOI
    作者列表:Altıntop MD,Özdemir A,Turan-Zitouni G,Ilgın S,Atlı Ö,İşcan G,Kaplancıklı ZA
    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。
  • 【发现链烯基硼酸作为神经保护剂,影响与阿尔茨海默氏病有关的多个生物靶标。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2012.11.068 复制DOI
    作者列表:Jiménez-Aligaga K,Bermejo-Bescós P,Martín-Aragón S,Csákÿ AG
    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。
  • 【白藜芦醇衍生物的设计,合成和评估,如a ß (派-) 聚集抑制剂,抗氧化剂和神经保护剂。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2012.09.105 复制DOI
    作者列表:Lu C,Guo Y,Li J,Yao M,Liao Q,Xie Z,Li X
    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。
  • 【八氢吡嗪 [2,1-a:5,4-a '] 二异喹啉衍生物作为有效抗癌剂的生物学评价。】 复制标题 收藏 收藏
    DOI:10.1177/1010428317701641 复制DOI
    作者列表:Gornowicz A,Pawłowska N,Czajkowska A,Czarnomysy R,Bielawska A,Bielawski K,Michalak O,Staszewska-Krajewska O,Kałuża Z
    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。
  • 【2-取代-4-(3 ',4',5 '-三甲氧基苯基)-5-芳基噻唑类抗癌剂的合成及生物学评价。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmc.2012.10.001 复制DOI
    作者列表:Romagnoli R,Baraldi PG,Salvador MK,Camacho ME,Preti D,Tabrizi MA,Bassetto M,Brancale A,Hamel E,Bortolozzi R,Basso G,Viola G
    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。
  • 【植物心理药物的临床试验。】 复制标题 收藏 收藏
    DOI:10.1016/S0944-7113(97)80050-5 复制DOI
    作者列表:Schulz V,Hübner WD,Ploch M
    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。
  • 【抗微管剂对草履虫细胞培养生长的影响。】 复制标题 收藏 收藏
    DOI:10.1016/S0932-4739(11)80066-0 复制DOI
    作者列表:Pape R,Kissmehl R,Glas-Albrecht R,Plattner H
    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。
  • 【在计划生育环境中容易插入宫内避孕器。】 复制标题 收藏 收藏
    DOI:10.1111/ajo.12007 复制DOI
    作者列表:Harvey C,Bateson D,Wattimena J,Black KI
    BACKGROUND & AIMS: BACKGROUND:Intrauterine devices (IUDs) provide highly effective contraception for women worldwide. Reluctance to insert IUDs in the primary care setting may relate to concern about potential difficulty and complications, particularly in nulliparous women. AIMS:To determine the practitioner, patient and procedural factors associated with abandoned IUD insertion, practitioner-reported difficulty of insertion and adverse events during IUD insertions in the family planning setting. METHODS:This was a prospective study over a 12-month period of consecutive IUD insertions in four family planning clinics across New South Wales and Queensland. Patient, practitioner and device-related factors associated with abandoned IUD insertion, practitioner-reported ease of insertion and immediate insertion-related adverse events were analysed using logistic regression. RESULTS:Of 996 insertion procedures, successful insertion occurred in 95%, and 90% were reported as easy by the inserting doctor, including 80% of those in nulliparous women. Patient characteristics associated with an abandoned insertion were nulliparity (AOR 5.19; 2.49-10.82) or caesarean section-only deliveries (AOR 5.38; 2.58-11.22) and with practitioner-reported difficult insertion, nulliparity alone (AOR 1.98; 1.11-3.54). Practitioners inserting fewer than 100 IUDs over the 12-month study period more frequently rated insertions as difficult (AOR 1.76; 1.08-2.88). Complications occurred in 34 women and were more likely in nulliparous women (AOR 4.51; 2.16-9.39). CONCLUSIONS:Most IUDs can be successfully inserted, even in nulliparous women, in a primary care setting. Referral to a specialist may be appropriate for some women who are nulliparous or had caesarean section-only deliveries, depending on the experience of the practitioner.
    背景与目标:
  • 【Kronos早期雌激素预防研究中与女性颈动脉内膜中层厚度和冠状动脉钙化相关的遗传多态性。】 复制标题 收藏 收藏
    DOI:10.1152/physiolgenomics.00114.2012 复制DOI
    作者列表:Miller VM,Petterson TM,Jeavons EN,Lnu AS,Rider DN,Heit JA,Cunningham JM,Huggins GS,Hodis HN,Budoff MJ,Santoro N,Hopkins PN,Lobo RA,Manson JE,Naftolin F,Taylor HS,Harman SM,de Andrade M
    BACKGROUND & AIMS: :Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10(-06)) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10(-05)), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = -0.043, P value = 3.59 × 10(-05); rs2291299, β = -0.032, P value = 5.59 × 10(-05)) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10(-04); and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10(-04)) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10(-04)) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.
    背景与目标: : 更年期激素治疗 (MHT) 可能会限制心血管疾病 (CVD) 的进展,但会带来血栓形成的风险。为了测试与颈动脉内膜中层厚度 (CIMT) 和冠状动脉钙化 (CAC) 定义的亚临床CVD相关的靶向候选基因变异,610参加Kronos早期雌激素预防研究 (KEEPS) 的妇女,MHT预防CVD进展的临床试验,在抗凝剂,促凝剂,纤溶或先天免疫途径的764基因内对13,229单核苷酸多态性 (snp) 进行基因分型。根据线性回归,欧洲血统的比例呈负相关,但入学年龄和脉压与CIMT呈正相关。调整这些变量,两个snp,一个在2号染色体上的MAP4K4基因 (rs2236935,β = 0.037,p值 = 2.36 × 10(-06)),一个在5号染色体上的IL5基因 (rs739318,β = 0.051,p值 = 5.02 × 10(-05)),与CIMT呈正相关; CCL5 17号染色体上的两个snp (rs4796119,β = -0.043,p值 = 3.59 × 10(-05); rs2291299,β = -0.032,p值 = 5.59 × 10(-05)) 与CIMT呈负相关; 校正多重测试后,只有rs2236935仍然显著。使用逻辑回归,当我们调整腰围时,两个snp (rs11465886,IRAK2,3号染色体,OR = 3.91,p值 = 1.10 × 10(-04); 和rs17751769,SERPINA1,14号染色体,OR = 1.96,p值 = 2.42 × 10(-04)) 与> 0 Agatston单位的CAC评分呈正相关; 1个SNP (rs630014,ABO,OR = 0.51,p值 = 2.51 × 10(-04)) 呈负相关; 校正多重测试后无显著。这些snp是否与CIMT和CAC相关,在随机分配到MHT的女性中仍有待确定。
  • 【丙型肝炎病毒的抗病毒耐药和直接作用抗病毒药物。】 复制标题 收藏 收藏
    DOI:10.3851/IMP2426 复制DOI
    作者列表:Aloia AL,Locarnini S,Beard MR
    BACKGROUND & AIMS: :Direct-acting antiviral (DAA) agents specifically target viral proteins. Two DAAs have been already been approved for the treatment of HCV infection and many more are in development. DAA treatment of HCV infection, however, leads to the selection of viral variants (produced by the error-prone HCV polymerase) that are resistant to the DAA agent in use. The selection of DAA-resistant HCV variants has been studied extensively in vitro and in vivo. Common amino acid substitution sites in each of the non-structural proteins are associated with DAA-resistance: D168, A155, A156 and V36 in NS3 protease; L31 and Y93 in NS5A; S282, S96, P495, M423, M414 and C316 in NS5B. In this review we cover the basic principles of DAA resistance, summarise the available resistance data for the various classes of DAAs and discuss the potential of DAA combination therapy for overcoming DAA-resistance, resulting in major advances in the treatment of HCV.
    背景与目标: : 直接作用抗病毒 (DAA) 药物专门针对病毒蛋白。已经批准了两种daa用于治疗HCV感染,并且还有更多的daa正在开发中。但是,对HCV感染的DAA治疗导致选择对使用中的DAA试剂具有抗性的病毒变体 (由易错的HCV聚合酶产生)。抗DAA HCV变体的选择已在体外和体内进行了广泛研究。每个非结构蛋白中常见的氨基酸取代位点与DAA抗性相关: NS3蛋白酶中的D168,A155,A156和V36; NS5A中的L31和Y93; NS5B中的S282,S96,P495,M423,M414和C316。在这篇综述中,我们涵盖了DAA耐药的基本原理,总结了各类DAA的可用耐药数据,并讨论了DAA联合疗法克服DAA耐药的潜力,从而在HCV治疗方面取得了重大进展。

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