• 【抗菌药物的使用和肺炎链球菌青霉素耐药性:时间关系模型。】 复制标题 收藏 收藏
    DOI:10.1089/mdr.2006.12.158 复制DOI
    作者列表:Mera RM,Miller LA,White A
    BACKGROUND & AIMS: :The nature of the temporal relationship between antibacterial consumption and Streptococcus pneumoniae penicillin resistance is investigated using population level data across time. IMS Health Global Services provided national outpatient antibiotic prescription data for the years 1996-2003 from France, Spain, Italy, Germany, the United Kingdom, and the United States. Surveillance data consist of S. pneumoniae isolates obtained from a surveillance database in the same geographic regions from 1996 to 2003. A linear mixed model for repeated measures was used to analyze the association between resistance and several antibacterial classes through time. Changes in penicillin resistance through time in any country are better explained by the weighted cumulative antibacterial consumption with a 2-year lag. Narrow-spectrum penicillins are associated with lower resistance rates. Large reductions in consumption at the population level are needed to affect resistance. There is a peak level of penicillin resistance associated with cumulative exposure to a combination of antibiotic classes that is unique for every country.
    背景与目标: :使用跨时间的人口水平数据调查了抗菌药物消费与肺炎链球菌青霉素耐药性之间时间关系的性质。 IMS Health Global Services提供了1996-2003年法国,西班牙,意大利,德国,英国和美国的国家门诊抗生素处方数据。监测数据由1996年至2003年从同一地理区域的监测数据库中获得的肺炎链球菌分离株组成。采用线性混合模型进行重复测量,以分析耐药性与一段时间内几种抗菌剂类别之间的关联。在任何国家,青霉素耐药性随时间的变化都可以通过加权累积抗菌药消费量(滞后2年)来更好地说明。窄谱青霉素与较低的耐药率有关。需要在人口一级大幅度减少消费量以影响抵抗力。青霉素耐药性的峰值与每个国家所独有的抗生素类药物的累积接触有关。
  • 【进入三级医院内科病房的患者不良药物反应的直接费用和临床方面】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tribiño G,Maldonado C,Segura O,Díaz J
    BACKGROUND & AIMS: INTRODUCTION:Adverse drug reactions (ADRs) occur frequently in hospitals and increase costs of health care; however, few studies have quantified the clinical and economic impact of ADRs in Colombia. OBJECTIVES:These impacts were evaluated by calculating costs associated with ADRs in patients hospitalized in the internal medicine ward of a Level 3 hospital located in Bogotá, Colombia. In addition, salient clinical features of ADRs were identified and characterized. MATERIAL AND METHODS:Intensive follow-ups for a cohort of patients were conducted for a five month period in order to detect ADRs; different ways to classify them, according to literature, were considered as well. Information was collected using the INVIMA reporting format, and causal probability was evaluated with the Naranjo algorithm. Direct costs were calculated from the perspective of payer, based on the following costs: additional hospital stay, medications, paraclinical tests, additional procedures, patient displacement to intermediate or intensive care units, and other costs. RESULTS:Of 836 patients admitted to the service, 268 adverse drug reactions were detected in 208 patients (incidence proportion 25.1%, occurence rate 0.32). About the ADRs found, 74.3% were classified as probable, 92.5% were type A, and 81.3% were moderate. The body system most often affected was the circulatory system (33.9%). Drugs acting on the blood were most frequently those ones associated with adverse reactions (37.6%). The costs resulting from medical care of adverse drug reactions varied from COL dollar 93,633,422 (USD dollar 35,014.92) to COL dollar 122,155,406 (USD dollar 45,680.94), according to insurance type, during the study period. CONCLUSIONS:Adverse drug reactions have a significant negative health and financial impact on patient welfare. Because of the substantial resources required for their medical care and the significant proportion of preventable adverse reactions, active programs of institutional pharmacovigilance are highly recommended.
    背景与目标: 简介:药物不良反应(ADR)在医院中经常发生,并增加了医疗保健费用;但是,很少有研究能够量化ADR在哥伦比亚的临床和经济影响。
    目的:通过计算在哥伦比亚波哥大三级医院内科病房住院的患者与ADR相关的费用来评估这些影响。此外,ADR的显着临床特征已得到鉴定和表征。
    材料与方法:对一组患者进行了为期五个月的强化随访,以检测ADR。根据文献,还考虑了不同的分类方法。使用INVIMA报告格式收集信息,并使用Naranjo算法评估因果概率。直接费用是根据以下费用从付款人的角度计算的:额外的住院时间,药物,辅助临床检查,其他程序,将患者转移到中级或重症监护室以及其他费用。
    结果:836例入院患者中,208例患者发生了268例药物不良反应(发生率25.1%,发生率0.32)。关于发现的ADR,有74.3%被归为可能,A型为92.5%,中度为81.3%。受影响最严重的身体系统是循环系统(33.9%)。作用于血液的药物最常见于那些与不良反应有关的药物(37.6%)。根据保险类型,在研究期间,药物不良反应的医疗费用从93,633,422美元(35,014.92美元)到122,155,406美元(45,680.94美元)不等。
    结论:药物不良反应会对患者的健康产生重大的负面健康和财务影响。由于其医疗服务所需的大量资源以及可预防的不良反应的比例很大,因此强烈建议积极进行机构药物警戒计划。
  • 【跳尾Orchesella cincta的气候抗逆性状的地理变异。】 复制标题 收藏 收藏
    DOI:10.1016/j.jinsphys.2006.06.005 复制DOI
    作者列表:Bahrndorff S,Holmstrup M,Petersen H,Loeschcke V
    BACKGROUND & AIMS: :Multiple traits of stress resistance were investigated in the epedaphic springtail Orchesella cincta. Second generation adults from five laboratory populations were compared with respect to resistance to extreme temperatures and desiccation, and traits relevant to climatic adaptation. Populations were collected along a 2000-km latitudinal gradient ranging from Denmark to southern Italy and reared under the same standard laboratory conditions. Traits investigated were resistance to high and low temperature, desiccation resistance, body size and water loss rate (WLR). Results showed genetically based differences in resistance to high and low temperature, desiccation, WLR, water pool and body size between populations. Individuals from the most northern population had the highest desiccation-and cold shock resistance, and the lowest heat shock resistance. Females were significantly more desiccation resistant than males. The results of cold shock resistance showed a positive increase with lowest environmental temperature recorded at the sites of population origin, whereas heat shock resistance showed a positive increase with highest recorded temperature at the sites of population origin. Desiccation resistance increased towards the most southern and northern population, suggesting that both low and high temperature extremes affect desiccation resistance. Body mass, water pool and WLR showed interpopulation as well as sex specific variation. This provides evidence for geographical variation in stress resistance of springtails related to climatic conditions.
    背景与目标: :研究了足立跳尾Orchesella cincta的多种抗逆性状。比较了来自五个实验室人群的第二代成年人对极端温度和干燥的抵抗力以及与气候适应有关的性状。从丹麦到意大利南部,沿着2000公里的纬度梯度收集种群,并在相同的标准实验室条件下进行饲养。研究的特征是对高温和低温的抗性,抗干燥性,体型和失水率(WLR)。结果显示,不同人群之间对高温和低温,干燥,WLR,水池和体重的遗传差异。来自最北部人口的个体具有最高的耐干燥性和抗冷震性,以及最低的抗热震性。女性的抗干燥能力明显高于男性。在种群起源点记录的最低环境温度下,抗冷震性结果呈正增长,而在种群起源点记录的最高温度下抗热震性呈正增长。大部分南部和北部人口的抗旱性增加,这表明低温和高温极端情况都会影响抗旱性。体重,水池和WLR表现出种群数量以及性别差异。这为与气候条件有关的跳尾抗逆性的地理变化提供了证据。
  • 【社区获得性耐甲氧西林金黄色葡萄球菌对奥沙西林耐药所需的VraS / VraR两组分调节系统。】 复制标题 收藏 收藏
    DOI:10.1111/j.1574-6968.2006.00384.x 复制DOI
    作者列表:Boyle-Vavra S,Yin S,Daum RS
    BACKGROUND & AIMS: :Methicillin/oxacillin (Oxa) resistance in Staphylococcus aureus is primarily mediated by the acquired penicillin-binding protein (PBP2a) encoded by mecA. PBP2a acts together with native PBP2 to mediate oxacillin resistance by contributing complementary transpeptidase and transglycosylase activities, respectively. The VraS/VraR two-component regulatory system is inducible by cell-wall antimicrobials (beta-lactams, glycopeptides) and controls transcriptional induction of many cell-wall genes including pbp2 and itself. We investigated the role of VraS/VraR in the phenotypic expression of oxacillin resistance by inactivating vraS in community-acquired MRSA clinical isolates that lack functional genes encoding the mecA regulatory sequences mecI and mecR1. Inactivation of vraS abrogated oxacillin resistance, and complementation with the vraS operon restored the resistance phenotype. mecA transcription increased in the vraS mutants; however, PBP2a abundance was similar to that of the wild type. Although pbp2 transcription decreased in the vraS mutants, overexpression of the pbp2 operon did not restore resistance. These data demonstrate that although expressions of mecA and pbp2 are required for oxacillin resistance, they are not sufficient. Therefore, the vraS/vraR regulatory system plays a crucial role in allowing MRSA to respond to beta-lactams by regulation of a gene target other than the known effectors of methicillin resistance.
    背景与目标: 金黄色葡萄球菌对甲氧西林/奥沙西林(Oxa)的耐药性主要由mecA编码的获得性青霉素结合蛋白(PBP2a)介导。 PBP2a与天然PBP2共同发挥作用,通过分别贡献互补的转肽酶和转糖基酶活性来介导奥沙西林抗性。 VraS / VraR两组分调节系统可通过细胞壁抗微生物剂(β-内酰胺,糖肽)诱导,并控制包括pbp2及其本身在内的许多细胞壁基因的转录诱导。我们通过灭活社区获得的MRSA临床分离株中的vraS而失活,研究了VraS / VraR在奥沙西林耐药性表型表达中的作用,该分离株缺乏编码mecA调控序列mecI和mecR1的功能基因。 vraS的失活消除了奥沙西林的耐药性,与vraS操纵子的互补恢复了耐药性表型。在vraS突变体中,mecA转录增加;但是,PBP2a的丰度与野生型相似。尽管在vraS突变体中pbp2转录降低,但是pbp2操纵子的过表达不能恢复抗性。这些数据表明,尽管抗mecA和pbp2的表达是奥沙西林耐药性所必需的,但它们还不够。因此,vraS / vraR调节系统在允许MRSA通过调节除已知的甲氧西林抗性效应子以外的基因靶标而对β-内酰胺作出响应中起着至关重要的作用。
  • 【吸毒规则:古代世界中的葡萄酒和罂粟衍生物。六。罂粟是食物和毒品的来源。】 复制标题 收藏 收藏
    DOI:10.3109/10826089709039375 复制DOI
    作者列表:Nencini P
    BACKGROUND & AIMS: :Poppies were widely used during antiquity as a source of food, therapeutics, and poisons. It is likely that the alimentary value of poppy seeds was known in the Neolithic age, and there is some evidence that the neuropsychopharmacological effects of poppy juice were exploited during the Minoan civilization in the eastern Mediterranean basin. The Minoan civilization dates the attribution to poppies of symbolic meanings connected with rites of agricultural fertility. The persistence throughout antiquity of this symbolism is testified by literary and iconographic evidence of the attribution of poppies to goddesses of fertility, such as Demeter, Aphrodite, and Ceres.
    背景与目标: :在古代,罂粟被广泛用作食物,治疗剂和毒药的来源。罂粟种子的营养价值很可能是在新石器时代就已经知道的,并且有一些证据表明,罂粟汁的神经心理药理作用是在地中海东部的米诺斯文明期间被利用的。米诺斯文明可追溯到象征意义的罂粟的归属,这些象征意义与农业生育的仪式有关。这种象征主义在整个上古时代的持久性通过文学和肖像学证据证明,罂粟归因于狄特耳特,阿芙罗狄蒂和谷神星等生育女神。
  • 【根瘤菌素在体外和体内对非P-糖蛋白介导的长春地辛抗性的调节。】 复制标题 收藏 收藏
    DOI:10.1007/BF01240315 复制DOI
    作者列表:Arioka H,Nishio K,Heike Y,Abe S,Saijo N
    BACKGROUND & AIMS: :Rhizoxin is an antineoplastic drug that inhibits tubulin polymerization. In this study, we demonstrated that rhizoxin was approximately twice as active in vitro against a human small-cell lung cancer cell line with non-P-glycoprotein-mediated resistance to vindesine, H69/VDS, as against its parental line, H69. Tubulin polymerization in H69/VDS, demonstrated by Western blot analysis, was inhibited markedly by rhizoxin compared with that in H69, in a concentration-dependent manner. A drug-accumulation study showed that the intracellular rhizoxin level in H69/VDS was 15% lower than that in H69, whereas efflux from H69/VDS was enhanced slightly. These results indicate that enhanced inhibition of tubulin polymerization rather than increased intracellular drug concentration accounted for the higher sensitivity of H69/VDS to rhizoxin. In an experiment using mice with severe combined immunodeficiency and inoculated subcutaneously with H69/VDS, in vivo tumor growth was reduced markedly by three intermittent intraperitoneal doses of rhizoxin compared with that in mice inoculated with H69. Three weeks after the last rhizoxin dose, the relative treated/untreated tumor volumes were 0.29 for H69, but only 0.06 for H69/VDS, indicating that H69/VDS regrowth was minimal even after a 3-week treatment-free period. In conclusion, rhizoxin conquers vindesine resistance of a human small-cell lung cancer cell line in vitro and in vivo.
    背景与目标: :Rhizoxin是一种抑制微管蛋白聚合的抗肿瘤药。在这项研究中,我们证明了根霉毒素在体外对人小细胞肺癌细胞株的活性约为非亲本糖蛋白对长春地辛H69 / VDS的抗性的P糖蛋白介导的,比其亲本株H69的活性高出两倍。 Western blot分析表明,与H69中的相比,根瘤菌素显着抑制了H69 / VDS中的微管蛋白聚合,并呈浓度依赖性。一项药物蓄积研究表明,H69 / VDS中的细胞内根瘤菌素水平比H69中的低15%,而H69 / VDS中的流出量则略有提高。这些结果表明,增强的对微管蛋白聚合的抑制而不是增加的细胞内药物浓度,说明了H69 / VDS对根瘤菌素的敏感性更高。在一项使用严重联合免疫缺陷小鼠并皮下接种H69 / VDS的小鼠进行的实验中,与接种H69的小鼠相比,腹膜内给予3种间断剂量的硫唑嗪显着降低了体内肿瘤的生长。最后一次根瘤菌素给药后三周,H69的相对治疗/未治疗肿瘤体积为0.29,而H69 / VDS仅为0.06,表明即使经过3周的无治疗期,H69 / VDS的再生长也很小。总之,根瘤菌素可在体外和体内克服人类小细胞肺癌细胞株的长春地辛耐药性。
  • 【与人类神经胶质瘤细胞系SNB-19中获得性替莫唑胺抗性相关的遗传改变。】 复制标题 收藏 收藏
    DOI:10.1158/1535-7163.MCT-05-0428 复制DOI
    作者列表:Auger N,Thillet J,Wanherdrick K,Idbaih A,Legrier ME,Dutrillaux B,Sanson M,Poupon MF
    BACKGROUND & AIMS: :Gliomas are highly lethal neoplasms that cannot be cured by currently available therapies. Temozolomide is a recently introduced alkylating agent that has yielded a significant benefit in the treatment of high-grade gliomas. However, either de novo or acquired chemoresistance occurs frequently and has been attributed to increased levels of O6-methylguanine-DNA methyltransferase or to the loss of mismatch repair capacity. However, very few gliomas overexpress O6-methylguanine-DNA methyltransferase or are mismatch repair-deficient, suggesting that other mechanisms may be involved in the resistance to temozolomide. The purpose of the present study was to generate temozolomide-resistant variants from a human glioma cell line (SNB-19) and to use large-scale genomic and transcriptional analyses to study the molecular basis of acquired temozolomide resistance. Two independently obtained temozolomide-resistant variants exhibited no cross-resistance to other alkylating agents [1,3-bis(2-chloroethyl)-1-nitrosourea and carboplatin] and shared genetic alterations, such as loss of a 2p region and loss of amplification of chromosome 4 and 16q regions. The karyotypic alterations were compatible with clonal selection of preexistent resistant cells in the parental SNB-19 cell line. Microarray analysis showed that 78 out of 17,000 genes were differentially expressed between parental cells and both temozolomide-resistant variants. None are implicated in known resistance mechanisms, such as DNA repair, whereas interestingly, several genes involved in differentiation were down-regulated. The data suggest that the acquisition of resistance to temozolomide in this model resulted from the selection of less differentiated preexistent resistant cells in the parental tumor.
    背景与目标: :胶质瘤是高度致死性的肿瘤,目前尚无法治愈。替莫唑胺是最近引入的烷基化剂,已在治疗高级神经胶质瘤中产生了显着的益处。然而,从头或获得性化学抗性经常发生,并且归因于O6-甲基鸟嘌呤-DNA甲基转移酶水平的增加或失配修复能力的丧失。但是,极少的神经胶质瘤过表达O6-甲基鸟嘌呤-DNA甲基转移酶或错配修复缺陷,提示其他机制可能与对替莫唑胺的抗性有关。本研究的目的是从人类神经胶质瘤细胞系(SNB-19)产生抗替莫唑胺的变体,并使用大规模的基因组和转录分析来研究获得的替莫唑胺抗性的分子基础。两个独立获得的替莫唑胺抗性变体对其他烷基化剂[1,3-双(2-氯乙基)-1-亚硝基脲和卡铂]无交叉抗性,并且共有遗传变异,例如2p区域丢失和扩增丢失染色体4和16q区域。核型改变与亲本SNB-19细胞系中先前存在的抗性细胞的克隆选择相容。基因芯片分析显示,在17,000个基因中,有78个在亲代细胞和两种替莫唑胺耐药变体之间差异表达。没有人参与已知的抗性机制,例如DNA修复,而有趣的是,参与分化的几个基因被下调。数据表明,在该模型中获得对替莫唑胺的抗药性是由于在亲本肿瘤中选择了分化程度较低的抗药性细胞而引起的。
  • 【耐药细胞提取物中癌基因依赖性细胞凋亡。】 复制标题 收藏 收藏
    DOI:10.1101/gad.11.10.1266 复制DOI
    作者列表:Fearnhead HO,McCurrach ME,O'Neill J,Zhang K,Lowe SW,Lazebnik YA
    BACKGROUND & AIMS: Many genotoxic agents kill tumor cells by inducing apoptosis; hence, mutations that suppress apoptosis produce resistance to chemotherapy. Although directly activating the apoptotic machinery may bypass these mutations, how to achieve this activation in cancer cells selectively is not clear. In this study, we show that the drug-resistant 293 cell line is unable to activate components of the apoptotic machinery-the ICE-like proteases (caspases)-following treatment with an anticancer drug. Remarkably, extracts from untreated cells spontaneously activate caspases and induce apoptosis in a cell-free system, indicating that drug-resistant cells have not only the apoptotic machinery but also its activator. Comparing extracts from cells with defined genetic differences, we show that this activator is generated by the adenovirus E1A oncogene and is absent from normal cells. We provide preliminary characterization of this oncogene generated activity (OGA) and show that partially purified OGA activates caspases when added to extracts from untransformed cells. We suggest that agents that link OGA to caspases in cells would kill tumor cells otherwise resistant to conventional cancer therapy. As this killing relies on an activity generated by an oncogene, the effect of these agents should be selective for transformed cells.

    背景与目标: 许多遗传毒性剂通过诱导细胞凋亡杀死肿瘤细胞。因此,抑制细胞凋亡的突变产生了对化学疗法的抗性。尽管直接激活凋亡机制可能绕过这些突变,但是如何在癌细胞中选择性地实现这种激活尚不清楚。在这项研究中,我们显示了抗药性293细胞系无法激活凋亡机制的成分(如ICE样蛋白酶(胱天蛋白酶)),随后进行了抗癌药物治疗。值得注意的是,未经处理的细胞提取物会自发激活胱天蛋白酶并在无细胞系统中诱导凋亡,这表明耐药细胞不仅具有凋亡机制,还具有其激活剂。比较具有确定的遗传差异的细胞提取物,我们表明该激活剂是由腺病毒E1A癌基因产生的,而正常细胞中却不存在。我们提供了此致癌基因产生的活性(OGA)的初步表征,并表明当添加到未转化细胞的提取物中时,部分纯化的OGA会激活胱天蛋白酶。我们建议将OGA与细胞中的半胱氨酸蛋白酶连接的药剂会杀死肿瘤细胞,否则它们会对常规癌症治疗产生抵抗力。由于这种杀伤作用依赖于癌基因产生的活性,因此这些药剂对转化细胞的作用应该是选择性的。

  • 【腺病毒对细胞蛋白质合成的抑制作用被药物2-氨基嘌呤阻止。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.18.7115 复制DOI
    作者列表:Huang JT,Schneider RJ
    BACKGROUND & AIMS: :Adenovirus infection results in the suppression of cellular protein synthesis, but the mechanism has not been established. In this report we demonstrate that the shut-off of cellular protein synthesis by adenovirus is prevented in cells by treatment with the drug 2-aminopurine. Treatment with 2-aminopurine is shown to prevent suppression of cellular translation without disrupting the normal viral block in the transport of cellular mRNAs from the nucleus to the cytoplasm. We show that viral suppression of cellular protein synthesis occurs concomitant with activation of the interferon-induced double-stranded RNA-activated inhibitor (DAI), a protein kinase, and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha), but that prevention of host cell shut-off by 2-aminopurine occurs without a decrease in kinase activity or a dephosphorylation of eIF-2 alpha. Results are presented that indicate that activation of DAI kinase and phosphorylation of eIF-2 alpha may be required but are not sufficient to achieve inhibition of cellular protein synthesis during adenovirus infection. We suggest that other events, in particular the modification of additional initiation factors, are likely involved in viral inhibition of cellular translation.
    背景与目标: :腺病毒感染导致细胞蛋白质合成受到抑制,但该机制尚未建立。在本报告中,我们证明了通过用2-氨基嘌呤药物治疗可防止腺病毒关闭细胞蛋白质合成。已显示用2-氨基嘌呤处理可防止细胞翻译受到抑制,而不会破坏细胞mRNA从细胞核到细胞质的运输过程中的正常病毒阻滞。我们显示病毒抑制细胞蛋白质合成的发生与干扰素诱导的双链RNA激活的抑制剂(DAI),蛋白激酶和真核生物起始因子2(eIF-2 alpha)的α亚基的磷酸化的激活同时发生。 ,但可以防止2-氨基嘌呤阻止宿主细胞的关闭,而不会降低激酶活性或eIF-2α的去磷酸化。结果表明,可能需要DAI激酶的激活和eIF-2α的磷酸化,但不足以抑制腺病毒感染期间细胞蛋白质合成。我们建议其他事件,特别是其他起始因子的修饰,可能与细胞翻译的病毒抑制有关。
  • 【保留,遵守和依从性:针对老年人的基于家庭和团体的抵抗训练计划的重要考虑因素。】 复制标题 收藏 收藏
    DOI:10.1016/j.jsams.2006.06.020 复制DOI
    作者列表:Cyarto EV,Brown WJ,Marshall AL
    BACKGROUND & AIMS: :Reports on the efficacy of physical activity intervention trials usually only include discussion of the primary outcomes. However, assessing factors such as participant retention, adherence and compliance can assist in the accurate interpretation of the overall impact of a program in terms of reach and appeal. A quasi-randomised trial was carried out to assess and compare retention and adherence rates, and compliance with, a twice weekly resistance training program provided either individually at home or in a group format. Retirement villages (n=6) were assigned to either 'Have A Try' (HAT, home-based) or 'Come Have A Try' (CHAT, group-based); both programs included nine strength and two balance exercises. The program involved a 20-week Intervention Phase a 24-week Maintenance Phase and a 20-week On-going Maintenance Phase. One hundred and nineteen participants (mean age 80+/-6 years) were recruited (HAT=38, CHAT=81). There was no difference in retention rates at the end of the Intervention Phase, but significantly more HAT than CHAT participants had dropped out of the study (p<0.01) after the Maintenance Phase and the On-going Maintenance Phase. During the Intervention Phase, over half the HAT and CHAT participants completed > or =75% of the prescribed activity sessions, but adherence was significantly greater in CHAT than HAT during the Maintenance Phase (p<0.01). Participants in CHAT were significantly more compliant than HAT participants (p<0.05). Both home- and group-based formats were successful over the short-term, but, in retirement villages, the group program had better adherence and compliance in the longer-term.
    背景与目标: :有关体育锻炼干预试验功效的报告通常仅包括对主要结局的讨论。但是,评估参与者的保留,遵守和遵守等因素可以帮助准确地解释计划在影响力和吸引力方面的总体影响。进行了一项半随机试验,以评估和比较保留率和依从率,以及是否遵守每周两次的在家中或以小组形式提供的每周两次阻力训练计划。退休村(n = 6)被分配为“尝试一下”(HAT,基于家庭)或“来一下尝试”(CHAT,基于组);这两个程序都包括九项力量和两项平衡练习。该计划包括20周的干预阶段,24周的维护阶段和20周的持续维护阶段。招募了119名参与者(平均年龄80 / -6岁)(HAT = 38,CHAT = 81)。在干预阶段结束时,保留率没有差异,但是在维护阶段和正在进行的维护阶段之后,HAT的退出人数比CHAT参与者退出研究的次数多(p <0.01)。在干预阶段,超过一半的HAT和CHAT参与者完成了规定活动的>或= 75%,但是在维持阶段,CHAT中的依从性明显高​​于HAT(p <0.01)。与CHAT参与者相比,CHAT参与者的依从性更高(p <0.05)。以家庭为基础和以团体为基础的形式在短期内都是成功的,但是在退休村,从长期来看,团体计划具有更好的遵守性和合规性。
  • 【胆囊体积的改变不会影响胆囊管阻力。】 复制标题 收藏 收藏
    DOI:10.1001/archsurg.1990.01410160046010 复制DOI
    作者列表:Sharp KW,Ross CB,Tillman VN,Williams LF Jr
    BACKGROUND & AIMS: :To our knowledge, the relationship between gallbladder volume and cystic duct function has not been studied. We hypothesized that changes in gallbladder volume would influence cystic duct resistance. The effect of gallbladder volume changes on cystic duct resistance to both prograde (emptying) and retrograde (filling) steady-state flow was tested in 12 dogs under basal cholecystokinin-stimulated conditions utilizing a multiport catheter with a highly compliant balloon placed within the gallbladder fundus. Gallbladder volume was regulated by varying balloon volume from empty to just beyond physiologic distention. Cystic duct resistance was not affected by balloon volume under basal or stimulated conditions or by the direction of perfusate flow. This study demonstrated no relationship between gallbladder volume and cystic duct resistance and did not demonstrate a cystic duct sphincter mechanism at physiologic gallbladder volumes.
    背景与目标: :据我们所知,尚未研究胆囊体积与胆囊管功能之间的关系。我们假设胆囊体积的变化会影响胆囊管阻力。胆囊体积变化对胆囊管抵抗顺行(空)和逆行(充盈)稳态血流的影响在12条经基础胆囊收缩素刺激的狗中使用多端口导管,并在胆囊内放置高度顺应性球囊进行了测试。胆囊体积的调节是通过将气囊体积从空变到生理上的变化来进行的。囊性导管阻力不受基础或刺激条件下的球囊容积或灌注液流向的影响。这项研究表明胆囊体积和胆囊管阻力之间没有关系,并且在生理胆囊体积上也没有证明胆囊括约肌的机制。
  • 【CHADS2评分与阵发性房颤患者抗心律失常药物治疗疗效之间的关系。】 复制标题 收藏 收藏
    DOI:10.1253/circj.cj-12-0854 复制DOI
    作者列表:Komatsu T,Sato Y,Ozawa M,Kunugita F,Ueda H,Tachibana H,Morino Y,Nakamura M
    BACKGROUND & AIMS: BACKGROUND:The Cardiac failure, Hypertension, Age, Diabetes, Stroke [Doubled] (CHADS(2)) score is a useful scheme for risk stratification of thromboembolism patients, but there is little information about its usefulness for the evaluation of antiarrhythmic drug (AAD) therapy. METHODS AND RESULTS:This study included 459 paroxysmal atrial fibrillation (AF) patients (309 men, mean age 66 ± 12 years, mean follow-up 50 ± 35 months) and prophylactic efficacy was analyzed on the basis of CHADS(2) score. (1) Survival rates free from AF recurrence at 1, 6, 12 and 24 months were, respectively, 89%, 74%, 63% and 47% in score-0 group (n=152); 92%, 68%, 59% and 48% in score-1 group (n=158); 86%, 64%, 56% and 46% in score-2 group (n=84); 81%, 65%, 51% and 35% in score-3 group (n=43); and 68%, 50%, 36% and 18% in ≥ score-4 group (n=22) (P<0.05; score-0, score-1 or score-2 vs. ≥ score-4 group). (2) Survival rates free from progression to chronic AF at 12, 36, 60 and 90 months were, respectively, 95%, 93%, 91% and 89% in score-0 group; 97%, 91%, 89% and 88% in score-1 group; 96%, 93%, 88% and 83% in score-2 group; 91%, 74%, 67% and 60% in score-3 group; and 91%, 82%, 68% and 55% in ≥ score-4 group (P<0.01; score-0, score-1 or score-2 vs. ≥ score-4 group). (3) In multivariate logistic regression analysis adjusted for potentially confounding variables, CHADS(2) score was associated with AF recurrence (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.16-1.81, P<0.001), and progression to chronic AF during AAD therapy (OR 1.64, 95% CI 1.04-2.69, P<0.001). CONCLUSIONS:When using a rhythm control strategy, the CHADS(2) score is a useful scheme for predicting the outcome of AAD treatment of patients with paroxysmal AF.  
    背景与目标: 背景:心脏衰竭,高血压,年龄,糖尿病,中风[加倍](CHADS(2))评分是对血栓栓塞患者进行风险分层的有用方案,但有关其对抗心律不齐药物(AAD)评估的有用性的信息很少) 治疗。
    方法与结果:这项研究纳入459例阵发性房颤(AF)患者(309名男性,平均年龄66±12岁,平均随访50±35个月),并根据CHADS(2)评分分析了其预防性疗效。 (1)得分为0的组在1、6、12和24个月无房颤复发的生存率分别为89%,74%,63%和47%(n = 152);得分1组(n = 158)为92%,68%,59%和48%;得分2组分别为86%,64%,56%和46%(n = 84);得分3组(n = 43)分别为81%,65%,51%和35%; ≥分数4组的患者分别为68%,50%,36%和18%(n = 22)(P <0.05;分数≥0,分数1或得分2与≥分数4组相比)。 (2)在0级评分组中,在12、36、60和90个月无进展为慢性房颤的生存率分别为95%,93%,91%和89%;得分1组分别为97%,91%,89%和88%;得分2组分别为96%,93%,88%和83%;分数3组的比例分别为91%,74%,67%和60%; ≥4分组分别为91%,82%,68%和55%(P <0.01; 0分,1分或2分与≥4分组比较)。 (3)在针对潜在混杂变量进行调整的多因素logistic回归分析中,CHADS(2)评分与房颤复发相关(优势比[OR] 1.45、95%置信区间[CI] 1.16-1.81,P <0.001)和进展到AAD治疗期间的慢性房颤(OR 1.64,95%CI 1.04-2.69,P <0.001)。
    结论:使用节律控制策略时,CHADS(2)评分是预测阵发性房颤患者AAD治疗结果的有用方案。
  • 【手性识别多沙唑嗪对映体在3个靶标中的治疗作用以及在动物实验中的不良药物反应。】 复制标题 收藏 收藏
    DOI:10.1139/y2012-129 复制DOI
    作者列表:Zhao D,Duan LH,Wang FY,Wang M,Lu HG,Wu ZG,Wang X,Ren LM
    BACKGROUND & AIMS: :Doxazosin used in benign prostatic hyperplasia has the side effects of causing hypotension and the risk of heart failure. The 3 targets of α(1A)-adrenoceptors (in the prostate), α(1D)-adrenoceptors (in the aorta), and an unknown mechanism (in the heart) are involved, respectively. We hypothesized that there is a chiral recognition of doxazosin enantiomers in the 3 targets. Using isolated rat aorta (α(1D)-adrenoceptors) and rabbit prostate (α(1A)-adrenoceptors), we examined pA(2) and pK(B) values of doxazosin enantiomers. We observed chronotropic and inotropic effects of doxazosin enantiomers in isolated rat and rabbit heart tissues. (-)Doxazosin and (+)doxazosin produced a shift to the right of concentration-contraction curves for noradrenalin (aorta) and phenylephrine (prostate smooth muscle). The pA(2) value of (-)doxazosin (8.625 ± 0.053) was smaller than (+)doxazosin (9.503 ± 0.051) in rat aorta, but their pK(B) values in rabbit prostate were the same. In rat and rabbit heart tissues, (+)doxazosin (3-30 µmol·L(-1)) significantly decreased atrial rate, and produced negative inotropic effects; however, (-)doxazosin did not affect the atrial rate, and produced positive inotropic effects in the atria. Thus, the chiral carbon atom of doxazosin does not affect its activity at the therapeutic target of α(1A)-adrenoceptors in the prostate, but significantly changes its blocking activity against α(1D)-adrenoceptors in the aorta, and produces opposite inotropic effects in the atria via an α(1)-adrenoceptor-independent mechanism.
    背景与目标: :多沙唑嗪用于前列腺增生症具有引起低血压和心力衰竭风险的副作用。 α(1A)-肾上腺素受体(在前列腺中),α(1D)-肾上腺素受体(在主动脉中)和未知机制(在心脏中)的3个靶点分别涉及。我们假设在3个靶标中有手性识别多沙唑嗪对映体。使用分离的大鼠主动脉(α(1D)-肾上腺素受体)和兔前列腺(α(1A)-肾上腺素受体),我们检查了多沙唑嗪对映体的pA(2)和pK(B)值​​。我们观察到了多沙唑嗪对映异构体在离体大鼠和兔心脏组织中的变时性和变力作用。 (-)多沙唑嗪和()多沙唑嗪使去甲肾上腺素(主动脉)和去氧肾上腺素(前列腺平滑肌)的浓度-收缩曲线向右移动。大鼠主动脉中(-)恶唑烷的pA(2)值(8.625±0.053)小于()恶唑烷(9.503±0.051),但它们在兔前列腺中的pK(B)值​​相同。在大鼠和兔子的心脏组织中,()多沙唑嗪(3-30 µmol·L(-1))显着降低心房率,并产生负性变力作用;然而,(-)doxazosin不会影响心房率,并在心房产生正性肌力作用。因此,多沙唑嗪的手性碳原子不影响其对前列腺中α(1A)-肾上腺素受体治疗靶点的活性,但会显着改变其对主动脉中α(1D)-肾上腺素受体的阻断活性,并产生相反的正性肌力作用通过独立于α(1)-肾上腺素受体机制的心房。
  • 【药房中抗肿瘤药污染水平的常规环境监测的应用和评估-MEWIP项目。】 复制标题 收藏 收藏
    DOI:10.1093/annhyg/mes081 复制DOI
    作者列表:Kiffmeyer TK,Tuerk J,Hahn M,Stuetzer H,Hadtstein C,Heinemann A,Eickmann U
    BACKGROUND & AIMS: :A large-scale study was carried out in order to determine the contamination level of antineoplastic drugs in pharmacies and to investigate the suitability and effects of wipe sample monitoring at regular intervals. A specific study design was developed. The 130 participating pharmacies were divided into a study and a control group, carrying out five and two wipe sampling cycles, respectively. The work practice was analyzed using questionnaires to identify factors that influence the contamination level. From 1269 wipe samples, 774 (61%) were contaminated with at least one of the analyzed cytotoxic drugs: cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, methotrexate, and paclitaxel. A significant decrease of the contamination with cyclophosphamide and 5-fluorouracil was observed in the study group. The Monitoring-Effect Study of Wipe Sampling in Pharmacies method has proven to be a reliable and affordable tool for contamination control. Based on the 90th percentile of the contamination values, a substance-independent performance-based guidance value of 0.1ng cm(-2) has been derived.
    背景与目标: :进行了一项大规模研究,以确定药房中抗肿瘤药的污染水平,并定期调查擦拭样品监测的适用性和效果。开发了具体的研究设计。将130家参与活动的药店分为研究组和对照组,分别进行了5次和2次擦拭采样。使用调查表对工作实践进行了分析,以找出影响污染水平的因素。从1269个擦拭样品中,有774个(61%)被至少一种分析的细胞毒性药物污染:环磷酰胺,多西他赛,依托泊苷,5-氟尿嘧啶,吉西他滨,异环磷酰胺,甲氨蝶呤和紫杉醇。在研究组中观察到环磷酰胺和5-氟尿嘧啶的污染显着降低。药房擦拭采样的监测效果研究方法被证明是一种可靠且负担得起的污染控制工具。基于污染值的第90个百分位数,得出了与物质无关的基于性能的指导值0.1ng cm(-2)。
  • 【基于多孔二氧化硅纳米粒子的难溶性水飞蓟宾的72小时释放制剂:比格犬的体外释放动力学和体内/体外相关性。】 复制标题 收藏 收藏
    DOI:10.1016/j.ejps.2012.10.012 复制DOI
    作者列表:Cao X,Deng W,Fu M,Zhu Y,Liu H,Wang L,Zeng J,Wei Y,Xu X,Yu J
    BACKGROUND & AIMS: :The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N(2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m(2)/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na(2)CO(3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.
    背景与目标: :这项研究的目的是使用固体分散体,凝胶基质和多孔二氧化硅纳米粒子(PSN)的组合制备水飞蓟宾(72 h-SLB)的72 h释放制剂,并研究体内/体外相关性( IVIVC)。扫描电子显微镜和N(2)吸附的结果表明,空的PSN具有球形,高度多孔的结构,较大的比表面积(385.89±1.12 m(2)/ g)和较小的孔径(2.74 nm)一般)。 Nah(2)CO(3)解决方案中不同浓度(0.01、0.06和0.08M)的72 h-SLB和水飞蓟宾加载的PSNs的体外溶出曲线显示0.06 M Na(2)CO(3)解决方案是最佳的培养基,其中水飞蓟宾可以从72 h-SLB中以一级释放动力学释放,而从PSN中以Higuchi动力学释放。此外,还建立了比格犬中72 h-SLB和水飞蓟宾的PSN的IVIVC。使用0.06 M Na(2)CO(3)解决方案作为体外溶出介质,可以为72 h-SLB和水飞蓟宾加载的PSNs都实现良好的线性关系。这些发现支持以下事实:72 h-SLB(由固体分散体,规则的凝胶基质和PSN组成)与Na(2)CO(3)解决方案一起作为体外溶出介质,可以开发为溶解性较差的有前途的制剂药物,享有良好的IVIVC。

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