• 【胸骨后甲状腺肿的甲状腺切除术。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tsai VW,Cameron RB,Wang MB
    BACKGROUND & AIMS: :We report an unusual case in which a patient presented with a large posterior mediastinal goiter that extended to the level of the aorta. The goiter was resected through a standard Kocher neck incision with mediastinoscopic assistance. The large goiter was completely excised without the need for a sternotomy.
    背景与目标: : 我们报告了一个不寻常的病例,其中患者出现了巨大的后纵隔甲状腺肿,并延伸到主动脉水平。在纵隔镜辅助下,通过标准的Kocher颈部切口切除甲状腺肿。大甲状腺肿被完全切除,无需进行胸骨切开术。
  • 【内镜经膀胱-经尿道入路修复膀胱阴道瘘: 初始病例报告。】 复制标题 收藏 收藏
    DOI:10.1089/end.1997.11.203 复制DOI
    作者列表:Okamura K,Kanai S,Kurokawa T,Kondo A
    BACKGROUND & AIMS: :Through an endoscopic transvesico-transurethral approach, we closed a vesicovaginal fistula that occurred after hysterectomy in a patient with uterine leiomyoma. The 3-mm fistula, located in the midportion of retrotrigone, was resected transurethrally and sutured in two layers through two 5-mm suprapubic trocars placed into the bladder and the urethral route under pneumobladder. The patient had no urine leakage from the vagina after surgery.
    背景与目标: : 通过内窥镜经膀胱-经尿道入路,我们关闭了子宫平滑肌瘤患者子宫切除术后发生的膀胱阴道瘘。位于后三叉肌中部的3毫米瘘管经尿道切除,并通过放置在膀胱和尿道下的两个5毫米耻骨上套管针缝合两层。患者术后无阴道漏尿。
  • 【意大利北部地区的综合废物管理: 堆肥生产和使用以及堆肥,土壤和作物的分析控制。】 复制标题 收藏 收藏
    DOI:10.1080/03601230600857031 复制DOI
    作者列表:Guerini G,Maffeis P,Allievi L,Gigliotti C
    BACKGROUND & AIMS: :Agricultural soils of two Italian maize farms were treated for five years with an industrially produced high-quality compost. Cattle manure and the usual mineral fertilizer were used for comparison purposes. The effects of the organic and mineral fertilizer treatments were studied by analyzing the compost and manure, cultured soils, and harvested material. The grain yield was also determined. Organic fertilization improved soil pH, CEC, content of organic matter and NPK. Soil respiration and N mineralization were found to be higher than in the purely mineral-treated soil. Plant K take-up was improved, whereas grain yield was not affected. It was confirmed that organic fertilization, particularly compost use, maintained and increased soil fertility. The study demonstrated the feasibility of using in loco analytical facilities to follow the entire recycling process-from waste to compost production-and the use of the final product in the field.
    背景与目标: : 意大利两个玉米农场的农业土壤用工业生产的高质量堆肥处理了五年。牛粪和通常的矿物肥料用于比较目的。通过分析堆肥和肥料,培养的土壤和收获的材料,研究了有机和矿物肥料处理的效果。还确定了谷物产量。有机施肥改善了土壤pH,CEC,有机质和NPK的含量。发现土壤呼吸作用和氮矿化作用高于纯矿物处理的土壤。提高了植物的K用量,而不影响谷物产量。已经证实,有机施肥,特别是堆肥的使用,可以维持和提高土壤肥力。该研究证明了在loco分析设施中使用从废物到堆肥生产的整个回收过程以及在现场使用最终产品的可行性。
  • 【经腋窝入路无气内镜甲状腺切除术30例。】 复制标题 收藏 收藏
    DOI:10.1097/00129689-200608000-00006 复制DOI
    作者列表:Yoon JH,Park CH,Chung WY
    BACKGROUND & AIMS: :Surgery for thyroid disease requires skin incisions that can result in postsurgical problems such as prominent scars, adhesions, hypesthesia, and paresthesia in the neck. To overcome these problems we performed gasless endoscopic thyroidectomy via an axillary approach. Between May 2004 and April 2005, 30 patients underwent gasless endoscopic thyroidectomy via an axillary approach. The mean operating time was 126.8+/-32.4 minutes, and the mean length of hospital stay was 4.3+/-1.1 days. No cases required conversion to open surgery and none involved significant intraoperative complications. Three patients (10.0%) complained of slight hypesthesia or paresthesia in the anterior chest wall, and only 2 patients (6.7%) complained of discomfort while swallowing 4 months after surgery. All patients were satisfied with the cosmetic results. Gasless endoscopic thyroidectomy via an axillary approach is feasible and safe and provides excellent cosmetic results with a minimal degree of postoperative complaints.
    背景与目标: 甲状腺疾病的手术需要皮肤切口,这可能会导致术后问题,如突出的疤痕、粘连、感觉减退和颈部感觉异常。为了克服这些问题,我们通过腋窝入路进行了无气内窥镜甲状腺切除术。在2004年5月和2005年4月之间,有30例患者通过腋窝入路接受了无气内窥镜甲状腺切除术。平均手术时间为126.8 +/-32.4分钟,平均住院时间为4.3 +/-1.1天。没有病例需要转换为开放手术,也没有涉及明显的术中并发症。3例患者 (10.0%) 主诉前胸壁轻微感觉减退或感觉异常,仅2例患者 (6.7%) 主诉术后4个月吞咽时不适。所有患者对美容结果均满意。通过腋窝入路进行的无气内窥镜甲状腺切除术是可行且安全的,并且可提供出色的美容效果,并且术后主诉程度最小。
  • 【白色念珠菌肉豆蔻酶a的选择性肽和拟肽抑制剂: 蛋白N-肉豆蔻酶转移酶: 抗真菌治疗的新方法。】 复制标题 收藏 收藏
    DOI:10.1002/(SICI)1097-0282(1997)43:1<43::AID-BIP5>3.0 复制DOI
    作者列表:Sikorski JA,Devadas B,Zupec ME,Freeman SK,Brown DL,Lu HF,Nagarajan S,Mehta PP,Wade AC,Kishore NS,Bryant ML,Getman DP,McWherter CA,Gordon JI
    BACKGROUND & AIMS: MyristoylCoA:protein N-myristoyltransferase (NMT) catalyzes the cotranslational covalent attachment of a rare cellular fatty acid, myristate, to the N-terminal Gly residue of a variety of eukaryotic proteins. The myristoyl moiety is often essential for expression of the biological functions for these proteins.

    Attachment of C14:0 alone provides barely enough hydrophobicity to allow stable association with membranes. The partitioning of N-myrisotylproteins is therefore often modulated by "switches" that function through additional covalent or noncovalent modifications. Candida albicans, the principal cause of systemic fungal infection in immunocompromised humans, contains a single NMT gene that is essential for its viability. The functional properties of the acylCoA binding site of human and C. albicans NMT are very similar. However, there are distinct differences in their peptide binding sites. An ADP ribosylation factor (Arf) is included among the few cellular protein substrates of the fungal enzyme. Alanine scanning mutagenesis of an octapeptide derived from an N-terminal Arf sequence (GLYASKLS-NH2) disclosed that Gly1, Ser5, and Lys6 play predominant roles in binding. ALYASKLS-NH2 is an inhibitor competitive for peptide [Ki(app) = 15.3 +/- 6.4 microM] and noncompetitive for myristoylCoA. Remarkably, replacement of the N-terminal tetrapeptide with an 11-aminoundecanoyl group results in a competitive inhibitor (11-aminoundecanoyl-SKLS-NH2) that is approximately 40-fold more potent [Ki(app) = 0.40 +/- 0.03 microM] than the starting octapeptide. Removal of Leu-Ser from the C-terminus generates a competitive dipeptide inhibitor (11-aminoundecanoyl-SK-NH2) with a Ki(app) of 11.7 +/- 0.4 microM, equivalent to that of the starting octapeptide. A derivative dipeptide inhibitor containing a C-terminal N-cyclohexylethyl lysinamide moiety has the advantage of being more potent (IC50 = 0.11 +/- 0.03 microM) and resistant to digestion by cellular carboxypeptidases. Rigidifying the flexible aminoundecanoyl chain results in very potent general NMT inhibitors (IC50 = 40-50 nM). Substituting a 2-methylimidazole for the N-terminal amine and adding a benzylic alpha-methyl group with R stereochemistry to the rigidifying element produces even more potent inhibitors (IC50 = 20-50 nM) that are up to 500-fold selective for the fungal compared to human enzyme. A related less potent member of this series of compounds is fungistatic. Its growth inhibitory effects are associated with a reduction in cellular protein N-myristoylation, judged using cellular Arf as a reporter. These studies establish that NMT is a new antifungal target.

    背景与目标: 肉豆蔻酰辅酶a : 蛋白质N-肉豆蔻酰转移酶 (NMT) 催化稀有细胞脂肪酸肉豆蔻酸酯与多种真核蛋白质的N末端Gly残基的共翻译共价连接。肉豆蔻酰部分对于表达这些蛋白质的生物学功能通常是必不可少的。
    C14的附着 :0仅提供了足够的疏水性,无法与膜稳定结合。因此,N-肉豆蔻基蛋白的分配通常由 “开关” 调节,该开关通过其他共价或非共价修饰起作用。白色念珠菌是免疫功能低下的人体全身性真菌感染的主要原因,它包含一个对其生存能力至关重要的NMT基因。人与白色念珠菌NMT的酰基辅酶a结合位点的功能特性非常相似。然而,它们的肽结合位点存在明显差异。真菌酶的少数细胞蛋白底物中包括ADP核糖基化因子 (Arf)。衍生自N-末端Arf序列 (GLYASKLS-NH2) 的八肽的丙氨酸扫描诱变揭示Gly1、Ser5和Lys6在结合中起主要作用。ALYASKLS-NH2是一种对肽 [Ki(app) = 15.3 +/- 6.4 microM] 有竞争力的抑制剂,对肉豆蔻酰辅酶a无竞争力。值得注意的是,用11-氨基十一酰取代N-末端四肽导致竞争性抑制剂 (11-氨基十一酰-skls-nh2) 的效力比起始八肽高约40倍 [Ki(app) = 0.40 +/- 0.03微米]。从C末端去除Leu-Ser会产生竞争性二肽抑制剂 (11-氨基十一酰-sk-nh2),Ki(app) 为11.7 +/- 0.4微米,相当于起始八肽。含有C-末端N-环己基乙基赖氨酰胺部分的衍生物二肽抑制剂具有更有效 (IC50 = 0.11 +/- 0.03微米) 和对细胞羧肽酶消化的抗性的优点。硬化柔性氨基十一酰链会产生非常有效的通用NMT抑制剂 (IC50 = 40-50nm)。用2-甲基咪唑代替N-末端胺并将具有R立体化学的苄基 α-甲基添加到硬化元件中,产生甚至更有效的抑制剂 (IC50 = 20-50nm),其对真菌的选择性与人酶相比高达500倍。该系列化合物中一个相关的效力较低的成员是真菌抑制剂。使用细胞Arf作为报告基因,其生长抑制作用与细胞蛋白N-肉豆蔻酰化的减少有关。这些研究表明,NMT是一种新的抗真菌靶标。
  • 【甲基-β-环糊精的分析表征,具有减少Niemann-Pick病C1型细胞中溶酶体胆固醇积累的药理活性。】 复制标题 收藏 收藏
    DOI:10.1089/adt.2017.774 复制DOI
    作者列表:Li R,Hao J,Fujiwara H,Xu M,Yang S,Dai S,Long Y,Swaroop M,Li C,Vu M,Marugan JJ,Ory DS,Zheng W
    BACKGROUND & AIMS: :Methyl-β-cyclodextrin (MβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MβCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MβCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MβCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MβCDs obtained from different batches and different sources. Furthermore, a proteomic analysis showed the differences of these three MβCD preparations on amelioration of dysregulated protein expression levels in NPC1 cells. The results demonstrate the importance of prescreening of different cyclodextrin preparations before use as a therapeutic agent. A combination of mass spectrum analysis, measurement of pharmacological activity, and proteomic profiling provides an effective analytical procedure for characterization of cyclodextrins for therapeutic applications.
    背景与目标: : 甲基-β-环糊精 (m β cd) 减少Niemann-Pick病C1 (NPC1) 患者成纤维细胞中的溶酶体胆固醇积累。但是,不同实验室报道的m β cd的药理活性有所不同。为了确定这种变异的潜在原因,我们分析了三种m β cds制剂的质谱特征,药理活性以及用不同来源的m β cds处理后NPC1患者成纤维细胞的蛋白表达谱。我们的数据揭示了从不同批次和不同来源获得的这三种m β cds制剂在NPC1成纤维细胞中减少溶酶体胆固醇积累的不同质谱谱和药理活性。此外,蛋白质组学分析表明,这三种m β cd制剂在改善NPC1细胞中蛋白表达水平失调方面存在差异。结果表明,在用作治疗剂之前,对不同的环糊精制剂进行预检查的重要性。质谱分析,药理活性测量和蛋白质组学分析相结合,为表征用于治疗应用的环糊精提供了有效的分析程序。
  • 【“生物碱harmalol与DNA的结合: 光物理和量热方法” 的勘误 [J. Photochem. Photobiol. B: Biol. 130 (2014) 272-280]。】 复制标题 收藏 收藏
    DOI:10.1016/j.jphotobiol.2015.03.003 复制DOI
    作者列表:Sarkar S,Bhadra K
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【当地卫生部门对儿童肥胖监测的协作方法。】 复制标题 收藏 收藏
    DOI:10.1097/PHH.0000000000000615 复制DOI
    作者列表:Alleman E,Murphy E,Baskerville K,Chugh R
    BACKGROUND & AIMS: :DuPage County Health Department collected de-identified data from health forms submitted by participating schools for academic years 2011-2015 for kindergarten, sixth-, and ninth-grade students to determine the prevalence of obesity and elevated blood pressure among public school students. The prevalence of obesity in students for the 2014-2015 school year was 15.1%, and the prevalence of elevated blood pressure was 22.8%. Students in the "obese" body mass index percentile category had an elevated blood pressure prevalence of 44.2%, which was higher than students in the "nonobese" category (P < .001). Significant differences were also observed both by sex and by grade. The results identify the need to support implementation and evaluation of policies to reduce childhood obesity and improve health outcomes. By partnering with schools to obtain preexisting health data, state or local health departments with limited resources may replicate these methods to develop a childhood obesity surveillance system.
    背景与目标: : 杜佩奇县卫生部门从参与学校提交的2011-2015学年幼儿园,六年级和九年级学生的健康表格中收集了不识别的数据,以确定公立学校学生中肥胖和血压升高的患病率。2014-2015学年学生的肥胖患病率为15.1%,血压升高的患病率为22.8%。“肥胖” 体重指数百分位类别的学生的血压患病率升高为44.2%,高于 “非肥胖” 类别的学生 (P <.001)。按性别和等级也观察到显着差异。结果表明需要支持实施和评估减少儿童肥胖和改善健康结果的政策。通过与学校合作以获取先前存在的健康数据,资源有限的州或地方卫生部门可以复制这些方法来开发儿童肥胖监测系统。
  • 【Α c螺旋位移作为蛋白质激酶变构调节的一般方法。】 复制标题 收藏 收藏
    DOI:10.1016/j.drudis.2012.11.009 复制DOI
    作者列表:Palmieri L,Rastelli G
    BACKGROUND & AIMS: :Owing to their crucial role in the modulation of cell pathways, protein kinases are important targets for several human diseases, including but not limited to cancer. The classic approach of targeting the ATP active site has recently come up against selectivity issues, which can be considerably reduced by following an allosteric modulation approach. Being closely related to protein kinase inactivation, allosteric targeting via displacement of the conserved structural αC helix enables a direct and specific modulation mechanism. A structure-based survey of the allosteric regulation of αC helix conformation in various kinase families is provided, highlighting key allosteric pockets and modulation mechanisms that appear to be more broadly conserved than was previously thought.
    背景与目标: : 由于其在调节细胞途径中的关键作用,蛋白激酶是多种人类疾病的重要靶标,包括但不限于癌症。靶向ATP活性位点的经典方法最近出现了选择性问题,通过采用变构调节方法可以大大减少选择性问题。与蛋白激酶失活密切相关,通过置换保守的结构 α c螺旋进行变构靶向可实现直接和特定的调节机制。提供了对各种激酶家族中 α c螺旋构象的变构调节的基于结构的调查,强调了关键的变构口袋和调节机制,这些机制似乎比以前认为的更为保守。
  • 【降低ST段抬高型心肌梗死放射状入路围手术期死亡率和出血率。来自ORPKI波兰国家注册中心的数据的倾向得分分析。】 复制标题 收藏 收藏
    DOI:10.4244/EIJ-D-17-00078 复制DOI
    作者列表:Siudak Z,Tokarek T,Dziewierz A,Wysocki T,Wiktorowicz A,Legutko J,Żmudka K,Dudek D
    BACKGROUND & AIMS: AIMS:We sought to evaluate bleeding complications and periprocedural outcomes of the radial approach (RA) as compared to the femoral approach (FA) during percutaneous coronary intervention (PCI) in "real-world" patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS:The study group consisted of 22,812 consecutive patients with STEMI treated with PCI and stent implantation between January 2014 and June 2015 in 151 tertiary invasive cardiology centres in Poland (the ORPKI Polish National Registry). Patients treated using the RA and FA were compared using a propensity score analysis to avoid possible selection bias. The analysis was carried out in an "as-treated" manner. The FA was used in 9,334 (40.9%) and the RA in 13,478 (59.1%) patients. After propensity score matching, a higher total amount of contrast (191.8±8.0 vs. 174.8±68.8 ml; p=0.001) and lower radiation doses (1,279.5±1,346.3 vs. 1,182.6±887 mGy; p=0.02) were reported in FA. More access-site-related bleeding complications after both angiography (0.17% vs. 0.02%; p=0.004) and PCI (0.23% vs. 0.09%; p=0.049) were reported in the FA group. Periprocedural death (1.94% vs. 0.93%; p=0.001) was more common after PCI performed with the FA. CONCLUSIONS:The radial approach was associated with a lower incidence of periprocedural death in STEMI patients as well as a significant reduction of bleeding complications at the access site.
    背景与目标:
  • 【遵循基于可水解酰基酶的机制的双底物酰基转移酶反应稳态动力学的理论方法。溶血磷脂酰胆碱的研究应用: rab的溶血磷脂酰胆碱酰基转移酶】 复制标题 收藏 收藏
    DOI:10.1042/bj2660047 复制DOI
    作者列表:Martín J,Pérez-Gil J,Acebal C,Arche R
    BACKGROUND & AIMS: :A kinetic model is proposed for catalysis by an enzyme that has several special characteristics: (i) it catalyses an acyl-transfer bi-substrate reaction between two identical molecules of substrate, (ii) the substrate is an amphiphilic molecule that can be present in two physical forms, namely monomers and micelles, and (iii) the reaction progresses through an acyl-enzyme-based mechanism and the covalent intermediate can react also with water to yield a secondary hydrolytic reaction. The theoretical kinetic equations for both reactions were deduced according to steady-state assumptions and the theoretical plots were predicted. The experimental kinetics of lysophosphatidylcholine:lysophosphatidylcholine acyltransferase from rabbit lung fitted the proposed equations with great accuracy. Also, kinetics of inhibition by products behaved as expected. It was concluded that the competition between two nucleophiles for the covalent acyl-enzyme intermediate, and not a different enzyme action depending on the physical state of the substrate, is responsible for the differences in kinetic pattern for the two activities of the enzyme. This conclusion, together with the fact that the kinetic equation for the transacylation is quadratic, generates a 'hysteretic' pattern that can provide the basis of self-regulatory properties for enzymes to which this model could be applied.
    背景与目标: : 提出了一种动力学模型,用于通过具有以下几个特殊特征的酶进行催化 :( i) 它催化两个相同的底物分子之间的酰基转移双底物反应,(ii) 底物是两亲分子,可以以两种物理形式存在,即单体和胶束,(iii) 反应通过基于酰基酶的机理进行,共价中间体也可以与水反应产生二次水解反应。根据稳态假设推导了两个反应的理论动力学方程,并预测了理论曲线。溶血磷脂酰胆碱的实验动力学: 来自兔肺的溶血磷脂酰胆碱酰基转移酶非常准确地拟合了所提出的方程。此外,产品抑制的动力学表现与预期的一样。结论是,两个亲核试剂之间对共价酰基酶中间体的竞争,而不是取决于底物物理状态的不同酶作用,是造成酶两种活性动力学模式差异的原因。该结论以及转酰化的动力学方程是二次的事实,产生了 “滞后” 模式,可以为可以应用该模型的酶提供自我调节特性的基础。
  • 【与消化类型和体重有关的大型食草动物的纤维消化率-体外方法。】 复制标题 收藏 收藏
    DOI:10.1016/j.cbpa.2012.10.026 复制DOI
    作者列表:Steuer P,Südekum KH,Müller DW,Kaandorp J,Clauss M,Hummel J
    BACKGROUND & AIMS: :The coexistence of different ungulate species in a given ecosystem has been the focus of many studies. Differences between ruminant foregut fermenters and hindgut fermenters were remarkable for example in the way they ingest and digest high fibre diets. Digestion trials based on total collections are difficult to conduct or are sometimes even not possible for wild animals in the field or in zoos. To gain information on the fibre digestion achieved by these animals and the influence of body mass (BM) thereon, a method using spot sampling is desirable. In this study, in vitro fermentation of faecal neutral detergent fibre (NDF) was used as a measure of fibre digestion in large ungulates. Food and faecal samples of 10 ruminant foregut fermenting and 7 hindgut fermenting species/breeds were collected. All animals received 100% grass hay with ad libitum access. The NDF of food and faeces was fermented in vitro in a Hohenheim gas test (HGT) for 96 h. The digestion type generally had an effect on the gas production (GP) of faecal NDF in the HGT with hindgut fermenters showing higher values than ruminant foregut fermenters. At any time interval of incubation, BM had no influence on GP. The results are in accordance with both findings that ruminant foregut fermenters have longer mean retention times and more comprehensive particle reduction and findings of a lack of influence of BM on digesta mean retention time. It can be stated that the HGT (96 h) is a useful and quick method to show also small differences within groups in fibre digestion.
    背景与目标: : 给定生态系统中不同有蹄类物种的共存一直是许多研究的重点。反刍动物前肠发酵罐和后肠发酵罐之间的差异很明显,例如它们在摄取和消化高纤维饮食的方式上。基于总收集物的消化试验很难进行,有时甚至无法进行野外或动物园中的野生动物。为了获得有关这些动物实现的纤维消化以及体重 (BM) 对其的影响的信息,需要使用斑点采样的方法。在这项研究中,粪便中性洗涤剂纤维 (NDF) 的体外发酵被用作大型有蹄类动物中纤维消化的量度。收集了10个反刍动物前肠发酵和7个后肠发酵物种/品种的食物和粪便样品。所有动物都可以随意访问100% 草干草。食物和粪便的NDF在Hohenheim气体测试 (HGT) 中体外发酵96小时。消化类型通常对HGT中粪便NDF的产气 (GP) 有影响,后肠发酵罐的产气值高于反刍前肠发酵罐。在任何孵育时间间隔,BM对GP均无影响。结果与反刍动物前肠发酵罐具有更长的平均保留时间和更全面的颗粒还原以及BM对消化平均保留时间缺乏影响的两个发现一致。可以说,HGT (96 h) 是一种有用且快速的方法,可以显示纤维消化组之间的微小差异。
  • 【减轻可卡因对细胞外多巴胺影响的直接方法: 靶向多巴胺转运蛋白。】 复制标题 收藏 收藏
    DOI:10.1002/(SICI)1098-2396(199708)26:4<423::AID-SYN10 复制DOI
    作者列表:Morgan AE,Porter SP,Clarkson FA,Volkow ND,Fowler JS,Dewey SL
    BACKGROUND & AIMS: Using in vivo microdialysis techniques, the effects of RTI-55 and/or cocaine on extracellular dopamine (DA) concentrations were measured in the nucleus accumbens (NACC) of freely moving rats. In control animals, cocaine (20 mg/kg) increased NACC DA approximately 458% 60 minutes following administration, returning to baseline values within 200 minutes. Similarly, RTI-55 administration (0.25 mg/kg) increased NACC DA levels approximately 347%. When combined, however, cocaine further increased NACC DA to 705% of baseline values when given 4 hours following RTI-55. This increase was significantly larger than cocaine alone (P < 0.05). In addition, chronic RTI-55 administration (5 days) further potentiated cocaine's ability to increase NACC DA (783%) but this did not reach statistical significance (P > 0.1) compared to acute RTI55/cocaine animals. These findings indicate that RTI-55, a drug that binds directly to the dopamine transporter (DAT) with higher affinity than cocaine, does not appear to be effective in attenuating cocaine's effects on NACC dopamine levels. In fact, acute RTI-55 potentiates cocaine's effects on NACC DA.

    背景与目标: 使用体内微透析技术,在自由运动的大鼠伏隔核 (NACC) 中测量了RTI-55和/或可卡因对细胞外多巴胺 (DA) 浓度的影响。在对照动物中,可卡因 (20 mg/kg) 在给药后约60分钟458% 增加NACC DA,在200分钟内恢复到基线值。类似地,RTI-55施用 (0.25 mg/kg) 使NACC DA水平增加约347%。然而,当合并时,当RTI-55后4小时给予时,可卡因进一步增加NACC DA至基线值的705%。这一增加显著大于单独使用可卡因 (P <0.05)。此外,慢性RTI-55给药 (5天) 进一步增强了可卡因增加NACC DA (783%) 的能力,但与急性RTI55/可卡因动物相比,这没有达到统计学意义 (P> 0.1)。这些发现表明,RTI-55是一种直接与多巴胺转运蛋白 (DAT) 结合的药物,其亲和力高于可卡因,似乎无法有效减轻可卡因对NACC多巴胺水平的影响。实际上,急性RTI-55增强了可卡因对NACC DA的影响。
  • 14 Dengue vaccines approach the finish line. 复制标题 收藏 收藏

    【登革热疫苗接近终点线。】 复制标题 收藏 收藏
    DOI:10.1086/518148 复制DOI
    作者列表:Edelman R
    BACKGROUND & AIMS: :The spread of dengue virus (DV) via its Aedes mosquito vector throughout most of the tropics has led to a worldwide resurgence of epidemic dengue, including dengue hemorrhagic fever. For the first time in 60 years, the pipeline of dengue vaccines looks promising. Strains of each of the 4 DV serotypes, attenuated by passage in tissue culture or by recombinant DNA technology, have been formulated into tetravalent vaccines and have entered successful phase 1 and 2 clinical trials in the United States and Southeast Asia. Antibody-dependent enhancement of wild-type DV infections by the vaccine represents a unique safety issue, which is under investigation. The Pediatric Dengue Vaccine Initiative (funded by the Bill and Melinda Gates Foundation), the World Health Organization, industry, the US military, and governments of tropical countries are collaborating to accelerate dengue vaccine development and phase 3 vaccine efficacy trials in countries where dengue is endemic. A protective tetravalent vaccine must be licensed soon if dengue is to be brought under control.
    背景与目标: : 登革热病毒 (DV) 通过其伊蚊传播媒介在整个热带地区的传播导致了包括登革出血发热在内的全球流行登革热的复兴。60年来第一次,登革热疫苗的管道看起来很有希望。通过组织培养中的传代或通过重组DNA技术减弱的4种DV血清型中的每种菌株已被配制成四价疫苗,并已在美国和东南亚成功进入1期和2期临床试验。疫苗对野生型DV感染的抗体依赖性增强是一个独特的安全性问题,正在研究中。小儿登革热疫苗倡议 (由比尔和梅琳达·盖茨基金会资助),世界卫生组织,工业界,美国军方和热带国家的政府正在合作,以加快登革热国家的登革热疫苗开发和3期疫苗功效试验流行。如果要控制登革热,必须尽快获得保护性四价疫苗的许可。
  • 【从参与式行动研究方法研究中风后社区生活和参与的障碍和支持。】 复制标题 收藏 收藏
    DOI:10.1310/5X2G-V1Y1-TBK7-Q27E 复制DOI
    作者列表:Hammel J,Jones R,Gossett A,Morgan E
    BACKGROUND & AIMS: :This participatory action research study focused on identifying community participation goals, barriers, and supports/strategies in partnership with people who have experienced a stroke. Goals demonstrate that participation is more than activity performance in context; instead, it relates to "being a part of" the community and having access to participation opportunities and supports. Results of community site audits from the first 20 participants document environmental (physical, cognitive, social) and system level barriers, as well as effective strategies for promoting participation via environmental modification and systems level changes. A consumer-directed, Web-based tool for documenting participation barriers and sharing strategies is discussed.
    背景与目标: : 这项参与性行动研究的重点是与中风患者合作,确定社区参与的目标,障碍和支持/策略。目标表明,参与不仅仅是活动绩效。相反,它与 “成为社区的一部分” 并获得参与机会和支持有关。前20名参与者的社区现场审核结果记录了环境 (物理,认知,社会) 和系统级障碍,以及通过环境修改和系统级变化促进参与的有效策略。讨论了一种以消费者为导向的基于Web的工具,用于记录参与障碍和共享策略。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录