• 【花生对2型糖尿病高危肥胖女性血糖反应和食欲的急性和二餐影响: 一项随机交叉临床试验.】 复制标题 收藏 收藏
    DOI:10.1017/S0007114512004217 复制DOI
    作者列表:Reis CE,Ribeiro DN,Costa NM,Bressan J,Alfenas RC,Mattes RD
    BACKGROUND & AIMS: :Nut consumption is associated with a reduced risk of type 2 diabetes mellitus (T2DM). The aim of the present study was to assess the effects of adding peanuts (whole or peanut butter) on first (0-240 min)- and second (240-490 min)-meal glucose metabolism and selected gut satiety hormone responses, appetite ratings and food intake in obese women with high T2DM risk. A group of fifteen women participated in a randomised cross-over clinical trial in which 42·5 g of whole peanuts without skins (WP), peanut butter (PB) or no peanuts (control) were added to a 75 g available carbohydrate-matched breakfast meal. Postprandial concentrations (0-490 min) of glucose, insulin, NEFA, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), appetitive sensations and food intake were assessed after breakfast treatments and a standard lunch. Postprandial NEFA incremental AUC (IAUC) (0-240 min) and glucose IAUC (240-490 min) responses were lower for the PB breakfast compared with the control breakfast. Insulin concentrations were higher at 120 and 370 min after the PB consumption than after the control consumption. Desire-to-eat ratings were lower, while PYY, GLP-1 and CCK concentrations were higher after the PB intake compared with the control intake. WP led to similar but non-significant effects. The addition of PB to breakfast moderated postprandial glucose and NEFA concentrations, enhanced gut satiety hormone secretion and reduced the desire to eat. The greater bioaccessibility of the lipid component in PB is probably responsible for the observed incremental post-ingestive responses between the nut forms. Inclusion of PB, and probably WP, to breakfast may help to moderate glucose concentrations and appetite in obese women.
    背景与目标: : 食用坚果与降低2型糖尿病 (T2DM) 的风险相关。本研究的目的是评估添加花生 (全或花生酱) 对第一 (0-240分钟) 和第二 (240-490分钟) 膳食葡萄糖代谢和选定的肠道饱腹激素反应的影响,高T2DM风险肥胖女性的食欲等级和食物摄入。一组15名妇女参加了一项随机交叉临床试验,其中将42·5克不含皮 (WP),花生酱 (PB) 或无花生 (对照) 的全花生添加到75克可用的碳水化合物匹配早餐中。在早餐治疗和标准午餐后,评估餐后葡萄糖,胰岛素,NEFA,胰高血糖素样肽-1 (GLP-1),肽YY (PYY),胆囊收缩素 (CCK),食欲感和食物摄入量的浓度 (0-490分钟)。与对照早餐相比,PB早餐的餐后NEFA增量AUC (IAUC) (0-240分钟) 和葡萄糖IAUC (240-490分钟) 响应较低。PB消耗后120和370分钟的胰岛素浓度高于对照消耗后的胰岛素浓度。与对照摄入量相比,摄入PB后的饮食欲望等级较低,而PYY,GLP-1和CCK浓度较高。WP导致了类似但不显著的影响。早餐中添加PB可降低餐后葡萄糖和NEFA的浓度,增强肠道饱腹激素的分泌并降低进食欲望。PB中脂质成分的更大的生物可及性可能是观察到的坚果形式之间摄入后的增量反应的原因。在早餐中加入PB (可能是WP) 可能有助于减轻肥胖女性的葡萄糖浓度和食欲。
  • 【儿童和青少年使用第二代抗精神病药相关代谢并发症的管理建议。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Ho J,Panagiotopoulos C,McCrindle B,Grisaru S,Pringsheim T,Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group.
    BACKGROUND & AIMS: BACKGROUND:Second-generation antipsychotics are commonly associated with metabolic complications. These medications are being used more frequently for the treatment of mental health disorders in children, which has stimulated the need for creating formal guidelines on monitoring their safety and effectiveness. Previous guidelines have been developed for monitoring metabolic and neurological complications. To assist practitioners who perform these monitoring procedures, a complementary set of treatment recommendations have been created for situations in which abnormal measurements or results are encountered. OBJECTIVE:To create evidence-based recommendations to assist in managing metabolic complications in children being treated with second-generation antipsychotics. METHODS:A systematic review of the literature on metabolic complications of second-generation antipsychotic medications in children was conducted. Members of the consensus group evaluated the information gathered from the systematic review of the literature and used a nominal group process to reach a consensus on treatment recommendations. Wherever possible, references were made to existing guidelines on the evaluation and treatment of metabolic abnormalities in children. RESULTS:Evidence-based recommendations are presented to assist in managing metabolic complications including weight gain; increased waist circumference; elevation in prolactin, cholesterol, triglyceride and glucose levels; abnormal liver function tests and abnormal thyroid studies. CONCLUSION:The use of second-generation antipsychotics requires proper monitoring procedures. The present treatment guideline provides guidance to clinicians on the clinical management of metabolic complications if they occur.
    背景与目标:
  • 【胶原: 酰胺I带手性二阶光学非线性的结构起源。】 复制标题 收藏 收藏
    DOI:10.1016/j.bpj.2012.10.017 复制DOI
    作者列表:Reiser KM,McCourt AB,Yankelevich DR,Knoesen A
    BACKGROUND & AIMS: :The molecular basis of nonlinear optical (NLO) chiral effects in the amide I region of type I collagen was investigated using sum-frequency generation vibrational spectroscopy; chiral and achiral tensor elements were separated using different input/output beam polarization conditions. Spectra were obtained from native rat tail tendon (RTT) collagen and from cholesteric liquid crystal-like (LC) type I collagen films. Although RTT and LC collagen both possess long-range order, LC collagen lacks the complex hierarchical organization of RTT collagen. Their spectra were compared to assess the role of such organization in NLO chirality. No significant differences were observed between RTT and LC with respect to chiral or achiral spectra. These findings suggest that amide I NLO chiral effects in type I collagen assemblies arise predominantly from the chiral organization of amide chromophores within individual collagen molecules, rather than from supramolecular structures. The study suggests that sum-frequency generation vibrational spectroscopy may be uniquely valuable in exploring fundamental aspects of chiral nonlinearity in complex macromolecular structures.
    背景与目标: : 使用和频产生振动光谱研究了I型胶原的酰胺I区域中非线性光学 (NLO) 手性效应的分子基础; 使用不同的输入/输出光束偏振条件分离手性和非手性张量元素。光谱是从天然的大鼠尾腱 (RTT) 胶原蛋白和胆甾型液晶样 (LC) I型胶原蛋白膜获得的。尽管RTT和LC胶原蛋白都具有长程顺序,但LC胶原蛋白缺乏RTT胶原蛋白的复杂层次组织。比较了它们的光谱,以评估这种组织在NLO手性中的作用。在手性或无手性光谱方面,RTT和LC之间未观察到显着差异。这些发现表明,I型胶原蛋白组装体中的酰胺I NLO手性作用主要来自单个胶原蛋白分子中酰胺发色团的手性组织,而不是超分子结构。研究表明,和频产生振动光谱在探索复杂大分子结构中手性非线性的基本方面可能具有独特的价值。
  • 【产前超声检查与胎儿尸检结果之间的一致性: 妊娠中期终止的回顾性研究。】 复制标题 收藏 收藏
    DOI:10.1055/s-0032-1325538 复制DOI
    作者列表:Lomax L,Johansson H,Valentin L,Sladkevicius P
    BACKGROUND & AIMS: OBJECTIVES:To estimate the agreement between prenatal ultrasonography observations at 16 - 21 gestational weeks and fetal autopsy findings in pregnancies terminated because of fetal anomalies. STUDY DESIGN:This 4½ year retrospective study includes consecutive fetuses that were terminated because of fetal malformation and/or chromosomal anomaly diagnosed in the second trimester. Only fetuses that had undergone fetal anatomy scanning by an obstetrician trained in fetal ultrasound before the termination and with available fetal autopsy reports were included. The cases were identified through the malformation registry database of our ultrasound unit. The sensitivity and specificity of ultrasound were calculated per organ system. When estimating the agreement between ultrasound results and autopsy findings, the cases were allocated to one of four categories according to the degree of concordance between ultrasound and autopsy findings: full agreement, near match, partial agreement and unconfirmed ultrasound findings. RESULTS:71 of 95 pregnancy terminations due to fetal malformations met the inclusion criteria and constitute our study population. The sensitivity of ultrasonography with regard to malformations in the brain and spine was 100 % (27/27) and with regard to malformations in the internal organ system (including malformations in the urogenital and gastrointestinal systems and in the abdominal wall and diaphragm) was 91 % (30/33). The corresponding figures for malformations in the cardiovascular and skeletal organ systems were 63 % (17/27) and 71 % (25/35), respectively. The specificity was lowest for malformations in the central nervous system and internal organ system (33/38, 87 % and 39/44, 89 %, respectively). There was full agreement between the ultrasound and autopsy findings in 44 % (31/71) of all cases and a near match in 46 % (33/71) of cases. In almost 10 % (7/71) of the pregnancies, the ultrasound findings were only partially confirmed or not confirmed by autopsy. In one case the discrepancy between the ultrasound and autopsy findings suggests that the pregnant woman might have decided to terminate the pregnancy on the basis of incorrect interpretation of ultrasound findings. CONCLUSION:Even though the agreement between ultrasound and autopsy findings was acceptable from a clinical point of view, agreement with regard to the detailed description of malformations was far from perfect. The detection rates were suboptimal for the cardiovascular and skeletal organ systems. :ZIEL:: Bewertung, inwieweit bei Schwangerschaftsabbrüchen aufgrund fetaler Anomalien die Befunde der pränatalen Ultraschalluntersuchung in der 16.–21. SSW mit dem Autopsiebefund des Feten übereinstimmen. METHODEN:Diese 4½ jährige retrospektive Studie schließt fortlaufend Feten ein, bei denen im 2. Trimenon ein Schwangerschaftsabbruch (TOP) aufgrund fetaler Fehlbildungen und/oder aufgrund von diagnostizierten Chromosomenanomalien erfolgt ist. Es wurden nur Feten einbezogen, bei denen vor dem Abbruch eine anatomische Untersuchung durch einen in der Fetalsonografie geübten Geburtshelfer durchgeführt wurde und bei denen fetale Autopsiebefunde vorlagen. Die Fälle wurden durch die Datenbank unserer Sonografieabteilung zur „Registrierung von Fehlbildungen“ ermittelt. Die Sensitivität und Spezifität der Sonografie wurde für jedes Organsystem berechnet. Zur Abschätzung der Übereinstimmung von Ultraschall- und Autopsiebefunden wurden die Fälle einer der vier Kategorien zugewiesen, je nach Grad der Übereinstimmung der Befunde: Solche mit völliger, sich fast entsprechender und nur teilweiser Übereinstimmung sowie nicht bestätigte Ultraschallbefunde. ERGEBNISSE:Die Einschlusskriterien erfüllten 71 von 95 Schwangerschaftsabbrüchen aufgrund fetaler Anomalien und bildeten somit unsere Studienpopulation. Die Sensitivität der Sonografie in Bezug auf Malformationen des Gehirns und Wirbelsäule betrug 100 % (27/27) und in Bezug auf Anomalien der inneren Organe (einschließlich der Fehlbildungen des Urogenital- und Magen-Darm-Systems, der Bauchdecke und des Diaphragmas) 91 % (31/33). Die entsprechende Rate für Anomalien des Herz-Kreislauf-Systems betrug 63 % (17/27) und für die des Skelettsystems 71 % (25/35). Die niedrigste Spezifität wurde für Malformationen des zentralen Nervensystems (33/38, 87 %) und der inneren Organe (39/44, 89 %) ermittelt. Eine völlige Übereinstimmung von Ultraschall- und Autopsiebefunden wurde in 44 % (31/71) und eine sich fast entsprechende Übereinstimmung in 46 % (33/71) aller Fälle gefunden. Bei beinahe 10 % (7/71) der Schwangerschaften konnten die Ultraschallbefunde nur teilweise beziehungsweise gar nicht durch die Autopsie bestätigt werden. In einem Fall mit diskrepanten Ultraschall- und Autopsiebefunden kann angenommen werden, dass die Schwangere die Entscheidung für einen Abbruch vermutlich aufgrund der fehlerhaften Interpretation des Ultraschallbefundes fällte. SCHLUSSFOLGERUNG:Obwohl die Übereinstimmung von Ultraschall- und Autopsiebefunden vom klinischen Standpunkt betrachtet akzeptierbar schien, war sie bezüglich der genauen Beschreibung der Fehlbildungen bei weitem nicht perfekt. Die Trefferquoten beim Herz-Kreislauf- und Skelettsystem waren suboptimal.
    背景与目标:
  • 【用于第二代生物燃料生产的宏基因组功能性纤维素酶的生物勘探: 综述。】 复制标题 收藏 收藏
    DOI:10.1080/1040841X.2017.1337713 复制DOI
    作者列表:Tiwari R,Nain L,Labrou NE,Shukla P
    BACKGROUND & AIMS: :Second generation biofuel production has been appeared as a sustainable and alternative energy option. The ultimate aim is the development of an industrially feasible and economic conversion process of lignocellulosic biomass into biofuel molecules. Since, cellulose is the most abundant biopolymer and also represented as the photosynthetically fixed form of carbon, the efficient hydrolysis of cellulose is the most important step towards the development of a sustainable biofuel production process. The enzymatic hydrolysis of cellulose by suites of hydrolytic enzymes underlines the importance of cellulase enzyme system in whole hydrolysis process. However, the selection of the suitable cellulolytic enzymes with enhanced activities remains a challenge for the biorefinery industry to obtain efficient enzymatic hydrolysis of biomass. The present review focuses on deciphering the novel and effective cellulases from different environmental niches by unculturable metagenomic approaches. Furthermore, a comprehensive functional aspect of cellulases is also presented and evaluated by assessing the structural and catalytic properties as well as sequence identities and expression patterns. This review summarizes the recent development in metagenomics based approaches for identifying and exploring novel cellulases which open new avenues for their successful application in biorefineries.
    背景与目标: : 第二代生物燃料生产已成为可持续和替代能源的选择。最终目的是开发一种工业上可行且经济地将木质纤维素生物质转化为生物燃料分子的过程。由于纤维素是最丰富的生物聚合物,也表示为光合固定形式的碳,因此纤维素的有效水解是发展可持续生物燃料生产过程的最重要步骤。通过一系列水解酶对纤维素进行酶促水解,突显了纤维素酶酶系统在整个水解过程中的重要性。然而,选择具有增强活性的合适的纤维素分解酶仍然是生物精炼工业获得生物质有效酶水解的挑战。本综述的重点是通过不可培养的宏基因组方法从不同的环境中破译新颖有效的纤维素酶。此外,还通过评估结构和催化特性以及序列同一性和表达模式来介绍和评估纤维素酶的综合功能方面。这篇综述总结了基于宏基因组学的方法在鉴定和探索新的纤维素酶方面的最新发展,为它们在生物精炼中的成功应用开辟了新的途径。
  • 【妊娠晚期二尖瓣腱索断裂引起的急性充血性心力衰竭。】 复制标题 收藏 收藏
    DOI:10.1111/j.1447-0756.2012.02014.x 复制DOI
    作者列表:Ohishi S,Nitta H,Chinen Y,Kinjo T,Masamoto H,Sakumoto K,Maeda T,Kuniyoshi Y,Aoki Y
    BACKGROUND & AIMS: :A 31-year-old woman complained of dyspnea and orthopnea at 38 weeks of gestation. A grade 3/6 pansystolic murmur was heard, and echocardiography revealed severe mitral regurgitation with a hyperechoic obstacle on the posterior mitral valve leaflet, consistent with a diagnosis of acute heart failure due to a ruptured chordae tendineae or an infectious endocarditis. An emergency cesarean section was performed under general anesthesia. A male infant was born weighing 2928 g with Apgar scores of 7 and 8 at 1 and 5 min, respectively. The patient was managed in the intensive care unit and underwent open-heart surgery for mitral valve repair on postpartum day 3. The two chordal tendineae appeared torn and frail, and a mitral annuloplasty was performed. No finding of infectious endocarditis was observed. Because it is a dramatic and life-threatening clinical situation, proper diagnosis and treatment in the intensive care unit assure a good outcome for both mother and fetus.
    背景与目标: : 一名31岁的妇女在妊娠38周时抱怨呼吸困难和正呼吸。听到了3/6级的全收缩期杂音,超声心动图显示严重的二尖瓣反流,二尖瓣后叶上有高回声障碍,这与由于腱索破裂或感染性心内膜炎引起的急性心力衰竭的诊断一致。在全身麻醉下进行紧急剖宫产。出生时体重为2928  g的男婴,分别在1和5  min时Apgar评分为7和8。该患者在重症监护病房接受治疗,并于产后第3天接受心脏直视手术进行二尖瓣修复。两个腱索出现撕裂和脆弱,并进行了二尖瓣环成形术。未发现感染性心内膜炎。由于这是一个戏剧性的,危及生命的临床情况,因此在重症监护病房中进行适当的诊断和治疗可确保母亲和胎儿的良好结局。
  • 【土耳其西部不同孕期和产后初期产妇白细胞总数和差异计数的参考值。】 复制标题 收藏 收藏
    DOI:10.1080/01443615.2016.1268575 复制DOI
    作者列表:Sanci M,Töz E,Ince O,Özcan A,Polater K,Inan AH,Beyan E,Akkaya E
    BACKGROUND & AIMS: :The aim of this study was to investigate alterations in the leukocyte and differential leukocyte counts in different trimesters of pregnancy and the initial postpartum period. The study population consisted of 40,325 pregnant women. A full blood count and automated differential leukocyte count were performed and all the haemogram results in the different trimesters of pregnancy were recorded. Percentiles were calculated using statistical software. A total of 82,786 complete blood count evaluations were performed in 40,325 subjects from the 6th to 41st week of pregnancy and in the initial postpartum period. The leukocyte counts increased from the 1st to the 3rd trimester and peaked in the initial postpartum period. Our reference values for the total and differential leukocyte counts may assist clinicians in distinguishing between leukocytosis and pathological elevation of the white blood cell count during pregnancy and the initial postpartum period. Impact statement Pregnancy requires profound adaptation by multiple systems to accommodate the demands of the developing foetus. Similar to all other systems, many haematological changes occur during pregnancy. Studies of normal variation in leukocyte counts were insufficient to distinguish normal from abnormal leukocyte counts during pregnancy and in the initial postpartum period, due to small numbers of patients and a lack of differential leukocyte counts. Without reference leukocyte levels, infections may be more difficult to assess during pregnancy and in the postpartum period. In this study, we report the 3rd, 5th, 10th, 50th, 95th and 99th percentile values for the total and differential leukocyte counts according to trimester in normal pregnancy and the initial postpartum period. Our reference values for the total and differential leukocyte counts in each trimester and the initial postpartum period may assist clinicians in distinguishing between normal leukocytosis and pathological elevation of the white blood cell count during pregnancy and the initial postpartum period. Our results may prevent misdiagnosis of physiological elevated leukocytes as bacterial infection that leads to unnecessary medication use that may compromise the foetus.
    背景与目标: : 这项研究的目的是调查妊娠不同三个月和产后初期白细胞和白细胞计数差异的变化。研究人群由40,325名孕妇组成。进行了全血细胞计数和自动差异白细胞计数,并记录了妊娠不同三个月的所有血象结果。使用统计软件计算百分位数。从怀孕的第6周至第41周和产后初期,对40,325名受试者进行了总共82,786次全血细胞计数评估。白细胞计数从第1个月到第3个月增加,并在产后初期达到峰值。我们的总白细胞计数和差异白细胞计数参考值可以帮助临床医生区分白细胞增多和妊娠和产后初期白细胞计数的病理升高。影响声明怀孕需要多个系统进行深刻的适应,以适应发育中的胎儿的需求。与所有其他系统相似,许多血液学变化发生在怀孕期间。由于患者人数少且缺乏差异的白细胞计数,对白细胞计数正常变化的研究不足以区分妊娠期间和产后初期的正常白细胞计数与异常白细胞计数。如果没有参考白细胞水平,则在怀孕期间和产后期间可能更难评估感染。在这项研究中,我们根据正常妊娠和产后初期的三个月报告了总白细胞计数和差异白细胞计数的第3、5、10、50、95和99个百分位数值。我们在每个孕期和产后初期的总白细胞计数和差异白细胞计数的参考值可以帮助临床医生区分正常的白细胞增多和妊娠和产后初期的白细胞计数的病理升高。我们的结果可以防止将生理性白细胞升高误诊为细菌感染,从而导致不必要的药物使用,从而可能损害胎儿。
  • 【新型香草素受体-1拮抗剂: 3。鉴定具有改善的理化和药代动力学特性的第二代临床候选者。】 复制标题 收藏 收藏
    DOI:10.1021/jm070191h 复制DOI
    作者列表:Wang HL,Katon J,Balan C,Bannon AW,Bernard C,Doherty EM,Dominguez C,Gavva NR,Gore V,Ma V,Nishimura N,Surapaneni S,Tang P,Tamir R,Thiel O,Treanor JJ,Norman MH
    BACKGROUND & AIMS: :Based on the previously reported clinical candidate, AMG 517 (compound 1), a series of related piperazinylpyrimidine analogues were synthesized and evaluated as antagonists of the vanilloid 1 receptor (VR1 or TRPV1). Optimization of in vitro potency and physicochemical and pharmacokinetic properties led to the discovery of (R)-N-(4-(6-(4-(1-(4-fluorophenyl)ethyl)piperazin-1-yl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide (16p), a potent TRPV1 antagonist [rTRPV1(CAP) IC50 = 3.7 nM] with excellent aqueous solubility (>or=200 microg/mL in 0.01 N HCl) and a reduced half-life (rat t1/2 = 3.8 h, dog t1/2 = 2.7 h, monkey t1/2 = 3.2 h) as compared to AMG 517. In addition, compound 16p was shown to be efficacious at blocking a TRPV1-mediated physiological response in vivo (ED50 = 1.9 mg/kg, p.o. in the capsaicin-induced flinch model in rats) and was also effective at reducing thermal hyperalgesia induced by complete Freund's adjuvant in rats (MED = 1 mg/kg, p.o). Based on its improved overall profile, compound 16p (AMG 628) was selected as a second-generation candidate for further evaluation in human clinical trials as a potential new treatment for chronic pain.
    背景与目标: : 基于先前报道的临床候选物AMG 517 (化合物1),合成了一系列相关的哌嗪基嘧啶类似物,并评估其作为香草酸1受体 (VR1或TRPV1) 的拮抗剂。体外效价和理化及药代动力学性质的优化导致发现 (R)-N-(4-(6-(4-(1-(4-氟苯基) 乙基) piperazin-1-yl)pyrimidin-4-yloxy) 苯并 [d]thiazol-2-yl) 乙酰胺 (16p),一种有效的TRPV1拮抗剂 [rTRPV1(CAP) IC50 = 3.7 nM],具有优异的水溶性 (在0.01 N HCl中> 或 = 200微克/毫升) 和减少的半衰期 (大鼠t1/2 = 3.8 h,狗t1/2 = 2.7 h,与AMG 517相比,猴子t1/2 = 3.2 h。此外,化合物16p在体内可有效阻断TRPV1-mediated生理反应 (ED50 = 1.9 mg/kg,p.o.在辣椒素诱导的大鼠退缩模型中),并且在减少完全弗氏佐剂诱导的大鼠热痛觉过敏方面也有效 (MED = 1 mg/kg,p.o)。基于其改善的总体特征,化合物16p (AMG 628) 被选为第二代候选物,用于在人类临床试验中进一步评估,作为潜在的慢性疼痛的新疗法。
  • 【第二代类固醇硫酸酯酶抑制剂STX213在激素依赖性乳腺癌治疗中的体内功效。】 复制标题 收藏 收藏
    DOI:10.1158/1078-0432.CCR-06-0632 复制DOI
    作者列表:Foster PA,Newman SP,Chander SK,Stengel C,Jhalli R,Woo LL,Potter BV,Reed MJ,Purohit A
    BACKGROUND & AIMS: PURPOSE:Steroid sulfatase (STS) inhibitors that can decrease or prevent the biosynthesis of estrogenic steroids via the sulfatase route may play an important role in the treatment of breast cancer. We compare the in vivo efficacy of two potent STS inhibitors, STX64 and STX213, in a xenograft breast cancer model. EXPERIMENTAL DESIGN:MCF-7 cells stably expressing STS cDNA (MCF-7STS) were generated. Ovariectomized MF-1 female nude mice receiving s.c. injections of estradiol sulfate (E2S) and bearing both MCF-7STS and wild-type MCF-7 (MCF-7WT) tumors were orally treated with STX64 and STX213. Treatment was given for 49 days followed by a recovery period of 35 days in which animals received only E2S. Mice were weighed, and tumor measurements were taken weekly. RESULTS:STX64 and STX213 exhibited potent STS inhibition in vivo. However, STX213 showed a greater duration of activity. In vehicle-treated nude mice receiving E2S, tumor volumes increased 5.5-fold for MCF-7WT and 3.8-fold for MCF-7STS after 49 days compared with day 0. MCF-7WT tumor growth was reduced by 56% by STX213 over the dosing period, and subsequent growth was retarded during the recovery period. All treatments fully inhibited growth of MCF-7STS tumors, and recovery of these tumors was significantly retarded (P<0.01). All compounds completely inhibited liver and tumor STS activity. Additionally, STS mRNA expression in the MCF-7STS tumors directly correlated with the corresponding STS enzyme activity. CONCLUSIONS:This study indicates that STS inhibitors attenuate hormone-dependent human breast cancer growth and therefore offer a potentially novel treatment for this condition.
    背景与目标:
  • 【人类怀孕和妊娠对运动过程中呼吸不适的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.resp.2006.08.004 复制DOI
    作者列表:Jensen D,Webb KA,Wolfe LA,O'Donnell DE
    BACKGROUND & AIMS: :This study examined the effects of human pregnancy and advancing gestation on the intensity of respiratory discomfort (dyspnea) during cycle exercise. Fourteen pregnant women (PG) performed a progressive cycle ergometer exercise test involving 20 W/min increases in work rate to symptom limitation and/or a heart rate of 170-175 beats/min at 19.7+/-1.2 weeks (ENTRY), 28.2+/-0.3 weeks (TM2) and 36.3+/-0.3 weeks (TM3) gestation. Eight, age-matched, sedentary non-pregnant women (CG) were also studied for comparison purposes. Measurements included dyspnea intensity (Borg scale), minute ventilation (VE), breathing pattern and other cardiorespiratory parameters. At peak exercise, neither pregnancy nor advancing gestation had an effect on dyspnea, VE, breathing pattern, oxygen uptake or work rate (p>0.05). VE was significantly greater (by 11 L/min at 100 W) in the PG at TM3 versus CG (p<0.05) at all submaximal work rates. VE also increased progressively from ENTRY to TM2 and TM3 during submaximal exercise. Dyspnea was not significantly different at any submaximal work rate in the PG at TM3 versus CG or with advancing gestation in the PG. In addition, dyspnea at a standardized exercise VE of 40 L/min was not different at TM3 versus ENTRY or in the PG at TM3 versus CG. Neither pregnancy nor advancing gestation were associated with increased respiratory discomfort during strenuous non-weight bearing cycle ergometer exercise, despite substantial increases in VE and progressive mechanical adaptations of the respiratory system to accommodate the increasing size of the gravid uterus.
    背景与目标: : 这项研究检查了人类怀孕和妊娠对周期运动期间呼吸不适 (呼吸困难) 强度的影响。14名孕妇 (PG) 进行了渐进式循环测力计运动测试,包括在19.7周 +/-1.2周 (进入) 时,工作速率增加20 W/min,以达到症状限制和/或心率170-175次/min,28.2 +/-0.3周 (TM2) 和36.3 +/-0.3周 (TM3)。为了比较目的,还研究了八名年龄匹配的久坐不动的非孕妇 (CG)。测量包括呼吸困难强度 (Borg量表),分钟通气量 (VE),呼吸模式和其他心肺参数。在运动高峰时,怀孕和妊娠均不会影响呼吸困难,VE,呼吸方式,摄氧量或工作效率 (p>0.05)。在所有次最大工作速率下,TM3的PG相对于CG (p<0.05) 的VE显着更高 (在100 W下为11 l/min)。在次最大运动期间,VE也从进入TM2和TM3逐渐增加。在TM3相对于CG的PG中,在任何亚最大工作速率下,或在PG中进行妊娠时,呼吸困难均无显着差异。此外,在标准化运动VE为40 l/min时的呼吸困难在TM3与ENTRY或PG在TM3与CG时没有差异。尽管VE的显着增加和呼吸系统的进行性机械适应以适应妊娠子宫的增加,但在剧烈的非负重循环测力计运动中,怀孕和妊娠都不会增加呼吸不适。
  • 【受唐氏综合症影响的妊娠中孕早期尿液游离 β-hCG,β 核心和总雌三醇: 颈项半透明和血清游离 β-hCG对孕早期筛查的影响。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0223(199706)17:6<525::aid-pd105 复制DOI
    作者列表:Spencer K,Noble P,Snijders RJ,Nicolaides KH
    BACKGROUND & AIMS: :We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Down's syndrome) in an attempt to see if any of the analytes have a value in Down's syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Down's syndrome with average multiple of the median levels of 1.81 and 2.91, respectively. Urine total oestriol was reduced (0.83) whilst maternal serum free beta hCG was increased (1.72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Down's group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false-positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first-trimester screening. Optimal first-trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy-associated plasma protein A.
    背景与目标: : 我们检查了母体尿液中 β 核心,游离 β 人绒毛膜促性腺激素 (hCG) 的浓度,以及373例对照妊娠和43例受非整倍性影响的妊娠 (包括22例唐氏综合征) 中的总雌三醇,试图在妊娠的第十周至第14周之间查看任何分析物在唐氏综合征筛查中是否具有价值。我们已经比较了这些分析物在妊娠同一时期与胎儿透明层测量结合母体血清游离 β hCG的性能。我们的结果表明,在唐氏综合症中,尿液游离的 β hCG和 β 核心水平分别增加了平均1.81和2.91水平的倍数。尿总雌三醇减少 (0.83),而母体血清游离 β-hCG增加 (1.72)。在18三体中,所有分析物的水平都降低了,尽管无血清 β-hCG是最有区别的。在对照组和唐氏组中,尿液 β 核心的结果传播是血清游离 β hCG的三倍以上,而尿液游离 β hCG的传播是其两倍。结合产妇年龄,尿总雌三醇检出率为32%,假阳性率固定为5%; 尿 β 核心34%,尿游离 β hCG 36%,母血清游离 β hCG 44%,颈项半透明82%。结合颈项半透明性,尿液总雌三醇额外增加了1% 的检测,尿液 β 核额外增加了2%,尿液游离 β hCG额外增加了3%,血清游离 β hCG额外增加了5%。在孕早期筛查中,任何尿液标志物都不太可能具有价值。在可预见的将来,最佳的孕早期筛查计划将依赖于颈项透明层,血清游离 β hCG以及可能与妊娠相关的血浆蛋白A。
  • 【在自由呼吸的幼儿的肺部通过0.3秒电影CT获得的吸气和呼气相图像上检测空气滞留。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.05.0895 复制DOI
    作者列表:Goo HW,Kim HJ
    BACKGROUND & AIMS: OBJECTIVE:The objective of our study was to evaluate whether 0.3-second cine CT can be used to detect air trapping in the lungs of young children. SUBJECTS AND METHODS:In 30 children (mean age, 25 months), 0.3-second cine CT was performed at six levels during 3 seconds of quiet breathing. The study population was divided into an air trapping group (n = 24) and a no-air trapping group (n = 6). Lung density was measured at an abnormal area (with or without air trapping) and an adjacent normal area on inspiratory and expiratory phase images. Lung density differences between inspiration and expiration were calculated and compared in abnormal areas (with or without air trapping) and in normal areas. Their percentages were calculated and compared between the two groups. In addition, lung density differences between abnormal and adjacent normal areas were calculated and compared between the two groups. RESULTS:Lung density differences between inspiration and expiration were smaller in areas with air trapping (mean +/- SD, -19 +/- 34 H) than in abnormal areas without air trapping (138 +/- 36 H) (p < 0.001) or in normal areas (111 +/- 49 H) (p < 0.001). Their percentages were smaller in the group with air trapping (-27% +/- 54%) than in the group with no air trapping (120% +/- 87%) (p < 0.001). In the group with air trapping, lung density differences were larger at the expiratory phase (260 +/- 77 H) than at the inspiratory phase (129 +/- 69 H) (p < 0.001), but did not change through the respiratory cycle in the group with no air trapping (p > 0.05). CONCLUSION:Air trapping can be accurately detected in the lungs of free-breathing young children using 0.3-second cine CT.
    背景与目标:
  • 【第二个大质粒编码O119:H2和一些典型的O111肠致病性大肠杆菌菌株中的结合转移和抗菌素耐药性。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00349-07 复制DOI
    作者列表:Nwaneshiudu AI,Mucci T,Pickard DJ,Okeke IN
    BACKGROUND & AIMS: :A novel and functional conjugative transfer system identified in O119:H2 enteropathogenic Escherichia coli (EPEC) strain MB80 by subtractive hybridization is encoded on a large multidrug resistance plasmid, distinct from the well-described EPEC adherence factor (EAF) plasmid. Variants of the MB80 conjugative resistance plasmid were identified in other EPEC strains, including the prototypical O111:NM strain B171, from which the EAF plasmid has been sequenced. This separate large plasmid and the selective advantage that it confers in the antibiotic era have been overlooked because it comigrates with the virulence plasmid on conventional gels.
    背景与目标: : 通过消减杂交在O119:H2肠致病性大肠杆菌 (EPEC) 菌株MB80中鉴定出的新颖且功能强大的共轭转移系统被编码在大型多药耐药质粒上,与描述明确的EPEC粘附因子 (EAF) 质粒不同。在其他EPEC菌株中鉴定了MB80共轭抗性质粒的变体,包括原型O111:NM菌株B171,从中对EAF质粒进行了测序。这种单独的大质粒及其在抗生素时代赋予的选择性优势被忽略了,因为它与常规凝胶上的毒力质粒共同存在。
  • 【正常妊娠期间对活化蛋白C反应的变异性。】 复制标题 收藏 收藏
    DOI:10.1097/00001721-199706000-00005 复制DOI
    作者列表:Bokarewa MI,Wramsby M,Bremme K,Blombäck M
    BACKGROUND & AIMS: The response to activated protein C (APC) was investigated in 28 healthy women, non-carriers of the Arg506-Gln mutation in factor V, throughout pregnancy (gestation weeks 12, 20, 28, 32 and 37) and after the delivery. A suppression of APC response was observed which reached lowest values by week 28 (nAPC-ratio 0.78 +/- 0.13), sustained low up to the end of pregnancy and rose after delivery (1.11 +/- 0.22; P < 0.05). APC resistance (nAPC ratio < 0.75) was registered in 16 of the 28 women (57%). A reduction of APC ratio was directly related to its value in the non-pregnant state, being most pronounced in the women with the highest APC ratio. Factor VIII increased during pregnancy and correlated inversely to APC ratio (Z coefficient = -0.645, P < 0.0001). The correlation became weaker in the course of pregnancy, losing significance by week 32. This was explained by the differences in profiles of the two variablesthe lowest measured APC ratio preceded the peak of factor VIII in most cases. The most pronounced rise of factor VIII was found in the women with minimal levels of APC ratio between 0.8 and 0.7. These results allowed us to speculate that APC response is closely regulated during pregnancy, aiming to maintain a certain relevant level. Transitory reduction of APC response is connected to factor VIII and discussed as a prevalent mechanism of functional APC resistance during pregnancy.

    背景与目标: 在整个妊娠期间 (妊娠第12、20、28、32和37周) 和分娩后,对28名健康妇女 (非因子V Arg506-Gln突变携带者) 的活化蛋白C (APC) 的反应进行了研究。观察到APC反应的抑制,其在第28周达到最低值 (nAPC比0.78 +/- 0.13),持续到妊娠结束并在分娩后上升 (1.11 +/- 0.22; P <0.05)。28名女性中有16名 (57% 名) 出现APC耐药 (nAPC比值 <0.75)。APC比率的降低与其在非怀孕状态下的价值直接相关,在APC比率最高的女性中最为明显。因子VIII在怀孕期间增加,并与APC比率成反比 (Z系数 = -0.645,P <0.0001)。相关性在怀孕过程中变弱,到第32周失去意义。这可以通过两个变量的分布差异来解释,在大多数情况下,最低的APC比率先于因子VIII的峰值。在0.8和0.7之间APC比率最低的女性中发现了因子VIII的最明显升高。这些结果使我们能够推测APC反应在怀孕期间受到密切调节,旨在维持一定的相关水平。APC反应的暂时性降低与因子VIII有关,并被认为是怀孕期间功能性APC抵抗的普遍机制。
  • 【妊娠唾液皮质醇分泌模式及其对评估方案的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.biopsycho.2006.07.005 复制DOI
    作者列表:Harville EW,Savitz DA,Dole N,Herring AH,Thorp JM,Light KC
    BACKGROUND & AIMS: :Cortisol is used in research as a biomarker of psychological stress. Logistical considerations argue for collecting as few samples as possible, balanced against diurnal rhythms and intra-individual variations. 100 pregnant women gave five saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m., 5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another sample was taken during a clinic visit. Using the 15 measures as the gold standard, correlations and mean area under the curve (AUC) were compared with subsets and the single clinic sample to evaluate alternate collection protocols. Five samples in 1 day, or protocols involving morning and night samples, had the highest correlations with mean AUC (correlation coefficient ranging from 0.82 to 0.88). Standardizing the clinic measurement to a single time of day did not substantially improve correlations with mean AUC. Correlations with measures of reported stress were also not strong.
    背景与目标: : 皮质醇在研究中被用作心理压力的生物标志物。后勤方面的考虑主张收集尽可能少的样本,并与昼夜节律和个体内部变化保持平衡。100名孕妇每天在醒来时,醒来后30分钟以及上午11:00,下午5:00和下午9:00时每天提供五个唾液样本收集时间由监视器确认。在诊所就诊时采集了另一个样本。使用15项措施作为金标准,将相关性和曲线下平均面积 (AUC) 与子集和单个临床样本进行比较,以评估替代收集方案。1天内的5个样品或涉及早晨和夜间样品的方案与平均AUC的相关性最高 (相关系数范围从0.82到0.88)。将临床测量标准化为一天中的单个时间并没有显着改善与平均AUC的相关性。与报告的压力度量的相关性也不强。

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