• 【与自我报告的谷物食品消费趋势相关的消费者态度和误解: 西澳大利亚成年人的横断面研究,1995 2012年。】 复制标题 收藏 收藏
    DOI:10.1186/s12889-017-4511-5 复制DOI
    作者列表:Pollard CM,Pulker CE,Meng X,Scott JA,Denham FC,Solah VA,Kerr DA
    BACKGROUND & AIMS: BACKGROUND:The reasons for low adherence to cereal dietary guidelines are not well understood but may be related to knowledge, attitudes, beliefs and perceived barriers. This study aims to assess trends in cereal foods consumption, intention to change and factors associated with intake among Western Australian (WA) adults 18 to 64 years. METHOD:Cross-sectional data from the 1995, 1998, 2001, 2004, 2009, and 2012 Nutrition Monitoring Survey Series involving 7044 adults were pooled. OUTCOME VARIABLES:types and amount of cereals (bread, rice, pasta, and breakfast cereal) eaten the day prior. Attitudes, knowledge, intentions, weight status and sociodemographic characteristics were measured. Descriptive statistics, multiple binary logistic and multinomial logistic regressions assess factors associated with consumption. RESULTS:Bread (78%) was the most commonly consumed cereal food. The proportion eating bread decreased across survey years (Odds Ratio OR = 0.31; 95% Confidence Interval; 0.24-0.40 in 2012 versus 1995), as did the amount (4.1 slices of bread in 1995 to 2.4 in 2012). The odds of consuming whole-grain cereal foods increased since 2009 (OR = 1.27; 1.02-1.58 versus 1995 p < 0.05). The likelihood of trying to eat less cereal food in the past year was greater in 2012 compared to 1995 (Relative Risk Ratio RRR 10.88; 6.81-17.4). Knowledge of cereal recommendations decreased over time (OR = 0.20; 0.15-0.27 in 2012 versus 1995 p < 0.001). Overweight and obese respondents were more likely than healthy weight respondents to have tried to eat less cereals (RRR 1.65; 1.22-2.24 and 1.88; 1.35-2.63 respectively). 'I already eat enough' was the main barrier (75% in 1995 to 84% in 2012 (p < 0.001)). CONCLUSIONS:WA adults are actively reducing the amount of cereal foods they eat and intake is associated with a misperception of adequacy of intake. Nutrition intervention is needed to increase awareness of the health benefits of cereal foods, particularly whole-grains, and to address barriers to incorporating them daily. TRIAL REGISTRATION:Not applicable.
    背景与目标:
  • 【90 kDa热休克蛋白在巴西副球菌适应不同环境条件期间的参与。】 复制标题 收藏 收藏
    DOI:10.1016/j.fgb.2012.11.005 复制DOI
    作者列表:Tamayo D,Muñoz JF,Torres I,Almeida AJ,Restrepo A,McEwen JG,Hernández O
    BACKGROUND & AIMS: :HSP90 is a molecular chaperone that participates in folding, stabilization, activation, and assembly of several proteins, all of which are key regulators in cell signaling. In dimorphic pathogenic fungi such as Paracoccidioides brasiliensis, the adaptation to a higher temperature, acid pH and oxidative stress, is an essential event for fungal survival and also for the establishing of the infectious process. To further understand the role of this protein, we used antisense RNA technology to generate a P. brasiliensis isolate with reduced PbHSP90 gene expression (PbHSP90-aRNA). Reduced expression of HSP90 decreased yeast cell viability during batch culture growth and increased susceptibility to acid pH environments and imposed oxidative stress. Also, PbHSP90-aRNA yeast cells presented reduced viability upon interaction with macrophages. The findings presented here suggest a protective role for HSP90 during adaptation to hostile environments, one that promotes survival of the fungus during host-pathogen interactions.
    背景与目标: : HSP90是一种分子伴侣,参与多种蛋白质的折叠,稳定,激活和组装,所有这些蛋白质都是细胞信号传导的关键调节剂。在双态致病性真菌 (例如巴西Paracoccidioides brasiliensis) 中,适应较高的温度,酸性pH和氧化应激是真菌存活以及建立感染过程的重要事件。为了进一步了解该蛋白的作用,我们使用反义RNA技术生成了具有降低PbHSP90基因表达 (PbHSP90-aRNA) 的巴西假单胞菌分离株。HSP90的表达降低了分批培养过程中酵母细胞的活力,并增加了对酸性pH环境的敏感性并施加了氧化应激。此外,PbHSP90-aRNA酵母细胞在与巨噬细胞相互作用时表现出降低的活力。此处提出的发现表明,HSP90在适应敌对环境期间具有保护作用,在宿主-病原体相互作用期间可促进真菌的存活。
  • 【古细菌酮体还原酶的鉴定和表征及其参与辅酶a生物合成的调控。】 复制标题 收藏 收藏
    DOI:10.1111/mmi.12363 复制DOI
    作者列表:Tomita H,Imanaka T,Atomi H
    BACKGROUND & AIMS: :Coenzyme A (CoA) biosynthesis in bacteria and eukaryotes is regulated primarily by feedback inhibition towards pantothenate kinase (PanK). As most archaea utilize a modified route for CoA biosynthesis and do not harbour PanK, the mechanisms governing regulation of CoA biosynthesis are unknown. Here we performed genetic and biochemical studies on the ketopantoate reductase (KPR) from the hyperthermophilic archaeon Thermococcus kodakarensis. KPR catalyses the second step in CoA biosynthesis, the reduction of 2-oxopantoate to pantoate. Gene disruption of TK1968, whose product was 20-29% identical to previously characterized KPRs from bacteria/eukaryotes, resulted in a strain with growth defects that were complemented by addition of pantoate. The TK1968 protein (Tk-KPR) displayed reductase activity specific for 2-oxopantoate and preferred NADH as the electron donor, distinct to the bacterial/eukaryotic NADPH-dependent enzymes. Tk-KPR activity decreased dramatically in the presence of CoA and KPR activity in cell-free extracts was also inhibited by CoA. Kinetic studies indicated that CoA inhibits KPR by competing with NADH. Inhibition of ketopantoate hydroxymethyltransferase, the first enzyme of the pathway, by CoA was not observed. Our results suggest that CoA biosynthesis in T. kodakarensis is regulated by feedback inhibition of KPR, providing a feasible regulation mechanism of CoA biosynthesis in archaea.
    背景与目标: : 细菌和真核生物中的辅酶a (CoA) 生物合成主要通过对泛酸激酶 (PanK) 的反馈抑制来调节。由于大多数古细菌利用改良的CoA生物合成途径并且不携带PanK,因此控制CoA生物合成的机制尚不清楚。在这里,我们对来自嗜热古细菌热球菌kodakarensis的酮托酸酯还原酶 (KPR) 进行了遗传和生化研究。KPR催化CoA生物合成的第二步,即2-氧尿囊酸酯还原为泛酸酯。TK1968的基因破坏 (其产物与先前来自细菌/真核生物的KPRs 20-29% 相同) 导致了具有生长缺陷的菌株,该菌株通过添加泛酸补充。TK1968蛋白 (Tk-KPR) 显示出对2-氧尿囊酸酯具有特异性的还原酶活性,并且首选NADH作为电子供体,与细菌/真核NADPH依赖性酶不同。在CoA存在下,tk-kpr活性显着降低,无细胞提取物中的KPR活性也受到CoA的抑制。动力学研究表明,CoA通过与NADH竞争来抑制KPR。未观察到CoA对该途径的第一个酶-酮体羟甲基转移酶的抑制作用。我们的研究结果表明,科达卡氏菌CoA的生物合成受KPR的反馈抑制调节,为古菌CoA的生物合成提供了可行的调控机制。
  • 【在发作期后不动综合征之后的抗伤害感受现象中,中缝大核和网状核的5-HT(2) 5-羟色胺能受体参与了巨核/副膜复合神经网络。】 复制标题 收藏 收藏
    DOI:10.1016/j.expneurol.2006.03.033 复制DOI
    作者列表:de Oliveira RC,de Oliveira R,Ferreira CM,Coimbra NC
    BACKGROUND & AIMS: :The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.
    背景与目标: : 发作期后不动综合症之后,动物和男性的伤害性阈值显着增加。在这种有趣的发作期后行为反应中,已经提出了内源性阿片肽介导的机制以及胆碱能介导的抗伤害感受过程。然而,考虑到许多血清素能下降途径与抗伤害感受反应有关,因此本工作的目的是研究5-HT(2)-血清素能受体亚家族在发作期抗伤害感受中的参与。每组7或8只Wistar大鼠通过甩尾试验测量镇痛效果。抽搐后,至少在发作后的120分钟内,甩尾潜伏期 (TFL) 具有统计学上的显着增加。雄性Wistar大鼠接受立体定向手术,以在菱形脑中引入引导套管,以瞄准中缝大核 (NRM) 或千兆体复合体。在独立的动物组中,这些核通过单侧微量注射ibotenic酸 (1.0 microg/0.2 microL) 被神经化学损伤。NRM或网状核巨囊细胞/旁囊细胞复合物的神经元损伤降低了发作后的镇痛作用。同样,在其他独立组中,在研究的所有发作期后,与对照组相比,将利坦色林 (5.0 microg/0.2 microL) 或生理盐水集中施用到每个研究的网状形成核中,引起抓住动物的TFL在统计学上显着降低。这些结果表明,脑桥和延髓网状核的5-羟色胺输入连接的神经元可能参与了发作期后的镇痛。
  • 【palytoxin诱导Na流入培养的牛肾上腺嗜铬细胞的机制: Na/H交换系统的可能参与。】 复制标题 收藏 收藏
    DOI:10.1016/0304-3940(91)90238-o 复制DOI
    作者列表:Yoshizumi M,Houchi H,Ishimura Y,Masuda Y,Morita K,Oka M
    BACKGROUND & AIMS: :To elucidate the mechanism of palytoxin (PTX)-induced Na+ influx, we examined the effect of amiloride, an inhibitor of Na+/H(+)-antiporter, on PTX-induced Na+ influx into cultured bovine adrenal chromaffin cells in relation to its effects on Ca2+ influx and catecholamine secretion. Amiloride dose-dependently inhibited PTX-induced 22Na+ influx, whereas tetrodotoxin (TTX) had no effect. Amiloride also inhibited PTX-induced Na(+)-dependent 45Ca2+ influx and catecholamine secretion. PTX alone did not significantly affect the intracellular pH, but it decreased in the presence of PTX and amiloride. These results indicate that an amiloride-sensitive Na+/H+ exchange mechanism is probably involved in PTX-induced, TTX-insensitive Na+ influx that triggers Ca2+ influx and catecholamine secretion from the cells.
    背景与目标: : 为了阐明palytoxin (PTX) 诱导的Na内流的机制,我们研究了Na/H ()-反转运蛋白抑制剂阿米洛利的作用,关于PTX诱导的Na流入培养的牛肾上腺嗜铬细胞及其对Ca2流入和儿茶酚胺分泌的影响。阿米洛利剂量依赖性地抑制PTX诱导的22Na内流,而河豚毒素 (TTX) 没有作用。阿米洛利还抑制PTX诱导的Na () 依赖性45Ca2内流和儿茶酚胺分泌。单独的PTX不会显着影响细胞内pH,但在PTX和阿米洛利存在下会降低。这些结果表明,对阿米洛利敏感的Na/H交换机制可能参与PTX诱导的,对TTX不敏感的Na内流,从而触发细胞中Ca2内流和儿茶酚胺分泌。
  • 【阴沟肠杆菌参与鱼类的死亡率。】 复制标题 收藏 收藏
    DOI:10.1111/j.1472-765X.2008.02365.x 复制DOI
    作者列表:Sekar VT,Santiago TC,Vijayan KK,Alavandi SV,Raj VS,Rajan JJ,Sanjuktha M,Kalaimani N
    BACKGROUND & AIMS: AIMS:To identify the causative agent of the mortality in the fish, Mugil cephalus, in Muttukadu lagoon. METHODS AND RESULTS:An enteric bacterium from the kidneys of moribund fish M. cephalus, was isolated and identified as Enterobacter cloacae (MK). Mugil cephalus was experimentally infected by this isolate and was re-isolated from the kidneys of the moribund fish. Enterobacter cloacae isolates from the lagoon water (MW1, MW2 and reference strain ATCC 13047) and the reference strain were not able to induce similar pathogenesis. The putative factor imparting pathogenicity to the MK isolate was identified as a cationic molecule, which migrated towards the cathode on agarose gel electrophoresis. CONCLUSIONS:The Ent. cloacae (MK) isolate harbouring a cationic factor was the causative agent for the mortality of M. cephalus, found in Muttukadu lagoon. SIGNIFICANCE AND IMPACT OF THE STUDY:This study reveals that human enteric bacteria MK which is considered as nonpathogenic to fish, may become pathogenic to fish when it harbours this cationic factor. This cationic factor is found to be pathogenic to the fish M. cephalus leading to mortality. It was also found to be pathogenic to mice. Therefore, the shuttling of Ent. cloacae, harbouring cationic factor, between human and fish may be of human health importance.
    背景与目标:
  • 【获得ART治疗的社会经济差异以及增加消费者成本的政策的不同影响。】 复制标题 收藏 收藏
    DOI:10.1093/humrep/det302 复制DOI
    作者列表:Chambers GM,Hoang VP,Illingworth PJ
    BACKGROUND & AIMS: STUDY QUESTION:What was the impact on access to assisted reproductive technology (ART) treatment by different socioeconomic status (SES) groups after the introduction of a policy that increased patient out-of-pocket costs? SUMMARY ANSWER:After the introduction of a policy that increased out-of-pocket costs in Australia, all SES groups experienced a similar percentage reduction in fresh ART cycles per 1000 women of reproductive age. Higher SES groups experienced a progressively greater reduction in absolute numbers of fresh ART cycles due to existing higher levels of utilization. WHAT IS KNOWN ALREADY:Australia has supportive public funding arrangements for ARTs. Policies that substantially increase out-of-pocket costs for ART treatment create financial barriers to access and an overall reduction in utilization. Data from the USA suggests that disparities exist in access to ART treatment based on ethnicity, education level and income. STUDY DESIGN, SIZE, DURATION:Time series analysis of utilization of ART, intrauterine insemination (IUI) and clomiphene citrate by women from varying SES groups before and after the introduction of a change in the level of public funding for ART. PARTICIPANTS/MATERIALS, SETTING, METHODS:Women undertaking fertility treatment in Australia between 2007 and 2010. MAIN RESULTS AND THE ROLE OF CHANCE:Women from higher SES quintiles use more ART treatment than those in lower SES quintiles, which likely reflects a greater ability to pay for treatment and a greater need for ART treatment as indicated by the trend to later childbearing. In 2009, 10.13 and 5.17 fresh ART cycles per 1000 women of reproductive age were performed in women in the highest and lowest SES quintiles respectively. In the 12 months after the introduction of a policy that increased out-of-pocket costs from ∼$1500 Australian dollars (€1000) to ∼$2500 (€1670) for a fresh IVF cycle, there was a 21-25% reduction in fresh ART cycles across all SES quintiles. The absolute reduction in fresh ART cycles in the highest SES quintile was double that in the lowest SES quintile. LIMITATIONS, REASONS FOR CAUTION:In this study, SES was based on the average relative socioeconomic advantage and disadvantage of small geographic areas, and therefore may not reflect the SES of an individual. Additionally, the policy impact was limited to the 12 months following its introduction, and may not reflect longer term trends in ART treatment. WIDER IMPLICATIONS OF THE FINDINGS:While financial barriers are an important obstacle to equitable access to ARTs, socioeconomic differences in utilization are likely to persist in countries with supportive public funding, due in part to differences in childbearing patterns and treatment seeking behaviour. Policy makers should be informed of the impact that changes in the level of cost subsidization have on access to ART treatment by different socioeconomic groups. STUDY FUNDING/COMPETING INTEREST(S):G.M.C. receives grant support to her institution from the Australian Government, Australian Research Council (ARC) Linkage Grant No LP1002165; ARC Linkage Grant Partner Organisations are IVFAustralia, Melbourne IVF and Queensland Fertility Group. V.P.H. is employed as an Economics Research Associate on the same grant. P.J.I. is Medical Director of the IVF Clinic, IVFAustralia and has a financial interest in the parent group, Virtus. TRIAL REGISTRATION NUMBER:N/A.
    背景与目标:
  • 【谷氨酸能机制在吸烟的认知和主观影响中的不同参与。】 复制标题 收藏 收藏
    DOI:10.1038/npp.2008.50 复制DOI
    作者列表:Jackson A,Nesic J,Groombridge C,Clowry O,Rusted J,Duka T
    BACKGROUND & AIMS: :There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior.
    背景与目标: : 越来越多的临床前证据表明谷氨酸参与尼古丁的行为行为。这项研究的目的是研究N-甲基-D-天冬氨酸 (NMDA) 受体在人类吸烟的认知和主观影响中的作用。60名普通吸烟者参加了这项双盲安慰剂对照研究,研究了NMDA拮抗剂美金刚 (40 mg) 和烟碱受体拮抗剂美加明胺 (10 mg) 对吸烟引起的持续关注任务性能的改善以及吸烟引起的主观影响和渴望变化的影响。美金刚逆转了吸烟后 “嗡嗡声” 的主观评分的增加,但美加明胺却没有。相反,美加明胺反对吸烟对快速视觉信息处理任务的改善,但美金刚反对。吸烟减少了对香烟的渴望,但两种药物都没有改变这种效果。我们的结果表明,谷氨酸能机制可能对吸烟的主观和认知作用有不同的参与。需要使用不同配体进行进一步研究,以充分表征谷氨酸在吸烟行为后果中的作用。
  • 【不同 μ 阿片受体亚型分别参与阿片类药物脊髓上作用诱发的瘙痒和镇痛的证据。】 复制标题 收藏 收藏
    DOI:10.1254/jphs.08004sc 复制DOI
    作者列表:Andoh T,Yageta Y,Konno M,Yamaguchi-Miyamoto T,Takahata H,Nojima H,Nemoto H,Kuraishi Y
    BACKGROUND & AIMS: :The common adverse effect of centrally-injected mu-opioid receptor (mu-OR) agonists is pruritus. This study was conducted using mice to examine whether different subtypes of mu-OR would be responsible for pruritus and analgesia. Intracisternal injections of morphine and morphine-6beta-glucronide (M6G), but not M3G, produced an antinociceptive effect. Morphine, but neither M6G nor M3G, induced facial scratching, a pruritus-related response. Facial scratching following morphine was not affected by the mu(1)-OR antagonist naloxonazine at doses that inhibited the antinociceptive effects. The results suggest that different subtype and/or splice variants of mu-OR are separately involved in pruritus and antinociception of opioids.
    背景与目标: : 集中注射mu-阿片受体 (mu-OR) 激动剂的常见不良反应是瘙痒。这项研究是使用小鼠进行的,以检查mu-OR的不同亚型是否会引起瘙痒和镇痛。脑内注射吗啡和morphine-6beta-glucronide (M6G),而不是M3G,产生抗伤害感受作用。吗啡,但M6G和M3G都不会引起面部抓挠,这是一种瘙痒相关的反应。吗啡后的面部抓挠不受mu(1) 或拮抗剂纳洛酮嗪抑制抗伤害感受作用的影响。结果表明,mu-or的不同亚型和/或剪接变体分别参与阿片类药物的瘙痒和抗伤害感受。
  • 【永久性局灶性缺血后老年小鼠大脑中的水肿和神经胶质细胞受累。】 复制标题 收藏 收藏
    DOI:10.1046/j.1365-2990.2000.00265.x 复制DOI
    作者列表:Fotheringham AP,Davies CA,Davies I
    BACKGROUND & AIMS: :This study examines the effect of age on oedema and brain swelling, and associated glial cell involvement on the size of the lesion in two models of permanent, focal cerebral ischaemia. Ischaemia was induced in male C57BL/Icrfat mice (4-6 and 26-31-month-old) by middle cerebral artery (MCA) occlusion using either electrocoagulation after craniotomy (MCA/craniotomy), or by an intraluminal filament through the carotid artery (MCA/icf). Twenty-four hours after inducing ischaemia, brain swelling and lesion size were measured in young and aged mice, and cerebral oedema by wet/dry brain weights. Histopathology and immunocytochemistry were performed on a separate set of perfusion fixed brains. The MCA/icf technique produced a significantly larger lesion than MCA/craniotomy in both age groups. The percentage of water taken into the brain was significantly greater after MCA/icf, with aged mice showing the greatest increase. When lesion size was corrected for brain swelling there was no age-related increase in the size of the lesion. The numbers of microglia and astroglia increased significantly in the parietal cortex of aged control animals, and there were qualitative differences in the glial response between the two stroke models. This study emphasizes the importance of age in models of permanent focal ischaemia, with oedema clearly being a significant factor. Differ-ences in the responsiveness of the glial cell population with age may be of fundamental importance in the progress of ischaemic brain damage.
    背景与目标: : 这项研究在两种永久性局灶性脑缺血模型中检查了年龄对水肿和脑肿胀以及相关的神经胶质细胞受累对病变大小的影响。在雄性C57BL/Icrfat小鼠 (4-6和26-31个月大) 中,通过开颅手术后的电凝 (MCA/开颅) 或通过腔内细丝通过大脑中动脉 (MCA) 闭塞诱发了缺血。颈动脉 (MCA/icf)。诱导缺血后24小时,在年轻和老年小鼠中测量脑肿胀和病变大小,并通过湿/干脑重量测量脑水肿。组织病理学和免疫细胞化学是在一组单独的灌注固定大脑上进行的。在两个年龄组中,MCA/icf技术产生的病变明显大于MCA/开颅手术。MCA/icf后,进入大脑的水百分比显着更高,其中衰老的小鼠显示出最大的增加。当将病变大小校正为脑肿胀时,病变大小没有与年龄相关的增加。老年对照动物的顶叶皮质中小胶质细胞和星形胶质细胞的数量显着增加,并且两种中风模型之间的神经胶质反应存在质的差异。这项研究强调了年龄在永久性局灶性缺血模型中的重要性,而水肿显然是一个重要因素。神经胶质细胞群体的反应性随年龄的变化可能对缺血性脑损伤的进展至关重要。
  • 【(-)-pindolol对DOI诱导的大鼠前向运动的非血清素能增强作用: 可能参与 β-肾上腺素受体?。】 复制标题 收藏 收藏
    DOI:10.1007/s007020070041 复制DOI
    作者列表:Kaur P,Ahlenius S
    BACKGROUND & AIMS: :[1] We have previously shown that the beta-adrenergic/5-HT1 receptor partial agonist (-)-pindolol (2.0-32.0 micromol kg(-1)) enhances the increase in forward locomotion in rats produced by the 5-HT2 receptor agonist DOI (0.7 micromol kg(-1)) via net activation of post-synaptic 5-HT2 receptors. [2] It was found that neither the 5-HT1A receptor agonist and partial agonist, (+/-) 8-OH-DPAT (0.2-2.4 micromol kg(-1)) and (S)-(-)-UH-301, respectively, nor the 5-HT1A receptor antagonist WAY-100635 (0.09-1.5 micromol kg(-1)), substituted for (-)-pindolol in this in vivo behavioral model. [3] This also applies to the 5-HT1B receptor agonist and antagonist anpirtoline (0.3-4.0 micromol kg(-1)) and isamoltane (1.0-64.0 micromol kg(-1)), respectively. Neither of these compounds mimicked (-)-pindolol in its interactions with DOI. [4] The (-)-pindolol/DOI-induced increase in forward locomotion could be antagonized by the beta1 adrenoceptor antagonist betaxolol (24 micromol kg(-1)). [5] It is suggested that the intrinsic efficacy of (-)-pindolol at beta-adrenoceptors is an important aspect of its in vivo pharmacodynamic profile.
    背景与目标: :[1] 我们以前已经表明,β-肾上腺素能/5-HT1受体部分激动剂 (-)-品多洛尔 (2.0-32.0微摩尔千克 (-1)) 通过净激活增强由5-HT2受体激动剂DOI (0.7微摩尔千克 (-1)) 产生的大鼠正向运动的增加突触后5-HT2受体。[2] 发现5-HT1A受体激动剂和部分激动剂 (+/-) 8-OH-DPAT (0.2-2.4 micromol kg(-1)) 和 (S)-(-)-UH-301分别,在该体内行为模型中,也没有用5-HT1A受体拮抗剂WAY-100635 (0.09-1.5 micromol kg(-1)) 代替 (-)-pindolol。[3] 这也分别适用于5-HT1B受体激动剂和拮抗剂anpirtoline (0.3-4.0 micromol kg(-1)) 和isamoltane (1.0-64.0 micromol kg(-1))。这两种化合物在与DOI的相互作用中都没有模仿 (-)-pindolol。[4] (-)-pindolol/DOI诱导的向前运动的增加可以被 β1肾上腺素受体拮抗剂betaxolol (24 micromol kg(-1)) 拮抗。[5] 建议 (-)-pindolol对 β-肾上腺素受体的内在功效是其体内药效学特征的重要方面。
  • 【克罗恩病患者大脑受累的新见解: 基于体素的形态计量学研究。】 复制标题 收藏 收藏
    DOI:10.1111/nmo.12017 复制DOI
    作者列表:Agostini A,Benuzzi F,Filippini N,Bertani A,Scarcelli A,Farinelli V,Marchetta C,Calabrese C,Rizzello F,Gionchetti P,Ercolani M,Campieri M,Nichelli P
    BACKGROUND & AIMS: BACKGROUND:Crohn's disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. METHODS:Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel-based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. KEY RESULTS:With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. CONCLUSIONS & INFERENCES:Crohn's disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders.
    背景与目标:
  • 【组织学分级可预测没有子宫肌层受累的子宫内膜样癌患者的复发。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Zaki MA,Robbins JR,Fatteh S,Mahan MG,Hanna RK,Elshaikh MA
    BACKGROUND & AIMS: AIM:To evaluate clinical outcomes and identify factors predictive for recurrence in patients with 1988 (FIGO) stage IA uterine endometrioid carcinoma. PATIENTS AND METHODS:Patients who underwent hysterectomy for stage IA carcinoma were identified in our database. Fisher's exact and χ(2) tests were used to identify factors that influenced outcome. Survival plots were generated according to Kaplan-Meier product-limit method and the log-rank test was used to determine significance. RESULTS:A total of 121 patients were identified. Eighty-seven percent (n=105) had tumor FIGO grade 1, 9% (n=11) grade 2, and 4% (n=5) grade 3 tumors. Six patients (5%) experienced recurrence. The 5-year recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were 93%, 95%, and 85%, respectively. On univariate analysis, tumor FIGO grade 2/3 was strongly associated with tumor recurrence (p=0.003), DSS (p=0.016), and OS (p=0.023). The 5-year RFS, DSS, and OS were 65.1%, 73.9%, and 63.9% respectively for patients with grade 2 and 3 tumors, which were significantly less than the corresponding rates of 97.5% (p ≤ 0.0001), 98.6% (p=0.001), and 87.7% (p=0.024) for patients with grade 1 tumors. CONCLUSION:In this large cohort of patients, RFS, DSS and OS were excellent. Patients with FIGO grade 2/3 tumors had worse outcomes compared to those with grade 1 tumors. Therefore, while most patients with stage IA disease do not need adjuvant treatment after hysterectomy, our results suggest that patients with higher-grade tumors have an increased likelihood for recurrence and they may benefit from counseling regarding adjuvant therapies.
    背景与目标:
  • 【居民参与对创伤护理结果的影响。】 复制标题 收藏 收藏
    DOI:10.1001/archsurg.2012.1672 复制DOI
    作者列表:Bukur M,Singer MB,Chung R,Ley EJ,Malinoski DJ,Margulies DR,Salim A
    BACKGROUND & AIMS: HYPOTHESIS:Discrepancies exist in complications and outcomes at teaching trauma centers (TTCs) vs nonteaching TCs (NTCs). DESIGN:Retrospective review of the National Trauma Data Bank research data sets (January 1, 2007, through December 31, 2008). SETTING:Level II TCs. PATIENTS:Patients at TTCs were compared with patients at NTCs using demographic, clinical, and outcome data. Regression modeling was used to adjust for confounding factors to determine the effect of house staff presence on failure to rescue, defined as mortality after an in-house complication. MAIN OUTCOME MEASURES:The primary outcome measures were major complications, in-hospital mortality, and failure to rescue. RESULTS:In total, 162 687 patients were available for analysis, 36 713 of whom (22.6%) were admitted to NTCs. Compared with patients admitted to TTCs, patients admitted to NTCs were older (52.8 vs 50.7 years), had more severe head injuries (8.3% vs 7.8%), and were more likely to undergo immediate operation (15.0% vs 13.2%) or ICU admission (28.1% vs 22.8%) (P < .01 for all). The mean Injury Severity Scores were similar between the groups (10.1 for patients admitted to NTCs vs 10.4 for patients admitted to TTCs, P < .01). Compared with patients admitted to TTCs, patients admitted to NTCs experienced fewer complications (adjusted odds ratio [aOR], 0.63; P < .01), had a lower adjusted mortality rate (aOR, 0.87; P = .01), and were less likely to experience failure to rescue (aOR, 0.81; P = .01). CONCLUSIONS:Admission to level II TTCs is associated with an increased risk for major complications and a higher rate of failure to rescue compared with admission to level II NTCs. Further investigation of the differences in care provided by level II TTCs vs NTCs may identify areas for improvement in residency training and processes of care.
    背景与目标:
  • 【肥胖儿童的肝脏受累。意大利人群在诊断和随访期间的超声检查和肝酶水平。】 复制标题 收藏 收藏
    DOI:10.1023/a:1018850223495 复制DOI
    作者列表:Franzese A,Vajro P,Argenziano A,Puzziello A,Iannucci MP,Saviano MC,Brunetti F,Rubino A
    BACKGROUND & AIMS: Our aim was to evaluate incidence and risk factors of liver involvement in obese Italian children as assessed by both ultrasonographic and biochemical parameters. In seventy-five consecutive obese children (age 9.5 +/- 2.9 years, males/females 41/34), serum levels of enzymes and ultrasonography of the liver were evaluated. Tests were repeated one, three, and six months after starting a moderate hypocaloric diet and an exercise program. Three obese children who were found to have chronic viral hepatitis were excluded from the study. Thirty-eight of 72 (53%) obese children had an ultrasonographic image of bright liver consistent with liver steatosis. The latter was severe in nine children, moderate in 16, and mild in 13. Eighteen obese children (25%) had elevated transaminase levels. Bright liver and hypertransaminasemia were not due to any of the most common causes of liver disease. Both were rapidly responsive to loss of weight, confirming that liver involvement was secondary to obesity and that steatosis or steatohepatitis rather than fibrosis were involved. Obesity duration not more than three years (odds ratio = 4.77), a higher degree of obesity (odds ratio = 2.09), and hypertransaminasemia (odds ratio = 2.15) appeared as important predictive factors of liver involvement at ultrasonography. Incidence of liver involvement assessed by means of ultrasonography is significantly higher than that revealed by measurement of serum liver enzymes. A short duration of obesity emerged as a potentially new risk factor of liver involvement in the pediatric obese population and needs to be confirmed in future studies.

    背景与目标: 我们的目的是通过超声和生化参数评估肥胖的意大利儿童肝脏受累的发生率和危险因素。在75名连续肥胖儿童 (年龄9.5 +/- 2.9岁,男性/女性41/34) 中,评估了血清酶水平和肝脏超声检查。在开始适度的低热量饮食和锻炼计划后的一个月,三个月和六个月重复测试。3名被发现患有慢性病毒性肝炎的肥胖儿童被排除在研究之外。72名 (53% 名) 肥胖儿童中有38名具有明亮肝脏的超声图像,与肝脏脂肪变性一致。后者严重于9名儿童,中度于16名,轻度于13名。18名肥胖儿童 (25%) 的转氨酶水平升高。明亮的肝脏和高转氨酶血症不是由肝病的任何最常见原因引起的。两者都对体重减轻迅速反应,证实肝脏受累是继发于肥胖的,并且脂肪变性或脂肪性肝炎而不是纤维化。肥胖持续时间不超过三年 (优势比 = 4.77),较高的肥胖程度 (优势比 = 2.09) 和高转氨酶血症 (优势比 = 2.15) 是超声检查肝脏受累的重要预测因素。通过超声检查评估的肝脏受累发生率明显高于通过血清肝酶测量显示的肝脏受累发生率。短期肥胖已成为小儿肥胖人群肝脏受累的潜在新危险因素,需要在未来的研究中得到证实。

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