BACKGROUND & AIMS: :The purpose of this study was to examine the acute effects of a caffeine-containing supplement on upper- and lower-body strength and muscular endurance as well as anaerobic capabilities. Thirty-seven resistance-trained men (mean +/- SD, age: 21 +/- 2 years) volunteered to participate in this study. On the first laboratory visit, the subjects performed 2 Wingate Anaerobic Tests (WAnTs) to determine peak power (PP) and mean power (MP), as well as tests for 1 repetition maximum (1RM), dynamic constant external resistance strength, and muscular endurance (TOTV; total volume of weight lifted during an endurance test with 80% of the 1RM) on the bilateral leg extension (LE) and free-weight bench press (BP) exercises. Following a minimum of 48 hours of rest, the subjects returned to the laboratory for the second testing session and were randomly assigned to 1 of 2 groups: a supplement group (SUPP; n = 17), which ingested a caffeine-containing supplement, or a placebo group (PLAC; n = 20), which ingested a cellulose placebo. One hour after ingesting either the caffeine-containing supplement or the placebo, the subjects performed 2 WAnTs and were tested for 1RM strength and muscular endurance on the LE and BP exercises. The results indicated that there was a significant (p < 0.05) increase in BP 1RM for the SUPP group, but not for the PLAC group. The caffeine-containing supplement had no effect, however, on LE 1RM, LE TOTV, BP TOTV, PP, and MP. Thus, the caffeine-containing supplement may be an effective supplement for increasing upper-body strength and, therefore, could be useful for competitive and recreational athletes who perform resistance training.

背景与目标： ：这项研究的目的是检查含咖啡因的补充剂对上，下半身的力量，肌肉耐力以及无氧能力的急性作用。三十七名经过抗性训练的男性（平均/-SD，年龄：21 /-2岁）自愿参加了这项研究。在第一次实验室访问中，受试者进行了2次Wingate无氧测试（WAnT），以确定峰值功率（PP）和平均功率（MP），以及1次重复最大值（1RM），动态恒定的外部阻力强度和肌肉的测试耐力（TOTV；在耐力测试中以1RM的80％进行测试时提升的总重量）在双腿伸展（LE）和自由重量卧推（BP）锻炼中。至少休息48小时后，受试者返回实验室进行第二次测试，并随机分为2组中的1组：补充组（SUPP; n = 17），摄入含咖啡因的补充剂，或服用纤维素安慰剂的安慰剂组（PLAC； n = 20）。摄入含咖啡因的补充剂或安慰剂一小时后，受试者进行了2次WAnT，并在LE和BP锻炼中测试了1RM强度和肌肉耐力。结果表明SUPP组的BP 1RM显着增加（p <0.05），而PLAC组则没有。但是，含咖啡因的补充剂对LE 1RM，LE TOTV，BP TOTV，PP和MP无作用。因此，含咖啡因的补充剂可能是增加上半身力量的有效补充剂，因此对进行阻力训练的竞技和休闲运动员有用。

BACKGROUND & AIMS: :Saccharomyces cerevisiae cells contain three omega-class glutathione transferases with glutaredoxin activity (Gto1, Gto2, and Gto3), in addition to two glutathione transferases (Gtt1 and Gtt2) not classifiable into standard classes. Gto1 is located at the peroxisomes, where it is targeted through a PTS1-type sequence, whereas Gto2 and Gto3 are in the cytosol. Among the GTO genes, GTO2 shows the strongest induction of expression by agents such as diamide, 1-chloro-2,4-dinitrobenzene, tert-butyl hydroperoxide or cadmium, in a manner that is dependent on transcriptional factors Yap1 and/or Msn2/4. Diamide and 1-chloro-2,4-dinitrobenzene (causing depletion of reduced glutathione) also induce expression of GTO1 over basal levels. Phenotypic analyses with single and multiple mutants in the S. cerevisiae glutathione transferase genes show that, in the absence of Gto1 and the two Gtt proteins, cells display increased sensitivity to cadmium. A gto1-null mutant also shows growth defects on oleic acid-based medium, which is indicative of abnormal peroxisomal functions, and altered expression of genes related to sulfur amino acid metabolism. As a consequence, growth of the gto1 mutant is delayed in growth medium without lysine, serine, or threonine, and the mutant cells have low levels of reduced glutathione. The role of Gto1 at the S. cerevisiae peroxisomes could be related to the redox regulation of the Str3 cystathionine beta-lyase protein. This protein is also located at the peroxisomes in S. cerevisiae, where it is involved in transulfuration of cysteine into homocysteine, and requires a conserved cysteine residue for its biological activity.

背景与目标： ：酿酒酵母细胞除含有两种无法分类为标准类别的谷胱甘肽转移酶（Gtt1和Gtt2）外，还包含三种具有谷胱甘肽毒素活性的欧米茄类谷胱甘肽转移酶（Gto1，Gto2和Gto3）。 Gto1位于过氧化物酶体，通过PTS1型序列被靶向，而Gto2和Gto3在细胞质中。在GTO基因中，GTO2以最依赖转录因子Yap1和/或Msn2 /的方式显示出最强的诱导作用，例如二酰胺，1-氯-2,4-二硝基苯，叔丁基氢过氧化物或镉。 4，二酰胺和1-氯-2,4-二硝基苯（导致减少的还原型谷胱甘肽）也诱导GTO1表达超过基础水平。对酿酒酵母谷胱甘肽转移酶基因中单个和多个突变体的表型分析表明，在缺少Gto1和两个Gtt蛋白的情况下，细胞对镉的敏感性增加。 gto1-null突变体还在基于油酸的培养基上显示出生长缺陷，这表明过氧化物酶体功能异常，并且改变了与硫氨基酸代谢相关的基因的表达。结果，在没有赖氨酸，丝氨酸或苏氨酸的生长培养基中，gto1突变体的生长被延迟，并且该突变体细胞具有低水平的还原型谷胱甘肽。 Gto1在酿酒酵母过氧化物酶体中的作用可能与Str3胱硫醚β-裂合酶蛋白的氧化还原调节有关。该蛋白也位于酿酒酵母中的过氧化物酶体处，在其中它参与半胱氨酸转硫为高半胱氨酸，并且需要保守的半胱氨酸残基才能发挥其生物学活性。

BACKGROUND & AIMS: These experiments were designed to determine whether glycogenolysis was influenced by the glycogen concentration of vascular smooth muscle. Segments of hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1-[13C]glucosyl units of glycogen. Artery segments were then isometrically contracted in the presence of 2-[13C]glucose. Prior to and after isometric contraction, measurements were made of tissue glycogen content and superfusate glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak intensities in the superfusate were measured using 13C-NMR spectroscopy. The tissue glycogen content decreased exponentially during the 4.5 h of isometric contraction (R2 = 0.990), despite more than a 3-fold range of glycogen concentration prior to contraction. The extent of glycogen utilization during a 3 h isometric contraction varied linearly with the precontraction glycogen concentration (R2 = 0.727). Lactate production specifically from glycogen breakdown increased with an increase in precontraction glycogen concentration (R2 = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2 = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002) varied with the precontraction glycogen concentration. It is concluded that the rate of glycogenolysis is determined by the content of glycogen during prolonged contractions. In addition, precontraction glycogen levels influence the pathway for glycogen utilization but not the pathway for glucose utilization. Therefore, glycolysis and glycogenolysis behave independently in vascular smooth muscle.

背景与目标： 设计这些实验以确定糖原分解是否受血管平滑肌糖原浓度的影响。允许猪颈动脉平滑肌节段合成糖原的1- [13C]葡糖基单元。然后在2- [13C]葡萄糖存在下，等距收缩动脉段。在等距收缩之前和之后，测量组织糖原含量和超融合葡萄糖和乳酸浓度。使用13C-NMR光谱法测量超熔液中的2- [13C]乳酸盐和3- [13C]乳酸盐峰强度。尽管在收缩前糖原浓度的3倍范围内，组织糖原含量在等长收缩的4.5小时内呈指数下降（R2 = 0.990）。在3小时的等距收缩过程中，糖原利用的程度随收缩前糖原浓度的变化而线性变化（R2 = 0.727）。特别是糖原分解产生的乳酸根随收缩前糖原浓度的增加而增加（R2 = 0.620）。在3小时的等距收缩过程中，葡萄糖利用量（R2 = 0.007）或由葡萄糖专门产生的乳酸产量（R2 = 0.00002）都不会随收缩前糖原浓度的变化而变化。结论是糖原分解的速率取决于长时间收缩过程中糖原的含量。另外，收缩前糖原水平影响糖原利用的途径，但不影响葡萄糖利用的途径。因此，糖酵解和糖原分解作用在血管平滑肌中独立发生。

BACKGROUND & AIMS: :Consonant identification was measured for a stationary and amplitude-modulated noise masker in four listeners with flat cochlear hearing loss, and four age-matched normal-hearing listeners. The masker modulation rate was systematically varied between 2 and 128 Hz. Masking release (MR), that is better identification performance in fluctuating, than in stationary noise, was highest in a masker fluctuating at 8-16 Hz in all normal-hearing listeners. In comparison, MR was only observed in two out of the four impaired listeners. In these listeners, MR was poorer than normal, and peaked at lower rates, that is 2 or 8 Hz. MR corresponded to increased reception of information for voicing, place, and manner between 2 and 64 Hz in all normal-hearing listeners. In impaired listeners, increased reception of information was mainly observed for manner, and mainly reduced for place, but these differences were not significant. For all phonetic features, MR was observed at lower masker fluctuation rates (< or =32 Hz) than in normal-hearing listeners. This study therefore shows that cochlear damage affects MR, both quantitatively and qualitatively.

背景与目标： ：在四个平直的人工耳聋听力下降的听众和四个年龄相匹配的正常听力的听众中，对平稳和调幅的噪声掩蔽器的辅音识别进行了测量。掩蔽调制率在2到128 Hz之间系统地变化。在所有正常听力的听众中，以8-16 Hz波动的掩蔽器中，掩蔽释放（MR）的波动性要好于平稳噪声，这在静态噪声中具有更好的识别性能。相比之下，只有四个受损听者中有两个观察到了MR。在这些听众中，MR比正常人差，并且以较低的频率（即2或8 Hz）达到峰值。 MR对应于在所有正常听力的收听者中2至64 Hz之间的声音，位置和方式信息接收的增加。在听力受损的听众中，主要是通过方式观察到了信息接收的增加，而对于场所则主要是观察到的减少，但是这些差异并不明显。对于所有的语音特征，与正常听力的听众相比，在较低的掩蔽者波动率（<或= 32 Hz）下观察到了MR。因此，这项研究表明，耳蜗损害在数量和质量上都影响MR。

BACKGROUND & AIMS: :In 4 experiments, the authors investigated the reversal of spatial congruency effects when participants concurrently practiced incompatible mapping rules (J. G. Marble & R. W. Proctor, 2000). The authors observed an effect of an explicit spatially incompatible mapping rule on the way numerical information was associated with spatial responses. The authors also observed an effect of an incompatible numerical mapping rule (if smaller than 5, press right; if larger than 5, press left) on the Simon effect. This effect was observed only when both tasks used the same effectors. The results point to a shared spatial representation for explicit spatial information (locations) and implicit spatial information (numbers).

背景与目标： ：在4个实验中，作者研究了参与者同时练习不兼容的映射规则时空间一致性效果的逆转（J. G. Marble和R. W. Proctor，2000）。作者观察到明确的空间不兼容映射规则对数字信息与空间响应相关联的方式的影响。作者还观察到不兼容的数字映射规则（如果小于5，请按向右；如果大于5，请按向左）对西蒙效果的影响。仅当两个任务使用相同的效应器时，才观察到这种效果。结果指向用于显式空间信息（位置）和隐式空间信息（数字）的共享空间表示。

BACKGROUND & AIMS: :In vitro experiments and expression patterns have long suggested important roles for the genetically related cytosolic fatty acid binding proteins (FABPs) in lipid metabolism. However, evidence for such roles in vivo has become available only recently from genetic manipulation of FABP expression in mice. Here, we summarize the fuel-metabolic phenotypes of mice lacking the genes encoding heart-type FABP (H-/- mice) or liver-type FABP (L-/- mice). Cytosolic extracts from H-/- heart and skeletal muscle and from L-/- liver showed massively reduced binding of long chain fatty acids (LCFA) and, in case of L-/- liver, also of LCFA-CoA. Uptake, oxidation, and esterification LCFA, when measured in vivo and/or ex vivo, were markedly reduced in H-/- heart and muscle and in L-/- liver. The reduced LCFA oxidation in H-/- heart and L-/- liver was not due to reduced activity of PPARa, a fatty acid-sensitive transcription factor that determines the lipid-oxidative capacity in these organs. In H-/- mice, mechanisms of compensation were partially studied and included a redistribution of muscle mitochondria as well as increases of cardiac and skeletal muscle glucose uptakes and of hepatic ketogenesis. In skeletal muscle, the altered glucose uptake included decreased basal but increased insulin-dependent components. Metabolic compensation was only partial, however, since the H-/- mice showed decreased exercise tolerance. In conclusion, the recent studies established H- and L-FABP as major determinants of regional LCFA utilization; therefore the H-/- and L-/- mice are attractive models for studying principles of fuel selection and metabolic homeostasis.

背景与目标： ：体外实验和表达模式长期以来一直表明遗传相关的胞质脂肪酸结合蛋白（FABPs）在脂质代谢中的重要作用。但是，体内这种作用的证据直到最近才从小鼠中FABP表达的基因操作中获得。在这里，我们总结了缺少编码心脏型FABP（H-/-小鼠）或肝型FABP（L-/-小鼠）的基因的小鼠的燃料代谢表型。 H-/-心脏和骨骼肌以及L-/-肝脏的胞质提取物显示长链脂肪酸（LCFA）的结合大大降低，对于L-/-肝脏，LCFA-CoA的结合也大大降低。当体内和/或离体测量时，LCFA的摄取，氧化和酯化作用在H-/-心脏和肌肉以及L-/-肝中显着降低。 H-/-心脏和L-/-肝脏中LCFA氧化的减少并不是由于PPARa的活性降低，PPARa是一种脂肪酸敏感的转录因子，决定了这些器官中脂质的氧化能力。在H-/-小鼠中，对补偿机制进行了部分研究，包括肌肉线粒体的重新分布以及心肌和骨骼肌葡萄糖摄取的增加以及肝脏生酮的发生。在骨骼肌中，葡萄糖摄取的改变包括基础减少，但胰岛素依赖性成分增加。但是，由于H-/-小鼠表现出降低的运动耐力，因此代谢补偿仅是部分的。总之，最近的研究确定了H-FABP和L-FABP是区域LCFA利用的主要决定因素。因此，H-/-和L-/-小鼠是用于研究燃料选择和代谢稳态的原理的有吸引力的模型。

BACKGROUND & AIMS: :The oxidative deamination of serotonin (5-HT) to 5-hydroxyindoleacetic acid (5-HIAA) by rat primary astrocyte cultures was investigated in intact cells using HPLC. All detectable 5-HIAA accumulated in the extracellular medium, and its rate of production was proportional to the 5-HT concentration over the tested range of 5 x 10(-7) to 10(-4) M. At 5 x 10(-7) M 5-HT, intracellular 5-HT was detectable only in astrocytes treated with monoamine oxidase (MAO) inhibitors. These findings are consistent with the idea that 5-HT taken up into astrocytes is not stored for re-release, but is rapidly metabolized to 5-HIAA, which is then extruded from the cell. At 5 x 10(-7) M 5-HT, 5-HIAA formation in intact cells was blocked 63% by the selective high-affinity 5-HT uptake inhibitor fluoxetine. 5-HT oxidation to 5-HIAA is carried out principally by MAO-A, because clorgyline was more effective at inhibiting the production of 5-HIAA than was pargyline. Radioenzymatic determinations of MAO activity in cell homogenates supported these findings, because under these conditions clorgyline was 1,000-fold more effective than pargyline at inhibiting MAO activity toward 14C-labelled 5-HT. However, the relatively selective MAO-B substrate beta-phenylethylamine (PEA) was also oxidized, showing that these cultures also contained MAO-B activity; the Km values for MAO-A oxidation of 5-HT and MAO-B oxidation of PEA were 135 and 45 microM, and Vmax values were 88 and 91 nmol/mg of total cell protein/h, respectively. Higher concentrations of PEA (greater than 20 microM) were oxidized by both MAO-A and MAO-B isozymes.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： ：使用高效液相色谱法研究了大鼠原代星形胶质细胞培养物中5-羟色胺（5-HT）氧化成5-羟基吲哚乙酸（5-HIAA）的过程。所有可检测到的5-HIAA都积累在细胞外培养基中，并且其产生速率与在5 x 10（-7）至10（-4）M的测试范围内的5-HT浓度成正比。在5 x 10（- 7）仅在用单胺氧化酶（MAO）抑制剂处理过的星形胶质细胞中检测到M 5-HT，细胞内5-HT。这些发现与以下想法相一致：摄取到星形胶质细胞中的5-HT不会被存储以重新释放，而是会迅速代谢为5-HIAA，然后从细胞中挤出。在5 x 10（-7）M 5-HT处，完整细胞中5-HIAA的形成被选择性的高亲和力5-HT摄取抑制剂氟西汀阻断了63％。 5-HT氧化成5-HIAA的方法主要是通过MAO-A进行的，因为氯丁香碱在抑制5-HIAA生成方面比Pargyline更有效。放射性酶法测定细胞匀浆中MAO的活性支持了这些发现，因为在这些条件下，高粱碱在抑制MAO对14C标记的5-HT的活性方面比Pargyline高1,000倍。但是，相对选择性的MAO-B底物β-苯乙胺（PEA）也被氧化，表明这些培养物也具有MAO-B活性； PEA的5-HT的MAO-A氧化和PEA的MAO-B氧化的Km值分别为135和45 microM，Vmax值分别为88和91 nmol / mg总细胞蛋白/ h。较高浓度的PEA（大于20 microM）被MAO-A和MAO-B同工酶氧化（摘要以250字截短）

BACKGROUND & AIMS: OBJECTIVE:The purpose of our study was to evaluate the effects of 0.3-second high-resolution CT (HRCT) of the lung using partial reconstruction on cardiac motion artifacts and image noise. SUBJECTS AND METHODS:Thirty-seven pairs of 0.3-second (partial reconstruction) and 0.75-second (full reconstruction) HRCT images were obtained for the lower lung zone during full-inspiration breath-holding. Imaging parameters other than temporal resolution were identical for each patient. Two radiologists visually graded motion artifacts of the cardiac border, bronchi, pulmonary vessels, and fissure in the left lung on a 4-point scale (with 4 indicating no artifacts). The maximum width of motion along the left cardiac border and the area percentage of motion artifacts in the left lung were calculated. Image noise in the air and lung was also determined. Cardiac motion artifacts and image noises were compared between the two sets of CT images. RESULTS:Visual grades for the cardiac border (4 +/- 0), bronchi (3.8 +/- 0.7), pulmonary vessels (3.6 +/- 0.8), and fissure (3.9 +/- 0.5) were higher for 0.3-second images than for 0.75-second images (1.7 +/- 0.7, 2.0 +/- 1.0, 1.6 +/- 0.7, and 2.4 +/- 0.9, respectively) (p < 0.001). The maximum width of motion along the left cardiac border (0.1 +/- 0.5 mm) and the area percentage of motion artifacts in the left lung (6.7% +/- 18.4%) were smaller for 0.3-second images than for 0.75-second images (4.5 +/- 1.7 mm and 36.2% +/- 20.9%, respectively) (p < 0.001). Image noises in the air (38.0 +/- 9.2) and the lung (86.0 +/- 23.1) were greater for 0.3-second images than for 0.75-second images (35.6 +/- 9.6 and 76.0 +/- 20.3, respectively) (p < 0.01). CONCLUSION:Compared with 0.75-second HRCT using full reconstruction, 0.3-second HRCT using partial reconstruction substantially reduces cardiac motion artifacts in the lung at the expense of increasing image noise.

背景与目标： 目的：本研究的目的是通过部分重建对心脏运动伪影和图像噪声的效果，评估0.3秒高分辨率肺部CT（HRCT）的影响。
研究对象和方法：在全屏吸气时，获得了37对0.3秒（部分重建）和0.75秒（完全重建）的HRCT图像，用于下肺区。对于每个患者，除时间分辨率以外的成像参数均相同。两位放射科医生对心脏边界，支气管，肺血管和左肺裂的运动伪影进行了4分制的视觉分级（其中4表示无伪影）。计算沿左心脏边界的最大运动宽度和左肺中运动伪影的面积百分比。还确定了空气和肺中的图像噪声。比较两组CT图像之间的心脏运动伪影和图像噪声。
结果：0.3秒图像的心脏边界（4 /-0），支气管（3.8 /-0.7），肺血管（3.6 /-0.8）和裂痕（3.9 /-0.5）的视觉等级高于0.75秒图像（分别为1.7 /-0.7、2.0 /-1.0、1.6 /-0.7和2.4 /-0.9）（p <0.001）。对于0.3秒的图像，沿左心脏边界的最大运动宽度（0.1 /-0.5 mm）和左肺中的运动伪影的面积百分比（6.7％/-18.4％）小于0.75秒的图像（分别为4.5±1.7毫米和36.2％±20.9％（p <0.001）。对于0.3秒的图像，空气（38.0 /-9.2）和肺（86.0 /-23.1）的图像噪声大于0.75秒的图像噪声（分别为35.6 /-9.6和76.0 /-20.3）（p <0.01 ）。
结论：与使用完全重建的0.75秒HRCT相比，使用部分重建的0.3秒HRCT可以显着减少肺部的心脏运动伪影，但会增加图像噪声。

BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.

背景与目标： ：Rhodopseudomonas palustris是一种紫色的兼性光养细菌，它利用氢气作为电子供体，在光养植物生长过程中固定二氧化碳，或在固氮过程中合成氨气。它还使用氢作为电子补充剂，以在光异养生长期间将氧化的碳化合物（例如苹果酸）完全同化到细胞材料中。 R. palustris基因组预测膜结合的镍铁摄取氢化酶和几种调节蛋白来控制氢化酶的合成。与氢化酶基因簇直接相邻的还有一个新的传感器激酶基因（RPA0981）。在这里，我们显示帕氏疟原虫调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用，以响应氢气激活氢化酶表达。转录组分析表明，HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统，推定的甲酸盐转运蛋白和谷氨酰胺合成酶的基因的表达。 RPA0981在抑制氢化酶合成方面作用很小。我们还确定了两组分系统RegS-RegR抑制摄取氢化酶的表达，可能是响应细胞内氧化还原状态的变化。转录组分析表明，与缺乏摄取氢酶的突变菌株相比，当在固氮条件下在苹果酸上光异养生长时，利用氢的pal.ris细胞中约有30个基因差异表达。由此看来，还原剂以氢的形式的循环利用对R. palustris的基因表达没有广泛的非特异性影响。

BACKGROUND & AIMS: :Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate dopamine D(1) and D(2) receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933-939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10 mg kg(-1)day(-1), p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1)day(-1)) was found to increase dopamine content by 110% in the striatum but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suggest that chronic treatment with high dose of simvastatin may affect DA tissue level in prefrontal cortex and striatum without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal dopaminergic disorders.

背景与目标： 他汀类药物已被用于治疗多种疾病，这些症状超出了降低胆固醇的最初指标。我们先前曾报道辛伐他汀会增加大鼠前额叶皮层中的多巴胺受体[Q.王伟丁宏阳黄，辛伐他汀大剂量上调大鼠前额叶皮层中的多巴胺D（1）和D（2）受体表达：可能与内皮一氧化氮合酶Br有关。 J.Pharmacol。 144（2005）933-939]，并在帕金森氏病（PD）模型中恢复了其下调[Q.王凤华Wang C.McLachlan，P.T. Wong，辛伐他汀逆转了6-羟基多巴胺诱导的帕金森病大鼠Brain Res的前额叶皮层中多巴胺D1和D2受体表达的下调。 1045（2005）229-233]。在这里，我们探讨辛伐他汀治疗对组织多巴胺含量和再摄取的影响。 Sprague-Dawley大鼠接受辛伐他汀（1和10 mg kg（-1）day（-1），口服）4周。取出前额叶皮层和纹状体的脑组织中的多巴胺含量并重新摄取。使用高效液相色谱质谱仪（HPLC-MS），发现辛伐他汀（10 mg kg（-1）day（-1））在纹状体中可使多巴胺含量增加110％，但在前额叶中减少76％皮层与生理盐水处理组相比。在两个大脑区域中，多巴胺（DA）的再摄取均未改变。这些结果表明，高剂量辛伐他汀的长期治疗可能会影响额叶前额叶皮层和纹状体中的DA组织水平，而不会改变DA的再摄取。这在精神病和纹状体多巴胺能障碍中可能具有重要的临床意义。

BACKGROUND & AIMS: :Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.

背景与目标： ：热休克蛋白90（HSP90）是结构折叠和维持各种蛋白质（包括与细胞信号相关的几种蛋白质）构象完整性的必需。利用HSP90抑制剂17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）的最新研究表明，在实体瘤中具有抗肿瘤作用。为了测试HSP90是否可以靶向于多发性骨髓瘤（MM）患者，我们首先通过免疫荧光和流式细胞术分析了骨髓瘤细胞系（U266）和原发性骨髓瘤细胞中HSP90的表达。在证明HSP90在骨髓瘤细胞中表达后，通过免疫过氧化物酶染色分析了32例MM患者的档案样本。在所有患者中，骨髓瘤细胞在所有样品中均表现出强烈的HSP90细胞质表达，并且55％的患者还表现出并发的核免疫阳性。与未处理的对照细胞相比，用17AAG处理U266细胞和原代MM细胞可导致凋亡明显增加。分析与17-AAG孵育的MM细胞中的抗凋亡BCL2家族蛋白和akt，表明BCL-2，BCL-XL，MCL-1和akt下调。此外，尽管低浓度的硼替佐米不会导致细胞死亡，但是17AAG和硼替佐米治疗的组合显示出对U266细胞系的协同凋亡作用。这些数据表明，针对HSP90的靶向抑制可能被证明是开发MM患者未来治疗选择的有效且创新的策略。

BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.

背景与目标： 氟达拉滨和阿仑单抗通常用于治疗B细胞慢性淋巴细胞性白血病（B-CLL）。本研究旨在比较氟达拉滨或alemtuzumab治疗后长期未维持的缓解/高原期的B-CLL患者的信号分子的表达和T细胞的细胞因子产生与惰性/未经治疗的B-CLL患者和健康供体的长期比较。通过流式细胞术检测TCR-CD3zeta链，p56lck，p59fyn，ZAP-70，PI3-激酶和干扰素（IFN）-γ/白介素（IL）-4在CD4和CD8 T细胞中的产生频率和强度。通过用纯化的蛋白质衍生物（PPD）和植物血凝素（PHA）刺激来评估T细胞功能。尽管数量减少，但患者T细胞中IFN-γ/ IL-4的表达明显高于健康供体。与健康供体相比，已治疗患者中大多数信号分子的强度相对未受影响，但低于未治疗的惰性患者。但是，表达每种信号分子的T细胞总数在患者中减少了，在氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中，对PHA而非TPD的T细胞反应降低。结果表明，尽管在用氟达拉滨和阿仑单抗治疗后，长期而言，尽管信号分子发生了某些变化并且T细胞数量有所减少，但总体T细胞功能仍可以得到较好的保留。

BACKGROUND & AIMS: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.

背景与目标： 背景：尽管最近在技术和患者选择方面已有改进，但ERCP后胰腺炎仍然是ERCP最常见和最可怕的并发症。最近的研究表明，用三硝酸甘油酯（GTN）进行预处理可以预防ERCP后胰腺炎并提高插管成功率。
目的：评价经皮GTN对ERCP插管成功和ERCP术后胰腺炎的影响。
设计：一项前瞻性，双盲，安慰剂对照试验。
单位：大专转诊大学医院。
患者：共有318例患者（平均年龄62岁，女性占61％）被随机分配到活动组（n = 155）或安慰剂组（n = 163）。
干预措施：主动贴片（GTN）与安慰剂贴片。
主要观察指标：排尿时间和成功率。 ERCP后胰腺炎发生率。
结果：主动或安慰剂组之间在以下方面没有显着差异：成功的初始插管（96.8％vs 98.8％），深层插管（96.1％vs 98.8％），成功插管的时间，使用导丝（27％vs 25％）或针刀（13％比13％）以及ERCP后胰腺炎（安慰剂患者为7.4％，活动患者为7.7％）。多变量分析确定女性，年轻患者，胰腺造影，乳头尝试次数以及混浊后胰管排空不良是ERCP后胰腺炎的危险因素。在任何已确定的高危人群中，经皮GTN均不能减轻ERCP后胰腺炎的发生。
结论：无论是普通患者还是高危患者，经皮GTN均不能提高ERCP插管成功率或预防ERCP术后胰腺炎。

BACKGROUND & AIMS: :Responses to [D-Ala2, MePhe4, Gly-ol5]enkephalin, a selective agonist for mu-receptors, were recorded intracellularly from 26 neurons in slices of guinea-pig hypothalamus. Of eight cells tested in the supraoptic nucleus, all of which had electrical properties characteristic of magnocellular neuroendocrine cells, four were sensitive to the agonist applied in the perfusion bath or with microdrops. The main effect was a decrease or suppression of spontaneous firing. In the paraventricular nucleus, seven of 18 cells tested also had electrophysiological characteristics similar to magnocellular neurons: two of them were sensitive to the mu-agonist and the effect was similar to that observed in the supraoptic nucleus. The remaining paraventricular neurons displayed low-threshold Ca2+ spikes, and thus had electrophysiological characteristics different from putative magnocellular neurons. Ten of 11 cells with low-threshold Ca2+ spikes were hyperpolarized by more than 10 mV by the mu-agonist, and showed a 33 +/- 1.9% (S.E.M.) decrease in input resistance. In both types of cells, when synaptic transmission was blocked with tetrodotoxin, the mu-agonist could still induce a hyperpolarization, suggesting that the effect was in part direct. Hyperpolarization was also obtained when the Cl- reversal potential was shifted to more positive values by using KCl electrodes, thus excluding a Cl- conductance mechanism. These results provide evidence that opioid peptides can directly inhibit hypothalamic neurons, that the mechanism is an increase in K+ conductance, and that two types of hypothalamic neurons appear to have different sensitivities to a mu-agonist.

背景与目标： ：对豚鼠下丘脑切片中26个神经元的细胞内记录了对[D-Ala2，MePhe4，Gly-ol5]脑啡肽（一种针对mu受体的选择性激动剂）的反应。在视上核中测试的8个细胞中，所有细胞均具有大细胞神经内分泌细胞的电特性，其中4个对灌注浴或微滴中使用的激动剂敏感。主要作用是减少或抑制自发放电。在脑室旁核中，测试的18个细胞中有7个也具有类似于大细胞神经元的电生理特性：其中两个对mu激动剂敏感，作用类似于在视上核中观察到的。其余的脑室旁神经元显示低阈值的Ca2尖峰，因此具有与假定的大细胞神经元不同的电生理特性。 mu激动剂将11个具有低阈值Ca2尖峰的细胞中的10个超极化了10 mV以上，显示输入电阻降低了33 /-1.9％（S.E.M.）。在两种类型的细胞中，当突触传递被河豚毒素阻断时，mu-激动剂仍可诱导超极化，这表明这种作用部分是直接的。当通过使用KCl电极将Cl-反转电位移动到更正值时，也获得了超极化，因此排除了Cl-电导机制。这些结果提供证据表明阿片样物质肽可以直接抑制下丘脑神经元，其机制是钾电导增加，并且两种类型的下丘脑神经元似乎对μ-激动剂具有不同的敏感性。

BACKGROUND & AIMS: BACKGROUND:Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (V(T)) while maintaining constant partial arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI). METHODS:ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n = 8 for each group), and subsequently ventilated with limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours. Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS:TGI resulted in significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5 +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T) [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg], SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3) mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02) ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24) mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05 vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS:In this animal model of ALI, TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.

背景与目标： 背景：肺表面活性物质功能障碍可能导致呼吸机诱发的肺损伤（VILI）的发展。气管内注气（TGI）是一种将新鲜气体引入气管并通过减少通气系统的死腔，降低通气压力和潮气量（V（T））并保持恒定的局部动脉CO2压力来增强通气的技术（ PaCO（2））。我们假设TGI限制了峰值吸气压力（PIP）和V（T），并且将传统机械通气（CMV）引起的肺表面活性剂功能异常减至最小，从而减轻了急性肺损伤（ALI）兔的VILI。
方法：通过气管内脂多糖经气管内施用麻醉的，通气的健康成年兔，以0.5 L / min（TGI组）或CMV组（每组n = 8）随机分配为连续TGI，然后在有限的PIP和通气条件下通气，从而诱发ALI。 V（T）将PaCO（2）维持在35至45 mmHg的范围内4个小时。监测生理死区与V（T）的比率（V（D）/ V（T）），动态呼吸顺应性（Cdyn）和部分动脉O（2）压力（PaO（2））。通气后，对肺中的总磷脂（TPL），总蛋白（TP），支气管肺泡灌洗液（BALF）中的肺表面活性剂小到大聚集比（SA / LA）进行分析，并测定肺泡体积密度（V（V）） ），髓过氧化物酶和白介素（IL）-8。
结果：TGI导致PIP显着降低（P <0.05或P <0.01）[（22.4 /-1.8）cmH2O与（29.5 /-1.1）cmH2O]，V（T）[（6.9 /-1.3）ml / kg vs（9.8 /-1.11）ml / kg]，V（D）/ V（T）[（32 /-5）％vs（46 /-2）％]，TP [（109 /-22）mg / kg vs（187 /-25）mg / kg]，SA / LA（2.5 /-0.4 vs 5.4 /-0.7），髓过氧化物酶[（6.2 /-0.5）U / g组织vs（12.3 /-0.8）U / g组织]和IL-8 [（987 /-106）ng / g组织vs（24 /-3）mN / m] BALF，Cdyn [（0.47 /-0.02）ml.cmH2O显着（P <0.05）增加（-1）.kg（-1）vs（0.31 /-0.02）ml.cmH2O（-1）.kg（-1）]，PaO（2）[（175 /-24）mmHg vs（135 /-26 ）mmHg]，TPL / TP（52 /-8 vs 33 /-11）和Vv（0.65 /-0.05 vs 0.44 /-0.07）。
结论：在这种ALI动物模型中，TGI降低了通气需求（PIP，V（T）和V（D）/ V（T）），与CMV相比，肺泡表面活性剂的肺泡表面活性剂组成和功能更佳，肺部损伤的严重程度更低。 TGI结合限压通气可能是ALI的肺保护策略。