• 【听力损失平坦的听众的语音掩蔽释放:掩蔽者波动率对识别分数和语音特征接收的影响。】 复制标题 收藏 收藏
    DOI:10.1080/14992020600753213 复制DOI
    作者列表:Lorenzi C,Husson M,Ardoint M,Debruille X
    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。
  • 【数学与语言是否在同一侧?右半球失语症和数学能力。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2006.07.063 复制DOI
    作者列表:Semenza C,Delazer M,Bertella L,Granà A,Mori I,Conti FM,Pignatti R,Bartha L,Domahs F,Benke T,Mauro A
    BACKGROUND & AIMS: :The main purpose of the present study was to learn how mathematical abilities are located and develop in the brain with respect to language. Mathematical abilities were assessed in six right-handed patients affected by aphasia following a lesion to their non-dominant hemisphere (crossed aphasia) and in two left-handed aphasics with a right-sided lesion. Acalculia, although in different degrees, was found in all cases. The type of acalculia depended on the type of aphasia, following patterns that have been previously observed in the most common aphasias resulting from left hemisphere lesions. No sign of right hemisphere or spatial acalculia (acalculia in left lateralised right-handed subjects) was detected. These results suggest that, as a rule, language and calculation share the same hemisphere. A primitive computational mechanism capable of recursion may be the precursor of both functions.
    背景与目标: :本研究的主要目的是学习关于语言的数学能力如何在大脑中定位和发展。评估了六名右撇子患者在非优势性半球病变(交叉性失​​语症)后患失语症的数学能力,以及两名左撇子右手病变的数学能力。在所有情况下均发现失语症,尽管程度不同。失语症的类型取决于失语症的类型,其遵循先前在左半球病变导致的最常见失语症中观察到的模式。未检测到右半球或空间失聪的迹象(左外侧右手受试者的眼球积水)。这些结果表明,通常,语言和计算共享相同的半球。能够递归的原始计算机制可能是这两种功能的先驱。
  • 【数字和空间的共享空间表示形式:SNARC和西蒙效应的逆转。】 复制标题 收藏 收藏
    DOI:10.1037/0096-1523.32.5.1197 复制DOI
    作者列表:Notebaert W,Gevers W,Verguts T,Fias W
    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。
  • 【使用部分与完全重建的肺部高分辨率CT对运动伪影和图像噪声的影响。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.05.0852 复制DOI
    作者列表:Ha HI,Goo HW,Seo JB,Song JW,Lee JS
    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。
  • 【拟南芥中吸收氢酶的调控和氢利用对基因表达的影响。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00381-06 复制DOI
    作者列表:Rey FE,Oda Y,Harwood CS
    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。
  • 【大剂量辛伐他汀对SD大鼠多巴胺水平及其在额叶前额叶皮层和纹状体中再摄取的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2006.09.009 复制DOI
    作者列表:Wang Q,Tang XN,Wang L,Yenari MA,Ying W,Goh BC,Lee HS,Wilder-Smith EP,Wong PT
    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。
  • 【多发性骨髓瘤中热休克蛋白90(HSP90)的表达和HSP90抑制剂(17-AAG)的作用分析。】 复制标题 收藏 收藏
    DOI:10.1080/10428190500472123 复制DOI
    作者列表:Duus J,Bahar HI,Venkataraman G,Ozpuyan F,Izban KF,Al-Masri H,Maududi T,Toor A,Alkan S
    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。
  • 【B细胞慢性淋巴细胞性白血病患者T细胞中的信号分子和细胞因子产生:氟达拉滨和alemtuzumab治疗的长期效果。】 复制标题 收藏 收藏
    DOI:10.1080/10428190600565503 复制DOI
    作者列表:Kiaii S,Choudhury A,Mozaffari F,Rezvany R,Lundin J,Mellstedt H,Osterborg A
    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。
  • 【透皮三硝酸甘油酯在ERCP中的前瞻性,随机,安慰剂对照试验:对技术成功和ERCP后胰腺炎的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.gie.2005.11.060 复制DOI
    作者列表:Kaffes AJ,Bourke MJ,Ding S,Alrubaie A,Kwan V,Williams SJ
    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。
  • 【对mu受体有选择性的阿片肽的直接作用:豚鼠心室旁和视上核中的细胞内记录。】 复制标题 收藏 收藏
    DOI:10.1016/0306-4522(90)90426-5 复制DOI
    作者列表:Wuarin JP,Dudek FE
    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。
  • 【限压通气过程中连续气管内气体注入对急性肺损伤家兔肺表面活性物质的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Zhu GF,Zhang W,Zong H,Liang Y
    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。
  • 【辐射诱发的旁观者和其他非靶向效应:癌症治疗中的新干预点?】 复制标题 收藏 收藏
    DOI:10.2174/156800906777723976 复制DOI
    作者列表:Mothersill C,Seymour C
    BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.
    背景与目标: :寻找新的癌症药物靶标的主要问题是该药物通常对正常组织有毒性,需要高剂量才能杀死肿瘤细胞。因此,细胞靶标似乎涉及对癌症治疗的低剂量反应,因此特别令人感兴趣,因为它们可以选择性地靶向未被治疗靶标的正常组织,因此可能引起令人不快的副作用,或者可能适合于剥削以改善治疗效果。治疗比率。辐射诱导的旁观者效应[RIBE]是本综述的主题之一,该效应导致在未辐射的细胞中观察到辐射样反应。 RIBE是一种新现象,表明在低剂量时,细胞信号传导比直接DNA损伤更为重要。从历史上看,DNA一直被认为是放射治疗的目标。人们日益认识到信号转导很重要,这开启了几种重要的治疗策略,本文将对此进行讨论。 RIBE似乎是组织或细胞中普遍的应激反应的结果,这种应激反应是在组织,器官或生物体的水平而不是单个细胞的水平表达的。信号可能由所有暴露的细胞产生,但响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET(X射线或γ射线)辐射暴露的主要反应是死亡反应。这具有许多细胞凋亡特征,但尽管在许多肿瘤细胞系中死亡反应受到抑制,但在没有p53表达的细胞系中可能检测到。虽然在肿瘤周围未照射的正常细胞中的死亡反应似乎是不利的,但实际上可以起到保护作用,并从群体中清除受损的细胞。如果利用得当,它可能会导致开发新药物,其目的不是破坏组织,而是使稳态机制能够控制肿瘤的扩展。在这种情况下,有害或有益反应的水平将与细胞群所携带的背景损伤以及决定对损伤的反应的遗传程序有关。当试图预测涉及放射线和其他细胞毒剂的混合疗法的后果时,这一重点可能很重要。在这篇综述中,我们对电离辐射诱发旁观者效应的潜在机制的现有知识进行了综述,并探讨了如何利用旁观者效应来生产旨在稳定组织稳态而不是稳定组织的新一代抗癌药物的问题。考虑组织破坏。
  • 【新的胆囊收缩素类似物(JMV 236)对大鼠食物摄入和脑单胺的影响。】 复制标题 收藏 收藏
    DOI:10.1016/0143-4179(90)90158-u 复制DOI
    作者列表:Gourch A,Orosco M,Rodriguez M,Martinez J,Cohen Y,Jacquot C
    BACKGROUND & AIMS: :JMV 236, a new cholecystokinin-octapeptide-sulfate (CCK 8 S) derivative (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) has been synthesized in the Centre de Pharmacologie-Endocrinologie (Montpellier). This peptide has been shown to present the same activity as CCK 8 S on pancreatic amylase secretion and has the advantage of a better chemical stability. With a view to further characterization, the effect of JMV 236 on food intake and brain monoamine and metabolite variations was assayed in the rat after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administrations. JMV 236 decreased food intake 2 and 3 hours after i.p. administration of 12.5 and 50 micrograms/kg but was inactive after i.c.v. injection. Its global action was similar to that of CCK 8 S, but was less marked with delayed onset of response. As in our previous work with CCK 8 S, JMV 236 was more potent in inducing monoaminergic variations after i.p. than after i.c.v. administration. The main effects were decreases in striatal dopamine metabolite levels and increases in hypothalamic and striatal serotonin metabolite (5-HIAA) levels. These effects are classically observed with CCK 8 S and are described in our previous reports. The interesting peptide will require further characterization and may serve as a possible reference compound for studies on CCK derivatives.
    背景与目标: :JMV 236是一种新的胆囊收缩素-八肽硫酸盐(CCK 8 S)衍生物(Boc-Tyr(SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2),已在药理学-内分泌中心(蒙彼利埃)。已显示该肽在胰腺淀粉酶分泌方面具有与CCK 8 S相同的活性,并且具有更好的化学稳定性的优点。为了进一步表征,在腹膜内(i.p.)和脑室内(i.c.v.)给药后,在大鼠中测定了JMV 236对食物摄入以及脑单胺和代谢产物变化的影响。腹腔注射后2和3小时,JMV 236的食物摄入量减少了。静脉注射12.5和50微克/公斤,但在静脉内注射后无效。注射。它的整体作用与CCK 8 S相似,但反应迟发的症状较少。正如我们以前使用CCK 8 S所做的工作一样,JMV 236腹腔注射后在诱导单胺能变化方面更有效。比在i.c.v.之后行政。主要影响是纹状体多巴胺代谢物水平降低,下丘脑和纹状体5-羟色胺代谢物(5-HIAA)水平升高。这些效应在CCK 8 S上得到了经典观察,并在我们以前的报告中有所描述。令人感兴趣的肽将需要进一步表征,并可能用作研究CCK衍生物的可能参考化合物。
  • 【ATP诱导的腿部血管舒张对人体最大运动过程中VO2峰值和腿部O2提取的影响。】 复制标题 收藏 收藏
    DOI:10.1152/ajpregu.00746.2005 复制DOI
    作者列表:Calbet JA,Lundby C,Sander M,Robach P,Saltin B,Boushel R
    BACKGROUND & AIMS: :During maximal whole body exercise VO2 peak is limited by O2 delivery. In turn, it is though that blood flow at near-maximal exercise must be restrained by the sympathetic nervous system to maintain mean arterial pressure. To determine whether enhancing vasodilation across the leg results in higher O2 delivery and leg VO2 during near-maximal and maximal exercise in humans, seven men performed two maximal incremental exercise tests on the cycle ergometer. In random order, one test was performed with and one without (control exercise) infusion of ATP (8 mg in 1 ml of isotonic saline solution) into the right femoral artery at a rate of 80 microg.kg body mass-1.min-1. During near-maximal exercise (92% of VO2 peak), the infusion of ATP increased leg vascular conductance (+43%, P<0.05), leg blood flow (+20%, 1.7 l/min, P<0.05), and leg O2 delivery (+20%, 0.3 l/min, P<0.05). No effects were observed on leg or systemic VO2. Leg O2 fractional extraction was decreased from 85+/-3 (control) to 78+/-4% (ATP) in the infused leg (P<0.05), while it remained unchanged in the left leg (84+/-2 and 83+/-2%; control and ATP; n=3). ATP infusion at maximal exercise increased leg vascular conductance by 17% (P<0.05), while leg blood flow tended to be elevated by 0.8 l/min (P=0.08). However, neither systemic nor leg peak VO2 values where enhanced due to a reduction of O2 extraction from 84+/-4 to 76+/-4%, in the control and ATP conditions, respectively (P<0.05). In summary, the VO2 of the skeletal muscles of the lower extremities is not enhanced by limb vasodilation at near-maximal or maximal exercise in humans. The fact that ATP infusion resulted in a reduction of O2 extraction across the exercising leg suggests a vasodilating effect of ATP on less-active muscle fibers and other noncontracting tissues and that under normal conditions these regions are under high vasoconstrictor influence to ensure the most efficient flow distribution of the available cardiac output to the most active muscle fibers of the exercising limb.
    背景与目标: :在最大程度的全身运动过程中,VO2峰值受O2释放量的限制。反过来,虽然必须在交感神经系统的约束下进行接近最大运动量的血流以维持平均动脉压。为了确定在近乎最大和最大运动量的情况下,增强腿部血管舒张程度是否会导致较高的O2输送量和腿部VO2,七名男性在自行车测功计上进行了两次最大的增量运动测试。以随机顺序进行一项试验,一项试验不进行(对照运动)以80 microg.kg体重-1.min-的速率向右股动脉中输注ATP(1毫升等渗盐溶液中8毫克)。 1。在接近最大运动量(VO2峰值的92%)期间,输注ATP可增加腿部血管电导率(43%,P <0.05),腿部血流量(20%,1.7 l / min,P <0.05)和腿部O2递送(20%,0.3l / min,P <0.05)。没有观察到对腿或全身VO2的影响。输注腿中的腿部O2分数提取率从85 / -3(对照)降至78 / -4%(ATP)(P <0.05),而在左腿中则保持不变(84 / -2和83 /- 2%;对照和ATP; n = 3)。进行最大运动量的ATP输注可使腿部血管电导增加17%(P <0.05),而腿部血流则倾向于增加0.8 l / min(P = 0.08)。但是,在对照和ATP条件下,由于O2提取量分别从84 / -4降低到76 / -4%,全身和腿部VO2峰值均未升高(P <0.05)。总之,在人类进行近乎最大或最大运动时,下肢骨骼肌的VO2不会因肢体血管扩张而得到增强。 ATP输注导致运动腿上的O2提取减少的事实表明ATP对不太活跃的肌纤维和其他非收缩性组织的血管舒张作用,并且在正常情况下,这些区域处于高血管收缩作用下,以确保最有效的血流有效心输出量到运动肢体最活跃的肌肉纤维的分布。
  • 【冷暴露对大鼠肾上腺酪氨酸羟化酶的影响:RNA,蛋白质,酶活性和辅因子水平的分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1471-4159.1990.tb01232.x 复制DOI
    作者列表:Baruchin A,Weisberg EP,Miner LL,Ennis D,Nisenbaum LK,Naylor E,Stricker EM,Zigmond MJ,Kaplan BB
    BACKGROUND & AIMS: :Long-term cold exposure (5-7 days) is known to induce concomitant increases in the levels of adrenomedullary tyrosine hydroxylase (TH) RNA, protein, and enzyme activity. In this report, we compare the time courses of these changes and investigate the effects of cold exposure on the levels of biopterin, the cofactor required for tyrosine hydroxylation. After only 1 h of cold exposure, TH mRNA abundance increased 71% compared with nonstressed controls. Increases in total cellular TH RNA levels were maximal (threefold over control values) within 3-6 h of cold exposure and remained elevated throughout the duration of the experiment (72 h). TH protein levels increased rapidly after 24 h of cold exposure and reached a maximal value threefold above that of controls at 48-72 h. Despite the relatively rapid and large elevations in TH RNA and protein content, only modest increases in TH activity were detected during the initial 48 h of cold exposure. Adrenomedullary biopterin increased rapidly after the onset of cold exposure, rising to a level approximately twofold that of the nonstressed controls at 24 h, and remained at this level throughout the duration of the stress period. Taken together, the results of this time course study indicate that cold-induced alterations in adrenal TH activity are mediated by multiple cellular control mechanisms, which may include pre- and posttranslational regulation. Our findings also suggest that cold stress-induced increases in the levels of the TH cofactor may represent another key event in the sympathoadrenal system's response to cold stress.
    背景与目标: :已知长期冷暴露(5-7天)会引起肾上腺髓质酪氨酸羟化酶(TH)RNA,蛋白质和酶活性的同时升高。在本报告中,我们比较了这些变化的时程,并研究了冷暴露对生物蝶呤水平的影响,生物蝶呤是酪氨酸羟化所需的辅助因子。低温暴露仅1小时后,与未受压力的对照组相比,TH mRNA的丰度增加了71%。在冷暴露的3-6小时内,总细胞TH RNA水平的增加最大(比对照值高三倍),并且在整个实验过程中(72小时)保持升高。在冷暴露24小时后,TH蛋白水平迅速升高,在48-72 h时达到最大值,是对照的三倍。尽管TH RNA和蛋白质含量的升高相对较快且幅度较大,但在冷暴露的最初48小时内仅检测到TH活性的适度增加。冷暴露开始后,肾上腺髓质生物蝶呤迅速增加,在24 h时升高至非应激对照组的两倍,并在整个应激期一直保持在该水平。两者合计,此时间过程研究的结果表明,冷诱导的肾上腺TH活性的改变是由多种细胞控制机制介导的,其中可能包括翻译前和翻译后调控。我们的发现还表明,冷应激诱导的TH辅助因子水平升高可能代表交感肾上腺系统对冷应激反应的另一个关键事件。

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