Benzo[b]thiophenesulphonamide 1,1-dioxide derivatives inhibit tNOX activity in a redox state-dependent manner

Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour-associated NADH oxidase (tNOX) activity of the plasma membrane has been described. To analyse the putative implication of tNOX in BTS-induced ROS generation, in this work we have synthesised and tested a new BTS derivative, the 6-[N-(2-phenylethyl)]benzo[b]thiophenesulphonamide 1,1-dioxide. According to its high lipophilicity, this compound showed a strong cytotoxic activity against a panel of six human tumour cell lines, including two human leukaemia (K-562 and CCRF-CEM) and four human solid tumours (HT-29, HTB54, HeLa and MEL-AC). We also tested the ability of this compound to inhibit the tNOX activity and we found an absolute dependence of this inhibition on the redox state of the tNOX: while under reducing conditions, that is, 100 mM GSH, the drug inhibits strongly the NOX activity with an EC(50) of about 0.1 nM, under oxidising conditions, there is no effect of the drug or just a slight stimulation of activity.     

Comparative Investigation by Two Analytical Approaches of Enthalpy Relaxation for Glassy Glucose,Sucrose, Maltose,and Trehalose

No HeadingPurpose. In an effort to understand the stability of glassy sugars such as glucose, sucrose, maltose, and trehalose, the molecular mobility below the glass transition temperature (T_g) was investigated by an enthalpy relaxation measurement with differential scanning calorimetry (DSC).Methods. The glassy sample was aged over several days at (T_g – 10) K to (T_g – 30) K, before a DSC heating scan was taken. The relaxed enthalpy (H_relax) was estimated from the endothermic peak area. The enthalpy relaxation time was analyzed from the time course of H_relax using two different approaches; Kohlrausch-Williams-Watts (KWW) and extended Adam-Gibbs (exAG).Results. ^KWW, which is defined as the mean average enthalpy relaxation time in a distribution, and ^eff₀ and ^eff, which correspond to the enthalpy relaxation time of the initial minimum and final maximum cooperative rearrangement region, were estimated by KWW and exAG, respectively. And three activation energies for enthalpy relaxation were calculated from the Arrhenius plot.Conclusions. Although these Es originated from different theoretical backgrounds, almost the same trend was observed for a comparison of the values of the four sugars. The finding that the Es of glassy trehalose were the largest among the four sugars may support the reason that glassy trehalose is an effective stabilizer.     

Up-regulation of telomere-binding TRF1, TRF2 related to reactive oxygen species induced by As(2)O(3) in MGC-803 cells

In this work, our study focused on As(2)O(3) action in view point of telomere. Results showed that treatment of human gastric cancer MGC-803 cells with arsenic trioxide could cause up-regulation of telomeric repeat binding factor TRF1 and TRF2 mRNA and protein levels, and induced G2/M phase arrest and cell apoptosis. At the same time, telomere length shortening and telomerase inhibitory were not obvious. Flow cytometry measurements indicated that the increase of TRF1 and TRF2 proteins is related to oxidative stress by arsenic trioxide. Results also indicate that after arsenic trioxide treatment, p53 protein levels increased significantly and also could bind directly at the telomere t-loop junction. These findings demonstrate arsenic trioxide-induced cell cycle arrest and apoptosis might involve a novel pathway related to TRF1, TRF2 protein.     

某地区受艾滋病影响儿童心理状况调查

目的调查山西某艾滋病比较集中的地区受艾滋病影响儿童的情绪状况、社会支持、应对方式和心理韧性等方面的现状。方法采用中文版儿童焦虑性情绪障碍筛查表(SCARED)、中文版儿童抑郁自评量表(DSRS)、社会支持评定量表(SSS)、简易应对方式问卷(SCSQ)及青少年心理韧性量表(RSCA)进行调查。结果①在焦虑、抑郁情绪得分上,受艾滋病影响儿童组即研究组(分别为23.45±11.32、11.37±4.37)与普通儿童组即对照组(分别为22.53±11.08、11.40±4.38)之间的差异不具有统计学意义(P>0.05);②在积极应对得分上,研究组(19.61±6.40)与对照组(22.70±5.28)之间的差异具有统计学意义(P<0.05);③在客观支持、主观支持以及社会支持总分上,研究组(分别为9.30±2.92、24.11±3.97、41.83±7.01)与对照组(分别为10.81±2.71、25.75±3.75、45.34±6.44)之间的差异具有统计学意义(P<0.05);④在目标专注、积极认知以及心理韧性总分得分上,研究组(分别为3.58±0.80、3.55±0.92、93.97±14.06)与对照组(分别为3.84±0.66、3.79±0.74、97.69±11.64)之间的差异具有统计学意义(P<0.05)。结论与普通儿童相比,受艾滋病影响儿童在社会支持的获得上存在明显的不足,同时,其积极应对的能力和心理韧性也需要进一步加强,有必要在这些方面对他们实施有针对性的心理辅导和干预。     

慢性心功能不全患者生活质量及其相关因素的临床研究

目的探讨慢性心功能不全患者的生活质量及其相关因素。方法用症状自评量表(SCL-90)和心功能不全生活质量量表(LHFQ)对80例住院慢性心功能不全患者进行测评。结果慢性心功能不全患者的生活质量总分为(64.2±14.4)分;SCL-90量表中躯体化(2.47±0.68)分,恐怖(1.79±0.43)分,焦虑(1.97±0.39)分,抑郁(1.86±0.55)分;生活质量与焦虑、抑郁情绪呈正相关(r=0.277～0.389,P<0.05,0.01),与文化程度、经济收入呈显著负相关(r=-0.288～0.415,P<0.05或0.01);与家庭负担、总病程以及既往住院次数呈显著正相关(r=0.279～0.398,P<0.05,0.01)。结论慢性心功能不全患者存在不良心理状态和相对较低的生活质量,生活质量受多方因素影响,有必要对其进行心理、社会支持,以提高其生活质量。     

An algorithm based on one or two nasal samples is accurate to identify persistent nasal carriers of Staphylococcus aureus

Persistent Staphylococcus aureus nasal carriers are at high risk of S. aureus infection. The present study delineates a simple strategy aimed at identifying rapidly and accurately this subset of subjects for clinical or epidemiological purposes. Ninety healthy volunteers were each identified as persistent, intermittent or non-nasal carriers of S. aureus by using seven specimens sampled over a 5-week period. By reference to this so-called reference standard, six other strategies aimed at simplifying and speeding the identification of persistent carriers and based on the qualitative or quantitative detection of S. aureus in one to three nasal samples were evaluated by the measure of the area under the curve of receiver operating characteristic diagrams. Among strategies using qualitative results, there was no statistical difference between protocols using seven and three samples. A threshold of 10³ CFU of S. aureus per swab was found capable of defining persistent nasal carriage with a sensitivity of 83.1% and a specificity of 95.6%. These figures reached 95.5% and 94.9%, respectively, by using an algorithm including one or two nasal specimens according to the threshold of 10³ CFU of S. aureus in the first swab. The latter two strategies were shown to be costly equivalents. The proposed algorithm-based strategy proved to be relevant to identify properly and consistently persistent nasal carriers of S. aureus. However, as it was built from data of healthy volunteers, it needs to be confirmed prospectively on patients potentially at risk for S. aureus infection.     

原发性高血压患者血栓前状态的研究

目的:检测原发性高血压患者血栓前状态相关指标,探讨血栓前状态(prothrombotic state,PTS)与原发性高血压的关系.方法:定量检测80例原发性高血压患者及30例正常对照组的血液流变学指标、纤维蛋白原( fibrinogen,FIB).结果:①高血压1和2级组FIB、血黏度高于正常对照组(P＜0.05).高血压1和2级组血小板聚集率显著高于正常对照组(P＜0.01).高血压3级组FIB高于正常对照组(P＜0.05).高血压3级组血黏度、血小板聚集率显著高于正常对照组(P＜0.01).高血压1和2级组与高血压3级组FIB、血黏度、血小板聚集率没有统计学意义(P＞0.05).②血浆黏度与FIB呈正相关(r =0.297,P＜0.01).结论:原发性高血压患者存在血栓前状态.     

A big-world network in ASD: dynamical connectivity analysis reflects a deficit in long-range connections and an excess of short-range connections

Over the last years, increasing evidence has fuelled the hypothesis that Autism Spectrum Disorder (ASD) is a condition of altered brain functional connectivity. The great majority of these empirical studies relies on functional magnetic resonance imaging (fMRI) which has a relatively poor temporal resolution. Only a handful of studies has examined networks emerging from dynamic coherence at the millisecond resolution and there are no investigations of coherence at the lowest frequencies in the power spectrum—which has recently been shown to reflect long-range cortico-cortical connections. Here we used electroencephalography (EEG) to assess dynamic brain connectivity in ASD focusing in the low-frequency (delta) range. We found that connectivity patterns were distinct in ASD and control populations and reflected a double dissociation: ASD subjects lacked long-range connections, with a most prominent deficit in fronto-occipital connections. Conversely, individuals with ASD showed increased short-range connections in lateral-frontal electrodes. This effect between categories showed a consistent parametric dependency: as ASD severity increased, short-range coherence was more pronounced and long-range coherence decreased. Theoretical arguments have been proposed arguing that distinct patterns of connectivity may result in networks with different efficiency in transmission of information. We show that the networks in ASD subjects have less Clustering coefficient, greater Characteristic Path Length than controls - indicating that the topology of the network departs from small-world behaviour - and greater modularity. Together these results show that delta-band coherence reveal qualitative and quantitative aspects associated with ASD pathology.     

静息态fMRI确定双手运动相关脑区——种子点选择对结果的影响

目的探讨种子点的选择对静息态fMRI确定双手运动相关脑区的影响。方法对31例(男15例,女16例)健康被试者行组块设计的双手运动和静息态fMRI扫描。采用DPARSFV2.0软件和SPM8软件进行数据处理,选取任务状态下各独立激活簇的最大激活点为种子点,分别计算静息状态下全脑功能连接图,计算静息状态下各功能连接图与任务状态激活图之间的空间相关系数。结果任务状态下得到15个独立的激活脑区,进而生成15个种子点,其中辅助运动区(SMA)为种子点的功能连接图与任务状态激活图空间分布一致性最强,空间相关系数最大;以初级运动皮质(M1区)及背侧前运动皮质(PMd)为种子点的功能连接图包括双侧M1区及SMA;以腹侧前运动皮质(PMv)为种子点所得功能连接图主要为PMv和PMd;以壳核(Pu)、丘脑(Th)、小脑前叶(CbAL)、小脑后叶(CbPL)为种子点所得功能连接图主要为种子点周围及其镜像脑区。结论静息状态下,以SMA为种子点能获得与手运动任务激活图有较好一致性的功能连接图,以M1及PMd为种子点能较好显示M1区。     

Intrascanner and interscanner variability of magnetization transfer‐sensitized balanced steady‐state free precession imaging

Recently, a new and fast three‐dimensional imaging technique for magnetization transfer ratio (MTR) imaging has been proposed based on a balanced steady‐state free precession protocol with modified radiofrequency pulses. In this study, optimal balanced steady‐state free precession MTR protocol parameters were derived for maximum stability and reproducibility. Variability between scans was assessed within white and gray matter for nine healthy volunteers using two different 1.5 T clinical systems at six different sites. Intrascanner and interscanner MTR measurements were well reproducible (coefficient of variation: c_v < 0.012 and c_v < 0.015, respectively) and results indicate a high stability across sites (c_v < 0.017) for optimal flip angle settings. This study demonstrates that balanced steady‐state free precession MTR not only benefits from short acquisition time and high signal‐to‐noise ratio but also offers excellent reproducibility and low variability, and it is thus proposed for clinical MTR scans at individual sites as well as for multicenter studies. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.