Discovery of SCH 900229, a Potent Presenilin 1 Selective γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

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韧带样瘤的MRI表现

目的探讨韧带样瘤的MRI表现,提高MRI对该病的诊断符水平。方法回顾分析6例经手术病理证实的韧带样瘤的MRI表现。结果 6例病理证实的病例中,浸润性生长3例,膨胀性生长3例,MRI信号混杂信号,T1WI以等信号为主,接近邻近肌肉信号,T2WI以略高信号为主,压脂序列呈高信号,所有病例中可见片状或索条状低信号,增强扫描肿瘤不均匀强化。结论 MRI检查显示韧带样瘤的形态、信号、强化方式等方面有一定的特征性,具有鉴别诊断价值。     

Emodin-induced microglial apoptosis is associated with TRB3 induction

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a natural anthraquinone compound isolated from the rhizome of rhubarb, has been reported to treat brain injury after intracerebral hemorrhage. Treatment of neurons with emodin is able to decrease glutamate excitotoxicity, modulate calcium homeostasis, and induce Bcl-2 expression. However, the effects of emodin on the brain-resident innate immune cells are unclear. In the present study, the mouse microglial cell line, BV-2, was selected to investigate the effects of emodin on microglial activation and apoptosis. Cell viability and apoptosis were sequentially measured with the CellTiter-Glo Luminescent Cell Viability Assay, YOPRO-1 and Caspase-Glo 3/7 Assay Systems. The degree of microglial activation was evaluated using quantitative RT-PCR to measure expression of inflammatory markers. Treatment of BV-2 cells with emodin caused caspase-mediated apoptosis in a dose-dependent manner, and emodin augmented LPS-induced microglial apoptosis to repress inflammatory activation. In response to emodin treatment, reactive oxygen species (ROS) production was increased, and TRB3 was markedly activated. siRNA knockdown of TRB3 attenuated emodin-induced microglial apoptosis. Ectopic overexpression of TRB3 decreased cell viability and was associated with dysregulation of the prosurvival Akt/FOXO3 pathway. These results demonstrate that emodin induces BV-2 cell apoptosis through TRB3 and consequently eliminates inflammatory microglia. Our findings provide a novel molecular basis through which emodin exerts neuroprotective effects, treating brain injury after intracerebral hemorrhage.     

Synergy of the antiretroviral protease inhibitor indinavir and chloroquine against malaria parasites in vitro and in vivo

Many malaria-endemic areas are also associated with high rates of human immunodeficiency virus (HIV) infection. An understanding of the chemotherapeutic interactions that occur during malaria and HIV co-infections is important. Our previous studies have demonstrated that some antiretroviral protease inhibitors are effective in inhibiting Plasmodium falciparum growth in vitro. Currently, studies examining the interactions between antiretroviral protease inhibitors and antimalarial drugs are being conducted, but the data are limited. In this study, we examined the synergistic interactions between the antiretroviral protease inhibitor indinavir and chloroquine (CQ) in chloroquine-resistant and chloroquine-sensitive malaria parasites in vitro and in vivo. In vitro, by using modified fixed-ratio isobologram method, fractional inhibitory concentrations index (FICI) was calculated to indicate the interaction between the two drugs. The results demonstrated that indinavir interacted synergistically with chloroquine against both chloroquine-sensitive P. falciparum clone 3D7 (mean FICI 0.784) and multidrug-resistant P. falciparum clone Dd2 (mean FICI 0.599). In vivo drug interactions were measured using a 4-day suppressive test in a rodent malaria model infected with Plasmodium chabaudi. We observed that indinavir enhanced the antimalarial activity of chloroquine against both the chloroquine-sensitive line P. chabaudi ASS and the chloroquine-resistant line P. chabaudi ASCQ. More importantly, chloroquine had a 100% clearance of asexual parasites when used in combination with indinavir at an appropriate dose ratio (10 mg/kg CQ + 1.8 g/kg indinavir) where there was no obvious toxicity. We conclude from this study that the combination of indinavir and chloroquine may become a novel antimalarial drug regimen.     

Fine Mapping Quantitative Trait Loci that Influence Alcohol Preference Behavior in the High and Low Alcohol Preferring (HAP and LAP) Mice

The High Alcohol Preferring (HAP1) and Low Alcohol Preferring (LAP1) mouse lines were selectively bred for differences in alcohol intake. The HAP1 and LAP1 mice are essentially non-inbred lines that originated from an outbred colony of HS/Ibg mice, a heterogeneous stock developed from intercrossing 8 inbred strains of mice. In a former genomewide SNP association study, we identified quantitative trait loci (QTL) on chromosomes 1, 3, 5, and 9 (Bice et al. 2009). Provisional QTL were also identified on chromosomes 8 and X. In the present study, using the same F2 DNA samples, we placed a much denser set of SNPs within each of those QTL regions. Using the same analytical approach employed previously, which utilizes ancestral recombination to fine map the QLT interval, we obtained significant LOD scores on chromosomes 1, 3, and 9, only. Our results using a dense set of SNP markers suggest that there are multiple loci contributing to alcohol preference on those three chromosomes.     

Development of the human fetal cerebellum in the second trimester: a post mortem magnetic resonance imaging evaluation

The cerebellum is one of the most important structures in the posterior cranial fossa, but the characterization of its development by magnetic resonance imaging (MRI) is incomplete. We scanned 40 fetuses that had no morphological brain disorder at 14-22 weeks of gestation using 7.0 T MRI. Amira 4.1 software was used to determine morphological parameters of the fetal cerebellum, which included the cerebellar volume (CV), transverse cerebellar diameter (TCD), and the length and width of the vermis. The relationship between these measurements and gestational age (GA) was analysed. We found that the primary fissure was visible at week 14 of gestation. From week 16, the prepyramidal fissure, the secondary fissure and the dentate nucleus could be identified. The posterolateral fissure and the fourth ventricle were recognized at week 17, whereas the tentorium of the cerebellum was visible at week 20. The relationships between GA and CV, TCD, and the width and length of the vermis were described adequately by second-order polynomial regression curves. The ratios between TCD and vermis length and between TCD and vermis width decreased with GA. These results show that 7.0 T MRI can show the trajectory of cerebellar development clearly. They increase our understanding of normal cerebellar development in the fetus, and will facilitate the diagnosis of pathological intrauterine changes in the cerebellum.     

序贯结肠透析辅助治疗重型乙型病毒性肝炎患者的护理

目的 探讨序贯结肠透析辅助治疗重型乙型病毒性肝炎患者的的疗效及护理方法.方法 对23例慢性重型乙型病毒性肝炎患者,在保肝、抗感染、支持疗法等综合治疗基础上行中药序贯结肠透析治疗,并用清肠养肝方保留灌肠,每周5次,4周为1个疗程.结果 显效7例,有效11例,无效5例;治疗后惠者发热、乏力、腹胀、口干症状显著改善(均P＜0.05).结论 中药序贯结肠透析治疗慢性重型乙型病毒性肝炎疗效较好,可显著减轻患者不适症状.做好透析前、透析中、透析后护理,可保证透析治疗顺利进行.     

蝶翼式与直式真空采血针采血的对照研究

目的 探讨蝶翼式真空采血针与直式真空采血针的使用效果.方法 将100例全面查体的老年糖尿痛患者随机分为实验组和对照组各50例,对照组采用直式真空采血针采血,实验组采用蝶翼式真空采血针采血,比较两组采血时间、凝血情况、患者疼痛感及皮下出血情况、一次采血成功率.结果 两组均无溶血发生;实验组患者皮下出血发生率及疼痛评分显著低于对照组,一次采血成功率及操作者感觉舒适率显著高于对照组(P＜0.05,P＜0.01),对照组采血时间较实验组快(P＜0.01).结论 蝶翼式真空采血针作为一项较新的设备,在减轻患者痛苦、提高一次采血成功率及护理人员操作舒适度上较直式真空采血针具有优势.     

结直肠癌术后患者癌因性疲乏与焦虑抑郁关系的研究

目的 探讨结直肠癌术后患者癌因性疲乏(CRF)与焦虑、抑郁的关系及CRF的影响因素.方法 采用简易疲乏量表中国版(BFI-C)与医院焦虑抑郁量表(HAD),对187例结直肠癌术后患者CRF、焦虑、抑郁状况进行调查.结果 结直肠癌术后患者CRF的发生率为86.63%,焦虑、抑郁的发生率分别为21.39%和16.04%,8.56%患者焦虑与抑郁并存,CRF与焦虑、抑郁呈显著正相关(均P<0.01);正在接受的治疗类型、焦虑、抑郁等为结直肠癌术后患者CRF发生的主要影响因素.结论 结直肠癌术后患者的CRF与心理问题的发生较普遍,应引起医护人员的关注.