载脂蛋白E基因、LDL受体相关蛋白基因与汉人Alzheimer病的相关性研究

目的探讨中国汉族人载脂蛋白E基因、低密度脂蛋白受体相关蛋白基因多态性与Alzheimer病(AD)的相关情况。方法应用PCR-RFLP方法,在67例AD患者和77例正常人中观察apoE基因、LRP基因多态性的分布,进行关联分析。结果apoEε4与AD有显著的关联,AD患者LRP基因C/C纯合子基因型频率及等位基因C频率均高于对照组(P<0.05)。结论中国汉族人群中,apoE基因多态性、LRP基因多态性与AD呈正相关。     

二苯乙烯苷对D-半乳糖拟痴呆小鼠海马基因表达的影响

目的　应用cDNA芯片探索二苯乙烯苷(TSG)干预D 半乳糖皮下注射的拟痴呆 (AD)小鼠海马的靶基因。方法　D 半乳糖 (5 0mg·kg- 1·d- 1,6 0d)皮下注射为模型组 ,造模加TSG (0 .1g·kg- 1·d- 1)灌胃为TSG组 ,对照组只注射相同体积的生理盐水。每组 6只小鼠用Morris水迷宫测试学习记忆能力。取海马组织抽提RNA ,掺入荧光分子Cy3和Cy5逆转录合成cDNA探针。以模型比正常组和TSG比正常组为组合混合探针 ,与两张小鼠 4 0 0 0点cDNA芯片杂交 ,经荧光信号扫描及GenePixPro3.0分析TSG组AD疾病相关基因调控得到改善的基因。结果　TSG可缩短小鼠游至目标的距离和时间 ,说明改善了学习记忆能力。TSG组与模型组表达差异的基因有 2 9条上调 ,12条下调 ,其中与AD相关的有 11条。结论　基因表达结果说明 ,TSG可能使能量代谢与神经营养作用增强 ,炎性反应和转录整体水平下降。     

Reducing post-lumbar puncture headaches with small bore atraumatic needles

Lumbar puncture for testing of Alzheimer’s disease pathophysiology for diagnostic confirmation is likely to become more common in the coming years. Minimizing adverse effects from this testing will be essential for clinical practice. Small bore, atraumatic needles reduce the occurrence of post-lumbar puncture headache (PLPH). Our goal was to extend this recommendation specifically to a well-characterized aging population. We assessed PLPH in the Alzheimer’s Disease Neuroimaging Initiative cohort and found that PLPH occurrence was reduced only when using a 24 gauge atraumatic needle. We recommend that lumbar punctures for clinical and research purposes in Alzheimer’s disease be conducted with 24 gauge atraumatic needles.     

Poly(ADP-ribose) polymerase inhibitors in the prevention of neuronal cell death

Poly(ADP-ribose) polymerase is a nucleic enzyme that promotes energy-dependent repair of DNA, thus helping to protect against DNA fragmentation. Overactivation of PARP, for example in the context of apoptosis, may contribute to neuronal cell death. This article briefly reviews claims for PARP inhibitors as agents for the prevention of neuronal cell death, registered in the period 1998 – December 2001. Biological data are sparse in these patents, few claims are backed by in vitro biochemical data and fewer still with in vivo animal model data. The latter have used animal models of ischaemia rather than of neurodegeneration. The place of PARP inhibitors as a clinical therapy to prevent neuronal cell death remains to be determined.     

Solubilization of flurbiprofen into aptamer-modified PEG–PLA micelles for targeted delivery to brain-derived endothelial cells in vitro

Abstract

Novel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients.     

Synthesis and bioassay of β-（1,4）-D-mannans as potential agents against Alzheimer＇s disease

Aim： Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Aβ peptide toxicity in vitro. Methods： The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aβ1-40 （2 pmol/L）, and the cell viability was detected using a CCK8 assay. Results： A series of β-（1,4）-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 pmol/L β-（1,4）-D-mannobiose 6, β-（1,4）-D-mannotriose 9 or β-（1,4）-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aβ1-40-induced toxicity. The efficacies were similar to those caused by 10 pmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. Conclusion： Synthetic homogeneous short chain β-（1,4）-D-mannans shows neuroprotective effect against Aβ peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.     

Huperzine alkaloids from Australasian and southeast Asian Huperzia

Context: The pharmaceutical alkaloid huperzine A (HupA), currently used in herbal supplements and medicines worldwide, is predominantly sourced from the Chinese lycopod Huperzia serrata (Thunb. ex Murray) Trev. (Lycopodiaceae), which on average contains only 0.08?mg HupA g^?1 dry weight, and is experiencing a rapid decline in China due to over-harvesting.

Objective: To find a high-yielding, natural source of HupA and/or the related huperzine B (HupB) that could potentially be used as the starting material in a commercial propagation program.

Materials and methods: We surveyed 17 Huperzia species (15 indigenous to Australia and southeast Asia) for their foliar HupA and HupB concentrations. We also studied intra-specific variation for the huperzines in four species that were available in sufficient numbers, and determined tissue-specific accumulation in larger specimens.

Results: HupA was detected in 11 Australasian and southeast Asian species, with eight also containing HupB, albeit at much lower concentrations. A H. elmeri (Herter) Holub plant from the Philippines had one of the highest HupA concentrations recorded (1.01?mg g^?1 dry wt) and it also had the highest HupB content of all plants surveyed (0.34?mg g^?1 dry wt). Intra-specific HupA and HupB concentrations were extremely variable, and at the intra-plant level, reproductive strobili were found to accumulate the highest HupA concentrations.

Discussion and conclusion: Select Huperzia species from Australia and southeast Asia have potential as the starting material for establishing commercial HupA plantations, but the high intra-specific variability observed suggests that detailed screening is needed to isolate high huperzine-yielding individuals.     

多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展

多奈哌齐是第2代胆碱酯酶抑制剂,对轻中度阿尔茨海默病有较好疗效。近年关于多奈哌齐作用机制的相关研究较为丰富,本文拟就我国阿尔茨海默病诊断与治疗现状和多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展进行概述。