Phytanic acid: production from phytol, its breakdown and role in human disease

Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place by α-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a general peroxisomal dysfunction or from a defect in one of the enzymes involved in α-oxidation. Research on Refsum disease, belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of α-oxidation, has extended our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human disease and the way it is produced from phytol. Received 4 October 2005; received after revision 24 February 2006; accepted 26 April 2006     

Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease

Deposition of amyloid β-protein (Aβ) in the brain is an early and invariant neuropathological feature of Alzheimer’s disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Aβ in the brain. Here, we review four anti-amyloidogenic strategies: (i) reduction of Aβ production, which has mainly been approached with secretase inhibition, (ii) promotion of the Aβ degrading catabolic pathway, including an Aβ degrading enzyme, neprilysin, (iii) immunotherapy for Aβ and (iv) inhibition of Aβ aggregation. We have reported that AD patients have a favorable molecular environment for Aβ aggregation and that various compounds, such as polyphenols, interfere with Aβ aggregation and destabilize preformed Aβ fibrils. Received 21 December 2005; received after revision 14 February 2006; accepted 29 March 2006     

Sialic acid-specific lectins: occurrence, specificity and function

Sialic acids consist of a family of acidic ninecarbon sugars that are typically located at the terminal positions of a variety of glycoconjugates. Naturally occurring sialic acids show an immense diversity of structure, and this reflects their involvement in a variety of biologically important processes. One such process involves the direct participation of sialic acids in recognition events through specific interactions with lectins, a family of proteins that recognise and bind sugars. This review will present a detailed overview of our current knowledge regarding the occurrence, specificity and function of sialic acid-specific lectins, particularly those that occur in viruses, bacteria and non-vertebrate eukaryotes. Received 13 December 2005; received after revision 9 February 2006; accepted 15 February 2006     

Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD. Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006     

快速老化小鼠SAM-P/8出现类帕金森病现象初探

目的探讨快速老化小鼠SAM-P/8的同向旋转现象与帕金森病动物模型的相关性。方法取发作旋转行为的7月龄雄性SAM-P/8和同源对照SAM-R/1小鼠各6只,分为旋转组和正常对照组两组,首先采用老化度评价标准对其老化度进行评定,其次根据帕金森病动物模型造模标准对其旋转行为进行评定。结果同月龄SAM-P/8的老化度高于SAM-R/1;SAM-P/8出现可重复的同向右侧旋转,频率为60 r/min,符合帕金森病动物模型造模成功的标准,SAM-R/1无旋转现象出现。结论初步认定SAM-P/8的同向旋转现象为类帕金森病现象,对帕金森病研究有重要意义。     

养牛场发生烈性传染病后的应对措施

从疫情报告、及时诊断、隔离和封锁、消毒等方面详细阐述了养牛场发生烈性传染病后的应对措施.     

浅谈沥青路面常见病害成因及防治对策

文章介绍了沥青路面常见病害的形式及其成因,并简要探讨了病害防治的对策。     

阿托伐他汀对冠心病慢性心力衰竭患者的心功能和预后的影响

目的:观察阿托伐他汀对冠心病慢性充血性心力衰竭患者的心功能和预后的影响.方法:选取2004年1月～2008年6月江汉大学附属医院心内科病区冠心病慢性充血性心力衰竭患者132例,随机分成治疗组(67例)和对照组(65例).两组患者均行冠心病慢性充血性心力衰竭的常规基础治疗.治疗组在常规治疗的基础上,加用阿托伐他汀10mg,每晚一次.总疗程26周.治疗前后检测血脂全套、左室射血分数(LVEF)、C反应蛋白(CRP),观察所有患者治疗后两年的住院次数、住院总日数和病死率.结果:治疗组与对照组比较,治疗6个月后,血清总胆固醇(TC),低密度脂蛋白胆固醇(LDL-C),CRP均有不同程度降低,LVEF明显提高,治疗后两年的住院次数和总日数相对减少,差异无显著性;病死率明显降低,差异有非常显著性(P<0.01).结论:阿托伐他汀治疗能改善冠心病慢性心衰患者的心功能和预后.     

基于复杂行为响应的传染病爆发问题的研究

在小世界网络拓扑结构上,研究信息影响力、接种比例和个体间信息传播概率的变化,对传染病传播的影响。研究发现小世界强度减弱时,信息影响力对传染病爆发概率和爆发规模的影响作用发生了逆转;在个体间信息传播速率增加的过程中,传染病的爆发概率和爆发规模呈现上升的趋势。     

Amyloid precursor protein and its homologues: a family of proteolysis-dependent receptors

The Alzheimer’s amyloid precursor protein (APP) belongs to a conserved gene family that also includes the mammalian APLP1 and APLP2, the Drosophila APPL, and the C. elegans APL-1. The biological function of APP is still not fully clear. However, it is known that the APP family proteins have redundant and partly overlapping functions, which demonstrates the importance of studying all APP family members to gain a more complete picture. When APP was first cloned, it was speculated that it could function as a receptor. This theory has been further substantiated by studies showing that APP and its homologues bind both extracellular ligands and intracellular adaptor proteins. The APP family proteins undergo regulated intramembrane proteolysis (RIP), generating secreted and cytoplasmic fragments that have been ascribed different functions. In this review, we will discuss the APP family with focus on biological functions, binding partners, and regulated processing.