160例住院阿茨海默氏型老年痴呆(SDAT)早期症状的分析

本文对160例住院阿茨海默氏型老年痴呆(SDAT)的早期症状进行临床分析。90例功能性精神障碍症状中,以躁狂状态(38例)、幻觉妄想状态(35例)、抑郁状态(17例)为主;70例器质性精神障碍症状中,以遗忘症状群(40例)、性格改变(26例)、老年期谵妄(4例)为主。表现为功能性精神障碍的早期症状,通常2～5年、平均1.3年确诊为SDAT,在1年内确诊SDAT者有65例(72％),仅17例(18％)需2.5年以上才能确诊。同时发现男性的早期症状以器质性症状多见;女性以功能性症状多见。因此,对病程较短、以功能性精神障碍为症状的老年患者,应考虑有SDAT的可能。

Learning from berberine: Treating chronic diseases through multiple targets

Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.

Copper ions influence the toxicity of β-amyloid(1-42) in a concen-tration-dependent manner in a Caenorhabditis elegans model of Alzheimer’s disease

β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often.In the present study,we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006.Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10-3 mol L-1 copper ions.However,the paralysis behavior was dramatically attenuated with exposure to 10-4 mol L-1 copper ions.The exogenous copper treatment also partially changed the homeostatic balance of zinc,manganese,and iron.Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006.The ROS generation induced by Aβ and copper appear to be through sod-1,prdx-2,skn-1,hsp-60 and hsp-16.2 genes.

Effect of Yizhitongxuan decoction on learning and memory ability,Gαq/11 expression and Na^+-K^+-ATP enzyme activity in rat models of Alzheimer's Disease

OBJECTIVE: To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gαq/11expression and Na+-K+-ATPenzymeactivityin rat models of Alzheimer's disease(AD) caused by injecting Aβ25-35 into the hippocampus.METHODS: Ninety male Wistar rats(age ≥10 months)were selected and injected with Aβ25-35 into their hippocampi to establish model animals,which were randomly divided into six groups including a sham-operated group(blank group), a model group, a donepezil HCL group(Western Medicinegroup),and ahigh/general/dilute concentrations of Yizhitongxuan decoction groups(TCMⅠⅡⅢgroup).The Morris watermaze was used to examine the learning and memory abilities of rats in each group by place navigation and spatial probe tests.Then, the rats were sacrificed to collect the hippocampi for biochemical tests, using western blotting to detect the expression of Gαq/11 and an ultramicro Na+-K+-ATP enzyme kit to measure Na+-K+-ATP enzyme activity.RESULTS:Yizhitongxuan decoction improved model rats' learning and memory abilities, and increased the expression of Gαq/11 in the hippocampus and the level of Na+-K+-ATP enzyme activity in braintissue.CONCLUSION: Yizhitongxuan decoction could improve model rats' learning and memory abilities,and had a regulating effect on the expression of Gαq/11and Na+-K+-ATP enzyme activity.

Ameliorating effect of Zhizi(Fructus Gardeniae) extract and its glycosides on scopolamine-induced memory impairment

OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and constituents on scopolamine-in- duced memory impairment in vivo using a passive avoidance task system and their inhibitory activi- ties on acetylcholinesterase （ACHE） in vitro were ex- amined. The isolation of components was per- formed by chromatographic techniques and their structures were identified on the basis of spectral analysis. RESULTS： Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and cr0cin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition （43.4% at a final dose of 0.03 mg/mL） and also ex- hibited outstanding efficacy （65.9% at a dose of2.50 mg/kg） in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activi- ty and a potent ameliorating effect on scopol- amine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. CONCLUSION： Geniposide, a main constituent of gardenia should be considered a candidate for fur- ther clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcho- line enhancing cholinergic nervous system.

New progress in active immunotherapy targeting to amyloid beta

Alzheimer's disease(AD) is one of the most common types of dementia whose hallmarks include neurofibrillary tangles and senile plaques. The latter are mainly composed of amyloid-β proteins(Aβ), and it's suggested that Aβ may be the causative factor in AD pathogenesis. Immunotherapy targeting Aβ for preventing aggregation of Aβ and mildly clearing amyloid plaques has been a hot topic since 1999. Although the first clinical trial of Aβ vaccine, AN-1792, failed in phase II, its results suggested some key points in the design of Aβ vaccines. Avoiding the possible toxic Aβ specific T cell response and inducing a Th2 type cellular immune response may be beneficial for Aβ immunotherapy. Many associations and research groups are working on Aβ vaccine and some progress has been made in recent years. In this review, we have provided a detailed summary of past Aβ vaccines, which have been sorted by the immunogen, and we also discuss some recent progress and future perspectives.