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101.
The aims of this study were to evaluate the duration of acetylcholinesterase inhibitors (AChEI) utilization as well as the patients' cognition maintenance. This study was using panel data from the Bureau of National Health Insurance (BNHI) of Taiwan from 2001 to 2004. Patients with mild or moderate AD were prescribed AChEI (donepezil, rivastigmine, or galantamine). By the regulation of BNHI, if the score of Mini-Mental Status Examination worsened by more than two points or clinical dementia rating (CDR) worsened by one or more grades in the follow-up every half year, the AChEI treatment would be terminated. Kaplan–Meier product-limit method was used to estimate duration of drug utilization. Regression model was performed to analyse the factors affecting the discontinuation of AChEI treatment. Our results showed female are more and younger than male in mild to moderate Alzheimer's dementia. The mean duration of use of AChEI was 432 days. Only 9.6% of patients maintained stable cognition tests results with continued drug refill for more than 3 years. Discontinuation rate in older patients (age ≥76 years) was higher than those in younger age ( P = 0.0009). The average duration for AChEI therapy is around 14 months. The elderly are at high risk for treatment discontinuation. 相似文献
102.
Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat 总被引:9,自引:0,他引:9
The present study represents the first comprehensive investigation of the effect of huperzine A (HUP-A), a new cholinesterase inhibitor (ChEI) isolated from a Lycopodium species, upon acetylcholinesterase (AChE) activity, acetylcholine (ACh) levels and release, and cholinergic receptors in rat brain following acute i.m. or i.p. administration. The study shows that HUP-A can produce a long-term inhibition of AChE activity in brain (up to 360 min) and an increase in the ACh levels up to 40% at 60 min. There is considerable regional variation in the degree of ACh elevation after HUP-A with maximal values seen in frontal (125%) and parietal (105%) cortex and smaller increases (22-65%) in other brain regions. HUP-A at concentrations of 10(-6) to 10(-4) M does not significantly alter the electrically evoked release of 3H-ACh from cortical slices. With the exception of the highest concentrations (6 X 10(-4) M) the displacement effect of HUP-A for cholinergic ligands is stronger for 3H-(-)nicotine than for 3H-QNB. A parallel autoradiographic study in the mouse shows that 60 min after i.v. injection (183 micrograms/kg) the drug is present in all brain regions, but it is particularly concentrated in certain areas such as frontoparietal cortex, nucleus accumbens, hippocampal, and striatal cortex. Radio-activity is practically absent in the whole body at 12 hr. Our study suggests that this new ChEI has interesting cholinomimetic properties, and its effects satisfy more closely established criteria for an ideal ChEI for therapeutic use than previously tested compounds. 相似文献
103.
近年来,人们在研究某些膳食营养素与肿瘤发生的关系时发现,人类某些恶性肿瘤的发病率与膳食中胡萝卜素水平存在密切关系[1]。类胡萝卜素的抗癌作用已被广泛承认,但对其作用机理尚未完全阐明。目前较一致的看法是类胡萝卜素可增进抗氧化作用,提高机体抗肿瘤免疫功能... 相似文献
104.
105.
Stereoselectivity of cholinesterase inhibition by galanthamine and tolerance in humans 总被引:2,自引:0,他引:2
T. Thomsen U. Bickel J. P. Fischer H. Kewitz 《European journal of clinical pharmacology》1990,39(6):603-605
Summary The effect of galanthamine (GAL) and its 2 major metabolites on human cholinesterases has been explored. Epigalanthamine, a diastereomer of GAL, was 130-times less potent in vitro in its effect on acetylcholinesterase (AChE) in erythrocytes than the parent compound, and it did not differ significantly from the ketone galanthaminone. In vivo, the maximal 36–55% inhibition of AChE was approached 30 min after oral administration of 10 mg GAL. The duration of the catalytic inhibition corresponded to an elimination half-life of approximately 5–7 h. GAL was well tolerated in 8/8 healthy volunteers, and 3/4 Alzheimer patients tolerated the drug up to a daily dose of 40 mg. 相似文献
106.
Half–life of plasma cholinesterase 总被引:7,自引:0,他引:7
D. Østergaard M.D. J. Viby–Mogensen H. K. Hanel L. T. Skovgaard 《Acta anaesthesiologica Scandinavica》1988,32(3):266-269
The half-life of plasma cholinesterase (acylcholine acylhydrolase EC 3.1.1.8) was determined in three patients homozygous for the atypical gene for plasma cholinesterase by measuring the rate of disappearance of enzyme activity following intravenous injection of concentrated human cholinesterase. Half-life values of 10.9, 11.1, and 11.3 days were estimated. The distribution volume was estimated to be 18.0, 18.2, and 13.8% of body weight, respectively. 相似文献
107.
采用连续监测法测定血清中的胆碱酯酶,其线性相关 r=0.9981,Y_(CHE)=1.08X—7.6,精密度实验批内 CV=3.05%,批间 CV=3.66%,平均回收率为103.0%。11.0mmol/LGLV,42umol/LTBIL 和0.5g/Hb 对测定结果干扰,用本法测定40例正常成人血清(男/女23/17)其=589ou/L 参考值范围(±1.96S)为3864—8096μ/L,本法简单快速,结果准确可靠,适合于日常临床生化检验工作中应用。 相似文献
108.
Multiple pathways from the superior colliculus to the extrageniculate visual thalamus of the cat 总被引:5,自引:0,他引:5
The projection from the cat's superior colliculus to the extrageniculate visual thalamus were examined by the anterograde and retrograde transport of WGA-HRP. An acetylthiocholinesterase (ATChE) stain was employed to facilitate the differentiation of regions within the posterior thalamus. On the basis of the distribution of terminal label as well as the laminar origin of projection neurons, four pathways were delineated. Cells in the stratum griseum superficiale (primarily sublaminae II and III) innervate two regions within the nucleus lateralis posterior (LP): the medial zone, which stains darkly for ATChE, and a restricted portion of the lateral zone, adjacent to the pulvinar. Both of these pathways were found to be topographically organized. By using the fluorescent retrograde tracers, fast blue and rhodamine labeled microspheres, it was determined that the inputs to the medial and lateral zones of LP originate primarily from separate cell populations since very few neurons were found to be double-labeled. A third pathway originates principally from cells in the stratum opticum and terminates in an area just below the cholinesterase-rich region of the LP, designated as the ventral division of the LP. The fourth projection is primarily from the stratum griseum intermedium to the suprageniculate complex. Each of these four pathways arises from a population of neurons with heterogeneous morphological characteristics, and for the most part, each pathway comprises morphologically similar cells. These results suggest that visual information from the superior colliculus is conveyed to the extrageniculate thalamus via multiple pathways that may subserve diverse functions. 相似文献
109.
Effects of 2 organophosphorus compounds, O,O-dimethyl O-(2,2-dichlorovinyl)phosphate (DDVP) and O,O-dimethyl O-(3-methyl 4-nitrophenyl)phosphorothioate (fenitrothion), on the brain cholinergic system were investigated in Japanese quail. Cholinergic signs, such as salivation and convulsions in legs and wings, were seen 7–15 min after administration with DDVP (3–4 mg/kg) or 6–120 min after administration with fenitrothion (250–350 mg/kg). In the DDVP-treated quail (10 min after dosage of 3 mg/kg), free acetylcholine (ACh), labile-bound ACh, increased significantly and acetylcholinesterase (AChE) decreased to 28% of the value determined in untreated quail. In the fenitrothion-treated group (60 min after dosage of 300 mg/kg), only free ACh increased and AChE activity decreased to 20% of the control value. In vitro, DDVP and fenitrothion inhibited AChE activity in brain homogenate with an I50 of 10?8 M and 10?5 M, respectively. It appeared that both organophosphorus compounds might have essentially the same effect on the brain cholinergic system. There were only small differences in the effect on various fractions of ACh between the 2 compounds, although there was a hundred-fold range in dose. 相似文献
110.
The catalytic efficiency of the field mouse (Mus booduga) brain acetyl cholinesterase (AChE, EC 3.1.1.7) was significantly (P less than 0.001) decreased probably through the reduction in the active site density of the enzyme content and elevation in the activation energy (delta E) requirements during repeated hexachlorophene (HCP) treatment. Fall in the activity potential of AChE may account for the interference of HCP or its reactive metabolites with the acetylcholine (ACh)-AChE system and deserve consideration in contributing to the neurotoxicity. 相似文献