诱导芳香烃羟化酶活性不同的大鼠肝微粒体理化特性研究

利用标记膜脂及蛋白质的荧光标记物DpH和N-(3芘)马来酰亚胺标记芳香烃羟化酶活性不同的大鼠肝微粒体,发现N-(3茈)马来酰亚胺标记蛋白质的SH基部分荧光偏振度有明显差异,而荧光激发及发射光潜图形、峰值及DpH标记的脂相部分荧光偏振度均无显著改变。     

Nogo(N-18)在大鼠脑干及小脑分布的免疫组织化学研究

采用免疫组织化学方法(SP法),研究了Nogo(N-18)在大鼠脑干及小脑的分布并探讨其存在的意义。结果表明,Nogo(N-18)在正常大鼠脑干以及小脑的神经核团有广泛的表达,阳性物质很强地表达于神经元的胞核内,神经元胞体、突起内表达较弱。结论:Nogo(N-18)在脑干及小脑的神经核团广泛表达提示其作为一种髓鞘源性神经突生长抑制因子在中枢神经系统中的存在,可能在正常的神经活动中起重要作用。     

大鼠β-内啡肽在垂体和脑的特异区域经历不同形式的处理

最近在垂体发现了两种与β-内啡肽(β-内啡肽_(1～31))有关的肽:C'-段(β-内啡肽_(1～27))和C'-段的去组氨酸衍生物(β-内啡肽_(1～26))。这两种肽和β-内啡肽还以α,N-乙酰化的形式存在。这样,通过不同的蛋白水解酶的裂解和乙酰化过程,可以从一个前体中衍生出六种肽。不同形式的β-内啡肽在垂体内的分布不同,提示前体的处理过程可能具有     

新疆锡伯族成人基础代谢率、体脂分布特征及其相关性

目的了解新疆锡伯族成人基础代谢率、体脂分布的特征,探讨基础代谢率与体脂分布的相关性。方法抽取3代均为新疆锡伯族且年龄为35~70岁的成人536例(男性263例,女性273例)作为研究对象,利用身体成分分析仪等仪器,检测皮下脂肪、内脏脂肪、体重、身高、去脂体重、体脂率和基础代谢率。应用回归分析法研究身体各部体脂含量与基础代谢率之间的相关关系,并计算出回归方程系数。结果新疆锡伯族成人不同年龄段比较,除男性的内脏脂肪与女性的皮下脂肪外,脂肪总量、去脂体重与体脂率的差异具有统计学意义(P<0.05);不同性别比较,除内脏脂肪外,皮下脂肪、脂肪总量和体脂率的差异均具有统计学意义(P<0.05);新疆锡伯族成人的内脏脂肪含量与基础代谢率成负相关(P<0.05)。结论新疆锡伯族成人体脂分布存在年龄差异和性别差异;内脏脂肪与基础代谢率成负相关。     

宁夏汉族青少年脂肪分布特点的分析

目的:分析宁夏汉族不同年龄段、不同性别青少年脂肪的分布特点。方法:采用生物电阻抗分析法,分析1831例宁夏汉族不同年龄段青少年(男性911例,女性920例)脂肪的分布规律,比较各指标均值在性别间的差异性。结果:宁夏汉族青少年脂肪总量、总体脂率及身体各部分(左上肢、左下肢、右上肢、右下肢、躯干)脂肪量和体脂率总体呈现随年龄变化而上升的特点;不同性别宁夏汉族青少年脂肪总量及总体脂率,身体各部分脂肪量及体脂率均值女性均高于男性,脂肪总量(9～19岁)、总体脂率(7～19岁),左上肢、躯干(12～19岁)、左下肢、右下肢(9～19岁)、右上肢(11～19岁)脂肪量及左上肢、左下肢(9～19岁)、右上肢、右下肢(7～19岁)、躯干(11～19岁)体脂率差异有统计学意义。结论:宁夏汉族青少年脂肪的分布具有性别差异,脂肪分布随年龄变化的特点可能与体内激素分泌水平有关。     

甲羟戊酸途径代谢酶HMGL研究概述

3-羟基-3-甲基戊二酰辅酶A裂解酶(HMGL)是一种参与生物体内3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)代谢的重要酶类,在自然界中广泛存在,具有多种功能。作为HMGL作用的前体物质,HMG-CoA在生物体内主要有两方面作用。首先,HMG-CoA可在HMGL作用下形成酮体,酮体能够提供能量;其次,作为甲羟戊酸途径中一个重要中间体,可用于合成甾体、辅酶Q、萜类等生命活性物     

应用反向高效液相色谱分析离体心脏灌流大鼠心肌组织中的多胺

目的：建立苯甲酰氯柱前衍生反向高效液相色谱分析大鼠心肌组织中多胺的方法。方法：以1，6-己二胺为内标，经苯甲酰氯柱前衍生，氯仿提取衍生物。高效液相色谱分析条件： Hypersil ODS C18柱(250 mm×4.6 mm，5 μm) 为固定相，甲醇与水（V∶V，65∶35）为流动相；流速0.4 mL/min；紫外检测波长229 nm，20 min完成洗脱。结果：多胺标准品浓度1-20 μmol/L，浓度与峰面积比呈良好的线性关系，相关系数(r)均大于0.998。多胺日内及日间变异系数分别为2.96%-5.48%、4.22%-9.30%。离体灌流大鼠心肌多胺含量在纳摩尔水平。结论：建立一种快速、准确、灵敏苯甲酰氯衍生反向高效液相色谱分析心肌组织中多胺的方法，此方法为分析其他生物样品中多胺提供参考。     

血浆生物标志物测定对早期诊断ACS患者的临床分析

目的:为了探讨血浆生物标志物对早期诊断急性冠状动脉综合征(ACS)患者的临床分析.方法:108例ACS患者[包括42例AMI和66例不稳定型心绞痛(UAP)患者]、32例稳定型心绞痛(SAP)和42例正常对照组,利用荧光免疫分析血浆中N-末端脑钠肽前体(NT-proBNP)水平,超敏免疫比浊法测定了血浆超敏C-反应蛋白...     

抗纤维蛋白和t-PA/UK双特异性单克隆抗体的制备和应用

目前常用于溶解血栓的药物有组织型纤溶酶原激活剂(tissue-type plasminogenactivator,t-PA)、尿激酶(urokinase,UK,u-PA)、单链型尿激酶(single-chainu-PA,Scu-PA)以及甲氧苯甲酰纤溶酶原—链激酶复合物(APSAC)等。t-PA因能与纤维蛋白结合而激活,认为是一种高     

河南回族成人肌肉量、脂肪量、去脂体质量的身体节段性分布

目的:探讨河南回族成人的肌肉、脂肪、去脂体质量在身体躯干、四肢的分布规律。方法:采用生物电阻抗法测量河南回族成人的肌肉量、脂肪量、去脂体质量,进行统计学分析。结果:河南回族成人肌肉量、脂肪量、去脂体质量躯干分布多于四肢,且随年龄增加呈先上升后下降的趋势,肌肉量峰值为30~岁组;脂肪量峰值为40~岁组。肌肉量、去脂体质量均为右下肢左下肢右上肢左上肢,男性大于女性;脂肪量右下肢左下肢、右上肢左上肢,女性大于男性。结论:河南回族成人身体的肌肉量、脂肪量、去脂体质量存在较大的左右差异、性别差异和年龄差异。     

Tetrahydroaminoacridine increases acetylcholine synthesis and glucose oxidation by mouse brain slices in vitro

1,2,3,4-Tetrahydro-5-aminoacridine (THA; tacrine) reportedly improves cognitive deficits in certain individuals with Alzheimer's disease. The present study describes increased glucose oxidation and acetylcholine (ACh) synthesis by mouse brain slices after THA treatment. THA increased [U-14C]glucose decarboxylation and ACh formation in a concentration-dependent manner in hippocampal slices (50 nM less than 50 microM less than microM). In striatal and cortical slices, 50 microM THA effectively elevated the oxidation of glucose and its incorporation into ACh. Thus the efficacy of THA treatment on Alzheimer patients may be partially related to increased ACh synthesis and oxidative metabolism.     

Acute effects of tetrahydroaminoacridine on beta-adrenoceptor-linked cyclic AMP accumulation in brain of young and middle-aged rats.

The effects of acute treatment with 1,2,3,4-tetrahydro-9-aminoacridine (THA), a 4-aminopyridine derivative clinically effective in Alzheimer's disease, on beta-adrenoceptor-linked cyclic AMP accumulation have been investigated in cortical and hippocampal structures of young and middle-aged rats. In a first series of experiments, pretreatment with 2.5 mg/kg THA decreased basal cyclic AMP accumulation. When a phosphodiesterase inhibitor was added to the preparation, THA again decreased cyclic AMP levels in young rats, but failed to significantly modify cyclic AMP accumulation in middle-aged animals. Finally, in isoprenaline-stimulated conditions, acute treatment with tacrine was able to diminish cyclic AMP accumulation in every group of rats. It is suggested that the neurochemical action of THA in mammalian brain is more complex than earlier has been anticipated and may involve an action on beta-adrenoceptors.     

Tetrahydroaminoacridine (THA) as a pharmacological probe in Alzheimer's disease (AD) and other neurodegenerative disorders

Unlike other potent enhancers of cholinergic function in the central nervous system (CNS), THA appears to sustain improved function in many moderately impaired AD patients when the Summers procedure is followed. THA has a complex pharmacology. In addition to its enhancement of cholinergic transmission a hydroxylated metabolite might chelate aluminum (A1), thereby removing multiple toxicological constraints on CNS function. This mobilized THA metabolite-A1 complex might either be re-distributed to less sensitive sites or removed from the CNS across the blood-brain barrier (BBB). Since the known presence of A1 in AD brain is not necessarily causal, a positivistic approach to research and treatment with THA and its metabolites might serve to clarify this difficult and challenging problem.     

A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB

The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood–brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80^®-coated poly-l-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-l-lactid acid nanoparticles (5 mg/kg), a saline solution of tacrine (5 mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine–lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.     

Effect of acute arecoline, tacrine and arecoline + tacrine post-training administration on retention in old mice

The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. A recent treatment strategy is to combine drugs to improve their memory enhancing effect. We previously reported that in young weakly trained mice, the combination of arecoline and tacrine was more effective on a mg/kg basis than either drug administered alone. This was true whether the route of administration was intracerebroventricular, subcutaneous or oral. We now report that 24 month old mice trained to avoid footshock in a T-maze show poor retention when tested one week later. Subcutaneous administration of arecoline, tacrine (also referred to as tetrahydroaminoacridine, THA) and arecoline plus tacrine administered immediately after T-maze footshock avoidance training enhanced retention of 24 month old mice compared to the saline-injected control. Since the combination was as effective as the single drug treatments even though 96% less arecoline and 99.7% less tacrine was administered, the combination showed marked potentiation of drug action of memory processing.     

诊断超声波联合微泡开放兔血脑屏障的初步研究

目的探讨诊断超声波联合微泡开放兔血脑屏障的可行性,为进一步定量研究大分子药物靶向释放脑组织确定较大动物模型。方法健康新西兰大白兔10只,雌雄不限,体质量(2.30±0.43)kg;分为定量分析组和荧光观察组,各5只。经兔耳缘静脉匀速输入微泡(0.5 mL/kg)的同时两组均用诊断超声波(1.75 MHz,MI 1.9)经颅骨连续辐照兔脑10 min。伊文思蓝(EB)示踪法对照观察靶区脑组织的通透性。结果诊断超声波联合微泡能够促EB跨兔血脑屏障进入脑组织,表现为辐照靶区脑组织蓝染,靶区组织EB含量[(32.25±5.85)mg/kg]明显高于非辐照区脑组织中EB含量[(3.00±5.85)mg/kg](P<0.001)。结论微泡介导下诊断超声波能够增加兔血脑屏障的通透性;新西兰大白兔有可能用于促大分子药物跨血脑屏障转运的自身对照研究。     

In vitro inactivation of rat brain acetylcholinesterase by DSP-4 and its derivatives OS-21 and OS-23 and protective activity of tacrine (9-amino-1,2,3,4-tetrahydroacridine)

Tertiary N-haloethylamines are able to cyclize to the corresponding aziridinium ions. The inhibitory activity of the DSP-4 (N-(o-brombenzyl)-N-ethyl-2-chlorethylamine) and its two derivatives OS-21 (N-benzyl-N-ethyl-2-chloroethylamine) and OS-23 (N-fenylethyl-N-ethyl-2-chloroethylamine) was studied toward rat brain acetylcholinesterase (AChE) in vitro. The influence of the THA (tacrine; 9-amino-1,2,3,4-tetrahydroacridine) on AChE inhibition by these substances was also evaluated. The results demonstrated that all of three aziridinium compounds formed in solution caused a time- and concentration-dependent irreversible enzyme inhibition. The association of aziridinium compounds with the AChE was a relatively slow second-order reaction. DSP-4 showed the fastest rate of AChE alkylation, OS-21 had a lowered rate and OS-23 displayed the lowest rate. Pretreatment of the enzyme by THA decreased the rate of alkylation by all three aziridinium compounds by allosteric mechanism.     

Reversibility of the inhibition of acetylcholinesterase by tacrine

Inhibition of bovine erythrocyte acetylcholinesterase (AChE) by 1,2,3,4-tetrahydro-9-acridinamine (tacrine) was independent of time of incubation and was partially reversed by dilution and by increased substrate concentration. It was fully reversed by dialysis. Similar results were obtained with AChE from other sources. The results are consistent with some reports in the literature, but not with others; none of these reports examined all four criteria of reversibility. The results do not explain the prolonged inhibition of AChE in vivo or the ability of tacrine to protect animals against the lethal effects of organophosphate anticholinesterases.     

A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas

A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in the interior of the fourth generation PAMAM dendrimers for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. It was found that, on average, 7 doxorubicine (DOX) molecules, over 30 PEG(1000) and PEG(2000) chains and one Tf group were bonded on the periphery of each G4 PAMAM dendrimer, while 29 TAM molecules were encapsulated into the interior of per dendrimer. The pH-triggered DOX release was 32% at pH 4.5 and 6% at pH 7.4, indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The in vitro assay of the drug transport across the BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher BBB transportation ability with the transporting ratio of 6.06% in 3 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model by the coactions of TfR-mediated endocytosis and the inhibition effect of TAM to the drug efflux transports. Moreover, it also displayed the in vitro accumulation of DOX in the avascular C6 glioma spheroids made the tumor volume effectively reduced.     

Age, steroids and bone mineral content

The possible existence of correlations between bone mineral content (BMC), age and serum levels of steroid hormones was investigated. It was found that dehydroepiandrosterone sulphate (DHEA-S), oestradiol (E2) and delta-4-androstenedione (A) were correlated with BMC, whereas oestrone (E1) and testosterone (T) were not. Partial correlations after adjustment for age were significant (P less than 0.05) only between E2 and DHEA-S and BMC at the L2-L4 lumbar site (BMC-1) and between DHEA-S (P less than 0.01) and BMC at the midradius site (BMC-r). Stepwise multiple regression analysis showed that, apart from age, E2 was the only factor to fit (P less than 0.05) into the mathematical model with BMC-1 as the dependent variable, while DHEA-S was the only factor to fit (P less than 0.01) with BMC-r as the dependent variable. These data suggest that different hormonal influences are related to BMC at different sites, namely E2 to lumbar trabecular bone (L2-L4) and DHEA-S to cortical bone (midradius).