智脑胶囊对实验性AD模型大鼠学习记忆及自由基代谢的影响1

目的 观察智脑胶囊对实验性AD模型大鼠学习记忆及自由基代谢的影响.方法采用β-淀粉样蛋白(β-AP)大鼠侧脑室注射,联用转移生长因子β1(TGF β1)脑内注射,制作实验性AD大鼠模型.在此基础上,应用避暗法和水迷路法测定AD模型大鼠学习记忆功能,并采用黄嘌呤氧化酶法、硫代巴比妥酸比色法分别测定实验性AD模型大鼠脑组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量.结果经改进由β-AP联用TGF β1诱导的AD模型大鼠既表现有行为学改变(学习记忆障碍),又有典型的AD病理学特征(β-AP沉积斑),同时模型大鼠脑组织SOD活性明显下降,MDA含量显著增加.智脑胶囊能有效地改善实验性AD模型大鼠学习记忆功能,提高模型大鼠脑组织SOD活性,减少MDA含量.结论智脑胶囊能明显提高β-AP联用TGF β1诱导的实验性AD模型大鼠学习记忆能力,其机制与清除自由基密切相关.     

健脑生智口服液对老年痴呆大鼠的学习记忆功能的影响

目的：研究健脑生智口服液对老年痴呆模型大鼠学习记忆功能的影响。方法：大鼠60只,采用腹腔注射东莨菪碱法和AlCl3法复制老年痴呆模型,随机分为正常对照组、模型组、阳性脑复康组（0．301g·kg^-1）、健脑生智口服液高剂量组（16．8g·kg^-1）、中剂量组（8．4g·kg^-1）、低剂量组（4．2g·kg^-1）,测定脑组织中SOD、MDA、Na^＋ -K^＋-ATP酶活性及血清、脑组织中AchE活性、脑蛋白含量。结果：健脑生智口服液能升高脑组织SOD活性、降低MDA活性,提高Na^＋-K^＋-ATP酶活性,降低脑、血清中AchE活性,增加脑蛋白含量。结论：健脑生智口服液能增强老年痴呆大鼠的学习记忆能力。     

益脑活血胶囊对血管性痴呆大鼠学习记忆及脑组织NO、ACh、SOD、MDA含量的影响

目的　研究益脑活血胶囊对血管性痴呆大鼠学习记忆及脑组织一氧化氮 (NO)、乙酰胆碱 (Ach)、超氧化物歧化酶 (SOD)、丙二醛 (MDA)含量的影响。方法　反复夹闭双侧颈总动脉 (CCA)结合腹腔注射硝普钠降低血压制备拟血管性痴呆大鼠模型 ,检测大鼠学习记忆能力及脑组织中 NO、ACh、SOD、MDA的含量或活性。结果　益脑活血胶囊能明显减少血管性痴呆大鼠跳台实验错误次数 ,明显缩短受电击时间 ,延长潜伏期。结论　益脑活血胶囊有改善血管性痴呆大鼠学习记忆的作用     

肉苁蓉总苷对β-淀粉样肽所致阿尔采末病小鼠模型学习记忆的影响及其机制

目的研究肉苁蓉总苷(G lycosides of c istanche,GCs)对β-淀粉样肽(β-AP)所致阿尔采末病(AD)模型小鼠的保护作用,并探讨其作用机制。方法采用小鼠脑室内一次性微量注射β-AP25-35诱发β-AP在脑内的沉积,造成AD小鼠模型。10 d后,一次性训练被动回避跳台实验测定AD小鼠学习记忆能力;检测脑组织SOD活性、MDA含量及GSH-Px活性;电子显微镜检测脑组织神经细胞的病理变化;TUNEL法检测脑细胞凋亡;免疫组化SABC法检测Bax/Bc l-2的表达。结果GCs可提高β-AP所致AD小鼠学习记忆水平;降低脑组织MDA含量,提高SOD及GSH-Px活性;使脑组织中某些病理改变得到改善;降低脑细胞凋亡率;使Bax的表达减弱,Bc l-2的表达增强。结论GCs对β-淀粉样肽所致AD小鼠学习记忆能力提高,其作用机制可能与其增强自由基清除酶活性,防止脂质过氧化作用,抑制β-AP在脑内的沉积及抑制脑细胞凋亡有关。     

补肾活血方对老年性痴呆模型大鼠的治疗作用研究

目的观察补肾活血方对Aβ联合D-半乳糖诱导大鼠老年性痴呆动物模型认知功能的干预作用及其机制。方法脑立体定位仪双侧海马内一次性脑内注射Aβ25-35联合长期颈部皮下注射D-半乳糖制作大鼠AD动物模型,注射24h后灌胃给药,连续4周,以Morris水迷宫实验进行认知行为学检测,ELISA法测定脑组织中SOD、MDA含量。结果补肾活血方组大鼠在安全岛象限的搜索时间和搜索距离较模型组大鼠明显延长。补肾活血方还可降低大鼠脑组织MDA含量,升高SOD活性水平。结论补肾活血方可明显改善Aβ联合D-半乳糖诱导的AD大鼠的学习记忆能力,其作用可能与调节脑内脂质过氧化物反应有关。     

六味地黄健脑方对AD小鼠学习记忆及脑组织SOD、MDA含量的影响

目的：观察六味地黄健脑方对阿尔茨海默病（AD）小鼠学习记忆能力及其脑组织超氧化物歧化酶（SOD）、微量丙二醛（MDA）含量的影响。方法：采用D-半乳糖联合氯化铝构建AD小鼠模型。疗程结束时,跳台实验观察各组对AD小鼠记忆能力的影响,测定脑组织中SOD活性和MDA的含量。结果：治疗组均可显著提高小鼠学习记忆能力及脑组织匀浆中SOD活性,降低潜伏时间及MDA含量,但以中药组作用较明显。结论：六味地黄健脑方可增强AD小鼠学习记忆的能力。     

怡心健脑颗粒对D-半乳糖合β-AP25-35诱导AD小鼠的药效研究

目的观察怡心健脑颗粒对老年痴呆症（AD）小鼠学习记忆及抗氧化能力的影响。方法运用D-半乳糖合β-AP25-35诱导小鼠AD模型,水迷宫法观察怡心健脑颗粒对AD小鼠学习记忆成绩的影响,并测定小鼠血清、肝脏与脑组织中丙二醛（MDA）、超氧化歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、谷胱甘肽（GSH）的含量。结果与对照组比较,模型组AD小鼠的学习记忆成绩明显下降,其血清、肝脏及脑组织中MDA含量明显升高,SOD、GSH、GSH-Px含量明显下降;与模型组比较给药组AD小鼠的学习记忆成绩明显提高,血清、肝脏及脑组织中SOD、GSH、GSH-Px含量明显升高,MDA含量降低。结论怡心健脑颗粒对D-半乳糖合β-AP25-35诱导的AD小鼠具有健脑益智药理作用,并能提高其抗氧化能力。     

酸性肽对AD大鼠学习记忆能力及Aβ表达的影响

目的：研究酸性肽（acidic peptide,AP）对AD大鼠学习记忆能力及Aβ表达的影响。方法：雄性SD大鼠84只,随机分成7组,每组12只。Ⅰ组为正常对照组,Ⅱ组为AD模型组,Ⅲ组为AD模型＋生理盐水组,Ⅳ组为AD模型＋谷氨酸0．3g／kg治疗纽,V组为AD模型＋AP15mg／kg治疗纽,Ⅵ组为AD模型＋AP30mg／kg治疗组,Ⅶ组为AD模型＋AP60mg／kg治疗组。采用大鼠脑组织立体定位微量注射技术,用鹅膏蕈氨酸（IBO）损毁大鼠双侧基底核（nbM）,建立AD动物模型,手术后用不同剂量AP对AD大鼠进行治疗,测定与学习、记忆有关的行为学指标及脑内与AD密切相关的Aβ水平的变化。结果：与模型组相比,酸性肽高、中剂量组均能显著提高AD大鼠的学习、记忆能力,并能显著降低Aβ的沉积。结论：AP能减少皮质中Aβ的沉积,对AD具有治疗作用。     

健脑生智口服液对老年痴呆模型大鼠的影响

目的研究健脑生智口服液的抗老年痴呆作用。方法腹腔注射D-半乳糖复制老年痴呆大鼠模型,测定Y型电迷路测试记忆成绩即每次大鼠逃入安全区的正确反应次数和大鼠脑组织超氧化物歧化酶(SOD)、乙酰胆碱酯酶(AchE)活性以及脑组织一氧化氮(NO)、脑蛋白含量。结果健脑生智口服液能显著增加大鼠Y型电迷路正确反应次数;升高大鼠脑组织SOD活性和脑蛋白含量,降低脑组织AchE活性和NO含量。结论健脑生智口服液具有抗老年痴呆的作用。     

脑康泰胶囊对阿尔茨海默氏病大鼠学习记忆作用的影响

目的：观察脑康泰胶囊对阿尔茨海默氏病模型大鼠学习记忆作用的影响。方法：采用脑立体定向颅内注射啉酸所致阿尔第默氏病（Alzheimers disease.AD)大鼠模型的方法。结果：脑康泰胶囊可显著增加强AD大鼠被动学习和主动学习的能力。调节脑组织中单胺类递质含量及血清中相关激素水平,并显著改善AD模型大鼠的脑电图。结论：脑康泰胶囊显著改善AD大鼠学习记忆能力的作用,其机制与其调节中枢递质及激素水平等相关。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.