Cocaine and "pharmacological kindling" in the rat

The concept of "pharmacological kindling" has been used to explain the behavioral sensitization to cocaine produced by repeated administration of subconvulsive doses. This idea was tested by the repeated administration of cocaine to rats followed by electrical kindling of the olfactory bulb (a site at which cocaine has prominent electrophysiologic effects). No significant effect of cocaine on kindling was found. The relationship of this finding to studies using other drugs is discussed.     

一种对阿尔茨海默病模型小鼠认知和记忆功能具有明显改善作用的中药方剂

目的 :探索对阿尔茨海默病 (AD)病人认知和记忆能力具有明显改善作用的中药方剂。方法 :通过Balb/c小鼠侧脑室微量注射聚集态 β 淀粉样多肽 (β-AP_25-35) ,建立模拟AD的小鼠动物模型 ,并通过行为学实验和脑组织组织化学检测 ,研究了中医经典药方柴胡加龙骨牡蛎汤、当归芍药散和作者自己研制的两种中药复方CHPI和CHPⅡ对该小鼠模型认知和记忆能力的疗效作用。同时 ,以西药脑复康做对照。结果 :CHPⅡ对AD模型小鼠的认知和记忆能力具有明显的改善。结论 :本研究提示从中药中寻找治疗AD的药物具有较好的前景。     

激素局部注射治疗儿童瘢痕的疗效分析

目的 探讨肾上腺皮质激素(醋酸曲安奈德)局部注射对儿童增生性瘢痕、瘢痕疙瘩的治疗效果及预防瘢痕形成的疗效。方法 对增生性瘢痕、瘢痕疙瘩及预防性注射治疗的患儿473例，共行1514次醋酸曲安奈德局部注射，观察临床效果并进行回顾性分析、评价和总结。结果 增生性瘢痕治疗效果良好，有效率达100％，对关节部位瘢痕的挛缩有明显减轻和预防的作用。瘢痕疙瘩直接注射效果较差，手术切除术后，进行预防性注射可收到良好效果。其余手术后经预防性注射，无增生性瘢痕发生。注射期间28例出现早期Cushings综合征表现，停药半年后消失，随访5年以上，无生长发育异常。结论 小剂量激素局部注射是治疗和预防儿童增生性瘢痕、瘢痕疙瘩的较为安全、可靠、有效的非手术治疗方式之一。     

防治痴呆新药的构效关系研究

阿尔茨海默病、帕金森病和血管性痴呆是严重危害老年人生命健康的多发病。目前临床应用的防治痴呆药物的作用机制主要涉及改善胆碱能神经递质、激动多巴胺(DA)受体、阻滞N-甲基-D门冬氨酸(NMDA)受体和改善脑血管功能等。综述了近年来报道的防治痴呆新药的构效关系研究进展。     

三七总皂苷对Alzheimer''''s病大鼠模型大脑胆碱能神经病理损害的保护作用

目的:观察三七总皂苷(PNS)对老年性痴呆(AD)大鼠模型大脑胆碱能神经病理损害的保护作用.方法:以d-半乳糖腹腔注射致亚急性损伤合并鹅膏蕈氨酸(IBA)损毁双侧大脑Meynert基底核建立AD大鼠动物模型,利用免疫组织化学方法检测大脑切片胆碱乙酰基转移酶(ChAT)免疫反应活性及阳性神经元数量及形态学改变.结果:PNS能明显减轻由d-半乳糖损害和鹅膏蕈氨酸损毁导致的大脑胆碱能神经元数量减少和ChAT水平降低.结论:PNS对AD大鼠模型大脑胆碱能神经的病理损害具有保护作用.     

新型胆碱酯酶抑制剂对AD大鼠空间记忆及海马结构胆碱能纤维的影响

目的探讨新型胆碱酯酶抑制剂(NAI)及水迷宫训练对AD大鼠海马结构胆碱能纤维的影响。方法用36只Wistar♂大鼠制作AD动物模型,随机分成3组:NAI组、石杉碱甲组(Hup组)、单纯损伤组(SO组)。水迷宫训练后,采用组织化学方法测定海马结构胆碱能纤维密度。结果①定位航行实验中,NAI组逃避潜伏期较SO组显著缩短(P<0.01)。②空间探索实验中,NAI组跨越各象限平台相应位置次数占总次数百分率较SO组明显增高(P<0.01)。③组化结果显示:NAI组海马结构胆碱能纤维密度较SO组明显增加(P<0.05)。尽管NAI组胆碱能纤维密度高于Hup组,但无统计学意义。结论经NAI治疗及水迷宫行为训练后的AD大鼠,海马结构内胆碱能纤维密度明显增加,提示NAI及水迷宫训练联合作用可促进AD大鼠海马结构胆碱能纤维重建。     

APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study

Asymptomatic Alzheimer''s disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOε2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOε2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.     

Cisplatin toxicity reduced in human cultured renal tubular cells by oxygen pretreatment

Abstract

Cisplatin is an effective and widely used chemotherapy agent and its side effects, particularly nephrotoxicity, limit its usage and related platinum-based drugs. Cisplatin nephrotoxicity is mainly due to extremely increase in reactive oxygen species (ROS) generation leading to kidney tubular cell death. Preconditioning with oxidative stress has been demonstrated to stimulate the cellular adaptation to subsequent severe oxidative stress. Short term oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on Cisplatin induced cell death was investigated in present research. We studied the effects of hyperoxic environment pre-exposure on Cisplatin toxicity in an in-vitro model of cultured human embryonic tubular epithelial cells (AD293). Viability of AD293 cells, as evaluated by MTT-assay, was affected by Cisplatin in a time (1–4?h) dependent model. Biochemical markers of cell apoptosis were evaluated using immunoblotting. Pretreatment with nearly pure oxygen (≥90%) for 2?h significantly reduced the level of cell damage. Activated caspase 3 and Bax/Bcl-2 ratio were significantly increased in Cisplatin-treated cells. Oxygen pretreatment inhibited caspase 3 activation and decreased Bax/Bcl-2 ratio. Oxygen pre-treatment itself not showed any cytotoxicity in exposure times up to 3?h. Our data indicate that hyperoxic preconditioning reduces Cisplatin toxicity in cultured human tubular epithelial cells. The exact mechanism of protection is unclear, though enhancement of some endogenous defense mechanisms and subsequently scavenging of free oxygen radicals may play an important role.     

A Review of: “ Handbook of Adaptive Designs in Pharmaceutical and Clinical Development,by A. Pong and S.-C. Chow (Eds.)”

In practice, there exist many disease processes with three ordinal disease classes; for example, in the detection of Alzheimer’s disease (AD) a patient can be classified as healthy (disease-free stage), mild cognitive impairment (early disease stage), or AD (full disease stage). The treatment interventions and effectiveness of such disease processes will depend on the disease stage. Therefore, it is important to develop diagnostic tests with the ability to discriminate between the three disease stages. Measuring the overall ability of diagnostic tests to discriminate between the three classes has been discussed extensively in the literature. However, there has been little proposed on how to select clinically meaningful thresholds for such diagnostic tests, except for a method based on the generalized Youden index by Nakas et al. (2010). In this article, we propose two new criteria for selecting diagnostic thresholds in the three-class setting. The numerical study demonstrated that the proposed methods may provide thresholds with less variability and more balance among the correct classification rates for the three stages. The proposed methods are applied to two real examples: the clinical diagnosis of AD from the Washington University Alzheimer’s Disease Research Center and the detection of liver cancer (LC) using protein segments.