长期服抗精神病药病人的隐性运动障碍

目的：评估抗精神病药对迟发性运动障碍（ＴＤ）的掩盖,即隐性运动障碍（ｃｏｖｅｒｔ ｄｙｓｋｉｎｅ－ｓｉａ）状况。方法应用Ｓｉｍｐｓｏｎ运动障碍评分表评定ＴＤ。入组的６９例病人有２３例病人完成了减药之前、停药三周后和再服药四个月后的ＴＤ评定,６９例次检查都给于隶像,并且两个评定者按照录像独立评定ＴＤ是否存在,评定ＴＤ的一致性良好（ＩＣＣ＝０．７５）。结果完成整个调查的２３例病人中,减药前ＴＤ出现率为     

拉呋替丁鼠伤寒沙门氏菌基因回复突变试验

目的　体外观察拉呋替丁能否诱发鼠伤寒沙门氏菌组氨酸营养缺陷型突变株的回复突变。方法　Ames试验用TA97、TA98、TA10 0、TA10 2菌株并分加与不加肝微粒体酶活化系统( +/ -S9)试验。结果　拉呋替丁对四个菌株各剂量组的回复菌落数都未超过自然回复菌落数,Ames试验结果为阴性。结论　未见拉呋替丁致突变性。     

海洛因依赖性人格概念的建构及其与心理健康的关系

目的:了解海洛因依赖性人格的概念结构,建立海洛因依赖性人格量表。方法:对10 5名海洛因戒除者的海洛因依赖性人格问卷的测试数据进行验证性因素分析。结果:(1)海洛因依赖性人格由海洛因渴求感和戒除效能感两个维度构成,二维模型对样本数据的拟合度较好;(2 )海洛因渴求感α=0 .86 6 ,戒断效能感α=0 . 92 3,所有项目与所属因素因子分的相关系数在0. 6 81- 0 . 876之间,P <0 .0 0 1,两个分量表的相关系数r =- 0 4 4 2 ,P <0 . 0 0 1;(3)海洛因渴求感和戒除效能感与自尊、孤独、抑郁的相关系数的绝对值在0 . 2 2 1- 0. 5 11之间,达到显著性水平;回归分析的结果显示,戒断效能感可解释自尊、孤独和抑郁14 . 4 %、10 . 8%和2 6 . 2 %的变异。结论:海洛因依赖性人格的概念的构想合理,其量表具有良好的项目区分度、内部一致性信度和效度。     

从我院药品盘点工作的改进浅析医院药品的管理

运用医院电脑信息系统的盘点程序来进行药品盘点工作,使盘点准确率大大提高,为药剂科完成实时库存的管理打下了扎实的基础     

Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by rat liver microsomes.

The current study evaluated the potential for two dipeptidyl peptidase-IV (DPP-IV) inhibitor analogs (1S)-1-(trans-4-([(4-trifluoromethoxyphenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride and (1S)-1-(trans-4-([(2,4-difluorophenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride (MRL-A and MRL-B), containing a fluoropyrrolidine moiety in the structure, to undergo metabolic activation. The irreversible binding of these tritium-labeled compounds to rat liver microsomal protein was time- and NADPH-dependent and was attenuated by the addition of reduced glutathione (GSH) or N-acetylcysteine (NAC) to the incubation, indicating that chemically reactive intermediates were formed and trapped by these nucleophiles. Mass spectrometric analyses and further trapping experiments with semicarbazide indicated that the fluoropyrrolidine ring had undergone sequential oxidation and defluorination events resulting in the formation of GSH or NAC conjugates of the pyrrolidine moiety. The bioactivation of MRL-A was catalyzed primarily by rat recombinant CYP3A1 and CYP3A2. Pretreatment of rats with prototypic CYP3A1 and 3A2 inducers (pregnenolone-16alpha-carbonitrile and dexamethasone) enhanced the extent of bioactivation which, in turn, led to a higher degree of in vitro irreversible binding to microsomal proteins (5- and 9-fold increase, respectively). Herein, we describe studies that demonstrate that the fluoropyrrolidine ring is prone to metabolic activation and that GSH or NAC can trap the reactive intermediates to form adducts that provide insight into the mechanisms of bioactivation.     

A mechanistic basis for the role of cycle arrest in the genetic toxicology of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking of meat, induces tumors of the prostate, colon, and mammary gland when fed to rats. PhIP is readily absorbed and efficiently metabolized to a genotoxic derivative by CYP1 enzymes. Although metabolism and mutational potential of PhIP have previously been well characterized, the intervening cellular and genomic responses to the chemical are not fully understood. We have examined the cellular response to PhIP exposure in human mammary epithelial MCF10A cells, which retain characteristics of normal breast epithelial cells. Because these cells fail to activate PhIP, they were cocultured with a human lymphoblastoid cell line MCL-5, which constitutively expresses CYP1A1, and have been transfected to express human CYPs1A2, 2A6, 3A4, and 2E1. The MCL-5 cells were irradiated (2,000 rads) prior to coculture, rendering them unable to replicate yet still retaining metabolic competency. MCF10A cells were treated (in the presence of MCL-5 cells) with PhIP (1-100 microM) and harvested at various time-points. Compared to DMSO control, treatment (24 or 48 h) with PhIP resulted in a significant dose-dependent fall in cell number. Cells treated for 48 h then cultured in the absence of PhIP (and MCL-5 cells) for a further 6 days showed a much greater dose-dependent reduction in cell number. Flow cytometric analysis indicated that PhIP treatment (48 h) resulted in a dose-dependent accumulation of cells in the G1 population. Western blotting revealed elevated expression of p53 and the cyclin dependent kinase inhibitor p21WAF1/CIP1 after PhIP treatment. Levels of MDM2, a negative regulator of p53, and the hypophosphorylated form of RB were also elevated, consistent with the triggering of G1 cell cycle checkpoint. These cell cycle effects are critical, as they enable cells to effect genome repair, accept mutation, or eliminate excessively damaged cells.     

N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors.

The active moiety of clozapine, the prototypical antipsychotic drug, consists of clozapine and its major metabolite, N-desmethylclozapine (NDMC). Previous studies have suggested that NDMC may be more important than the patent compound itself for the improvement in cognition in patients with schizophrenia treated with clozapine. While the pharmacology of clozapine and NDMC are similar in most respects, NDMC has been shown to be an M1 muscarinic receptor partial agonist whereas clozapine is an M1 antagonist in vitro and in vivo. We hypothesized that NDMC may improve cognition by increasing dopamine (DA) and acetylcholine (ACh) release in medial prefrontal cortex (mPFC) via direct stimulation of M1 receptors, whereas both NDMC and clozapine itself would do so by other mechanisms as well, and that clozapine would inhibit the M1 agonist effect of NDMC. In the present study, using microdialysis in awake, freely moving rats, we found that NDMC at doses of 10 and 20, but not 5 mg/kg, significantly increased DA and ACh release in the mPFC and HIP, but not in the nucleus accumbens (NAC). The M1-preferring antagonist, telenzepine (3 mg/kg), completely blocked NDMC (10 mg/kg)-induced increases in cortical DA and ACh release. Clozapine (1.25 mg/kg), which by itself had no effect on DA or ACh release in the cortex, blocked NDMC (10 mg/kg)-induced ACh, but not DA, release in the mPFC. The 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg) blocked NDMC (20 mg/kg)-induced cortical DA but not ACh release. These findings suggest that: (1) NDMC is an M1 agonist while clozapine is an M1 antagonist in vivo; (2) M1 agonism of NDMC can contribute to the release of cortical ACh and DA release; (3) NDMC, because of its M1 agonism, may more effectively treat the cognitive impairments observed in schizophrenia than clozapine itself; and (4) M1 receptor agonism may be a valuable target for the development of drugs that can improve cognitive deficit in schizophrenia, and perhaps other neuropsychiatric disorders as well.     

胃灵颗粒治疗消化性溃疡的临床与实验研究

目的:研究胃灵颗粒对消化性溃疡愈合质量(QOUH)和大鼠乙酸慢性胃溃疡愈合质量的影响.方法:用随机分组的方法,观察临床消化性溃疡的复发率并用苏木精-伊红染色对大鼠愈合性胃溃疡再生黏膜进行定量观察,测定胃壁结合黏液量、胃酸、胃蛋白酶活性.结果:胃灵颗粒组能降低消化性溃疡的复发率,改善胃溃疡大鼠胃黏膜的组织损伤并提高胃壁结合黏液量,减少胃酸的排出.结论:胃灵颗粒能提高QOUH,是临床抗消化性溃疡复发的可能机制之一.     

银胶菊内酯对PGCL3细胞uPA活性和表达的影响

目的:研究银胶菊内酯对人肺癌细胞PGCL3尿激酶型纤溶酶原激活物(uPA)蛋白表达及活性的影响,探讨其抗肿瘤的作用机制.方法:MTT法检测银胶菊内酯对PGCL3细胞的增殖抑制作用;发色底物法检测银胶菊内酯对PGCL3细胞分泌的uPA活性的影响;Western blot法检测银胶菊内酯对uPA表达的影响.结果:5～160μmol/L的银胶菊内酯作用PGCL3细胞24 h后,明显抑制PGCL3细胞的增殖,IC50值为17.6 μmol/L;5、10、20 μmol/L银胶菊内酯明显降低PGCL3细胞分泌的uPA活性;银胶菊内酯还能降低PGCL3细胞uPA蛋白表达.结论:银胶菊内酯抗肿瘤活性与uPA蛋白表达及活性有关.     

黄精多糖对新生大鼠大脑皮层神经细胞缺氧性凋亡的影响

目的:探讨黄精多糖对体外培养的新生大鼠大脑皮层神经细胞缺氧性凋亡的保护作用.方法:采用"Neurobasal加B27 Supplement"体外培养新生大鼠大脑皮层神经细胞,使用Hoechst 33342荧光染色、免疫细胞化学染色观察黄精多糖对缺氧复氧性神经细胞凋亡的保护作用.结果:缺氧前加入500μg/ml～1.5mg/ml的黄精多糖能显著地降低缺氧复氧培养诱导的神经细胞凋亡率,增加缺氧的神经细胞Bcl-2蛋白的表达,减少Bax蛋白的表达,提高Bcl-2/Bax比值.而缺氧12h后加入黄精多糖则无明显的抗凋亡作用.结论:缺氧前加入黄精多糖可以通过上调缺氧神经细胞Bcl-2表达、下调Bax表达和提高Bcl-2/Bax的比值以避免缺氧的神经细胞凋亡.