谷氨酸脱羧酶抑制剂L-苹果酸对小鼠学习记忆的影响

跳台法和Y迷宫法试验表明,小鼠po L-苹果酸600mg·kg^-1连续5d后对记忆的获得、巩固和再现均有明显的改善作用,并能促进空间辨别学习能力;L-苹果酸改善记忆的作用能被NMDA受体拮抗剂氯胺酮所拮抗。脑内游离氨基酸测定显示,L-苹果酸可明显降低小鼠脑内GABA水平,提高Glu/GABA比值。实验结果表明,脑内GABA水平下降,Glu/GABA比值升高对学习记忆有正性调节作用。     

控制和影响神经干细胞增殖分化为神经元细胞的途径及因素

目的:探讨控制和影响神经干细胞向神经元细胞转化途径的因素。资料来源:应用计算机检索Medline和cnki数据库1990-01/2006-06期间的有关神经干细胞和增殖与分化关系的文献,检索词“NSC,proliferation,differentiation”,并限定文章语言种类为English。同时计算机检索中国生物医学文献数据库1990-01/2006-06期间的相关文献,限定文章语言种类为中文,检索词“神经干细胞、增殖、分化”。资料选择:选取关于影响神经干细胞增殖与分化特别是机制方面的相关文献,删除未进行对照的试验研究的文章,然后查余下的文献全文,进一步判断是否采用对照。纳入标准:平行对照组,即未采用影响神经干细胞增殖与分化的因素或正常对照;实验组为采用干扰神经干细胞增殖与分化的因素。排除明显不随机的试验。质量评价主要考察资料的真实性,调查设计是否严密,实施过程是否严格,统计学处理是否合理。资料提炼:共检索43篇关于神经干细胞增殖与分化分别与基因调控、生长因子、细胞因子及微环境信号等因素密切相关文章,31编符合纳入标准。排除的12篇试验中,8篇是因重复的同一研究,4篇是Meta分析研究。资料综合:神经干细胞是一种具有强大的自我更新能力和多向分化潜能的细胞,它具有分化为中枢神经系统内神经元、星形胶质细胞和少突胶质细胞的能力;其增殖与分化与基因调控、生长因子、细胞因子及微环境信号等因素密切相关,基本螺旋-环-螺旋基因、凋亡相关基因Bc1-XL、sox2等参与了神经干细胞的定向分化机制,notch信号通路、过氧化物酶体增殖分化激活受体Y信号通路也影响神经干细胞的分化方向。结论:神经干细胞的增殖与分化机制尚不十分清楚,其分化及调控机制是多因素调节和多因素相互作用的结果。     

Pancreaticoduodenectomy with vascular reconstruction for adenocarcinoma of the pancreas with borderline resectability

AIM: To analyze whether pancreaticoduodenectomy with simultaneous resection of tumor-involved vessels is a safe approach with acceptable patient survival.METHODS: Between January 2001 and March 2012, 136 patients received pancreaticoduodenectomy for adenocarcinoma at our hospital. Seventy-eight patients diagnosed with pancreatic head carcinoma were included in this study. Among them, 46 patients received standard pancreaticoduodenectomy (group 1) and 32 patients received pancreaticoduodenectomy with simultaneous resection of the portal vein or the superior mesenteric vein or artery (group 2) followed by reconstruction. The immediate surgical outcomes and survivals were compared between the groups. Fifty-five patients with unresectable adenocarcinoma of the pancreas without liver metastasis who received only bypass operations (group 3) were selected for additional survival comparison.RESULTS: The median ages of patients were 67 years (range: 37-82 years) in group 1, and 63 years (range: 35-86 years) in group 2. All group 2 patients had resection of the portal vein or the superior mesenteric vein and three patients had resection of the superior mesenteric artery. The pancreatic fistula formation rate was 21.7% (10/46) in group 1 and 15.6% (5/32) in group 2 (P = 0.662). Two hospital deaths (4.3%) occurred in group 1 and one hospital death (3.1%) occurred in group 2 (P = 0.641). The one-year, three-year and five-year overall survival rates in group 1 were 71.1%, 23.6% and 13.5%, respectively. The corresponding rates in group 2 were 70.6%, 33.3% and 22.2% (P = 0.815). The one-year survival rate in group 3 was 13.8%. Pancreaticoduodenectomy with simultaneous vascular resection was safe for pancreatic head adenocarcinoma.CONCLUSION: The short-term and survival outcomes with simultaneous resection were not compromised when compared with that of standard pancreaticoduodenectomy.     

Preimplantation genetic diagnosis using combined strategies on a breast cancer patient with a novel genomic deletion in BRCA2

Purpose

To perform Preimplantation Genetic Diagnosis (PGD) on a paternal Brca2 unknown mutation carrier with early-onset breast cancer, whose paternal grandmother and mother had breast cancer at 60s.

Method

Elucidating the linkage via single sperm haplotyping on patient''s carrier brother, and identifying the genomic deletion via BLAST followed by PCR screening. PGD was subsequently conducted.

Result

The mutant allele was found by using 4 microsatellite and 2 intragenic SNP markers. Recombination was detected in 8 % of sperms. BLAST was utilized to locate putative hairpin structure(s), followed by PCR screening with seven sets of primers. A novel 2,596 bp deletion containing exon 15 ~ 16 was identified. Due to the severity of phenotype and the integrity of exon 11 encoding RAD51 binding domain, and the fact that the patient''s mother also had breast cancer at her 60s, we speculate a possible coexistence of maternal breast cancer risk allele(s). Embryo biopsy was performed on day 3. Unaffected morula and blastocyst were replaced on day 5, resulting in a singleton livebirth. A breast lump appeared in the patient after delivery without the presence of malignant cells.

Conclusion

Concerning the assisted reproductive option for breast cancer patients, the possibility of coexistence of multiple familial risk alleles and the significance of each mutation to the phenotype should be evaluated. To eliminate misdiagnosis resulting from recombination and/or allelic drop-out, both direct mutation detection and linkage analysis approaches may be necessary. BLAST is a very useful and cost-effective tool for identifying large genomic deletion.     

带有蛋白转导结构域的bcr/abl癌蛋白片段表达及其跨膜转运

0　引言　人类免疫缺陷病毒 (human immunodeficiencyvirus,HIV) - 1编码的反式激活蛋白 TAT具有独特的跨膜运转方式 ,而且有转导速度快 ,效率高的特点 ,被称为蛋白转导结构域 (protein transduction domain,PTD) [1 ,2 ] .本研究用PCR扩增了慢性粒细胞白血病慢粒 bcr/ abl融合蛋白的基因片段 ,在其 5′端融合 PTD结构域的编码区后在大肠杆菌中进行了表达 .表达产物经纯化后 ,加入培养的 HL 6 0细胞 ,表达的蛋白可直接进入细胞内 .这一结果为用外源蛋白负载(L oading)免疫细胞提供了新的途径 .1　材料和方法1.1　 DNA重组　人工合…     

醋氨己酸锌在大鼠的药代动力学

测定了醋氨已酸锌(ZAC)在大鼠体内的药代动力学。结果表明:大鼠poZAC吸收迅速,给药后1.5h即可达峰,其后稍快下降。3个剂量组的吸收峰时及半衰期基本一致,T_1/2约在1.5h,峰浓度、AUC及CL/F呈剂量依赖关系。ZAC在大鼠的药代动力学模型为一室模型。组织分布的实验结果表明:服药2h后药物可广泛分布于各组织中,主要集中在胃、肠;肾、肝、血浆及肺次之;心、脾、脑较低;肌肉、子宫未检出。6h后胃中含锌量稍降,肺中含量变化不大,其它组织的药物浓度普遍明显下降,表明该药在组织中不易蓄积。ZACpo后主要经粪排出,尿及胆汁仅排出少量药物。     

神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

海藻酸钠-氯化钡微囊对大鼠胰岛体外胰岛素分泌功能的影响

目的　观察海藻酸钠 -氯化钡微囊对大鼠胰岛体外胰岛素分泌功能有无影响。方法　以海藻酸钠和氯化钡为材料 ,采用气体吹喷制囊法将新鲜分离纯化的大鼠胰岛制成微囊化胰岛 ,取空微囊、微囊化大鼠胰岛与未微囊化大鼠胰岛各 5 0 0只 ,分为 10份 ,置于培养板中培养 ,用放免法测定并比较第 2、4、6 d培养液中基础胰岛素浓度。结果　空微囊组第 2、4、6 d的基础胰岛素平均浓度均为 0 nm ol/ 1/ 5 0 ,微囊化大鼠胰岛组第 2、4、6 d的基础胰岛素平均浓度为 5 .179、5 .80 6、5 .5 5 8nm ol/ 1/5 0只 ,未微囊化大鼠胰岛组第 2、4、6 d的基础胰岛素平均浓度为 5 .4 4 1、6 .0 80、5 .4 6 8nmol/ 1/ 5 0只 ,后两者差异无显著性意义 (P>0 .0 5 )。结论　海藻酸钠 -氯化钡微囊对大鼠胰岛体外胰岛素分泌功能无影响     

溃结Ⅰ号的制备与稳定性考察

目的提高医院临时处方溃结Ⅰ号保留灌肠剂的稳定性,并对其中的主要成分含量进行控制。方法制备时加入助悬剂,用沉降容积比和再分散性选择适宜的助悬剂及其最佳助悬浓度,并用紫外分光光度法对主要成分柳氮磺吡啶的含量进行测定。结果在制剂中加入卡波母作为助悬剂0.15%就可以达到良好的助悬效果,而且制备的制剂再分散性好。结论加入卡波母作为助悬剂制备的制剂稳定,再分散性好,便于使用和保存。