青蒿琥酯在奶牛体内的药代动力学与代谢

青蒿琥酯(artesunate,AS)是抗疟新药青蒿素的一个活性衍生物。近年来我国兽医工作者将其用于治疗牛羊泰勒氏焦虫病及双芽、巴贝斯焦虫病、鸡球虫病和耕牛血吸虫病,也收到了满意的效果。AS在大白鼠、兔、狗及人体内的药代动力学研究已见报道。本     

Identification of three mutations and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with variegate porphyria

Mutation analysis of genomic DNA samples obtained from 17 unrelated South African patients with variegate porphyria (VP) revealed three novel missense mutations in the protoporphyrinogen oxidase (PPOX) gene. A common C to T transition at nucleotide position 452 (R59W) was identified in 15 of the patients analysed, while base changes at positions 336 (H20P) and 779 (R168C) were identified in the remaining two patients. Using protein analysis software we were able to predict that all three mutations have a similar biophysical effect on the protein, being the disturbance of amphiphatic regions within the protein, which might result in misfolding of the protein. Mutation R59W, identified in the majority of South African VP families, was shown to create a Styl restriction site, while mutation R168C would abolish a Dsal restriction site in genomic DNA of affected individuals. As 100% of the index patients analysed were molecularly characterized, the combined use of restriction enzyme and single-strand conformation polymorphism (SSCP) analysis now allows a rapid and accurate diagnosis of VP in South Africa. Mutation R59W was furthermore shown to be in association with one of four potential haplotypes defined by two newly described polymorphisms in exon 1 of the PPOX gene. Our molecular data thus strongly support the founder hypothesis for VP in South Africa.      

喉全切除环咽吻合(Arslan)术后误咽重及拔管率低的原因

目的：探讨喉全切除环咽吻合（Arslan)术后误咽重，拔管率低的原因，方法：对21例喉全切除环咽吻合术患者的环状软骨，会厌，舌骨及舌根管部位进行了形态学测量，结果：会厌横径比环状软骨内横径大1倍，会厌纵径比环状软骨内纵径大0.5倍，本组应用改进术式后，12例无误咽，9例有轻度误咽，除1例切除患侧1/3环状软骨术后喉腔变窄未能拔管外，其余均在1-2个月内拔管，结论：环状软骨与舌骨吻合是误咽重，拔管率低的根本原因，改进术式切除舌骨将环状软骨与舌根及会厌切缘吻合是克服误咽，提高拔管率的有效措施。     

后勤生活服务对职业院校学生心理健康的影响

目的:评价职业院校学生的心理健康状况,分析后勤生活服务对其的影响。方法:①于2006-04采取整群分层随机抽样方法抽取湖南、广西两所医科职业院校1￣4年级(2002/2005)在校学生900名为测试对象,平均年龄(18±1)岁。②采用症状自评量表和自编后勤生活服务条目进行团体测评和比较分析。就餐方式包括4种:学生食堂大锅菜、学生食堂小炒、校外排档、自家吃饭或亲戚家搭餐;住宿去处包括4种:带公厕普通宿舍、带卫生间的公寓、校外租房、走读住家。后勤生活服务态度包括5种:很差、较差、一般、较好、很好。症状自评量表90个条目,采用从1￣5的5级计分。包括10个因子即躯体化、强迫症状、人际关系、抑郁、焦虑、敌对、恐怖、偏执、精神病性、其他,总分,阳性项目数(90个条目中≥2之条目数),分数越高表示心理状况越差。症状自评量表因子分≥2表示阳性分,≥3表示有明显的心理问题。③两组间比较采用独立样本t检验,多组间比较采用单因素方差检验。结果:发放问卷900份,其中湘环职院468份,南宁卫校432份,全部回收合格,有效率100%。①就餐方式间差异:校外排档就餐学生各因子分和总分及阳性项目数均比其他就餐方式高,食堂小炒学生和自家吃饭学生相对较低。不同就餐方式学生症状自评量表中人际关系、偏执2个因子和阳性项目数评分比较,差异明显(F=3.5,3.7,2.65,P≤0.05)。②住宿去处间差异:校外租房学生各因子分和总分均比其他住宿去处学生高,不同住宿去处学生症状自评量表中躯体化、焦虑和精神病性评分差异明显(F=3.32,2.77,2.91,P<0.05)。③后勤生活服务态度间差异:后勤生活服务态度从差到好,所有因子分和总分及阳性项目数基本上依次降低,除其他因子外的其余9个因子分比较,差异明显(F=2.60￣5.78,P<0.05￣0.01)。④后勤服务对职业院校学生心理健康状况的影响因素分析:后勤服务态度、住宿条件为对心理健康有影响的主要因素(t=-4.358,2.552,P<0.01,0.05)。⑤心理健康问题检出率:2所院校900名抽样学生中,有548人(60.9%)症状自评量表因子分≥2,存在各种轻度的不良心理反应;126人(14.0%)因子分≥3,存在比较明显的心理健康问题;196人(21.8%)总均分≥2,整体心理健康出现不良,强迫症状、抑郁和人际关系因子人数最多;16人(1.8%)总均分≥3,整体心理健康有着明显的不良倾向,人际关系、强迫症状和敌对因子为检出率的前3位。结论:①医科职业院校学生的心理健康状况总体较差,校外排档、校外租房、遭遇后勤生活服务态度很差的学生心理健康状况最差。②后勤生活服务特别是服务态度和住宿条件对学生心理健康的影响最大。     

高+Gx对猴肝细胞c-fos表达的影响

目的:观察航天应急返回过程中高正加速度( Gx)对肝脏细胞c-fos基因表达的影响．方法:选用♂猕猴(共9只)为对象,随机分为4组,对照组承受 1Gx,300 s的超重作用;实验组根据承受过载峰值的大小分为3个亚组,其承受过载峰值分别为 15Gx,200 s; 18Gx, 165 s; 21Gx,140 s．观察高 Gx对猴肝脏细胞c-fos基因表达的影响．结果:实验组肝脏细胞胞质呈现不同程度的水肿及泡状变性,c-fos基因表达明显增强,呈弥漫性细胞质内棕黄色着色;肝细胞c-fos基因表达程度随超重剂量的增加有增强趋势．对照组肝脏组织病理学改变程度明显较实验组轻微,c-fos基因表达亦明显减弱．结论: Gx可引起猴肝脏组织细胞c-fos基因表达增强,提示有早期肝脏组织损伤．     

体外循环血浆对体外培养犬隐静脉内皮细胞的损伤

目的:观察经人工器官体外循环后人体炎性血浆对体外培养的犬隐静脉内皮细胞的影响。方法:实验于2005-01/2005-06在解放军第四军医大学西京医院全军心血管病研究所外科实验室完成。体外循环血浆采自解放军第四军医大学西京医院全军心血管病研究所心血管外科手术患者,患者均知情同意。将已培养好的犬隐静脉内皮细胞按所加入的血浆不同分为4组,即对照组(加入正常培养基2mL和体外循环刚开始(0min)时的血浆1mL)、体外循环25min血浆组(加入体外循环25min血浆1mL和正常培养基共3mL)、体外循环50min血浆组(加入体外循环50min血浆1mL和正常培养基共3mL)及体外循环50min含抑肽酶血浆组(加入体外循环50min含有抑肽酶的血浆1mL和正常培养基共3mL)。将以上培养板置入培养箱内培养4h,然后更换正常培养液3mL,培养2h。观察未贴壁悬浮内皮细胞数(多为凋亡或坏死细胞)、6-酮-前列腺素F1(扩张血管)、内皮素1(收缩血管)及一氧化氮(扩张血管)含量,检测各组内皮细胞的凋亡率。结果:①对照组的悬浮细胞数、6-酮-前列腺素F1及内皮素1含量均显著低于其他各组(P<0.01),体外循环50min血浆组明显高于体外循环25min血浆组和体外循环50min含抑肽酶血浆组(P<0.01)。体外循环50min血浆组、体外循环50min含抑肽酶血浆组一氧化氮含量显著低于对照组(P<0.01)。②对照组、体外循环25min血浆组、体外循环50min血浆组及体外循环50min含抑肽酶血浆组内皮细胞凋亡率分别为(1.45±0.60)%,(8.10±1.25)%,(16.32±1.39)%及(12.38±1.8)%,对照组显著高于其余3组(P均<0.01),体外循环50min含抑肽酶血浆组明显低于体外循环50min血浆组(P<0.01)。结论:经人工器官的体外循环过程可导致血管内皮细胞的广泛损伤/活化,抑肽酶可减轻此作用。     

反向遗传操作技术在流感病毒中的应用研究

反向遗传操作技术(reverse genetics, RG)是近年来比较热门的一门技术,该技术可以在DNA水平上对病毒基因组进行各种修饰或改造,然后通过拯救病毒的表型变化来判断这些基因操作的效果,从而可以对病毒基因组表达调控机制、病毒致病的分子机理等进行研究.我们通过对近年来国外有关文献的回顾,希望能够正确看待病毒拯救技术的利弊,注意生物安全性,希望能够为防治可能发生的流感病毒流散和传播提供新的思路.     

Restricted TCR Valpha gene rearrangements in T cells recognizing an immunodominant peptide of myelin basic protein in DR2 patients with multiple sclerosis

T cell responses to myelin basic protein (MBP) are thought to play an important role in the pathogenesis of multiple sclerosis (MS). The response to the 83-99 region of MBP represents a dominant response to MBP in patients with MS and is associated with HLA-DR2 that is linked with susceptibility to MS. Although T cell clones reactive to various regions of MBP have been found to exhibit heterogeneous TCR Vbeta gene usage in patients with MS, it is unclear whether T cell clones uniformly recognizing the 83-99 peptide of MBP in the context of the same DR molecule would have restricted TCR V gene rearrangements and recognition motifs. In this study, a panel of DR2- or DR4-restricted T cell clones specific for the MBP83-99 peptide were derived from 11 patients with MS and examined for TCR V gene usage by PCR and the recognition motifs using analog peptides. Our study revealed that despite a few T cell clone pairs having similar recognition motifs and shared sequence homology in the CDR3, the overall recognition motifs of MBP83-99-specific T cells were considerably diverse. Interestingly, the DR2-restricted T cell clones displayed a biased V gene usage for Valpha3 and Valpha8, while Vbeta gene rearrangements were highly heterogeneous. This study provided experimental evidence suggesting a limited heterogeneity in TCR Valpha gene rearrangements of MBP-reactive T cells in DR2 patients with MS.