血塞通及川芎嗪对细胞色素P450不同亚型代谢酶影响的研究

目的 研究血塞通和川芎秦对肝微粒体细胞色素P450(CYP450)酶系统不同亚型的影响,预测它们之间及与其他药物问的相互作用,并为临床合理用药提供参考.方法 通过研究CYP450亚型CYP1A2、CYP3A4的专属探针药物咖啡因、氨苯砜的体外代谢变化,评价血塞通和川芎秦对这两个酶的诱导或抑制作用.结果 对照组、血塞通组和川芎嗪组中咖啡因和氨苯砜的浓度均随时间延长而降低,3组间差异无统计学意义.血塞通组探针药物咖啡因体外半衰期明显短于对照组[(19.24±2.37)min比(25.15±2.02)min,P<0.01),川芎嗪组咖啡因体外半衰期[(27.67±4.64)min]与对照组无明显差异,说明血塞通对肝药酶CYP1A2有诱导作用,而对CYP3A4无影响;血塞通组和川芎嗪组探针药物氨苯砜体外半衰期与对照组比较差异均无统计学意义[(16.29±2.94)min、(15.16±1.67)min比(16.16±1.51)min,P均>0.05],说明川芎嗪对肝药酶CYP1A2和CYP3A4均无影响.结论 药物对CYP450各亚型酶的影响不同.血塞通在同CYP1A2代谢相关的药物合用时,应充分考虑其对CYP1A2的影响,以避免可能出现的毒性反应或不良反应.     

富氧对海拔3 700m高原人体血液流变学的影响

目的探讨在高原建立富氧室对机体血液流变学的影响.方法在海拔3 700m高原室内充氧,使氧浓度提高为24%～25%.12名受试者在富氧条件下睡眠10h,出富氧室4h后,检测红细胞压积(HCT)、血液粘度(ηb)、血浆粘度(ηp)、还原粘度(ηr)、红细胞刚性指数(IR)、红细胞变形系数(TK)和血细胞聚集系数(VAl).结果富氧后较富氧前ηb、ηp、IR、TK和VAI均降低,有显著性差异(P<0.05),HCT、ηr无统计学意义(P>0.05).结论富氧10h可改善高原机体缺氧,并且增强机体的氧储备可持续4h以上.     

下颌骨牵引成骨过程中应变测试动物模型的设计和建立

目的:设计并装配用于下颌骨牵引成骨应变测试的牵引器,建立一种操作简便的下颌骨牵引成骨的应变测试动物模型。方法:自行设计并装配可用于下颌骨牵引成骨过程中应变测试的牵引器,12只大耳白兔下颌角与体部交界处行骨切开术后,用黏固有应变片改制的颌骨牵引器牵引,并比较不同聚氨酯和硅橡胶包封剂,寻找适合的包封剂,牵引完成后,通过大体和X射线观察牵引成骨的情况。结果:动物均完成牵引实验,聚氨酯包封剂组没有完成牵引应变的测试,硅橡胶包封剂组成功完成测试。结论:使用硅橡胶包封的动物模型是理想的牵引成骨应变测试动物模型。     

人脐血贴壁层细胞对脐血造血细胞体外扩增的作用

实验于2004-10/2005-06在吉林省肿瘤防治研究所和吉林医药学院病原教研室完成。脐血采自长春市妇产医院健康产妇,知情同意,足月顺产,待胎儿娩出后,无菌经脐静脉穿刺取血,枸橼酸钠抗凝。Ficoll-paque淋巴细胞分层液(相对体积质量:1.077±0.22)密度梯度离心法分离出脐带血单个核细胞后,采用长期液体培养法培养脐带血贴壁层细胞,并与脐带血单个核细胞共同培养,观察细胞生长形态并通过流式细胞仪分析细胞周期。结果显示,脐带血贴壁层细胞与脐带血单个核细胞共培养7d后,与无贴壁层细胞培养的脐带血单个核细胞的细胞周期相比,贴壁层细胞能明显促进细胞的增殖,S G2 M期细胞百分数明显增高,差异具有显著性意义[(42.7±1.1)%,(35.5±2.8)%,P<0.05]。脐血贴壁层细胞能促进脐血单个核细胞进入细胞周期,体外扩增后的脐血单个核细胞集落形成能力明显大于无贴壁细胞[(57.7±4.7)个/5×104,(40.3±5.1)个/5×104,P<0.01]。     

武汉地区门诊患者喹诺酮耐药鼠伤寒沙门菌耐药机制分析

目的 研究分析腹泻门诊患者中分离的喹诺酮耐药鼠伤寒沙门菌的耐药机制和遗传关系.方法 对2002-2005年问武汉同济医院腹泻门诊患者中分离的36株喹诺酮耐药鼠伤寒沙门菌进行了耐药谱测定,并通过PCR方法和序列测定对整合子、β内酰胺酶基因、喹诺酮耐药决定区的突变、qnr基因和aac(6')-Ib-cr基因进行了分析,运用脉冲场电泳方法(pulsed-field gel electrophoresis,PFGE)对所收集的菌株进行了分子分型,分析喹诺酮耐药鼠伤寒沙门菌的耐药机制和遗传关系.结果 喹诺酮耐药鼠伤寒沙门菌均为多重耐药株,普遍携带有Ⅰ类整合子,环丙沙星耐药菌株与敏感菌株在PFGE谱型上存在显著性差异,31株环丙沙星耐药菌株在喹诺酮耐药决定区中至少携带GyrA和ParC上的3个点突变,且在这些菌株中均检出了OXA-30基因,这些菌株对头孢吡肟的敏感性出现了不同程度的下降.结论 对环丙沙星耐药的鼠伤寒沙门菌在武汉地区已普遍存在,且这些菌株具有独特的遗传背景,建议在今后的细菌耐药性监测工作中应对这类细菌的耐药谱变化进行重点监测,尤其应加强对氟喹诺酮-三代头孢类抗菌药物均耐药菌株的针对性预警监测.     

Human JC virus-like particles as a gene delivery vector

INTRODUCTION: As a viral gene delivery vector, the recombinant JC virus-like particles (VLPs) can be easily generated in large quantities and at low cost. Exogenous genes of interest can be packaged by the VLP without the involvement of viral genetic material and then delivered into any tissue susceptible to JC virus (JCV) to allow gene transduction. Therefore, it should be possible in the future to develop a gene delivery vector using the human JC VLPs that will allow gene therapy. AREAS COVERED: Development of a gene delivery vector using the polyomavirus VLPs is reviewed in this article. The advantages and disadvantages of using JC VLP for gene delivery are discussed. EXPERT OPINION: Human JC VLPs are readily produced and can be engineered with ease; they allow specific targeting without the presence of any viral genetic material. For therapeutic purposes, gene(s) of interest or other compounds can be packaged into the VLP and delivered to JCV-susceptible cells at high efficiency.     

Higher levels of collagen and facilitated healing protect against ventricular rupture following myocardial infarction

The mechanism of cardiac rupture after MI (myocardial infarction) is not fully understood. Rupture has not been reported in most laboratory species, including the rat, but does occur in mice. We have reported previously that beta2-TG mice (transgenic mice with cardiac-restricted overexpression of beta2-adrenergic receptors) had a lower incidence of rupture compared with NTG (non-transgenic) littermates. We hypothesized that the difference in the incidence of rupture between rodents and specific mouse strains is due to the difference in collagen content following MI. In the present study, we compared the difference in matrix remodelling post-MI between beta2-TG and NTG mice and between mice and rats. MI was induced by ligation of the left main coronary artery. Following MI, tensile strength, insoluble and soluble collagen content and gelatinase expression were determined in the infarcted and non-infarcted myocardium. Better preserved tensile strength measured as TTR [tension-to-rupture; 88+/-14 and 58+/-3% of the respective sham group values for beta2-TG compared with NTG mice (P<0.05); 108+/-7 and 32+/-4% of the respective sham group values for rats compared with 129sv mice (P<0.01)] and less severe acute infarct expansion after MI were found in rats compared with mice or in beta2-TG compared with NTG mice. These differences were associated with a higher content of pre-existing fibril collagen in the normal myocardium of beta2-TG compared with NTG mice (1.6-fold) or rats compared with 129sv mice (2-fold) and an accelerated fibrotic healing in the infarcted myocardium. Additionally, a less pronounced increase in MMP-9 (matrix metalloproteinase-9) activity was observed in the infarcted myocardium of rats compared with 129sv mice. We conclude that a higher collagen level is associated with facilitated fibrotic healing of an infarct and preserves the tensile strength of infarcted myocardium, thereby preventing cardiac rupture and acute ventricular remodelling.     

急性髓系白血病患者hPer3基因启动子甲基化状态及其去甲基化对白血病细胞增殖的影响

目的 探讨急性髓系白血病(AML)患者hPer3基因启动子甲基化检测的临床意义,并观察地西他滨(DCA)诱导hPer3基冈表达对AML细胞系HL-60和U937增殖的影响.方法 应用甲基化聚合酶链反应(MS-PCR)和实时荧光定量PCR(RT-PCR)检测206例AML患者骨髓细胞hPer3基因启动子甲基化状态和mRNA表达,以40例缺铁性贫血患者骨髓细胞作为对照.用不同浓度的DCA处理HL-60和U937细胞48和72 h,检测其hPer3基因启动子甲基化状态及其mRNA表达,用MTT法检测细胞增殖抑制率,Annexin V-FITC/PI标记法检测细胞凋亡,用流式细胞术检测CD14、CD11b抗原表达.结果 AML患者初发组、部分缓解组、完全缓解组、复发组中,hPer3基因启动子甲基化阳性率分别为93.65%(63例中59例)、54.39%(57例中31例)、24.66%(73例中18例)、61.54%(13例中8例),对照组无一例甲基化;hPer3 mRNA表达分别为0.19±0.08、6.28±2.11、52.76±14.17、8.18±4.36,明显低于对照组(75.03±18.16),除部分缓解组与复发组相比差异无统计学意义(P>0.05)外,其余组别两两比较差异均有统计学意义(P<0.01).DCA处理HL-60和U937细胞后,hPer3基因启动子甲基化水平降低,mRNA表达升高,细胞出现凋亡,CD14和CD11b表达升高,并呈剂量和时间依赖性.结论 AML患者骨髓细胞hPer3基因启动子甲基化状态和mRNA表达水平可能作为AML患者病情缓解程度的一个评价指标.体外应用DCA有助于诱导hPer3基因表达和促AML细胞凋亡.

Abstract：

Objective To investigate the clinical significance of promoter methylation status of hPer3 gene in acute myeloid leukemia( AML) patients and the in vitro effect of decitabine( DCA) on AML cell lines HL-60 and U937. Methods The promoter methylation status of hPer3 gene and mRNA expression levels in bone marrow of 206 AML and 40 iron deficiency anemia( IDA) patients ( as control) were detected by methylation specific PCR(MS-PCR) and real-time PCR(RT-PCR). The HL-60 and U937 cell lines were treated with different concertrations of DCA for 48 and 72 h. The inhibition rates of cell proliferation were detected by methyl thiazolyl tetrazolium(MTT) ;the early apoptosis rates by staining with Annexin V and PI; the CD14 and CD11b expressions by flow cytometry( FCM) ; the promoter methylation status of hPer3 gene by MS-PCR;and the hPer3 mRNA expressions levels by RT-PCR. Results The promoter methylation rates of hPer3 in newly diagnosed( ND) group, partial remission ( PR) group, complete remission ( CR ) group, relapse (R)group and control group were 93.65% (59/63) ,54. 39% (31/57) ,24. 66% (18/73) ,61. 54% (8/13) and 0% (0/40), and the hPer3 mRNA expression levels were 0. 19 ±0.08,6.28 ±2. 11,52.76 ± 14.17,8. 18 ±4.36,75.03 ±18. 16, respeatively. There was a significant statistic difference between any two group (P <0.01) excepting for between PR and R group(P>0.05). After DCA treatment,the promoter hypermethylation status of hPer3 was reduced and the mRNA and CD14,CD11b expression levels were up regulated in a dose dependent manner with an induction of cell apoptosis. Conclusions Promoter methylation status and mRNA expression of hPer3 gene may be indicators for evaluating AML. DCA can induce the expression of hPer3 gene and cells apoptosis in AML.     

不规则抗体的筛查和输血安全

红细胞ABO血型以外的不规则抗体是引起输血不良反应、新生儿溶血病、血型鉴定困难及疑难配型等的主要原因，患者常由于输血和妊娠产生免疫抗体，导致输血不良反应和输血相关疾病的发生。因此，在输血前进行患者血清中不规则抗体的筛查，对于保障输血安全、避免输血反应非常重要。2003年11月～2005年12月笔者对2268例有输血史及妊娠史而需要输血的住院患者进行输血前不规则抗体的筛查和鉴定，结果检出抗体阳性17例，现报告如下。     

A developmental psychopathology framework of the psychosocial needs of children orphaned by HIV

In addition to the obstacles to a successful resolution of grief normally faced by children whose parents have died, children orphaned by AIDS may face additional psychological and social challenges. However, limited attention has been paid to psychosocial and developmental needs of children orphaned by HIV/AIDS, particularly in resource-poor countries or regions. In this article the authors review the global literature on child bereavement and AIDS orphan care experiences in developing countries and present a developmental psychopathology model of the psychosocial issues facing AIDS orphans. The authors identify gaps in the literature and provide suggestions for future research on AIDS orphans in resource-poor countries and regions. They emphasize that future studies need to assess the status of behaviors and mental health of children orphaned by AIDS within a developmental framework, identify those individual and social factors associated with grief, and examine the long-term impact of quality of care, developmental maturation, and attachment with caregivers on the psychosocial well-being of AIDS orphans.