糖尿病通过抑制VEGF/VEGFR2通路加重大鼠缺血性脑损伤

目的 探讨缺血皮质血管内皮生长因子(vascular endothelial growth factor,VEGF)和VEGF受体2(VEGF receptor 2,VEGFR2)表达对糖尿病大鼠缺血性脑损伤的影响.方法 36只健康雄性Sprague-Dawley大鼠按随机数字表法分为假手术组、脑缺血组和糖尿病脑缺血组.腹腔注射链脲佐菌素制作糖尿病模型,然后再应用栓线法建立大鼠永久性局灶性脑缺血模型.在缺血后24 h进行神经功能缺损评分,氯化三苯基四氮唑染色测量梗死体积,TUNEL法检测凋亡细胞,实时荧光定量聚合酶链反应检测VEGF和VEGFR2 mRNA表达水平,蛋白质印迹法检测VEGF和VEGFR2蛋白表达水平.结果 假手术组无神经功能缺损,无梗死灶,仅有少量凋亡细胞以及少量VEGF和VEGFR2mRNA和蛋白表达.糖尿病脑缺血组神经功能评分[(4.25±0.54)分对(2.86±0.73)分;t=5.303,P ＜0.001]、梗死体积[(51.69 ±2.26)mm3对(30.15 ±2.08)mm3;=23.166,P＜0.001]和凋亡细胞数量[(24.22±1.34)个/HP对(13.28 ±0.37)个/HP;t =27.261,P＜0.001]均较脑缺血组显著增高和增加,而VEGF和VEGFR2 mRNA以及蛋白表达水平则较脑缺血组显著降低(VEGF mRNA:4.74±0.54对6.71 ±0.91,P＜0.001;VEGFR2 mRNA:4.06±0.60对6.16±0.96,P＜0.001;VEGF蛋白:0.99 ±0.13对1.55 ±0.23,P＜0.001;VEGFR2蛋白:4.12±0.74对6.23±0.76,P＜0.001).结论 VEGF/VEGFR2信号通路参与了糖尿病加重脑缺血损伤的过程,VEGF和VEGFR2表达下调可能是糖尿病加重脑缺血损伤的机制之一.     

缺血性脑小血管病患者轻度认知障碍的危险因素和临床特征:回顾性病例系列研究

目的 探讨缺血性脑小血管病(small vessel disease,SVD)患者轻度认知障碍(mild cognitive impairment,MCI)的危险因素和临床特征,为早期诊断和早期干预提供依据.方法 应用蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)筛查MCI,收集相关危险因素和其他临床资料,并进行其他神经心理学测试.根据MRI表现将SVD分为脑白质疏松(leukoaraiosis,LA)、腔隙性梗死(lacunar infarction,LI)和LA与LI并存(LA-LI)3种类型.结果 共纳入143例SVD患者,其中MCI组68例,非MCI组75例.单变量分析显示,MCI组年龄、性别构成比与非MCI组无显著差异,但MCI组受教育年限显著短于非MCI组,而高血压(69.11％对45.33％;x2=8.215,P=0.004)、糖尿病(57.35％对40.00％;x2=4.301,P=0.038)、高脂血症(48.53％对24.00％;x2 =9.352,P=0.002)、颈动脉粥样硬化(41.18％对21.33％;x2=6.592,P=0.010)和吸烟(32.35％对14.67％;x2=6.285,P=0.012)的构成比以及尿酸[(351.81±83.21)mmol/L对(323.03±80.43)mmol/L;t=2.102,P=0.037]和总胆固醇[(5.26±1.26) mmol/L对(4.56±1.23) mmol/L;=3.326,P=0.001]水平显著高于非MCI组.多变量logistic回归分析显示,高血压[优势比(odds ratio,OR)2.227,95％可信区间(confidence interval,CI)1.001 ～4.954;P =0.026]、糖尿病(OR 2.056,95％ CI 1.862～4.937;P=0.046)、高脂血症(OR 2.528,95％ CI 1.361 ～5.770;P=0.028)、颈动脉粥样硬化(OR 2.658,95％ CI 1.110 ～6.367; P=0.029)、吸烟(OR2.566,95％ CI1.017 ～6.474;P=0.046)和受教育年限(OR0.825,95％ CI 0.745～0.914;P=0.000)是SVD患者出现MCI的独立危险因素.MCI组MoCA总分[(18.44±5.60)分对(27.09±1.37)分;t=-12.422,P=0.000]以及视空间/执行能力[(2.65±1.39)分对(4.49±0.74)分;t=-9.762,P=0.000]、注意力[(4.48±1.70)分对(5.89±0.31)分;t=6.706,P=0.000]、语言[(1.69±0.80)分对(2.41 ±0.95)分;t=4.893,P=0.018]、抽象能力[(0.85±0.69)分对(1.71 ±0.53)分;t=-7.081,P=0.000]、延迟回忆[(1.29±1.01)分对(4.04±0.99)分;t=13.824,P=0.000]等亚项得分均显著低于非MCI组,而命名和定向力得分无显著差异.在MCI组中,LA-LI组MoCA总分[(17.04±6.15)分对(21.04±3.98)分;P＜0.05]以及视空间/执行功能[(1.68± 1.16)分对(3.24±1.13)分;P＜0.05]、注意力[(3.92±2.03)分对(5.19±0.87)分;P＜0.05]、延迟回忆[(1.35±1.01)分对(1.86±1.58)分;P＜0.05]等亚项得分显著低于U组;LA组MoCA总分[(18.18±5.31)分对(21.04±3.98)分;P＜0.05]以及视空间/执行功能[(2.56±1.78)分对(3.24±1.13)分;P＜0.05]、语言[(0.64±0.23)分对(1.24±0.83)分;P＜ 0.05]、延迟回忆[(0.69±0.58)分对(1.86±1.58)分;P＜0.01]等亚项得分显著低于LI组;LA-LI组视空间/执行功能评分显著低于LA组[(1.68±1.16)分对(2.56±1.78)分;P＜0.05]和LI组[(1.68±1.16)分对(3.24±1.13)分;P＜0.05].结论 高血压、糖尿病、高脂血症、颈动脉粥样硬化、吸烟和受教育水平较低是SVD患者MCI的独立危险因素.SVD后MCI的认知损害表现为包括视空间/执行功能、延迟回忆在内的多个认知域损害,不同类型脑小血管病之间的认知损害有所不同.     

AMP-活化蛋白激酶对局灶性脑缺血再灌注小鼠皮质胱天蛋白酶-8、-3表达和细胞凋亡的影响

目的 探讨抑制AMP-活化蛋白激酶(AMP-activated protein kinase,AMPK)活性对局灶性脑缺血再灌注小鼠梗死体积、缺血皮质胱天蛋白酶-8、-3表达以及细胞凋亡的影响.方法 72只雄性C57BL/6小鼠,随机数字表法分为假手术组、缺血再灌注组和AMPK抑制剂组.线栓法建立大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型.AMPK抑制剂组在MCAO即刻腹腔注射Compound C(20 mg/kg),假手术组及缺血再灌注组在相同时间点腹腔注射等量生理盐水.应用2,3,5-三苯基氯化四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色法测量脑梗死体积,免疫组化染色法检测胱天蛋白酶-8、-3表达水平,TUNEL染色法检测细胞凋亡.结果 假手术组未见梗死灶,无胱天蛋白酶-8、-3以及凋亡阳性细胞.与缺血再灌注组比较,AMPK抑制剂组梗死体积显著缩小[(45.34±7.20)mm3对(22.71±4.93)mm3;t=5.730,P=0.037],大脑皮质胱天蛋白酶-8[(17.58±8.62)个/HP对(6.87±4.32)个/HP;t=3.631,P=0.023]、胱天蛋白酶-3[(16.21±5.46)个/HP对(8.22±4.64)个/HP;t=2.630,P=0.021]和凋亡[(78.44±8.32)个/HP对(55.73±6.71)个/HP;=5.541,P=0.042]阳性细胞数量均显著减少.结论 抑制AMPK活性可缩小局灶性脑缺血再灌注小鼠梗死体积,其机制可能与下调胱天蛋白酶-8、-3表达和减少细胞凋亡有关.     

组织型激肽释放酶对脑缺血再灌注大鼠缺血脑组织缓激肽及其受体表达的影响

目的 探讨组织型激肽释放酶(tissue kallikrein,TK)对脑缺血再灌注大鼠缺血脑组织缓激肽、缓激肽B1受体(bradykinin B1 rgceptor,B1R)和缓激肽B2受体(bradykinin B2 receptor,B2R)表达的影响.方法 54只SD大鼠随机分为3组,每组18只.3组分别为假手术组;生理盐水(normal saline,NS)处理组(Ns组):NS 2 ml/(kg·d),连用3 d;TK(处理组(TK组):TK 17.5×10-3U/(kg·d),连用3 d.3 d后分别进行神经功能缺损评分、脑梗死体积测定.酶联免疫吸附法检测缺血区缓激肽含量;采用逆转录聚合酶链反应和Western印迹法分别检测缺血脑组织B1R、B2R mRNA和蛋白表达.结果 与NS组比较,TK组神经功能缺损显著减轻[(6.17±1.17)分对(8.17 4±1.33)分,t=2.000,P=0.004],脑梗死体积明显缩小[(29.67±3.78)%对(37.50±6.72)%,t=0.078,P=0.005];缺血脑组织缓激肽含量升高[(9.25 4±1.13)对(15.53±1.68),t=6.283,P:0.000];B2RmRNA表达显著上调[(1.21±0.17)对(2.15±0.20),t=0.943,P=0.000),而B1R mRNA表达上调不明显[(0.51±0.05)对(0.57±0.06),t=0.058,P=0.141)];B2R蛋白表达显著上调[(1.15±0.16)对(1.88 4±0.21),t=0.737,P=0.0001,B1R蛋白表达上调不明显[(0.50±0.04)对(0.53±0.05),t=1.326,P=0.214].结论 TK 对脑缺血再灌注大鼠具有保护作用,能使缺血脑组织缓激肽含量增高,B2R表达上调,而对B1R表达影响不大.由此推测,B2R在TK保护缺血脑组织中发挥着主要作用.     

白细胞介素-10对上皮-间质转化及内质网应激在肠纤维化中的影响

目的 探讨白细胞介素(IL)-10对小鼠肠道纤维化及上皮-间质转化(EMT)的作用,以及该作用与内质网应激(ERS)的关系.方法 42只IL-10-/-小鼠分为纤维化模型组(n=18)、IL-10治疗组(n=12)和溶剂对照组(n=12),另取18只野生型小鼠作为阴性对照组.IL-10治疗组和溶剂对照组分别于第12周开始腹腔内注射IL-10和0.9％NaCl溶液,纤维化模型组和阴性对照组不予处理.采用HE染色及Masson胶原三色染色观察小鼠结肠组织损伤和纤维化变化,采用荧光定量PCR法检测小鼠结肠组织中胶原Ⅰ、葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)、平滑肌肌动蛋白(α-SMA)、E-细胞钙黏蛋白(E-cad)mRNA的表达.采用定量免疫组织化学染色检测小鼠结肠组织中α-SMA和E-cad的表达.结果 16周纤维化模型组、溶剂对照组结肠黏膜组织损伤评分(7.00±0.90和7.17±1.17)及胶原面积比[(17.78±4.15)％和(18.56±3.81)％]较阴性对照组[1.50±1.38和(9.11±2.99)％]和IL-10治疗组[4.33±0.82和(12.56±1.39)％]均明显升高(F=36.150,F=11.280;P=0.000).12、14、16周纤维化模型组、溶剂对照组GRP78、α-SMA、胶原Ⅰ表达量较同期阴性对照组均明显升高(均P＜0.05),E-cad表达量较阴性对照组明显降低(P＜0.05).12周纤维化模型组CHOP mRNA表达量[(0.95±0.12)％]较阴性对照组[(0.21±0.12)％]明显升高(t=5.188,P=0.000),但在14、16周各组之间差异无统计学意义(P＞0.05).14、16周IL-10治疗组GRP78、α-SMA、胶原Ⅰ表达量[14周:(0.73±0.31)％,(1.18.±0.11)％,(1.10±0.49)％;16周:(0.57±0.16)％,(0.81±0.50)％,(0.76±0.25)％]较纤维化模型组均明显降低(P＜0.05),E-cad表达量[14周:(0.73±0.29)％;16周:(0.97±0.25)％]较纤维化模型组[14周:(0.37±0.17)％;16周:(0.35±0.20)％]明显升高(F=6.524,P=0.003;,F=17.493,P=0.000).16周IL-10治疗组α-SMA表达量较溶剂对照组[(1.82±0.22)％]明显降低(F=9.842,P=0.000),E-cad表达量较溶剂对照组[(0.47±0.25)％]明显升高(F=17.493,P=0.000).结论 IL-10具有抑制EMT,减轻小鼠肠道纤维化的作用,可能与IL-10对ERS的调控有关.     

缺血性卒中患者的认知功能与脑微出血:回顾性病例系列研究

目的 探讨血管性认知损害的危险因素以及脑微出血(cerebral microbleed,CMB)对缺血性卒中患者认知功能的影响.方法 收集50岁以上缺血性卒中患者的资料.采用MRI评价CMB、白质损害和梗死体积.采用蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)、阿尔茨海默病评定量表认知分表评价认知功能、汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)评价抑郁状况以排除抑郁患者.根据量表评价结果将缺血性卒中患者分为认知损害组和无认知损害组,比较两组人口统计学和临床特征,并采用多变量logistic回归分析寻找缺血性卒中患者认知损害的独立危险因素.采用Spearman等级相关法分析CMB程度与MoCA总分和MoCA各认知领域评分的相关性.结果 共纳入169例缺血性卒中患者.认知损害组80例,无认知损害组89例;34例存在CMB,135例无CMB.认知损害组年龄较大[(71.99±6.01)岁对(64.47 ±6.15)岁;t=8.014,P=0.000],受教育年限较少[(4.51±1.534)年对(6.94±2.357)年;t=8.023,p=0.000],收缩压较高[(156.19±17.53)mm Hg对(142.04±16.03) mmHg(1 mmHg=0.133 kPa);t=5.479,P=0.000],脑白质损害评分较高[(7.33±2.04)分对(4.39±2.17)分;t=8.951,P=0.000],脑梗死体积较大[(7 123.8±1 587.11)mm3对(5 628.4±1 017.76)mm3;=7.201,P=0.000],既往卒中或短暂性脑缺血发作史比例较高(46.2％对28.1％;x2 =5.982,P=0.014),CMB数量较多(x2=17.565,P=0.000).多变量logistic回归分析显示,年龄[优势比(odds ratio,OR)1.115,95％可信区间(confidence interval,CI)1.013 ～1.227;P=0.026]、受教育年限少(OR0.490,95％ CI0.325 ～0.739;P=0.001)、收缩压(OR1.048,95％ CI1.014～1.083;P=0.005)、脑白质损害(OR 2.044,95％ CI 1.466～2.851;P=0.000)和脑梗死体积(OR2.204,95％ CI1.386 ～3.503;P=0.001)均为缺血性卒中患者认知损害的独立危险因素.与无CMB组比较,CMB组患者年龄较大[(72.06±5.59)岁对(67.01 ±7.15)岁;t=4.427,P=0.000],受教育年限较少[(3.97±1.381)年对(6.25 ±2.317)年;=7.367,P=0.000],收缩压较高[(155.03 ±20.16) mm Hg对(147.16±17.32)mm Hg;t =2.290,P=0.023],脑白质损害评分较高[(7.03±2.139)分对(5.47±2.591)分;t=3.247,P=0.001],脑梗死体积较大[(6 968.5±1 507.37) mm3对(6 177.0±1 477.08) mm3;t =2.735,P=0.007],高血压(82.4％对41.5％;x2=18.149,P=0.000)、高脂血症(88.2％对39.3％;x2 =26.067,P=0.000)、既往卒中或短暂性脑缺血发作史(70.6％对28.1％;x2 =21.061,P=0.000)及冠心病(94.1％对45.2％;x2 =26.278,P=0.000)比例较高.CMB组MoCA总分[M(Q1～Q3)][24 (24 ～ 25)分对28(27 ～28)分;Z=-7.092,P=0.000]及注意力[6(5 ～6)分对6(6 ～6)分;Z=-2.502,P=0.012]、抽象思维[2(1 ～2)分对2(2 ～2)分;Z=-2.382,P=0.017]、视空间执行功能[2(1 ～2)分对4(4 ～5)分;Z=-7.321,P=0.000]评分均显著性低于无CMB组(P均＜0.05).Spearman等级相关分析显示,CMB分级与MoCA总分(rs=-0.879,P=0.000)、视空间执行功能(rs=-0.895,P=0.000)、注意力(rs=-0.337,P=0.005)和抽象思维(rs=-0.333,P=0.006)评分呈负相关.结论 年龄、受教育年限、收缩压、脑白质损害程度和脑梗死体积是血管性认知损害的危险因素.伴有CMB的缺血性卒中患者视空间执行功能障碍、注意力和抽象思维减退明显.CMB及其数量与认知功能损害密切相关,CMB数目越多,认知功能损害越显著.     

AT1受体自身抗体对糖尿病肾病大鼠肾脏内质网应激通路相关分子葡萄糖调节蛋白78和CCAAT/增强子结合蛋白同源蛋白表达的影响

目的 探讨AT1受体自身抗体(AT1-AA)对DN大鼠肾脏内质网应激(ERS)通路相关分子葡萄糖调节蛋白78(GRP78)和CCAAT/增强子结合蛋白同源蛋白(CHOP)表达的影响. 方法 制备DN大鼠模型,ELISA检测血清AT1-AA,根据ELISA结果随机选择AT1-AA阳性和阴性DN大鼠纳入DN组(n=12),同时设立正常对照组(NC,n=6).电镜观察肾脏超微结构变化;TUNEL法检测肾脏细胞凋亡;RT-PCR测定大鼠肾组织GRP78和CHOP mRNA水平;Western blot分析肾组织中GRP78和CHOP蛋白的表达量. 结果 DN组肾脏细胞凋亡率较NC组升高,其中,AT1-AA阳性大鼠凋亡率高于AT1-AA阴性大鼠[(20.05±1.71)％vs(13.24±4.93)％](P＜0.01).与NC组相比,DN组肾组织GRP78、CHOP蛋白和mRNA水平均上调;进一步比较发现,AT1-AA阳性DN大鼠GRP78,CHOP蛋白及mRNA水平升高较AT1-AA阴性DN大鼠更明显. 结论 AT1-AA可能通过诱导DN大鼠肾脏ERS反应,并经ERS相关的CHOP凋亡信号通路而促进肾脏细胞凋亡,加重肾脏损害.     

自体骨髓来源内皮祖细胞移植改善脑缺血再灌注大鼠神经功能转归

目的 探讨目体骨髓米源内皮祖细肥(endothehalprogenitor cell,EPC)移植对脑缺血大鼠神经功能转归的影响及其可能机制.方法 体外分离培养自体骨髓来源EPC并用5-溴脱氧尿嘧啶核苷(5 -bromodeoxyuridine,BrdU)标记.线栓法制作大鼠大脑中动脉闭塞(middle cerebral arteryocclusion,MCAO)模型.EPC组大鼠经颈外静脉移植自体EPC[ 106/ml·kg)],对照组注射磷酸盐缓冲液(1 ml/kg),假手术组不进行任何处理(n=15).改良神经功能缺损严重程度评分(modifiedneurological severity score,mNSS)观察大鼠神经功能变化情况.BrdU免疫组化染色评价EPC增殖和分化.三维共聚焦图像分析检测脑缺血区血管结构和密度.TUNEL染色检测缺血脑组织凋亡细胞.酶联免疫吸附法检测血浆血管内皮生长因子(vascular endothelial growth factor,VEGF)浓度.结果 EPC组mNSS评分显著低于对照组[第8天时;(6.43±0.69)分对(8.86±0.95)分;q=2.673,P=0.035;第14天时:(4.55±0.89)分对(6.73±1.06)分;q=5.360,P=0.035].EPC组BrdU阳性细胞数量显著多于对照组[(42.2±5.76)对(25.67±5.49);q=4.020,P=0.030].EPC组毛细血管直径显著小于对照组[(4.51±0.21)μm对(6.34±0.24) μm;q=3.980,P =0.003];血管密度[(212.64±8.02)/0.002 mm3对(153.60±7.21 )/0.002 mn3;q =9.670,P=0.001]和微血管总表面积[(92 013±5 132)μm3/0.002 mm3对(71 366±4 538) μm2/0.002 mm3;q=4.180,P=0.014]显著高于和大于对照组;EPC组凋亡细胞数量显著少于对照组[(36.26±6.91)对(78.34±7.21);t=-4.834,P=0.003];EPC组血浆VEGF浓度显著高于对照组[(54.91±5.71)pg/ml对(13.81±4.25)pg/ml;q=12.300,P=0.002].结论 自体EPC移植对大鼠缺血脑组织具有保护作用,可能与VEGF相关联的血管再生和神经保护有关,其在治疗缺血性脑血管病中具有重要的应用前景.     

青少年高血压的研究进展

随着人们生活和行为方式的改变,高血压发病明显呈年轻化趋势。在青少年时期识别高血压病高危人群有助于早期进行有效干预和治疗,降低未来高血压的发生率及其严重性。现试从青少年高血压的诊断、发病因素、特点、治疗策略等方面的研究进展作一综述。     

Morbidity in cardiovascular diseases in immigrants in Sweden

INTRODUCTION: Although immigration to Sweden has increased in the last few decades, the incidence rates of cardiovascular disease and coronary heart disease in immigrants are unknown. The aim of the present study is to estimate whether place of birth affects the incidence rates of cardiovascular disease and coronary heart disease. MATERIAL AND METHODS: The study was designed as a follow-up study on morbidity in cardiovascular disease and coronary heart disease between 1 January 1997 and 31 December 1998, including three and a half million persons with age range 35-64 years, of whom 550 000 were born abroad, from the database MigMed consisting of the whole Swedish population. Incidence rates and relative risks were estimated by indirect standardization and a proportional hazard model. RESULTS: The age-adjusted risk of coronary heart disease was higher in most foreign-born groups than in Swedes. For example, in nine of 12 male groups, the relative risks varied between 1.1 and 2.2, and in seven of 12 female groups, the relative risks varied between 1.4 and 2.5. When also adjusting for level of education and employment status, the risks were still high, but on a lower level. CONCLUSIONS: Foreign-born people possess an over-risk of cardiovascular or coronary heart disease(CVD/CHD) compared with Swedish-born persons, also when level of education and employment status are taken into account.     

C·肉毒杀鼠素(冻干剂)应用研究

目的为研究C·肉毒杀鼠索对杀灭达乌尔黄鼠(简称黄鼠)的大面积应用情况和对家畜、家禽的毒害作用,进行了C·肉毒杀鼠素的应用研究.方法大面积投毒采用ES-2药饵撒播机[1],间隔约80m进行条投.羊、鸡采用直接灌胃.结果大面积应用的灭鼠率为83.72%.对羊、鸡最高剂量分别为500万MLD、150万MLD,均未出现中毒现象.结论 C·肉毒杀鼠素是较为理想的草原大面积杀灭黄鼠的理想、首选药物.     

高龄老年高血压的临床研究进展

随着社会老龄化进程的加快,80岁以上高龄老人的绝对数量以及占总人口的比例均在增加,如何提高高龄老年高血压的防治水平备受关注。现试从高龄老年高血压的临床特点、治疗策略等方面的临床研究进展作一综述。     

中国老年性耳聋的研究与干预进展

老年性耳聋已成为影响我国老年人生活质量的最主要的慢性病之一。助听器是目前帮助听力损失的老年人克服交流障碍的主要手段。在我国,数字助听器已逐渐取代模拟助听器并且体现出了更好的效果。但是老年听力损失患者中使用助听器的比例仍然很小。人工耳蜗植入也已被应用在老年患者中。我国针对老年人的听力康复服务还有较长的路要走。     

Sex Differences in Ethanol-induced Dopamine Release in Nucleus Accumbens and in Ethanol Consumption in Rats

In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DO-PAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/ kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system.     

Epstein-Barr virus in malignancies in renal transplant recipients in Japan

A role for Epstein-Barr virus (EBV) in the development of malignancies including lymphomas, and carcinoma of the stomach, nasopharynx, thymus and salivary gland is suggested. It is indicated that EBV evokes polyclonal-B-cell-proliferative diseases in immunocompromised hosts, such as transplant patients, which results in monoclonal malignant lymphomas. The suppression of immune functions in these patients is thought to lead to incomplete elimination of the cells expressing EBV latent infection genes. To examine the etiological role of EBV in the development of malignancies following renal transplant in Japan, 42 malignancies in 1744 cases of renal transplant were studied for the presence and type of EBV. The polymerase chain reaction revealed that 5 malignancies were positive for EBV, all type A: 2 of 2 cases of non-Hodgkin's lymphoma (NHL), 2 of 8 cases of gastric adenocarcinoma of the common type, and 1 of 2 cases of gastric plasmacytoma. In situ hybridization revealed positive signals in the nucleus of tumor cells in 2 cases of NHL and 1 of plasmacytoma. Positive signals were found in the small lymphoid cells but not in the tumor cells in 2 cases of gastric carcinoma. On the basis of these findings, a role for EBV in the development of malignancies in renal transplant patients is unlikely except for lymphoid neoplasias.Abbreviations PCB polymerase chain reaction - EBV Epstein-Barr virus - NHL non-Hodgkin's lymphoma     

糖尿病大鼠心室肌细胞钾通道的改变

目的研究糖尿病大鼠心室肌细胞钾通道的改变及增加葡萄糖代谢对其的作用。方法取体重150～200g的雄性SpragueDawley大鼠,腹腔注射链脲菌素(STZ)建立糖尿病模型,采用酶解法获得单个心室肌细胞,应用膜片钳全细胞记录技术记录钾电流。结果糖尿病大鼠心室肌细胞瞬间外向性钾流(Ito)密度较对照组显著降低[ 60mV时,分别为(15.90±1.19)pA/pF(n=25)和(28.55±0.97)pA/pF(n=12),P<0.001];分别用100nmol/L胰岛素及1.5mmol/L二氯乙酸在体外预处理心室肌细胞4～5h和3～4h使Ito密度恢复至对照组水平[ 60mV时,分别为(29.40±0.38)pA/pF(n=20)和(27.35±0.97)pA/pF(n=12)]。结论糖尿病大鼠心室肌细胞钾通道功能发生改变,增加葡萄糖代谢可逆转这一改变,提示葡萄糖代谢与Ito功能间存在一定关系。