钙调神经磷酸酶调控精氨酸升压素诱导大鼠心脏成纤维细胞增殖的作用

目的探讨钙调神经磷酸酶(CaN)信号通路对精氨酸升压素(AVP)诱导新生大鼠心脏成纤维细胞(CFs)增殖的调控作用.方法采用胰酶消化法培养新生Sprague-Dawley大鼠CFs,MTT比色法测定细胞数目,应用流式细胞仪分析细胞周期,CaN活性通过分光光度计测定.结果 (1)CFs的 MTT比色法吸光度A490值随着AVP作用浓度的升高而增加,其中10-7 mol/L AVP和10-6 mol/L AVP组A490值(分别为0.17±0.01和0.18±0.01)与空白对照组(0.11±0.01)比较有显著差异(P<0.01);不同浓度的AVP+CsA组A490值均较相应的AVP组降低,其中10-7mol/L AVP+CsA组和10-6 mol/L AVP+CsA组分别为0.13±0.01和0.15±0.01,与10-7mol/L AVP和10-6 mol/L AVP组比较显著降低,并有统计学意义(P<0.01).(2)10-7mol /L AVP 作用下CFs细胞周期S期百分率为17.86 ±3.18,与空白对照组(12.10±2.38)比较明显升高,并有统计学意义(P<0.01).10-7mol /L AVP +CsA组CFs细胞周期S期百分率(13.76±2.52)与10-7mol /L AVP组比较有显著差异(P<0.05).(3)10-7 mol/L AVP组CFs的CaN活性为0.30±0.06 kU/mg,与对照组(0.14±0.03 kU/mg)比较差异显著(P<0.01).结论 CaN的特异性抑制剂环孢素A(CsA)可抑制AVP诱导的CFs增殖,AVP可升高CFs内CaN活性,表明CaN信号通路在AVP诱导CFs增殖过程中起到了重要的调控作用.     

血管紧张素（1～7）对血管加压素诱导心脏成纤维细胞增殖的影响及其与钙调神经磷酸酶的关系

目的探讨血管紧张素(1～7)[Ang(1～7)]对血管加压素(AVP)诱导心脏成纤维细胞(CFs)增殖的影响及其与钙调神经磷酸酶(CaN)的关系。方法分离培养SD仔鼠CFs,四氮唑盐(MTT)比色法检测细胞增殖,采用流式细胞分析仪技术测定细胞周期,发色底物法测定细胞内CaN的活性。结果(1)10-7mol/LAVP干预24h后,CFs的MTT吸光度值(0.24±0.01)较对照组(0.14±0.01)明显增高(P<0.01);给予10-9～10-6mol/LAng(1～7)和AVP共同干预后,CFs的吸光度值呈递减趋势,分别为0.22±0.01、0.21±0.01、0.18±0.01和0.16±0.01,均较AVP组降低,差异有统计学意义(P<0.01)。(2)AVP刺激后,CFs的S期百分率(14.00±0.94)和增殖指数(23.4±1.8)较对照组(分别为5.4±0.7和10.8±2.4)明显增高(P<0.01);10-7mol/LAng(1～7)和AVP共同作用后S期百分率(8.5±0.7)和增殖指数(16.2±2.0)较AVP组降低,差异有统计学意义(P<0.01)。(3)AVP组CFs内CaN活性(0.27±0.02kU/mg)较对照组(0.12±0.01)kU/mg明显增加(P<0.01),给予10-9～10-6mol/LAng(1～7)和AVP共同干预后,CaN活性分别为0.25±0.01、0.20±0.02、0.17±0.01和0.15±0.02(kU/mg),均较AVP组降低,差异有统计学意义(P<0.01)。结论Ang(1～7)能抑制AVP诱导CFs增殖,CaN活性降低可能是其分子生物学机制之一。     

血管紧张素(1～7)对血管加压素诱导心脏成纤维细胞增殖的影响及其与钙调神经磷酸酶的关系

目的探讨血管紧张素(1～7)[Ang(1～7)]对血管加压素(AVP)诱导心脏成纤维细胞(CFs)增殖的影响及其与钙调神经磷酸酶(CaN)的关系.方法分离培养SD仔鼠CFs,四氮唑盐(MTT)比色法检测细胞增殖,采用流式细胞分析仪技术测定细胞周期,发色底物法测定细胞内CaN的活性.结果 (1)10-7 mol/L AVP干预24 h后,CFs的MTT吸光度值(0.24±0.01)较对照组(0.14±0.01)明显增高(P<0.01);给予10-9～10-6 mol/L Ang(1～7)和AVP共同干预后,CFs的吸光度值呈递减趋势,分别为0.22±0.01、0.21±0.01、0.18±0.01和0.16±0.01,均较AVP组降低,差异有统计学意义(P<0.01).(2)AVP刺激后, CFs 的S期百分率(14.00±0.94)和增殖指数(23.4±1.8)较对照组(分别为5.4±0.7和10.8±2.4)明显增高(P<0.01);10-7 mol/L Ang(1～7) 和AVP共同作用后S期百分率(8.5±0.7)和增殖指数(16.2±2.0)较AVP组降低,差异有统计学意义(P<0.01).(3)AVP组CFs内CaN活性(0.27±0.02 kU/mg)较对照组(0.12±0.01)kU/mg明显增加(P<0.01),给予10-9～10-6 mol/L Ang(1～7) 和AVP共同干预后,CaN活性分别为0.25±0.01、0.20±0.02、0.17±0.01和0.15±0.02(kU/mg),均较AVP组降低,差异有统计学意义(P<0.01).结论 Ang(1～7)能抑制AVP诱导CFs增殖,CaN活性降低可能是其分子生物学机制之一.     

拉西地平对AVP诱导的大鼠心脏成纤维细胞增殖的影响及其与ERK1/2的关系

目的观察拉西地平对血管加压素（AVP）诱导的大鼠心脏成纤维细胞（CFs）增殖的影响及其与细胞外信号调节激酶（ERK）1/2的关系。方法以培养的新生SD大鼠CFs为实验模型,采用四氮唑盐比色法测定细胞数目;用流式细胞术分析细胞周期;用蛋白免疫印迹法测定总细胞外信号调节激酶（t-ERK）1/2和磷酸化细胞外信号调节激酶（p-ERK）1/2在细胞内的表达。实验按照给予CFs干预因素的不同,分为对照组、10-7mol/L AVP处理组、10-910-6mol/L拉西地平+10-7mol/L AVP干预组和10-7mol/L拉西地平单独干预组。结果①10-7mol/LAVP干预24 h后,CFs的A490值（0.232±0.013）较对照组（0.132±0.008）显著增高（P<0.01）。在10-910-6mol/L拉西地平和10-7mol/L AVP共同干预下,拉西地平可呈浓度依赖性地下调CFs的A490值,分别为0.216±0.01、0.203±0.01、0.176±0.01和0.160±0.01,均显著低于AVP组（P<0.01）。②细胞周期分析显示,AVP组CFs在S期的百分率和增殖指数（PI）分别为13.06±0.83和21.70±1.55,与对照组（分别为4.60±0.60和8.97±1.56）比较显著增高（P<0.01）。在10-7mol/L拉西地平干预下,细胞在S期的百分率（8.84±0.80）和PI（15.46±1.84）较AVP组显著降低（P<0.01）。③AVP组CFs的p-ERK1/2表达显著高于对照组（P<0.01）,10-9、10-8、10-7和10-6mol/L拉西地平组CFs中p-ERK1/2的表达与AVP组比较呈浓度依赖性地降低（P<0.01）。结论拉西地平可抑制AVP诱导的大鼠CFs增殖,提示拉西地平对预防和逆转心脏重构具有一定的作用,其机制可能与ERK1/2的磷酸化有关。     

β_1整合素反义寡核苷酸抑制精氨酸加压素诱导下心脏成纤维细胞DNA合成的作用

目的:探讨β1整合素反义寡核苷酸(ASODN)对精氨酸加压素(AVP)诱导大鼠心脏成纤维细胞(CFs)DNA合成功能的抑制作用。方法:以胰蛋白酶消化法分离、培养SD大鼠的CFs,采用MTT吸光度法及3H-胸腺嘧啶核苷(3H-TdR)掺入法,原位酶联免疫吸附测定(ELISA)等技术,观察基础状态下β1整合素ASODN对CFs细胞数目及DNA合成功能的影响;β1整合素ASODN对AVP诱导的β1整合素表达,CFs增殖及DNA合成功能的影响;基础状态下设空白对照组、反义链组和正义链组;AVP诱导下设空白对照组、1×10-7mol/L AVP组、反义链+1×10-7mol/L AVP组和正义链+1×10-7mol/L AVP组,每组均为8个复孔。结果:①反义链组的CFs细胞数目及3H-TdR掺入率明显低于空白对照组及正义链组,并且均有统计学意义(P0.01);正义链组与对照组比较无统计学意义。②1×10-7mol/LAVP组和正义链+1×10-7mol/LAVP组的β1整合素表达水平,CFs细胞数目均高于空白对照组(P0.05),β1整合素ASODN与AVP共同作用组的β1整合素表达水平,CFs细胞数目明显低于1×10-7mol/LAVP组和正义链+1×10-7mol/L AVP组,并且均有非常显著性意义(P0.01)。③1×10-7mol/L AVP组和正义链+1×10-7mol/L AVP组的CFs3H-TdR掺入率均高于空白对照组(P0.05),β1整合素ASODN与AVP共同作用组的CFs3H-TdR掺入率明显低于空白对照组、1×10-7mol/L AVP组和正义链+1×10-7mol/L AVP组,并且均有非常显著性意义(P0.01)。结论:β1整合素ASODN不但抑制基础状态下CFs生长及DNA合成代谢,而且抑制AVP刺激β1整合素表达、CFs增殖、DNA合成的作用,说明针对特异性靶基因片段合成的ASODN可能抑制β1整合素遗传信息传递的某个环节,干扰细胞内外信息的传递,影响β1整合素介导的CFs与细胞外基质的黏附,从而产生拮抗AVP刺激心脏间质重构形成的作用。进一步提示应用反义药物防治高血压心脏间质重构的可能性。     

V1受体拮抗剂对精氨酸升压素诱导的大鼠心脏成纤维细胞增殖的影响

目的探讨V1受体拮抗剂[d(CH2)5-Tyr2(Me)]AVP对精氨酸升压素(AVP)诱导的大鼠心脏成纤维细胞增殖的影响. 方法采用胰酶消化法培养新生Sprague-Dawley (SD)大鼠心脏成纤维细胞(CFs),以3H-TdR掺入法测定CFs的DNA合成功能,MTT比色法测定CFs数目,并应用流式细胞仪进行CFs细胞周期分析. 结果①CFs的3H-TdR掺入率随着AVP干预浓度的增加而增高,其中10-7mol/L AVP和10-6mol/L AVP组每5000个细胞的3H-TdR掺入率分别为(243±61)cpm和(328±68)cpm,均明显高于对照组3H-TdR掺入率(117±32)cpm(P<0.01);②MTT比色法吸光度(A490 nm)值随AVP浓度的增加而增高,其中10-7mol/L AVP、10-6mol/L AVP组的A490 nm值分别为0.24±0.01和0.29±0.02,均较对照组A490 nm值(0.16±0.01)显著增高(P<0.01);③10-7mol/L AVP组CFs细胞周期S期百分率显著高于对照组(30.20±0.88)% vs (26.86±1.06)%( P<0.01);④10-7mol/L AVP+10-7 mol/L [d(CH2)5-Tyr2(Me)]AVP组的每5000个细胞的3H-TdR掺入率、MTT比色法A490 nm值和S期百分率分别为(143±40)cpm、0.17±0.01和(25.02±0.51)%,均显著低于10-7mol/L AVP组(分别P<0.05,P<0.01,P<0.01). 结论 AVP可诱导CFs的DNA合成功能增强和细胞数目增加,其作用可被V1受体拮抗剂[d(CH2)5-Tyr2(Me)] AVP所阻断,表明V1受体可能介导了AVP促CFs增殖效应.     

精氨酸升压素对大鼠心肌成纤维细胞诱导型一氧化氮合酶-一氧化氮系统活性的影响

目的　研究精氨酸升压素 (AVP)对大鼠心肌成纤维细胞诱导型一氧化氮合酶 (iNOS) 一氧化氮 (NO)系统活性的影响。方法　胰酶消化法分离培养Sprague Dawley仔鼠心肌成纤维细胞 ,采用硝酸还原酶法、蛋白质印迹和逆转录 聚合酶链式反应观察AVP对心肌成纤维细胞的NO含量、iNOS蛋白水平和iNOSmRNA表达的影响。结果　 (1)不同浓度AVP干预下 ,心肌成纤维细胞的NO含量、iNOS蛋白水平和iNOSmRNA表达都随AVP浓度的增高而增加。其中 10 -7mol/LAVP组和 10 -6mol/LAVP组的NO含量 [(6 9 0 5± 5 5 6 ) μmol/L和 (6 2 86± 6 0 5 ) μmol/L]、iNOS蛋白水平 (0 73± 0 0 6和 0 6 4± 0 0 5 )和iNOSmRNA表达 (0 70± 0 0 3和 0 6 6± 0 0 6 )都显著高于对照组 [(2 9 34± 5 34)μmol/L ,0 2 0± 0 0 5 ,0 2 5± 0 0 4 ]、10 -9mol/LAVP组 [(31 79± 6 5 9) μmol/L ,0 2 4± 0 0 7,0 30±0 0 6 ]和 10 -8mol/LAVP组 [(36 87± 7 89) μmol/L ,0 30± 0 0 9,0 31± 0 0 3]。但 10 -6mol/LAVP组的NO含量、iNOS蛋白水平和iNOSmRNA表达都低于 10 -7mol/LAVP组。 (2 ) 10 -7mol/LAVP干预下CFs的NO含量、iNOS蛋白水平和iNOSmRNA表达都随培养时间的延长而增加。其中 2 4h组和 36h组的NO含量 [(6 5     

白细胞介素10对血管升压素诱导心脏成纤维细胞增殖及胶原合成的影响

目的研究白细胞介素10(IL-10)对血管升压素(AVP)诱导大鼠心脏成纤维细胞(CFs)增殖及Ⅰ、Ⅲ型胶原合成的影响。方法以培养的新生SD大鼠CFs为实验模型,四氮唑盐(MTT)比色法检测CFs增殖,流式细胞仪技术(FCM)测定细胞周期,逆转录聚合酶链式反应(RT-PCR)检测Ⅰ、Ⅲ型胶原mRNA表达水平。结果(1)10-7mol/L AVP作用24h,CFs的吸光度(A490)为0·216±0·013,较对照组(0·132±0·006)显著增加(P<0·01)。(2)IL-10呈浓度依赖性下调AVP诱导的CFs的A490的增加,其10-8g/mLIL-10干预组CFs的A490(0·157±0·029)较AVP组显著降低(P<0·01)。(3)AVP组CFs的S期百分率及增殖指数(12·30±0·71,19·58±0·88)较对照组(4·22±0·48,7·12±0·62)显著增加(P<0·01);而10-9g/mLIL-10干预组,CFs的S期百分率及增殖指数(9·56±1·13,13·86±1·28)较AVP组显著降低(P<0·01)。(4)AVP组Ⅰ、Ⅲ型胶原mRNA表达水平(1·45±0·06,1·06±0·06)较对照组(1·03±0·05,0·77±0·05)显著增加(P<0·01)。而IL-10可浓度依赖性的下调AVP诱导的CFs的Ⅰ、Ⅲ型胶原mRNA表达,其10-8g/mL IL-10干预组Ⅰ、Ⅲ型胶原mRNA表达水平(1·14±0·06,0·88±0·02)显著低于AVP组(P<0·01)。结论IL-10具有抑制AVP诱导CFs增殖和胶原合成的作用,这可能对预防和逆转心脏重构有一定的价值。     

白细胞介素-6对血管升压素调控心脏成纤维细胞增殖及p27蛋白表达的干预效应

目的 :观察白细胞介素 6 （interleukin 6 ,IL 6 ）对血管升压素 （argipressin ,AVP）诱导的心脏成纤维细胞 （CFs）增殖及p2 7蛋白表达的影响。方法 :以培养的新生Sprague Dawley（SD）大鼠CFs为实验模型 ,四氮唑盐 （MTT）比色法检测细胞增殖 ,流式细胞分析仪 （FCM）技术测定细胞周期及p2 7蛋白表达阳性率。结果 :① 10 0 0 0U/mlIL 6作用于CFs 4 8h ,MTT法A值 （0 .38± 0 .0 1）显著高于基础状态组 （0 .32± 0 .0 1,P <0 .0 1） ;10 -7mol/LAVP和 10 0 0 0U/mlIL 6共同作用组CFs的A值 （0 .4 1± 0 .0 1）也明显高于AVP单独作用组 （0 .39± 0 .0 1,P <0 .0 1）。②IL 6作用组CFs的S期细胞百分率 （13.0 %± 3.5 % ）和细胞增殖指数 （PI） （2 9.4 %± 1.9% ）均高于基础状态组 （7.5 %± 1.0 %和 2 6 .0 %± 1.0 % ,P <0 .0 1） ,G0 /G1期细胞百分率 （70 .6 %± 1.9% ）低于基础状态组 （74 .0 %± 1.0 % ） ;AVP +IL 6组CFs的S期细胞百分率和PI分别为 18.8%± 1.5 %和 35 .2 %± 1.6 % ,明显高于AVP组 （15 .5 %± 1.4 %和 31.4 %± 1.5 % ,P<0 .0 1） ,而G0 /G1期细胞百分率 （6 4 .8%± 1.6 % ）明显低于AVP组 （6 8.6 %± 1.5 % ,P <0 .0 1）。 （3）IL 6组CFsp2 7蛋白表达阳性率 （72 .6 %± 2 .5 % ）明显低于基础状态组 (78.4 %±     

辛伐他汀对血管加压素诱导大鼠心肌成纤维细胞增殖的影响及其与小窝蛋白-1表达的关系

目的研究辛伐他汀（simvastatin,Sim）对精氨酸血管加压素（arginine vasopressin,AVP,简称血管加压素）诱导成年大鼠心肌成纤维细胞（CFs）增殖的影响及其与小窝蛋白-1（caveolin-1,cav1）的关系。方法离体培养成年大鼠CFs,以四氮唑盐（MTT）比色法检测CFs的增殖,流式细胞分析仪测定其细胞周期,蛋白免疫印迹法检测cav1蛋白的表达。观察cav1在AVP诱导大鼠CFs增殖前后及Sim干预后的变化。结果10-7mol/LAVP干预24 h后,MTT比色法检测CFs的吸光值（A）（0.24±0.03）较对照组（0.15±0.02）显著增高（P<0.01）;给予10-810-5mol/L的Sim和AVP共同干预后,CFs的A值呈递减趋势,分别为0.22±0.03、0.21±0.02、0.19±0.02和0.17±0.02,均较AVP组降低,差异具有统计学意义（P<0.05,P<0.01）。以10-7mol/L的AVP干预24 h后,CFs S期的百分率（19.52±1.07）和增殖指数（48.25±1.27）较对照组（分别为7.02±0.27和18.93±3.03）均显著增高（均P<0.01）;10-710-5mol/L Sim与10-7mol/L AVP联合干预组CFs S期的百分率和增殖指数均较AVP单独干预组降低,差异具有统计学意义（P<0.05,P<0.01）。10-7mol/L的AVP分别与10-810-5mol/L的Sim共同干预后,cav1蛋白的表达呈浓度依赖性地减少。甲羟戊酸（MVA）可逆转Sim对CFs增殖的抑制效应,并拮抗Sim诱导的cav1蛋白表达的降低。结论Sim可抑制AVP诱导的CFs增殖,Sim的干预效应可能受到cav1蛋白表达的调节。     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.     

Dénervation rénale pour HTA réfractaire sans anesthésie générale : intérêt d’un protocole MEOPA Morphine. Expérience préliminaire

Renal denervation using the technique of radiofrequency is used only recently for the treatment of resistant hypertension. Normally, it is done under general anesthesia because the ablation point technique is painful. We suggest an alternative to general anesthesia comprising an association of morphin 0.1 mg/kg IV to MEOPA (gas combining oxygen and azot protoxyd) delivered through an oxygen mask. Our series includes 12 consecutive patients treated between October 2011 and June 2013, the first five patients (group 1) have received only an hydroxizin and morphin sedation. Every five have felt the ablation painful, in two cases bearable pain (EVA < 5), in three cases intense (EVA > 5) pain leading to increasing doses of morphin, (total dose of 0.25 mg/kg in two cases, 0.17 mg in one case). For the seven following patients, a protocol including hydroxyzin, morphin and MEOPA given through a mask has been set up. Only one patient has felt a mild pain (EVA 5) leading to an increasing dose of morphin (total dose 0.17 mg/kg). None of the six other patients has felt any pain during the procedure. The average dose of morphin is 0.17 mg/kg in group 1, 0.11 mg/kg in group 2. This is a preliminary study; if confirmed, it will allow a lot of hospitals without on-site possibilities of general anesthesia, to realize such procedures. Conclusion: regarding pain, the procedure of renal ablation was well tolerated for six among seven patients receiving the association MEOPA and IV morphin. In contrast, in the five patients treated only with IV morphin, we observed a less good tolerance to pain and the need to increase the doses of IV morphin.     

Scale‐up of TB and HIV programme collaborative activities in Zambia – a 10‐year review

Objective To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade. Methods Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000–2010. Results The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti‐retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV‐infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co‐trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010. Conclusions The scale‐up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti‐retroviral (ARV) rollout with improved treatment outcomes among TB patients co‐infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).     

C-MET在非小细胞肺癌对表皮生长因子受体酪氨酸激酶抑制剂耐药中的作用研究进展

以表皮生长因子受体(EGFR)为靶点的酪氨酸酶抑制剂(TKI)是近年来非小细胞肺癌(NSCLC)治疗的重大突破.但是随着临床的广泛应用,耐药成为新的难点.新近研究已发现对EGFRTKI的耐药产生主要涉及原癌基因C-MET的扩增突变.C-MET是原癌基因,是蛋白产物肝细胞生长因子/离散离子(HGF/SF)的受体,具有酪氨酸酶活性,C-MET基因扩增激活ErbB3-PI3K信号途径导致NSCLC对EGFR-TKI产生耐药,大量研究证实NSCLC患者对EGFR-TKI耐药约20％归因于C-MET基因扩增.     

Artificial intelligence in pancreaticobiliary endoscopy

Artificial intelligence (AI) applications in health care have exponentially increased in recent years, and a few of these are related to pancreatobiliary disorders. AI‐based methods were applied to extract information, in prognostication, to guide clinical treatment decisions and in pancreatobiliary endoscopy to characterize lesions. AI applications in endoscopy are expected to reduce inter‐operator variability, improve the accuracy of diagnosis, and assist in therapeutic decision‐making in real time. AI‐based literature must however be interpreted with caution given the limited external validation. A multidisciplinary approach combining clinical and imaging or endoscopy data will better utilize AI‐based technologies to further improve patient care.