血管紧张素Ⅱ和NADPH氧化酶与血管衰老的相关性研究

目的探讨血管紧张素Ⅱ（AngⅡ）和NADPH氧化酶在血管衰老中的地位及作用机理.方法健康Wistar大鼠分为青年组、老龄组、Valsantan组,分析各组大鼠主动脉形态结构及功能;测定血浆和主动脉AngⅡ水平、主动脉活性氧水平;分别应用RT-PCR和Western bolt检测各组大鼠AngⅡ1型和2型受体（AT1R和AT2R）、NADPH氧化酶p22phox的mRNA及蛋白表达.结果随增龄大鼠主动脉管壁增厚,纤维化程度增高,内皮功能受损,活性氧产生增加;主动脉AngⅡ含量增高,AT2R、p22phox的mRNA及蛋白表达上调,AT1R表达下降;Valsantan（AngⅡ1型受体特异性阻断剂）干预后,p22phox表达下降,活性氧水平降低,衰老血管形态结构和功能异常有所改善.结论衰老血管有其特征性结构和功能改变;AngⅡ经由AT1R上调NADPH氧化酶的基因表达可能是血管衰老的重要机制之一.     

4羟基2.2.6.6四甲基哌啶对肾性高血压大鼠主动脉重构的影响

背景 线粒体是活性氧产生的主要来源之一,4羟基2.2.6.6四甲基哌啶(Tempol)可作用于线粒体,清除活性氧.目的 探讨Tempol对肾性高血压大鼠主动脉功能和结构的影响以及作用机理.方法 两肾一夹的方法 建立肾性高血压大鼠模型,术后4周随机分为假手术组(n=8)、高血压组(n=6)及治疗组(n=6),治疗组给予含Tempol 1 mmol/L饮用水.干预8周后观察血压、血管紧张素Ⅱ(AngⅡ)、一氧化氮(NO)、8异前列腺素F2α、胸主动脉NADPH氧化酶亚单位p22 phox mRNA表达的变化;对胸主动脉进行离体血管环实验和HE染色观察其舒张功能和结构的变化.结果 1)模型高血压组与假手术组比较,血压、主动脉中膜厚度、中膜厚度/内径显著增加(P均＜0.01);AngⅡ、8异前列腺素F2α、NO显著降低(P均＜0.01);离体主动脉环对乙酰胆碱(Ach)引起的最大舒张百分数显著下降(P＜0.01);主动脉NADPH p22 phox mRNA表达上调.2)治疗组用Tempol治疗8周后与高血压组比较,血压、主动脉中膜厚度、中膜厚度/内径下降;AngⅡ、8异前列腺素F2α显著下降(P均＜0.01);NO水平上升(P＜0.05);离体主动脉环对Ach引起的最大舒张百分比显著上升(P＜0.01);主动脉p22 phox mRNA表达下调;AngⅡ比较没有差异.3)各组间离体主动脉环对硝普钠引起的最大舒张百分比无差异;用L硝基精氨酸甲酯(L-NAME)抑制NO后,各组间离体主动脉环对Ach最大舒张反应无差异.结论 Tempol可以明显降低肾性高血压大鼠中氧化应激水平,改善NO代谢,降低血压,其降压机制与其改善NO代谢有关,Tempol还可下调主动脉p22 phox mRNA表达改善主动脉内皮依赖性的舒张功能.     

高温应激对大鼠心肌血管紧张素Ⅱ的影响及其与心肌p22phox表达的关系

目的 观察高温应激对大鼠心肌血管紧张素Ⅱ（AngⅡ)的影响,探讨心肌AngⅡ与心肌p22phox表达的关系。方法 将24只成年雄性SD大鼠,随机分为:对照组、高温组、高温高湿组,每组8只。喂养4周后,颈动脉插管测定平均动脉压。用放射免疫法测定血浆和心肌AngⅡ浓度。用比色法测定心肌活性氧(ROS)水平。应用逆转录聚合酶链式反应（RT-PCR）和免疫组化法检测心肌p22phox mRNA及蛋白的表达水平。结果 高温组和高温高湿组大鼠平均动脉压、AngⅡ浓度、ROS水平、p22phox mRNA及蛋白的表达水平与对照组比较,均有显著升高（P<0.01）;高温高湿组与高温组比较,无显著性差异。结论 高温应激使大鼠血压升高,这可能与AngⅡ水平上调有关。AngⅡ介导ROS生成增加,其机制可能是高温应激引起p22phox超常表达所致,提示高温应激可引起心脏损害。     

阿托伐他汀对高胆固醇血症患者血小板血管紧张素Ⅱ受体表达的影响

目的 通过观察高胆固醇血症患者血小板血管紧张素Ⅱ1型受体(AT1R)、血管紧张素Ⅱ2型受体(AT2R)表达的变化及阿托伐他汀对其表达变化的影响,探讨肾素血管紧张素系统(RAS)在高血压及动脉粥样硬化(AS)发生中的作用及他汀多效性作用的机制.方法 在我院健康查体中心随机选取健康对照60例和高胆固醇血症患者80例,分别为对照组和高脂组;高脂组予以阿托伐他汀20 mg/d,睡前口服,共12周.于试验开始前及高脂组服药12周时,肘静脉取血,分离血清、血浆并提取血小板.放射免疫法检测血浆的血管紧张素Ⅱ(AngⅡ)水平,RT-PCR和Western blot方法分别检测血小板AT1R、AT2R的mRNA和蛋白质表达水平.结果 阿托伐他汀组的胆圊醇相较高脂组明显降低(他汀组:5.57±1.27比高脂组:7.08±1.23 mmol/L,P＜0.05):①高脂组的血浆AngⅡ水平较对照组显著升高(P＜0.01),他汀治疗后较治疗前明显降低(P＜0.05).②阿托伐他汀治疗明显下降高脂组血小板的AT1R mRNA(治疗前:0.93±0.22比治疗后:0.52±0.13,P＜0.01)和蛋白质表达(治疗前:1.35±0.32比治疗后:0.72±0.16,P＜0.01).③阿托伐他汀治疗明显升高高脂组血小板的AT2R mRNA(治疗前:0.85±0.16比治疗后:1.24±0.28,P＜0.01)和蛋白质表达(治疗前:0.81±0.17比治疗后:1.23±0.25,P＜0.01).④高脂组血小板AT1R、AT2R的表达均与血浆的AngⅡ水平呈显著正相关(r=0.389,P＜0.01;r=0.356,P＜0.01).结论 阿托伐他汀下调高胆固醇血症患者血小板AT1R表达的增高,但进一步上调AT2R表达的增高.     

血管紧张素转化酶抑制剂和抗氧化剂对湿热应激性大鼠心肌AngⅡ和p22phox表达的影响

目的:观察血管紧张素转化酶抑制剂(ACEI)卡托普利(Captopril,CTP)和抗氧化剂（维生素C,VitC）对湿热应激(HHS)大鼠心肌组织中血管紧张素Ⅱ（AngⅡ)、活性氧簇（ROS）和p22phox表达的影响。方法: 将32只成年雄性SD大鼠随机分为:对照组、HHS组、CTP组(HHS+CTP)及VitC组(HHS+VitC),每组8只。喂养4周后,颈动脉插管测定大鼠血压,计算大鼠左心室质量指数。用放射免疫法测定心肌组织中AngⅡ的浓度。用比色法测定心肌组织中ROS的水平。应用RT-PCR检测p22phox mRNA的表达。用免疫组化染色法检测大鼠心肌中p22phox的分布特征。结果: 平均动脉压、AngⅡ和ROS和p22phox的水平,HHS组与对照组比较,VitC组和CTP组与HHS组比较,均有非常显著性差异（P<0.01）;两个药物组之间比较无统计学意义。结论: HHS可增加大鼠心肌组织中AngⅡ表达,同时上调p22phox mRNA和其蛋白的表达,介导心肌细胞内ROS生成增加。用抗氧化剂和ACEI阻滞后,AngⅡ表达减少,p22phox mRNA和其蛋白的表达降低,心肌细胞内ROS生成减少,其机制可能与HHS导致AngⅡ诱导ROS产生有关。以上提示,HHS可引起心脏损害,抗氧化剂和ACEI对HHS性心脏损害具有拮抗作用。     

阿托伐他汀对高胆固醇血症患者AT1表达的影响

目的 通过观察高胆固醇血症患者血管紧张素Ⅱ(AngⅡ)1型受体(AT1)表达的变化及阿托伐他汀对其表达变化的影响,探讨肾素-血管紧张素系统(RAS)在动脉粥样硬化(AS)发生的作用及他汀多效性作用的机制.方法 在该院健康查体中心随机选取健康对照者40例和高胆固醇血症患者60例,分别为对照组和高脂组;高脂组予以阿托伐他汀20 mg/d,睡前口服,共12 w.对照组、高脂组他汀治疗前及治疗后,肘静脉取血,分离血清、血浆并提取血小板.放射免疫分析法检测血浆的AngⅡ水平,RT-PCR和Western印迹方法分别检测血小板AT1的mRNA和蛋白质表达水平.结果 ①高脂组治疗前的血浆AngⅡ水平较对照组明显升高[(92.13±22.27)pg/ml vs(50.85±12.15)pg/ml](P＜0.01),治疗后的血浆AngⅡ水平较治疗前明显降低[(78.57±18.33)pg/ml vs(92.13±22.27)pg/ml](P＜0.05).②高脂组治疗前血小板的AT1 mRNA和蛋白质表达较对照组明显升高[0.93±0.22 vs 0.25±0.06(P＜0.01)和1.35±0.32 vs 0.42±0.10(P＜0.01)],治疗后血小板的AT1 mRNA和蛋白质表达较治疗前明显降低[(0.52±0.13 vs 0.93±0.22(P＜0.01)和0.72±0.16 vs 1.35±0.32(P＜0.01)].③高脂组治疗前AngⅡ与AT1表达的相关分析显示,AT1表达与血浆的AngⅡ呈显著正相关(r=0.607,P＜0.01).结论 阿托伐他汀下调高胆固醇血症患者血小板AT1表达的增高.     

缬沙坦对自发性高血压大鼠血管紧张素ⅡⅠ型受体密度及亲和力干预的研究

目的研究缬沙坦对自发性高血压大鼠左室心肌血管紧张素ⅡⅠ型受体(AT1)密度及亲和力的影响,探讨高血压左室肥厚的细胞分子机制及缬沙坦的干预机制.方法 (1)12只6周龄雄性自发性高血压大鼠(SHR)分二组自发性高血压大鼠(SHR)6只为阳性对照组;缬沙坦干预组(SHR-V)6只 缬沙坦 20 mg*kg-1*d-1;同源正常血压大鼠(WKY)6只为正常对照组.(2)用放射配基结合分析法测定左室心肌AT1受体密度及亲和力;用放免法测定血液及左室心肌血管紧张素Ⅱ(Ang Ⅱ)浓度;测量血压、左室重量/体重及左室厚度/体重.结果 (1)AT1受体密度及亲和力的变化SHR组左室心肌AT1受体亲和力较WKY组增强(P<0.05),但AT1受体密度降低(P<0.01);SHR-V组较SHR组AT1受体亲和力降低(P<0.05),与WKY组无明显的差异,在SHR-V组,AT1受体密度明显高于SHR组(P<0.01).(2)Ang Ⅱ浓度的变化SHR组心肌Ang Ⅱ水平较WKY组明显升高(P<0.01),但血浆Ang Ⅱ水平无明显差异;SHR-V组心肌Ang Ⅱ水平明显低于SHR组(P<0.01),而血浆Ang Ⅱ浓度较另二组明显升高(P<0.01).(3)血压及左室结构的变化缬沙坦可显著降低SHR的血压、左室重量/体重及左室厚度/体重(P<0.01).结论 (1)左室心肌AT1受体亲和力增强及Ang Ⅱ水平升高在高血压左室肥厚的发生、发展中起着重要的作用.(2)缬沙坦除可降低血压外,尚可降低左室心肌AT1受体亲和力及Ang Ⅱ水平,逆转左室肥厚.     

氯沙坦对自发性高血压大鼠糖基化终末产物及其受体诱导的血管损伤的影响

背景晚期糖基化终末产物(AGEs)及其受体RAGE系统在糖尿病靶器官损伤的病理过程中起非常重要的作用,有研究报道血管紧张素Ⅱ1型受体拮抗剂(ARB)能减少体内外2型糖尿病动物AGEs聚集以及氧化应激反应.目的 探讨血管氧化应激与AGE水平及其受体RAGE及核转录因子(NF-kB)等在高血压血管损伤进程中的变化及氯沙坦对其损伤路径的影响.方法 选30 周龄自发性高血压大鼠(SHR)随机分为SHR组、氯沙坦组[30 mg/(kg·d)],WKY组为对照.干预12周,用放免法测定血浆血管紧张素Ⅱ(AngⅡ)水平;免疫荧光检测血管晚期糖基化终末产物(AGEs)表达;免疫组化法检测血管RAGE表达.RT-PCR检测AT1 mRNA、NF-KB mRNA、NADPH氧化酶p47 phox mRNA表达.结果 12周后,SHR组的血压稳定在治疗前水平[(222±5)mmHg],氯沙坦组血压降至[(158±4)mmHg],且明显低于SHR组(P<0.01);氯沙坦组血浆Ang Ⅱ水平达(67.4±5.4)pg/mL,明显高于SHR组[(49.5±4.6)pg/mL,P<0.01];氯沙坦组及WKY组血管AGEs表达显著低于SHR组;氯沙坦组RAGE蛋白表达指数(6.5±0.7)显著低于SHR组(8.33±0.95,P<0.01);氯沙坦组ATl mRNA、NF-kB mRNA、NADPH oxidase p47 phox mRNA 表达相对系数分别是0.51±0.06、0.39±0.07、0.36±0.05明显低于SHR组(0.91±0.12、0.54±0.1、0.54±0.06,P<0.01).结论 高血压病血管内皮细胞氧化应激增加,氯沙坦能通过阻止Ang Ⅱ与血管紧张素Ⅱ 1型受体结合,降低氧化应激抑制AGEs水平和RAGE及NF-KB活化等,改善高血压血管重塑.     

阿托伐他汀对血管损伤小鼠血管重构的干预研究

目的观察不同剂量阿托伐他汀对血管损伤小鼠血管重构的影响。方法在雄性C57BL/6小鼠股动脉外套上聚乙烯套管,制作成血管损伤模型。320只小鼠随机分为5组：正常对照组（正常组）、假手术对照组（假手术组）、手术对照组（手术组）、阿托伐他汀低剂量干预组[低剂量组,2.5（mg/kg·d）],阿托伐他汀高剂量干预组[高剂量组,5（mg/kg·d）],每组64只,通过灌胃给药,分别于造模术后第7d、第14d处死小鼠。取小鼠股动脉标本,分别采用HE染色及NIH图像分析软件测量血管内膜及中膜面积,RT-PCR法检测NAD（P）H氧化酶系统主要亚单位p22phox,p47phox,rac-1mRNA表达水平,应用光泽精化学发光法测定股动脉O2-·的含量。各组随机抽取16只老鼠测造模前后血脂及肝功能。结果手术组及药物干预组均有血管内膜过度增生,正常组及假手术组未见新生内膜形成,造模术后14d阿托伐他汀两干预组股动脉内膜增厚速度显著减缓（P〈0.05）。术后14d两干预组,股动脉O2-·含量较手术组及术后7d时均显著降低,有统计学差异（P〈0.05）。术后14d两干预组股动脉p22phox,p47phox,rac-1mRNA的相对表达量较手术组及术后7d时显著降低（P〈0.05）。各组实验前后血脂、肝功无明显差异（P〉0.05）。小鼠股动脉p47phox,p22phox,rac-1mRNA表达量与O2-·含量之间呈正相关,相关系数分别为0.907,0.918,0.920（P均〈0.05）。结论短期应用阿托伐他汀能通过抑制小鼠股动脉p22phox,p47phox,rac-1mRNA的表达,减轻损伤血管重构。     

4羟基2.2.6.6四甲基哌啶对肾性高血压大鼠主动脉重构的影响

背景线粒体是活性氧产生的主要来源之一，4羟基2．2．6．6四甲基哌啶（Temp01）可作用于线粒体，清除活性氧。目的探讨Tempol对肾性高血压大鼠主动脉功能和结构的影响以及作用机理。方法两肾-夹的方法建立肾性高血压大鼠模型，术后4周随机分为假手术组（n=8）、高血压组（n=6）及治疗组（n=6），治疗组给予含Tempol 1 mmol／L饮用水。干预8周后观察血压、血管紧张素Ⅱ（AngⅡ）、一氧化氮（NO）、8异前列腺素F2a、胸主动脉NADPH氧化酶亚单位p22 phox mRNA表达的变化；对胸主动脉进行离体血管环实验和HE染色观察其舒张功能和结构的变化。结果1）模型高血压组与假手术组比较，血压、主动脉中膜厚度、中膜厚度／内径显著增加（P均〈0．01）；AngⅡ、8异前列腺素F2a、NO显著降低（P均〈0．01）；离体主动脉环对乙酰胆碱（Ach）引起的最大舒张百分数显著下降（P〈0．01）；主动脉NADPHp22phoxmRNA表达上调。2）治疗组用Tempol治疗8周后与高血压组比较，血压、主动脉中膜厚度、中膜厚度／内径下降；AngⅡ、8异前列腺素F2a显著下降（P均〈0．01）；NO水平上升（P〈0．05）；离体主动脉环对Ach引起的最大舒张百分比显著上升（P〈0．01）；主动脉p22 phox mRNA表达下调；AngⅡ比较没有差异。3）各组间离体主动脉环对硝普钠引起的最大舒张百分比无差异；用L硝基精氨酸甲酯（L-NAME）抑制NO后，各组间离体主动脉环对Ach最大舒张反应无差异。结论Tempol可以明显降低肾性高血压大鼠中氧化应激水平，改善NO代谢，降低血压，其降压机制与其改善NO代谢有关，Tempol还可下调主动脉p22phoxmRNA表达改善主动脉内皮依赖性的舒张功能。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.