阿托伐他汀对大鼠再狭窄血管醛糖还原酶表达及内膜增生的抑制作用

目的研究醛糖还原酶在大鼠再狭窄血管中的表达,探讨醛糖还原酶表达与内膜增生之间的关系,以及阿托伐他汀对醛糖还原酶表达及内膜增生的抑制作用。方法24只健康雄性SD大鼠,随机分成手术未干预组、假手术组及阿托伐他汀组,每组8只。用通气—干燥法损伤手术未干预组及阿托伐他汀组中的右侧颈总动脉,左侧颈总动脉作为对照。分别于第7天及14天处死动物,HE染色以观察内膜及中膜增生情况,并计算内膜和中膜面积及其比值,FISH原位杂交及免疫组织化学检测醛糖还原酶及核因子κB的表达。结果术后第7天损伤侧血管内膜增生明显,第14天内膜增生进一步加重,对照血管无明显增生。阿托伐他汀组血管内膜面积、内膜与中膜面积比值明显低于手术未干预组(P<0.05或P<0.01)。醛糖还原酶及核因子κB在损伤侧血管中的表达明显强于对照侧。阿托伐他汀组醛糖还原酶及核因子κB的表达明显低于手术未干预组(P<0.05或P<0.01)。结论醛糖还原酶可能参与了大鼠颈动脉损伤后内膜增生及再狭窄的形成。阿托伐他汀可抑制血管内膜增生及再狭窄的形成。阿托伐他汀可能是通过抑制醛糖还原酶及核因子κB而抑制再狭窄的形成。     

自发性高血压大鼠一侧颈动脉去外膜后血管内膜增生及阿托伐他汀的干预作用

目的研究自发性高血压大鼠(SHR)一侧颈动脉外膜去除后血管内膜增生及阿托伐他汀的干预作用。方法24只13周龄雄性SHR去除右侧颈动脉外膜后,随机分为3组(每组8只),分别为SHR组、阿托伐他汀组、缬沙坦组;8只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)。机械和化学方法去除大鼠右侧颈动脉外膜,左侧作假手术对照。4周后,放免法测定血浆及双侧颈动脉血管紧张素Ⅱ(AngⅡ)浓度,取双侧颈动脉制成光镜标本,病理图像分析系统测颈动脉管腔横截面积(LA)、内弹力层围绕面积(IELA)、外弹力层围绕面积(EELA),评价内膜和中膜增生程度。RT—PCR法检测颈动脉血管紧张素转换酶2 mRNA(ACE2 mRNA)表达,免疫组化法检测ACE2 mRNA、蛋白激酶C-ζ(PKC-ζ)和胞外信号调节激酶1／2(ERKl／2)蛋白表达。结果(1)与WKY组比较,SHR组双侧血管内膜明显增生(P<0．01),中膜面积显著增大[分别为(0．0240±0．0074)mm2和(0．0160±0．0052)mm2,P<0．05;(0．0250±0．0054)mM2和(0．0190±0．0035)mm2, P<0．01)],去外膜侧内膜增生较外膜完整侧显著(P<0．05);与SHR组比较,阿托伐他汀组内膜增生不显著(P<0．01);(2)与外膜完整侧比较,去外膜侧颈动脉AngⅡ浓度和PKC-ζ、ERK1／2蛋白表达均显著增高(P<0．01),ACE2 mRNA和蛋白表达均明显降低(P<0．01);与SHR组比较,阿托伐他汀组颈动脉AngⅡ浓度及PKC-ζ、ERK1／2蛋白表达显著降低(P<0．01),血浆AngⅡ浓度、ACE2 mRNA和蛋白表达显著升高(P<0．01)。结论SHR去除一侧颈动脉外膜后血管内膜增生明显,中膜面积增大,阿托伐他汀可显著改善这种改变。     

阿托伐他汀对高血压大鼠心脏血管紧张素转换酶2表达的影响

目的 观察阿托伐他汀对两肾一夹高血压大鼠心脏血管紧张素转换酶2及心肌重构表达的影响,探讨阿托伐他汀改善心肌重构可能的新作用机制.方法 40只雄性Wistar大鼠随机分为5组,每组8只:假手术组、血管紧张素转换酶2高血压组、缬沙坦组、阿托伐他汀10 mg/(kg·d)组和阿托伐他汀30 mg/(kg·d)组.测定药物干预后血压变化及全心重量、左心室重量、左心室重量指数;免疫组织化学法检测心脏血管紧张素转换酶2蛋白表达;放射免疫法测定心肌组织血管紧张素Ⅱ水平;逆转录聚合酶链反应法检测心脏血管紧张素转换酶2 mRNA表达.结果 (1)高剂量阿托伐他汀组较高血压组血压降低显著(P<0.01).(2)药物干预后高剂量阿托伐他汀组全心重量、左心室重量、左心室重量指数低于高血压组(P<0.05).(3)高剂量阿托伐他汀组较高血压组降低心肌组织血管紧张素Ⅱ浓度显著(P<0.01).(4)缬沙坦组、阿托伐他汀组心脏血管紧张素转换酶2蛋白表达较高血压组增强.(5)逆转录聚合酶链反应显示各组大鼠心脏组织中均有血管紧张素转换酶2 mRNA的表达,缬沙坦组,低剂量、高剂量阿托伐他汀组较高血压组不同程度增高(P<0.05).结论 阿托伐他汀在降低血压的同时,具有改善心肌重构作用,其可能是通过降低心肌组织血管紧张素Ⅱ浓度,增加心脏组织血管紧张素转换酶2蛋白表达,增加心脏组织血管紧张素转换酶2 mRNA表达来实现的.     

阿托伐他汀对自发性高血压大鼠去外膜颈动脉血管阻力的影响

目的:观察阿托伐他汀对自发性高血压大鼠(SHR)去外膜血管重塑的影响和血管反应性。方法:36只16周龄雄性SHR去除一侧颈动脉外膜后,随机分为3组:阿托伐他汀组、缬沙坦组和对照组,分别灌胃给药4和8周后处死。给药前及给药后每2周测量大鼠安静清醒状态下尾动脉收缩压;给药后第4和8周电磁血流仪测量双侧颈动脉血流量。结果:给药前,各组收缩压差异无统计学意义(P>0.05),给药后第4周,阿托伐他汀组收缩压下降,至第6、8周时[(166.17±7.20)、(159.00±11.21)mmHg]较对照组[(183.50±8.46)mmHg]显著下降(P<0.05,P<0.01);去外膜侧第4周血管阻力指数轻度降低,第8周时略大于正常侧;阿托伐他汀组和缬沙坦组[(4.937±0.359),(3.673±0.161)]均较对照组(5.327±0.371)显著减小(P<0.05,P<0.01)。结论:SHR去外膜后早期血管阻力轻度下降,至后期略有升高,阿托伐他汀可显著降低SHR的血管阻力,包括未去外膜血管。     

阿托伐他汀对自发性高血压大鼠血压和心肌血管紧张素Ⅱ1型和2型受体表达的影响

目的　观察阿托伐他汀对自发性高血压大鼠血压和心肌血管紧张素Ⅱ受体 1和血管紧张素Ⅱ受体 2的调节作用。方法　采用免疫组织化学染色法检测心肌血管紧张素Ⅱ受体 1和血管紧张素Ⅱ受体 2蛋白表达 ,原位杂交法测定心肌血管紧张素Ⅱ受体 1和血管紧张素Ⅱ受体 2mRNA表达水平。于给药前和给药后每两周测量大鼠尾动脉收缩压 ,并测定血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇及低密度脂蛋白胆固醇水平。结果　实验前自发性高血压大鼠各组收缩压均显著高于Wistar kyoto大鼠组 (P <0 .0 1)。给药后第 4周和第 6周 ,5 0mg阿托伐他汀组收缩压明显下降 (P <0 .0 1) ,总胆固醇、甘油三酯及低密度脂蛋白胆固醇水平明显降低 (P <0 .0 5 ,P <0 .0 1) ;自发性高血压大鼠对照组心肌血管紧张素Ⅱ受体 1和血管紧张素Ⅱ受体 2蛋白阳性表达及其mRNA表达均明显高于Wistar kyoto大鼠组 (P <0 .0 1) ,6周后 ,5 0mg阿托伐他汀组血管紧张素Ⅱ受体 1蛋白和其mRNA表达明显降低 (P <0 .0 1) ,而血管紧张素Ⅱ受体 2蛋白和其mRNA表达明显高于自发性高血压大鼠对照组 (P <0 .0 1)。结论　阿托伐他汀能降低自发性高血压大鼠的血压 ,并对心肌血管紧张素Ⅱ受体有双重调节作用 ,即使血管紧张素Ⅱ受体 1下调、血管紧张素Ⅱ受体 2上调     

瑞舒伐他汀对大鼠颈动脉球囊损伤后内膜增生及线粒体融合素2表达的影响

目的研究瑞舒伐他汀对大鼠颈动脉球囊损伤后内膜增生及线粒体融合素2表达的影响。方法选取雄性Wistar大鼠32只,随机分为假手术组、模型组、瑞舒伐他汀1组和瑞舒伐他汀2组,每组8只。瑞舒伐他汀1组于术前3天开始每日给予瑞舒伐他汀5 mg/kg灌胃,瑞舒伐他汀2组每日给予20 mg/kg灌胃,模型组以蒸馏水灌胃,随后制备颈动脉球囊损伤模型。建模后14天处死大鼠取颈动脉,HE染色行组织形态学观察,测量内膜/中膜面积比;免疫组织化学、免疫印迹法检测线粒体融合素2和增殖细胞核抗原的表达;依文思蓝染色观察血管内皮修复。结果与假手术组比较,模型组、瑞舒伐他汀1组和瑞舒伐他汀2组血管内膜增生,内膜/中膜面积比值显著增加(P<0.01),增殖细胞核抗原阳性细胞比值显著增加(P<0.01),线粒体融合素2表达显著降低(P<0.01);与模型组比较,瑞舒伐他汀1组、瑞舒伐他汀2组血管内膜/中膜面积比值显著降低(P<0.01),增殖细胞核抗原阳性细胞比值显著降低(P<0.01),线粒体融合素2表达显著增高(P<0.05),且瑞舒伐他汀2组较瑞舒伐他汀1组变化更显著(P<0.01)。依文思蓝染色显示,瑞舒伐他汀1组、瑞舒伐他汀2组再内皮化程度显著好于模型组(P<0.05)。结论瑞舒伐他汀可抑制大鼠颈动脉球囊损伤后内膜增生,同时促进内皮修复,其作用可能与上调线粒体融合素2表达有关。     

氧化型低密度脂蛋白及阿托伐他汀对培养的人脐静脉内皮细胞血管紧张素转化酶2表达的影响

目的探讨氧化型低密度脂蛋白对人血管内皮细胞血管紧张素转化酶2表达的影响及阿托伐他汀的干预作用。方法用正常人新鲜血浆制备氧化型低密度脂蛋白,人脐静脉内皮细胞株复苏、传代后取生长良好3~6代用于实验。分为空白对照组、不同浓度氧化型低密度脂蛋白组(终浓度分别为20、40及80 mg/L)、不同浓度阿托伐他汀组(1、5和10μmol/L)、不同时间组(40 mg/L氧化型低密度脂蛋白和5μmol/L阿托伐他汀分别刺激6、12和24 h及混合刺激组(5μmol/L阿托伐他汀 40 mg/L氧化型低密度脂蛋白刺激24 h)。提取细胞总RNA及蛋白,逆转录聚合酶链反应检测血管紧张素转化酶2 mRNA的表达,免疫印迹法检测血管紧张素转化酶2蛋白的表达。结果氧化型低密度脂蛋白呈剂量和时间依赖性下调血管紧张素转化酶2 mRNA及蛋白的表达。与空白对照组比较,不同浓度氧化型低密度脂蛋白组血管紧张素转化酶2 mRNA的表达分别降低为73%、51%和33%,蛋白的表达降低为81%、50%及32%,不同浓度组间比较差异亦有显著性(P>0.01);氧化型低密度脂蛋白培养6、12和24 h时间组血管紧张素转化酶2 mRNA与对照组比较分别减少为66%、55%和50%,蛋白的表达与对照组比较降低为63%、53%及49%(P>0.01)。不同浓度阿托伐他汀及其培养不同时间组血管紧张素转化酶2 mRNA和蛋白的表达与对照组比较差异无统计学意义。阿托伐他汀能抑制氧化型低密度脂蛋白对血管紧张素转化酶2 mRNA和蛋白表达的下调,mRNA表达增加为1.63倍,蛋白表达增加为1.60倍(P>0.01)。结论氧化型低密度脂蛋白呈剂量和时间依赖性下调血管紧张素转化酶2 mRNA和蛋白的表达,阿托伐他汀能抑制这种作用。     

阿托伐他汀对高血压大鼠动脉血压和血管平滑肌细胞离子泵活性的影响

目的探讨阿托伐他汀对自发性高血压大鼠的动脉血压及血管平滑肌细胞离子泵活性的影响。方法选用12周龄自发性高血压大鼠12只,随机分为阿托伐他汀治疗组(简称阿托伐他汀组,n=6)和蒸馏水组(n=6),并以正常血压大鼠作为对照组。阿托伐他汀组大鼠给以阿托伐他汀[50mg(kg·d)]加适量蒸馏水灌胃12周。观察给药前后大鼠尾动脉血压的变化,测定大鼠血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇浓度,以及胸主动脉平滑肌细胞Na K ATP酶和Ca2 Mg2 ATP酶活性。结果阿托伐他汀组动脉血压显著低于蒸馏水组(161.8±9.9比192.9±10.4,P<0.05);阿托伐他汀组大鼠胸主动脉平滑肌细胞Na K ATP酶和Ca2 Mg2 ATP酶活性明显高于蒸馏水组(5.20±0.54比3.06±0.42,P<0.01;4.62±0.35比2.98±0.17,P<0.05),略低于对照组,而蒸馏水组则显著低于对照组(3.06±0.42比5.92±0.31,P<0.01;2.98±0.17比4.86±0.26,P<0.01)。Na K ATP酶活性、Ca2 Mg2 ATP酶活性与血压呈显著负相关(r=-0.426、r=-0.359,P<0.01)。结论长期应用阿托伐他汀可以显著降低自发性高血压大鼠血压。阿托伐他汀可能通过增高血管平滑肌细胞离子泵活性而影响血压形成的过程。     

球囊损伤大鼠主动脉内皮后血管紧张素Ⅱ2型受体的表达及瑞舒伐他汀的干预作用

目的 通过观察血管内皮损伤后血管紧张素Ⅱ2型受体表达的变化及瑞舒伐他汀对其表达的影响,探讨血管紧张素Ⅱ2型受体在再狭窄中的作用.方法 建立球囊损伤大鼠主动脉内皮模型,并将大鼠随机分为对照组、手术组和瑞舒伐他汀组,每组分别于术后14天、28天取主动脉组织,并行HE染色观察血管内皮厚度的变化,用逆转录聚合酶链反应检测主动脉组织血管紧张素Ⅱ2型受体 mRNA的表达,免疫组织化学法检测主动脉组织血管紧张素Ⅱ2型受体蛋白的表达.结果 大鼠主动脉球囊损伤术后14天及28天血管内皮较对照组显著增厚(P<0.01),瑞舒伐他汀治疗14天及28天大鼠主动脉内膜增生较手术组明显减轻.术后14天及28天,手术组血管紧张素Ⅱ2型受体 mRNA和蛋白表达较对照组显著升高(P<0.05),瑞舒伐他汀组血管紧张素Ⅱ2型受体 mRNA和蛋白表达较手术组增加(P<0.05).结论 瑞舒伐他汀可抑制大鼠主动脉内皮损伤后的血管增生,并上调血管内皮血管紧张素Ⅱ2型受体的表达.     

Ang-Ⅱ对血管内皮细胞线粒体膜电位的影响及阿托伐他汀的保护作用

目的:观察血管紧张素-Ⅱ(Ang-Ⅱ)对血管内皮细胞线粒体膜电位的影响及阿托伐他汀的保护作用.方法:将血管内皮细胞分为:空白对照组(仅给予细胞培养液)、Ang-Ⅱ组(细胞培养液中加入Ang-Ⅱ,使其终浓度为10-7mol/L)、Ang-Ⅱ加小剂量阿托伐他汀组(在单纯Ang-Ⅱ组的基础上加入阿托伐他汀,使阿托伐他汀的终浓度为0.1 μmol/L)、Ang-Ⅱ加大剂量阿托伐他汀组(在单纯Ang-Ⅱ组的基础上加入阿托伐他汀,使阿托伐他汀的终浓度为1 μmol/L).用激光共聚焦显微镜测量各组细胞的线粒体膜电位水平.结果:①Ang-Ⅱ组的线粒体膜电位显著低于空白对照组(P<0.01);②Ang-Ⅱ加阿托伐他汀组的线粒体膜电位显著高于Ang-Ⅱ组(P<0.01).③Ang-Ⅱ加大剂量阿托伐他汀组的线粒体膜电位水平高于Ang-Ⅱ加小剂量阿托伐他汀组(P<0.05).结论:Ang-Ⅱ可引起血管内皮细胞线粒体膜电位的显著降低,而阿托伐他汀可呈剂量依赖性的逆转Ang-Ⅱ的这一作用.     

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。     

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。     

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。     

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.     

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon

Angiography using Prostaglandin El^® was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups:1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of abovementioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.