血管紧张素(1-7)对颈动脉去外膜后内膜和中膜增生的影响

目的 研究血管紧张素(1～7)[Ang(1～7)]对自发性高血压大鼠(SHR)一侧颈动脉外膜去除后血管内膜增生的影响.方法 13周龄雄性SHR 24只去除右侧颈动脉外膜后,随机分为3组(每组8只):SHR对照组、Ang(1～7)组(25 μg/kg·h)和Ang(1～7)拮抗剂(Ang 779)组(25 μg/kg·h);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.采用微渗泵植入技术经颈静脉给药2周,鼠尾袖法测量尾动脉收缩压(SBP),放免法测定血浆及双侧颈动脉血管紧张素Ⅱ(Ang Ⅱ)浓度.取双侧颈动脉制成光镜标本,病理图像分析系统测定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状况.免疫组织化学方法测定双侧颈动脉血管紧张素Ⅱ 1型受体(AT 1R)蛋白、蛋白激酶C-ζ(PKC-ζ)和胞外信号调节激酶1/2(ERK 1/2)蛋白表达.结果 Ang (1～7)明显降低SBP(P＜0.01),与SHR对照组和Ang 779组去外膜侧颈动脉内膜增生比较,Ang (1～7)明显改善因去外膜后引起的血管内膜增殖(P＜0.01).虽然Ang (1～7)未能减少去外膜后颈动脉壁的Ang Ⅱ浓度,但能明显降低颈动脉AT1R蛋白表达(P＜0.01)和减少因去外膜后引起的管壁PKC-ζ及ERK1/2蛋白表达(P＜0.01).结论 Ang(1～7)可显著抑制SHR去外膜后颈动脉的内膜增生,这一作用可能是其通过下调颈动脉AT 1R和减少PKC-ζ及ERK1/2蛋白表达而实现的.     

血管紧张素(1-7)对颈动脉去外膜后内膜和中膜增生的影响

目的研究血管紧张素(1～7)[Ang(1～7)]对自发性高血压大鼠(SHR)一侧颈动脉外膜去除后血管内膜增生的影响。方法13周龄雄性SHR24只去除右侧颈动脉外膜后,随机分为3组(每组8只):SHR对照组、Ang(1～7)组(25μg/kg.h)和Ang(1～7)拮抗剂(Ang779)组(25μg/kg.h);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。采用微渗泵植入技术经颈静脉给药2周,鼠尾袖法测量尾动脉收缩压(SBP),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定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状况。免疫组织化学方法测定双侧颈动脉血管紧张素Ⅱ1型受体(AT1R)蛋白、蛋白激酶C-ζ(PKC-ζ)和胞外信号调节激酶1/2(ERK1/2)蛋白表达。结果Ang(1～7)明显降低SBP(P<0.01),与SHR对照组和Ang779组去外膜侧颈动脉内膜增生比较,Ang(1～7)明显改善因去外膜后引起的血管内膜增殖(P<0.01)。虽然Ang(1～7)未能减少去外膜后颈动脉壁的AngⅡ浓度,但能明显降低颈动脉AT1R蛋白表达(P<0.01)和减少因去外膜后引起的管壁PKC-ζ及ERK1/2蛋白表达(P<0.01)。结论Ang(1～7)可显著抑制SHR去外膜后颈动脉的内膜增生,这一作用可能是其通过下调颈动脉ATR和减少PKC-ζ及ERK1/2蛋白表达而实现的。     

阿托伐他汀对自发性高血压大鼠去外膜颈动脉内膜增生的影响

目的研究阿托伐他汀对自发性高血压大鼠颈动脉外膜去除后血管内膜增生的影响。方法24只13周龄雄性自发性高血压大鼠去除右侧颈动脉外膜后,随机分为自发性高血压组、阿托伐他汀组和缬沙坦组,每组8只;8只同周龄雄性WKY大鼠作为正常对照组。机械和化学法去除大鼠右侧颈动脉外膜,左侧作假手术对照。4周后,放射免疫法测定血浆及双侧颈动脉血管紧张素Ⅱ浓度,取双侧颈动脉制成光镜标本,病理图像分析系统测定颈动脉管腔横截面积、内弹力层围绕面积、外弹力层围绕面积,评价内膜和中膜增生程度。逆转录聚合酶链反应检测颈动脉血管紧张素转化酶2 mRNA表达,免疫组织化学法检测血管紧张素转换酶2蛋白表达。结果自发性高血压大鼠对照组去外膜侧和外膜完整侧血管内膜增生较正常对照组明显(P<0.01),中膜面积显著增大(P<0.05或P<0.01),去外膜侧内膜增生较外膜完整侧显著(P<0.05);阿托伐他汀组较自发性高血压组内膜增生显著降低(P<0.01)。与外膜完整侧比较,去外膜侧颈动脉血管紧张素Ⅱ浓度显著增高(P<0.01),血管紧张素转化酶2mRNA和蛋白表达明显减弱(P<0.01);与自发性高血压组比较,阿托伐他汀组颈动脉血管紧张素Ⅱ浓度显著降低(P<0.01),血浆血管紧张素Ⅱ浓度、血管紧张素转化酶2 mRNA和蛋白表达显著升高(P<0.01)。结论阿托伐他汀可显著抑制自发性高血压大鼠颈动脉去外膜后血管内膜增生,其机制可能是通过上调血管局部血管紧张素转化酶2而实现的。     

阿托伐他汀改善自发性高血压大鼠心室重构的机制

目的研究阿托伐他汀(Ato)对自发性高血压大鼠(SHR)心室重构的作用,并探讨其作用机制。方法16周龄雄性SHR40只,随机分为4组,即SHR组、阿托伐他汀10mg组(Ato-1组)、25mg组(Ato-2组)和50mg组(Ato-3组)。Wistar-Kyoto(WKY)大鼠10只作为正常对照组(WKY组)。Ato-1组、Ato-2组和Ato-3组每日分别用阿托伐他汀10、25、50mg/kg灌胃。实验8周后,测定血液动力学指标,左室质量指数(LVMI),RT-PCR检测心肌转化生长因子β1(TGFβ1) mRNA、Smad3 mRNA和Smad7 mRNA。结果SHR组心室功能障碍,LVMI明显增高[(3.20±0.21)mg/g比WKY:(2.10±0.14)mg/g](P<0.01),心肌TGFβ1 mRNA(125.4±3.2比WKY:73.6±2.1,P<0.01)、Smad3 mRNA(6.40±0.43比WKY:3.10±0.75,P<0.01)增加,心肌Smad7 mRNA(2.30±0.86比WKY:4.10±1.23,P<0.01)降低。Ato呈剂量依赖性改善左室功能,降低SHRLVMI,降低心肌TGFβ1 mRNA、Smad3 mRNA,增加心肌Smad7 mRNA。结论阿托伐他汀可能通过下调心肌TGFβ1 mRNA、Smad3 mRNA和上调心肌Smad7 mRNA,改善SHR心室重构。     

伊贝沙坦对自发性高血压大鼠肾脏血管紧张素转换酶2基因表达的影响

目的观察自发性高血压大鼠(SHR)肾脏血管紧张素转换酶2(ACE2)的表达,探讨伊贝沙坦对SHR肾脏ACE2 mRNA表达的调节作用。方法20只14周龄雄性SHR分为SHR组和伊贝沙坦组,各10只。伊贝沙坦组每只大鼠予以伊贝沙坦50 mg·kg-1·d-1灌胃,给药时间12周。同时取14周龄雄性京都种Wistar大鼠10只为对照组。SHR组和对照组给予等量蒸馏水灌胃12周。采用免疫组织化学和逆转录聚合酶链反应检测各组大鼠肾脏ACE2表达,利用放射免疫测定法检测各组大鼠血浆血管紧张素(Ang)Ⅱ浓度。结果与对照组比较,SHR组ACE2 mRNA表达显著减少(0．72±0．11对1．11±0．15);与SHR组比较,伊贝沙坦组经12周治疗后,ACE2 mRNA表达明显提高(1．03±0．13对0．72±0．11),均为P<0．05。SHR肾脏ACE2 mRNA表达与血浆AngⅡ浓度成正相关(r=0．83,P<0．05)。结论ACE2在高血压大鼠肾脏表达显著减少,可能是高血压病理生理变化之一。AngⅡ-1型受体阻滞剂伊贝沙坦上调SHR肾组织ACE2 mRNA表达,提示这可能是该药物反向调节过度激活的肾素-血管紧张素系统又一新途径。     

阿托伐他汀改善心室重构作用及其抗氧化机制研究

目的研究阿托伐他汀改善心室重构作用及其抗氧化机制。方法选用16周龄雄性自发性高血压大鼠(SHR)18只,随机分为3组,每组6只:阿托伐他汀组、阳性对照组(缬沙坦组)和阴性对照组(SHR组),另选同周龄雄性Wistar-Kyoto大鼠(WKY)6只作为正常对照组(WKY组),给药6周后测定全心重量(HW)、左心室重量(LVW)、左心室重量指数(LVWI)、心肌羟脯氨酸含量和胶原蛋白含量,透射电镜观察心肌超微结构,同时检测血清和心肌组织超氧化物化酶(SOD)活力、丙二醛(MDA)含量。结果给药6周后,阿托伐他汀组HW、LVW、LVWI、心肌羟脯氨酸含量和胶原蛋白含量明显低于SHR组(P<0.05);电镜显示阿托伐他汀组心肌与SHR对照组比较,肌原纤维较清晰,排列整齐,横纹清楚,间质胶原纤维无明显增生;阿托伐他汀组血清和心肌组织SOD活力明显高于SHR组、MDA含量明显低于SHR组(P<0.05)。结论阿托伐他汀有明显改善心室重构的作用,其机制可能与其抗氧化作用有关。     

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。     

阿托伐他汀改善自发性高血压大鼠心室重构的机制

目的 研究阿托伐他汀(Ato)对自发性高血压大鼠(SHR)心室重构的作用,并探讨其作用机制.方法 16周龄雄性SHR 40只,随机分为4组,即SHR组、阿托伐他汀10 mg组(Ato-1组)、25 mg组(Ato-2组)和50 mg组(Ato-3组).Wistar-Kyoto(WKY)大鼠10只作为正常对照组(WKY组).Ato-1组、Ato-2组和Ato-3组每日分别用阿托伐他汀10、25、50 mg/kg灌胃.实验8周后,测定血液动力学指标,左室质量指数(LVMI),RT-PCR检测心肌转化生长因子β1(TGFβ1)mRNA、Smad3 mRNA和Smad7 mRNA.结果 SHR组心室功能障碍,LVMI明显增高[(3.20±0.21)mg/g比WKY:(2.10±0.14)mg/g](P＜0.01),心肌TGFβ1 mRNA(125.4±3.2比WKY:73.6±2.1,P＜0.01)、Smad3 mRNA(6.40±0.43比WKY:3.10±0.75,P＜0.01)增加,心肌Smad7 mRNA(2.30±0.86比WKY:4.10±1.23,P＜0.01)降低.Ato呈剂量依赖性改善左室功能,降低SHRLVMI,降低心肌TGFβ1 mRNA、Smad3 mRNA,增加心肌Smad7 mRNA.结论 阿托伐他汀可能通过下调心肌TGFβ1 mRNA、Smad3 mRNA和上调心肌Smad7 mRNA,改善SHR心室重构.     

氯沙坦对自发性高血压大鼠心脏血管紧张素转换酶2-血管紧张素(1～7)-MAS-ERK通路的影响

目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌中血管紧张素转换酶2(ACE2)-血管紧张素(1～7)[Ang(1-7)]-MAS-ERK通路的影响。方法30周龄SHR随机分为SHR组(n=11)、氯沙坦组[氯沙坦灌胃30mg/(kg·d),n=12],以Wistar大鼠(WKY)作正常对照(n=12)。处理12周后,应用放射免疫法检测大鼠血浆及心肌组织血管紧张素Ⅱ(AngⅡ)、血管紧张素(1～7)[Ang-(1-7)]水平;采用RT-PCR法检测各组大鼠心肌血管紧张素转换酶(ACE)、ACE2和MAS受体mRNA水平;采用Western blot法检测ACE、ACE2和磷酸化细胞外信号调节激酶(pERK1/2)蛋白表达水平。结果用药12周后,氯沙坦组血压明显低于SHR组[(164.3±21.6)比(241.3±24.5)mmHg,P<0.01];SHR组心肌ACE mRNA和蛋白表达水平显著高于WKY组,而ACE2 mRNA和蛋白表达、心肌MAS受体mRNA表达水平明显低于WKY组,差异有统计学意义(P<0.01);氯沙坦组ACE2 mRNA和蛋白表达、MAS mRNA表达水平高于SHR组(P<0.01),心...     

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。     

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.     

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.     

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.     

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。     

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     

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。     

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.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。