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。     

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。     

阿托伐他汀逆转腹主动脉缩窄型高血压大鼠心肌重构的机制

目的 观察阿托伐他汀对腹主动脉缩窄型高血压大鼠血清血管紧张素(1-7)浓度及左心室肥厚心肌组织中p-ERK1/2表达水平的影响,探讨阿托伐他汀逆转心肌重构的可能机制.方法 50只SD雄性大鼠随机分为5组:假手术组、模型组、10 mg/(kg·d)阿托伐他汀组、30 mg/(kg·d)阿托伐他汀组及缬沙坦组,每组10只.术后第1天,将阿托伐他汀研磨成粉,溶于少量蒸馏水中制成悬液,采用灌胃法给药;假手术组和模型组大鼠均用等量生理盐水灌胃.每日上午定时一次,共4周.鼠尾容积法测定药物干预前及干预后2周、4周的血压变化.4周后处死大鼠,测定大鼠体重、左心室重量、左心室重量指数;HE染色检测心肌细胞平均直径;酶联免疫吸附法测定血清血管紧张素(1-7)浓度;免疫印迹法检测心肌p-ERK1/2蛋白表达水平.结果 30 mg/(kg·d)阿托伐他汀组和10 mg/(kg·d)阿托伐他汀组收缩压明显低于模型组(P<0.01),30 mg/(kg·d)阿托伐他汀组收缩压明显低于10mg/(kg·d)阿托伐他汀组(P<0.01),缬沙坦组收缩压明显低于30 mg/(kg·d)阿托伐他汀组和10 ms/(kg·d)阿托伐他汀组(P<0.01);假手术组、30 mg/(kg·d)阿托伐他汀组、10 mg/(kg·d)阿托伐他汀组及缬沙坦组左心室重量指数明显低于模型组(P<0.01),30 mg/(kg·d)阿托伐他汀组左心室重量指数明显低于10 mg/(kg·d)阿托伐他汀组(P<0.05);假手术组、30 mg/(kg·d)阿托伐他汀组及缬沙坦组心肌细胞平均直径明显低于模型组(P<0.01).10 mg(kg·d)阿托伐他汀组与模型组无差异(P>0.05);10 mg/(kg·d)阿托伐他汀组、30 mg/(kg·d)阿托伐他汀组及缬沙坦组血清Ang-(1-7)浓度显著高于模型组(P<0.01),30 mg/(kg·d)阿托伐他汀组及缬沙坦组血清Ang.(1-7)浓度明显高于10 mg/(kg·d)阿托伐他汀组(P<0.05);10 mg/(kg·d)阿托伐他汀组、30mg/(kg·d)阿托伐他汀组及缬沙坦组p-ERK1/2蛋白表达水平显著低于模型组(P<0.01),但高于假手术组.结论 阿托伐他汀对腹主动脉缩窄型高血压大鼠心肌重构具有逆转作用,其机制与降低压力负荷诱导的心肌肥厚组织中p-ERK1/2 蛋白表述水平有关.     

阿托伐他汀增加高血压患者外周血内皮祖细胞数量

目的观察阿托伐他汀对无脂代谢紊乱的高血压患者外周血内皮祖细胞(EPCs)数量及血压的影响。方法原发性高血压患者38例随机分为单用常规降压药物组(常规组,n=18)和常规降压药物与阿托伐他汀(20mg 睡前)联合用药组(联合组,n=20)。8例健康志愿者口服阿托伐他汀8周作为对照组(n=8)。于治疗前和治疗后8周分别测血压并抽取外周血进行 EPCs 的分离培养,第10天对 EPCs 进行鉴定并于倒置相差显微镜下计数内皮祖细胞克隆形成单位(EPC-CFU)以评估外周血 EPCs 水平。结果 1)常规组和联合组治疗前后收缩压均有显著下降,分别为(165.8±10.3)vs(132.7±10.3)mmHg 和(163.7±10.2)vs(127.9±10.1)mmHg;加用阿托伐他汀血压下降幅度较单用降压药大[(35.7±3.4)vs(33.1±2.4)mmHg,P<0.05]。对照组服药前后收缩压的差异无统计学意义(114.2±18.4)vs(108.4±21.6)mmHg。2)常规降压药8周后 EPC-CFU 从(8.8±2.0)升为(12.1±2.2);联合用药后 EPC-CFU 从(9.2±1.9)升为(13...     

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。     

阿托伐他汀防止压力负荷导致心肌肥厚的抗炎机制

背景他汀类药物具有多种临床功效包括调脂、改善内皮功能等,有报道表明他汀类药物可以防治压力负荷增大引起的心肌肥厚,但其确切机制尚不明确.目的 观察阿托伐他汀对压力负荷导致的心肌肥厚的保护作用,并探讨其可能的机制.方法 缩窄腹主动脉的方法 制备大鼠心肌肥厚模型.Wistar大鼠随机分为未治疗组(n=10)、阿托伐他汀组(n=10),假手术组(n=10)、空白对照组(n=10).阿托伐他汀组术后每日灌胃给予阿托伐他汀2 mg/kg,余各组给予生理盐水灌胃.实验结束后处死大鼠,测定其心脏/体质量、左心室/体质量及病理切片左室壁厚度和心肌细胞直径.通过RT-PCR方法 检测心肌组织中心肌营养素1(CT-1)和白细胞介素18(IL-18)的表达.结果 未治疗组[(174±9)mmHg]收缩压明显高于对照组[(112±15)mmHg](P<0.01),虽然阿托伐他汀组[(169±8)mmHg]血压仅有不明显下降(P>0.05),但能减轻心脏质量/体质量[阿托伐他汀:(3.2±0.2)×10-3比未治疗组(4.2±0.29)×10-3,P<0.05]、左心室质量/体质量[阿托伐他汀:(2.2±0.09)×10-3比未治疗组(2.8±0.27)×10-3,P<0.05]、阿托伐他汀还降低心肌中炎症因子,如CT-1[阿托伐他汀:(0.244±0.042)比未治疗组(0.371±0.054),P<0.05]、IL-18 mRNA含量[阿托伐他汀:(0.231±0.071)比未治疗组(0.462±0.038),P<0.05]及心肌细胞直径[阿托伐他汀:(9.74±0.38)μm比未治疗组(10.94±0.65)μm,P<0.05].结论 阿托伐他汀对压力负荷导致的心肌肥厚有明显的保护作用,同时伴有炎症因子水平的降低,说明阿托伐他汀的保护作用可能与其抗炎作用有关.     

阿托伐他汀增加高血压患者外周血内皮祖细胞数量

目的 观察阿托伐他汀对无脂代谢紊乱的高血压患者外周血内皮祖细胞(EPCs)数量及血压的影响.方法 原发性高血压患者38例随机分为单用常规降压药物组(常规组,n=18)和常规降压药物与阿托伐他汀(20 mg睡前)联合用药组(联合组,n=20).8例健康志愿者口服阿托伐他汀8周作为对照组(n=8).于治疗前和治疗后8周分别测血压并抽取外周血进行EPCs的分离培养,第10天对EPCs进行鉴定并于倒置相差显微镜下计数内皮祖细胞克隆形成单位(EPC-CFU)以评估外周血EPCs水平.结果 1)常规组和联合组治疗前后收缩压均有显著下降,分别为(165 8±10 3)vs(132 7±10 3)mmHg和(163 7±10 2) vs(127 9±10 1)mmHg;加用阿托伐他汀血压下降幅度较单用降压药大[(35 7±3 4)vs(33 1±2 4)mmHg,P<0 05].对照组服药前后收缩压的差异无统计学意义(114 2±18 4)vs(108 4±21 6)mmHg.2)常规降压药8周后EPC-CFU从(8 8±2 0)升为(12 1±2 2);联合用药后EPC-CFU从(9 2±1 9)升为(13 6±2 2)个.两组EPC-CFU改变值[(3 3±0 6)vs(4 5±1 1)]的差异有统计学意义(P<0 05).对照组服药前后EPC-CFU为(13 2±2 8)vs(16 2±3 5).3)联合组治疗前后血压下降幅度与EPC-CFU改变值呈正相关(r=0 581,P=0 007).结论 高血压可减少外周血EPCs数量,在应用常规降压药物基础上加用阿托伐他汀可增加外周血EPCs数量并进一步降低血压.     

冠心病与颈动脉粥样硬化的相关性及应用阿托伐他汀干预的疗效

目的探讨颈动脉粥样硬化与冠心病的相关性及应用阿托伐他汀治疗颈动脉斑块的疗效。方法选取冠心病患者80例,根据患者是否使用阿托伐他汀治疗分为他汀组及非他汀组,各40例,选取非冠心病者30例作为对照组。应用超声测量患者颈动脉内中层厚度(CIMT)并计算斑块积分,比较三组患者治疗3、6个月后CIMT及斑块积分变化情况以及斑块检出率。结果冠心病患者CIMT及斑块积分[(1.16±0.15)mm,8.12±5.18]明显高于对照组[(0.85±0.20)mm,2.65±1.68,P<0.05],冠状动脉重度狭窄者[(1.18±0.13)mm,9.27±3.26]与中度狭窄者[(1.12±0.15)mm,7.69±4.52],中度狭窄者与轻度狭窄者[(1.01±0.13)mm,5.28±4.39]差异均有统计学意义(均P<0.05)。他汀组及非他汀组CIMT[(1.16±0.14),(1.15±0.16)mm]及斑块积分(8.45±4.35,7.85±5.26)明显高于对照组(P<0.05)。他汀组在应用阿托伐他汀治疗3个月后,CIMT及斑块积分[(1.13±0.16)mm,6.88±3.58]虽低于治疗前及同期非他汀组[(1.14±0.15)mm,7.18±4.59],但差异均无统计学差异(均P>0.05);在应用阿托伐他汀治疗6个月后,CIMT[(1.06±0.16)mm]及斑块积分(4.39±4.12)明显低于治疗3个月及治疗前(P<0.05),也明显低于同期非他汀组[(1.14±0.13)mm,6.89±4.73,P<0.05]。非他汀组及对照组在相关治疗3、6个月后CIMT及斑块积分差异无统计学意义(P>0.05)。结论颈动脉粥样硬化程度与冠状动脉粥样硬化程度息息相关,是冠心病高危预测因素之一。长期应用阿托伐他汀可以有效逆转血管狭窄,减少心血管事件发生。     

阿托伐他汀改善自发性高血压大鼠的心肌脂质代谢和抑制心肌肥厚

目的通过研究阿托伐他汀对自发性高血压大鼠(SHR)心肌中PPARα、CPTⅠ表达和心肌脂质代谢变化及心肌肥厚指标的影响,探讨阿托伐他汀对SHR心肌肥厚的改善作用及其机理。方法观察阿托伐他汀灌胃10周的SHR心肌肥厚指标、血清和心肌游离脂肪酸含量及心肌PPARα、CPTⅠmRNA表达的改变。结果与WKY(n=6)比较,SHR(n=6)心肌中PPARαmRNA(0.285±0.062比WKY:0.478±0.093,P<0.01)与CPTⅠmRNA(0.795±0.139比WKY:1.115±0.109,P<0.01)表达减少,血清及心肌中游离脂肪酸含量增加,分别为[(798.2±38.0比WKY:354.7±27.7)nmol/L,P<0.01]和[(635.0±77.4比WKY:245.3±47.3)nmol/L,P<0.01],心室质量指数增加(VWI)[(3.16±0.08比WKY:2.99±0.10)g/kg,P<0.05],心肌细胞直径增加(TDM)[(21.3±1.3比WKY:18.18±0.75)μm,P<0.01];阿托伐他汀50mg/kg·d治疗10周后(n=6),心肌中PPARα、CPTⅠmRNA表达增加,心肌中游离脂肪酸含量明显降低、VWI降低,TDM降低。结论阿托伐他汀能够增加心肌中PPARα、CPTⅠmRNA表达,降低心肌中游离脂肪酸含量,改善心肌脂质代谢障碍,可能是其抑制心肌肥厚发生与发展的机制之一。     

不同剂量阿托伐他汀对高血压合并高脂血症患者血压、血脂及血管内皮功能的影响

目的:探讨不同剂量阿托伐他汀对高血压合并高脂血症患者的血压、血脂及血管内皮功能的影响。方法:2017年1月至10月间我院心内科收治的100例高血压合并血症患者被随机均分为阿托伐他汀低剂量组(阿托伐他汀10mg/d)和高剂量组(阿托伐他汀20mg/d),两组均同时接受常规治疗,疗程8周。另选择50例来我院体检的健康者为健康对照组。治疗前后测量比较三组血压、血脂、NO、ET-1和hsCRP等水平。结果:与低剂量组比较,高剂量组治疗8周后SBP[(147.33±11.37)mmHg比(140.51±10.85)mmHg]、DBP[(96.35±7.38)mmHg比(92.56±6.83)mmHg]、TG[(2.38±0.59) mmol/L比(1.55±0.46)mmol/L]、TC[(6.48±0.58)mmol/L比(5.38±0.52)mmol/L]、LDL-C[(4.24±0.41) mmol/L比(3.26±0.42) mmol/L]、hsCRP[(6.38±1.53)mg/L比(5.05±1.38)mg/L]、ET-1[(80.78±18.54)pg/ml比(73.22±10.98) pg/ml]水平均显著降低,HDL-C [(1.13±0.27) mmol/L比(1.29±0.25)mmol/L]水平显著升高,P0.05或0.01。结论:不同剂量阿托伐他汀对高血压合并高脂血症患者的疗效不同,20mg降低血压、血脂及改善血管内皮功能及降低炎性因子水平的效果要显著强于10mg,值得推广。     

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.