知芪益肾汤对实验性糖尿病大鼠肾功能的作用机制研究

目的探讨知芪益肾汤对糖尿病肾病（DN）大鼠肾脏的保护作用及其发生机制。方法腹腔注射链尿佐菌素（STZ）建立糖尿病模型,检测血糖、UAER、Ccr,应用免疫组化法检测CTGF及TGF-β1的蛋白表达。结果知芪益肾汤组UAER、Ccr显著低于糖尿病组（P〈0.01）,且肾脏CTGF及TGF-β1阳性表达相对面积较糖尿病组明显下调（P〈0.01）。结论早期应用知芪益肾汤对STZ诱导的糖尿病大鼠有肾保护作用。     

小剂量厄贝沙坦治疗2型糖尿病早期肾病的临床研究

目的探讨血管紧张素受体拮抗剂厄贝沙坦对2型糖尿病肾病尿白蛋白排泄率（UAE）的影响。方法28例患者在原有治疗基础上口服厄贝沙坦40mg,每日1次,治疗6个月。于治疗前及治疗6个月后测定患者UAE、血压、血糖、血脂、体重指数（BMI）及内生肌酐清除率（Ccr）。结果小剂量厄贝沙坦治疗前后患者血糖、血脂、血压、BMI和Ccr均无显著变化（P〉0.05）,治疗后UAE较治疗前显著下降（P〈0.01）,且下降程度与初始UAE水平成负相关（r=-0.990,P〈0.01）。结论除有降血压效应之外,厄贝沙坦对2型糖尿病肾病也有肾脏保护作用。     

沃丽汀对糖尿病肾病大鼠CGRP与VEGF的影响

目的观察沃丽汀对糖尿病肾病大鼠肾脏的保护作用，并探讨其作用机制。方法将雄性Wistar大鼠随机分为正常对照组（NC组），糖尿病肾病组（DN组）和沃丽汀治疗组（D＋J组）各10只。DN组与D＋J组采用链脲佐菌素（STZ）诱导制作糖尿病大鼠模型。模型制作成功后，NC组与DN组给予0.9%氯化钠溶液10 mL•kg 1灌胃，D＋J组于模型制作成功后第3天开始给予沃丽汀灌胃，0.9 mg•kg 1•d 1。8周后采用放免法检测大鼠血浆降钙素基因相关肽（CGRP）含量，免疫组织化学方法检测肾小球血管内皮生长因子（VEGF）表达情况，同时检测24 h尿清蛋白排泄率（24 hUAER）、尿肌酐清除率（Ccr）、肾重指数（KMI）、体重及血糖。结果与NC组比较，DN组血浆中CGRP水平、Ccr及体重均显著降低（均P＜0.01），24 hUAER、KMI、肾脏VEGF表达及血糖均显著升高（均P＜0.01）。与DN组比较，D＋J组CGRP水平差异无显著性，Ccr显著升高（P＜0.05），肾脏VEGF表达显著降低（P＜0.01）。结论沃丽汀对糖尿病肾病大鼠血浆CGRP水平无显著影响，但能抑制肾组织VEGF表达，一定程度上延缓糖尿病肾病发展。     

贝那普利和厄贝沙坦对糖尿病肾病肾组织表达KLK1的影响

目的探讨贝那普利和厄贝沙坦阻断肾素 血管紧张肽系统（RAS）对糖尿病肾病（DN）肾组织表达激肽释放酶1（KLK1）的影响。方法将10只雄性SD大鼠以普通饲料喂养,作为正常对照组（A组）。将雄性SD大鼠以高糖高脂饮食加小剂量链脲佐菌素诱导DN模型,造模成功后随机分为4组,每组10只：DN组（B组）、贝那普利干预组（C组）、厄贝沙坦干预组（D组）、贝那普利联用厄贝沙坦干预组（E组）。干预8周后测定肾质量/体质量、24 h 尿蛋白与血肌酐、尿素氮等评估肾功能情况,免疫组化半定量测定肾组织KLK1蛋白表达水平。结果B、C、D、E组大鼠肾组织表达KLK1蛋白水平显著高于A组（P＜0.01）;C、D、E组大鼠肾组织表达KLK1蛋白水平显著高于B组（P＜0.05）;E组表达KLK1高于C组和D组（P＜0.01）;C组和D组差异无统计学意义。结论DN大鼠肾组织表达KLK1蛋白高于正常大鼠,贝那普利和厄贝沙坦通过阻断RAS上调肾脏KLK1蛋白表达。     

厄贝沙坦片联合盐酸贝尼地平片治疗高血压肾病的临床疗效

目的：探讨厄贝沙坦片联合盐酸贝尼地平片治疗高血压肾病的临床疗效。方法选取2011年1月—2014年1月魏县人民医院收治的高血压肾病患者132例,采用随机数字表法将患者分为厄贝沙坦组（49例）,贝尼地平组（43例）,联合治疗组（40例）。厄贝沙坦组患者予以厄贝沙坦片治疗;贝尼地平组患者予以盐酸贝尼地平片治疗;联合治疗组患者予以厄贝沙坦片联合盐酸贝尼地平片治疗。观察3组患者治疗前后血压、肾功能〔24h 尿蛋白定量、血肌酐（Scr）、血尿素氮（BUN）、内生肌酐清除率（Ccr）〕及不良反应发生情况。结果治疗前3组患者收缩压、舒张压、24h 尿蛋白定量、Scr、BUN、Ccr 比较,差异无统计学意义（P ﹥0.05）;治疗后3组患者收缩压、舒张压、24h 尿蛋白定量、Scr、BUN、Ccr 比较,差异有统计学意义（ P ﹤0.05）;联合治疗组患者收缩压、舒张压、24h 尿蛋白定量、Scr、BUN 低于厄贝沙坦组和贝尼地平组,Ccr 高于厄贝沙坦组和贝尼地平组,差异有统计学意义（P ﹤0.05）;3组患者不良反应发生率比较,差异无统计学意义（P ﹥0.05）。结论厄贝沙坦联合贝尼地平治疗高血压肾病的临床疗效显著,可改善患者临床症状,且不良反应小。     

辛伐他汀联合厄贝沙坦治疗早期糖尿病肾病80例观察

目的糖尿病肾病（DN）是糖尿病最常见的微血管并发症,是终末期肾病的主要病因,积极控制糖尿病肾病尿微量白蛋白的进一步增加,可延缓糖尿病肾病的进展。本文通过观察我院80例早期糖尿病肾病治疗前后尿微量白蛋白（UAER）、TC、TG、LDL-C来探讨治疗早期糖尿病肾病的方法。方法将80例早期糖尿病肾病（DN）患者随机分成3组,对照组为积极控制血糖、血压;厄贝沙坦组为在此基础上加口服厄贝沙坦150mg.d^-1;厄贝沙坦＋辛伐他汀组在厄贝沙坦组基础上加辛伐他汀20mg.d^-1。结果两治疗组治疗后较对照组尿白蛋白排泄率均明显减少（P〈0.05）,厄贝沙坦＋辛伐他汀组减少程度较厄贝沙坦组更明显（P〈0.05）;厄贝沙坦＋辛伐他汀组治疗后血脂水平明显下降（P〈0.05）。结论表明早期DN患者应用辛伐他汀联合厄贝沙坦治疗能有效延缓肾损害进展。     

芪母益肾煎抗实验性糖尿病肾病作用及其可能机制

目的 探讨芪母益肾煎对实验大鼠糖尿病肾病（DN）的治疗作用及其可能机制.方法 Wistar健康大鼠24只，随机分为对照组、模型组、中药组，每组8只.用链脲佐菌素（STZ）诱导糖尿病大鼠模型.8 wk后测BG、BUN、Ccr、Scr、UPER、TG、TC.处死Wistar大鼠，取其肾脏，观察肾脏组织形态改变，用免疫组化检测血管内皮生长因子（VEGF）和胰岛素样生长因子-1（IGF-1）蛋白表达水平.结果 中药组VEGF和IGF-1的表达量明显低于模型组（P＜0.01），血脂明显低于模型组（P＜0.01），并且BUN、UPER、Scr低于模型组（P＜0.05），肾脏损伤明显轻于模型组.结论 在一定程度上，芪母益肾煎具有抗实验性糖尿病肾病和保护肾功能的作用，其可能机制是抑制VEGF和IGF-1在肾脏中的表达.     

厄贝沙坦治疗糖尿病早期肾病60例的疗效观察

目的：探讨厄贝沙坦对糖尿病肾病（DN）患者的肾脏保护作用。方法：将DN患者60例,随机分为3组：（1）对照组,（2）厄贝沙坦治疗（B组）．（3）厄贝沙坦双倍剂量治疗（C组）。对所有纳入对象在治疗前后测定血压、血脂、糖化血红蛋白（HbAlc）、24小时尿白蛋白排泄率（UAER）、内生肌酐清除率。结果：B组和C组治疗前后UAER水平明显下降（P〈0．05）;3组治疗后C组与其他两组比较UAER降低更显著,内生肌酐清除率显著升高（P〈0．05）。结论：厄贝沙坦有独立于降压之外的肾脏保护作用,能延缓DN的进展,建议DN早期患者常规使用。     

低分子肝素钠联合厄贝沙坦对78例糖尿病肾病的疗效观察

目的观察低分子肝素钠联合厄贝沙坦治疗糖尿病肾病显性蛋白尿的效果。方法将78例糖尿病肾病蛋白尿患者用随机分为2组,在综合疗法控制血糖基础上,对照组26例口服厄贝沙坦150mg/d,治疗组52例口服厄贝沙坦150mg/d,同时皮下注射低分子肝素钠5000IU/d,疗程均为8周。结果观察用药前后24h尿蛋白定量、尿白蛋白排泄（UAER）、血肌酐（SCr）、尿素氮（BUN）、空腹血糖。结果2组治疗后24h尿蛋白定量、UAER均显著下降（P〈0.05）,组间比较,治疗组疗效优于其对照组（P〈0.05）;2组在SCr、BUN、空腹血糖治疗前后及组间比较差异无统计学意义（P〉0.05）。结论低分子肝素钠联合厄贝沙坦对糖尿病肾病临床蛋白尿的治疗有明显效果,有效率治疗组92.31%明显优于对照组69.23%（P〈0.05）,对糖尿病肾病患者的血肌酐、尿素氮、血糖均无影响。     

厄贝沙坦联合百令胶囊治疗早期糖尿病肾病的疗效观察

目的探讨厄贝沙坦联合百令胶囊治疗早期糖尿病肾病的疗效。方法 64例2型早期糖尿病肾病患者随机分为对照组和治疗组各32例,对照组应用厄贝沙坦（150mg/d）,治疗组应用厄贝沙坦（150mg/d）联合百令胶囊（3.0g/d）治疗,疗程12周。观察治疗前后2组患者的24h尿蛋白定量、血清尿素氮、肌酐、空腹血糖等水平,同时观察治疗期间有无严重不良反应。结果 64例患者治疗期间无严重不良反应发生。2组治疗后24h尿蛋白定量均降低,与本组治疗前比较,差异有统计学意义（P〈0.05或〈0.01）,治疗组比对照组降低更显著（P〈0.05）。2组治疗后血清尿素氮、肌酐、空腹血糖水平较治疗前略有下降,差异无统计学意义（P〉0.05）。结论厄贝沙坦联合百令胶囊能明显降低早期糖尿病肾病患者24h尿蛋白水平,减轻肾脏损伤,较单用厄贝沙坦疗效显著。     

联合检测血清Hcy和Lp (a)与UA对冠心病患者预后评估的价值探讨

目的 探讨血清同型半胱氨酸(Hcy)、脂蛋白a[Lp(a)]和尿酸(UA)联合检测对冠状动脉粥样硬化性心脏病(CHD)的病情及预后的评估价值.方法 选取CHD患者96例(疾病组)和体检健康者50例(正常组),采集清晨空腹静脉血,检测血清Hcy、Lp(a)和UA.观察组(疾病组)随访1年,91例病情缓解或无进展,5例发展为急性心肌梗死(AMI).采用受试者工作特征曲线分析血清Hcy、Lp(a)和UA单独及联合检测对CHD患者预后的诊断价值.结果 疾病组血清Hcy、Lp(a)和UA水平均高于正常组(均P＜ 0.05);随访发展为AMI患者入院时血清Hcy、Lp(a)和UA水平均高于病情缓解或无进展者(均P＜ 0.01).Hcy、Lp(a)和UA联合检测对CHD患者预后评估的AUC为0.855、敏感性为89.4％、特异性为80.2％、阳性预测值86.4％,均高于3项单独检测.结论 冠状动脉粥样硬化性心脏病患者血清Hcy、Lp (a)和UA水平均升高,其水平变化可反映冠状动脉粥样硬化性心脏病病情,三者联合检测可提高对患者预后的判断价值.     

Comparison of the inhibition potential of parthenolide and micheliolide on various UDP-glucuronosyltransferase isoforms

Abstract

1. Parthenolide (PTL) and micheliolide (MCL) are sesquiterpene lactones with similar structures, and both of them have been reported to exhibit multiple biochemical and pharmacological activities. This study aims to investigate the inhibition of these two compounds on the activity of UDP-glucuronosyltransferases (UGTs).

2. In vitro incubation mixture for recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition kinetics (including inhibition type and parameters) were determined, and in silico docking was employed to elucidate the inhibition difference between PTL and MCL on UGT1A1.

3. MCL showed no inhibition toward all the UGT isoforms, and PTL showed strong inhibition toward UGT1A1. The half-maximal inhibitory concentration (IC₅₀) of PTL on the activity of UGT1A1 was determined to be 64.4?μM. Inhibition kinetics determination showed that PTL exerted noncompetitive inhibition toward UGT1A1, and the inhibition kinetic constant (K_i) was determined to be 12.1?μM. In silico docking method has been employed to show that hydrogen bonds between PTL and the activity cavity of UGT1A1 contributed to the stronger inhibition of PTL on the activity of UGT1A1 than MCL. In conclusion, PTL can more easily induce drug–drug interaction (DDI) with clinical drugs mainly undergoing UGT1A1-catalyzed glucuronidation.

     

The effect of halothane on the stability of Ca2+ transport activity of isolated fragmented sarcoplasmic reticulum

The effects of the inhalation anaesthetic agent, halothane (CF₃CHBrCl), on the stability of the calcium transport system of isolated rabbit white skeletal muscle sarcoplasmic reticulum have been studied. Calcium transport activity was unaffected when suspensions of sarcoplasmic reticulum vesicles were preincubated at 37° and pH 6.8 at concentrations of halothane below 5 mM, but was progressively inactivated at higher concentrations. (Ca²⁺,Mg²⁺)-ATPase activity was enhanced during inactivation of calcium transport. At pH 6.3 and 5.8, halothane increased the first order rate constants of inactivation and effects were noted in the anaesthetic range of concentration (1–2 mM). The inulin inaccessible space of membrane vesicles did not change appreciably during the period of treatment with halothane, excluding increased permeability as an explanation of the inhibition of calcium accumulation. Inactivation was irreversible and highly temperature dependent, with an activation energy of 52.7 kcal/mol. Calcium ions had a protective effect against inactivation (K_{0.5 (Ca2+) = 1.5 × 10^?6M}), as did ATP ($\text{K}{}_{\mathrm{<mtext>0.5\; (</mtext><mtext>Atp</mtext><mtext>)</mtext>}}\text{? 10}{}^{\mathrm{?6}}\text{M}$). It is concluded that mild acid conditions and halothane act synergistically during inactivation of the calcium transport system of sarcoplasmic reticulum membranes. These studies suggest that halothane interacts with the (Ca²⁺, Mg²⁺)-ATPase protein at the ATP-specific binding site or that it disrupts protein-lipid associations in the membrane. In either case the destabilizing effect of halothane may be modified by the conformational state of the protein.     

运动对糖尿病肾病早期相关指标的影响

目的研究运动对糖尿病肾病(DN)早期诊断指标如尿微量白蛋白(Alb)、尿转铁蛋白(TRF)、尿铜蓝蛋白(CP)、尿视黄醇结合蛋白(RBP)的影响。方法对45名2型糖尿病患者做次极量运动试验,运动前后分别测尿Alb、尿TRF、尿CP、尿RBP及尿肌酐(Cr),并以26名非糖尿病人做对照。结果糖尿病患者运动后尿Alb/Cr较运动前增加(P>0.01),尿TRF/Cr,CP/Cr,RBP/Cr运动前后无明显改变;非糖尿病人运动后尿Alb/Cr也较运动前增加(P>0.05),尿TRF/Cr,CP/Cr,RBP/Cr运动前后也无明显改变。而在相关分析中发现,尿RBP/Cr与Alb/Cr无显著相关性。尿TRF/Cr,CP/Cr与Alb/Cr有显著相关性。结论尿Alb/Cr受运动影响而尿TRF/Cr、CP/Cr不受运动影响,可作为DN早期诊断指标之一。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

AFP、AFU、DSA-GGT联合检测对原发性肝癌的诊断价值

目的探讨甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)和欧蔓陀罗凝集素(DSA)强结合的γ-谷氨酰转移酶(DSA-GGT)联合检测对原发性肝癌(PHC)的诊断价值。方法对58例PHC和167例良性肝病患者,以及36例其它肿瘤患者,进行AFP、AFU和DSA-GGT指标联合检测,分析3项指标对PHC的诊断价值。结果PHC组的AFP、AFU、DSA-GGT的阳性率均明显高于良性肝病和其它肿瘤组(P<0.01);AFP、AFU和DSA-GGT对PHC的诊断敏感性分别为68.97%、67.24%和65.52%,特异性分别为90.64%,89.66%和91.13%;PHC患者血清AFP、AFU、DSA-GGT之间无相关性,联合检测对PHC有互补诊断价值,阳性率达96.55%。结论AFP、AFU和DSA-GGT等3个指标联合应用,可提高PHC的诊断灵敏度,提高诊断水平。     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

脑脊液转铁蛋白及免疫球蛋白含量变化在小儿中枢神经系统感染时的临床意义

目的　通过对小儿中枢神经系统感染时Tf、Ig在脑脊液中含量的变化及其相关性分析 ,为鉴别诊断及更切实的判定病情和估计预后提供参考依据。方法　应用速率散射比浊法测定脑脊液中Tf、Ig。结果　 (1 )三组急性期脑脊液中Tf、Ig含量均高于恢复期。 (2 )结脑组Tf、IgG增高明显 ,化脑组IgM增高明显。病脑组变化最小。 (3)恢复期脑脊液中Tf、Ig含量与对照组比较 ,结脑中Tf、IgG、IgM高于对照组 ,化脑和病脑组IgM均高于对照组 ,Tf、IgG均无差异 ,各组IgA与对照组相比无显著性差异。 (4)病脑急性期Tf与IgG呈正相关 ,恢复期与IgA呈正相关 ;化脑组急性期Tf与IgM、IgG呈正相关 ,恢复期与IgM呈正相关 ;结脑急性期Tf与IgA、IgM均呈正相关 ,恢复期与IgG呈正相关。结论　 (1 )Tf与IgG是诊断结脑的良好指标 ,IgM是诊断化脑的良好指标 ,当脑脊液中IgM >30mg L时 ,可基本除外病脑 ,当脑脊液中IgM <60mg L时 ,化脑的可能性较小。 (2 )Tf与Ig一样 ,可作为判断中枢神经系统感染时血脑屏障及脑损伤与恢复程度的重要指标     

GC法检测浙八味药材中有机氯农药的残留

目的 测定与分析白术、白芍、玄参等8种药材中9种有机氯农药残留量.方法 以混合溶剂超声提取样品、浓硫酸磺化净化,采用毛细管气相色谱,用HP-5弹性石英毛细管柱程序升温分离,微电子捕获检测器检测,峰面积外标法定量.结果 延胡索、麦冬和杭白菊均检出滴滴涕,含量分别为0.439、45.017、5.434 ng·g<'-1>;杭白菊检出五氯硝基苯,含量为1.030 ng·g<'-1>;其余药材均未检出有机氯农药残留.结论 浙八味药材大部分未检出有机氯农药残留或含量较低,均在规定的安全范围内.     

Issues in the interpretation of associations of PCBs and IQ

The literature concerning the relationship between polychlorinated biphenyl (PCB) exposure and Intelligence (IQ) is not entirely consistent. Two studies showed inverse associations between PCBs and IQ in cohorts of children whose mothers consumed Great Lakes fish contaminated with PCBs and other organochlorines (Jacobson & Jacobson 1996; Stewart et al. 2008). Another study from the general US population, where women were exposed to background levels of PCBs, showed no association between PCBs and IQ (Gray et al. 2005). The current report examines two potential sources of inconsistency across studies: 1) confounding with non-PCB organochlorines [Hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and Mirex]; and 2) the presence of negative confounding (i.e., suppressor variables). The former could confound PCBs and lead to spurious associations (Type I errors), while the latter could suppress PCB associations and obscure true associations (Type II errors). These issues were explored through the analysis of associations between placental levels of organochlorines and IQ in children at 9 and 11 years of age in the Oswego study. Neither DDE nor mirex was related to lower IQ at either age; PCBs predicted lower IQ at both ages; and hexachlorobenzene (HCB) appeared as a significant predictor of IQ at the 11-year assessment. However, analysis of the IQ data set as a whole showed that both PCBs and HCB predicted lower IQ in a generally independent fashion. There was, however, overlap in the variance in some cases, and the pattern of findings between the two was remarkably similar. These results may provide some evidence for the potential involvement of non-PCB organochlorines in the Oswego study. To explore negative confounding, we analyzed the relationships between PCB exposure and demographic variables as well as the unadjusted and adjusted relationships between PCB and IQ. Results revealed that placental PCB levels were associated with older mothers who were more educated and came from higher socioeconomic strata. Due to this fact, unadjusted relationships between PCBs and IQ appeared null or slightly positive. After control for confounders, several significant negative associations between PCBs and IQ were revealed. These data might suggest that inadequate control for confounders in PCB studies, where negative confounding is present, may bias results toward the null (Type II error) rather than spurious associations (Type I error). This pattern of confounding with PCB exposure in the Oswego study also has implications for the assessment of risk. The most highly exposed children came from families with somewhat higher socioeconomic status, and tended to score in the average to above-average range, well above IQ scores that are considered “at risk.” Further, such children were exposed prenatally to PCBs through maternal consumption of PCB-contaminated Great Lakes fish in the early 1990s, when PCB levels were higher than today.