黄芪对低氧性肺动脉高压大鼠肺血管结构重建干预作用及机制的研究

目的 探讨黄芪注射液对低氧性肺动脉高压(HPH)大鼠肺腺泡内肺动脉结构重建及肺组织内皮素-1(ET-1)、一氧化氮(NO)的影响。方法雄性Wistar大鼠21只,每组7只,随机分为3组,正常对照组、低氧组、低氧+黄芪治疗组。低氧30d,分别用右心导管法测定肺动脉平均压(mPAP)、颈动脉平均压(mCAP),右心室肥大指数(RVHI),分光光度法测定肺组织中NO含量和放射免疫法测定肺组织中ET-1含量,计算MA、PMA、NMA比例及肺中、小肌型动脉相对中膜厚度(RMT)与相对中膜面积(RMA)。结果①低氧组mPAP、RVHI、ET-1含量较对照组明显升高(P<0.01或P0.05)。结论慢性低氧可引起大鼠肺血管结构重建,导致mPAP上升、肺组织ET-1升高、NO下降,黄芪注射液可调节肺组织ET-1、NO含量,可部分逆转肺血管结构重建,降低肺动脉高压,对HPH有一定防治作用。     

血栓素A2合成酶抑制剂治疗大鼠低氧性肺动脉高压的研究

目的探讨花生四烯酸(TXA2,又称血栓素A2)合成酶抑制剂奥扎格雷钠治疗大鼠低氧性肺动脉高压的疗效及机制.方法Wister大鼠21只,随机分为3组,正常对照组7只,单纯低氧组7只,奥扎格雷钠治疗组7只.采用间断性低氧法复制大鼠低氧性肺动脉高压动物模型,观察奥扎格雷钠对低氧21天大鼠肺动脉平均压(MPAP)、右心室肥厚、血浆TXA2代谢产物血栓素B2(TXB2)和前列环素(PGI2)代谢产物6-酮-前列腺素F1α(6-K-PGF)浓度及其TXB2/6-K-PGF等的影响.结果单纯低氧组大鼠MPAP、右心室湿重、右心室湿重/(左心室 室间隔)湿重、血浆TXB2含量和TXB2/6-K-PGF均明显增加,与正常对照组相比均有显著差异(P＜0.05);奥扎格雷钠治疗组较单纯低氧组明显降低(P＜0.05～0.001),但仍高于正常对照组(P＜0.05).各组血浆6-K-PGF和体动脉平均压无显著差异.结论奥扎格雷钠可明显降低低氧大鼠肺动脉高压、减轻右心室肥厚程度,降低低氧大鼠血浆TXA2代谢产物TXB2水平和改善反应TXA2/PGI2水平的TXB2/6-K-PGF.     

银杏叶提取物对慢性间歇性缺氧大鼠肺动脉高压血管内皮损伤的保护作用

目的 观察银杏叶提取物银杏酮酯(GBE50)对缺氧大鼠肺动脉高压血管内皮损伤的保护效应,并初步探讨其作用机制.方法 复制常压低氧肺动脉高压大鼠模型.30只健康SD大鼠随机分为正常对照组(N)、模型组(M)和GBE50组.GBE50组于每天缺氧后口服GBE50,21d后观察右室/左室+室间隔重量比值(R/L+S)、肺动脉管壁面积/管总面积(WA).用生化、放免法分别测血浆中一氧化氮(NO)、内皮素-1(ET-1)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量.结果 与正常对照组相比,模型组R/L+S、WA及血浆ET -1、SOD、MDA、NO明显升高(P＜0.05),提示缺氧导致参与氧化的酶明显失衡,发生内皮损伤和肺动脉高压.GBE50组R/L+S、LA明显下降,NO、WA和SOD含量显著升高(P＜0.05).结论 用GBE50治疗后可改善参与氧化反应系列酶失衡的状况,减轻肺动脉高压和内皮的损伤.GBE50对慢性间歇性缺氧大鼠肺动脉高压血管内皮损伤有一定的保护作用.     

缺氧对肺动脉血管内皮细胞线粒体膜电位的影响及Ghrelin的保护作用

目的观察缺氧对人肺动脉血管内皮细胞线粒体膜电位(MMP)的影响及Ghrelin的保护作用。方法将培养的人肺动脉血管内皮细胞分为对照组、单纯缺氧组和缺氧+Ghrelin组。应用激光共聚焦显微镜扫描,并测定标记的人肺动脉血管内皮细胞每秒钟MMP值;采用硝酸还原酶法和放射免疫分析技术检测人肺动脉血管内皮细胞上液中一氧化氮(NO)和内皮素(ET-1)含量。结果与对照组相比,单纯缺氧组MMP水平显著降低(P<0.05);与单纯缺氧组相比,缺氧+Ghrelin组内皮细胞MMP水平显著升高(P<0.05),缺氧+Ghrelin组与对照组内皮细胞MMP水平差异不明显(P>0.05)。单纯缺氧组上清液NO含量明显低于对照组(P<0.05),缺氧+Ghrelin组上清液NO含量明显高于单纯缺氧组(P<0.05)。单纯缺氧组上清液ET-1含量明显高于对照组(P<0.05),缺氧+Ghrelin组上清液ET-1含量明显低于单纯缺氧组(P<0.05)。结论缺氧引起人肺血管内皮细胞MMP降低,Ghrelin可抑制缺氧损伤所致MMP降低;同时Ghrelin还可以促进人肺血管内皮细胞释放NO,抑制缺氧引起的ET-1高释放。     

辛伐他汀治疗COPD合并肺动脉高压的临床研究

目的 探讨辛伐他汀治疗慢性阻塞性肺疾病(COPD)合并肺动脉高压(PH)患者肺动脉压、动脉血气、肺功能以及对血浆内皮素-1 (ET-1)、脑钠肽(BNP)的影响.方法 选择稳定期COPD合并PH患者36名,随机分成治疗组和对照组,两组患者均按COPD常规治疗,治疗组加用辛伐他汀40 mg/d,于治疗前及治疗三月后检测肺动脉压、动脉血气、肺功能以及血浆ET-1、BNP水平.结果 治疗组和对照组临床疗效分别66.7％和50.0％.治疗组优于对照组;两组肺动脉平均压治疗后均降低(P＜0.05),治疗组较对照组降低更显著(P＜0.05);治疗组肺功能改善较对照组更明显(P＜0.05);治疗组治疗3个月时ET-1和BNP的水平与对照组比较明显下降(P＜0.05,P ＜0.05).结论 辛伐他汀治疗COPD合并PH,可降低BNP的水平,降低肺动脉平均压及改善肺功能;并能降低ET-1改善内皮功能.     

血管内皮生长因子和内皮素在低氧性肺血管重建中的作用

目的探讨血管内皮生长因子(VEGF)和内皮素(ET)-1在低氧性肺动脉高压(HPH)及其肺血管重建中的作用,并观察钾通道开放剂(pinacidil)对HPH的防治作用及对VEGF和ET-1的影响.方法Wister大鼠46只,随机分为3组,对照组15只,低氧组16只,治疗组15只.缺氧组和治疗组大鼠缺氧[氧浓度为(10.0±0.5)%]4周,每天缺氧8h,其中治疗组大鼠于每天缺氧前腹腔注射pinacidil3mg/kg.缺氧4周后测定各组大鼠血清VEGF和血浆ET-1水平、平均肺动脉压(mPAP)、右心室(RV)/[左心室(LV)+室间隔(S)]比值及肺小动脉病理及其形态计量学.结果(1)缺氧组大鼠血清VEGF[(118.73±55.40)ng/L]和血浆ET-1[(221.2±56.2)ng/L]水平明显高于对照组(P＜0.01);缺氧组较对照组mPAP升高,RV/(LV+S)比值增高,肺小动脉血管壁显著增厚,管腔明显狭窄.(2)治疗组大鼠血清VEGF[(78.20±16.45)ng/L]和血浆ET-1[(181.6±30.5)ng/L]水平明显低于缺氧组(P＜0.01);治疗组较缺氧组mPAP下降(P＜0.01),肺小动脉血管壁增厚、管腔狭窄等明显减轻,但治疗组上述各指标仍未完全恢复到对照组水平.结论VEGF和ET-1在HPH及其肺血管重建中发挥重要作用,钾通道开放剂对HPH及其肺血管重建具有一定的逆转作用.     

慢性间歇低氧对大鼠血管内皮功能的影响以及抗氧化剂干预作用

目的 通过测定血清中血管活性物质,探讨慢性间歇低氧(CIH)对大鼠血管内皮功能的影响,以及抗氧化剂4-羟基-2,2,6,6四甲基哌啶(Tempol)的防治作用.方法 将48只Wistar雄性大鼠随机分为6组,每组8只,包括常氧对照组(NC组)、间歇低氧组(IH组)和4组间歇低氧Tempol干预及其对照组:IHT1组、IHT2组、IHN1组、IHN2组.IHT1、IHT2组分别为实验前和实验后第28天给予10％ Tempol100mg· kg-1·d-1腹腔注射,IHN1、IHN2组于相同时间给予等量生理盐水腹腔注射.结果 IHT2组与IHN2组比较,ET-1水平显著降低(P＜0.05),NO、eNOS水平升高(P值均＜0.05);但ET-1水平仍高于NC组(P＜0.01),NO、eNOS较其降低(P值均＜0.01).IHT1组ET-1水平低于IHT2组(P＜0.01),NO、eNOS水平较其升高(P值均＜0.01);各指标与NC组差异无统计学意义.IH组与IHN1组、IHN2组相比,各指标差异均无统计学意义.结论 CIH可能通过氧化应激引起血清ET-1、NO含量失衡,导致内皮功能障碍.抗氧化剂Tempol可减轻血管内皮氧化应激损伤,在改善血管内皮功能方面具有一定的意义.     

硫酸镁对低氧性肺动脉高压大鼠血中丙二醛和超氧化物歧化酶的影响

目的 :探讨硫酸镁对低氧性肺动脉高压大鼠血中丙二醛 (MDA)和超氧化物歧化酶(SOD)的影响。方法 :将 2 4只Wistar大鼠随机分为缺氧组、硫酸镁组和对照组。 4周后测血浆MDA含量和红细胞SOD活性。结果 :硫酸镁组较缺氧组血中MDA含量显著降低 (P <0 .0 5 ) ,而SOD活性显著升高 (P <0 .0 1)。结论 :低氧时脂质过氧化反应增强 ,硫酸镁能抑制脂质过氧化和降低肺动脉压。     

消臌软坚丸对肝硬化大鼠血细胞因子及血管活性因子的影响

目的:研究消臌软坚丸对肝硬化大鼠模型血清肿瘤坏死因子(TNF)、白细胞介素1、6(IL-1、IL-6)、一氧化氮及其合酶(NO、NOS)及血浆内皮素1(ET-1)的调控作用.方法:采用四氯化碳为主的复合因素造模法复制肝硬化大鼠模型,分为正常组、模型组、消臌软坚丸低剂量组和高剂量组及阳性药对照组(复方鳖甲软肝片),5组均于造模结束后第2天连续灌服0.85%氯化钠液或药物28 d后断头取血,分别检测血清TNF、IL-1、IL-6、NO、NOS及ET-1含量.结果:①消臌软坚丸各治疗组TNF、IL-1、IL-6的含量均低于模型组(P＜0.01),高剂量组低于对照组(P＜0.05或＜0.01);低剂量组IL-1、TNF的含量低于对照组(P＜0.01),而IL-6的含量与对照组之间差异无统计学意义(P＞0.05);高、低剂量组之间差异未见统计学意义(P＞0.05).②消臌软坚丸各治疗组NO、NOS的含量均低于模型组(P＜0.01);高剂量组NO、NOS的含量均低于低剂量组和对照组(P＜0.01);低剂量组NOS的含量低于对照组(P＜0.01).③消臌软坚丸各治疗组均能明显降低血浆ET-1的含量(P＜0.01).高、低剂量组ET-1的含量均低于对照组(P＜0.01).高剂量组ET-1的含量低于低剂量组(P＜0.01).结论:①消臌软坚丸可显著下调肝硬化模型大鼠血清异常升高的TNF、IL-1、IL-6的水平;②消臌软坚丸可显著降低肝硬化大鼠血NO、NOS、ET的含量.从而减轻炎症损害,改善系统高动力循环状态,缓解门脉高压及肝微循环障碍,减缓或抑制腹水的发生发展.     

补肺益肾活血法对慢性低氧性肺动脉高压大鼠血管活性物质的影响

目的 探讨补肺益肾活血法治疗肺动脉高压的作用机制.方法 取健康SD大鼠40只,随机分为空白对照组、模型组、中药芪葶合剂组、卡托普利组.各组动物在同等条件下饲养,将后3组大鼠放入常压缺氧箱内缺氧造模4 w,各组分别用等量生理盐水、芪葶合剂及卡托普利溶液灌胃.4 w之后用右心导管法检测大鼠肺动脉平均压(mPAP)、颈动脉平均压(mCAP);用放免法检测内皮素(ET-1)、血栓素(TXB2).结果 芪葶合剂组、卡托普利组与模型组比较肺动脉平均压降低,而颈动脉平均压则无明显变化.芪葶合剂组、卡托普利组肺组织中ET-1和TXB2水平下降(P＜0.05或P＜0.01).结论 芪葶合剂能降低肺组织中ET-1和TXB2含量,改善肺动脉高压.     

Biliary microlithiasis,sludge,crystals,microcrystallization,and usefulness of assessment of nucleation time

BACKGROUND:The process of microcrystallization,its sequel and the assessment of nucleation time is ignored.This systematic review aimed to highlight the importance of biliary microlithiasis,sludge,and crystals,and their association with gallstones,unexplained biliary pain,idiopathic pancreatitis, and sphincter of Oddi dysfunction.DATA SOURCES:Three reviewers performed a literature search of the PubMed database.Key words used were"biliary microlithiasis","biliary sludge","bile crystals","cholesterol crystallisation","bile microscopy","microcrystal formation of bile","cholesterol monohydrate crystals","nucleation time of cholesterol","gallstone formation","sphincter of Oddi dysfunction"and"idiopathic pancreatitis".Additional articles were sourced from references within the studies from the PubMed search.RESULTS:We found that biliary microcrystals account for almost all patients with gallstone disease,7%to 79%with idiopathic pancreatitis,83%with unexplained biliary pain, and 25%to 60%with altered biliary and pancreatic sphincter function.Overall,the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55%to 87%and a specificity of 100%.In idiopathic pancreatitis,the presence of microcrystals ranges from 47%to 90%.A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100%for cholesterol gallstone disease.CONCLUSIONS:Biliary crystals are associated with gallstone disease,idiopathic pancreatitis,sphincter of Oddi dysfunction, unexplained biliary pain,and post-cholecystectomy biliary pain.Pathways of cholesterol super-saturation,crystallisation, and gallstone formation have been described with scientificsupport.Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.     

Antibacterial activity of cefpodoxime in comparison with cefixime,cefdinir, cefetamet,ceftibuten, loracarbef,cefprozil, BAY 3522, cefuroxime,cefaclor and cefadroxil

Summary The new oral cephalosporins cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten demonstrate enhanced activity against Enterobacteriaceae susceptible to the established compounds as well (e.g. cefuroxime, cefaclor, cefadroxil). In addition, cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten include in their spectrum species hitherto resistant to oral cephalosporins (Proteus vulgaris, Providencia spp.,Yersinia enterocolitica). Besides, the majority of these compounds demonstrate relevant activity (MIC₅₀ equal to or below 2 mg/l) againstEnterobacter spp.,Citrobacter freundii, Serratia spp. andMorganella morganii. Ceftibuten is the most potent oral cephalosporin against most of the Enterobacteriaceae. Non-fermentative bacilli (Acinetobacter spp.,Pseudomonas spp.) remain completely resistant to oral cephalosporins (except someAcinetobacter species against cefdinir andPseudomonas cepacia against ceftibuten). Antistaphylococcal activity for oral cephalosporins is highest for cefdinir followed by BAY 3522, cefprozil, cefuroxime and cefpodoxime. Loracarbef, cefaclor and cefadroxil are about equally active, while the other compounds are only weakly active (cefixime) or inactive (cefetamet, ceftibuten). Enterococci are insensitive to new generation oral cephalosporins as they have been to established compounds. The most active oral cephalosporins against hemolytic streptococci are cefdinir and cefprozil.Streptococcus pneumoniae, Streptococcus milleri andStreptococcus mitior are most susceptible to cefpodoxime, cefdinir, cefuroxime and BAY 3522. Penicillin resistant pneumococci have to be regarded as resistant to all oral cephalosporins. Fastidious pathogens likeHaemophilus spp.,Moraxella catarrhalis andNeisseria gonorrhoeae are more susceptible to cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten than to the other oral cephalosporins. The activity of oral cephalosporins is only weak againstListeria spp.,Helicobacter pylori and anaerobic pathogens (except BAY 3522).Bordetella pertussis remains resistant to all absorbable cephalosporins. Progress in antibacterial activity of oral cephalosporins was mainly achieved by cefpodoxime, cefixime, cefdinir, cefetamet and ceftibuten against Enterobacteriaceae and the fastidious pathogens and against staphylococci and the nonenterococcal streptococci by cefdinir, BAY 3522, cefprozil and cefpodoxime.

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Antibakterielle Aktivität von Cefpodoxim im Vergleich mit anderen oralen Cephalosporinen

Zusammenfassung Die neuen oralen Cephalosporine Cefpodoxim, Cefixim, Cefdinir, Cefetamet und Ceftibuten zeigen eine verstärkte Aktivität auch gegen solche Enterobacteriaceae, die gegen etablierte Substanzen empfindlich sind (z.B. Cefuroxim, Cefaclor, Cefadroxil). Zusätzlich schließt das Spektrum von Cefpodoxim, Cefixim, Cefdinir, Cefetamet und Ceftibuten Spezies ein, die gegen die bisherigen oralen Cephalosporine resistent waren (Proteus vulgaris, Providencia spp.,Yersinia enterocolitica). Daneben zeigt die Mehrheit der neuen Substanzen erhöhte Aktivität (MHK₅₀<2 mg/l) gegenEnterobacter spp.,Citrobacter freundii, Serratia spp. undMorganella morganii. Gegen die meisten Enterobacteriaceae ist Ceftibuten das wirksamste orale Cephalosporin. Non-Fermenter (Acinetobacter spp.,Pseudomonas spp.) bleiben gegenüber oralen Cephalosporinen vollständig resistent (mit Ausnahme einigerAcinetobacter-Spezies gegen Cefdinir undPseudomonas cepacia gegen Ceftibuten). Die Antistaphylokokken-Aktivität oraler Cephalosporine ist am höchsten bei Cefdinir, gefolgt von BAY 3522, Cefprozil, Cefuroxim und Cefpodoxim. Loracarbef, Cefaclor und Cefadroxil sind etwa gleich aktiv, während die anderen Substanzen nur schwach aktiv (Cefixim) oder inaktiv sind (Cefetamet, Ceftibuten). Enterokokken sind gegenüber der neuen Generation oraler Cephalosporine ebenso unempfindlich wie gegenüber den etablierten Substanzen. Die aktivsten oralen Cephalosporine gegen hämolysierende Streptokokken sind Cefdinir und Cefprozil.Streptococcus pneumoniae, Streptococcus milleri undStreptococcus mitior sind am empfindlichsten gegen Cefpodoxim, Cefdinir, Cefuroxim und BAY 3522. Penicillin-resistente Pneumokokken müssen als resistent gegenüber allen oralen Cephalosporinen betrachtet werden. Anspruchsvolle Erreger wieHaemophilus spp.,Moraxella catarrhalis undNeisseria gonorrhoeae sind gegen Cefpodoxim, Cefixim, Cefdinir, Cefetamet und Ceftibuten empfindlicher als gegen die anderen oralen Cephalosporine. Die Aktivität oraler Cephalosporine gegenListeria spp.,Helicobacter pylori und Anaerobier (Ausnahme BAY 3522) ist nur schwach.Bordetella pertussis bleibt gegen alle resorbierbaren Cephalosporine resistent. Der Fortschritt in der antibakteriellen Aktivität oraler Cephalosporine wurde gegen Enterobacteriaceae und anspruchsvolle Erreger hauptsächlich durch Cefpodoxim, Cefixim, Cefdinir, Cefetamet und Ceftibuten erlangt, gegen Staphylokokken und Streptokokken (außer Enterokokken) durch Cefdinir, BAY 3522, Cefprozil und Cefpodoxim.

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Supported by Luitpold-Werk, a company of the Sankyo group.     

Clinical trials update: highlights of the scientific sessions of The American College of Cardiology 2002: LIFE,DANAMI 2, MADIT-2, MIRACLE-ICD,OVERTURE, OCTAVE,ENABLE 1 & 2, CHRISTMAS,AFFIRM, RACE,WIZARD, AZACS,REMATCH, BNP trial and HARDBALL

This article continues a series of reports updating recent research developments of particular interest to personnel involved in the treatment and management of patients with heart failure. This is a summary of selected presentations made at the American College of Cardiology 51st Annual Scientific Session held in Atlanta on 17-20 March 2002. Reports of the following clinical studies are included: LIFE, DANAMI 2, MADIT-2, MIRACLE-ICD, OVERTURE, OCTAVE, ENABLE 1 & 2, CHRISTMAS, AFFIRM, RACE, WIZARD, AZACS, REMATCH, BNP trial and HARDBALL.     

Electrochemical Recovery and Behaviors of Rare Earth (La,Ce, Pr,Nd, Sm,Eu, Gd,Tb, Dy,Ho, Er,Tm, and Yb) Ions on Ni Sheets

The electrochemical behaviors of rare earth (RE) ions have extensively been studied because of their high potential applications to the reprocessing of used nuclear fuels and RE-containing materials. In the present study, we fully investigated the electrochemical behaviors of RE(III) (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) ions over a Ni sheet electrode in 0.1 M NaClO₄ electrolyte solution by cyclic voltammetry between +0.5 and −1.5 V (vs. Ag/AgCl). Amperometry electrodeposition experiments were performed between −1.2 and −0.9 V to recover RE elements over the Ni sheet. The successfully RE-recovered Ni sheets were fully characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy. The newly reported recovery data for RE(III) ions over a metal electrode provide valuable information on the development of the treatment methods of RE elements.