心脏兴奋收缩偶联

在参与心脏活动的离子中，Ca^2＋被认为可能是最重要的。人体内存在一种促使心脏收缩舒张的关键机制，这一机制即为兴奋收缩偶联。充分了解Ca^2＋如何在各种细胞器间的转运并引发兴奋收缩偶联，对于深入理解心脏功能的生理基础具有十分重要的意义。心脏兴奋收缩偶联是指由心肌电兴奋开始到心脏收缩并泵血这一过程。在心电活动中，Ca^2＋作为普遍存在的第二信使，起着关键的作用。它能够直接兴奋肌丝，从而引起心脏收缩。心肌Ca^2＋失调是引起心脏收缩功能障碍和心律失常等病理生理状态的关键原因。在心肌动作电位中，Ca^2＋通过去极化兴奋Ca^2＋进入细胞形成Ca^2＋内流（ICa），参与心电活动周期中平台期的形成。Ca^2＋内流会触发肌浆网（SR）释放Ca^2＋。这种Ca^2＋的内流和释放，使得细胞内Ca^2＋浓度迅速升高，随后Ca^2＋与肌纤蛋白-肌钙蛋白C结合，引发收缩机制。若是心脏发生舒张活动，[Ca^2＋]i必须下降，从而使得Ca^2＋由肌钙蛋白上释放出来。这一过程需将Ca^2＋转运出胞浆，主要通过以下四条途径来实现：①肌浆网（SR）Ca^2＋-ATPase；②肌纤维膜Na^＋-Ca^2＋交换（NCX）；③肌纤维膜Ca^2＋-ATPase；④线粒体Ca^2＋单向转运。本文将着重论述心肌细胞Ca^2＋转运体系及其调节机制。     

心肌缺血再灌注损伤亚细胞Ca^2＋反常与ATP酶泵功能抑制

目的：研究心肌缺血再灌注损伤亚细胞Ca^2 分布、含量及ATPase活性变化,探讨Ca^2 反常与ATP酶泵功能抑制的关系。方法：采用离体心脏灌注模型,电子探针显微分析测定心肌缺血再灌注原位亚细胞Ca^2 变化;电镜酶细胞化学及生化方法测定ATPase分布及活性变化。结果：心肌缺血30min再灌注30、60min肌浆网及肌膜Ca^2 明显减少（P＜0．01）,而胞浆及线粒体内Ca^2 明显增加（P＜0．01）。再灌注肌浆网及肌膜Ca^2 减少与胞浆及线粒体Ca^2 增加呈负线性相关,γ分别为－0．964和－0．994,胞浆与线粒体Ca^2 变化呈正线性相关,γ为0．997。心肌缺血30minATPase活性明显降低,缺血30min再灌注30及60min进一步加重。结论：心肌缺血再灌注Ca^2＋超载发生在亚细胞水平,即亚细胞Ca^2 的重新分布。ATPase泵功能抑制是心肌缺血再灌注亚细胞Ca^2 紊乱的直接原因之一。     

mGluR1选择性拮抗剂LY367385对脑星形胶质细胞Na^＋-K^＋-ATP酶和Ca^2＋-Mg^2＋-ATP酶的影响

背景：脑星形胶质细胞肿胀是肝衰竭时脑水肿的特征,但其机制尚未完全阐明。目的：研究代谢型谷氨酸受体1亚型（mGluR1）选择性拮抗剂LY367385对脑星形胶质细胞Na^＋-K^＋-ATP酶和Ca^2＋-Mg^2＋-ATP酶的影响。方法：分离、培养小鼠脑星形胶质细胞,分为谷氨酸组、谷氨酸＋LY367385组、谷氨酸＋DMSO组和空白对照组,以定磷法检测Na^＋-K^＋-ATP酶和Ca^2＋-Mg^2＋-ATP酶活性,以高效液相色谱法测定ATP含量。结果：与空白对照组相比,谷氨酸组、谷氨酸＋LY367385组和谷氨酸＋DMSO组Na^＋-K^＋-ATP酶活性、Ca^2＋-Mg^2＋-ATP酶活性和ATP水平显著降低（P〈0.05）;谷氨酸＋LY367385组和谷氨酸＋DMSO组显著高于谷氨酸组（P〈0.001）,两组间则无明显差异。结论：mGluR1选择性拮抗剂LY367385可提高Na^＋-K^＋-ATP酶和Ca^2＋-Mg^2＋-ATP酶活性,减少ATP消耗,从而有效保护脑星形胶质细胞,有望成为预防和治疗肝性脑病的药物。     

大电导钙离子激活钾通道与糖尿病冠状动脉病变

钙离子（Ca^2＋）激活钾通道根据电导大小和药理特性的差异可分为3类：即大电导ca^2＋激活钾通道（BK）、中电导Ca^2＋激活钾通道（IK）和小电导Ca^2＋激活钾通道（SK），其中BK通道因其对血管调节作用较大且分布广泛而备受关注^[1].BK通道广泛存在于兴奋和非兴奋细胞，在血管平滑肌细胞（VSMCs）膜上表达尤为丰富，不仅参与细胞膜电位的。     

肥厚心肌细胞Na^＋／Ca^2＋交换活性对β—肾上腺素能药物的反应性降低

目的 探讨肥厚心肌细胞Na^ /Ca^2 交换对β-类肾上腺素能药物刺激的反应及发生这种改变的可能机制。方法 采用胶原酶消化的高血压大鼠单个心室肌细胞及全细胞膜片钳技术，记录Na^ /Ca^2 交换电流并观察药物对它的影响。结果 (1)异丙肾上腺患可浓度依赖性地增加正常及肥厚大鼠心室肌细胞的Na^ /Ca^2 交换电流，但其对肥厚心室肌细胞Na^ /Ca^2 交换电流的增强作用要弱于正常心室肌细胞(P＜0．05)。(2)cAMP可浓度依赖性地增加正常及肥厚大鼠心室肌细胞的Na^ /Ca^2 交换电流，其对正常及肥厚大鼠心室肌细胞Na^ /Ca^2 交换电流的增强作用无差别(P＞0．05)。结论 高血压大鼠心室肌细胞Na^ /Ca^2 交换对β-类肾上腺患能药物的反应性降低，可随与翘厚心肌细胞的g—受体数目及功能、G蛋白及腺昔酸环化酶的活性改变等环节有关，此种反应可能是肥厚心肌收缩及舒张功能障碍的机制之一。     

肌浆网Ca2+-ATP酶及磷酸受钙蛋白与心力衰竭的基因治疗

心力衰竭（CHF）是各种心血管疾病的严重或终末阶段，其发病率和死亡率均呈上升趋势，且预后较差，不断开发的药物治疗也未能解决这一难题。随着分子生物学的飞速发展，基因治疗作为一种新的治疗策略为CHF的治疗提供了新的途径。CHF的基本表现为心肌收缩和（或）舒张功能的障碍，其中，Ca2＋是心肌舒缩活动的中心环节，肌浆网Ca2^＋-ATP酶（sarcoplasmic reticulum Ca2^＋-ATPase，SERCA）则是心肌Ca^2＋调控的重要机制。     

慢性心房颤动患者心房肌中钙调神经磷酸酶的活性及表达

钙调神经磷酸酶（calcineurin，CaN）是迄今所知的惟一一种受Ca^2＋／钙调蛋白调节的丝氨酸／苏氨酸蛋白磷酸酶。CaN广泛分布于机体内各种组织中，参与多种受Ca^2＋调节的信号转导通路，并通过作用于不同的底物而产生不同的生物学效应。新近研究表明，CaN信号通路的下游信号因子——T细胞激活核因子在心房颤动（房颤）的发生发展中起重要作用，本研究的目的是明确慢性房颤患者心房肌中是否存在CaN的活性和表达异常。[第一段]     

Ghrelin对胰岛β细胞作用及机制的研究

Ghrelin是一种脑肠肽，表达于人体各种不同的器官和组织中，其中包括胰岛。Ghrelin在体内以乙酰化和非乙酰化两种结构存在，发挥胰岛素调节作用的主要是乙酰化ghrelin。Ghrelin通过与生长激素促分泌素受体结合发挥重要的内分泌作用。研究表明，ghrelin可通过作用于胰岛β细胞的电压门控Ca^2＋通道、受体门控Ca^2＋通道调节胰岛素的分泌。此外，ghrelin还可以通过磷脂酶C等细胞内信号途径及K^＋通道调节胰岛素的分泌反应。     

压力超负荷下大鼠心肌细胞核钙调节系统的变化

目的：通过腹主动脉缩窄（abdominal aortic coaretation，AAC）心肌肥厚大鼠模型制备、差速离心提纯心肌细胞核、酶学方法测定Ca^2＋-ATPase活性、^45Ca^2＋同位素法测定核钙摄取和^3H放射配基受体分析心肌细胞核膜IP3R和RyR的动力学特性，初步揭示压力超负荷心肌肥厚大鼠心肌细胞核钙转导异常的环节。结果发现：AAC术后4周大鼠心肌显著肥厚，伴有明显的血流动力学异常，与对照组比较，AAC大鼠心肌细胞核Ca^2＋-ATPase活性减少51．93％（P〈0．001），但核^45Ca^2＋摄入量（核外[Ca^2＋]浓度为800-1600nmol／L时）明显增加（P〈0．05）；AAC大鼠心肌细胞核IP3R的Bmax和Kd与对照组比较分别增加1．217和2．149倍（P〈0．01），其细胞核RyR的最大结合（Bmax）较对照组减少57．8％（P〈0．001），解离常数（Kd）较对照组降低54．4％（P〈0．05）。结论为心肌细胞核Ca^2＋转运系统发生改变（Ca^2＋．ATPase活性减少、核^45Ca^2＋摄取增加、IP3R密度上调和亲和力降低，而细胞核RyR密度下调而亲和力增加），可能参与压力超负荷心肌肥厚的发生过程。     

钙信号转导与急性胰腺炎

急性胰腺炎（AP）是胰腺腺泡细胞内胰蛋白酶原激活引起细胞自溶的过程。它的早期病理改变包括：胰腺腺泡细胞内酶原激活，细胞骨架裂解，分泌极性丧失，酶原空泡形成。这些病理改变均以细胞内Ca^2＋浓度异常增高为前提，应用Ca^2＋螯合剂能够抑制Ca^2＋浓度增高和胰蛋白酶原的激活。[第一段]     

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.     

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.     

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.