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Search Results: 1 - 10 of 25 matches for " Hergé "
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Liposome mitigation of curcumin inhibition of cardiac potassium delayed-rectifier current
Helson L, Shopp G, Bouchard A, Majeed M
Journal of Receptor, Ligand and Channel Research , 2012, DOI: http://dx.doi.org/10.2147/JRLCR.S37138
Abstract: some mitigation of curcumin inhibition of cardiac potassium delayed-rectifier current Original Research (1081) Total Article Views Authors: Helson L, Shopp G, Bouchard A, Majeed M Published Date November 2012 Volume 2012:5 Pages 1 - 8 DOI: http://dx.doi.org/10.2147/JRLCR.S37138 Received: 18 August 2012 Accepted: 23 September 2012 Published: 16 November 2012 Lawrence Helson,1 George Shopp,2 Annie Bouchard,3 Muhammad Majeed4 1SignPath Pharma, Quakertown, PA, USA; 2Shopp Nonclinical Consulting, Boulder, CO, USA; 3IPS Therapeutique Inc, Sherbrooke, Quebec, Canada; 4Sabinsa Inc, Princeton, NJ, USA Background: The duration of the QT interval on the standard electrocardiogram (ECG) is measured from the beginning of the QRS complex (depolarization of the cardiac myocyte) to the end of the T-wave (completion of the repolarization phase of the cardiac myocyte). Repolarization is a result of currents generated by the outward flow of K+ through the K+ channels. Obstruction of ion flow in the channel leads to delayed repolarization, evidenced by a prolonged QT interval. Clinically, this is known as the long QT syndrome (LQTS), which, when expressed, can lead to severe cardiac arrhythmias and sudden death. Obstruction of K+ ion flow can result from gene mutations (eg, the human ether-a-go-go-related gene [hERG]) resulting in phenotypic abnormalities in K+ channels and/or common structurally diverse drugs. These gene abnormalities or drug-induced changes result in decreased cardiac delayed-rectifier K+ current (IKr, or KV11.1) in congenital or acquired LQTS, respectively. Increased risk of LQTS is a major drug development hurdle, and many drugs have been withdrawn during preclinical development, assigned black box warnings following approval, or withdrawn from the market. Autosomal recessive or dominant LQTS based upon 500 possible mutations in ten different genes coding for K+ channels has an incidence of 1:3000 or about 100,000 persons in the USA. Prolonged QT intervals or risk of LQTS occurs in 2.5% of the asymptomatic US population. The probability of cardiac death in patients with asymptomatic congenital LQTS who are concomitantly medicated with LQTS-inducing drugs appears to have increased. Methods: E-4031 (methanesulfanalide), terfenadine (Seldane ), curcumin, liposomal curcumin, empty liposomes, empty liposomes vortexed with E-4031, or terfenadine and empty liposomes vortexed with curcumin were assayed for their effects on the K+-selective IKr tail current inhibition using human embryonic kidney (HEK 293) cells stably transfected with the hERG gene via the whole-cell manual patch clamp technique. Results: E-4031, terfenadine, and curcumin inhibit IKr channel following nM-to-μM exposures. Empty liposomes had no effect on IKr. Both the liposomal curcumin formulation and vortexed mixtures of empty liposomes and curcumin prevented the IKr inhibitory effect of curcumin in a dose-dependent manner. Empty liposomes vortexed with E-4031 prevented the effect of E
Hergé, Extrême-Orient et bande dessinée
Jean-Pierre BOUDINEAU
Mappemonde , 1992,
Abstract: Le Lotus bleu, dessiné en 1934-1935, diffusé surtout à partir de 1946, fut, pour quelques générations d’enfants, une des premières rencontres avec l’Asie. Le succès toujours présent de cet album, quasi sexagénaire, s’explique par la richesse du scénario, par le sens narratif et poétique d’Hergé, mais aussi par un indiscutable souci de vérité historique et géographique. Le dessinateur belge et Tchang-Tchong Jen, son ami, ont en réalité produit une oeuvre engagée autant qu’un divertissement.
Tintín a Catalunya [Tintin in Catalonia]
Soldevilla Albertí, Joan Manuel
Zeitschrift für Katalanistik , 2012,
Abstract: This article offers a perspective of the different stages which marked the arrival of "The Adventures of Tintin", a series that has been widely popular and highly influential in the Catalan-speaking areas. We will first illustrate the importance of Hergé’s work in the context of the 20th century media and will continue with an account of how this comic reached our nation. The essay analyzes the implementation strategies in the book market, describes how the series consolidated its position, how it eventually managed to become a modern icon in the 1980s and how the new century has witnessed a rebirth of people’s interest in Hergé’s work.
Toward a New Gold Standard for Early Safety: Automated Temperature-Controlled hERG Test on the PatchLiner?
Liudmila Polonchuk
Frontiers in Pharmacology , 2012, DOI: 10.3389/fphar.2012.00003
Abstract: The Patchliner? temperature-controlled automated patch clamp system was evaluated for testing drug effects on potassium currents through human ether-à-go-go related gene (hERG) channels expressed in Chinese hamster ovary cells at 35–37°C. IC50 values for a set of reference drugs were compared with those obtained using the conventional voltage clamp technique. The results showed good correlation between the data obtained using automated and conventional electrophysiology. Based on these results, the Patchliner? represents an innovative automated electrophysiology platform for conducting the hERG assay that substantially increases throughput and has the advantage of operating at physiological temperature. It allows fast, accurate, and direct assessment of channel function to identify potential proarrhythmic side effects and sets a new standard in ion channel research for drug safety testing.
重金属Cd2+对细胞外向K+通道的影响
杜春蕾,王丽红,江娜,黄晓华
化学学报 , 2011,
Abstract: 重金属镉(Cd)污染及其对动植物的伤害机理,已成为中外相关专家研究的热点,但是细胞毒害机理依然不清楚.分布于细胞膜上的通道蛋白,不仅是外来物质作用于生物体的首要位点,且会影响离子通道的功能.为阐释镉(Cd)污染致病与毒害的细胞学机理,选择具有重要生理功能的细胞钾离子(K+)通道为示踪,并应用全细胞膜片钳技术,研究了Cd2+对hERG(K+)通道电流的影响.结果表明(1)Cd2+能显著抑制hERGK+通道的稳态电流和尾电流,干扰通道蛋白正常开关|(2)当10,50,200μg/LCd2+作用细胞后,hERG(K+)通道激活曲线右移,斜率因子不变|(3)当10μg/LCd2+作用细胞后,hERGK+通道电流迅速下降,且随Cd2+浓度增加,此抑制作用未发生明显改变.本工作从一新的角度揭示了Cd2+细胞毒性机理.结果提示,钾通道可作为镉污染致病与毒害的细胞学机理研究的靶点.
cho-k1细胞株的建立及其在药物安全性筛选方面的应用
张之东?,陈 慧?,郝六平?,魏 转?,李丽娟?
河北科技大学学报 , 2010, DOI: 10.7535/hbkd.2010yx02012
Abstract: 研究了稳定表达herg基因的cho-k1(中国仓鼠卵巢细胞)细胞株及其在药物研发安全性筛选方面的应用。使用lipofectamine2000系统将herg基因转染入cho-k1细胞,用westernblot检测其表达,并进一步通过fluxortmthalliumassaykits验证;同时使用fluxortmthalliumassaykits检测cisapride和dofetilide对herg通道的抑制性。建立了4株稳定表达herg基因的cho-k1细胞株,cisapride和dofetilide对herg通道的ic50分别为86.7nmol·l-1和28.1nmol·l-1。herg基因成功地在cho-k1细胞株实现了稳定表达,此细胞株可用于fluxortmthalliumassaykits系统,用于药物研发安全性筛选,以评估化合物潜在的心脏毒性。
herg收益框架及其在学术研究影响评价中的应用
孙志茹,张志强
情报资料工作 , 2011,
Abstract: ?文章首先简要介绍该框架的理论基础和组成部分,然后通过几个具体的学术研究影响评价项目对该框架的应用及发展状况做详细分析,最后对该框架的优点及存在的一些问题作了进一步讨论。
herg基因g572r突变体表达载体的构建及其稳定转染细胞系的建立
杨阳,黄娜,高岭,常素娥,郭波,胡丽丽,宋土生,黄辰
南方医科大学学报 , 2014,
Abstract: 目的构建herg基因g572r突变体表达载体并建立其稳定转染hek293的细胞系。方法应用重叠延伸pcr构建herg-g572r突变体表达载体,经g418筛选稳定转染细胞系,通过real-timepcr,westernblot及测序鉴定稳定转染细胞系。结果经序列比对,证明hek-herg-g572r突变体表达载体构建成功,real-timepcr,westernblot及测序证明稳定转染细胞系构建成功。结论该方法可成功构建的hke-herg-g572r细胞株,为药物个体化治疗提供工具。
先天性长QT综合征2型hERG基因G604S突变真核表达载体的构建和表达
Construction and expression of congenital LQT2 relating hERG gene G604S mutation eukaryotic expression vector

韩稳琦,霍建华,李国良,蒋永荣,武金娥,孙超峰
- , 2015,
Abstract: 目的:构建长QT综合征(LQTS)2型hERG 基因G604S突变的真核表达载体G604S??hERG??pcDNA3、G604S??hERG??pEGFP。方法:采用重叠延伸PCR法在pEGM??hERG基础上构建G604S突变体PGEM??hERG??G604S,通过限制性内切酶法和基因重组技术将突变体插入到真核表达载体pcDNA3和pEGFP??C2中并测序验证,用脂质体转染法将G604S??hERG??pEGFP转染至HEK293细胞并观察其荧光表达。结果:构建的含有突变位点的真核表达载体经DNA测序均成功验证hERG基因1 810位点碱基G突变为A,构建的G604S??hERG??pEGFP在HEK293细胞中成功表达绿色荧光。结论:成功构建hERG基因G604S??hERG??pcDNA3和G604S??hERG??pEGFP表达载体。
Aim: To construct eukaryotic expression vectors G604S??hERG??pcDNA3 and G604S??hERG??pEGFP linked to LQT2.Methods: PGEM??hERG??G604S containing G604S fragment was constructed using pEGM??hERG as a template by overlap extension PCR and then validated by DNA sequencing, then hERG??G604S sequence was subcloned into pcDNA3 and pEGFP??C2 vectors using restriction enzymes and gene recombination technology, respectively. After sequencing, G604S??hERG??pcDNA3 and G604S??hERG??pEGFP expression vectors were transfected into HEK293 cells to obtain heterologous expression system.Results: G604S??hERG??pcDNA3 and G604S??hERG??pEGFP eukaryotic expression vectors were constructed successfully, a missense mutation in hERG 1 810 site nucleotide G mutant to A was identified using DNA sequencing,hERG mutant was correctly combined to eukaryotic expression vector pEGFP??C2 and expressing green fluorescent protein confusion mutant G604S in HEK293 cells.Conclusion: The protocol can be used to construct the eukaryotic expression vector G604S??hERG??pcDNA3 and green fluorescent protein expression vector G604S??hERG??pEGFP.?
New Trends in Cancer Therapy: Targeting Ion Channels and Transporters
Annarosa Arcangeli,Andrea Becchetti
Pharmaceuticals , 2010, DOI: 10.3390/ph3041202
Abstract: The expression and activity of different channel types mark and regulate specific stages of cancer establishment and progression. Blocking channel activity impairs the growth of some tumors, both in vitro and in vivo, which opens a new field for pharmaceutical research. However, ion channel blockers may produce serious side effects, such as cardiac arrhythmias. For instance, K v11.1 (hERG1) channels are aberrantly expressed in several human cancers, in which they control different aspects of the neoplastic cell behaviour. hERG1 blockers tend to inhibit cancer growth. However they also retard the cardiac repolarization, thus lengthening the electrocardiographic QT interval, which can lead to life-threatening ventricular arrhythmias. Several possibilities exist to produce less harmful compounds, such as developing specific drugs that bind hERG1 channels in the open state or disassemble the ion channel/integrin complex which appears to be crucial in certain stages of neoplastic progression. The potential approaches to improve the efficacy and safety of ion channel targeting in oncology include: (1) targeting specific conformational channel states; (2) finding ever more specific inhibitors, including peptide toxins, for channel subtypes mainly expressed in well-identified tumors; (3) using specific ligands to convey traceable or cytotoxic compounds; (4) developing channel blocking antibodies; (5) designing new molecular tools to decrease channel expression in selected cancer types. Similar concepts apply to ion transporters such as the Na +/K + pump and the Na +/H + exchanger. Pharmacological targeting of these transporters is also currently being considered in anti-neoplastic therapy.
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