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Abela D Ritchie H Ababneh D Gavin C Nilsson MF Khan MK Carlsson K Webster WS 《Birth defects research. Part B, Developmental and reproductive toxicology》2010,89(5):429-440
This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the I(Kr)/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or I(Kr)/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing. 相似文献
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SUNG JIN CHO PYO YUN CHO MYUNG SIK LEE YOUNGEUN NA JOO HUN LEE KI SEOK KOH 《Invertebrate reproduction & development.》2013,57(2-3):103-108
Summary Previous studies have shown that spatiotemporal regulation of extracellular matrix (ECM) by proteinases is implicated in the initial step of regeneration. In amphibian regeneration, the up-regulation of proteinases such as metalloproteinases (MMPs) and cathepsin D, and proteinase-related proteins such as proteinase tissue inhibitors and activators has been demonstrated. Since the earthworm could provide a unique and valuable model to investigate the mechanism of regeneration, we studied the developmental change in proteinase expression during earthworm tail regeneration. Zymographic analysis revealed that proteinase activities began to increase within 1 h after amputation and reached a maximum at 7 days post-amputation. This peak in activity was approximately 22-fold greater than the unamputated controls. Thereafter, the proteinase activities tended to decrease followed by another peak at 30 days before returning to control levels. At least four types of proteinase were distinguishable at 7 and 30 days post-amputation, with molecular weights of 25, 28, 38, and 44 kDa, respectively. All proteinase activities were strongly inhibited by addition of phenylmethylsulfonyl fluoride (PMSF) and aprotinin, specific inhibitors for serine proteinase. Pepstatin A, E-64, iodoacetamide and a metal ion-free medium were not effective inhibitors, indicating that proteinases expressed during earthworm tail regeneration would be serine proteinases. In addition, we were able to detect two types of plasminogen activator (PA) with molecular weights of 40 and 47 kDa, respectively. PA activities were predominantly expressed at 1, 5, and 25 days post-amputation, which preceded two peaks of serine proteinase activities appearing at approximately 7 and 30 days after amputation, respectively. This fact supports the view that serine proteinases expressed in respond to tail amputation may be plasmin-like proteinases activated by PA. 相似文献
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DORIS GOMEZ CHRISTINA RICHARDSON MARC THÉRY THIERRY LENGAGNE JEAN‐PAUL LÉNA SANDRINE PLÉNET PIERRE JOLY 《Biological journal of the Linnean Society. Linnean Society of London》2011,103(3):633-647
In nocturnal treefrogs, mate choice implies the use of acoustic and visual signals. Multimodality is suspected to have evolved for either information redundancy or information complementariness. It is essential to explore multimodality in a natural context to understand the selection pressures operating on the signals. In the present study, we investigated calling and coloration in relation to male biometry and condition in four populations of European treefrog (Hyla arborea) varying in size and genetic isolation. We compared the signal intensity between core and satellite populations to estimate the impact of genetic diversity on male secondary sexual traits. The results obtained show important regional variations in both traits, likely as a result of local adaptations. Call and coloration are weakly correlated within an individual, implying that these traits likely convey different information about the signaller's identity or quality, thus supporting the hypothesis of complementariness of multiple messages. By contrast to the experimental evidence, we find that call and coloration are not related to male condition (as estimated by the residual of mass over size), suggesting that the condition‐dependence of these traits may be mediated by complex mechanisms not accurately reflected by the chosen estimator. Finally, male call and colour phenotypes present no robust pattern of variation with isolation status, probably because of variation in local selective pressures and in history of population dynamics. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 103 , 633–647. 相似文献
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目的:通过检测SD大鼠脑缺血再灌注模型血清中血管内皮生长因子(VEGF)与神经元凋亡动态表迭变化的关系,以探讨两者之间的相关性。方法:将40只大鼠随机分为8组:对照组、假手术组和脑缺血30min再灌注12h组、1d组、3d组、5d组、7d组、及14d组,每组5只。采用ELISA双抗夹心法检测大鼠血清中血管内皮生长因子、原位细胞凋亡TUNEL法检测脑组织中的凋亡神经细胞数。结果:再灌注12h、1d、3d、5d、7d及14d大鼠血清VEGF表达和凋亡神经元百分比的变化均为负相关性(均为P〈0.05)。结论:在脑缺血再灌注大鼠模型中,缺血诱导使VEGF的表达发生变化,VEGF通过直接或间接的途径抑制神经元凋亡。 相似文献
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弦音器是昆虫类特有的一种机械感受器,亦称弦音感受器或剑梢感受器。它主要具有感知外界声压和体内肌肉运动的听觉功能,研究弦音器的机能结构对揭秘昆虫听觉的神经机制有重要的科学意义。本文从弦音器多样性和进化入手,重点综述了弦音器的微细结构、基因功能定位、声音感受分子机制及其声压增幅分子生物物理学原理,为昆虫听觉仿生学的研究提供了理论依据。 相似文献