解剖学和形态学
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听力与言语-语言病理学
行为科学
心脏和心血管系统
细胞和组织工程学
临床神经病学
危重症监护医学
牙科,口腔外科和医学
皮肤病学
急诊医学
内分泌学和新陈代谢
肠胃学和肝脏学
老人病学和老年医学
卫生保健科学和服务
血液学
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传染病
综合和补充性医学
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医学,全科和内科
医学,法律
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神经系统科学
护理
营养学和饮食学
产科医学和妇科医学
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眼科学
整形外科学
耳鼻喉科学
病理学
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药理学和药剂学
生理学
基本医疗保健
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热带医学
泌尿学和肾脏学
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健康政策和服务
心理学,临床
abstract:INTRODUCTION:Drug-induced prolongation of the electrocardiographic QT interval (long QT syndrome) has been associated with increased risk of a serious ventricular arrhythmia, torsade de pointes. Inhibition of hERG, a cardiac potassium channel that controls action potential repolarization, is the most common cause of QT...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2008.10.004
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Drug-induced cardiovascular effects identified in conscious cynomolgus monkeys equipped with tethers and prepared for radiotelemetry were compared with results from anesthetized non-human primate (cynomolgus and rhesus) models. METHODS:Remifentanil (4.0 microg/kg, bolus), esmolol (2.0 mg/kg, bolus) and do...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2008.05.004
更新日期:2008-09-01 00:00:00
abstract:INTRODUCTION:Recent EU/US pediatric legislation and FDA/EMEA guidelines recognize the potential differences in safety profiles of drugs in adults versus young patients. Hence safety studies are recommended to investigate key functional domains of e.g. the developing CNS. METHODS:Selected psychoactive stimulants (caffe...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2008.06.001
更新日期:2008-09-01 00:00:00
abstract:INTRODUCTION:The aim of this experiment was to establish the usefulness of assessing temporal variability of the QT interval and changes in the T wave morphology in dogs as markers of pro-arrhythmic risk in humans. For this purpose, the electrocardiographic effects of astemizole and cisapride, two well known pro-arrhyt...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2008.03.001
更新日期:2008-05-01 00:00:00
abstract:INTRODUCTION:The aim of this work was to compare the suitability of different pharmacodynamic models for PK-PD modeling of verapamil cardiovascular effects in aortic coarctated rats (ACo), a model of renovascular hypertension. METHODS:A "shunt" microdialysis probe was inserted in a carotid artery of anaesthetized sham...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2008.03.002
更新日期:2008-05-01 00:00:00
abstract:INTRODUCTION:Recently we have demonstrated that to the choice of tissue type is important in identifying I(Kr) and I(Ks)-induced prolongation of the action potential. However, the differential sensitivity of cardiac tissues to other ionic current blockers or modulators is relatively unknown. The aim of the present stud...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.06.005
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:A Tecan-based enzyme inhibition assay has been developed for the determination of atorvastatin-derived 'active' and 'total' (active inhibitors plus atorvastatin lactone and other potential inhibitors following base hydrolysis) 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitor concentratio...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.06.002
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:The aim of the present study was to compare sensitivity in detecting the drug-induced QT interval prolongation in three dog models: conscious telemetered at sinus rhythm and conscious and anesthetized dogs during atrial pacing. The test substances used represent different chemical classes with different ph...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.05.002
更新日期:2007-09-01 00:00:00
abstract:INTRODUCTION:The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT i...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.04.002
更新日期:2007-09-01 00:00:00
abstract:INTRODUCTION:The evaluation of drug disposition properties of chemical entities in drug discovery research typically involves the conduct of pharmacokinetic studies in rodents that requires blood sampling over several time points, preferably without disrupting the physiological status of the animals. Several blood with...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.05.006
更新日期:2007-09-01 00:00:00
abstract:INTRODUCTION:Intracellular calcium concentration ([Ca(2+)](i)) modifications in endothelial and smooth muscle cells represent a key element in the pathogenesis of cerebral artery vasospasm. Therefore, the present study documented potential application of confocal laser microscopy in the determination of contractile and...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.03.002
更新日期:2007-07-01 00:00:00
abstract:INTRODUCTION:A large number of drugs from a variety of pharmacological classes have been demonstrated to cause adverse effects on cardiac rhythm, including the life-threatening arrhythmia Torsades de Pointes. These side effects are often associated with prolongation of the QT interval and are mediated via blockade of t...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2006.09.003
更新日期:2007-05-01 00:00:00
abstract:INTRODUCTION:Drug-induced QT interval prolongation has been one of the critical issues for developing new chemical entities and pharmaceutical companies need to evaluate the risk early in the development stage. At such stage, guinea pigs are appropriate due to their small size requiring only small amounts of test drugs...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2006.11.002
更新日期:2007-05-01 00:00:00
abstract::The isolated perfused mammalian heart preparation was established in 1897 by Oscar Langendorff. The method was developed on the basis of the isolated perfused frog heart established by Elias Cyon at the Carl Ludwig Institute of Physiology in Leipzig, Germany in 1866. Observations made using both methods at the end of ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.vascn.2006.05.006
更新日期:2007-03-01 00:00:00
abstract:INTRODUCTION:Methods to determine infarct size following ischemia-reperfusion injury include gross staining with triphenyltetrazolium chloride (TTC) and perfusion of colored dyes to demarcate the non-ischemic zone. Infarcted tissue (INF) can typically appear a mottled tan to brownish color, making a border between INF ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2006.06.005
更新日期:2007-03-01 00:00:00
abstract:INTRODUCTION:Challenge of guinea-pig tracheal epithelium with hyperosmolar solution alters ion transport and evokes the release of epithelium-derived relaxing factor (EpDRF). Cultured tracheal epithelial cells (CE) offer the potential to examine biochemical pathways related to EpDRF release, but whether the bioelectric...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2006.04.005
更新日期:2007-03-01 00:00:00
abstract:INTRODUCTION:Drug-induced QT interval prolongation may lead to ventricular arrhythmias. The aim of the study was to optimize QT interval data processing to quantify drug-induced QT interval prolongation in the telemetry instrumented conscious dog model. METHODS:The test substances cisapride, dofetilide, haloperidol, a...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2006.02.009
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Affymetrix oligonucleotide microarrays are widely used in basic and applied research (Lander, E.S., (1999). Array of hope. Nature Genetics 21, 3-4; Lockhart, D.J. & Winzeler, E.A. (2000) Genomics, gene expression and DNA arrays. Nature 405, 827-836.) The need for a significant amount of starting RNA has li...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.02.004
更新日期:2006-03-01 00:00:00
abstract:INTRODUCTION:Most preclinical trials are designed to identify potential torsadogenicity test only for surrogates of torsade de pointes, most commonly prolongation of the heart rate corrected QT interval (QTc). This study was conducted to determine which correction method best accounts for the effects of changes in the ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.04.013
更新日期:2006-03-01 00:00:00
abstract:INTRODUCTION:Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.02.003
更新日期:2006-01-01 00:00:00
abstract::Toxicogenomics, the application of genomic data to elucidate or predict an organism's response to a toxicant, can inform the drug development process in important ways. It is apparent that standardized approaches to many types of toxicogenomic questions are still being formulated. Specifically, a significant body of p...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,评审
doi:10.1016/j.vascn.2005.05.006
更新日期:2006-01-01 00:00:00
abstract::A method for determination of cis-diaminedichloroplatinum (II) (cisplatin) in ultrafiltered plasma, cell, and tumour samples is described. Cisplatin separation was carried out on a reversed-phase column using methanol-acetonitrile-water as the mobile phase. The flow rate was maintained constant at 1.6 mL/min and analy...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.06.005
更新日期:2005-11-01 00:00:00
abstract:INTRODUCTION:In the present study, a model was developed to determine the effect of secretase inhibition on beta-amyloid peptide (Abeta) levels in the cerebrospinal fluid (CSF) of freely moving adult rats. METHODS:Rats were chronically implanted with a cannula into the cisterna magna and CSF samples were collected at ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.02.002
更新日期:2005-09-01 00:00:00
abstract:INTRODUCTION:In this paper the activity of cytoplasmatic antioxidant enzymes after multiple freeze-thaw cycles of samples of cytoplasm was assayed in order to characterise the limits that would be necessary to impose on experimental design. METHODS:The activities of antioxidant enzymes in samples of rat liver cytoplas...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.03.002
更新日期:2005-09-01 00:00:00
abstract::Small interfering RNA (siRNA) directs the targeted destruction of mRNA encoding a specific protein, in a process known as RNA interference (RNAi). This stops translation of the targeted mRNA into protein, effectively silencing the gene. RNAi is a recent discovery, identified in mammalian cells in 2001, but it has rapi...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.08.012
更新日期:2005-05-01 00:00:00
abstract:INTRODUCTION:MEKK1 is a 196-kDa serine-threonine kinase activated in response to a variety of stimuli, including EGF, lysophosphatidic acid, osmotic stress, UV light, and microtubule toxins. However, there are few reports about the expression level of MEKK1 in cancers. METHODS:In this report, a direct competitive ELIS...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.08.004
更新日期:2005-03-01 00:00:00
abstract:INTRODUCTION:Laboratory investigations into cholestatic liver disease and the effects of cholemia on organ function are long-standing subjects of scientific enquiry. A widely-used strategy to investigate these topics relies on animal-based research using experimental animal models. Targeted inactivation of the spgp gen...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.06.002
更新日期:2004-11-01 00:00:00
abstract:INTRODUCTION:The standard Ficoll-Hypaque method used to isolate peripheral blood mononuclear cells (PBMC) gives very variable results when used with cynomolgus monkey blood. We have improved the method by using special cell processing tubes (CP-tubes), originally developed for clinical use. METHODS:Blood samples were ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.04.003
更新日期:2004-09-01 00:00:00
abstract:INTRODUCTION:cDNA microarray technology has greatly facilitated mechanistic studies in pharmacology and toxicology. A clean hybridization with minimal background is critical for successful microarray analysis and is highly desired. However, clean hybridization alone is not enough; verification is needed. METHODS:Total...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.02.001
更新日期:2004-07-01 00:00:00
abstract::The origins of safety pharmacology are grounded upon observations that organ functions (like organ structures) can be toxicological targets in humans exposed to novel therapeutic agents, and that drug effects on organ functions (unlike organ structures) are not readily detected by standard toxicological testing. Safet...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,评审
doi:10.1016/j.vascn.2004.02.007
更新日期:2004-05-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to determine the sensitivity and specificity for predicting the liability of a compound to lengthen QTc using isolated, perfused guinea pig hearts (Langendorff preparation). METHODS:QTc (Fridericia correction) was calculated from bipolar transventricular electrograms. Hearts ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2003.08.003
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to optimize carbon tetrachloride-induced hepatotoxicity in the rat with respect to dose, route of injection, and time course. METHODS:Male Wistar albino rats, 4 to 6 weeks old and weighing 130-180 g were used. Hepatotoxicity was evaluated by measuring the activity of serum en...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/S1056-8719(03)00019-4
更新日期:2002-07-01 00:00:00
abstract:INTRODUCTION:In order to investigate the pharmacokinetics of water-borne chemicals while eliminating exposures by other routes, a dermal exposure system was developed to expose the hand and forearm of human subjects. METHODS:The goal was, primarily, to study the dermal pharmacokinetics of methyl tertiary butyl ether (...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/S1056-8719(03)00004-2
更新日期:2002-05-01 00:00:00
abstract:INTRODUCTION:Measurement of tail skin temperature (T(sk)) of the rat can provide important information on mechanisms pertaining to physiology, pharmacology, and toxicology. T(sk) is largely under control of peripheral vascular tone, which is also sensitive to most experimental manipulations such as handling and restrai...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(02)00219-8
更新日期:2002-03-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to evaluate the feasibility of using gel electrophoresis combined with autoradiographic image analysis for quantitating protein drug concentrations in biological fluid for pharmacokinetic studies. METHODS:Protein drugs were iodinated using the Iodogen reagent and injected int...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(02)00203-4
更新日期:2002-01-01 00:00:00
abstract:INTRODUCTION:The quantification of [(3)H]noradrenaline spillover from electrically stimulated, sympathetic nerves is a widely used method to study presynaptic effects of hormones, transmitters and drugs. Although a straightforward approach, the execution of the experiments is not trivial. This holds true mainly for a r...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(02)00170-3
更新日期:2001-11-01 00:00:00
abstract:INTRODUCTION:The aim of this investigation was to evaluate methods for increasing Caco-2 cell throughput for assessing drug intestinal absorption. The use of 6-, 12-, and 24-well membranes and the effect of membrane size on permeability and the integrity of the Caco-2 cell monolayer were assessed. In an effort to optim...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(01)00161-7
更新日期:2001-07-01 00:00:00
abstract:INTRODUCTION:Xenobiotic metabolism in extrahepatic tissues has been extensively studied in vitro, but it is difficult to estimate in vivo the share of xenobiotic transformation in extrahepatic tissues for lack of a suitable approach. In this paper an in vivo rat model for assessment of extrahepatic metabolism is descri...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(01)00135-6
更新日期:2001-05-01 00:00:00
abstract::Fluorescent labeling of amine functional groups using dansyl chloride (DNS-Cl), and in sodium carbonate buffer, allowed the detection of 1 microg amounts of analytes. The methodology presented allows dansylation of primary, secondary, and tertiary amine groups at a temperature of 25 degrees C. The dansylation of terti...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(01)00157-5
更新日期:2001-05-01 00:00:00
abstract::The application of microdialysis technique for the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of probe performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investiga...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(00)00117-9
更新日期:2000-11-01 00:00:00