Abstract：
:Many xenobiotics cause hepatobiliary toxicity and cholestasis in the rat. Initial assessment of hepatobiliary damage in rats can be accomplished by measuring serum concentrations of bile acids and bilirubin, serum activities of liver-associated enzymes such as 5'-nucleotidase, alkaline phosphatase, gamma-glutamyltranspeptidase, and plasma clearances of dyes [e.g., bromosulfophthalein (BSP)] excreted primarily through the bile. More detailed evaluation of hepatobiliary disturbances involves cannulation of the bile duct of anesthetized rats and subsequent measurement of rates of bile flow, bile acid excretion, and bile composition. Canalicular bile flow can be estimated from clearances of nonmetabolized sugars (i.e., erythritol) which enter bile via paracellular transport. Tight junction permeability also can be assessed by either biliary excretion of such a marker as horseradish peroxidase or sucrose following portal vein infusion or via retrograde biliary infusion. Subsequent morphologic evaluation of the liver provides information on damage to cells which may contribute to hepatobiliary dysfunction (i.e., bile duct obstruction). Isolated perfused livers offer the ability to measure all of the above mentioned parameters as well as to make a more accurate determination of the effects of xenobiotics on bile acid-dependent and -independent bile flow. A good example of the advantage of combining techniques as well as following complete time courses of changes in hepatobiliary function is provided by using studies of alpha-naphthylisothiocyanate-induced hepatotoxicity.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Handler JA,Kossor DC,Goldstein RSdoi
10.1016/1056-8719(94)90024-8subject
Has Abstractpub_date
1994-02-01 00:00:00pages
11-9issue
1eissn
1056-8719issn
1873-488Xpii
1056-8719(94)90024-8journal_volume
31pub_type
杂志文章,评审abstract：INTRODUCTION:Excitation of Acetylcholine-mediated (Ach) transmission (especially if irreversible) may pose life-threatening adverse events by increasing neuronal network activity. Unfortunately, adequate detection of this liability during early drug development is hampered, because published ex vivo electrophysiologica...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.12.001
更新日期：2015-01-01 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：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：:Hemodynamic and biochemical changes were studied on 36 white ELCO-rabbits, seven adult older than 150 days, seven immatures between 21 and 27 days, and seven neonatals between 7 and 14 days. Five supplementary hearts of each age group served for preischemic biochemical values. Protection during 60 min of global ischem...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(93)90016-8
更新日期：1993-12-01 00:00:00
abstract：:There is a need for short-term, reliable and reproducible animal model of chronic pancreatitis (CP) in small animals like mice. This study was aimed to establish the 9 exposures of cerulein-induced CP in mice. Repeated intraperitoneal cerulein injections were performed at 6 consecutive doses (50 μg/kg)/day, 3 days a w...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2019.01.002
更新日期：2019-01-01 00:00:00
abstract：:This article describes the application of a Microplate Filtration System (MFS) to a binding assay, with the results being compared to those obtained with a conventional 24-Well Filtration Manifold (24WFM). The data reported here characterize the PAF receptor on rabbit platelet membranes using [3H]apafant. The results ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(96)00074-3
更新日期：1996-09-01 00:00:00
abstract：INTRODUCTION:Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2015.05.002
更新日期：2015-09-01 00:00:00
abstract：:The properties of the ternary complex model (TCM) of drug action at G protein-coupled receptors (GPCRs) were examined, using theoretical computer simulations, with regard to the predicted effects of the presence of a fixed concentration of one agonist on the competition binding profile of another. Subsequently, the bi...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(00)00078-2
更新日期：2000-01-01 00:00:00
abstract：:Multiple ECG analysis strategies are used in safety pharmacology in a framework focused on accurate ECG complex interval quantification and arrhythmia detection. Automated arrhythmia detection is commonly used in the clinic and adapted tools may be used to facilitate analysis of large non-clinical datasets in safety p...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2010.06.005
更新日期：2010-09-01 00:00:00
abstract：:Induction of acute myocardial infarction in the rat is an established model for studying effects of therapeutic interventions. Images of sections of the rat left ventricle, stained with nitroblue tetrazolium, were digitized and several parameters estimated by dedicated software on an image analyzer (IBAS 2.0). The met...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(95)00019-e
更新日期：1995-08-01 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：:For the rapid assay of norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) in the mouse brain, we developed a simple method using isocratic HPLC with coulometric detection. This method permits NE and MHPG assay within 5 min in one chromatographic run. Within-run coefficients of variati...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(94)90060-4
更新日期：1994-10-01 00:00:00
abstract：:The purpose of this study was to develop a simple and noninvasive method for the quantitative evaluation of neuromuscular blockade in mice. The sciatic nerve in anesthetized animals (etomidate, 50 mg/kg or mephenesin, 250 mg/kg) was stimulated using transcutaneous electrodes; repetitive supramaximal stimulations (3 Hz...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(92)90033-w
更新日期：1992-05-01 00:00:00
abstract：INTRODUCTION:Voltage-sensitive optical (VSO) sensors offer a minimally invasive method to study the time course of repolarization of the cardiac action potential (AP). This Comprehensive in vitro Proarrhythmia Assay (CiPA) cross-platform study investigates protocol design and measurement variability of VSO sensors for ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2019.106612
更新日期：2019-01-01 00:00:00
abstract：:Abnormal water barrier function occurs in irritated skin and certain cutaneous diseases. Methods have been compared for separating the epidermis (site of the barrier) from the whole skin without disturbing the barrier function. The epidermis was separated from newborn rat skin by (1) exposure to 10% trypsin at 4 degre...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(98)00044-6
更新日期：1998-10-01 00:00:00
abstract：:A method, using quantitative electroencephalography (qEEG), was developed for screening xenobiotics in conjunction with neurological examinations, for defining toxicodynamic profiles of certain drugs and chemicals in the dog. The standard 10-channel montage was used to evaluate normotonic, auditory, visual, and somato...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(94)90008-6
更新日期：1994-08-01 00:00:00
abstract：INTRODUCTION:Accurate preclinical modeling of diabetic complications such as retinopathy, nephropathy and neuropathy is crucial to enable the development of novel preventative therapies. The aims of this study were to establish a model of long-term diabetes with sustained medium scale hyperglycemia and characterize the...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2015.11.003
更新日期：2016-03-01 00:00:00
abstract：:The majority of articles published in J Pharmacol Tox Methods describe new approaches, or modifications to those established (Curtis, 2006). However, even established methods have their limitations. It is part of the practice of research to troubleshoot: to identify methodological weaknesses and correct them. This pro...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 社论
doi：10.1016/j.vascn.2010.02.013
更新日期：2010-03-01 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:Regulatory guidelines recommend the use of conscious, unrestrained animals for comprehensive cardiovascular safety assessment of a new therapeutic agent. Cardiovascular safety pharmacology studies normally use internal telemetry (surgical implants) in free-moving animals to monitor key ECG endpoints, like ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2009.04.196
更新日期：2009-07-01 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:Oxidative stress plays an important role in drug-induced toxicity. Oxidative stress-mediated toxicities can be detected using conventional animal models but their sensitivity is insufficient, and novel models to improve susceptibility to oxidative stress have been researched. In recent years, gene targetin...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2018.12.006
更新日期：2019-01-01 00:00:00
abstract：:A method for the rapid detection of intracellular nitric oxide (NO) generation in dissociated cerebellar granule cells using dichlorofluorescin (DCFH) and flow cytometry was developed. DCFH can be oxidized specifically by NO and this was assessed by 1) the use of SIN-1 (10 nM-100 microM), an NO donor, that induced a c...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(97)00066-x
更新日期：1997-10-01 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：:In this study a new model of cerebral ischemia, based on a middle cerebral artery (MCA) thrombosis in rats is described. Furthermore, the effect of the novel plasminogen activator (SUN9216), a plasminogen-plasminogen activator chimera, comprising the fibrin kringle 1 domain of a plasminogen, and the two kringles, and ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(93)90068-p
更新日期：1993-06-01 00:00:00
abstract：INTRODUCTION:There has been an increasing need to conduct investigative safety pharmacology studies to complement regulatory-required studies, particularly as it applies to a comprehensive assessment of cardiovascular (CV) risk. METHODS:We describe refined methodology using a combination of telemetry and direct signal...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2016.05.002
更新日期：2016-09-01 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:A credible animal overactive bladder model used in basic research is an indispensable harbinger of safe and ethical clinical trials on human subjects. Our objective was to develop a new animal model of a hyperactive bladder that will be void of inflammatory urothelium lesions and display significant sensit...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2015.04.006
更新日期：2015-07-01 00:00:00
abstract：:Escherichia coli produces a heat-stable (STa) enterotoxin that belongs to a family of peptides that mediate several diarrheal diseases, including traveler's diarrhea and epidemic diarrhea in infants and newborns. The STa enterotoxin consists of 18 or 19 amino acids and is encoded by genes specified on a transposon. In...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/1056-8719(92)90049-7
更新日期：1992-09-01 00:00:00
abstract：:In a typical flowchart for discovery of novel analgesic (or other) agents, a critical path often involves maximization of the separation of the therapeutic endpoint from known adverse-effect (AE) endpoint(s). Although strategies can easily be designed for in vitro paradigms such as high-throughput screening, extension...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/s1056-8719(00)00041-1
更新日期：1999-11-01 00:00:00
