Abstract:
INTRODUCTION:Bioimpedance spectroscopy (BIS) has been used in human and large animal research to assess body fluid compartment volumes (BFC) such as total body water (TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV). To date, the application of BIS for determination of BFC in small research animals has been limited. METHODS:We sought to evaluate the sensitivity and consistency of BIS for the determination of BFC in male SD rats. Thus, in separate series of experiments, we a) compared BFC values determined using BIS to BFC values obtained using radioisotope indicator dilution methods; b) examined day-to-day intra- and inter-rat BFC variability in small (267.8±5.4 g) and large (372.6±5.6 g) rats (n=8/group) as compared to empirical normative mammalian values; c) evaluated the sensitivity of BIS to detect time-dependent responses to repeated administration of a potent diuretic; and d) compared empirically generated BFC data to predicted osmotically-induced ECFV and ICFV shifts in response to i.v. administration of hypotonic (0.3%), isotonic (0.9%) or hypertonic (3.0%) saline (n=6/concentration). RESULTS:BFC values generated using radioisotope dilution agreed with those generated using BIS. BIS reliably detected differences between small and large rats (p<0.001), and was associated with low (<3.5%) day-to-day, intra-animal coefficient of variation (%=Standard Deviation/mean). BIS detected small reductions (~10%) in ECFV induced by as few as 2 days of the loop diuretic, furosemide, relative to vehicle treatment (70.8±1.5 ml vs. 84.0±1.5 ml; respectively, p<0.05). BIS rapidly detected shifts between ECFV and ICFV in response to osmotic saline challenge, and these responses were similar to physiologically predicted responses. DISCUSSION:The current studies support using BIS as a means of sensitively and reliably performing repeated measurements of BFC in rats of a) differing sizes, b) in response to therapeutic agents known to influence renal sodium handling and c) in response to osmotic challenge.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Hu L,Maslanik T,Zerebeckyj M,Plato CFdoi
10.1016/j.vascn.2012.02.001subject
Has Abstractpub_date
2012-03-01 00:00:00pages
75-82issue
2eissn
1056-8719issn
1873-488Xpii
S1056-8719(12)00018-4journal_volume
65pub_type
杂志文章abstract:INTRODUCTION:Detection of drug effects on neuronal synapses is important for predicting their adverse effects. We have used drebrin as a marker to detect the synaptic changes in cultured neurons. High concentration of glutamate decreases the amount of drebrin in synapses. To increase the availability of this method for...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2019.106607
更新日期:2019-01-01 00:00:00
abstract::Undesired immune responses against protein therapeutics may adversely affect the pharmacokinetics, efficacy, and safety of the product. The presence of anti-drug-antibodies (ADA) has been the key determinant of immunogenic responses. Here we describe the use of a capillary electrophoresis platform for the identificati...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2020.106872
更新日期:2020-01-01 00:00:00
abstract::We have developed a method for the rapid isolation of hepatocyte nuclei, which employs gentle homogenization and centrifugation conditions, and involves minimal processing time. The purified nuclei were morphologically unaltered when observed by light and electron microscopy. No significant contamination from cytoplas...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(97)00082-8
更新日期:1997-11-01 00:00:00
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::Regulation of brain temperature during and after cerebral ischemia plays an important role in the evolution of neuronal damage. Therefore, it is essential to maintain brain temperature at 37 degrees C during and after the ischemic insult. To get information about brain temperature during the experimental procedure, re...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(92)90016-t
更新日期:1992-03-01 00:00:00
abstract::The potentiation of the antinociceptive effect of morphine by dipyrone (metamizol) and the possible participation of a peripheral mechanism on such synergism were studied with the use of the formalin test in the rat. Nociception was induced by the intraplantar injection of diluted formalin (1%) in the right hind paw. ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(00)00046-0
更新日期:1999-10-01 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::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:INTRODUCTION:Mouse models of chronic heart failure (HF) have been widely used in HF research. However, the current HF models most often use the C57BL/6 mouse strain and do not show the clinically relevant characteristics of pulmonary congestion. In this study, we developed a robust mouse model of HF in the BALB/c mouse...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2019.02.001
更新日期:2019-01-01 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::Lipid peroxidation is a major consequence of oxidative stress and an important cause of neuronal damage in ischaemic injuries and neurodegenerative disorders such as Parkinson's disease. Recent research has focused on the development of antioxidant drugs which may delay or minimize neurodegeneration. Rapid and reliabl...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(98)00022-7
更新日期:1998-04-01 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:In response to the ongoing shift of the regulatory cardiac safety paradigm, a recent White Paper proposed general principles for developing and implementing proarrhythmia risk prediction models. These principles included development strategies to validate models, and implementation strategies to ensure a m...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2020.106890
更新日期:2020-09-01 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::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: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::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-glutamyltrans...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,评审
doi:10.1016/1056-8719(94)90024-8
更新日期:1994-02-01 00:00:00
abstract::Evaluation of angiotensin II (AII) receptor binding often necessitates freezing of the tissue of interest prior to assay of radioligand binding. This study evaluated the effects of freezing of various rat tissues at different rates on 125I-sarcosine1, isoleucine8 angiotensin II (125I-SI AII) binding to AII receptor su...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(94)00061-8
更新日期:1995-04-01 00:00:00
abstract::The objective of this research is to determine whether the administration of a complete soft food formula to sub-lethal irradiated animals from three different transgenic mouse strains over a period of 21 consecutive days will have a significant impact on the clinical signs, and the general survival rate of the animal...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.12.003
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Evaluation of drug candidates in in-vitro assays of action potential duration (APD) is one component of preclinical safety assessment. Current assays are limited by technically-demanding, time-consuming electrophysiological methods. This study aimed to assess whether a voltage-sensitive dye-based assay cou...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2009.03.005
更新日期:2009-07-01 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: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: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:INTRODUCTION:RL-14 cells, human fetal ventricular cardiomyocytes, are a commercially available cell line that has been established from non-proliferating primary cultures derived from human fetal heart tissue. However, the expression of different drug metabolizing enzymes (DMEs) in RL-14 cells has not been elucidated y...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.11.005
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Ex vivo studies of human fetal hepatic drug metabolism are uncommon as it requires access to functional liver tissue and therefore raises practical and ethical concerns. Large animal models provide an alternative opportunity to study changes in cytochrome P450 (CYP) activity in the mother and fetus during ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2020.106934
更新日期:2020-01-01 00:00:00
abstract:INTRODUCTION:Understanding the appropriate application of telemetry and other technologies for nonclinical investigation of functional safety issues in the context of ongoing toxicology evaluations is a current industry challenge. One major issue is related to the potential impact of surgical implantation of a telemetr...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2013.02.006
更新日期:2013-05-01 00:00:00
abstract::High-content screening (HCS) systems can be used for high-throughput screening of drugs in human embryonic stem cells (hESCs). However, hESCs require immunofluorescence staining with stemness markers (e.g., Oct-4) prior to HCS, which can be time consuming and labor intensive. In this study, we employed transgenic hESC...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2020.106913
更新日期:2020-01-01 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:INTRODUCTION:An increase in striatal dopamine is considered essential for the rewarding and reinforcing effects of drugs of abuse. We have developed and validated an ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the analysis of dopamine in rat brain extracellular fluid (...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2015.06.002
更新日期:2015-07-01 00:00:00
abstract:INTRODUCTION:Fosmidomycin is a phosphonic acid derivative originally isolated as a natural antibiotic from Streptomyces lavendulae. It was originally used as an antibiotic, and later on as an antimalarial drug. A simple, sensitive, selective and reproducible bioassay based on colorimetric method was developed for the d...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2010.02.012
更新日期:2010-05-01 00:00:00