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 different time points from the same animal without anaesthesia. The levels of CSF Abeta were measured by a sandwich ELISA assay. RESULTS:Administration of DAPT, a functional gamma-secretase inhibitor, resulted in a substantial reduction of Abeta40 and Abeta42, confirming the in vivo functionality of the CSF as a biomarker source for endogenous APP processing modulation by secretase inhibitors. DISCUSSION:Thus, the present work provides clear evidence for the usefulness of CSF sampling from the freely moving rat model for testing the effectiveness of small molecule inhibitors of Abeta production.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
El Mouedden M,Haseldonckx M,Mackie C,Meert T,Mercken Mdoi
10.1016/j.vascn.2005.02.002keywords:
subject
Has Abstractpub_date
2005-09-01 00:00:00pages
229-33issue
2eissn
1056-8719issn
1873-488Xpii
S1056-8719(05)00020-1journal_volume
52pub_type
杂志文章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：INTRODUCTION:Opioid withdrawal syndrome is a critical component of opioid abuse and consists of a wide array of symptoms including increases in pain sensitivity (hyperalgesia). A reliable preclinical model of hyperalgesia during opioid withdrawal is needed to evaluate possible interventions to alleviate withdrawal. The...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2013.02.003
更新日期：2013-05-01 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：:All new molecular entities (NMEs) with targeted or indirect effects on the central nervous system (CNS) must be evaluated for their abuse liability as a part of their nonclinical development plan. Inherently key in the drug control review is the term "relative abuse liability". The basis for determination of drug cont...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/j.vascn.2018.08.001
更新日期：2018-01-01 00:00:00
abstract：:A comparison is made of four rat aortic preparations, that is, single ring, spiral strip, zig-zag strip, and multiple-ring, on the basis of the responses to norepinephrine (NE) and acetylcholine (ACh). The single ring preparation was suitable under isometric, but not under isotonic conditions, because of the small iso...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(96)00023-8
更新日期：1996-06-01 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：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 researc...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2012.02.001
更新日期：2012-03-01 00:00:00
abstract：INTRODUCTION:IonWorks automated patch clamp systems are being widely used for ion channel drug discovery, but the perforated patch mode of these systems makes it difficult to obtain a steady intracellular Ca(2+) concentration ([Ca(2+)](i)). This difficulty prevents obtaining high-quality data regarding Ca(2+)-activated...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2012.10.005
更新日期：2013-01-01 00:00:00
abstract：:Electrical field stimulation (EFS, 2.5 Hz, 60 V, 1 ms, trains of 5 sec every 5 min) of the rat external urethral sphincter (EUS) produced contractile responses characterized by a "slow" tonic contraction on which was superimposed a series of phasic "twitch-like" contractions. Both responses were abolished by tetrodoto...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/1056-8719(92)90052-3
更新日期：1992-09-01 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: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: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: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：INTRODUCTION:The pharmacological assessment of the factors for gastric protection of a test substance should involve experimental models that can determine the involvement of cytoprotective factors, as well as their influence on the secretion of hydrochloric acid. The original protocol of pylorus ligation in rats propo...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2012.09.002
更新日期：2013-03-01 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:In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect of morphine on three objectiv...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.vascn.2015.01.005
更新日期：2015-05-01 00:00:00
abstract：:Evaluation of the myocardial relaxation has become important in the last years. An impaired relaxation may precede contractile dysfunctions and even cause heart failure. To treat this impaired lusitropism it is necessary to properly assess the lusitropic state of the heart and understand how drugs affect the cellular ...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,评审
doi：10.1016/1056-8719(94)90011-6
更新日期：1994-09-01 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: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:Different methods for the analysis of behavioral observation data were compared to evaluate how the interpretation of a data set may depend on the analysis method employed. METHODS:Three methods of analysis were used to evaluate the same four sets of rodent behavioral FOB data: (1) evaluation by a trained...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2010.06.001
更新日期：2010-09-01 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：: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：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：INTRODUCTION:Although the effects of relatively high concentrations of endotoxin on endothelial activation/dysfunction and kidney markers has been described in literature, detailed insight in the LPS concentration-effect relationship, the magnitude, variability and timing of the response, and potential effects of endot...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.vascn.2017.10.004
更新日期：2018-01-01 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：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：: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:Although therapeutically beneficial in the treatment of certain diseases, L-type calcium channel antagonism can result in unwanted off-target pharmacology leading to adverse drug reactions and to the termination of the development of otherwise promising compounds. In the present study three marketed calciu...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2016.11.002
更新日期：2017-01-01 00:00:00
abstract：INTRODUCTION:Gastrointestinal (GI) motility disorders include many clinical manifestations associated with various pathologies. They are widespread and can be considered a primary symptom or can be associated to other diseases, such as Parkinson's disease. Understanding the type and site of GI dysmotility is crucial to...
journal_title：Journal of pharmacological and toxicological methods
pub_type： 杂志文章
doi：10.1016/j.vascn.2014.08.003
更新日期：2014-09-01 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
