Murine models of psoriasis and its applications in drug development
Publication date: Available online 18 November 2019Source: Journal of Pharmacological and Toxicological MethodsAuthor(s): Tingting Luo, Yang Ma, Wei WeiAbstractPsoriasis is an autoimmune skin disease which characteristic of a well-demarcated, erythematous, raised lesion with silvery-white dry scale. Although the mechanism of psoriasis has not been fully understood so far, much progress has been made in understanding many of its complex potential mechanism, particularly the crucial role of the IL-23/Th17 axis. There are a large number of psoriasis models that reflect the complexity of the psoriasis mechanisms. In this revie...
Source: Journal of Pharmacological and Toxicological Methods - November 20, 2019 Category: Drugs & Pharmacology Source Type: research

A DNAzyme based knockdown model for Fragile-X syndrome in zebrafish reveals a critical window for therapeutic intervention
In this study, we have used a novel DNAzyme based approach to create a larval model of FXS in zebrafish with specific focus on the early developmental window.MethodsFmr1specific DNAzymes were electroporated into embryos to create theknockdown. Changes in RNA and protein levels of FMRP and relevant biomarkers were measured in the 0-7dpf window. Behavioral tests to measure anxiety, cognitive impairments and irritability in the larvae were conducted at the 7dpf stage. Drug treatment was carried out at various time points in the 0-7dpf window to identify the critical window for pharmacological intervention.ResultsThe DNAzyme b...
Source: Journal of Pharmacological and Toxicological Methods - November 15, 2019 Category: Drugs & Pharmacology Source Type: research

A fully validated simple new method for environmental monitoring by surface sampling for cytotoxics
Publication date: Available online 15 November 2019Source: Journal of Pharmacological and Toxicological MethodsAuthor(s): E. Rossignol, M.B. Amiand, J. Sorrieul, J.M. Bard, C. Bobin-DubigeonAbstractA wipe sampling procedure followed by a simple ultra-performance liquid chromatography – tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) and gemcitabine (GEM), as surrogate markers for occupational exposure.After a solid-phase extraction of wiping fi...
Source: Journal of Pharmacological and Toxicological Methods - November 15, 2019 Category: Drugs & Pharmacology Source Type: research

Investigating the applicability of different amounts of solutions used in experiments, which performed in rat knee joints: Determining the optimal intraarticular injection volume
In conclusion, the injection volume for the knee joints of rats should not exceed the 30 μL for optimum efficiency. (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 14, 2019 Category: Drugs & Pharmacology Source Type: research

Variation in diagnostic NAFLD/NASH read-outs in paired liver samples from rodent models
DiscussionDependent on animal model, both histopathological and biochemical end-points differed between sampling sites in the liver. Based on these findings, we recommend that sample site location is highly standardized and properly reported in order to minimize potential sampling variation and to optimize reproducibility and meaningful comparisons of preclinical studies of NAFLD. (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 14, 2019 Category: Drugs & Pharmacology Source Type: research

Corrigendum to “Derivation and presentation of formulas for drug concentrations in two-, three- and four-compartment pharmacokinetic models” [Journal of Pharmacological and Toxicological Methods 100 (2019) 106621]
Publication date: January–February 2020Source: Journal of Pharmacological and Toxicological Methods, Volume 101Author(s): Cyprian Świętaszczyk, Lars Jødal (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 14, 2019 Category: Drugs & Pharmacology Source Type: research

Refinement of the rodent pentylenetetrazole proconvulsion assay, which is a good predictor of convulsions in repeat-dose toxicology studies
DiscussionRisk assessment at an early stage of drug development supports candidate selection and, along that approach, the PTZ proconvulsion assay was proven to be a good predictor of convulsions in subsequent toxicology studies. It was also demonstrated that a relatively lower PTZ dose (60 mg/kg) improved the dose-response-curve of the positive control tested, decreased mortality overall and, therefore, contributes to refining this standard procedure for CNS safety evaluation. (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 14, 2019 Category: Drugs & Pharmacology Source Type: research

Rat multicellular 3D liver microtissues to explore TGF-β1 induced effects
Publication date: Available online 13 November 2019Source: Journal of Pharmacological and Toxicological MethodsAuthor(s): Vincenzo Prestigiacomo, Anna Weston, Laura Suter-DickAbstractChronic liver damage can lead to fibrosis, encompassing hepatocellular injury, activation of Kupffer cells (KC), and activation of hepatic stellate cells (HSC). Inflammation and TGF-β1 are known mediators in the liver fibrosis adverse outcome pathway (AOP). The aim of this project was to develop a suitable rodent cell culture model for the investigation of key events involved in the development of liver fibrosis, specifically the responses to...
Source: Journal of Pharmacological and Toxicological Methods - November 14, 2019 Category: Drugs & Pharmacology Source Type: research

Improving prediction of torsadogenic risk in the CiPA in silico model by appropriately accounting for clinical exposure
Publication date: Available online 13 November 2019Source: Journal of Pharmacological and Toxicological MethodsAuthor(s): Derek J. LeishmanAbstractAny adverse event is reliant on three properties: the appropriate pharmacology to trigger the event, the appropriate exposure of compound, and intrinsic patient factors. Each alone is necessary but insufficient to predict the event. The Comprehensive in vitro Proarrhythmia Assessment (CiPA) initiative attempts to predict the risk of torsade de pointes (TdP) by focusing on an in-silico model with thresholds determined at modest multiples of the therapeutic exposure for the parent...
Source: Journal of Pharmacological and Toxicological Methods - November 14, 2019 Category: Drugs & Pharmacology Source Type: research

Erratum to “Derivation and presentation of formulas for drug concentrations in two-, three- and four-compartment pharmacokinetic models” [Journal of Pharmacological and Toxicological Methods 100 (2019), 106621]
Publication date: Available online 13 November 2019Source: Journal of Pharmacological and Toxicological MethodsAuthor(s): Lars Jødal (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 14, 2019 Category: Drugs & Pharmacology Source Type: research

Comparison of several immunoassays used in drugs of abuse screening: Assessment against gold standard methods and calculation of measurement uncertainty
ConclusionsThis study covered a fundamental gap in available knowledge by evaluating the performance of screening the current new generation of immunoassays methods for drugs of abuse in urine against gold standard methods. (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 12, 2019 Category: Drugs & Pharmacology Source Type: research

Resolving the reversed rate effect of calcium channel blockers on human induced pluripotent stem cell-derived cardiomyocytes and the impact on in vitro cardiac safety evaluation
Publication date: September–October 2019Source: Journal of Pharmacological and Toxicological Methods, Volume 99Author(s): Haoyu Zeng, Jixin Wang, Holly Clouse, Armando Lagrutta, Frederick Sannajust (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 5, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: November–December 2019Source: Journal of Pharmacological and Toxicological Methods, Volume 100Author(s): (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 5, 2019 Category: Drugs & Pharmacology Source Type: research

Comparison of in silico action potential modeling (AP-Predict) and the hiPSc-CM MEA assay in predicting drug-induced cardiotoxicity
Publication date: September–October 2019Source: Journal of Pharmacological and Toxicological Methods, Volume 99Author(s): Shuya Wang, Patricia A. Valentine, Matthew J. Cato, Anthony Bahinski, Khuram W. Chaudhary (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 1, 2019 Category: Drugs & Pharmacology Source Type: research

Comparison of effects of moxifloxacin on QT, JTpeak and Tpe in conscious telemetered dogs and nonhuman primates
Publication date: September–October 2019Source: Journal of Pharmacological and Toxicological Methods, Volume 99Author(s): Todd Wisialowski, William Gorczyca, Peter Harris (Source: Journal of Pharmacological and Toxicological Methods)
Source: Journal of Pharmacological and Toxicological Methods - November 1, 2019 Category: Drugs & Pharmacology Source Type: research