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Journal of Pharmacological and Toxicological Methods

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https://www.readbyqxmd.com/read/30594530/increased-susceptibility-to-oxidative-stress-induced-toxicological-evaluation-by-genetically-modified-nrf2a-deficient-zebrafish
#1
Akihito Yamashita, Jiro Deguchi, Yayoi Honda, Toru Yamada, Izuru Miyawaki, Yuhei Nishimura, Toshio Tanaka
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 targeting methods in zebrafish have been developed, making it possible to generate homozygous null mutants. In this study, we established zebrafish deficient in the nuclear factor erythroid 2-related factor 2a (nrf2a), a key antioxidant-responsive gene, and its potential to detect oxidative stress-mediated toxicity was examined...
December 27, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30583015/availability-of-multistep-light-stimulus-method-for-evaluation-of-visual-dysfunctions
#2
Naohisa Umeya, Yuki Yoshizawa, Kosuke Fukuda, Keigo Ikeda, Mami Kamada, Izuru Miyawaki
In the field of drug safety research, electroretinography (ERG) is commonly conducted according to the international standard method propounded by the International Society for Clinical Electrophysiology of Vision (ISCEV) in recent years. However, various ERG methods other than the ISCEV standard method are also utilized depending on the intended purpose of the evaluation. In this study, we investigated the availability of a multistep light stimulus method for evaluation of rod function in Long-Evans rats using sildenafil, which is known to inhibit phosphodiesterase 6 (PDE6) in phototransduction and induce visual dysfunctions in humans...
December 21, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30580044/impact-of-disease-state-on-arrhythmic-event-detection-by-action-potential-modelling-in-cardiac-safety-pharmacology
#3
Bernard Christophe, William J Crumb
INTRODUCTION: The use of in silico cardiac action potential simulations is one of the pillars of the CiPA initiative (Comprehensive in vitro Proarrhythmia Assay) currently under evaluation designed to detect more accurately proarrhythmic liabilities of new drug candidate. In order to take into account the variability of clinical situations, we propose to improve this method by studying the impact of various disease states on arrhythmic events induced by 30 torsadogenic or non-torsadogenic compounds...
December 20, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30553974/assessing-the-risk-of-drug-crystallization-in-vivo
#4
Stefan Ruepp, Evan Janovitz, Thomas Brodie, Randy White, Joseph Santella, John Hynes, Julie Carman, Duohai Pan, Yang Wu, Umesh Hanumegowda, Brian Gemzik, John Megill, Janet DiPiero, Dieter Drexler, Ching-Chiang Su, Michael Hageman
INTRODUCTION: Low intrinsic solubility leading to poor oral bioavailability is a common challenge in drug discovery that can often be overcome by formulation strategies, however, it remains a potential limitation that can pose challenges for early risk assessment and represent a significant obstacle to drug development. We identified a selective inhibitor (BMS-986126) of the IL-1 receptor-associated kinase 4 (IRAK4) with favorable properties as a lead candidate, but with unusually low intrinsic solubility of <1 μg/mL...
December 13, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30552958/protocol-for-evaluation-of-topical-ophthalmic-drug-products-in-different-compartments-of-fresh-eye-tissues-in-a-rabbit-model
#5
Ashok Chockalingam, Lin Xu, Sharron Stewart, Maxime LeMerdy, Eleftheria Tsakalozou, Jianghong Fan, Vikram Patel, Rodney Rouse
Topical ophthalmic drugs are the most commonly used dosage form to treat diseases of the anterior segment of the eye. Although this dosage form has the advantages of ease of application, small volume dose, and rapid action and is largely devoid of systemic adverse effects, the bioavailability is low due to pre-corneal anatomical barriers and the nature of the drug formulation itself. Some complex generic formulations (suspensions, ointments, gels) for topical ophthalmic products face impediments to rapid regulatory approval because of the complex nature of the formulations and difficulties in determining bioequivalence with the innovator product...
December 12, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30529169/hydrophobic-drug-adsorption-loss-to-syringe-filters-from-a-perspective-of-drug-delivery
#6
Xiaoli Li, Xiaoxu Ding, Chengying Bian, Shaoqun Wu, Miao Chen, Weizhuo Wang, Jingjie Wang, Lingyun Cheng
Filtering with a syringe filter is a common operation in pharmaceutical analysis. Ophthalmic research often has a limited amount of sample and low amount of drug which is vulnerable to filtering membrane adsorption loss but not well recognized in the research community. Current study investigated drug adsorption by 11 types of syringe filters for 4 hydrophobic compounds commonly encountered in transscleral drug delivery. Among the 11 types of syringe filters surveyed, polytetrafluoroethylene - NBA, polytetrafluoroethylene - NLA, and polypropylene filters caused the least adsorptive drug loss for these four drugs studied...
December 4, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30502391/preparation-of-phenylephrine-3-o-sulfate-as-the-major-in-vivo-metabolite-of-phenylephrine-to-facilitate-its-pharmacokinetic-and-metabolism-studies
#7
Zhenxian Zhang, Yan Zhang, Phillip M Gerk
INTRODUCTION: The in vivo disposition and metabolism of phenylephrine have not been establishedby previous analytical methods and there is a lack of available standards for quantitating the metabolites. METHODS: We pursued and compared the preparation of sulfation metabolites of phenylephrine and its ethyl analog etilefrine via chemical and bio-synthesis. RESULTS: Both sulfates were obtained in higher yield and purity through chemical syntheses compared to biosynthesis...
November 28, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30502390/development-of-a-bioreactor-system-for-cytotoxic-evaluation-of-pharmacological-compounds-in-living-cells-using-nmr-spectroscopy
#8
Josué Carvalho, Sara Alves, M Margarida C A Castro, Carlos F G C Geraldes, João A Queiroz, Carla P Fonsec, Carla Cruz
INTRODUCTION: The evaluation of drug's cytotoxicity is a crucial step in the development of new pharmacological compounds. 31 P NMR can be a tool for toxicological screening, as it enables the study of drugs' cytotoxicity and their effect on cell energy metabolism in a real-time, in a non- invasive and non-destructive way. This paper details a step-by-step protocol to implement a bioreactor system able to maintain cell viability during NMR acquisitions, at high cell densities and for several hours, enabling toxicological evaluation of pharmacological compounds in living cells...
November 28, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30500431/larval-zebrafish-model-for-studying-the-effects-of-valproic-acid-on-neurodevelopment-an-approach-towards-modeling-autism
#9
Shubham Dwivedi, Raghavender Medishetti, Rita Rani, Aarti Sevilimedu, Pushkar Kulkarni, Perumal Yogeeswari
INTRODUCTION: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder of early onset, characterized by impaired sociability, cognitive function and stereotypies. The etiology of ASD involves a multidimensional link between genetic, neurobiological and environmental factors. Since existing, comprehensive animal models for ASD are time consuming and laborious, the need for simple, quick approaches to study subsets of ASD-associated characteristics has always been in demand for better understanding of disease...
November 27, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30476623/a-novel-high-content-imaging-based-technique-for-measuring-binding-of-dickkopf-1-to-low-density-lipoprotein-receptor-related-protein-6
#10
Richard S Priestley, Jonathan Cheung, Emma J Murphy, Matthias T Ehebauer, John B Davis, Elena Di Daniel
INTRODUCTION: Dickkopf-related protein 1 (Dkk1) is a secreted protein ligand of low-density lipoprotein receptor-related protein 6 (LRP6), which antagonises canonical Wnt signalling. Elevated Dkk1 levels have been linked to Alzheimer's disease (AD), with protein blockade protective in pre-clinical AD models, suggesting inhibitors of Dkk1-LRP6 binding may have therapeutic utility against AD. Cell-based Dkk1-LRP6 assays reported in the literature use either modified Dkk1 protein and/or do not possess suitable throughput for drug screening...
November 23, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30476622/relative-equivalence-of-cns-safety-fob-assessment-outcomes-in-male-and-female-wistar-han-and-sprague-dawley-rats
#11
David V Gauvin, Jill A Dalton, Marci L Harter, David Holdsworth, Jonelle May, Rachel Tapp, Zachary J Zimmermann, Quinn Kilgus, Theodore J Baird
In 2006 the National Toxicology Program (NTP) of the FDA shifted to the preferred use of Wistar-Han rats from the more commonly used Sprague-Dawley (SD) strain - and industry followed. While European laboratories preferred the Wistar-Han line, there was a paucity of relevant historical control data in many US research institutions for the new "industry standard" rat strain. In 2010 the NTP reversed its decision and shifted back to SD rats because of reproductive issues with the Wistar strain. For post hoc comparative analyses, we report minimal practical differences in Functional Observational Battery (FOB) data from a large sample of male and female Wistar-Han and SD rats...
November 23, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30476621/a-novel-experimental-intraperitoneal-infection-model-for-haemophilus-parasuis-in-neutropenic-guinea-pigs
#12
Yong-da Zhao, Bao-Tao Liu, Li-Li Guo, Hu Shan, Bing-Hu Fang
INTRODUCTION: Haemophilus parasuis, one of the major swine pathogens, has at least fifteen different types, all of which have significant economic effects on the global swine industry. The aim of this study was to establish an experimental intraperitoneal infection model for H. parasuis in neutropenic guinea pigs. METHODS: Intraperitoneal administration of cyclophosphamide and Haemophilus parasuis was conducted in guinea pigs. Clinical signs, gross pathology, and histopathology were observed in neutropenic guinea pigs infected with H...
November 23, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30476620/influence-of-incubation-conditions-on-microsomal-metabolism-of-xanthine-derived-a-1-adenosine-receptor-ligands
#13
Daniela Schneider, Dirk Bier, Andreas Bauer, Bernd Neumaier, Marcus Holschbach
INTRODUCTION: In vitro metabolism models such as liver microsomes represent an important tool for the development of novel radioligands. Comparability and physiological relevance of in vitro metabolism data critically depend on the careful evaluation and optimization of assay protocols. We therefore investigated the influence of incubation conditions on the microsomal stability of xanthine-derived A1 adenosine receptor (A1 AR) ligands which have been developed for positron emission tomography (PET)...
November 23, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30476619/individual-variability-in-female-and-male-mice-in-a-test-retest-protocol-of-the-forced-swim-test
#14
Lydmila Kazavchinsky, Anat Dafna, Haim Einat
BACKGROUND: The challenges to embody the complexity of symptoms and biological mechanism of affective disorders question the value of animal models as well as their reproducibility and validity. Validity is further hindered by large individual variability in many models. Whereas individual variability presents a challenge, it can also be used to study susceptibility and resistance. One of the frequently used models for screening antidepressants and interventions related to depression is the forced swim test (FST)...
November 23, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30399523/corrigendum-to-an-overview-of-the-safety-pharmacology-society-strategic-plan-journal-of-pharmacological-and-toxicological-methods-93-2018-35-45
#15
M K Pugsley, S Authier, J E Koerner, W S Redfern, C G Markgraf, T Brabham, K Correll, M V Soloviev, A Botchway, M Engwall, M Traebert, J-P Valentin, T J Mow, A Greiter-Wilke, D J Leishman, H M Vargas
No abstract text is available yet for this article.
November 3, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30481558/two-immunoassays-for-the-detection-of-2c-b-and-related-hallucinogenic-phenethylamines
#16
Anna Šuláková, Lucie Fojtíková, Barbora Holubová, Kateřina Bártová, Oldřich Lapčík, Martin Kuchař
INTRODUCTION: The use of new psychoactive substances as drugs of abuse has dramatically increased over the last years. Hallucinogenic phenethylamines gained particular popularity as they have both stimulating and psychedelic effects. Although generally perceived as safe, these illicit drugs pose a serious health risk; they have been linked to cases of severe poisoning or even deaths. Therefore, simple, cost-effective and reliable methods are needed for rapid determination of abused hallucinogens...
January 2019: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/30031827/comparison-of-different-microscopy-approaches-to-quantification-of-inhibitory-effect-on-thrombus-formation-under-flow-conditions-by-the-example-of-adenosine-receptor-agonist-he-neca
#17
Tomasz Przygodzki, Nina Wolska, Marcin Talar, Dawid Polak, Magdalena Gapinska, Cezary Watala
INTRODUCTION: Thrombus formation in vitro in flow conditions and its visualization and quantification with the use of microscopy are widely utilized to evaluate activity of compounds with a potential antithrombotic activity. Visualization and quantification of thrombi can be performed with the use of wide-field or confocal microscopy. Acquiring reliable numerical data from wide-field microscopy images of objects which have a complex three-dimensional structure is strongly influenced by the methods used for image analysis...
November 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29906510/evaluation-of-warming-devices-for-lateral-tail-vein-blood-collection-in-mice-mus-musculus
#18
John M David, Xian Chen
No abstract text is available yet for this article.
November 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29906509/photothrombotically-induced-unilateral-selective-hippocampal-ischemia-in-rat
#19
Sayed Masoud Hosseini, Hamid Gholami Pourbadie, Nima Naderi, Mohammad Sayyah, Mohammad Ismail Zibaii
INTRODUCTION: The vulnerability of hippocampal formation to ischemic insult has been documented in both humans and animal models. Ischemic injury induction through photothrombosis is an invasive and reproducible model of ischemic stroke which provides the ability to induce ischemia selectively in any desired area. In this study, we describe a method to induce selective unilateral hippocampal ischemia in rat through modified photothrombotic model. METHODS: Male wistar rats (n = 66) were subjected to stereotaxic surgery to insert a guide cannula just above the ascending part of hippocampal fissure...
November 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29859814/quantitation-of-sevoflurane-in-whole-blood-and-aqueous-solutions-by-volatile-organic-compound-sensing
#20
Yuri Hase, Kuniaki Suzuki, Nobuhito Kamekura, Makiko Shibuya, Yu Takahashi, Kosuke Namba, Toshiaki Fujisawa
INTRODUCTION: It is difficult to quantify poorly soluble volatile anesthetics in aqueous solutions; this necessitates the development of alternative prompt methods to analyze the in vivo blood concentrations of anesthetics for the clinical assessment of anesthesia depth. In this study, we demonstrated that the difficulties can be overcome by using volatile organic compound (VOC) sensors, which allow the levels of vaporized VOCs to be quantified in several seconds and obviate the need for conventional techniques such as gas chromatography or nuclear magnetic resonance (NMR)...
November 2018: Journal of Pharmacological and Toxicological Methods
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