Read by QxMD icon Read

Journal of Pharmacological and Toxicological Methods

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
Bernard Fermini, Kevin P Coyne, Shawn T Coyne
The ever-increasing cost of drug discovery and development represents a significant challenge for the pharmaceutical industry and new strategies to bridge studies between preclinical testing and clinical trials are needed to reduce the knowledge gap prior to first human exposures, and to allow earlier decisions to be made on the further development of drugs. A number of studies have demonstrated that various cell types differentiated from human induced pluripotent stem cells (iPSCs) do not just respond similarly to human tissues in general, but rather recapitulate the drug response of their specific donor's, when exposed to the same drug in vivo...
September 26, 2018: Journal of Pharmacological and Toxicological Methods
François Noël, Pedro Azalim, Fernando M do Monte, Luis Eduardo M Quintas, Adriana Katz, Steven J D Karlish
INTRODUCTION: Ouabain and digoxin are classical inhibitors of the Na+ ,K+ -ATPase. In addition to their conventional uses as therapeutic agents or experimental tools there is renewed interest due to evidence suggesting they could be endogenous hormones. Somewhat surprisingly, different publications show large discrepancies in potency for inhibiting Na+ ,K+ -ATPase activity (IC50 ), particularly for the slow binding inhibitors, ouabain and digoxin. METHODS: Using purified pig kidney Na+ ,K+ -ATPase (α1β1FXYD2) and purified detergent-soluble recombinant human Na+ ,K+ -ATPase (α1β1FXYD1) we have re-evaluated binding and inhibition kinetics and effects of K+ concentration for ouabain, digoxin, ouabagenin and digoxigenin...
September 20, 2018: Journal of Pharmacological and Toxicological Methods
Kim A Henderson, R Brandon Borders, John B Ross, Amir Abdulalil, Seth Gibbs, Anthony J Skowronek, Katherine Knostman, Jay Bailey, Jeremy Smith, Tom Vinci, Brandon Wood, Michael V Knopp, Brian M Roche
The isolated rat heart (Langendorff) assay combined with NMR spectroscopy and histology were used to elucidate functional, metabolic, and histological signs of cardiotoxicity resulting from acute exposure to clinically relevant concentrations of doxorubicin and its metabolite dox-ol. Doxorubicin blood concentrations and pharmacokinetic parameters were assessed following a clinically relevant dose of 2 mg/kg in order to select concentrations for isolated heart perfusions. Isolated rat hearts were exposed to 1 or 10 μM of doxorubicin or 0...
September 6, 2018: Journal of Pharmacological and Toxicological Methods
Valeria Avataneo, Amedeo De Nicolò, Franco Rabbia, Mauro Sciandra, Francesco Tosello, Jessica Cusato, Elisa Perlo, Giovanna Fatiguso, Sarah Allegra, Fabio Favata, Paolo Mulatero, Franco Veglio, Giovanni Di Perri, Antonio D'Avolio
INTRODUCTION: Nowadays, the treatment of hypertension represents an important issue, particularly in developed countries. While in most cases the standard therapeutic approaches, consisting in the administration of 1 to 3 drugs, are adequate to reach adequate blood pressure levels, in some cases more drugs are needed: this condition is called "resistant hypertension". In this context, the administration of a diuretic, such as spironolactone or canrenoate salts, represents a standard practice...
August 28, 2018: Journal of Pharmacological and Toxicological Methods
Debbie Grønlund, Lene Vase, Stine Abildgaard Knudsen, Maria Christensen, Asbjørn Mohr Drewes, Anne Estrup Olesen
INTRODUCTION: Correlations between subjective and objective measures of constipation have seldom been demonstrated. This could be due to multiple confounding factors in clinical studies and the broad span of symptoms represented in questionnaires used to assess constipation. We developed a new method for categorizing gastrointestinal (GI) symptoms into relevant symptom groups, and used this in a controlled experimental study aimed to investigate whether GI transit times and colonic volumes were correlated to self-reported GI symptoms...
August 24, 2018: Journal of Pharmacological and Toxicological Methods
David V Gauvin, Zachary J Zimmermann, Theodore J Baird
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 control is critically dependent on the nonclinical assessment of the reinforcing attributes of the NME in animals (rat is the regulatory preferred species) in a standard operant conditioning paradigm...
August 18, 2018: Journal of Pharmacological and Toxicological Methods
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
John M David, Xian Chen
No abstract text is available yet for this article.
November 2018: Journal of Pharmacological and Toxicological Methods
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
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
Tully Erwin, Satish P Rekulapally, Thomas S Abraham, Qinfeng Liu
INTRODUCTION: Calcium/Calmodulin-dependent protein kinase II (CaMKII) is a multifunctional protein kinase that phosphorylates and regulates activity of many substrates in various tissues. Traditional CaMKII activity assays rely on incorporation of radioactivity onto a CaMKII substrate by utilizing γ-32 P ATP, which has a short half-life and can pose health risks to the researchers. METHODS: An 8-minute HPLC-MS method was developed to measure a CaMKII-specific peptide substrate autocamtide-2 (AC-2) and its phosphorylated form, phosphoautocamtide-2 (PAC-2)...
November 2018: Journal of Pharmacological and Toxicological Methods
David V Gauvin, Zachary J Zimmermann, Joshua Yoder, Marci Harter, David Holdsworth, Quinn Kilgus, Jonelle May, Jill Dalton, Theodore J Baird
Three significant contributions to the field of safety pharmacology were recently published detailing the use of electroencephalography (EEG) by telemetry in a critical role in the successful evaluation of a compound during drug development (1] Authier, Delatte, Kallman, Stevens & Markgraf; JPTM 2016; 81:274-285; 2] Accardi, Pugsley, Forster, Troncy, Huang & Authier; JPTM; 81: 47-59; 3] Bassett, Troncy, Pouliot, Paquette, Ascaha, & Authier; JPTM 2016; 70: 230-240). These authors present a convincing case for monitoring neocortical biopotential waveforms (EEG, ECoG, etc) during preclinical toxicology studies as an opportunity for early identification of a central nervous system (CNS) risk during Investigational New Drug (IND) Enabling Studies...
November 2018: Journal of Pharmacological and Toxicological Methods
Haley K Andersen, Gerardo G Piroli, Kenneth B Walsh
The cannabinoid CB1 receptor is expressed throughout the central nervous system where it functions to regulate neurotransmitter release and synaptic plasticity. While the CB1 receptor has been identified as a target for both natural and synthetic cannabinoids, the specific downstream signaling pathways activated by these various ligands have not been fully described. In this study, we developed a real-time membrane potential fluorescent assay for cannabinoids using pituitary AtT20 cells that endogenously express G protein-gated inward rectifier K+ (GIRK) channels and were stably transfected with the CB1 receptor using a recombinant lentivirus...
November 2018: Journal of Pharmacological and Toxicological Methods
Chang Z Zhu, Kelly J Doyle, Arthur L Nikkel, Lauren Olsen, Marian T Namovic, Katherine Salte, Deborah Widomski, Zhi Su, Diana L Donnelly-Roberts, Murali M Gopalakrishnan, Steve McGaraughty
INTRODUCTION: The adenine model of kidney disease typically involves dietary delivery of adenine over several weeks. This model can be variable in its disease progression and can result in significant mortality. In the current study, the amount of adenine delivered to rats was controlled by utilizing oral gavage administration over a short period in an attempt to induce robust renal pathology while addressing variability and viability of the animals. METHODS: Adenine (150 or 200 mg/kg) was administered via oral gavage for 10 consecutive days, and assessed over a total of 20 days...
November 2018: Journal of Pharmacological and Toxicological Methods
Sharmila Rajan, Junichiro Sonoda, Timothy Tully, Ambrose J Williams, Feng Yang, Frank Macchi, Terry Hudson, Mark Z Chen, Shannon Liu, Nicole Valle, Kyra Cowan, Thomas Gelzleichter
INTRODUCTION: bFKB1 is a humanized bispecific IgG1 antibody, created by conjoining an anti-Fibroblast Growth Factor Receptor 1 (FGFR1) half-antibody to an anti-Klothoβ (KLB) half-antibody, using the knobs-into-holes strategy. bFKB1 acts as a highly selective agonist for the FGFR1/KLB receptor complex and is intended to ameliorate obesity-associated metabolic defects by mimicking the activity of the hormone FGF21. An important aspect of the biologics product manufacturing process is to establish meaningful product specifications regarding the tolerable levels of impurities that copurify with the drug product...
November 2018: Journal of Pharmacological and Toxicological Methods
Rafael Campos, Samara F Bittencourt, Julio Alejandro Rojas-Moscoso, Lorenzo Pissinatti, Lu Shi Chen, Marcovan Porto, Ronilson Agnaldo Moreno, Gustavo D Mendes, Gilberto De Nucci
INTRODUCTION: Vaginal route is often used in topical antifungal formulations. Vaginal permeability assays are generally performed as in vitro tests. METHOD: An in vivo vaginal permeability assay was developed using female rabbits. Fenticonazole permeability was evaluated by assessing fenticonazole bioavailability in plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Toxicity was monitored histopathologically after 8 consecutive days of antifungal treatment (20 mg/animal)...
November 2018: Journal of Pharmacological and Toxicological Methods
Daniela Figueroa, Mohammad Asaduzzaman, Fiona Young
The detection of reactive oxygen species (ROS) using 2',7'-dichlorofluorescin diacetate (DCFDA) is commonly performed by a single measurement of fluorescence but this fails to capture a profile of ROS generation over time. This study aimed to develop a real-time monitoring method to increase the utility of the assay, to incorporate cytotoxicity screening and to describe the combined effects of DCFDA and the ROS generator, Ter-butyl hydrogen peroxide (TBHP). Breast cancer MCF-7 cells were loaded with DCFDA (0-50 μM) for 45 min, and then exposed to TBHP (0-50 μM)...
November 2018: Journal of Pharmacological and Toxicological Methods
Karen Tse, Rowland Sillito, Amy Keerie, Rachel Collier, Claire Grant, Natasha A Karp, Cathy Vickers, Kathryn Chapman, J Douglas Armstrong, William S Redfern
BACKGROUND: The ActualHCA™ system continuously monitors the activity, temperature and behavior of group-housed rats without invasive surgery. The system was validated to detect the contrasting effects of sedative and stimulant test agents (chlorpromazine, clonidine and amphetamine), and compared with the modified Irwin test (mIT) with rectal temperature measurements. METHODS: Six male Han Wistar rats per group were used to assess each test agent and vehicle controls in separate ActualHCA™ recordings and mIT...
November 2018: Journal of Pharmacological and Toxicological Methods
Corina T Bot, Krisztina Juhasz, Fabian Haeusermann, Liudmila Polonchuk, Martin Traebert, Sonja Stoelzle-Feix
INTRODUCTION: Since 2005 the S7B and E14 guidances from ICH and FDA have been in place to assess a potential drug candidate's ability to cause long QT syndrome. To refine these guidelines, the FDA proposed the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, where the assessment of drug effects on cardiac repolarization was one subject of investigation. Within the myocyte validation study, effects of pharmaceutical compounds on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were assessed and this article will focus on the evaluation of the proarrhythmic potential of 23 blinded drugs in four hiPSC-CM cell lines...
September 2018: Journal of Pharmacological and Toxicological Methods
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"