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Journal of Pharmacological and Toxicological Methods

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https://www.readbyqxmd.com/read/28989077/comparison-of-efficiencies-of-selected-sample-extraction-techniques-for-the-analysis-of-selected-antiretroviral-drugs-in-human-plasma-using-lc-ms
#1
Kwenga Sichilongo, Elliott Mwando, Enoch Sepako, Amos Massele
INTRODUCTION: Sample preparation in bio analytical chemistry poses a challenge because it can be compound dependent. We compared six sample extraction techniques i.e. QuEChERS (Q), liquid extraction (LE), protein precipitation (PPT), Q-PPT, Q-LE and LE-PPT for the extraction of antiretroviral drugs emtricitabine, tenofovir, efavirenz, lopinavir and rotinavir in human blood plasma. METHOD: A multiple reaction monitoring liquid chromatography- tandem mass spectrometry method for the determination of the same antiretroviral drugs developed and validated in this laboratory was used...
October 5, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28974368/correlation-of-pharmacokinetics-and-brain-penetration-data-of-adult-zebrafish-with-higher-mammals-including-humans
#2
Pushkar Kulkarni, Raghavender Medishetti, Nagaraju Nune, Swapna Yellanki, Vijaykumar Sripuram, Pallavi Rao, Dharmarajan Sriram, Uday Saxena, Srinivas Oruganti, Perumal Yogeeswari
INTRODUCTION: Adult zebrafish pharmacology is evolving rapidly for creating efficacy and safety models for drug discovery. However, there is very limited research in understanding pharmacokinetics (PK) in adult zebrafish. Methods for understanding PK will help in conducting pharmacokinetic - pharmacodynamic (PK-PD) correlations and improving the quality and applicability of data obtained using zebrafish. METHODS: We conducted adult zebrafish PK and brain penetration studies on two known compounds (irinotecan and lorcaserin) with distinct PK and brain penetration properties using validated LCMS/MS method...
September 30, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28970182/pathophysiological-profiles-of-sdt-fatty-rats-a-potential-new-diabetic-peripheral-neuropathy-model
#3
Tatsuya Maekawa, Hironobu Tadaki, Tomohiko Sasase, Yu Motohashi, Katsuhiro Miyajima, Takeshi Ohta, Shinichi Kume
INTRODUCTION: To establish an animal model for diabetic peripheral neuropathy (DPN) at an earlier stage, we performed functional and pathophysiological evaluations in Spontaneously Diabetic Torii (SDT) fatty rats before 16weeks of age. METHODS: Male SDT fatty rats were treated with vehicle or phlorizin (100 to 150mg/kg/day) from 5 to 16weeks. Sprague-Dawley (SD) rats were used as age-matched controls. Body weights and biochemical parameters were measured over time...
September 29, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28962917/a-novel-luminol-based-enhanced-chemiluminescence-antioxidant-capacity-microplate-assay-for-use-in-different-biological-matrices
#4
Tamás Kőszegi, Nikolett Sali, Maja Raknić, Zoltán Horváth-Szalai, Rita Csepregi, Marijana Zovko Končić, Nóra Papp, Miklós Poór
INTRODUCTION: Reactive oxygen species (ROS) are normal metabolic products of living cells. However, a decrease of the defense mechanisms against the effects of ROS or increased ROS production maybe one important causative factor of cellular damage. A non-enzymatic scavenger system is considered to be responsible for the maintenance of total antioxidant capacity (TAC) as a protection against oxidative injuries that exist in all higher plants and in mammals as well. METHODS: In our work, we optimized and validated a luminol-peroxidase-4-iodophenol-H2O2 enhanced chemiluminescence-based (ECL) TAC measurement technique...
September 28, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28962918/gene-expression-analysis-of-arc-mrna-as-a-neuronal-cell-activity-marker-in-the-hippocampus-and-amygdala-in-two-way-active-avoidance-test-in-rats
#5
Kyohei Yasuno, Erika Takahashi, Isao Igarashi, Takuma Iguchi, Yoshimi Tsuchiya, Kiyonori Kai, Kazuhiko Mori
INTRODUCTION: Immediate early genes are widely used as neuronal cell activity markers in neuroscience. The present study investigated the relationship between their expression and abnormality in context fear conditioning. METHODS: The learning test (two-way active avoidance test) was conducted in male rats administered with nonselective muscarinic antagonist scopolamine or selective dopamine D1-like receptor antagonist SCH 23390 at a dose level of 2.0 or 0.1mg/kg, respectively, for 4days...
September 27, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28927990/down-for-the-count-the-critical-endpoint-in-ototoxicity-remains-the-cytocochleogram
#6
REVIEW
David V Gauvin, Joshua Yoder, Andrea Koch, Zachary J Zimmermann, Rachel L Tapp
There are three major assays that must be conducted in standard investigational new drug (IND) -enabling ototoxicity study designs: 1) functional acoustic threshold measurements (Auditory Brainstem Respsonse, ABR); 2) otohistopathology and 3) cytocochleograms. We provide evidence to demonstrate the unreliability of auditory threshold shifts (ABRs) to predict cochlear cell death and build a case for conducting full cochlea processing and cell count measurements from the complete cochlea from apex to base.
September 18, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28830713/characterization-of-loperamide-mediated-block-of-herg-channels-at-physiological-temperature-and-its-proarrhythmia-propensity
#7
Jiansong Sheng, Phu N Tran, Zhihua Li, Sara Dutta, Kelly Chang, Thomas Colatsky, Wendy W Wu
BACKGROUND: Loperamide (Immodium®) is indicated for symptomatic control of diarrhea. It is a μ-opioid receptor agonist, and recently has been associated with misuse and abuse. At therapeutic doses loperamide has not been associated with cardiotoxicity. However, loperamide overdose is associated with proarrhythmia and death - two effects that are likely attributable to its block of cardiac ion channels that are critical for generating action potentials. In this study, we defined loperamide-hERG channel interaction characteristics, and used a ventricular myocyte action potential model to compare loperamide's proarrhythmia propensity to twelve drugs with defined levels of clinical risk...
August 19, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28827132/establishment-and-evaluation-of-immortalized-human-epidermal-keratinocytes-for-an-alternative-skin-irritation-test
#8
Cho-Won Kim, Chang Deok Kim, Kyung-Chul Choi
Human skin is located at the outermost part of the body, and various cosmetics and chemicals that may come in contact with human skin need to be evaluated for their potential to cause irritation. Until recently, the Draize test was considered the standard method for skin irritation; however, this technique has disadvantages such as the need to sacrifice many rabbits and subjective scoring. Thus, to contribute to the development of an animal-free alternative skin irritation test, we investigated the cytotoxicity and inflammatory response to standard skin irritants in SV40 large T antigen-transformed human epidermal keratinocyte 2 cells (SV-HEK2 cells)...
August 19, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28818556/receptor-binding-kinetics-equations-derivation-using-the-laplace-transform-method
#9
Sam R J Hoare
INTRODUCTION: Measuring unlabeled ligand receptor binding kinetics is valuable in optimizing and understanding drug action. Unfortunately, deriving equations for estimating kinetic parameters is challenging because it involves calculus; integration can be a frustrating barrier to the pharmacologist seeking to measure simple rate parameters. Here, a well-known tool for simplifying the derivation, the Laplace transform, is applied to models of receptor-ligand interaction. The method transforms differential equations to a form in which simple algebra can be applied to solve for the variable of interest, for example the concentration of ligand-bound receptor...
August 14, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28807796/high-content-image-analysis-hcia-assay-has-the-highest-correlation-with-direct-counting-cell-suspension-compared-to-the-atp-wst-8-and-alamar-blue-assays-for-measurement-of-cytotoxicity
#10
Haruna Tahara, Shun Matsuda, Yusuke Yamamoto, Hiroe Yoshizawa, Masaharu Fujita, Yasuhiro Katsuoka, Toshihiko Kasahara
INTRODUCTION: Various cytotoxicity assays measuring indicators such as enzyme activity, dye uptake, or cellular ATP content are often performed using 96-well microplates. However, recent reports show that cytotoxicity assays such as the ATP assay and MTS assay underestimate cytotoxicity when compounds such as anti-cancer drugs or mutagens induce cell hypertrophy whilst increasing intracellular ATP content. Therefore, we attempted to evaluate the reliability of a high-content image analysis (HCIA) assay to count cell number in a 96-well microplate automatically without using a cell-number indicator...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28797764/inflammatory-pain-assessment-in-the-arthritis-of-the-temporomandibular-joint-in-rats-a-comparison-between-two-phlogistic-agents
#11
Joana Cláudia Bezerra de Araújo, Delane Viana Gondim, André Luiz Cunha Cavalcante, Mario Roberto Pontes Lisboa, Gerly Anne de Castro Brito, Mariana Lima Vale
Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28797763/the-safety-pharmacology-society-salary-survey
#12
Michael K Pugsley, Simon Authier, Tiffini Brabham, Maxim Soloviev, Carrie G Markgraf, Krystle Correll, Martin Traebert, Andrea Greiter-Wilke, Jean-Pierre Valentin, Hugo Vargas, Alfred Botchway, Derek J Leishman, Michael J Curtis
INTRODUCTION: Safety pharmacology is a growing discipline with scientists broadly distributed across international geographical regions. This electronic salary survey is the first to be distributed amongst the entire Safety Pharmacology Society (SPS) membership. An electronic survey was sent to all members of the Society. Categorical survey questions assessed membership employment types, annual incomes, and professional certifications, along with other associated career attributes. METHODS: This survey was distributed to the SPS membership that is comprised of safety pharmacologists, toxicologists and pharmacologists working globally in the pharmaceutical industry, at contract research organizations (CRO), regulatory agencies, and academia or within the technology provider industry...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28780373/provision-of-food-and-water-in-rodent-whole-body-plethysmography-safety-pharmacology-respiratory-studies-impact-on-animal-welfare-and-data-quality
#13
Claire Grant, Louise Marks, Helen Prior
INTRODUCTION: We evaluated the feasibility of providing food and water to rodents during whole body plethysmography (WBP) studies as a welfare improvement to standard conditions. METHODS: Male Han Wistar rats or CD1 mice (n=8) were placed in WBP chambers and respiratory parameters recorded for approximately 6h on four separate occasions. On each occasion the animals were exposed to a different plethysmography chamber environment using a randomised design: no food/water (the standard conditions), water bottle, hydrating gel and wet food...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28716665/applying-label-free-dynamic-mass-redistribution-assay-for-studying-endogenous-fpr1-receptor-signalling-in-human-neutrophils
#14
Hanna B Christensen, David E Gloriam, Daniel Sejer Pedersen, Jack B Cowland, Niels Borregaard, Hans Bräuner-Osborne
INTRODUCTION: The label-free dynamic mass redistribution-based assay (DMR) is a powerful method for studying signalling pathways of G protein-coupled receptors (GPCRs). Herein we present the label-free DMR assay as a robust readout for pharmacological characterization of formyl peptide receptors (FPRs) in human neutrophils. METHODS: Neutrophils were isolated from fresh human blood and their responses to FPR1 and FPR2 agonists, i.e. compound 43, fMLF and WKYMVm were measured in a label-free DMR assay using Epic Benchtop System from Corning®...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28712933/measuring-drug-absorption-improves-interpretation-of-behavioral-responses-in-a-larval-zebrafish-locomotor-assay-for-predicting-seizure-liability
#15
Steven Cassar, Laura Breidenbach, Amanda Olson, Xin Huang, Heather Britton, Clarissa Woody, Pankajkumar Sancheti, DeAnne Stolarik, Karsten Wicke, Katja Hempel, Bruce LeRoy
INTRODUCTION: Unanticipated effects on the central nervous system are a concern during new drug development. A larval zebrafish locomotor assay can reveal seizure liability of experimental molecules before testing in mammals. Relative absorption of compounds by larvae is lacking in prior reports of such assays; having those data may be valuable for interpreting seizure liability assay performance. METHODS: Twenty-eight reference drugs were tested at multiple dose levels in fish water and analyzed by a blinded investigator...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28688881/the-abdominal-skin-of-female-sprague-dawley-rats-is-more-sensitive-than-the-back-skin-to-drug-induced-phototoxicity
#16
Kazuhiro Kuga, Hironobu Yasuno, Yumi Sakai, Yumiko Harada, Fumi Shimizu, Yumiko Miyamoto, Yuki Takamatsu, Makoto Miyamoto, Keiichiro Sato
In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm(2) ultraviolet A...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28658603/physiological-approaches-to-assess-diminished-sympathetic-activity-in-the-conscious-rat
#17
Matthew R Zahner, Chang-Ning Liu, Vincent Bernardo, Carrie Northcott, Cheryl Tyszkiewicz, Carlin Okerberg, Magalie Boucher, Ingrid Pardo, Chris J Somps
The purpose of this study was to evaluate functional measures of diminished sympathetic activity after postganglionic neuronal loss in the conscious rat. To produce variable degrees of sympathetic postganglionic neuronal loss, adult rats were treated daily with toxic doses of guanethidine (100mg/kg) for either 5days or 11days, followed by a recovery period of at least 18days. Heart rate, blood pressure, cardiac baroreflex responsiveness, urinalysis (for catecholamine metabolite, 3-methoxy-4-hydroxyphenylethylenglycol; MHPG), and pupillometry were performed during the recovery period...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28642085/comparison-of-glutathione-levels-measured-using-optimized-monochlorobimane-assay-with-those-from-ortho-phthalaldehyde-assay-in-intact-cells
#18
Jan Čapek, Martina Hauschke, Lenka Brůčková, Tomáš Roušar
Fluorometric glutathione assays have been generally preferred for their high specificity and sensitivity. An additional advantage offered by fluorescent bimane dyes is their ability to penetrate inside the cell. Their ability to react with glutathione within intact cells is frequently useful in flow cytometry and microscopy. Hence, the aims of our study were to use monochlorobimane for optimizing a spectrofluorometric glutathione assay in cells and then to compare that assay with the frequently used ortho-phthalaldehyde assay...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28552277/the-determination-of-hepatic-glutathione-at-tissue-and-subcellular-level
#19
Tamás Lőrincz, András Szarka
INTRODUCTION: Glutathione (GSH) through its important function in the antioxidant protection of cells and in the conjugation of drugs and xenobiotics has crucial importance in pharmacology and toxicology. Since GSH is most often measured in liver tissue and different cell organelles it is important to choose the method that best suits for the determination of GSH. METHODS: The GSH content of cell organelles isolated from control and BSO-treated liver tissues was determined by the GSH-NEM-HPLC-UV, monochlorobimane-GSH-HPLC-fluorescence method and DTNB-GSH recycling assay to find the most suitable method for GSH determination from cell organelles...
November 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28522142/integration-and-validation-of-the-ex-vivo-human-placenta-perfusion-model
#20
Sigrid Conings, Frédéric Amant, Pieter Annaert, Kristel Van Calsteren
INTRODUCTION: The ex vivo human placenta perfusion model is an effective and non-invasive method to study transplacental passage of drugs and environmental compounds in humans. Due to many challenges and its high complexity it remains difficult to incorporate it routinely into laboratories. METHODS: This article describes a step-by-step protocol for the implementation and validation of a closed-closed ex vivo perfusion model. Antipyrine, a small molecule that passes the placental barrier by passive diffusion, was used as a measurement of overlap between foetal and maternal circulation...
November 2017: Journal of Pharmacological and Toxicological Methods
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