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Clinical Toxicology

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https://www.readbyqxmd.com/read/28541461/screening-with-quantification-for-64-drugs-and-metabolites-in-human-urine-using-uplc-ms-ms-analysis-and-a-threshold-accurate-calibration
#1
Thomas G Rosano, Patrice Y Ohouo, Michelle Wood
Drug and metabolite (analytes) identification together with quantification is an important analytical tool in forensic and clinical toxicology. We report the development and validation of a definitive detection and quantification method (UPLC-MS-MS) for initial screening of 64 analytes in urine. The principle of the method is a quantitative extension of a recently reported threshold accurate calibration (TAC) technique which employs a rapid dual-specimen analysis i.e., with and without addition of a reference-analyte standard for normalization of matrix effects...
May 24, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28540608/ethics-and-medical-toxicology-research
#2
Jeremy Sugarman, Andrew Stolbach
Optimizing care in medical toxicology necessitates designing and conducting ethical research. Nevertheless, the context of medical toxicology can make clinical research ethically challenging for a variety of reasons: medical toxicology is typified by relative rare conditions; making precise and rapid diagnoses is often fraught with uncertainty; emergent and urgent clinical exigencies make consent difficult or impossible; and some exposures are stigmatized or related to illegal activities that can compromise collecting accurate data from patients...
May 24, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28540501/morphometric-characterization-of-rat-and-human-alveolar-macrophage-cell-models-and-their-response-to-amiodarone-using-high-content-image-analysis
#3
Ewelina Hoffman, Aateka Patel, Doug Ball, Jan Klapwijk, Val Millar, Abhinav Kumar, Abigail Martin, Rhamiya Mahendran, Lea Ann Dailey, Ben Forbes, Victoria Hutter
PURPOSE: Progress to the clinic may be delayed or prevented when vacuolated or "foamy" alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures. METHODS: Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation...
May 24, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28540455/yellow-sac-spider-cheiracanthium-punctorium-bites-in-slovenia-case-series-and-review
#4
REVIEW
Tanja Varl, Damjan Grenc, Rok Kostanjšek, Miran Brvar
In Central Europe, reports of human envenomation by Cheiracanthium punctorium, commonly known as the yellow sac spider, are sporadic, despite the fact that this species is widespread in Europe. However, in recent years, C. punctorium has been repeatedly described globally in medical and toxicological literature. Its venom was found to possess insecticidal, haemolytic, cytotoxic, and membrane-damaging activities. Its bite is often very painful, frequently associated with local and transient cutaneous and neurotoxic effects, but sometimes also with systemic symptoms which require medical help...
May 24, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28539737/preclinical-toxicological-evaluation-of-idm01-the-botanical-composition-of-4-hydroxyisoleucine-and-trigonelline-based-standardized-fenugreek-seed-extract
#5
Pallavi O Deshpande, Vishwaraman Mohan, Prasad Arvind Thakurdesai
OBJECTIVE: To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek (Trigonella foenum-graecum L) seed extract in laboratory rats. MATERIALS AND METHODS: The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No...
April 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28536863/chemical-exposure-and-infant-leukaemia-development-of-an-adverse-outcome-pathway-aop-for-aetiology-and-risk-assessment-research
#6
REVIEW
Olavi Pelkonen, Andrea Terron, Antonio F Hernandez, Pablo Menendez, Susanne Hougaard Bennekou
Infant leukaemia (<1 year old) is a rare disease of an in utero origin at an early phase of foetal development. Rearrangements of the mixed-lineage leukaemia (MLL) gene producing abnormal fusion proteins are the most frequent genetic/molecular findings in infant B cell-acute lymphoblastic leukaemia. In small epidemiological studies, mother/foetus exposures to some chemicals including pesticides have been associated with infant leukaemia; however, the strength of evidence and power of these studies are weak at best...
May 23, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28534261/the-role-of-drug-metabolites-in-the-inhibition-of-cytochrome-p450-enzymes
#7
Momir Mikov, Maja Đanić, Nebojša Pavlović, Bojan Stanimirov, Svetlana Goločorbin-Kon, Karmen Stankov, Hani Al-Salami
Following the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug-drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contribute to its pharmacokinetic properties and pharmacological as well as its toxicological effects...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28533120/evaluation-of-new-chemical-entities-as-substrates-of-liver-transporters-in-the-pharmaceutical-industry-response-to-regulatory-requirements-and-future-steps
#8
Noriko Okudaira
This article discusses the evaluation of drug candidates as hepatic transporter substrates. Recently, research on the applications of hepatic transporters in the pharmaceutical industry has improved to meet the requirements of the regulatory guidelines for the evaluation of drug interactions. To identify the risk of transporter-mediated drug-drug interactions (DDIs) at an early stage of drug development, we employed a strategy of reviewing the in vivo animal pharmacokinetics and tissue distribution data obtained in the discovery stage together with the in vitro data obtained for regulatory submission...
May 19, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28532423/the-various-aspects-of-genetic-and-epigenetic-toxicology-testing-methods-and-clinical-applications
#9
REVIEW
Ning Ren, Manar Atyah, Wan-Yong Chen, Chen-Hao Zhou
Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells...
May 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28527645/energy-drinks-and-atrial-fibrillation-in-young-adults
#10
Anna Vittoria Mattioli, Sonia Pennella, Alberto Farinetti, Antonio Manenti
The present paper evaluates the association between Energy Drinks (EDs) and occurrence of atrial fibrillation (AF) in young people. Data from three clinical cases of AF after EDs consumption are reported. All patients presented with palpitations, nausea and anxiety. ECG showed AF with high ventricular response (135-170 bpm range frequency). Anamnestic record reported a high consumption of EDs during the previous 8 h from the onset of AF. In one case ED was associated with a moderate quantity of alcohol. Patients were successfully cardioverted both spontaneously and after pharmacological treatment...
May 6, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28526658/nonclinical-pharmacology-and-toxicology-of-the-first-biosimilar-insulin-glargine-drug-product-basaglar-%C3%A2-abasaglar-%C3%A2-approved-in-the-european-union
#11
Richard A Byrd, Rebecca A Owens, Jamie L Blackbourne, David E Coutant, Mark W Farmen, M Dodson Michael, Julie S Moyers, A Eric Schultze, Michael K Sievert, Niraj K Tripathi, John L Vahle
Basaglar(®)/Abasaglar(®) (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus(®) (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity...
May 16, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28522587/preclinical-evaluation-of-medi0641-a-pyrrolobenzodiazepine-conjugated-antibody-drug-conjugate-targeting-5t4
#12
Jay Harper, Christopher Lloyd, Nazzareno Dimasi, Dorin Toader, Rose Marwood, Leeanne Lewis, David Bannister, Jelena Jovanovic, Ryan Fleming, Francois d'Hooge, Shenlan Mao, Allison M Marrero, Martin Korade, Patrick Strout, Linda Xu, Cui Chen, Leslie Wetzel, Shannon Breen, Lilian van Vlerken-Ysla, Sanjoo Jalla, Marlon Rebelatto, Helen Zhong, Elaine M Hurt, Mary Jane Hinrichs, Keven Huang, Philip W Howard, David A Tice, Robert E Hollingsworth, Ronald Herbst, Adeela Kamal
Antibody-drug conjugates (ADCs) are used to selectively deliver cytotoxic agents to tumors and have the potential for increased clinical benefit to cancer patients. 5T4 is an oncofetal antigen overexpressed on the cell surface in many carcinomas on both bulk tumor cells as well as cancer stem cells (CSCs), has very limited normal tissue expression, and can internalize when bound by an antibody. An anti-5T4 antibody was identified and optimized for efficient binding and internalization in a target-specific manner, and engineered cysteines were incorporated into the molecule for site-specific conjugation...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521388/non-targeted-high-resolution-mass-spectrometry-strategy-for-simultaneous-monitoring-of-xenobiotics-and-endogenous-compounds-in-green-sea-turtles-on-the-great-barrier-reef
#13
Amy L Heffernan, Maria M Gómez-Ramos, Caroline Gaus, Soumini Vijayasarathy, Ian Bell, Christine Hof, Jochen F Mueller, Maria J Gómez-Ramos
Chemical contamination poses a threat to ecosystem, biota and human health, and identifying these hazards is a complex challenge. Traditional hazard identification relies on a priori-defined targets of limited chemical scope, and is generally inappropriate for exploratory studies such as explaining toxicological effects in environmental systems. Here we present a non-target high resolution mass spectrometry environmental monitoring study with multivariate statistical analysis to simultaneously detect biomarkers of exposure (e...
May 14, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28520935/safety-evaluation-of-daidzein-in-laying-hens-effects-on-laying-performance-hatchability-egg-quality-clinical-blood-parameters-and-organ-development
#14
J Lu, L Qu, M M Shen, S M Li, T C Dou, Y P Hu, K H Wang
Daidzein has become increasingly popular as a dietary supplement, particularly for postpeak-estrus animals, as a safe and natural alternative estrogen-like compound. However, there is little available safety data of daidzein in laying hens. A study was conducted to examine if high-dose daidzein affected the safety of hens, including mortality, laying performance, egg quality, hematological parameters, clinical chemical parameters, organ development parameters, and hatchability. A total of 2,448 42-wk-old Rugao laying hens were randomly assigned to 4 groups with 6 replicates of 102 birds each (612 laying hens per group)...
May 17, 2017: Poultry Science
https://www.readbyqxmd.com/read/28515222/zebrafish-models-for-functional-and-toxicological-screening-of-nanoscale-drug-delivery-systems-promoting-preclinical-applications
#15
Keon Yong Lee, Gun Hyuk Jang, Cho Hyun Byun, Minhong Jeun, Peter Searson, Kwan Hyi Lee
Preclinical screening with animal models is an important initial step in clinical translation of new drug delivery systems. However, establishing efficacy, biodistribution, and biotoxicity of complex, multicomponent systems in small animal models can be expensive and time consuming. Zebrafish models represent an alternative for preclinical studies of nanoscale drug delivery systems. These models allow easy optical imaging, large sample size, and organ-specific studies, and hence an increasing number of preclinical studies are employing zebrafish models...
May 17, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28506817/in-vitro-cyp-mediated-drug-metabolism-in-the-zebrafish-embryo-using-human-reference-compounds
#16
Moayad Saad, An Matheeussen, Sebastiaan Bijttebier, Evy Verbueken, Casper Pype, Christophe Casteleyn, Chris Van Ginneken, Sandra Apers, Louis Maes, Paul Cos, Steven Van Cruchten
The increasing use of zebrafish embryos as an alternative model for toxicological and pharmacological studies necessitates a better understanding of xenobiotic biotransformation in this species. As cytochrome P450 enzymes (CYPs) play an essential role in this process, in vitro drug metabolism of four human CYP-specific substrates, i.e. dextromethorphan (DXM), diclofenac (DIC), testosterone (TST) and midazolam (MDZ) was investigated in adult male and female zebrafish, and in zebrafish embryos and larvae up to 120hours post-fertilization...
May 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28501917/a-primer-on-systematic-reviews-in-toxicology
#17
REVIEW
Sebastian Hoffmann, Rob B M de Vries, Martin L Stephens, Nancy B Beck, Hubert A A M Dirven, John R Fowle, Julie E Goodman, Thomas Hartung, Ian Kimber, Manoj M Lalu, Kristina Thayer, Paul Whaley, Daniele Wikoff, Katya Tsaioun
Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored...
May 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28501712/3d-bioprinting-for-drug-discovery-and-development-in-pharmaceutics
#18
REVIEW
Weijie Peng, Pallab Datta, Bugra Ayan, Veli Ozbolat, Donna Sosnoski, Ibrahim T Ozbolat
Successful launch of a commercial drug requires significant investment of time and financial resources wherein late-stage failures become a reason for catastrophic failures in drug discovery. This calls for infusing constant innovations in technologies, which can give reliable prediction of efficacy, and more importantly, toxicology of the compound early in the drug discovery process before clinical trials. Though computational advances have resulted in more rationale in silico designing, in vitro experimental studies still require gaining industry confidence and improving in vitro-in vivo correlations...
May 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28497450/the-role-of-hemodialysis-in-treatment-of-acute-acetic-acid-poisonings
#19
Andon Chibishev, Lidija Petkovska, Liljana Tozija, Milka Zdravkovska, Emilija Shikole
INTRODUCTION: The aim of this study is to show the importance of hemodialysis as an active method in treatment of acute acetic acid poisonings. Its main role is to support the renal function during the state of the intoxication when patients develop acute renal failure. METHODS: We analyzed data from a 10-year period, a total of 71 patients who ingested acetic acid, either intentionally or accidentally. Patients with a need of hemodialysis (HD) treatment underwent 3- to 4-hour HD sessions every day or every second day, according to clinical assessment, as needed, until recovery of kidney function...
May 10, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28496482/evaluation-of-the-synergistic-effect-of-tomatidine-with-several-antibiotics-against-standard-and-clinical-isolates-of-staphylococcus-aureus-enterococcus-faecalis-pseudomonas-aeruginosa-and-escherichia-coli
#20
Rasool Soltani, Hossein Fazeli, Rahim Bahri Najafi, Alireza Jelokhanian
Antibiotic resistance is an important problem in antibiotic treatment of infections, particularly in hospitals. Tomatidine is a plant secondary metabolite with antimicrobial and antifungal effects. This study examined the possible synergistic effect tomatidine with several antibiotics against standard and clinical strains of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. After determining the minimum inhibitory concentrations (MICs) of antibiotics and tomatidine against the bacterial isolates using broth microdilution method, the synergistic effect between tomatidine and antibiotics was evaluated by checkerboard method and calculation of FIC indices...
2017: Iranian Journal of Pharmaceutical Research: IJPR
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