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Clinical Toxicology

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https://www.readbyqxmd.com/read/29456831/early-afterdepolarisation-tendency-as-a-simulated-pro-arrhythmic-risk-indicator
#1
Beth McMillan, David J Gavaghan, Gary R Mirams
Drug-induced Torsades de Pointes (TdP) arrhythmia is of major interest in predictive toxicology. Drugs which cause TdP block the hERG cardiac potassium channel. However, not all drugs that block hERG cause TdP. As such, further understanding of the mechanistic route to TdP is needed. Early afterdepolarisations (EADs) are a cell-level phenomenon in which the membrane of a cardiac cell depolarises a second time before repolarisation, and EADs are seen in hearts during TdP. Therefore, we propose a method of predicting TdP using induced EADs combined with multiple ion channel block in simulations using biophysically-based mathematical models of human ventricular cell electrophysiology...
November 1, 2017: Toxicology Research
https://www.readbyqxmd.com/read/29454888/bioequivalence-decision-for-nanoparticular-iron-complex-drugs-for-parenteral-administration-based-on-their-disposition
#2
Julia Schnorr, Sören Fütterer, Karsten Spicher, Maria Catarinolo, Christoph Schlösser, Harald Enzmann, Peter Langguth
Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents...
February 15, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29451045/modified-release-paracetamol-overdose-a-prospective-observational-study-atom-3
#3
Angela L Chiew, Geoffrey K Isbister, Colin B Page, Katharine A Kirby, Betty S H Chan, Nicholas A Buckley
BACKGROUND: Modified-release (MR) paracetamol is available in many countries as 665 mg tablets of which 69% is MR and 31% is immediate release. There are concerns that MR paracetamol overdose has higher rates of liver injury despite standard treatment algorithms. The objective of this study was to describe the clinical characteristics and outcomes of acute MR paracetamol overdose. METHODS: Prospective observational study, recruiting patients from January 2013 to June 2017, from five clinical toxicology units and calls to two Poisons Information Centres in Australia...
February 16, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29447029/nanosilver-and-the-microbiological-activity-of-the-particulate-solids-versus-the-leached-soluble-silver
#4
Merisa B Faiz, Rose Amal, Christopher P Marquis, Elizabeth J Harry, Georgios A Sotiriou, Scott A Rice, Cindy Gunawan
Nanosilver (Ag NPs) is currently one of the most commercialized antimicrobial nanoparticles with as yet, still unresolved cytotoxicity origins. To date, research efforts have mostly described the antimicrobial contribution from the leaching of soluble silver, while the undissolved solid Ag particulates are often considered as being microbiologically inert, serving only as source of the cytotoxic Ag ions. Here, we show the rapid stimulation of lethal cellular oxidative stress in bacteria by the presence of the undissolved Ag particulates...
February 15, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29445628/medicinal-properties-of-adiantum-capillus-veneris-linn-in-traditional-medicine-and-modern-phytotherapy-a-review-article
#5
REVIEW
Sahar Dehdari, Homa Hajimehdipoor
Background: Adiantum capillus-veneris Linn (Maidenhair fern) is an herb belonging to the family Pteridaceae. It is named as " Pare-siavashan " in medical and pharmaceutical textbooks of Iranian Traditional Medicine. The fronds of Maidenhair fern were mainly administrated by ancient physicians as single medicine or in combination with other plants in multi-herbal formulations for curing different diseases. Because of different chemical compositions, the herb fronds were also assessed for its numerous pharmacological effects...
February 2018: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/29444633/talaromycosis-penicilliosis-in-a-cynomolgus-macaque
#6
William O Iverson, Subramanya Karanth, Angela Wilcox, Cau D Pham, Shawn R Lockhart, Simone M Nicholson
A sexually mature Chinese-origin female Macaca fascicularis assigned to the high-dose group in a 26-week toxicology study with an experimental immunomodulatory therapeutic antibody (a CD40 L antagonist fusion protein) was euthanized at the scheduled terminal sacrifice on study day 192. The animal was healthy at study initiation and remained clinically normal throughout the study. On study day 141, abnormal clinical pathology changes were found during a scheduled evaluation; splenomegaly was detected on study day 149 and supported by ultrasound examination...
January 1, 2018: Veterinary Pathology
https://www.readbyqxmd.com/read/29443781/unexpected-custodial-death-due-to-acute-epiglottitis-a-rare-autopsy-case-report
#7
Shifan Wu, Luo Zhuo, Xingang Qiu, Zijiao Ding, Mingzhen Yang, Meichen Pan, Qian Liu
RATIONALE: Acute epiglottitis is a potentially life-threaten disease, which makes it more challenging to save the life for doctors. Unexpected deaths in custody are a primary cause of concern for the forensic community and doctor worldwide. PATIENT CONCERNS: We present a case of a 44-year-old male detainee who was clinically suspected of dying of acute epiglottitis. The man experienced failure of resuscitation and died after admitted to a hospital. DIAGNOSES: The autopsy, toxicological testing, the test of immunoglobulin E and bacterial culture suggested the patient died of acute epiglottitis...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29428304/suitability-of-biomarkers-of-biological-effects-bobes-for-assessing-the-likelihood-of-reducing-the-tobacco-related-disease-risk-by-new-and-innovative-tobacco-products-a-literature-review
#8
REVIEW
Gerhard Scherer
The health risk of tobacco smoking can best be avoided or reduced by not taking up or quitting the habit. The use of new and innovative tobacco (NTPs, e.g. electronic cigarettes) can either be an aid for smoking cessation or, for those who are not able or willing to quit, an alternative for smoking conventional tobacco products. Before the use of an NTP can be regarded as an effective approach in tobacco harm reduction (THR), the implicated risk has to be evaluated by suitable toxicological methods such as the analysis of the chemical composition as well as assessment of detrimental effects in animal and in vitro studies...
February 8, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29428241/ethnomedical-uses-and-pharmacological-activities-of-most-prevalent-species-of-genus-piper-in-panama-a-review
#9
REVIEW
Armando A Durant-Archibold, Ana I Santana, Mahabir P Gupta
ETHNOPHARMACOGICAL RELEVANCE: Piperaceae is the fifth largest family of plants in Panama. This review focuses on the ethnomedical uses of the most prevalent Panamanian species and biological activities of their extracts and/or constituents both in Panama and worldwide. Many species have a plethora of ethnomedical uses such as antibacterial, antifungal, anti-inflammatory, anticancer, antidiabetic, anti-Helicobacter pylori, antiulcer, antiprotozoal, estrogenic, insecticidal, local anesthetic, diuretic, and for women's health conditions...
February 8, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29425331/modafinil-in-forensic-and-clinical-toxicology-case-reports-analytics-and-literature
#10
Lars Radünz, Hannah Reuter, Hilke Andresen-Streichert
Modafinil is used because of its wakefulness-promoting properties for treatment of diseases associated with extreme sleepiness (i.e., narcolepsy). Additionally, it is misused as a "cognitive enhancer" to increase alertness and to improve concentration. We present modafinil concentrations in serum samples in five cases of our routine work measured by high-performance liquid chromatography coupled with a photo diode array detector after solid-phase extraction. One sample was analyzed for clinical toxicology purposes...
February 7, 2018: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29424474/a-critical-review-of-the-application-of-polymer-of-low-concern-and-regulatory-criteria-to-fluoropolymers
#11
REVIEW
Barbara J Henry, Joseph P Carlin, Jon A Hammerschmidt, Robert C Buck, L William Buxton, Heidelore Fiedler, Jennifer Seed, Oscar Hernandez
Per- and poly-fluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers within the PFAS group, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative and biological stability...
February 9, 2018: Integrated Environmental Assessment and Management
https://www.readbyqxmd.com/read/29421996/role-of-abc-transporters-in-veterinary-medicine-pharmaco-toxicological-implications
#12
Guillermo Virkel, Mariana Ballent, Carlos Lanusse, Adrian Lifschitz
Unlike physicians, veterinary practitioners must deal with a number of animal species with crucial differences in anatomy, physiology and metabolism. Accordingly, the pharmacokinetic behaviour, the clinical efficacy and the adverse or toxic effects of drugs may differ across domestic animals. Moreover, the use of drugs in food-producing species may impose a risk for humans due to the generation of chemical residues in edible products, a major concern for public health and consumer's safety. As is clearly known in human beings, the ATP binding cassette (ABC) of transport proteins may influence the bioavailability and elimination of numerous drugs and other xenobiotics in domestic animals as well...
January 31, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29416931/single-oral-dose-acute-and-subacute-toxicity-of-a-c-met-tyrosine-kinase-inhibitor-and-cdk-4-6-inhibitor-combination-drug-therapy
#13
Brian Smith, Yi-Hsin Hsu, Rene Flores, Mihai Gagea, Suzanne Craig, Mien-Chie Hung
c-MET inhibitor, crizotinib, and CDK 4/6 inhibitor, palbociclib, have been evaluated in combination as cancer treatment in vitro. Because the toxicological data for the combination of these drugs is limited, we investigated the toxicity of the crizotinib and palbociclib combination in 80 ICR (CD-1) mice (average age = ~20 weeks). Treatments were arranged as a 2 × 2 × 2 factorial and included sex (female vs. male), crizotinib (0 or 4 mg), and palbociclib (0 or 1 mg). Drugs were administered to mice by oral gavage 24 hours (n = 40) and 7 days (n = 40) prior to the collection of blood and tissue samples to determine serum chemistry, hematology, and histopathology...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29416592/accelerated-bottom-up-drug-design-platform-enables-the-discovery-of-novel-stearoyl-coa-desaturase-1-inhibitors-for-cancer-therapy
#14
Christina A von Roemeling, Thomas R Caulfield, Laura Marlow, Ilah Bok, Jiang Wen, James L Miller, Robert Hughes, Lori Hazlehurst, Anthony B Pinkerton, Derek C Radisky, Han W Tun, Yon Son Betty Kim, Amy L Lane, John A Copland
Here we present an innovative computational-based drug discovery strategy, coupled with machine-based learning and functional assessment, for the rational design of novel small molecule inhibitors of the lipogenic enzyme stearoyl-CoA desaturase 1 (SCD1). Our methods resulted in the discovery of several unique molecules, of which our lead compound SSI-4 demonstrates potent anti-tumor activity, with an excellent pharmacokinetic and toxicology profile. We improve upon key characteristics, including chemoinformatics and absorption/distribution/metabolism/excretion (ADME) toxicity, while driving the IC50 to 0...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29413992/high-throughput-determination-of-valproate-in-human-samples-by-modified-quechers-extraction-and-gc-ms-ms
#15
Shun Mizuno, Xiao-Pen Lee, Masaya Fujishiro, Takaaki Matsuyama, Miho Yamada, Yuki Sakamoto, Maiko Kusano, Kei Zaitsu, Chika Hasegawa, Iwao Hasegawa, Takeshi Kumazawa, Akira Ishii, Keizo Sato
A new high-throughput method was developed for analysis of valproate in human plasma samples by QuEChERS extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS). Plasma samples (0.2 ml) spiked with valproate and secobarbital-d5 (internal standard) were diluted with 1.3 ml of distilled water. Acetonitrile (1 ml) was added followed by 0.4 g MgSO4 and 0.1 g NaOAC. After a centrifugation step (2000 g for 10 min), 1 ml of the supernatant was transferred to a dispersive-solid phase extraction (dSPE) tube containing 150 mg MgSO4 and 50 mg C18...
February 3, 2018: Legal Medicine
https://www.readbyqxmd.com/read/29408723/the-distribution-and-redistribution-of-fentanyl-norfentanyl-in-post-mortem-samples
#16
C N Chatterton, M Scott-Ham
This article compares 249 post mortem case reports that were positive for fentanyl/norfentanyl. All the cases were submitted to, and analyzed by, the toxicology department of the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada. This study highlights the varied distribution of fentanyl in the body after death as a result of misadventure, i.e., these are accidental drug overdose cases as opposed to a study of analytical data resulting from fentanyl use/administration in a clinical environment and/or death as a result of suicide...
December 28, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29407774/relevance-to-investigate-different-stages-of-pregnancy-to-highlight-toxic-effects-of-nanoparticles-the-example-of-silica
#17
Antonio Pietroiusti, Lucia Vecchione, Maria Ada Malvindi, Cinzia Aru, Micol Massimiani, Antonella Camaioni, Andrea Magrini, Roberta Bernardini, Stefania Sabella, Pier Paolo Pompa, Luisa Campagnolo
Amorphous silica nanoparticles (SiO2NPs) have been recognized as safe nanomaterial, hence their use in biomedical applications has been explored. Data, however, suggest potential toxicity of SiO2 NPs in pregnant individuals. However, no studies relating nanoparticle biokinetic/toxicity to the different gestational stages are currently available. In this respect, we have investigated the possible embryotoxic effects of three-size and two-surface functionalization SiO2NPs in mice. After intravenous administration of different concentrations at different stages of pregnancy, clinical and histopathological evaluations, performed close to parturition, did not show signs of maternal toxicity, nor effects on placental/fetal development, except for amino-functionalized 25 nm NPs...
January 31, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29407773/preclinical-evaluation-of-the-mono-pegylated-recombinant-human-interleukin-11-in-cynomolgus-monkeys
#18
Kuo-Ming Yu, Johnson Yiu-Nam Lau, Manson Fok, Yuk-Keung Yeung, Siu-Ping Fok, Suxing Zhang, Peizhen Ye, Kezhi Zhang, Xiaobo Li, Juan Li, Qin Xu, Wing-Tak Wong, Qui-Lim Choo
The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t1/2=6...
February 2, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29407764/rimonabant-a-potent-cb1-cannabinoid-receptor-antagonist-is-a-g%C3%AE-i-o-protein-inhibitor
#19
Alessandra Porcu, Miriam Melis, Rostislav Turecek, Celine Ullrich, Ignazia Mocci, Bernhard Bettler, Gian Luigi Gessa, M Paola Castelli
Rimonabant is a potent and selective cannabinoid CB1 receptor antagonist widely used in animal and clinical studies. Besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at CB1 receptors. The mechanism underpinning this activity is unclear. Here we show that micromolar concentrations of rimonabant inhibited Gαi/o-type G proteins, resulting in a receptor-independent block of G protein signaling. Accordingly, rimonabant decreased basal and agonist stimulated [35S]GTPγS binding to cortical membranes of CB1- and GABAB-receptor KO mice and Chinese Hamster Ovary (CHO) cell membranes stably transfected with GABAB or D2 dopamine receptors...
January 27, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29407203/toxicological-evaluation-of-3-sialyllactose-sodium-salt
#20
Daehee Kim, Rit Bahadur Gurung, Wonmin Seo, Albert W Lee, Jinsuk Woo
The safety of 3'-sialyllactose (3'-SL) sodium salt was evaluated by testing for gene mutations, in vivo and in vitro clastogenic activity, and animal toxicity in beagle dogs and rats. The results of all mutagenicity and genotoxicity tests were negative, indicating that 3'-SL does not have any mutagenic or clastogenic potential. The mean lethal dose (LD50) of 3'-SL sodium salt was well above 20 g/kg body weight (bw) in rats. A dose escalation acute toxicity study in Beagle dogs also indicated no treatment-related abnormalities...
January 26, 2018: Regulatory Toxicology and Pharmacology: RTP
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