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Clinical Toxicology

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https://www.readbyqxmd.com/read/28075189/11-analytically-confirmed-cases-of-mexedrone-use-among-polydrug-users
#1
Liam Roberts, Loretta Ford, Neel Patel, J Allister Vale, Sally M Bradberry
INTRODUCTION: Mexedrone, 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one, is the alpha-methoxy-derivative of mephedrone (4-methyl-N-methyl cathinone). Mexedrone inhibits the re-uptake of serotonin and dopamine in a dose-dependent manner and has affinity for serotonin and dopamine membrane transporters and receptors (5-HT2 and D2 receptors), producing sympathomimetic effects similar to amfetamines. To date there are no published clinical reports on mexedrone use that are analytically confirmed...
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28074704/the-toxicology-of-zinc-chloride-smoke-producing-bombs-and-screens
#2
Ayman El Idrissi, Lisanne van Berkel, Nadia E Bonekamp, Diana J Z Dalemans, Marcel A G van der Heyden
CONTEXT: Zinc chloride (ZnCl2)-based smoke bombs and screens are in use since the Second World War (1939-1945). Many case descriptions on ZnCl2 smoke inhalation incidents appeared since 1945. OBJECTIVE: We provide a comprehensive overview of the clinical symptoms and underlying pathophysiology due to exposure to fumes from ZnCl2 smoke producing bombs. In addition, we give a historical overview of treatment regimens and their outcomes. METHODOLOGY: We performed a literature search on Medline, Scopus and Google Scholar databases using combinations of the following search terms "smoke bomb", "smoke screen", "ZnCl2", "intoxication", "poisoning", "case report", "HE smoke", "hexachloroethane smoke", "smoke inhalation" and "white smoke"...
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28074670/metabolism-of-psilocybin-and-psilocin-clinical-and-forensic-toxicological-relevance
#3
Ricardo Jorge Dinis-Oliveira
Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites...
January 11, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28073600/e-cigarettes-and-urologic-health-a-collaborative-review-of-toxicology-epidemiology-and-potential-risks
#4
REVIEW
Liam Bourke, Linda Bauld, Christopher Bullen, Marcus Cumberbatch, Edward Giovannucci, Farhad Islami, Hayden McRobbie, Debra T Silverman, James W F Catto
CONTEXT: Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. OBJECTIVE: To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks...
January 7, 2017: European Urology
https://www.readbyqxmd.com/read/28070107/effects-of-reduced-food-intake-for-4-weeks-on-physiological-parameters-in-toxicity-studies-in-dogs
#5
Junya Morita, Tomoko Izumi, Bunichiro Ogawa, Yoshiki Ban, Hironori Takagi, Minoru Sasaki, Shunsuke Tsutsumi
This study sought to clarify the effects of reduced feeding on physiological parameters in dogs to enable appropriate evaluations of the safety and toxicity of test compounds. We measured alkaline phosphatase isozymes and the circulating blood volume, as well as clinical signs, body weight, hematology, blood chemistry, electrocardiography, organ weight, and histopathology, in male beagle dogs fed a diet consisting of 300 g/day or 150 g/day for 4 weeks. There were no abnormal clinical signs in any of the dogs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28068099/mechanisms-and-barriers-in-cancer-nanomedicine-addressing-challenges-looking-for-solutions
#6
Thomas J Anchordoquy, Yechezkel Barenholz, Diana Boraschi, Michael Chorny, Paolo Decuzzi, Marina A Dobrovolskaia, Z Shadi Farhangrazi, Dorothy Farrell, Alberto Gabizon, Hamidreza Ghandehari, Biana Godin, Ninh M La-Beck, Julia Ljubimova, S Moein Moghimi, Len Pagliaro, Ji-Ho Park, Dan Peer, Erkki Ruoslahti, Natalie J Serkova, Dmitri Simberg
Remarkable progress has recently been made in the synthesis and characterization of engineered nanoparticles for imaging and treatment of cancers, resulting in several promising candidates in clinical trials. Despite these advances, clinical applications of nanoparticle-based therapeutic/imaging agents remain limited by biological, immunological, and translational barriers. In order to overcome the existing status quo in drug delivery, there is a need for open and frank discussion in the nanomedicine community on what is needed to make qualitative leaps toward translation...
January 9, 2017: ACS Nano
https://www.readbyqxmd.com/read/28068062/sequence-defined-backbone-modifications-regulate-antibacterial-activity-of-oligoteas
#7
Mintu Porel, Dana N Thornlow, Christine M Artim, Christopher A Alabi
In response to the urgent need for new antibiotic development strategies, antimicrobial peptides (AMPs) and other synthetic polymers are being actively investigated as promising alternatives to traditional antibiotics. Although most AMPs display lytic activity against several types of bacteria, they have poor toxicology profiles and are susceptible to proteolysis in vivo. While many synthetic variants have been created to mimic AMPs by tuning the hydrophobic to cationic ratio of the side-chain groups, few have decoupled the effects of charge from hydrophobicity in discrete systems, and none have investigated the effect of backbone hydrophobicity...
January 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28067687/a-case-of-toxic-breast-feeding
#8
Megan L Schultz, Mark Kostic, Sigmund Kharasch
Opiates are frequently prescribed postpartum for pain relief after cesarean delivery, episiotomies, and headaches. It is estimated that greater than 30% of breast-feeding mothers in the United States are prescribed opiates for pain relief associated with childbirth. Many opiates are readily transferred to human milk, although life-threatening events are rare. We report a 6-day-old breast-feeding infant whose mother was taking hydromorphone for pain relief from a cesarean delivery and whose clinical course was suggestive of opiate toxicity...
January 6, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28063329/determination-of-ethyl-glucuronide-in-human-hair-samples-a-multivariate-analysis-of-the-impact-of-extraction-conditions-on-quantitative-results
#9
Alexander Mueller, Hilke Jungen, Stefanie Iwersen-Bergmann, Lars Raduenz, Susanne Lezius, Hilke Andresen-Streichert
BACKGROUND: Ethyl glucuronide (EtG), a minor metabolite of ethanol, is used as a direct alcohol biomarker for the prolonged detection of ethanol consumption. Hair testing for EtG offers retrospective, long-term detection of ethanol exposition for several months and has gained practical importance in forensic and clinical toxicology. Since quantitative results of EtG hair testings are included in interpretations, a rugged quantitation of EtG in hair matrix is important. As generally known, sample preparation is critical in hair testing, and the scope of this study was on extraction of EtG from hair matrix...
December 19, 2016: Forensic Science International
https://www.readbyqxmd.com/read/28063270/identification-and-analytical-characterization-of-six-synthetic-cannabinoids-nnl-3-5%C3%A2-f-npb-22-7%C3%A2-n-5%C3%A2-f-akb-48-7%C3%A2-n-5%C3%A2-f-edmb-pinaca-emb-fubinaca-and-eg-018
#10
Cuimei Liu, Wei Jia, Zhendong Hua, Zhenhua Qian
Clinical and forensic toxicology laboratories are continuously confronted by analytical challenges when dealing with the new psychoactive substances phenomenon. The number of synthetic cannabinoids, the chemical diversity, and the speed of emergence make this group of compounds particularly challenging in terms of detection, monitoring, and responding. Three indazole 7 N positional isomer synthetic cannabinoids, two ethyl 2-amino-3-methylbutanoate-type synthetic cannabinoids, and one 9H-carbazole substituted synthetic cannabinoid were identified in seized materials...
January 7, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28059038/toxicities-of-receptor-tyrosine-kinase-inhibitors-in-cancer-pharmacotherapy-management-with-clinical-pharmacology
#11
Ken-Ichi Fujita, Hiroo Ishida, Yutaro Kubota, Yasutsuna Sasaki
A number of molecularly targeted anticancer drugs that efficiently inhibit receptor tyrosine kinases, so-called receptor tyrosine kinase inhibitors (TKIs), have been developed. Although these receptor TKIs are generally well tolerated, unexpected toxicities sometimes occur in various organs. TKI-induced adverse events not only lower the quality of life of cancer patients but also reduce dose intensity, and sometimes result in treatment discontinuation. To reduce adverse drug events and increase treatment efficacy, oncologists and clinical pharmacologists have made efforts to establish strategies to treat patients via optimal selection and dosing of TKIs...
January 5, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28056663/principles-for-assessing-adversity-in-toxicologic-clinical-pathology
#12
Lila Ramaiah, Lindsay Tomlinson, Niraj K Tripathi, Laura C Cregar, Allison Vitsky, Barbara von Beust, Valerie G Barlow, William J Reagan, Daniela Ennulat
There is limited direction in the literature or regulatory guidance on determination of adversity for clinical pathology (CP) biomarkers in preclinical safety studies. Toxicologic clinical pathologists representing the American Society for Veterinary Clinical Pathology-Regulatory Affairs Committee and Society of Toxicologic Pathology-Clinical Pathology Interest Group identified principles, overall approach, and unique considerations for assessing adversity in CP data interpretation to provide a consensus opinion...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28055331/review-of-ginkgo-biloba-induced-toxicity-from-experimental-studies-to-human-case-reports
#13
Nan Mei, Xiaoqing Guo, Zhen Ren, Daisuke Kobayashi, Keiji Wada, Lei Guo
Ginkgo biloba has been used as a traditional herbal remedy for many thousand years and its leaf extract has been consumed as a botanical dietary supplement for decades. Ginkgo biloba extract is a complex mixture with numerous components, including flavonol glycosides and terpene lactones, and is one of the most widely sold botanical dietary supplements worldwide. Concerns about potential health risks for the general population have been raised because of the widespread human exposure to Ginkgo biloba and its potential toxic and carcinogenic activities in rodents...
January 5, 2017: Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews
https://www.readbyqxmd.com/read/28054971/the-development-of-urease-inhibitors-what-opportunities-exist-for-better-treatment-of-helicobacter-pylori-infection-in-children
#14
Sherif T S Hassan, Miroslava Šudomová
Stomach infection with Helicobacter pylori (H. pylori) causes severe gastroduodenal diseases in a large number of patients worldwide. The H. pylori infection breaks up in early childhood, persists lifelong if not treated, and is associated with chronic gastritis and an increased risk of peptic ulcers and gastric cancer. In recent years, the problem of drug-resistant strains has become a global concern that makes the treatment more complicated and the infection persistent at higher levels when the antibiotic treatment is stopped...
January 4, 2017: Children
https://www.readbyqxmd.com/read/28054742/evaluation-of-dna-damage-in-hepg2-cells-and-mutagenicity-of-garcinielliptone-fc-a-bioactive-benzophenone
#15
Lismare da Silva Prado, Juliana da Silva, Ana Letícia Hilario Garcia, Fernanda Brião Menezes Boaretto, Ivana Grivicich, Lucas Umpierre Conter, Aguisson de Oliveira Salvi, Flávio Henrique Reginatto, Suele Bierhals Vencato, Alexandre de Barros Falcão Ferraz, Jaqueline Nascimento Picada
Garcinielliptone FC (GFC) is a polyprenylated benzophenone isolated from the hexanic extract of Platonia insignis seeds with potential pharmacological effects on the central nervous system. In a pre-clinical study, this compound showed anticonvulsant action, becoming a candidate to treat epilepsy disorders. However, genotoxicological aspects of GFC should be known to ensure its safe use. This study investigated the cytotoxic, genotoxic and mutagenic effects of GFC. Cytotoxicity was evaluated using the colourimetric assay of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) in human hepatoma cells (HepG2) (2 - 100 μg/mL) for 3, 6 and 24 hr...
January 5, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28053065/data-standardization-pharmaceutical-drug-development-and-the-3rs
#16
Laura Kaufman, Katrina Gore, Joyce Chandler Zandee
Despite the efforts, cost, and extensive use of animals for nonclinical research, only a small number of studies have methodically compared findings from animal toxicology studies to those from human clinical trials. Impediments to understanding the translation of nonclinical safety have included the lack of easy access to data and the need for extensive data curation given the diverse terminologies, formats, and data platforms in use. SEND and SDTM study data standards, developed by CDISC and about to become mandated by FDA, can address this and other drug development issues by facilitating access to data in ways that are not currently feasible...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28038978/management-of-organic-impurities-in-small-molecule-medicinal-products-deriving-safe-limits-for-use-in-early-development
#17
James Harvey, Andrew Fleetwood, Ron Ogilvie, Andrew Teasdale, Phil Wilcox, Steven Spanhaak
Management of organic non-mutagenic impurities (NMIs) in medicinal products is regulated by the ICH Q3A, B and C guidelines that are applicable at late stages of clinical development (Phase III onwards) and as a consequence there is no guidance for the assessment and control of NMIs in early clinical trials. An analysis of several key in vivo toxicology databases supports the ICH Q3A defined concept that a lifetime dose to 1 mg/day of a NMI would not represent a safety concern to patients. In conjunction with routine (Q)SAR approaches, this 1 mg/day value could be used as a universal qualification threshold for a NMI during any stage of clinical development...
December 27, 2016: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28035699/lack-of-respiratory-depression-in-paracetamol-codeine-combination-overdoses
#18
Simon P E Heppell, Geoffrey K Isbister
BACKGROUND: Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine combination overdoses caused respiratory depression more than paracetamol alone. METHODS: We reviewed deliberate self-poisoning admissions with paracetamol (>2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay[LOS], mechanical ventilation) were extracted from a prospective database...
December 30, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28017656/primary-human-testicular-cells-self-organize-into-organoids-with-testicular-properties
#19
Yoni Baert, Joery De Kock, João P Alves-Lopes, Olle Söder, Jan-Bernd Stukenborg, Ellen Goossens
So far, successful de novo formation of testicular tissue followed by complete spermatogenesis in vitro has been achieved only in rodents. Our findings reveal that primary human testicular cells are able to self-organize into human testicular organoids (TOs), i.e., multi-cellular tissue surrogates, either with or without support of a biological scaffold. Despite lacking testis-specific topography, these mini-tissues harbored spermatogonia and their important niche cells, which retained specific functionalities during long-term culture...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28017287/-retrospective-study-of-the-assessment-and-management-of-benzodiazepine-withdrawal-syndrome-in-hospital-between-2000-and-2015
#20
A Martin-Kleisch, A-A Zulfiqar
INTRODUCTION: Benzodiazepines are prescribed in many indications and are provider of adverse effects in case of abrupt withdrawal or poorly framed. Withdrawal rules are established by the High Authority for Health. METHODS: To evaluate the diagnostic and therapeutic modalities of the benzodiazepine withdrawal syndrome, we performed a retrospective single-center study at the University Hospital of Reims, between January 2000 and May 2015, in patients with a withdrawal syndrome following hospital coding...
December 22, 2016: Annales Pharmaceutiques Françaises
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