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Clinical Toxicology

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https://www.readbyqxmd.com/read/28817277/discovery-and-characterization-of-r-6-neopentyl-2-pyridin-2-ylmethoxy-6-7-dihydropyrimido-2-1-c-1-4-oxazin-4-9h-one-pf-06462894-an-alkyne-lacking-metabotropic-glutamate-receptor-5-negative-allosteric-modulator-profiled-in-both-rat-and-non-human-primates
#1
Antonia F Stepan, Michelle M Claffey, Matthew R Reese, Gayatri Balan, Gabriela Barreiro, Jason Barricklow, Michael J Bohanon, Brian P Boscoe, Gregg D Cappon, Lois K Chenard, Julie Cianfrogna, Laigao Chen, Karen J Coffman, Susan E Drozda, Joshua R Dunetz, Somraj Ghosh, Xinjun Hou, Christopher Houle, Kapil Karki, John T Lazzaro, Jessica Y Mancuso, John M Marcek, Emily L Miller, Mark A Moen, Steven V O'Neil, Isao Sakurada, Marc Skaddan, Vinod Parikh, Deborah L Smith, Patrick E Trapa, Jamison B Tuttle, Patrick R Verhoest, Daniel P Walker, Annie C Won, Ann S Wright, Jessica Whritenour, Kenneth Zasadny, Margaret M Zaleska, Lei Zhang, Christopher L Shaffer
We previously observed a cutaneous type IV immune response in non-human primates (NHP) with the mGlu5 negative allosteric modulator (NAM) 7. To determine if this adverse event was chemotype- or mechanism-based, we evaluated a distinct series of mGlu5 NAMs. Increasing the sp(3) character of high-throughput screening hit 40 afforded a novel morpholinopyrimidone mGlu5 NAM series. Its prototype, (R)-6-neopentyl-2-(pyridin-2-ylmethoxy)-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-one (PF-06462894, 8), possessed favorable properties and a predicted low clinical dose (2 mg twice daily)...
August 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28815938/optimization-of-recombinant-%C3%AE-glucuronidase-hydrolysis-and-quantification-of-eight-urinary-cannabinoids-and-metabolites-by-liquid-chromatography-tandem-mass-spectrometry
#2
Cristina Sempio, Karl B Scheidweiler, Allan J Barnes, Marilyn A Huestis
Prolonged urinary cannabinoid excretion in chronic frequent cannabis users confounds identification of recent cannabis intake that may be important in treatment, workplace, clinical, and forensic testing programs. In addition, differentiation of synthetic Δ9-tetrahydrocannabinol (THC) intake from cannabis plant products might be an important interpretive issue. THC, 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THCCOOH) urine concentrations were evaluated during previous controlled cannabis administration studies following tandem alkaline/E...
June 14, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28815392/strategy-for-cyp3a-induction-risk-assessment-from-preclinical-signal-to-human-a-case-example-of-a-late-stage-discovery-compound
#3
Jialin Mao, Peter Fan, Susan Wong, Jianshuang Wang, Moulay Hicham Alaoui Ismaili, Brian Dean, Cornelis E C A Hop, Matthew Wright, Yuan Chen
PURPOSE: The exposure of G2917 decreased by four-fold at oral doses of 100 mg/kg twice daily for seven days in cynomolgus monkeys. Additional investigative work was conducted to understand: (1) the causes for the significant reduction in G2917 exposure in monkeys; (2) the extrapolation of in vitro induction data to in vivo findings in monkeys, and (3) the relevance of this pre-clinical finding to humans at the projected human efficacious dose. METHODS: Pharmacokinetic and induction potency (in vitro and in vivo) of G2917 in monkeys, and the in vitro human induction potency were studied...
August 16, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28814119/correction-to-north-american-congress-of-clinical-toxicology-nacct-abstracts-2017
#4
(no author information available yet)
No abstract text is available yet for this article.
August 17, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28811247/pharmacological-analysis-of-poecilotheria-spider-venoms-in-mice-provides-clues-for-human-treatment
#5
Alexander Andreev-Andrievskiy, Anfisa Popova, Evgeniia Lagereva, Daniil Osipov, Antonina Berkut, Eugene Grishin, Alexander Vassilevski
Bites of tiger spiders belonging to Poecilotheria genus cause moderate to severe pain and long-lasting local or generalized muscle cramps in humans. Bites occur in regions of the spiders' natural habitat, India and Sri Lanka, but the popularity of these colorful tarantulas as pets leads to reports of envenomation cases worldwide. Treatment is predominantly symptomatic and often inadequate since there is almost no clinical or toxicology research data available, and physicians outside India or Sri Lanka typically have no experience in treating such cases...
August 12, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28809115/an-intuitive-approach-for-predicting-potential-human-health-risk-with-the-tox21-10k-library
#6
Nisha S Sipes, John F Wambaugh, Robert Pearce, Scott S Auerbach, Barbara Anne Wetmore, Jui-Hua Hsieh, Andrew J Shapiro, Daniel Svoboda, Michael J DeVito, Stephen S Ferguson
In vitro-in vivo extrapolation (IVIVE) analyses translating high-throughput screening (HTS) data to human relevance have been limited. This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration-response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug-drug interactions...
August 15, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28802093/clinical-aspects-of-opium-adulterated-with-lead-in-iran-a-review
#7
Samira Alinejad, Jan Aaseth, Mohammad Abdollahi, Hossein Hassanian-Moghaddam, Omid Mehrpour
Adulteration of drugs with poisonous substances during production or consumption has caused numerous health problems. Among contaminants that have the potential of producing poisonous effects are the heavy metals lead, arsenic and thallium that make up an important group of toxic substances. The emergence of these new health problems related to opioid abuse has precipitated this MiniReview on the status of the most hazardous and common opioid adulterants. In fact, adulterated opium is a major public health problem and can threaten the health of users...
August 12, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28797958/quantification-of-paracetamol-and-5-oxoproline-in-serum-by-capillary-electrophoresis-implication-for-clinical-toxicology
#8
Tomáš Hložek, Tomáš Křížek, Petr Tůma, Miroslava Bursová, Pavel Coufal, Radomír Čabala
High anion gap metabolic acidosis frequently complicates acute paracetamol overdose and is generally attributed to lactic acidosis or compromised hepatic function. However, metabolic acidosis can also be caused by organic acid 5-oxoproline (pyroglutamic acid). Paracetamol's toxic intermediate, N-acetyl-p-benzoquinoneimine irreversibly binds to glutathione and its depletion leads to subsequent disruption of the gamma glutamyl cycle and an excessive 5-oxoproline generation. This is undoubtedly an underdiagnosed condition because measurement of serum 5-oxoproline level is not readily available...
July 26, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28796812/toxicological-and-bio-distribution-profile-of-a-gm-csf-expressing-double-targeted-chimeric-oncolytic-adenovirus-oncos-102-support-for-clinical-studies-on-advanced-cancer-treatment
#9
Lukasz Kuryk, Lotta Vassilev, Tuuli Ranki, Akseli Hemminki, Aila Karioja-Kallio, Onerva Levälampi, Antti Vuolanto, Vincenzo Cerullo, Sari Pesonen
The purpose of this work was to carry out preclinical toxicity and bio-distribution studies required for regulatory approval of a clinical trial application for Phase I clinical studies of ONCOS-102 (Ad5/3-D24-GM-CSF) for therapy of advanced cancers (NCT01598129). The study design, route of administration and dosage differs from the clinical protocol and in more detail, investigate bio-distribution and toxicological profile of ONCOS-102 treatment in animal model. The study was carried out in 300 hamsters divided into nine test groups-three bio-distribution groups and six groups for analysis of toxicity...
2017: PloS One
https://www.readbyqxmd.com/read/28795659/role-of-mycotoxins-in-the-pathobiology-of-autism-a-first-evidence
#10
Barbara De Santis, Carlo Brera, Alessandra Mezzelani, Sabina Soricelli, Francesca Ciceri, Giorgio Moretti, Francesca Debegnach, Maria Clara Bonaglia, Laura Villa, Massimo Molteni, Maria Elisabetta Raggi
OBJECTIVES: Gene-environment interaction is an emerging hypothesis to expound not only the autism pathogenesis but also the increased incidence of neurodevelopmental disorders (such as autistic spectrum disorder, attention-deficit, hyperactivity disorder). Among xenobiotics, mycotoxins are worldwide contaminants of food that provoke toxicological effects, crucially resembling several symptoms associated with autism such as oxidative stress, intestinal permeability, and inflammation. Here, we focused on a group of mycotoxins to test their role in the manifestation of autism, try to explain their mechanism of action, and discuss possible preventive and therapeutic interventions...
August 10, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28782580/new-psychoactive-substances-studies-on-the-metabolism-of-xlr-11-ab-pinaca-fub-pb-22-4-methoxy-%C3%AE-pvp-25-i-nbome-and-meclonazepam-using-human-liver-preparations-in-comparison-to-primary-human-hepatocytes-and-human-urine
#11
Lilian H J Richter, Hans H Maurer, Markus R Meyer
New psychoactive substances (NPS) are an increasing problem in clinical and forensic toxicology. The knowledge of their metabolism is important for toxicological risk assessment and for developing toxicological urine screenings. Considering the huge numbers of NPS annually appearing on the market, metabolism studies should be realized in a fast, simple, cost efficient, and reliable way. Primary human hepatocytes (PHH) were recommended to be the gold standard for in vitro metabolism studies as they are expected to contain natural enzyme clusters, co-substrates, and drug transporters...
August 3, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28782575/toxicological-evaluation-of-neoagarooligosaccharides-prepared-by-enzymatic-hydrolysis-of-agar
#12
Sun Joo Hong, Je-Hyeon Lee, Eun Joo Kim, Hea Jung Yang, Jae-Seon Park, Soon-Kwang Hong
Agar, a heterogeneous polymer of galactose, is the main component of the cell wall of marine red algae. It is well established as a safe, non-digestible carbohydrate in Oriental countries. Although neoagarooligosaccharides (NAOs) prepared by the hydrolysis of agar by β-agarase have been reported to exert various biological activities, the safety of these compounds has not been reported to date. For safety evaluation, NAOs containing mainly neoagarotetraose and neoagarohexaose were prepared from agar by enzymatic hydrolysis using β-agarase DagA from Streptomyces coelicolor...
August 3, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28781900/blending-of-rodenticide-and-battery-acid-a-rare-and-fatal-suicide-mix
#13
Nisreen Abdul Rahman, Siddhartha Das, Vinod Ashok Chaudhari, Suresh Nandagopal, Bhawana Badhe
BACKGROUND: Self-poisoning usually occurs by the ingestion of a single lethal compound and majority of the poisoning cases in our country are due to the pesticides. Suicide by ingestion of more than one poisonous substance is rare except alcohol and multiple drugs. To the best of our knowledge, suicidal ingestion of a mixture of rodenticide and battery acid has not been reported before in medical literature. CASE PRESENTATION: Here we are discussing a case of simultaneous ingestion of two poisonous substances, i...
2017: Egyptian journal of forensic sciences
https://www.readbyqxmd.com/read/28777878/a-multi-analyte-approach-to-help-in-assessing-the-severity-of-acute-poisonings-development-and-validation-of-a-fast-lc-ms-ms-quantification-approach-for-45-drugs-and-relevant-metabolites-with-one-point-calibration
#14
Julian A Michely, Hans H Maurer
In emergency toxicology, diagnosis, monitoring of the efficiency of detoxification, and estimating the prognosis of acute poisonings are important tasks. Comprehensive screening and quantification of relevant substances by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) help in assessing the severity of most acute poisonings. Turnaround time for such analyses must be short enough for having impact on clinical decisions. Therefore, a multi-analyte LC-MS/MS approach with a 5-min gradient was developed and validated for 45 drugs and active metabolites as complement to an existing GC-MS approach using the same liquid-liquid extraction...
August 4, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28777439/combining-cytotoxicity-assessment-and-xenopus-laevis-phenotypic-abnormality-assay-as-a-predictor-of-nanomaterial-safety
#15
Karamallah Al-Yousuf, Carl A Webster, Grant N Wheeler, Francesca Baldelli Bombelli, Victoria Sherwood
The African clawed frog, Xenopus laevis, has been used as an efficient pre-clinical screening tool to predict drug safety during the early stages of the drug discovery process. X. laevis is a relatively inexpensive model that can be used in whole organism high-throughput assays whilst maintaining a high degree of homology to the higher vertebrate models often used in scientific research. Despite an ever-increasing volume of biomedical nanoparticles (NPs) in development, their unique physico-chemical properties challenge the use of standard toxicology assays...
August 4, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28771645/opportunity-for-collaboration-between-radiation-injury-treatment-network-centers-and-medical-toxicology-specialists
#16
Elizabeth Davlantes, Samuel Shartar, Jennifer Venero, Alaina Steck, Amelia Langston, Ziad N Kazzi
OBJECTIVES: The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers...
August 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28771410/international-variability-in-gastrointestinal-decontamination-with-acute-poisonings
#17
Santiago Mintegi, Stuart R Dalziel, Beatriz Azkunaga, Javier Prego, Eunate Arana-Arri, Yordana Acedo, Lorea Martinez-Indart, Javier Benito, Nathan Kuppermann
BACKGROUND AND OBJECTIVES: Identifying international differences in the management of acute pediatric poisonings may help improve the quality of care. The objective of this study was to assess the international variation and appropriateness of gastrointestinal decontamination (GID) procedures performed in children and adolescents who present with acute poisonings to emergency departments. METHODS: This was an international, multicenter, cross-sectional prospective study including children <18 years with poisoning exposures presenting to 105 emergency departments in 20 countries from 8 global regions belonging to the Pediatric Emergency Research Networks...
August 2017: Pediatrics
https://www.readbyqxmd.com/read/28766237/the-toxicology-investigators-consortium-case-registry-the-2016-experience
#18
Lynn A Farrugia, Sean H Rhyee, Diane P Calello, Sharan L Campleman, Anne M Riederer, Hannah R Malashock, Anthony Pizon, Timothy Wiegand, Paul M Wax, Jeffrey Brent
The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry contains data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. Currently, 83% of accredited medical toxicology fellowship programs in the USA participate. The Registry continues to grow each year, and as of 31 December 2016, a new milestone was reached, with more than 50,000 cases reported since its inception...
August 1, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28763096/tillg%C3%A3-ng-till-snabb-laboratorieanalys-vid-akut-f%C3%A3-rgiftning-ger-b%C3%A3-ttre-och-s%C3%A3-krare-v%C3%A3-rd-men-m%C3%A3-jligheten-till-akuta-prov%C3%A2-%C3%A2-svar-varierar-%C3%A3-ver-landet
#19
Eva Olsson, Olof Beck, Anders Elmgren, Therese Hansson, Anders Helander
Access to rapid laboratory analytical services in cases of acute poisoning provides better and safer patient care The Swedish Poisons Information Centre, a nationwide 24/7 service to healthcare providers and the public, answers many questions about serious cases of acute poisoning. In some of these, prompt and proper treatment recommendations can be crucial for the clinical outcome. In cases where self-reported information is missing or considered unreliable, more emphasis is placed on the clinical symptoms and results of toxicological analyses...
July 26, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28762882/acute-pesticide-related-illness-among-farmworkers-barriers-to-reporting-to-public-health-authorities
#20
Joanne Bonnar Prado, Prakash R Mulay, Edward J Kasner, Heidi K Bojes, Geoffrey M Calvert
Farmworkers are at high risk of acute occupational pesticide-related illness (AOPI) and AOPI surveillance is vital to preventing these illnesses. Data on such illnesses are collected and analyzed to identify high risk groups, high risk pesticides, and root causes. Interventions to address these risks and root causes include farmworker outreach, education, and regulation. Unfortunately, it is well known that AOPI is under-reported, meaning that the true burden of this condition remains unknown. This paper reviews the barriers to reporting of farmworker AOPI to public health authorities and provides some practical solutions...
August 1, 2017: Journal of Agromedicine
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