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Clinical Toxicology

Anatoly Margolis, Paola Rosca, Rena Kurs, Sharon R Sznitman, Alexander Grinshpoon
OBJECTIVE: This study investigates the proportion of drug users among patients with mental disorders that attended the emergency department of one major psychiatric hospital in Northern Israel, the most frequent psychiatric diagnoses associated with drug use and the impact of confirmed drug use on hospital admission. We hypothesized that the proportion of individuals with positive urine drug test results presenting at the psychiatric emergency department during the study period would be 20-30%...
October 25, 2016: Journal of Dual Diagnosis
Marlies Decleer, Andreja Rajkovic, Benedikt Sas, Annemieke Madder, Sarah De Saeger
Rapid and accurate UPLC-MS/MS methods for the simultaneous determination of beauvericin and the related enniatins (A, A1, B, B1), together with cereulide were successfully developed and validated in cereal and cereal-based food matrices such as wheat, maize, rice and pasta. Although these emerging foodborne toxins are of different microbial origin, the similar structural, toxicological and food safety features provided rationale for their concurrent detection in relevant food matrices. A Waters Acquity UPLC system coupled to a Waters Quattro Premier XE™ Mass Spectrometer operating in ESI+ mode was employed...
October 4, 2016: Journal of Chromatography. A
Peter M Fischer
Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation...
October 24, 2016: Medicinal Research Reviews
Christopher Goldring, Daniel J Antoine, Frank Bonner, Jonathan Crozier, Chris Denning, Robert J Fontana, Neil A Hanley, David C Hay, Magnus Ingelman-Sundberg, Satu Juhila, Neil Kitteringham, Beatriz Silva-Lima, Alan Norris, Chris Pridgeon, James A Ross, Rowena Sison Young, Danilo Tagle, Belen Tornesi, Bob van de Water, Richard J Weaver, Fang Zhang, B Kevin Park
Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalised toxicology to determine inter-individual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury (DILI) means that no current single cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human DILI...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Oksana N Khokhlova, Elena A Tukhovskaya, Irina N Kravchenko, Elena S Sadovnikova, Irina A Pakhomova, Elena A Kalabina, Alexander V Lobanov, Elvira R Shaykhutdinova, Alina M Ismailova, Arkady N Murashev
INTRODUCTION: It is important that the method of anesthesia of mice does not considerably alter the animal's physiological and metabolic status before terminal blood sampling taken in order to analyze clinical pathology parameters. METHODS: Hematology, hemostasis, and clinical chemistry parameters were compared in male and female BALB/c mice exposed to either tiletamine-zolazepam-xylazine (TZX) anesthesia or euthanasia in carbon dioxide (CO2) chamber to reveal an alternative method of anesthesia vs...
October 20, 2016: Journal of Pharmacological and Toxicological Methods
Nicola J Stagg, Ben-Quan Shen, Flavia Brunstein, Chunze Li, Amrita V Kamath, Fiona Zhong, Melissa Schutten, Bernard M Fine
Antibody drug conjugates (ADC) consist of potent cytotoxic drugs conjugated to antibodies via chemical linkers, which enables specific targeting of tumor cells while reducing systemic exposure to the cytotoxic drug and improving the therapeutic window. The valine citrulline monomethyl auristatin E (vcMMAE, conventional linker-drug) ADC platform has shown promising clinical activity in several cancers, but peripheral neuropathy (PN) is a frequent adverse event leading to treatment discontinuation and dose reduction...
October 20, 2016: Regulatory Toxicology and Pharmacology: RTP
Arun R Pandiri, Roy L Kerlin, Peter C Mann, Nancy E Everds, Alok K Sharma, L Peyton Myers, Thomas J Steinbach
One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA...
October 21, 2016: Toxicologic Pathology
Alema Galijatovic-Idrizbegovic, Judith E Miller, Wendy D Cornell, James A Butler, Gordon K Wollenberg, Frank D Sistare, Joseph J DeGeorge
Chronic (>3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration...
October 18, 2016: Regulatory Toxicology and Pharmacology: RTP
Karen Peynshaert, Stefaan J Soenen, Bella B Manshian, Shareen H Doak, Kevin Braeckmans, Stefaan C De Smedt, Katrien Remaut
: In the last decade the interest in autophagy got an incredible boost and the phenomenon quickly turned into an extensive research field. Interestingly, dysfunction of this cytoplasmic clearance system has been proposed to lie at the root of multiple diseases including cancer. We therefore consider it crucial from a toxicological point of view to investigate if nanomaterials that are developed for biomedical applications interfere with this cellular process. Here, we study the highly promising 'gradient alloyed' quantum dots (QDs) that differ from conventional ones by their gradient core composition which allows for better fluorescent properties...
October 17, 2016: Acta Biomaterialia
Zygmunt Zdrojewicz, Marek Stebnicki, Michał Stebnicki
Sosnowsky's hogweed (Heracleum sosnowskyi Manden.) is a genus of plants in the family Apiaceae which also includes Giant Hogweed (Heracleum mantegazzianum Sommier and Levier). They are both found in Central Europe, mainly in neglected green areas or riversides. Sosnowsky's hogweed was brought to Poland from the Soviet Union in the 1950s to be used in animal feed production. Intended goals couldn't be achieved and the plant spread throughout grounds distant to the primarily cultivated lands. Sosnowsky's hogweed is especially hazardous in direct contact with human skin...
September 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Jamie Suki Chang, Margot Kushel, Christine Miaskowski, Rachel Ceasar, Kara Zamora, Emily Hurstak, Kelly R Knight
BACKGROUND: In the United States and internationally, providers have adopted guidelines on the management of prescription opioids for chronic noncancer pain (CNCP). For "high-risk" patients with co-occurring CNCP and a history of substance use, guidelines advise that providers monitor patients using urine toxicology screening tests, develop opioid management plans, and refer patients to substance use treatment. OBJECTIVE: We report primary care provider experiences in the safety net interpreting and implementing prescription opioid guideline recommendations for patients with CNCP and substance use...
October 18, 2016: Substance Use & Misuse
Justin D Vidal
Evaluation of the female reproductive system in a general toxicity setting can be challenging for the toxicologic pathologist due to the cyclic nature of the estrous and menstrual cycles, timing of puberty and reproductive senescence, and species differences. Age in particular can have a significant impact on the histologic appearance of the female reproductive system and create challenges when trying to distinguish test article-related findings from normal developmental or senescent changes. This review describes the key physiologic and histologic features of immaturity, the transition through puberty, sexual maturity, and reproductive senescence in the female reproductive system, with an emphasis on practical applications for the toxicologic pathologist, and includes recommendations for distinguishing and documenting these developmental periods...
October 17, 2016: Toxicologic Pathology
Andrew V Stachulski, Karl Swift, Mark Cooper, Stephen Reynolds, Daniel Norton, Steven D Slonecker, Jean-François Rossignol
Thiazolides are polypharmacology agents with at least three mechanisms of action against a broad spectrum of parasites, bacteria and viruses. In respiratory viruses they inhibit the replication of orthomyxoviridae and paramyxoviridae at a post-translational level. Nitazoxanide 1a, the prototype thiazolide, was originally developed as an antiparasitic agent and later repurposed for the treatment of viral respiratory infections. The second generation thiazolides following nitazoxanide, such as the 5-chloro analogue RM-5038 2a, are also broad-spectrum antiviral agents as we have reported...
September 26, 2016: European Journal of Medicinal Chemistry
Ye Yuan, John D Meeker, Kelly K Ferguson
Exposure to polybrominated diphenyl ethers (PBDEs) has been associated with various adverse health outcomes related to liver, neural and endocrine systems. Some of these may be the result of PBDE-induced oxidative stress or inflammation, but these associations have been explored minimally in humans. In the present study we examined the relationship between PBDE concentrations and biomarkers of oxidative stress and inflammation measured in blood samples among a representative US sample from the National Health and Nutrition Examination Survey...
October 14, 2016: Science of the Total Environment
Catherine Bennetau-Pelissero
PURPOSE OF REVIEW: The estrogenic effects of genistein, as reconfirmed by the American National Toxicology Program (USA-NTP), have led to several new clinical studies being undertaken. Here, we highlight the most relevant recent data, reporting either beneficial or adverse effects. RECENT FINDINGS: Phytoestrogens are natural molecules from edible plants exhibiting estrogenic activities. Post-USA-NTP studies investigated both human and animal reproductive and other physiological issues...
November 2016: Current Opinion in Clinical Nutrition and Metabolic Care
Chiguru Vishnuvardhan, Saibaba Baikadi, Roshan M Borkar, R Srinivas, N Satheeshkumar
Silodosin (SLD) is a novel α1-adrenoceptor antagonist which has shown promising clinical efficacy and safety in patients with benign prostatic hyperplasia (BPH). However, lack of information about metabolism of SLD prompted us to investigate metabolic fate of SLD in rats. To identify in vivo metabolites of SLD, urine, feces and plasma were collected from Sprague-Dawley rats after its oral administration. The samples were prepared using an optimized sample preparation approach involving protein precipitation followed by solid-phase extraction and then subjected to LC/HR-MS/MS analysis...
October 2016: Journal of Mass Spectrometry: JMS
Michela De Bellis, Roberta Carbonara, Julien Roussel, Alessandro Farinato, Ada Massari, Sabata Pierno, Marilena Muraglia, Filomena Corbo, Carlo Franchini, Maria Rosaria Carratù, Annamaria De Luca, Diana Conte Camerino, Jean-François Desaphy
Although the sodium channel blocker, mexiletine, is the first choice drug in myotonia, some myotonic patients remain unsatisfied due to contraindications, lack of tolerability, or incomplete response. More therapeutic options are thus needed for myotonic patients, which require clinical trials based on solid preclinical data. In previous structure-activity relationship studies, we identified two newly-synthesized derivatives of tocainide, To040 and To042, with greatly enhanced potency and use-dependent behavior in inhibiting sodium currents in frog skeletal muscle fibers...
October 12, 2016: Neuropharmacology
Rongshuai Wang, Luo Zhuo, Yunyun Wang, Liang Ren, Qian Liu, Liang Liu
BACKGROUND: Tetramine (tetramethylene disulphotetramine, TETS) and fluoroacetamide (FAA) are known as illegal rodenticides with high toxicity to animal species and human beings, which could lead to severe clinical features, including reduction of consciousness, convulsions, coma, and even death. METHODS AND RESULTS: We presented 2 cases that involved rodenticides poisoning. Even though the patients showed severe manifestations, they were initially misdiagnosed, resulting in 2 persons finally died from TETS and FAA poisoning in homicide cases...
October 2016: Medicine (Baltimore)
Min Wu, Qingxiong Yu, Qingfeng Li
Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction...
October 12, 2016: Oncotarget
Andrea E Steuer, Elena Williner, Sandra Staeheli, Thomas Kraemer
Increasing numbers of new psychoactive substances (NPS) among them fentanyl derivatives has been reported by the European monitoring centre for drugs and drug addiction (EMCDDA). Butyrfentanyl is a new fentanyl derivative whose potency ratio was found to be seven compared to morphine and 0.13 compared to fentanyl. Several case reports on butyrfentanyl intoxications have been described. Little is known about its pharmacokinetic properties including its metabolism. However, knowledge of metabolism is essential for analytical detection in clinical and forensic toxicology...
October 13, 2016: Drug Testing and Analysis
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