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Clinical Toxicology

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https://www.readbyqxmd.com/read/27905047/endoscopic-ultrasound-guided-fine-needle-aspiration-biopsy-eus-fna-in-insulinomas-indications-and-clinical-relevance-in-a-single-investigator-cohort-of-47-patients
#1
Peter Herbert Kann, Roland Moll, Detlef Bartsch, Andreas Pfützner, Thomas Forst, Gianluca Tamagno, Joachim N Goebel, Verena Fourkiotis, Simona Raluca Bergmann, Maike Collienne
PURPOSE: This study was aimed to investigate the role and relevance of endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of insulinomas. METHODS: We have analysed the frequency, clinical indications, success rate (obtaining diagnostic tissue), diagnostic accuracy (in comparison to the pathological diagnosis after surgery), complications, and tolerability of endoscopic ultrasound-guided fine-needle aspiration biopsy and the localization and size of the lesions in 47 consecutive patients (29 females, 18 males; 46 ± 15 years) who had surgery for insulinoma following fasting test and were explored by single investigator EUS 1994-2015...
November 30, 2016: Endocrine
https://www.readbyqxmd.com/read/27897111/aggressive-antioxidant-reductive-stress-impairs-brain-endothelial-cell-angiogenesis-and-blood-brain-barrier-function
#2
Shireen Mentor, David Fisher
Oxidative stress in the brain microvasculature is a common characteristic in models of cerebrovascular disease. Considering the effects of reactive oxygen species activity in vascular-derived insults, it is naturally prudent to hypothesize those interventions inhibiting reactive oxygen species activity, such as antioxidant supplementation, may be beneficial for cerebrovascular disease. Hyper doses of antioxidant supplements, and foods with high antioxidant concentrations, are commonly used as an ongoing remedial and 'over-the-counter' treatments for most seasonal ailments...
November 29, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27896556/towards-standardized-automated-immunomonitoring-an-automated-elispot-assay-for-safe-and-parallelized-functionality-analysis-of-immune-cells
#3
J C Neubauer, I Sébastien, A Germann, S C Müller, A Meyerhans, H von Briesen, H Zimmermann
The ELISpot assay is used for the detection of T cell responses in clinical trials and vaccine evaluations. Standardization and reproducibility are necessary to compare the results worldwide, inter- and intra-assay variability being critical factors. To assure operator safety as well as high-quality experiment performance, the ELISpot assay was implemented on an automated liquid handling platform, a Tecan Freedom EVO. After validation of the liquid handling, automated loading of plates with cells and reagents was investigated...
November 28, 2016: Cytotechnology
https://www.readbyqxmd.com/read/27895264/sex-differences-in-human-and-animal-toxicology-toxicokinetics
#4
Michael Gochfeld
Sex, the states of being female or male, potentially interacts with all xenobiotic exposures, both inadvertent and deliberate, and influences their toxicokinetics (TK), toxicodynamics, and outcomes. Sex differences occur in behavior, exposure, anatomy, physiology, biochemistry, and genetics, accounting for female-male differences in responses to environmental chemicals, diet, and pharmaceuticals, including adverse drug reactions (ADRs). Often viewed as an annoying confounder, researchers have studied only one sex, adjusted for sex, or ignored it...
November 28, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27889952/effects-of-different-doses-of-2-3-dimercaptosuccinic-acid-modified-fe2-o3-nanoparticles-on-intercalated-discs-in-engineered-cardiac-tissues
#5
Yongchao Mou, Shuanghong Lv, Fei Xiong, Yao Han, Yuwei Zhao, Junjie Li, Ning Gu, Jin Zhou
Although iron oxide nanoparticles (IRONs) were applied in clinical magnetic resonance imaging in vivo and magnetic tissue engineering in vitro widely, the underlying effects of IRONs on the development of cardiomyocytes especially the intercellular junctions, intercalated discs (IDs), remain an unknown issue. Given the critical role of three-dimensional (3D) engineered cardiac tissues (ECTs) in evaluation of nanoparticles toxicology, it remained necessary to understand the effects of IRONs on IDs assembly of cardiomyocytes in 3D environment...
November 27, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/27879439/interpreting-and-integrating-clinical-and-anatomic-pathology-results-pulling-it-all-together
#6
Lila Ramaiah, Mary Jane Hinrichs, Elizabeth V Skuba, William O Iverson, Daniela Ennulat
The continuing education course on integrating clinical and anatomical pathology data was designed to communicate the importance of using a weight of evidence approach to interpret safety findings in toxicology studies. This approach is necessary, as neither clinical nor anatomic pathology data can be relied upon in isolation to fully understand the relationship between study findings and the test article. Basic principles for correlating anatomic pathology and clinical pathology findings and for integrating these with other study end points were reviewed...
November 13, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27872646/mercury-vapour-long-lasting-exposure-lymphocyte-muscarinic-receptors-as-neurochemical-markers-of-accidental-intoxication
#7
E Roda, A Giampreti, S Vecchio, P Apostoli, T Coccini
Introduction. Chronic poisoning may result in home setting after mercury (Hg) vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg) monitoring were performed from admission (t0), until 1 year later (t2), paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs)...
2016: Case Reports in Medicine
https://www.readbyqxmd.com/read/27871868/quantitative-risk-assessment-for-skin-sensitization-success-or-failure
#8
Ian Kimber, G Frank Gerberick, David A Basketter
Skin sensitization is unique in the world of toxicology. There is a combination of reliable, validated predictive test methods for identification of skin sensitizing chemicals, a clearly documented and transparent approach to risk assessment, and effective feedback from dermatology clinics around the world delivering evidence of the success or failure of the hazard identification/risk assessment/management process. Recent epidemics of contact allergy, particularly to preservatives, have raised questions of whether the safety/risk assessment process is working in an optimal manner (or indeed is working at all!)...
November 18, 2016: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#9
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27863698/striatal-h3k27-acetylation-linked-to-glutamatergic-gene-dysregulation-in-human-heroin-abusers-holds-promise-as-therapeutic-target
#10
Gabor Egervari, Joseph Landry, James Callens, John F Fullard, Panos Roussos, Eva Keller, Yasmin L Hurd
BACKGROUND: Opiate abuse and overdose reached epidemic levels in the United States. However, despite significant advances in animal and in vitro models, little knowledge has been directly accrued regarding the neurobiology of the opiate-addicted human brain. METHODS: We used postmortem human brain specimens from a homogeneous European Caucasian population of heroin users for transcriptional and epigenetic profiling, as well as direct assessment of chromatin accessibility in the striatum, a brain region central to reward and emotion...
September 28, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27863142/identification-and-analytical-characterization-of-nine-synthetic-cathinone-derivatives-n-ethylhexedrone-4-cl-pentedrone-4-cl-%C3%AE-eapp-propylone-n-ethylnorpentylone-6-meo-bk-mdma-%C3%AE-pihp-4-cl-%C3%AE-php-and-4-f-%C3%AE-php
#11
Cuimei Liu, Wei Jia, Tao Li, Zhendong Hua, Zhenhua Qian
Clinical and forensic toxicology laboratories are continuously confronted by analytical challenges when dealing with the new psychoactive substances phenomenon. In this study, the analytical characterization of nine synthetic cathinones is described: 2-(ethylamino)-1-phenylhexan-1-one (N-ethylhexedrone 1), 1-(4-chlorophenyl)-2-(methylamino)pentan-1-one (4-Cl-pentedrone 2), 1-(4-chlorophenyl)-2-(ethylamino)pentan-1-one (4-Cl-α-EAPP 3), 1-(3,4-methylenedioxyphenyl)-2-propylaminopropan-1-one (propylone 4), 1-(3,4-methylenedioxyphenyl)-2-ethylaminopentan-1-one (N-ethylnorpentylone 5), 1-(6-methoxy-3,4-methylenedioxyphenyl)-2-methylaminopropan-1-one (6-MeO-bk-MDMA 6), 4-methyl-1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PiHP 7), 1-(4-chlorophenyl)-2-(pyrrolidin-1-yl)hexan-1-one (4-Cl-α-PHP 8), and 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)hexan-1-one (4-F-α-PHP 9)...
November 9, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27860547/the-discovery-of-suvorexant-the-first-orexin-receptor-drug-for-insomnia
#12
Paul J Coleman, Anthony L Gotter, W Joseph Herring, Christopher J Winrow, John J Renger
Historically, pharmacological therapies have used mechanisms such as γ- aminobutyric acid A (GABAA) receptor potentiation to drive sleep through broad suppression of central nervous system activity. With the discovery of orexin signaling loss as the etiology underlying narcolepsy, a disorder associated with hypersomnolence, orexin antagonism emerged as an alternative approach to attenuate orexin-induced wakefulness more selectively. Dual orexin receptor antagonists (DORAs) block the activity of orexin 1 and 2 receptors to both reduce the threshold to transition into sleep and attenuate orexin-mediated arousal...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27859025/modeling-drug-induced-neuropathy-using-human-ipscs-for-predictive-toxicology
#13
Ryo Ohara, Keiko Imamura, Fukiko Morii, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Ran Shibukawa, Toshiki Mizuno, Masanori Nakagawa, Haruhisa Inoue
Drugs under development can cause unpredicted toxicity in humans due to differential drug responsiveness between humans and other disease models, resulting in clinical trial failures. Human induced pluripotent stem cells (iPSCs) are expected to represent a useful tool for toxicity testing. However, among many assays, appropriate cellular assays for predicting neurotoxicity in an iPSC-based model are still uncertain. Here, we generated neurons from iPSCs of Charcot-Marie-Tooth disease (CMT) patients, who are sensitive to anti-cancer drugs and present with the adverse reaction of neuropathy, and analyzed cellular phenotypes...
November 9, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27858217/alternative-animal-and-non-animal-models-for-drug-discovery-and-development-bonus-or-burden
#14
Irlan Almeida Freires, Janaina de Cássia Orlandi Sardi, Ricardo Dias de Castro, Pedro Luiz Rosalen
Mammalian models have served as a basis for R&D over the past decades. Nevertheless, these models are expensive, laborious, may yield results that cannot always be translated into the human in vivo situation and, more recently, have reverberated great social and ethical dilemmas. Hence, the prospect of changes in the global scientific scenario and the Three Rs principle (Reduction, Replacement and Refinement) have encouraged the development of alternative methods to the use of mammals. Despite the efforts, suitable alternative tests are not available in all areas of biomedical research, as regulatory acceptance requires time, prior validation and robust financial and scientific investment...
November 17, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27858165/nmr-study-of-the-effects-of-some-bleomycin-c-termini-on-the-structure-of-a-dna-hairpin-with-the-5-gc-3-binding-site
#15
Teresa E Lehmann, Sally A Murray, Azure D Ingersoll, Teresa M Reilly, Shelby E Follett, Kevin E Macartney, Mark H Harpster
The antibiotics known as bleomycins constitute a family of natural products clinically employed for the treatment of a wide spectrum of cancers. The drug acts as an antitumor agent by virtue of the ability of a metal complex of the antibiotic to cleave DNA. Bleomycins are differentiated by their C-terminal regions. Previous structural studies involving metal-bleomycin-DNA triads have allowed the identification of the bithiazole-(C-terminus substituent) segment in this molecule as the one that most closely interacts with DNA...
November 17, 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/27855664/challenges-in-detecting-and-diagnosing-substance-use-in-women-in-the-acute-psychiatric-department-a-naturalistic-cohort-study
#16
Torill Vassli Sallaup, Arne Einar Vaaler, Valentina Cabral Iversen, Ismail Cuneyt Guzey
BACKGROUND: This study examines sex differences in substance use and substance use disorder in the acute psychiatric department, and possible interactions between sex and clinical and social factors associated with this phenomenon. METHODS: Data concerning substance use were collected in a naturalistic cohort study (n = 384, 51.6% male, 48.4% female) in an acute psychiatric department. Recent intake of substances at admission, diagnosis of substance use disorder and demographic and socioeconomic information were recorded...
November 17, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27854228/toxicological-characterization-of-exon-skipping-phosphorodiamidate-morpholino-oligomers-pmos-in-non-human-primates
#17
Michael P Carver, Jay S Charleston, Courtney Shanks, Jianbo Zhang, Mark Mense, Alok K Sharma, Harjeet Kaur, Peter Sazani
BACKGROUND: Phosphorodiamidate morpholino oligomers (PMOs) are a class of exon skipping drugs including eteplirsen, which has shown considerable promise for treatment of the degenerative neuromuscular disease, Duchenne musculardystrophy (DMD). OBJECTIVE: Toxicity studies in non-human primates (NHPs) of 12 weeks duration with two new PMOs for DMD, SRP-4045 and SRP-4053, along with results from a chronic study in NHPs of 39 weeks duration for eteplirsen, are described here...
August 30, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27854216/therapeutic-potential-of-tricyclo-dna-antisense-oligonucleotides
#18
Aurelie Goyenvalle, Christian Leumann, Luis Garcia
Oligonucleotide therapeutics hold great promise for the treatment of various diseases and the antisense field is constantly gaining interest due to the development of more potent and nuclease resistant chemistries. Despite a rather low success rate with only three antisense drugs being clinically approved, the frontiers of AON therapeutic applications have increased over the past three decades and continue to expand thanks to a steady increase in understanding the mechanisms of action of these molecules, progress in chemical modification and delivery...
May 27, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27851687/determination-of-antidepressants-in-hair-via-uhplc-ms-ms-as-a-complementary-informative-tool-for-clinical-and-forensic-toxicological-assessments
#19
María Del Mar Ramírez Fernández, Sarah M R Wille, Virginia Hill, Nele Samyn
BACKGROUND: Hair analysis is a complementary approach for the detection of antidepressants (ADs) in clinical and forensic schemes because it yields a picture of long-term exposure over a time window depending on the length of the hair. METHODS: A fast and sensitive ultra-high performance liquid chromatography tandem mass spectrometry method using a BEH C18 column with a mobile phase consisting of ammonium acetate/acetonitrile was developed and validated according to international guidelines for the simultaneous analysis of 24 ADs in hair...
December 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27848887/metabolism-and-toxicological-implications-of-commonly-used-chemopreventive-drugs-against-breast-cancer-carcinogenesis
#20
Aliyu Muhammad, Mohammed Auwal Ibrahim, Ochuko Lucky Erukainure, Ibrahim Malami, Hadiza Sani, Hafsat Abdullahi Mohammed
BACKGROUND: Breast cancer has been reported to be among the frequently diagnosed cancer in women worldwide despite advances in early detection and treatment. Several drugs are currently used for chemoprevention as a result of a number of drawbacks associated with breast cancer therapy. AIM: This review focuses on the metabolism and toxicological implications of these drugs against breast cancer/carcinogenesis. METHODOLOGY: Relevant articles on the commonly used anti-breast cancer drugs (raloxifene, tamoxifen, anastrozole, letrozole and exemestane) used in chemoprevention were searched using the major scientific databases including Scopus, Embase, PubMed/ Medline, Sciencedirect and Google Scholar...
November 16, 2016: Current Drug Metabolism
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