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Toxicologic Emergencies

Megan M Niedzwiecki, Douglas I Walker, Roel Vermeulen, Marc Chadeau-Hyam, Dean P Jones, Gary W Miller
Derived from the term exposure, the exposome is an omic-scale characterization of the nongenetic drivers of health and disease. With the genome, it defines the phenome of an individual. The measurement of complex environmental factors that exert pressure on our health has not kept pace with genomics and historically has not provided a similar level of resolution. Emerging technologies make it possible to obtain detailed information on drugs, toxicants, pollutants, nutrients, and physical and psychological stressors on an omic scale...
August 10, 2018: Annual Review of Pharmacology and Toxicology
Ondrej Adamovsky, Amanda Buerger, Alexis M Wormington, Naomi Ector, Robert J Griffitt, Joseph H Bisesi, Christopher J Martyniuk
The microbiome plays an essential role in the health and onset of diseases in all animals, including humans. The microbiome has emerged as a central theme in environmental toxicology, as microbes interact with the host immune system in addition to its role in chemical detoxification. Pathophysiological changes in the gastrointestinal tissue caused by ingested chemicals, and metabolites generated from microbial biodegradation, can lead to systemic adverse effects. This critical review dissects what we know about the impacts of environmental contaminants on the microbiome of aquatic species, with special emphasis on the gut microbiome...
August 10, 2018: Environmental Toxicology and Chemistry
Caren Weinhouse, Lisa Truong, Joel N Meyer, Patrick Allard
The roundworm Caenorhabitis elegans has been an established model organism for the study of genetics and developmental biology, including studies of transcriptional regulation, since the 1970s. This model organism has continued to be used as a classical model system as the field of transcriptional regulation has expanded to include scientific advances in epigenetics and chromatin biology. In the last several decades, C. elegans has emerged as a powerful model for environmental toxicology, particularly for the study of chemical genotoxicity...
August 9, 2018: Environmental and Molecular Mutagenesis
Vincenzo De Leo, Francesco Milano, Aurora Paiano, Roberta Bramato, Livia Giotta, Roberto Comparelli, Silvia Ruscigno, Angela Agostiano, Cecilia Bucci, Lucia Catucci
The use of fluorescent nanocrystals (NCs) as probes for bioimaging applications has emerged as an advantageous alternative to conventional organic fluorescent dyes. Therefore their toxicological evaluation and intracellular delivery are currently a primary field of research. In this work, hydrophobic and highly fluorescent CdSe@ZnS NCs were encapsulated into the lipid bilayer of liposomes by the micelle-to-vesicle transition (MVT) method. The obtained aqueous NC-liposome suspensions preserved the spectroscopic characteristics of the native NCs...
November 1, 2017: Toxicology Research
Drew R Luellen, Mark J LaGuardia, Troy D Tuckey, Mary C Fabrizio, Gary W Rice, Robert C Hale
Since introduction into the Chesapeake Bay watershed in the 1970s, blue catfish (Ictalurus furcatus) populations have increased, impacting native species. One strategy suggested to limit their growing numbers is to expand the existing commercial fishery. However, the promotion of human consumption of this large, omnivorous fish may increase exposure to contaminants of concern (COC). However, there are few published data on contaminants in blue catfish. To evaluate this possibility, we measured COC (PCBs, PBDEs, OCs, Hg) in individual fillets and compared levels to established consumption advisory limits...
August 6, 2018: Environmental Science and Pollution Research International
Magdalene H Y Tang, Y K Chong, Candace Y Chan, C K Ching, C K Lai, Y K Li, Tony W L Mak
Ketamine and phencyclidine are well-known drugs of abuse of the arylcyclohexylamine class, the backbone of which is used for the synthesis of new psychoactive substances (NPS). In October 2017, a cluster of acute intoxications was encountered where patients presented with ketamine-like toxidrome. Upon initial toxicology screening, however, neither ketamine nor other causative agents were detected in the patients' urine. Instead, an unidentified substance was consistently detected. Further investigations using gas- and liquid-chromatography mass spectrometry led to the identification of an arylcyclohexylamine analogue, 2-oxo-PCE...
July 24, 2018: Forensic Science International
James M Samet, Phillip A Wages
Oxidative stress is arguably the most common mechanism in the toxicology of environmental agents, unifying the action of broad classes of physichochemically disparate environmental pollutants, including oxidant gases, organic compounds, particulate surfaces, and metal ions. As advances in redox biology identify previously unrecognized targets for disruption by exposure to xenobiotics, redox toxicology has emerged as a new field of investigation. Environmental contaminants can induce oxidative stress on cells through mechanisms that are direct, indirect or involve the disruption of metabolic or bioenergetic processes that are regulated by thiol redox switches...
February 20, 2018: Current Opinion in Toxicology
Kenneth A Stauderman
Calcium release-activated calcium (CRAC) channels have been the target of drug discovery for many years. The identification of STIM and Orai proteins as key components of CRAC channels greatly facilitated this process because their co-expression in cell lines produced electrophysiological currents (ICRAC ) much larger than those in native cells, making it easier to confirm and characterize the effects of modulatory compounds. A driving force in the quest for CRAC channel drugs has been the immunocompromised phenotype displayed by humans and mice with null or loss-of-function mutations in STIM1 or Orai1, suggesting that CRAC channel inhibitors could be useful therapeutics for autoimmune or inflammatory conditions...
July 18, 2018: Cell Calcium
Elizabeth K Peterson, Hugh E Long
Emergent properties and external factors (population-level and ecosystem-level interactions, in particular) play important roles in mediating ecologically-important endpoints, though they are rarely considered in toxicological studies. D. melanogaster is emerging as a toxicology model for the behavioral, neurological, and genetic impacts of toxicants, to name a few. More importantly, species in the genus Drosophila can be utilized as a model system for an integrative framework approach to incorporate emergent properties and answer ecologically-relevant questions in toxicology research...
July 10, 2018: Journal of Visualized Experiments: JoVE
Karolina Paziana, Edmund Timpano, Andrew Stolbach
Objectives: Our primary objective was to use the Delphi method (DM) to choose learning objectives for an Internet-based pain management teaching module for emergency care providers. The DM is a structured communication technique that uses systematic, interactive data gathering to reach a consensus among a panel of experts. Methods: We extracted preliminary educational objectives from nationwide pain fellowship training programs. After redundant objectives and those relating to procedures outside the scope of emergency medicine (EM) were removed, 23 preliminary objectives remained...
April 2018: AEM education and training
Agnes L Karmaus, Ron Osborn, Mansi Krishan
Packaging is an indispensable component of the food manufacturing and food supply process. This scientific workshop was convened to bring together scientists from government, academia, and industry to discuss the state of the science regarding the safety of food packaging, prompted by rapidly advancing research to improve food packaging that continues to impact packaging technology, toxicology, exposure, risk assessment, and sustainability. The opening session focused on scientific challenges in the safety assessment of food packaging materials...
July 24, 2018: Regulatory Toxicology and Pharmacology: RTP
Berthold Langguth, Ana Belen Elgoyhen, Christopher R Cederroth
Tinnitus is a highly prevalent condition that is associated with hearing loss in most cases. In the absence of external stimuli, phantom perceptions of sounds emerge from alterations in neuronal activity within central auditory and nonauditory structures. Pioneering studies using lidocaine revealed that tinnitus is susceptible to pharmacological interventions. However, lidocaine is not effective in all patients, and no other drug has been identified with clear efficacy for the long-term treatment of tinnitus...
July 25, 2018: Annual Review of Pharmacology and Toxicology
Rodolfo Abarca-Vargas, Vera L Petricevich
This review discusses the current knowledge of the phytochemistry and in vitro and in vivo evaluations carried out using the extracts and, where appropriate, the main active components isolated from the genus Bougainvillea . Out of 18 species, most phytochemical, pharmacological, and toxicological studies focused on four species with different cultivars and one hybrid. Some plants are used for the treatment of various health disorders. Numerous phytochemical investigations of plants in this genus confirm the presence of aliphatic hydrocarbons, fatty acids, fatty alcohols, volatile compounds, phenolic compounds, peltogynoids, flavonoids, phytosterols, terpenes, carbohydrates, and betalains...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Starlaine Mascarenhas, Srikanth Mutnuri, Anasuya Ganguly
Silica is a trace-geogenic compound with limited-bioavailability. It inflicts health-perils like pulmonary-silicosis and chronic kidney disease (CKD), when available via anthropogenic-disturbances. Amidst silica-imposed pathologies, pulmonary toxicological-mechanisms are well-described, ignoring the renal-pathophysiological mechanisms. Hence, the present-study aimed to elucidate cellular-cum-molecular toxicological-mechanisms underlying silica-induced renal-pathology in-vitro. Various toxicity-assessments were used to study effects of silica on the physiological-functions of HK-cells (human-kidney proximal-tubular cells - the toxin's prime target) on chronic (1-7 days) sub-toxic (80 mg/L) and toxic (100-120 mg/L) dosing...
July 16, 2018: Science of the Total Environment
Nestor Ponce-García, Sergio O Serna-Saldivar, Silverio Garcia-Lara
One of the food security problems faced worldwide is the occurrence of mycotoxins in grains and their foods. Fumonisins (FBs) are mycotoxins which are prevalent in corn (Zea mays L.) and its based foods. Their intake and exposure have been epidemiologically and inconclusively associated with esophageal cancer and neural tube defects in humans, and other harmful health effects in animals. The toxic effects of FBs can be acute or chronic and these metabolites bioaccumulate mainly in liver and kidney tissues. Among FBs, fumonisin B1 (FB1 ) is the most relevant moiety although the 'hidden' forms produced after food thermal processes are becoming relevant...
July 20, 2018: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
Hyunjin Jeon, Euiyeon Lee, Dahee Kim, Minhyung Lee, Jeahee Ryu, Chungwon Kang, Soyoun Kim, Youngeun Kwon
Live-cell-based biosensors have emerged as a useful tool for biotechnology and chemical biology. Genetically encoded sensor cells often use bimolecular fluorescence complementation or fluorescence resonance energy transfer to build a reporter unit that suffers from nonspecific signal activation at high concentrations. Here, we designed genetically encoded sensor cells that can report the presence of biologically active molecules via fluorescence-translocation based on split intein-mediated conditional protein trans-splicing (PTS) and conditional protein trans-cleavage (PTC) reactions...
August 3, 2018: Analytical Chemistry
Frank R Brennan, Laura Andrews, Antonio R Arulanandam, Jorg Blumel, Jim Fikes, Christine Grimaldi, Janice Lansita, Lise I Loberg, Tim MacLachlan, Mark Milton, Suezanne Parker, Jay Tibbitts, Jayanthi Wolf, Krishna P Allamneni
Nonclinical safety testing of biopharmaceuticals can present significant challenges to human risk assessment with these innovative and often complex drugs. Emerging topics in this field were discussed recently at the 2016 Annual US BioSafe General Membership meeting. The presentations and subsequent discussions from the main sessions are summarized. The topics covered included: (i) specialty biologics (oncolytic virus, gene therapy, and gene editing-based technologies), (ii) the value of non-human primates (NHPs) for safety assessment, (iii) challenges in the safety assessment of immuno-oncology drugs (T cell-dependent bispecifics, checkpoint inhibitors, and costimulatory agonists), (iv) emerging therapeutic approaches and modalities focused on microbiome, oligonucleotide, messenger ribonucleic acid (mRNA) therapeutics, (v) first in human (FIH) dose selection and the minimum anticipated biological effect level (MABEL), (vi) an update on current regulatory guidelines, International Council for Harmonization (ICH) S1, S3a, S5, S9 and S11 and (vii) breakout sessions that focused on bioanalytical and PK/PD challenges with bispecific antibodies, cytokine release in nonclinical studies, determining adversity and NOAEL for biologics, the value of second species for toxicology assessment and what to do if there is no relevant toxicology species...
July 17, 2018: Regulatory Toxicology and Pharmacology: RTP
Katie M Rubin
At present, the inability to meaningfully and reliably conduct toxicological testing on human skeletal material represents a significant gap in forensic practice, especially in a time when the U.S. has declared opioid use a public health emergency and chemical weapon use in both mass and isolated attacks is prevalent in international news. In recent years, an increasing number of case studies and experiments have been published in an attempt to fill this knowledge gap. These papers are reviewed, and their valuable and pertinent findings discussed...
August 2018: Forensic Science International
Nicolai Nistor, Otilia Elena Frasinariu, Aniela Rugină, Irina Mihaela Ciomaga, Cristina Jităreanu, Violeta Ştreangă
Accidental poisonongs are an important cause of morbidity and even mortality, especially in young children.We performed a retrospective observational study on a group of children admitted at the Regional Center of Toxicology at the Children's Emergency Hospital "St. Mary" Iasi with accidental intoxication within a period of 3 years. Data were collected from patients' files and processed with a SPPS 18.0 database and a 95% confidence interval.During this period, 480 children were admitted with accidental intoxication...
July 2018: Medicine (Baltimore)
Yimeng Zhou, Ning Li, Zhixia Qiu, Xiaoyu Lu, Min Fang, Xijing Chen, Lili Ren, Guangji Wang, Pingkai Ouyang
Triacontanol (TA, C30 H62 O), abundantly present in plant cuticle waxes and bee waxes, has been found to display promising anti-neoplastic potentials. As a long chain fatty alcohol, TA possesses limited aqueous solubility, which hinders its medicinal application. To overcome its solubility barrier, a polymer prodrug was synthesized through attaching TA to poly ethylene glycol (PEG), using succinic acid as a linker with bifunctional amide and ester bonds. Anti-neoplastic effects of PEG-TA were assessed in LoVo and MCF7 cells, anti-proliferative and apoptosis-inducing activities were subsequently confirmed in mouse xenograft model...
November 2018: Drug Delivery
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