Browsing by Subject "Toxicology"

Now showing 1 - 10 of 15
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    A Retrospective Cohort Study Examining the Utility of Perinatal Urine Toxicology Testing to Guide Breastfeeding Initiation
    (Wolters Kluwer, 2021) Harris, Miriam; Joseph, Kathleen; Hoeppner, Bettina; Wachman, Elisha M.; Gray, Jessica R.; Saia, Kelley; Wakeman, Sarah; Bair-Merritt, Megan H.; Schiff, Davida M.; Emergency Medicine, School of Medicine
    Objective: National guidelines advise against breastfeeding for women who use nonprescribed substances in the third trimester. This reduces the number of women who are supported in breastfeeding initiation despite limited evidence on the prognostic value of third trimester substance use. We sought to examine the degree to which prenatal nonprescribed substance use is associated with non-prescribed use postpartum. Methods: Retrospective cohort study of pregnant women with opioid use disorder on methadone or buprenorphine between 2006 and 2015. Nonprescribed use was defined by a positive urine drug testing (UDT). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated comparing 3 prenatal periods with postpartum UDT results. Generalized estimating equations were used to examine the extent to which prenatal nonprescribed use was associated with postpartum use. Results: Included were 545 deliveries by 503 women. Mean age was 28.3 years, 88% were White/non-Hispanic, 93% had public insurance, and 43% received adequate prenatal care. The predictive value of UDT's 90 to 31 days before delivery, 30 to 0 days before delivery, and at delivery showed low sensitivity (44, 26, 27%, respectively) and positive predictive value (36, 36, 56%, respectively), but higher negative predictive value (80, 85, and 78%, respectively), P-values all <0.05. In the final adjusted model, only nonprescribed use at delivery was significantly associated with postpartum nonprescribed use. Conclusions: Nonprescribed use at delivery was most strongly associated with postpartum use compared with earlier time periods currently prioritized in guidelines. In women with opioid use disorder prenatal UDT results alone are insufficient to guide breastfeeding decisions.
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    ACMT Position Statement: Determining Brain Death in Adults After Drug Overdose
    (Springer Nature, 2017-09) Neavyn, Mark J.; Stolbach, Andrew; Greer, David M.; Nelson, Lewis S.; Smith, Silas W.; Brent, Jeffrey; Tormoehlen, Laura M.; Neurology, School of Medicine
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    Chronic-plus-binge alcohol intake induces production of proinflammatory mtDNA-enriched extracellular vesicles and steatohepatitis via ASK1/p38MAPKα-dependent mechanisms
    (American Society for Clinical Investigation, 2020-06-16) Ma, Jing; Cao, Haixia; Rodrigues, Robim M.; Xu, Mingjiang; Ren, Tianyi; He, Yong; Hwang, Seonghwan; Feng, Dechun; Ren, Ruixue; Yang, Peixin; Liangpunsakul, Suthat; Sun, Jian; Gao, Bin; Medicine, School of Medicine
    Alcohol-associated liver disease is a spectrum of liver disorders with histopathological changes ranging from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Recent data suggest that chronic-plus-binge ethanol intake induces steatohepatitis by promoting release by hepatocytes of proinflammatory mitochondrial DNA–enriched (mtDNA-enriched) extracellular vesicles (EVs). The aim of the present study was to investigate the role of the stress kinase apoptosis signal–regulating kinase 1 (ASK1) and p38 mitogen-activated protein kinase (p38) in chronic-plus-binge ethanol–induced steatohepatitis and mtDNA-enriched EV release. Microarray analysis revealed the greatest hepatic upregulation of metallothionein 1 and 2 (Mt1/2), which encode 2 of the most potent antioxidant proteins. Genetic deletion of the Mt1 and Mt2 genes aggravated ethanol-induced liver injury, as evidenced by elevation of serum ALT, neutrophil infiltration, oxidative stress, and ASK1/p38 activation in the liver. Inhibition or genetic deletion of Ask1 or p38 ameliorated ethanol-induced liver injury, inflammation, ROS levels, and expression of phagocytic oxidase and ER stress markers in the liver. In addition, inhibition of ASK1 or p38 also attenuated ethanol-induced mtDNA-enriched EV secretion from hepatocytes. Taken together, these findings indicate that induction of hepatic mtDNA-enriched EVs by ethanol is dependent on ASK1 and p38, thereby promoting alcoholic steatohepatitis.
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    Controversial COVID-19 Cures: Hydroxychloroquine and Oleander Pediatric Ingestion Simulation Cases
    (Springer, 2022-06-21) Solano, Joshua J.; Mendelsohn, Rebecca A.; Ahmed, Rami A.; Shih, Richard D.; Clayton, Lisa M.; Alter, Scott M.; Hughes, Patrick G.; Emergency Medicine, School of Medicine
    Introduction: The use of hydroxychloroquine has dramatically increased since being touted as a potential therapeutic in combating coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus. This newfound popularity increases the risk of accidental pediatric ingestion, whereby just one or two tablets causes morbidity and mortality from seizures, cardiac dysrhythmias, and cardiogenic shock. The unique management of hydroxychloroquine overdose makes it imperative for emergency medicine physicians to have familiarity with treating this condition. Similarly, ​​during the COVID-19 pandemic, there have been publicized cases touting extracts of oleander as being a potential therapeutic against the illness. Since it is commonly available and potentially lethal ingestion with a possible antidote, we developed a simulation case based on the available literature. The two cases were combined to create a pediatric toxicology curriculum for emergency medicine residents and medical students. Both of these treatments were selected as simulation cases since they were being touted by prominent national figures as potential cures for COVID-19. Methods: Two series of simulation cases were conducted in a high-fidelity simulation lab with emergency medicine residents and medical students. The hydroxychloroquine simulation case involved the management of a four-year-old male who presented to the emergency department with nausea, vomiting, and tachycardia after ingesting hydroxychloroquine tablets. As the case unfolded, the child became increasingly unstable, eventually experiencing QT prolongation, torsades de pointes, and ventricular fibrillation arrest requiring appropriate resuscitation to achieve a return of spontaneous circulation. The oleander simulation case involved the management of a three-year-old male who presented to the emergency department with nausea, vomiting, and tachycardia after ingesting parts of an unknown plant. As that case progresses, the child becomes increasingly unstable, eventually experiencing atrial fibrillation, bradycardia, and degenerating into pulseless electrical activity and cardiac arrest requiring appropriate resuscitation to achieve the return of spontaneous circulation. Both series of simulation cases were modifiable based on trainee level and had the ability to include ancillary emergency department staff. Results: Each simulation case was performed six times at our simulation center, with a total of 22 learners for the hydroxychloroquine case, and 14 for the oleander case. Through pre- and post-simulation confidence assessments, learners demonstrated increases in knowledge of toxidromes, evaluating pediatric overdoses, treating cardiac dysrhythmias, performing pediatric advanced life support, and managing post-arrest care. Learners also demonstrated improvements in recognizing the unique treatment of hydroxychloroquine and oleander toxicity, the toxic dose of both substances in a child, and the most common electrolyte anomaly seen in each toxicity. Discussion: Simulation training enables learners to manage rare and complex disease processes. These cases were designed to educate trainees in recognizing and treating rare overdoses of emerging "therapeutics" that were touted early in the COVID-19 pandemic.
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    Detecting Attomolar DNA-Damaging Anticancer Drug Activity in Cell Lysates with Electrochemical DNA Devices
    (American Chemical Society, 2021-07-23) Wettasinghe, Ashan P.; Singh, Naveen; Starcher, Colton L.; DiTusa, Chloe C.; Ishak-Boushaki, Zakari; Kahanda, Dimithree; McMullen, Reema; Motea, Edward A.; Slinker, Jason D.; Biochemistry and Molecular Biology, School of Medicine
    Here, we utilize electrochemical DNA devices to quantify and understand the cancer-specific DNA-damaging activity of an emerging drug in cellular lysates at femtomolar and attomolar concentrations. Isobutyl-deoxynyboquinone (IB-DNQ), a potent and tumor-selective NAD(P)H quinone oxidoreductase 1 (NQO1) bioactivatable drug, was prepared and biochemically verified in cancer cells highly expressing NQO1 (NQO1+) and knockdowns with low NQO1 expression (NQO1−) by Western blot, NQO1 activity analysis, survival assays, oxygen consumption rate, extracellular acidification rate, and peroxide production. Lysates from these cells and the IB-DNQ drug were then introduced to a chip system bearing an array of DNA-modified electrodes, and their DNA-damaging activity was quantified by changes in DNA-mediated electrochemistry arising from base-excision repair. Device-level controls of NQO1 activity and kinetic analysis were used to verify and further understand the IB-DNQ activity. A 380 aM IB-DNQ limit of detection and a 1.3 fM midpoint of damage were observed in NQO1+ lysates, both metrics 2 orders of magnitude lower than NQO1− lysates, indicating the high IB-DNQ potency and selectivity for NQO1+ cancers. The device-level damage midpoint concentration in NQO1+ lysates was over 8 orders of magnitude lower than cell survival benchmarks, likely due to poor IB-DNQ cellular uptake, demonstrating that these devices can identify promising drugs requiring improved cell permeability. Ultimately, these results indicate the noteworthy potency and selectivity of IB-DNQ and the high sensitivity and precision of electrochemical DNA devices to analyze agents/drugs involved in DNA-damaging chemotherapies.
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    Epidemiologic Trends In Children With Toxicologic Exposures Requiring Intensive Care Before and During the COVID-19 Pandemic
    (Pediatric Pharmacy Association, 2024) Hughes, Kaitlin; Overberg, Adam; Satterfield, Kennedi; Voss, Hannah; Rogerson, Colin; Pediatrics, School of Medicine
    Objective: Pediatric poison exposures are a common reason for pediatric intensive care unit (PICU) -admission. The purpose of this study was to examine the exposure trends and patient outcomes in 2018-2019 compared with 2020-2021 amidst the COVID-19 pandemic. Methods: This was a retrospective cohort study of patients 18 years of age or younger with a suspected toxicologic exposure from January 2018 to March 2021. The primary endpoint was rate of PICU admissions between the 2 cohorts. Secondary endpoints included medical outcome stratified by severity, PICU length of stay, and need for mechanical ventilation. Results: Our study included a total of 340 patients with median age 14.5 (IQR, 11.9-16.1) years. There was no significant difference in age, sex, or race between the 2 cohorts. The percentage of patients admitted to the PICU for poison exposures was significantly higher in the COVID-19 cohort compared with the pre-COVID-19 cohort (8.4% vs 3.7%, p < 0.01). Severity of medical outcomes differed between the groups; the COVID-19 cohort had more extreme clinical presentations of no effect or death (p < 0.01). No significant difference was found among the remaining secondary outcomes. Classes of substances ingested were comparable with baseline poison center data. Conclusions: Poisoning-related PICU admissions occurred at more than twice the pre-pandemic rate. This may emphasize the effect of the COVID-19 pandemic on pediatric access and exposure to poisons.
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    Essential Oils Produce Developmental Toxicity in Zebrafish Embryos and Cause Behavior Changes in Zebrafish Larvae
    (MDPI, 2023-10-18) da Silva, Ivanildo Inacio, Jr.; da Silva, Niely Priscila Correia; Marrs, James A.; Cadena, Pabyton Gonçalves; Biology, School of Science
    Essential oils have gained significant popularity in various industries due to their biological properties, but their potential toxic effects on living organisms have been poorly investigated. This study aimed to evaluate the effects of lemongrass, thyme, and oregano essential oils on zebrafish embryos and larvae as animal models. Embryos were exposed to different concentrations of essential oils, and various endpoints were assessed, including epiboly, mortality (LC50), morphometry, and behavioral changes. All three essential oils reduced epiboly, affecting embryonic development. LC50 values were calculated for lemongrass (3.7 µg/mL), thyme (14.4 µg/mL), and oregano (5.3 µg/mL) oils. Larvae exposed to these oils displayed morphological defects, including growth reduction, spinal deformation, pericardial edema, eye size reduction, and reduced swim-bladder inflation. Morphometric analysis confirmed reduced larval length at higher oil concentrations. Essential-oil exposure altered zebrafish larval swimming behavior, with lemongrass oil reducing dark-cycle activity and oregano oil increasing light-cycle activity, suggesting neurodevelopmental toxicity. These findings illustrate the adverse effects of these oils on zebrafish embryos and larvae and reveal essential-oil toxicity, indicating careful use should be considered, particularly during pregnancy.
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    Fan of black licorice? Beware of its dark side − it can be dangerous for your health
    (The Conversation US, Inc., 2020-10-26) Sullivan, Bill
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    The Genius of the Zebrafish Model: Insights on Development and Disease
    (MDPI, 2021-05) Marrs, James A.; Sarmah, Swapnalee; Biology, School of Science