2,459 research outputs found

    Human Food Safety Implications of Variation in Food Animal Drug Metabolism

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    Citation: Lin, Z., Vahl, C. I., & Riviere, J. E. (2016). Human Food Safety Implications of Variation in Food Animal Drug Metabolism. Scientific Reports, 6. doi:10.1038/srep27907Violative drug residues in animal-derived foods are a global food safety concern. The use of a fixed main metabolite to parent drug (M/D) ratio determined in healthy animals to establish drug tolerances and withdrawal times in diseased animals results in frequent residue violations in food-producing animals. We created a general physiologically based pharmacokinetic model for representative drugs (ceftiofur, enrofloxacin, flunixin, and sulfamethazine) in cattle and swine based on extensive published literature. Simulation results showed that the M/D ratio was not a fixed value, but a time-dependent range. Disease changed M/D ratios substantially and extended withdrawal times; these effects exhibited drug-and species-specificity. These results challenge the interpretation of violative residues based on the use of the M/D ratio to establish tolerances for metabolized drugs

    Microbial enrichment culture responsible for the complete oxidative biodegradation of 3‑Amino-1,2,4-triazol-5-one (ATO), the reduced daughter product of the insensitive munitions compound 3‑Nitro-1,2,4-triazol-5-one (NTO)

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    3-Nitro-1,2,4-triazol-5-one (NTO) is one of the main ingredients of many insensitive munitions, which are being used as replacements for conventional explosives. As its use becomes widespread, more research is needed to assess its environmental fate. Previous studies have shown that NTO is biologically reduced to 3-amino-1,2,4-triazol-5-one (ATO). However, the final degradation products of ATO are still unknown. We have studied the aerobic degradation of ATO by enrichment cultures derived from the soil. After multiple transfers, ATO degradation was monitored in closed bottles through measurements of inorganic carbon and nitrogen species. The results indicate that the members of the enrichment culture utilize ATO as the sole source of carbon and nitrogen. As ATO was mineralized to CO₂, N₂, and NH₄⁺, microbial growth was observed in the culture. Co-substrates addition did not increase the ATO degradation rate. Quantitative polymerase chain reaction analysis revealed that the organisms that enriched using ATO as carbon and nitrogen source were Terrimonas spp., Ramlibacter-related spp., Mesorhizobium spp., Hydrogenophaga spp., Ralstonia spp., Pseudomonas spp., Ectothiorhodospiraceae, and Sphingopyxis. This is the first study to report the complete mineralization of ATO by soil microorganisms, expanding our understanding of natural attenuation and bioremediation of the explosive NTO.Journal ArticleFinal article publishe

    Michael Rodriguez interviews Jim Daniels, Professor of English and Creative Writing at Carnegie Mellon University

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    Detroit native Jim Daniels, Professor of English and Creative Writing at Carnegie Mellon University, talks about being identified as a Detroit writer and poet, reading in Detroit with author Philip Levine, script and short story writing, challenging himself to try new things and developing a character over time. Daniels also explains how our ideas of movies have influenced expectations in writing and changed the way many writers approach their craft and suggests that contemporary writers have dropped the idea of writing the great American novel for writing the great American screenplay. Daniels is interviewed by Michael Rodriguez for the Michigan State University Libraries' Michigan Writers Series

    Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach

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    Citation: Lin, Z. M., Cuneo, M., Rowe, J. D., Li, M. J., Tell, L. A., Allison, S., . . . Gehring, R. (2016). Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach. Bmc Veterinary Research, 12, 10. https://doi.org/10.1186/s12917-016-0884-4Background: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. Results: All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. Conclusions: The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach for treating pulmonary infections in lactating goats, but a prolonged withdrawal time of at least 39 days after the second injection should be considered to prevent violative residues in milk and any dairy goat being used for meat should have an extended meat withdrawal time

    Authors and auteurs: the uses of theory

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    Analyzing bond characteristics between composites and quasi-brittle substrates in the repair of bridges and other concrete structures

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    During the last two decades, externally bonded fiber-reinforced polymer (FRP) composites have been widely used for strengthening, repairing, and rehabilitating reinforced concrete (RC) structural members. The bond characteristics contribute to the effectiveness of the stress transfer achieved between the FRP composite and the concrete substrate. Debonding of the FRP composite reinforcement is the most critical concern in this type of application. Under monotonic and fatigue-loading conditions, FRP-concrete shear debonding has been idealized as a Mode-II fracture problem along the bi-material interface. A cohesive material law is used to describe the interfacial stress transfer at the macroscopic level. The area under the entire curve represents the fracture energy, and is related to the load-carrying capacity of the interface. In this chapter, previous experimental results published by the author are discussed to show how the fracture energy can be considered a true fracture parameter. The results are instrumental in discussing the strain limits provided in international codes and guidelines. Future research needed and newly developed composites are introduced at the end of the chapter
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