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  1. Article ; Online: Phosphine toxicity: a story of disrupted mitochondrial metabolism.

    Sciuto, Alfred M / Wong, Benjamin J / Martens, Margaret E / Hoard-Fruchey, Heidi / Perkins, Michael W

    Annals of the New York Academy of Sciences

    2016  Volume 1374, Issue 1, Page(s) 41–51

    Abstract: Rodenticides and pesticides pose a significant threat not only to the environment but also directly to humans by way of accidental and/or intentional exposure. Metal phosphides, such as aluminum, magnesium, and zinc phosphides, have gained popularity ... ...

    Abstract Rodenticides and pesticides pose a significant threat not only to the environment but also directly to humans by way of accidental and/or intentional exposure. Metal phosphides, such as aluminum, magnesium, and zinc phosphides, have gained popularity owing to ease of manufacture and application. These agents and their hydrolysis by-product phosphine gas (PH3 ) are more than adequate for eliminating pests, primarily in the grain storage industry. In addition to the potential for accidental exposures in the manufacture and use of these agents, intentional exposures must also be considered. As examples, ingestion of metal phosphides is a well-known suicide route, especially in Asia; and intentional release of PH3 in a populated area cannot be discounted. Metal phosphides cause a wide array of effects that include cellular poisoning, oxidative stress, cholinesterase inhibition, circulatory failure, cardiotoxicity, gastrointestinal and pulmonary toxicity, hepatic damage, neurological toxicity, electrolyte imbalance, and overall metabolic disturbances. Mortality rates often exceed 70%. There are no specific antidotes against metal phosphide poisoning. Current therapeutic intervention is limited to supportive care. The development of beneficial medical countermeasures will rely on investigative mechanistic toxicology; the ultimate goal will be to identify specific treatments and therapeutic windows for intervention.
    MeSH term(s) Animals ; Cell Death/drug effects ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Models, Biological ; Oxidative Stress/drug effects ; Phosphines/toxicity ; Reactive Oxygen Species/metabolism
    Chemical Substances Phosphines ; Reactive Oxygen Species ; phosphine (FW6947296I)
    Language English
    Publishing date 2016-05-24
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.13081
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Precise quantification of nanoparticle internalization.

    Gottstein, Claudia / Wu, Guohui / Wong, Benjamin J / Zasadzinski, Joseph Anthony

    ACS nano

    2013  Volume 7, Issue 6, Page(s) 4933–4945

    Abstract: Nanoparticles have opened new exciting avenues for both diagnostic and therapeutic applications in human disease, and targeted nanoparticles are increasingly used as specific drug delivery vehicles. The precise quantification of nanoparticle ... ...

    Abstract Nanoparticles have opened new exciting avenues for both diagnostic and therapeutic applications in human disease, and targeted nanoparticles are increasingly used as specific drug delivery vehicles. The precise quantification of nanoparticle internalization is of importance to measure the impact of physical and chemical properties on the uptake of nanoparticles into target cells or into cells responsible for rapid clearance. Internalization of nanoparticles has been measured by various techniques, but comparability of data between different laboratories is impeded by lack of a generally accepted standardized assay. Furthermore, the distinction between associated and internalized particles has been a challenge for many years, although this distinction is critical for most research questions. Previously used methods to verify intracellular location are typically not quantitative and do not lend themselves to high-throughput analysis. Here, we developed a mathematical model which integrates the data from high-throughput flow cytometry measurements with data from quantitative confocal microscopy. The generic method described here will be a useful tool in biomedical nanotechnology studies. The method was then applied to measure the impact of surface coatings of vesosomes on their internalization by cells of the reticuloendothelial system (RES). RES cells are responsible for rapid clearance of nanoparticles, and the resulting fast blood clearance is one of the major challenges in biomedical applications of nanoparticles. Coating of vesosomes with long chain polyethylene glycol showed a trend for lower internalization by RES cells.
    MeSH term(s) Animals ; Biological Transport ; Cell Line ; Humans ; Macrophages/metabolism ; Mice ; Mononuclear Phagocyte System/cytology ; Nanoparticles ; Polystyrenes/chemistry ; Polystyrenes/metabolism
    Chemical Substances Polystyrenes
    Language English
    Publishing date 2013-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1936-086X
    ISSN (online) 1936-086X
    DOI 10.1021/nn400243d
    Database MEDical Literature Analysis and Retrieval System OnLINE

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