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  • 1
    In: Molecules, MDPI AG, Vol. 25, No. 21 ( 2020-10-27), p. 4957-
    Abstract: The therapeutic utility of the copper ionophore disulfiram was investigated in a diet-induced obesity mouse model (C57BL/6J background), both through administration in feed (0.05 to 1% (w/w)) and via oral gavage (150 mg/kg) for up to eight weeks. Mice were monitored for body weight, fat deposition (perigonadal fat pads), metabolic changes (e.g., glucose dyshomeostasis) and pathologies (e.g., hepatic steatosis, hyperglycaemia and hypertriglyceridemia) associated with a high-fat diet. Metal-related pharmacological effects across major organs and serums were investigated using inductively coupled plasma mass spectrometry (ICP-MS). Disulfiram treatments (all modes) augmented hepatic copper in mice, markedly moderated body weight and abolished the deleterious systemic changes associated with a high-fat diet. Likewise, another chemically distinct copper ionophore H2(gtsm), administered daily (oral gavage), also augmented hepatic copper and moderated mouse body weight. Postmortem histological examinations of the liver and other major organs, together with serum aminotransferases, supported the reported therapeutic safety of disulfiram. Disulfiram specifically altered systemic copper in mice and altered hepatic copper metabolism, perturbing the incorporation of copper into ceruloplasmin (holo-ceruloplasmin biosynthesis) and subsequently reducing serum copper concentrations. Serum ceruloplasmin represents a biomarker for disulfiram activity. Our results establish copper ionophores as a potential class of antiobesity agents.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 2
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 2 ( 2023-01-12), p. 1367-
    Abstract: Research has linked specific COVID-19-related stressors to the mental health burden, yet most previous studies have examined only a limited number of stressors and have paid little attention to their clinical significance. This study tested the hypothesis that individuals who reported greater COVID-19-related stressors would be more likely to have elevated levels of anxiety, posttraumatic stress symptoms, and serious psychological distress. Methods: An online survey was administered to a convenience sample from 18 June to 19 July 2020, in US states that were most affected by COVID-19 infections and deaths at the time. Individuals who were 18 or older and residents of five Northeast US states were eligible to participate (N = 1079). In preregistered analyses, we used logistic regression models to test the associations of COVID-19 stressors with symptoms on the Generalized Anxiety Disorder-7 (GAD-7), Impact of Event Scale-Revised, and K6, adjusting for sociodemographic covariates. Results: COVID-19-related stressors (i.e., essential worker status, worry about COVID-19 infection, knowing someone hospitalized by COVID-19, having children under 14 at home, loneliness, barriers to environmental rewards, food insecurity, loss of employment) were associated with meeting thresholds (i.e., positive screening) for anxiety, posttraumatic stress, and/or serious psychological distress. Loneliness and barriers to environmental rewards were associated with all mental health outcomes. Limitations: We used a non-probability sample and cannot assume temporal precedence of stressors with regard to development of mental health symptoms. Conclusions: These findings link specific stressors to the mental health burden of the COVID-19 pandemic.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2175195-X
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