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  • 1
    ISSN: 1573-7241
    Keywords: antiplatelet agents ; platelet aggregation ; 7E3 ; monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The platelet glycoprotein (GP) IIb/IIIa receptor can bind fibrinogen, von Willebrand factor, and other adhesive ligands; this binding is the final common pathway mediating platelet aggregation. The purpose of this study was to evaluate the safety and platelet inhibitory characteristics of the Fab fragment of the murine monoclonal anti-GPIIb/IIIa 7E3 antibody (m7E3 Fab) when administered intravenously as a single bolus dose, as a single and repeat bolus dose, and as a single bolus dose followed by continuous infusions of varying duration. Various dosage regimens of m7E3 Fab were studied in 74 patients with stable angina. Dosage regimens included single doses of m7E3 Fab from 0.1 to 0.3 mg/kg, a single dose of 0.20–0.30 mg/kg, and a repeat dose of 0.05 mg/kg, or a loading dose followed by a continuous infusion of m7E3 Fab for up to 36 hours. To assess the effect of m7E3 Fab on platelet function, quantitative blockade of GPIIb/IIIa receptors, inhibition of ex vivo platelet aggregation, and template bleeding time were measured in all patients. Dose-dependent inhibition of platelet function was evident in response to escalating bolus doses of m7E3 Fab, with maximum inhibition observed at 0.25–0.30 mg/kg body weight; at the 0.30 mg/kg dose, mean (±SE) GPIIb/IIIa receptor blockade was 81±3%, ex vivo platelet aggregation in response to 20 µM ADP was 14±6% of baseline, and the median bleeding time was 〉20 minutes. Although platelet function gradually recovered following a single bolus injection, platelet inhibition could be sustained by continuous, low-dose infusion of the antibody. Platelet inhibition occurred within minutes, but m7E3 Fab that did not bind to platelets cleared rapidly from circulation. Sixteen percent of the m7E3 Fab-injected subjects exhibited low titer, human anti-murine antibody responses. No significant bleeding or allergic reactions were observed in any patients. One of the 74 patients developed transient thrombocytopenia soon after receiving m7E3 Fab. These studies establish that m7E3 Fab can be administered safely at doses that cause profound inhibition of platelet function.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2022-10-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Levin, L. A., Bett, B. J., Gates, A. R., Heimbach, P., Howe, B. M., Janssen, F., McCurdy, A., Ruhl, H. A., Snelgrove, P., Stocks, K., I., Bailey, D., Baumann-Pickering, S., Beaverson, C., Benfield, M. C., Booth, D. J., Carreiro-Silva, M., Colaco, A., Eble, M. C., Fowler, A. M., Gjerde, K. M., Jones, D. O. B., Katsumata, K., Kelley, D., Le Bris, N., Leonardi, A. P., Lejzerowicz, F., Macreadie, P., I., McLean, D., Meitz, F., Morato, T., Netburn, A., Pawlowski, J., Smith, C. R., Sun, S., Uchida, H., Vardaro, M. F., Venkatesan, R., & Weller, R. A. Global observing needs in the deep ocean. Frontiers in Marine Science, 6, (2019):241, doi: 10.3389/fmars.2019.00241.
    Description: The deep ocean below 200 m water depth is the least observed, but largest habitat on our planet by volume and area. Over 150 years of exploration has revealed that this dynamic system provides critical climate regulation, houses a wealth of energy, mineral, and biological resources, and represents a vast repository of biological diversity. A long history of deep-ocean exploration and observation led to the initial concept for the Deep-Ocean Observing Strategy (DOOS), under the auspices of the Global Ocean Observing System (GOOS). Here we discuss the scientific need for globally integrated deep-ocean observing, its status, and the key scientific questions and societal mandates driving observing requirements over the next decade. We consider the Essential Ocean Variables (EOVs) needed to address deep-ocean challenges within the physical, biogeochemical, and biological/ecosystem sciences according to the Framework for Ocean Observing (FOO), and map these onto scientific questions. Opportunities for new and expanded synergies among deep-ocean stakeholders are discussed, including academic-industry partnerships with the oil and gas, mining, cable and fishing industries, the ocean exploration and mapping community, and biodiversity conservation initiatives. Future deep-ocean observing will benefit from the greater integration across traditional disciplines and sectors, achieved through demonstration projects and facilitated reuse and repurposing of existing deep-sea data efforts. We highlight examples of existing and emerging deep-sea methods and technologies, noting key challenges associated with data volume, preservation, standardization, and accessibility. Emerging technologies relevant to deep-ocean sustainability and the blue economy include novel genomics approaches, imaging technologies, and ultra-deep hydrographic measurements. Capacity building will be necessary to integrate capabilities into programs and projects at a global scale. Progress can be facilitated by Open Science and Findable, Accessible, Interoperable, Reusable (FAIR) data principles and converge on agreed to data standards, practices, vocabularies, and registries. We envision expansion of the deep-ocean observing community to embrace the participation of academia, industry, NGOs, national governments, international governmental organizations, and the public at large in order to unlock critical knowledge contained in the deep ocean over coming decades, and to realize the mutual benefits of thoughtful deep-ocean observing for all elements of a sustainable ocean.
    Description: Preparation of this manuscript was supported by NNX16AJ87A (NASA) Consortium for Ocean Leadership, Sub-Award No. SA16-33. AC was supported by FCT-Investigador contract (IF/00029/2014/CP1230/CT0002). LL was supported by a NASA subaward from the Consortium for Ocean Leadership. AG and HR were supported by Horizon 2020, EU Project “EMSO Link” grant ID 731036. AG, BB, DJ, and HR contributions were supported by the UK Natural Environment Research Council Climate Linked Atlantic Section Science project (NE/R015953/1). JP was funded by the Swiss Network for International Studies, and the Swiss National Science Foundation (grant 31003A_179125). TM was supported by Program Investigador FCT (IF/01194/2013), IFCT Exploratory Project (IF/01194/2013/CP1199/CT0002), H2020 Atlas project (GA 678760), and the H2020 MERCES project (GA 689518). This is PMEL contribution number 4965.
    Keywords: Deep sea ; Ocean observation ; Blue economy ; Essential ocean variables ; Biodiversity ; Ocean sensors
    Repository Name: Woods Hole Open Access Server
    Type: Article
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