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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 12 (1995), S. 895-901 
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Retrospective application of allometric scaling techniques to tebufelone, a nonsteroidal antiinflammatory agent, in order to better understand the systemic exposure relationships between the doses administered to the species used in toxicology studies and the doses given to human subjects and patients in clinical studies. Methods. Non-compartmental estimates of tebufelone's total body volume of distribution during the terminal phase (Vz) and clearance (CL) obtained from intravenous dosing to rat, monkey, dog, and human were allometrically scaled to body weight, and body weight and brain weight, respectively. AUCs determined from single or multiple dose pharmacokinetic studies and from preclinical toxicology studies were plotted versus dose adjusted for bioavailability and divided by allometrically scaled clearance to produce an allometric relationship suggesting a non-linear increase in AUC with dose across the four species. Results. Segmental linear regression analysis of this relationship indicates a change point associated with an AUC of approximately 2,300 ng-hr/mL. Elevations in serum levels of various liver enzymes or associated signs of hepatic toxicity occur in some, but not all of the animals exposed for more than three weeks in repeat dosing studies at the actual dose that this represents. Conclusions. The analysis suggests that doses producing tebufelone plasma levels above a certain threshold AUC and duration of exposure to parent tebufelone are associated with increased risks of hepatic effects. Whether this is because metabolic shifts occur at these doses cannot be determined from these data.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 11 (1994), S. 1747-1754 
    ISSN: 1573-904X
    Keywords: in vitro skin penetration ; human cadaver skin ; statistics ; data transformations ; data analysis ; sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The institution of a readily-implemented sample screening and data handling procedure for in vitro skin penetration studies yields substantial improvements in sensitivity for distinguishing between formulations, treatments, penetrants, etc. The procedure involves four steps: 1) prescreen the tissue samples to determine their intrinsic permeability; 2) apply treatments using a randomized complete block (RGB) design, with blocking by tissue permeability; 3) apply a variance-stabilizing transformation to the penetration data, followed by outlier testing; and 4) analyze the transformed data according to an RGB analysis of variance, using tissue permeability as the blocking variable. For penetration studies in which high sample variability is a concern, the above procedure commonly yields a sensitivity advantage of several-fold versus alternative methods of comparison.
    Type of Medium: Electronic Resource
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  • 3
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    PANGAEA
    In:  Supplement to: McCave, I Nick; Crowhurst, Simon J; Kuhn, Gerhard; Hillenbrand, Claus-Dieter; Meredith, Michael P (2014): Minimal change in Antarctic Circumpolar Current flow speed between the last glacial and Holocene. Nature Geoscience, 7, 113–116, https://doi.org/10.1038/ngeo2037
    Publication Date: 2023-05-12
    Description: The Antarctic Circumpolar Current is key to the mixing and ventilation of the world's oceans. This current flows from west to east between about 45° and 70° S connecting the Atlantic, Pacific and Indian oceans, and is driven by westerly winds and buoyancy forcing. High levels of productivity in the current regulate atmospheric CO2 concentrations. Reconstructions of the current during the last glacial period suggest that flow speeds were faster or similar to present, and it is uncertain whether the strength and position of the westerly winds changed. Here we reconstruct Antarctic Circumpolar Current bottom speeds through the constricting Drake Passage and Scotia Sea during the Last Glacial Maximum and Holocene based on the mean grain size of sortable silt from a suite of sediment cores. We find essentially no change in bottom flow speeds through the region, and, given that the momentum imparted by winds, and modulated by sea-ice cover, is balanced by the interaction of these flows with the seabed, this argues against substantial changes in wind stress. However, glacial flow speeds in the sea-ice zone south of 56° S were significantly slower than present, whereas flow in the north was faster, but not significantly so. We suggest that slower flow over the rough topography south of 56° S may have reduced diapycnal mixing in this region during the last glacial period, possibly reducing the diapycnal contribution to the Southern Ocean overturning circulation.
    Type: Dataset
    Format: application/zip, 12 datasets
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  • 4
    Publication Date: 2023-02-12
    Keywords: DATE/TIME; DEPTH, water; LATITUDE; LONGITUDE; Meredith1999a; OCE; Oceanography; Salinity; Temperature, water, potential; δ18O, water
    Type: Dataset
    Format: text/tab-separated-values, 597 data points
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  • 5
    Publication Date: 2023-02-12
    Keywords: DATE/TIME; DEPTH, water; LATITUDE; LONGITUDE; Meredith1999b; OCE; Oceanography; Salinity; Temperature, water, potential; δ18O, water
    Type: Dataset
    Format: text/tab-separated-values, 594 data points
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  • 6
    Publication Date: 2023-05-12
    Keywords: AGE; Age, comment; COMPCORE; Composite Core; Coulter Multisizer (Electrical Sensing Zone Method); Depth, bottom/max; DEPTH, sediment/rock; Depth, top/min; Sortable-silt mean; TPC287; Weddell Sea
    Type: Dataset
    Format: text/tab-separated-values, 80 data points
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  • 7
    Publication Date: 2023-05-12
    Keywords: AGE; Age, comment; COMPCORE; Composite Core; Coulter Multisizer (Electrical Sensing Zone Method); Depth, bottom/max; DEPTH, sediment/rock; Depth, top/min; Scotia Sea; Sortable-silt mean; TPC077
    Type: Dataset
    Format: text/tab-separated-values, 80 data points
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  • 8
    Publication Date: 2023-05-12
    Keywords: AGE; Age, comment; COMPCORE; Composite Core; Coulter Multisizer (Electrical Sensing Zone Method); Depth, bottom/max; DEPTH, sediment/rock; Depth, top/min; Scotia Sea; Sortable-silt mean; TPC288
    Type: Dataset
    Format: text/tab-separated-values, 132 data points
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  • 9
    Publication Date: 2023-06-27
    Keywords: AGE; Age, comment; ANT-X/5; Coulter Multisizer (Electrical Sensing Zone Method); Depth, bottom/max; DEPTH, sediment/rock; Depth, top/min; Gravity corer (Kiel type); Polarstern; PS22/817; PS22 06AQANTX_5; PS2319-1; Scotia Sea; SL; Sortable-silt mean
    Type: Dataset
    Format: text/tab-separated-values, 80 data points
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  • 10
    Publication Date: 2023-06-27
    Keywords: AGE; Age, comment; ANT-XXII/4; Coulter Multisizer (Electrical Sensing Zone Method); Depth, bottom/max; DEPTH, sediment/rock; Depth, top/min; PC; Piston corer; Polarstern; PS67; PS67/197-1; Scotia Sea; Sortable-silt mean
    Type: Dataset
    Format: text/tab-separated-values, 80 data points
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