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  • 1
    Electronic Resource
    Electronic Resource
    Pancreatic Lipase-Catalyzed Hydrolysis of Esters of Hydroxymethyl Phenytoin Dissolved in Various Metabolizable Vehicles, Dispersed in Micellar Systems, and in Aqueous Suspensions (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 555-563 
    Details
    ISSN: 1573-904X
    Keywords: pancreatic lipase ; lipase, phenytoin ; prodrugs ; prodrug hydrolysis ; emulsions ; micelles ; lipolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Lipase-catalyzed hydrolysis of fatty acid esters of 3-hydroxymethyl phenytoin was studied in various triglyceride and ethyl oleate emulsions, dispersed in micellar solutions, and suspended in an aqueous buffered solution. Phenytoin release from ethyl oleate emulsions of the prodrugs show apparent first-order kinetics with the pentanoate to nonanoate derivatives and sigmoidal kinetics with the long-chain fatty acid derivatives (stearate and oleate). A transition in the kinetic behavior, between the short- and the long-chain acyl prodrugs, was observed with the decanoate derivative. These observations are accounted for by a proposed kinetic model. Phenytoin release from the solid prodrugs follows zero-order kinetics and is independent of the total amounts of suspended material but directly proportional to the lipase concentration. Lipolysis of the solid suspended prodrugs was dependent on the length of the acyl side chain of the prodrug, with maxima for the pentanoate and the octanoate derivatives. The short-chain derivatives, acetate and propionate, as well as the long-chain prodrug, stearate, showed the slowest lipolysis rate when present as solid dispersions. The zero-order rate is qualitatively correlated with the melting point of the prodrugs. This result might be expected if the melting point is taken as a measure of the cohesivity or packing of the molecules at the surface of a crystal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015993112678
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  • 2
    Electronic Resource
    Electronic Resource
    Differential uptake of systemic fluorochrome Hoechst 33342 in lung and liver metastasis of B16 melanoma (1992)
    Springer
    Virchows Archiv 421 (1992), S. 485-490 
    Details
    ISSN: 1432-2307
    Keywords: Metastasis ; Tumour growth ; Tumour vascularization ; Fluorescent DNA staining ; Fluorochrome diffusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The growth and vascularization patterns of B16 melanoma colonies in the liver and lungs were measured and compared by histological techniques and dye diffusion patterns after injection of the fluorochrome Hoechst 33342. In the liver, the fluorescent pattern of dye diffusion revealed that uninodular tumours measuring up to 146 μn in diameter were not functionally vascularized. However, when the nodules fused to give rise to multinodular tumours measuring between 256 and 366 μn in diameter, a reticular dye diffusion pattern revealed functional tumour vascularization. In the lungs, subpleural, parenchymal and peritubular (i.e. surrounding blood vessels and airways) tumours were observed. The two former classes were vascularized down to thicknesses and diameters of 49 and 24 μm respectively. In contrast, dye diffusion was never seen in peritubular tumour cuffs up to 609 μm in thickness. The results indicate differences in vascularization patterns in B16 tumours in the liver and lungs, and differences between tumours growing in different sites within the lungs. If these results are applicable to metastases in these two organs, they indicate potential diffusion-mediated resistance to chemotherapy, and potential hypoxia-mediated resistance to radiotherapy of both metastases and micrometastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01606877
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  • 3
    Electronic Resource
    Electronic Resource
    Isolation of the trail recruitment pheromone ofSolenopsis invicta (1988)
    Springer
    Journal of chemical ecology 14 (1988), S. 825-838 
    Details
    ISSN: 1573-1561
    Keywords: Solenopsis invicta ; Hymenoptera ; Formicidae ; imported fire ant ; Dufour's gland ; trail pheromone ; pheromone ; (Z,E)-a-farnesene ; sesquiterpene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract TheSolenopsis invicta trail pheromone is synthesized by the Dufour's gland and is released through the sting apparatus. The recruitment subcategory of theS. invicta trail pheromone was shown to be composed of a mixture of the orientation pheromone, (Z,E)-α-farnesene and an unidentified homosesquiterpene consisting of three rings and one double bond (C-1). C-1 is present in worker Dufour's glands at only 75 pg per worker equivalent. This is the first report that demonstrates that different exocrine products from the same gland control different subcategories of behavior related to mass recruitment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01018776
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  • 4
    Electronic Resource
    Electronic Resource
    The Role of Calcium Ions and Bile Salts on the Pancreatic Lipase-Catalyzed Hydrolysis of Triglyceride Emulsions Stabilized with Lecithin (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 449-457 
    Details
    ISSN: 1573-904X
    Keywords: pancreatic lipase ; lipase ; lipolysis ; triglycerides ; kinetics ; mechanism ; calcium ; bile salts ; lecithin ; emulsions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Lecithin-stabilized triglyceride emulsions are subject to hydrolysis by pancreatic lipase. The time profiles of these reactions are characterized by a lag-phase and a zero-order phase. Lag phases are more pronounced with long-chain triglycerides. Ca2+ is effective in reducing the lag-phase and activating lipase. Kinetic analysis of the reactions suggests that, like previous findings by others, taurodeoxycholate (TDC) micellar solutions combine with the lipase–colipase complex to form another catalytically active enzyme form. This enzyme form exhibits reduced activity in the absence of Ca2+. In the presence of Ca2+ the mixed micelle–lipase complex becomes more active and opens a new pathway for lipolysis. It is suggested that this enzyme form can bind more easily to interfaces with different physicochemical properties. Under these conditions, Ca2+ activates the lipolysis of short-, medium-, and long-chain triglycerides by a similar mechanism. Maximum activities were measured in the presence of approximately 6 mM TDC and 30 mM Ca2+. The experimental conditions approximate the physiological conditions in the gastrointestinal tract since all of the factors studied here have been reported to be necessary for in vivo lipolysis and/or absorption of triglycerides. A mechanistic model for lipolysis in the presence of Ca2+ and the bile salt TDC is proposed which accounts for most of the experimental observations in a quantitative manner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015956104500
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  • 5
    Electronic Resource
    Electronic Resource
    Kinetics and Mechanism of Degradation of Zileuton, a Potent 5-Lipoxygenase Inhibitor (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 1465-1473 
    Details
    ISSN: 1573-904X
    Keywords: lipoxygenase ; 5-lipoxygenase inhibitor ; kinetics ; borate catalysis ; N-hydroxyurea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Zileuton (N-(1-benzo[b]thien-2-ylethyl)N-hydroxyurea) is a powerful 5-lipoxygenase inhibitor. The chemical degradation of Zileuton and related hydroxyurea derivatives was studied in aqueous solutions as a function of pH and temperature. The pH profile for the degradation of Zileuton shows an acid-catalyzed region at pH values below 2, water hydrolysis of the protonated form at pH values from 3 to 8, and water hydrolysis of the unprotonated form at pH values greater than 9. Hydrolysis of the hydroxyurea moiety to give the hydroxylamine derivative represents the main degradation pathway for Zileuton. This product, however, is not stable and is present at low concentrations at pH values below 6 and not observed at pH values greater than 7. Further decomposition of the hydroxylamine derivative leads to the observed degradation products. Air oxidation to the isomeric oximes accounts for the observed products at pH values greater than 7. Hydrolysis of the oximes to the ketone derivative accounts for the observed products at pH values 2 to 6. Parallel decomposition pathways to the alcohol derivative were noted under strongly acidic conditions, pH 0 to 2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015819115075
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  • 6
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    The South Atlantic Anticyclone as a key player for the representation of the tropical Atlantic climate in coupled climate models (2016)
    Springer
    In:  EPIC3Climate Dynamics, Springer, ISSN: 0930-7575
    Details
    Publication Date: 2016-09-19
    Description: The key role of the South Atlantic Anticyclone (SAA) on the seasonal cycle of the tropical Atlantic is investigated with a regionally coupled atmosphere–ocean model for two different coupled domains. Both domains include the equatorial Atlantic and a large portion of the northern tropical Atlantic, but one extends southward, and the other northwestward. The SAA is simulated as internal model variability in the former, and is prescribed as external forcing in the latter. In the first case, the model shows significant warm biases in sea surface temperature (SST) in the Angola-Benguela front zone. If the SAA is externally prescribed, these biases are substantially reduced. The biases are both of oceanic and atmospheric origin, and are influenced by ocean–atmosphere interactions in coupled runs. The strong SST austral summer biases are associated with a weaker SAA, which weakens the winds over the southeastern tropical Atlantic, deepens the thermocline and prevents the local coastal upwelling of colder water. The biases in the basins interior in this season could be related to the advection and eddy transport of the coastal warm anomalies. In winter, the deeper thermocline and atmospheric fluxes are probably the main biases sources. Biases in incoming solar radiation and thus cloudiness seem to be a secondary effect only observed in austral winter. We conclude that the external prescription of the SAA south of 20°S improves the simulation of the seasonal cycle over the tropical Atlantic, revealing the fundamental role of this anticyclone in shaping the climate over this region.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
    Format: application/pdf
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