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  • 1
    ISSN: 1432-2307
    Schlagwort(e): Metastasis ; Tumour growth ; Tumour vascularization ; Fluorescent DNA staining ; Fluorochrome diffusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    ISSN: 1573-904X
    Schlagwort(e): pancreatic lipase ; lipase ; lipolysis ; triglycerides ; kinetics ; mechanism ; calcium ; bile salts ; lecithin ; emulsions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    ISSN: 1573-904X
    Schlagwort(e): pancreatic lipase ; lipase, phenytoin ; prodrugs ; prodrug hydrolysis ; emulsions ; micelles ; lipolysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: 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.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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