Ernst Simonson (1898-1974).
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Biomedical subjects
Publications and source records attributed to H Schaefer.
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The absolute concentrations of an antimycotic drug, econazole, 1-[2,4-dichloro-beta-(p-chlorobenzyloxy)-phenethyl]-imidazole nitrate, in the different layers of the skin are reported when the agent is applied to human skin in vitro and in vivo. The drug was tritium-labelled and incorporated into an ointment to give a 1% concentration as it is used in the therapy of dermatomycoses. This ointment was applied to the skin surface. After fixed time intervals, the skin was sliced parallel to the surface and the amount in each layer determined by liquid scintillation counting. In the in vivo investigations, the excretion of the drug in the urine was also determined. The results reveal that though up to 90% of the drug remain on the surface, about 20 mug/ml epidermal tissue and 1.5 mug/ml dermal tissue can be achieved. The amount which is excreted in the urine is equivalent to the quantity which enters the skin, i.e., the penetrating drug is absorbed by the circulatory system.
Absolute concentrations in the horny layer, epidermis, and dermis of therapeutical doses of topically applied hydrocortisone to human skin (in vivo) are reported. Using vaseline as vehicle 2-10(-4) molar concentrations are found in the epidermis and 3-10(-5) molar concentrations in the dermis. Further, three vehicles revealed minor concentrations. Comparison of the results with similar in vitro-investigations, reported earlier, allow to judge the resorption rate by the intact capillary system. Uptake of hydrocortisone by the vessels is observed. With high rates of penetration vasoconstriction seems to limit the resorption, while this is not the case with low rates, for instance with polyethyleneglycol as vehicle. Thus a differing drug liberation from the vehicle causes qualitatively different permeation kinetics. The elimination by urine, however, was practically the same. It is concluded that different vehicles may cause different therapeutic concentrations of the drug in the skin, but equal systemic side effects.
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The pharmacokinetics of dithranol (anthralin) and its triacetate were investigated by employing a method which determines the quantity of the drug that penetrated into single layers of the human skin in vivo. For this purpose, tritium-labeled dithranol or triacetyl-dithranol was incorporated into four different ointments. The ointments were applied to the skin and biopsies were taken after 10, 30, 100, and 1000 min. The horny layer was removed before biopsy by Scotch tape stripping. The biopsies were sliced horizontally and the tritium determined in each sample. Dithranol as well as its triacetate penetrated best from more hydropholic ointments (Vaseline and aqueous wool-wax-alcohol ointment). From hydrophilic ointments (polyethylene glycol ointment and aqueous hydrophilic cream), only poor penetration was observed. Dithranol penetrated in far greater amounts than its triacetate, and the two compounds revealed fundamentally different penetration kinetics in epidermis and dermis. The data indicate that the triacetate was not split into its parent compound, dithranol, in substantial quantity, as the data obtained show the criteria of two independent substances.
Most mammalian cells cultivated in vitro can be infected with lymphocytic choriomeningitis (LCM) virus. In addition to infectious virus, the cells produce antigenic material that fixes complement in the presence of antibody and is precipitated by antiserum. Intracellular antigen can also be demonstrated by the immunofluorescence procedure. When infected cells are viewed with the electron microscope, viral structures are seen either budding from or in association with the cell membranes. Immunoelectron microscopy, immunofluorescence, and cytotoxicity tests reveal virus-specific antigens on the surface of intact cells. Virus multiplication may be succeeded by cytolysis. Two LCM virus-specific antigens (or antigenic groups) can at present be distinguished. One corresponds to the infectious virus; the other is the complement-fixing "soluble" antigen. This extractable complement-fixing activity is produced by infected cells and is also a structural component of the infectious virus. It is not represented on the surface of either the virion or the infected cell. The cytolytic potential of LCM virus varies and is dependent on its previous passage history. Cytolytic and "attenuated" variants are able to initiate persistent infection of Mus musculus.Together with infectious virus, particles are produced that temporarily protect cells against standard virus. They appear to be by-products of virus multiplication, not in the sense of deletion mutants but of virus structures insufficiently equipped for their own active or passive replication, though capable of interfering with infectious virus. No evidence has been found for the generation of "defective interfering" particles, though their presence has not yet been excluded.
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