[The effect of methylcatechol on melanin producing cells (author's transl)].
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Biomedical subjects
Publications and source records attributed to W Wohlrab.
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The influence of urea on the percutaneous permeation under different conditions of application and on the epidermal effectiveness of 5-fluorouracil (FU) as an example for water-soluble agents is reported. The proceedings of permeation of FU are accelerated by admixture of, or pretreatment with, urea and by increasing the hydration of the horny layer by pretreatment with NaCl. The effectiveness of FU on the epidermis is increased simultaneously. However, the permeation rate of FU is decreased by pretreatment with HTH as an example of a stabilized urea emulsion; on the other hand, the most favourable therapeutic effect is demonstrable. Therefore, the permeation of an agent may be both enhanced and inhibited by different modes of urea application. These findings appear to be important for both the optimization of topical treatment and the industrial medicine's point of view.
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Long-term application up to 8 weeks of a 10% urea solution provokes an epidermal thinning expressed in a decreased number of DNA-synthetizing cells. This epidermal reaction cannot be established after topical use of HTH emulsion. Even by daily application during 8 weeks no change was seen. The absence of epidermal thinning after HTH exposure can be explained as an additive effect of urea and the other constituents of the HTH emulsion. This opinion is supported by the results after application of urea together with Tween 60 in that the acanthogenic effect of Tween 60 is decreased by addition of urea. On the other side, the therapeutic efficiency of 10% 5-fluorouracil solution can be increased remarkably by preliminary treatment with HTH emulsion. These findings could reach importance in the topical therapy with regard to the possibility to improve the effectiveness of any drug by addition of, or preliminary treatment with, urea.
As a reaction of the epidermis subsequent upon contact with urea, a thinning is ascertainable 5 days later, for which corresponding enzymological and autoradiographical findings cause to presume the DNA being the working point. Further information about the mechanism of this reaction was obtained first by short time tests, whence by means of 3H thymidine autoradiography not later than the second day after contact with urea a decreased number of cells synthesizing DNA in the stratum basale were to be secured. These findings obtained using the model of the guinea-pig's ear are also ascertainable in the human skin, an unspecified effect, also to be released by other non-electrolytes, having been excluded by controls of glucose replacing urea. The quick invasion of urea into the epidermis, deducible from the short time tests, was proved by 14C traced urea, ascertainable not later than 15 min after its contact with the skin amongst the blood - even if in little activity. Hence, the urea enters into the cutis speedily, releasing there a disturbance in the process of the epidermal proliferation, which conducts in the sequel to an epidermal thinning.
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The epidermis thins in response to short-term contact with urea, and the results of extensive enzymological and autoradiographical studies suggest that urea acts on processes involved in epidermal proliferation. After long-term exposure of skin to urea, lasting more than 2, 4, or 6 weeks, no further thinning occurs, and there is no tendency for atrophy to develop during this period. This assertion is made on the basis of biometrical, autoradiographical, and cytophotometrical data. It is likely, however that a reduced number of cells synthesizing DNA is not the only change in normal epidermal proliferation leading to the peidermal thinning that was measured. The urea could also alter factors regulating either cell entry into DNA synthesis or the synthetic process itself, or both. These findings clearly are of significance not only in industrial medicine but also in the use of urea in topical dermatological therapy.
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