Biomedical subjects
Publications and source records attributed to H Pratzel.
Due to its mechanical properties circonia is an interesting implantation material. However, it may contain a certain amount of radioactive isotopes. The measurement of alpha-emission reveals varying amounts of radiation. As a result, a declaration of radioactivity should be required for circonia implants and only circonia with low emission levels should be used for implantation purposes.
Indomethacin can permeate the normal skin of laboratory animals as well as humans, therefore, we investigated whether and what extent this process may be intensified by sonophoresis or iontophoresis. To 6 pigs Amuno-Gel (MSD Sharp & Dohme) (indocid gel) containing 1% indomethacin was applied over 5 h iontophoretically through the skin of the back, and the blood and urine concentrations were measured by high performance liquid chromatography with inline post column hydrolysis and fluorimetric detection. Nonassisted skin uptake was measured 1 to 2 weeks later in the same animals each serving as its own control. Iontophoresis (0.1 mA/cm2) increased maximum indomethacin levels from 32 (controls) to 82 ng/ml and urinary excretion over 5 h from 29.4 to 181.1 ng/cm2 of treated skin area. Sonophoresis did not improve indomethacin absorption. In 7 human volunteers, iontophoretic application of indomethacin over 1 h onto the skin of the back (1380 cm2 surface area) increased maximum plasma levels from 43 ng/ml (controls) to 221 ng/ml, and the urinary excretion over a total of 5 h from 18.1 (controls) to 97.6 ng/cm2. As calculated from the fraction of indomethacin excreted in the urine, about 0.2 microgram indomethacin/cm2 of treated skin area taken up spontaneously and about 1.0 microgram/cm2 was transported by iontophoresis.
Insight into the mechanisms of contamination is a necessary prerequisite for efficient and meaningful decontamination. The incorporation of anorganic ions into human skin has been studied with aqueous solutions of radionuclides. Within 30 min of wetting about 1 microliter fluid per cm2 skin area penetrates into the capillary spaces of the horny layer, promoted by surface-active properties of the sebaceous lipids. Adsorption onto horny layer constituents is especially important for polyvalent cations. In general it is dependent on pH and on the ionic charge. For all substances in aqueous solution the structure of the horny layer causes a nearly exponential decay of concentration with depth of penetration (about 100:1 across the horny layer at 1 mg keratin/cm2 skin area). This is the reason for the very low penetration rates. The results may be used to establish some rules for skin decontamination.
The human horny layer contains insoluble arginase, which is tied to keratinic cells, with an activity of about 1 mU/cm2 skinsurface. About 50 p.c. of arginase is inhibited by water soluble substances of horny layer or by using soaps and syndets. By washing the skinsurface with water the activity increases. Presumable the horny layer arginase has a function in the urea production of sweat.
By repeated uv-irradiation the quantity of all free amino acids (per surface unit) in human horny layer increase considerably. 4 different groups of substances are found by taking the relative values in mole per cent. 1. No difference for urea, threonine, serine, glutamine, tyrosine and ammonia. 2. Decrease of about 20 p.c. for glutaminic acid, citrulline, arginine, histidine. 3. Increase of about 20 p.c. for urocanic acid, aspartic acid, proline, glycine, valine, isoleucine. 4. The rest of amino acids increase about 30--50 p.c.
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Skin uptake of salicylic acid methylester (SAM) by bathing in PERNIONIN -Teilbad (Krewel-Werke, Eitorf) and KNEIPP-Wacholderölbad (Kneipp-Werke, Würzburg) was researched with pigs and human volunteers. In plasma, no SAM was found, only salicylic acid (SA) and traces of salicyluric acid (SU). Skin uptake increased after every new application in 2 h. About 30 mg SAM permeated through an area of pig's skin of 300 cm2 in this time. Plasma levels after whole body bathing of man with PERNIONIN at 36 degrees C were about 0.63 micrograms/g and with Wacholderölbad about 0.37 microgram/g SA. With Wacholderölbad at 38-42 degrees C plasma levels increased to about 1 micrograms/g SA. In 24 h after bathing at 36 degrees C 329 and 304 mg SU were eliminated in urine and after bathing at 38-42 degrees C only 17.8 mg SU. From these SAM baths we found maximal plasma levels of SS in contrast to any other topical applied SS drug. Tissue levels from the application area were higher than the systemic concentration. SAM bathing is one of the most effective methods of local SS application in rheumatology.
Cutaneous absorption of ionized substances is forced by iontophoresis. This was shown by Pratzel and Hillmeier's investigation of the permeation of salicylic acid (increasing factor 150) and Pratzel and Dittrich's experiments with indomethacin (factor 10) in pigs. In the present paper it is shown that in human volunteers iontophoretic application of indomethacin for one hour onto the skin of the back (surface 1380 cm2) increased indomethacin plasma levels after 2 hours to a maximum of 221 ng/ml, and increased urinary excretion of indomethacin from 24 micrograms (control) to 138.7 micrograms in 5 hours. Iontophoretic application of salicylic acid for one hour daily in human volunteers onto a skin area of 400 cm2 increased serum levels in five days to 690 ng/ml and urinary excretion of salicylic acid and salicyluric acid to 24 mg, as opposed to 2.5 mg by control without current. However, after 30 min iontophoresis only 4 mg is excreted in the urine. In conclusion, if the iontophoresis is practised over a long period of time on large skin areas, systemic effects can be expected.
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