Thesis (doctoral)--Köln, 1987.

Zugl.: Hannover, Tierärztliche Hochsch., Diss., 2008.

Zugl.: Berlin, Freie Univ., Diss., 2003 / Hergestellt on demand

Zugl.: Berlin, Freie University, Diss., 2009.

Zielsetzung dieser Arbeit war es, das Verhalten der in modernen Sonnenschutzmitteln eingesetzten Titandioxid-Mikropartikel mit quantitativen Methoden zu bestimmen, um Aussagen über ihre Eignung zu erhalten. Dabei stand die Frage nach der Verteilung der Substanz innerhalb des Stratum corneum im Mittelpunkt der Untersuchungen. Insbesondere war wegen der bekannten photokatalytischen Aktivität von Titandioxid zu klären, ob ein Kontakt mit den lebenden Bereichen der Haut ausgeschlossen werden kann. Für die Messungen wurden zwei kommerziell genutzte, unterschiedlich beschichtete Titandioxid-Mikropartikel eingesetzt. Eine wesentliche Voraussetzung für diese Untersuchungen war die Anwendung der Abrissmethode (Tape stripping) in Kombination mit der spektroskopischen Bestimmung der Extinktion im sichtbaren Bereich zur Berechnung des Hornschichtprofils. Die Konzentration der Titandioxid-Partikel wurde mit Hilfe von Röntgenfluoreszenz-Messungen bestimmt. So war es erstmals möglich, in vivo standardisierte und reproduzierbare Untersuchungen zum Penetrationsverhalten von beschichteten Titandioxid-Mikropartikeln in die Hornschicht der menschlichen Haut durchzuführen. Durch Langzeitapplikation der Substanzen und die Beobachtung der Titandioxid-konzentrationen in der Hornschicht über mehrere Tage konnten auch Aussagen zum Penetrationsverhalten der applizierten Mikropartikel gemacht werden. Es wurde eindeutig gezeigt, dass die untersuchten Substanzen unabhängig von ihrer Struktur, von ihrer Beschichtung und vom Probanden hauptsächlich in den obersten Schichten des Stratum corneum lokalisiert sind. Nach Klärung dieser grundsätzlichen Fragen war es notwendig, die Ursache für das Auftreten extrem geringer Titandioxid-Konzentrationen auf Abrissen zu bestimmen, die aus tieferen Schichten des Stratum corneum entnommen wurden. Durch die Kombination der Abrissmethode mit einem speziellen Färbeverfahren und der Laser-Scan-Mikroskopie ergaben sich deutliche Hinweise auf die Bedeutung der Follikelkanäle für das beobachtete Phänomen. Röntgenspektroskopische Untersuchungen an Biopsien zeigten, dass diese Mikropartikel in die Haarfollikel eindringen und damit Bereiche unterhalb des Stratum corneum erreichen. Hierbei wurden die Mikropartikel in dieser Region nur in Follikelkanälen, nicht aber im Bereich der lebenden Zellen nachgewiesen. Diese Ergebnisse belegen, dass Titandioxid nur in einzelne Follikelkanäle penetriert, eine Aussage, die im Rahmen der vorliegenden Untersuchungen erstmals beschrieben wurde. In Übereinstimmung mit der Zielsetzung der Arbeit konnte unter Einsatz unterschiedlicher Untersuchungsmethoden gezeigt werden, dass die beschichteten Titandioxid-Mikropartikel im oberen Bereich der Hornschicht lokalisiert sind und damit als hocheffiziente Lichtschutzfilter den Schutz der darunter liegenden lebenden Bereiche der Haut garantieren. Der sichere Nachweis der Titandioxid-Mikropartikel innerhalb einzelner Follikelkanäle besitzt grundsätzliche Bedeutung für das Verständnis von Penetrationswegen. / The objective of this work was to determine the behaviour of titanium dioxide microparticles, used in modern sunscreen agents, with quantitative methods in order to receive statements about their suitability. The focal point of the investigations was the question on the distribution of the substance within the stratum corneum. Because of the well-known photocatalytic activity of titanium dioxide, our aim was to clarify whether a contact with the living cells of the skin could be excluded. For these measurements, two commercial titanium dioxide micro particles were used, covered with different coating materials. The calculation of the stratum corneum profile was a substantial prerequisite for these investigations. This was done by application of the tape stripping method in combination with the spectroscopic determination of the absorption in the visible range. The concentration of the titanium dioxide particles on the tape strips was determined by X-ray fluorescence measurements. In this manner it was possible for the first time, to perform standardized and reproducible in vivo measurements to investigate the penetration behaviour of coated titanium dioxide micro particles into the horny layer of the human skin. Predications could be made about the penetration behaviour of the applied micro particles by observation of the titanium dioxide concentrations in the stratum corneum during several days after long-term application of the substances. It could be shown that the examined substances were localized mainly in the upper layers of the stratum corneum, independently of their structure, coating and the volunteers. After clarifying these basic questions, it was necessary to explain the occurrence of extremely small concentrations of titanium-dioxide on tape strips, which were taken from deeper layers of the stratum corneum. This observed phenomenon was investigated by combining tape stripping with a selective staining of the tapes and with laser scanning microscopy. Investigations of a biopsy with x ray fluorescence measurements showed that the micro particles penetrate into the hair follicles, and in this manner reached areas below the stratum corneum. In this region, the micro particles were found only in follicle channels, but not within the area of the living cells. These results prove that titanium dioxide micro particles only penetrate into single follicle channels, a statement, which has been described here for the first time. In agreement with the objective of this thesis, it was shown, that the coated titanium dioxide micro particles were localized within the upper area of the horny layer and as high efficient sunscreen filters consequently guarantee, the protection of the living areas of the skin below. The proof of the titanium dioxide micro particles within individual follicle channels has basic importance for the understanding of the penetration pathways.

Unmyelinated low threshold C-tactile fibers moderate pleasant aspects of touch. These fibers respond optimally to stroking stimulation of the skin with slow velocities (1–10 cm/s). Low threshold mechanoreceptors are arranged around hair follicles in rodent skin. If valid also in humans, hair follicle density (HFD) may relate to the perceived pleasantness of stroking tactile stimulation. We conducted two studies that examined the relation between HFD and affective touch perception in humans. In total, 138 healthy volunteers were stroked on the forearm and rated the pleasantness and intensity. Stimulation was performed by a robotic tactile stimulator delivering C-tactile optimal (1, 3, 10 cm/s) and non-optimal (0.1, 0.3, 30 cm/s) stroking velocities. Additionally, a measure of discriminative touch was applied in study 2. HFD of the same forearm was determined using the Cyanoacrylate Skin Stripping Method (CSSM), which we validated in a pretest. Women had higher HFD than men, which was explained by body size and weight. Furthermore, women rated affective touch stimuli as more pleasant and had higher tactile acuity. Depilation did not affect touch perception. A weak relationship was found between the C-tactile specific aspects of affective touch perception and HFD, and the hypothesis of HFD relating to pleasant aspects of stroking only received weak support.

Unmyelinated low threshold C-tactile fibers moderate pleasant aspects of touch. These fibers respond optimally to stroking stimulation of the skin with slow velocities (1–10 cm/s). Low threshold mechanoreceptors are arranged around hair follicles in rodent skin. If valid also in humans, hair follicle density (HFD) may relate to the perceived pleasantness of stroking tactile stimulation. We conducted two studies that examined the relation between HFD and affective touch perception in humans. In total, 138 healthy volunteers were stroked on the forearm and rated the pleasantness and intensity. Stimulation was performed by a robotic tactile stimulator delivering C-tactile optimal (1, 3, 10 cm/s) and non-optimal (0.1, 0.3, 30 cm/s) stroking velocities. Additionally, a measure of discriminative touch was applied in study 2. HFD of the same forearm was determined using the Cyanoacrylate Skin Stripping Method (CSSM), which we validated in a pretest. Women had higher HFD than men, which was explained by body size and weight. Furthermore, women rated affective touch stimuli as more pleasant and had higher tactile acuity. Depilation did not affect touch perception. A weak relationship was found between the C-tactile specific aspects of affective touch perception and HFD, and the hypothesis of HFD relating to pleasant aspects of stroking only received weak support.