Age-related mechanical properties of human skin: an in vivo study.

We have investigated in vivo how various viscoelastic parameters that describe the mechanical properties of the human skin may vary with age. Accordingly, we have used a mechanical device that records the torsional extensibility of the skin. When submitted to a low torque, the time-response curve of the skin affords the determination of the immediate extensibility (UE), the immediate recovery (UR), the viscoelastic part of the deformation (UV), the elastic recovery (UR/UE), and the creep relaxation time (tau). Because the skin thickness varies with age and primarily governs the mechanical properties, it was measured through an ultrasound technique at the same sites (forearm) where the torque was applied. The results show that the skin maintains its thickness and extensibility up to the seventh decade as opposed to its elasticity or recovery capacities, which decrease from an early age. The viscous part of the deformation is constant through life, whereas the creep relaxation time decreases linearily with age. Except for skin thickness, no differences in these parameters between men and women were detected. The significance of these results are discussed in terms of structure alterations. The determination of the elastic recovery (UR/UE) appears to be a parameter of choice for illustrating skin aging.

Protective effect of trimethylpsoralen against UV-B erythema.

Vitiliginous patients undergoing photochemotherapy with TMP were less susceptible to a sun burn. To investigate this point, the MED for UV-B was measured before, 2 h, and 24 h after oral intake of TMP in 10 healthy volunteers. There was an increase of MED when UV exposure had taken place 2 h after TMP intake (P < 0.01). This was no longer detectable when the exposure had taken place 24 h after intake. MED increase was 11.8% for 0.19 mg/kg TMP, 21.0% for 0.37 mg/kg, and 23.7% for 0.74 mg/kg. This dose-dependence was significant (P < 0.01). The protective effect of TMP against UV-B erythema seemed related to UV absorption by the drug while it was in the blood stream.

Mechanical properties and Young's modulus of human skin in vivo.

The mechanical properties of the in vivo dermis were measured by means of a torque applied to the skin. The resulting deformation of 2-6 degrees, including the immediate and delayed visco-elastic components, as well as the relaxation were measured, and the raw values corrected for a constant skin thickness. The experiment performed on 138 individuals from 3 to 89 years old revealed a diminished elasticity and stretchability after the age of 30, associated with an increase in the visco-elastic component. The Young's modulus doubles with age. The results are discussed in terms of the various models proposed to explain dermal structure.

Influence of ageing on the in vivo extensibility of human skin at a low stress.

The response of the forearm skin to a 9 . 10(-3) N . m torque was measured on 141 subjects aged 3-89 years. The results for each age class were adjusted to a skin thickness of 1 mm by use of a skinfold caliper. Results indicate a maximum skin thickness around the age of 40 years. Standardised skin extensibility decreases with age, the skin of females being less extensible than that of males. These results, which should be considered in relation to the total water content of the skin, are compared to those of other papers dealing with this subject.

Heterogeneous keratohyalin formation in warts.

The heterogenecity of keratohyalin (KH) has been demonstrated in rats, then in human warts where similar morphological features have been found and among them, dense homogeneous ovoïd single granules (SG) and composite granules (CG) apparently made up of single granules "coated" with a matrix. This work compares the ultrastructure of the KH of the tongue of newborn rats with that of common warts with and without post-fixation by OsO4, after oxydation by H2O2 and after pepsin treatment. The osmiophily of the SG is confirmed as well as the absence of osmiophily of the matrix of the CG. In man, however, the SG are resistant to oxydation by H2O2 and the CG matrix is oxydation sensitive whereas the opposite is observed in the case of rats. These differences show that it is impossible to deduce the composition of the KH in human warts from that of the rat despite their close ultrastructural resemblance but that important modification of the keratogenesis and KH formation are induced in the cells parasited by the virus of common warts.

Effect of UV-B erythema of psoralen, trimethylpsoralen, and 8 methoxypsoralen.

The MED for UV-B was measured 2 h and 24 h after oral intake of Psoralen (P) 0.49 mg/kg in 10 healthy volunteers. MED was increased when UV exposure had taken place 2 h after intake. The same increase was observed after 0.24 mg/kg and 0.98 mg/kg, with a non-significant dose dependence. This effect was not detectable when UV exposure had taken place 24 h after oral intake of the drug. In a second experiment the effects of oral intake of both trimethylpsoralen (TMP) and 8 Methoxypsoralen (8 MOP) mg/kg, were assessed in 29 subjects. While TMP increased MED when taken 2 h before UV exposure (p less than 0.001), 8 MOP had the opposite effect (p less than 0.01). TMP effect was observed mainly in fair-haired people (p less than 0.05) and 8 MOP effect mainly in females (p less than 0.05).

Chronopharmacokinetics of 5-methoxypsoralen.

Diurnal variations in drug pharmacokinetics are a well known phenomenon. Chronopharmacology studies now appear to be attracting increasing interest with a view to establishing an optimum therapeutic prescription. In order to determine possible chronobiological variations of 5-methoxypsoralen (5-MOP) pharmacokinetic, 5-MOP blood concentrations were quantified in 8 healthy subjects after drug ingestion at different times during the day. Stolk's High Performance Liquid Chromatography technique was used to assess the 5-MOP serum concentrations. Each subject underwent three pharmacokinetic studies after oral ingestion of 5-MOP (1.2 mg/kg), in conjunction with a standardized low-lipid meal. The first pharmacokinetic study was started in the morning, the second in the afternoon and the third in the evening. Drug intake was at intervals of 2 days, to avoid drug accumulation. The results showed that the evening intake of the drug induced a higher 5-MOP maximum concentration and a higher 'area under curve' than morning or afternoon ingestion. This study suggests an optimized PUVA therapy, when performed in the evening.