ISSN:1660-5527    

DOI:10.1159/000211077

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Transcutaneous gas measurements offer a useful tool for non-invasive monitoring of skin function, but are affected by several variables that restrict their use in clinical and investigative dermatology. Skin thickness, stratum corneum and barrier function damage, blood vessel reactivity, arterial-gas concentration, skin and environmental temperature are important factors influencing transcutaneous gas flux. Improvement of techniques and standardization of methods with guidelines for operators should improve this interesting research approach.

ISSN:1660-5527    

DOI:10.1159/000211078

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Vitamin A derivatives (retinoids) affect a large variety of fundamental biological processes. Understanding of the signaling mechanism has been greatly advanced by the cloning of specific retinoid receptors. These regulatory proteins belong to the steroid/thyroid hormone nuclear receptor superfamily. Two types of retinoid receptors have been identified, the retinoic acid receptors (RARα, βand γ) and the retinoid X receptors (RXRα, β, and γ). Similar to the steroid hormone receptors, the retinoid receptors bind to specific DNA sequences that have diad symmetries. However, the RARs require hete-rodimerization with RXRs for efficient DNA binding and gene regulation, while the RXRs can bind to DNA and function as homodimers in the presence of 9-cis-retinoic acid. In addition, RXRs can form heterodimers with thyroid hormone receptors and the vitamin D3 receptor and other receptors. Thus the RXRs have a very central role in serving as a partner for several hormone and vitamin receptors and thus may allow cross talk between different hormone signals. Retinoid responses can be restricted by the COUP-TF orphan receptors which bind to overlapping DNA sequences. Besides the classical way of action via DNA binding, the retinoid receptors can also interfere with other signaling pathways by interacting with the transcription factor AP-1. The advances made in understanding the mechanism of action of retinoids promise to contribute to the understanding and control of physiological responses and diseases

ISSN:1660-5527    

DOI:10.1159/000211158

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In human epidermis, basal keratinocytes are the main source of interleukin-1 (IL-1), and IL-1α is the predominant form, whereas IL-1β appears to exist predominantly in cultured keratinocytes. We investigated the effects of retinoic acid (RA) treatments on IL-1α and -β protein and mRNA expression of normal human keratinocytes cultured in low-calcium defined medium with or without hydrocortisone. Radioimmunoassay showed that after stimulation by RA, the IL-1β intracellular level is predominantly increased, with no significant modification of IL-1α expression. The addition of hydrocortisone in the culture medium resulted in a decrease in RA-induced IL-1β overexpression, without notable modifications in untreated cultures. Release of both IL-1α and -β in culture super-natants was detectable only after RA treatment and in the absence of hydrocortisone. The overexpression of IL-1β in control and RA-treated cultures mainly concerned the 52- and 31- to 36-kD biologically inactive precursor forms. Northern blot using specific IL-1α and -β oligonucleotide probes showed that IL-1β mRNA predominate over IL-1α mRNA and reach a maximal level 6 h before the IL-1β protein peak. These findings indicate that in cultured keratinocytes intracellular IL-1β is preferentially increased by RA but in its immature forms. The significance of this overexpression remains t

ISSN:1660-5527    

DOI:10.1159/000211079

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Topical retinoids are therapeutically active at low pharmaceutical concentrations, i.e. in essence lack of penetration is not a problem. Thus studies on the cutaneous pharmacokinetics focus on the distribution pattern in the skin, the penetration pathways, the cutaneous metabolism, the systemic body load and the mode of excretion. Two basically different pathways have to be taken into account: the transepidermal pathway, which gives rise to a typical epidermal/dermal concentration gradient and which is certainly part of the mode of action in disorders of keratinization, and the transfollicular pathway, which sheds some light on the activity in follicular disorders like acne. The cutaneous part of the pharmacokinetics of retinoids depends largely on their chemical structure and thus differs. However, common features are relatively high cutaneous concentrations, whereas the spillover to the systemic compartment appears to be slow and small, giving rise to low or hardly detectable bodyloads. Concerning pharmacokinetics topical application of retinoids presents major advantages over systemic medication. They can be targeted to the intended site of action, furthermore systemic toxicity is of much lesser concern.

ISSN:1660-5527    

DOI:10.1159/000211160

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Incubation of murine epidermal cells with delta-aminolevulinic acid (ALA) resulted in a dose- and time-dependent accumulation of porphyrins, predominantly of protoporphyrin. Porphyrin accumulation decreased in the presence of iron, and the iron-mediated decrease was partially reversed by CaMg EDTA (1.25–10.0 mM), suggesting that there is functionally active ferrochelatase in these cells. This study suggests that these cells may be a useful model for the study of cutaneous porphyrin metabolism involving ferrochelatase activit

ISSN:1660-5527    

DOI:10.1159/000211080

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Retinoids exert profound pleiotropic effects in skin, affecting many aspects of cell differentiation and proliferation. For this reason, retinoids have prominent pharmacological effects on major skin cells (keratinocytes, dermal fibroblasts, melanocytes, sebocytes) and have shown great potential as therapeutic agents in dermatology. In keratinocytes, retinoids induce proliferation, resulting in epidermal hyperplasia. Retinoids also modulate epidermal differentiation, however, many of the suppressive effects of retinoids observed in vitro do not occur in vivo. Dermal fibroblasts are important target cells of retinoids and are stimulated to produce extracellular matrix proteins, particularly when skin is damaged by wounding, ultraviolet radiation or glucocorticoids. Retinoids regulate pigmentation and can lighten hyperpigmented skin in animals and humans. Studies with cultured melanocytic cells show that tyrosinase activity is reduced by retinoids. The powerful sebosuppressive effect of some retinoids, such as 13 cis-retinoic acid, demonstrates that sebocyte differentiation is altered by retinoids. Retinoids inhibit proliferation and lipid synthesis in cultured human sebocytes and alter their keratin expression.

ISSN:1660-5527    

DOI:10.1159/000211161

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We have employed morphometric computerized analysis to quantify changes in atrophic skin. Atrophy was induced on volunteers by means of the Duhring chamber assay, using two commercial corticosteroids with a steroid-free base as control. After 20 days, atrophy was assessed by subjective examination and rated on a five-point scale. After 10 and 20 days, positive replicas of the areas under test were obtained. Photographic reproductions of these replicas were stored in the image memory of an interactive automatic computerized image analysis system, Kontron Zeiss Ibas 2, and processed with a suitable program. After selection of the measurement area by means of a circular measurement window, the ‘continuous tone’ image was converted to a ‘binary’ one by means of a dynamic discrimination function, in order to perform an automatic evaluation of the percentage area corresponding to the shadows cast by the surface markings. Morphometric computerized analysis proved to be a sensitive method for quantifying skin atrophy. A high degree of correspondence with subjective examination was shown. The method allows an objective differentiation between a mid-potency and a high-potency topical cortico

ISSN:1660-5527    

DOI:10.1159/000211081

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

An analytical model and the corresponding experimental procedure are presented, which make it possible to separately analyze the viscous and elastic components of human hair. Moreover, a computerized experimental system is described with which a standardized quantitative determination of the most important mechanical parameters of human hair can be performed. Comparative investigations of the mechanical behavior of hair specimens obtained from the frontoparietal and occipital scalp regions of 10 healthy human subjects showed no statistically significant differences with regard to their mechanical parameters. Nevertheless, the paired analysis of the mechanical parameters of thin and thick hair specimens revealed that the values of two of these parameters are significantly higher in thin than in thick hair specimens. These findings suggest that there are mechanical parameters of human hair related to gross hair morphology, whereas others depend on hair microstructure.

ISSN:1660-5527    

DOI:10.1159/000211082

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

All-trans-retinoic acid is a potent developmental toxicant in all species examined. The teratogenic risk of topical all- trans-retinoic acid is reviewed. Experimental studies are limited because of the high maternal toxicity, including skin irritation, with doses below those resulting in significant teratogenic response with other application routes, such as oral application. The maximal systemic availability reported for transdermal exposure of all- trans-retinoic acid was 5-6% in the rat, 9.6% in the monkey (48% with dermatitic skin) and 5-7% in the human. Oral administration of threshold teratogenic doses of all- trans-retinoic acid (6 mg/kg/day) to Wistar rats and Swiss hare rabbits resulted in embryonic area under the concentration time curve levels (approximately 1,000 ng·h/g) which were 2- to 4-fold higher than the endogenous all- trans-retinoic acid levels; corresponding maternal plasma area under the concentration time curve values were 98 and 321 ng·h/ml in rat and rabbit, respectively. The 4-oxo-metab-olite was also found in maternal plasma and embryo. Large, controlled studies on the possible developmental toxicity of topical all- trans -retinoic acid in the human are not available. Isolated case reports appeared in the literature claiming teratogenic outcome resembling effects after oral iso-tretinoin use or those observed in experimental studies with oral or paren-teral all- trans-retinoic acid administration. The dose absorbed from daily cosmetic or therapeutic application of all- trans -retinoic acid is expected to be below 0.015 mg/kg, which is at least 30-fold lower than the lowest teratogenic dose of isotretinoin in the human. Topical all- trans -retinoic acid application did not appreciably alter endogenous plasma retinoid levels. The influence of nutrition, diurnal variation and in particular oral vitamin A supplements are more important determinants of plasma retinoic acid compounds than topical all- trans -retinoic acid. These results imply a low risk of therapeutic or cosmetic application of topical all-trans-retinoic acid. However, the highly specific spatial and temporal distribution of binding proteins and nuclear receptors in the embryo suggests that even small alterations in endogenous levels of all- trans -retinoic acid in the embryo may alter crucial developmental processes such as morphogenes; this aspect should be further investigated.

ISSN:1660-5527    

DOI:10.1159/000211162

出版商:S. Karger AG    

年代:1993

数据来源: Karger