摘要:

Vitamin D3 is produced in the skin. It is metabolized primarily in the liver to the major circulating form 25-hydroxy vitamin D3, [25(OH)D3] which is metabolized in the kidney to produce the biologically active form of the hormone, 1,25-dihydroxy vitamin D3, [1,25(OH)2D3]. The skin not only participates in the production of vitamin D3, but also contains receptors for 1,25(OH)2D3 suggesting a role of this hormone in the growth and differentiation of this tissue. 1,25(OH)2D3 appears to play a role in epidermopoiesis and melanin pigmentation. Recently, using cultures of neonatal human foreskin keratinocytes, we have demonstrated that these cells produce abundant quantities of 1,25(OH)2D3 from 25(OH)D3. The production of 1,25(OH)2D3 varies with the degree of differentiation of keratinocytes and is regulated by exogenous 1,25(OH)2D3. 1,25(OH)2D3 induces differentiation possibly because of its ability to increase intracellular free calcium levels. A tentative model is provided to demonstrate potential mechanisms by which 1,25(OH)2D3-induced changes in intracellular calcium could regulate epidermal differentiation.

ISSN:0302-3427    

DOI:10.1159/000210769

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In order to better understand the respective roles of the nuclear retinoic acid receptors (RARs) and the cytosolic retinoic acid binding protein (CRABP) in the mode of action of retinoic acid (RA), several types of RA analogs have been synthesized. Representative compounds have been radiolabeled to a high specific activity and their binding (direct and competition) to RARs and CRABP was determined. Their biological activity on F9 embryonal carcinoma cell differentiation has been determined by a quantitative assay of plasminogen activator (PA). All biologically active analogs studied in this work bound to RARs. A good correlation was found between PA induction and affinity for the RARs, with the exception of RA itself which was a good ligand but a moderate inducer of F9 differentiation. Two biologically active analogs (compounds II and III) did not bind to the CRABP. One biologically inactive analog (compound VIII) bound to CRABP. These results strongly suggest that retinoids must bind to RARs but not necessarily to CRABP in order to induce cell differentiation in F9 cells.

ISSN:0302-3427    

DOI:10.1159/000210770

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Epidermal microsomes, prepared from neonatal Wistar or Sprague-Dawley rats, show low levels of retinoic acid (RA) metabolism. The specific activities (as fmol/min/mg protein) of epidermal microsomes, using [15–14C]-RA as substrate, are 232 (Wistar rats) and 222 (Sprague-Dawley rats). Topical application of RA (1 mg) on 4-day-old rats induces a 3.3-and 3.9-fold increase in epidermis microsomal RA metabolism. A 4.6- to 8.1-fold increase is observed 24 h after topical application of 3-methylcholanthrene (0.5 mg). By contrast, phenobarbital (1 mg topically) has a much smaller inducing effect. So far the chemical structure of the metabolites has not been identified. The Rf values of two major compounds correspond with those of 4-hydroxy- and 4-ketoretinoic acid, formed after incubation of hamster liver microsomes in the presence of [15–14C]-RA. The RA metabolism in rat epidermal micromes shows the typical characteristics of a cytochrome-P-450 (P450)-dependent enzyme system, i.e. a requirement for NADPH and oxygen and inhibition by CO and SKF-525A. Ketoconazole and miconazole, imidazole antifungal agents and inhibitors of some fungal and mammalian P450-dependent enzymes, inhibit in vitro RA metabolism by rat epidermal microsomes. 50% inhibition is achieved at 6.5 × 10-7 and ≧ 10-5 mol/l, respectively. The triazole antifungal agent, itraconazole, has no effect at concentrations up to 10-5 mol/l. Topical treatment of 4-day-old Wistar rats with ketoconazole, at doses of 1, 5 and 10 mg/kg, 1 h before the application of RA (1 mg/rat) results in a dose-dependent inhibition of RA metabolism by epidermal microsomes, prepared 24 h later. Our data show a P450-dependent RA metabolism in rat epidermal microsomes and suggest that ketoconazole may prove to be effective in maintaining biologically active levels of RA in epidermal

ISSN:0302-3427    

DOI:10.1159/000210771

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The biochemical basis of ultraviolet-induced cutaneous inflammation in polymorphous light eruption (PLE) is not known. We investigated the potential role of eicosa-noids – derivatives of arachidonic acid – as mediators of inflammation in this common disorder. 13 patients were investigated, in whom skin lesions could be experimentally reproduced by repeated UV-A but not UV-B irradiation. Peripheral blood leukocytes of these patients were irradiated with UV-A or UV-B, and the release of leukotriene B4 (LTB4), LTC4 and prostaglandin E2 (PGE2) was measured. Cells from PLE patients, but not healthy controls, released selectively high amounts of LTB4 in response to UV-A. The UV-A-induced LTB4 release was light-dose-dependent. This phenomenon was not observed with UV-B. The selective UV-A-induced release of LTB4 could play a major role in the pathophysiology of cutaneous inflammation in PLE.

ISSN:0302-3427    

DOI:10.1159/000210772

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

A controlled, randomized, double-blind, cross-over study was performed in 10 healthy volunteers in order to compare changes of cutaneous blood flow values (CBFV, laser Doppler flowmetry, Periflux, Perimed, S) in histamine-challenged skin before and after administration of a capsule containing either 10 mg cetirizine or 60 mg terfenadine. The overall pattern of the basal cutaneous wheal and flare response to the agonists (histamine: aqueous solution: Hsol, or Phazet®: Hprick) and control saline solution, showed the expected range of clinical effects, i.e. Hsol > Hprick > saline. Similarly, the increase of CBFV on the flare area was higher around the histamine injections as compared with saline. Surprisingly, CBFV was decreased at the site of Hsol and Hprick injections as compared with the levels recorded at the control injections. The following changes were noted after intake of H1-blocking agents. (1) There was a reduction of the areas of wheal and flare at all injection sites after administration of the H1 blockers, this reduction being consistently greater under cetirizine than terfenadine. (2) CBFV, measured 1 cm from the site of Hsol injection (i.e., within the area of normal flare response), was decreased only with cetirizine. In the smaller flare area induced by Hprick, CBFV was equally suppressed by both drugs. (3) At the site of agonist injection, along with a reduction of the size of the wheal, we observed significant increases in CBFV after drug intake. Under these experimental conditions, this quantitative pharmacologic in vivo assay of agonist-antagonist interactions suggests that after initial administration of normally prescribed doses, cetirizine may possess more anti-H1 activity than terfenadine.

ISSN:0302-3427    

DOI:10.1159/000210773

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In this investigation skin fold thinning was determined after topical application of several potent corticosteroids in hairless mice using a simple mechanical measuring device. The skin thinning effect of prednicarbate was compared with other corticosteroids (amcinonide, β-methasone-17-valerate, clobetasol-17-propionate, diflorasone-17,21 -diacetate, hydrocortisone-21 -acetate). Prednicarbate produced a clear thinning of skin. Like other tested dermatocorticoids prednicarbate caused a significant atrophy of the mouse tail epidermis. By prednicarbate the 3H-thymidine triphosphate incorporation into epidermal DNA was inhibited.

ISSN:0302-3427    

DOI:10.1159/000210774

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The effects of occlusion on skin function are described and reviewed. Occlusion seems to be not only a device applied on the skin surface, but, under certain conditions, a powerful treatment capable of inducing several changes on epidermal metabolism, skin flora, sweat glands and epidermal morphology.

ISSN:0302-3427    

DOI:10.1159/000210775

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000210776

出版商:S. Karger AG    

年代:1988

数据来源: Karger