摘要:

Nicotine is rapidly taken up by human keratinocytes (HaCaT cells) and after 3 h the uptake is approximately 50% of maximum. Cotinine, a metabolite of nicotine, was detected, thus demonstrating the metabolism of nicotine in HaCaT cells. Low nicotine concentrations (0.1–200 μg/ml) did not influence the incorporation rate of thymidine into DNA or ami-no acids into proteins. Inhibition of DNA and protein synthesis was only observed at concentrations > 200 μg/ml. After application of 400 μg/ml nicotine, the cells were vacuolated. This process was reversed after nicotine withdrawal. At low nicotine concentrations, no changes in microtubules and actin filaments could be detected. However, in the presence of nicotine (1-10μg/ml), keratin filaments showed a more orderly pattern that controls, and the expression of the suprabasal keratins 1 and 10/11 was induced and increased according to the concentration of nicotine. The number of cornified envelopes also increased markedly. Nicotine concentrations > 100 μg/ml led to a disarrangement of keratin filaments and to a decrease in keratin expression and cornified envelope formation. Our results suggest that nicotine at concentrations up to 100 μg/ml is not an irritant but may induce cornification of the skin.

ISSN:1660-5527    

DOI:10.1159/000211311

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Occlusion of the skin with a water-vapor-impermeable membrane following disruption of the permeability barrier prevents the epidermal changes which lead to the restoration of barrier function, suggesting that water transit could be an important regulatory signal for barrier repair. However, occlusion with a water-vapor-impermeable membrane also prevents the movement of gases, which could also potentially influence permeability barrier homeostasis. Since O2 is known to have an effect on epidermal cell function, we have determined the effect of gases containing different levels of O2 on barrier repair 6 h following topical treatment of hairless mice with acetone. The disrupted barrier of air-exposed animals (O2 ∼ 20%) recovered by 50.8 ± 3.4% (mean ± SEM) after 6 h. Under flowing air (O2 ∼ 20%), O2/CO2 95/5 % and argon (O2 = 0%) the barrier recovered by 43.9 ± 28, 36.2 ± 8.5 and 39.2 ± 4.6%, respectively. These values were not statistically different from each other. The slightly lower levels of recovery at 6 h with the flowing gases in comparison to exposure to static air probably can be attributed to a slight cooling of the skin caused by the flowing gases. These results suggest that exogenous O2 is neither required for barrier repair nor a signal for barrier repair.

ISSN:1660-5527    

DOI:10.1159/000211312

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Doses of 3 and 10 mg/kg/day acitretin were orally administered to female Wistar rats over a period of 6 weeks. Phospho-lipid classes, P-450 content, aminopyrine-N-demethylase (ADM) and 7-ethoxyresorufin-O-deethylase (7-ERO-D) activities were determined in the liver microsomes of the treated animals. Both dosages caused statistically significant alterations in rat liver microsomal phospholipid composition which may be associated with changes in the metabolic activity, ionic transport, cell-cell interaction and other processes of the hepatic cellular components. Furthermore, statistically significant alterations of P-450 isozyme activities were induced by both dosages. Our data suggest a possible interaction of acitretin with other drugs and endogenous substances metabolized by these enzyme systems.

ISSN:1660-5527    

DOI:10.1159/000211313

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Topical administration of lipoxygenase and cyclooxygenase inhibitors, antipsoriatic drugs and some immunomodulating drugs on adult mouse tail scales showed variable induction of of orthokeratosis. Dithranol and retinoic acid showed ED50 concentrations of 0.5% and 0.23%, respectively. The lipoxygenase inhibitors catechol and octyl gallate showed ED50 of 2.5 and 13.4%. 10% lonapalene showed 20% activity, curcumin, linoleic acid, primrose oil and AA673 10–15% activity, methyl and ethyl gallate 5% activity, nordihydroguaiaretic acid, diethylcarbamazine, ebselen, esculetin, quercetin, AA861, gallic acid, dodecyl gallate and 15-hydroxyeicosatetraenoic acid no activity. The cyclooxygenase inhibitors indomethacin, acetylsalicylic acid and bufexamac were inactive, benoxaprof-en showed 14% activity. The immunomodulating drugs fluo-rouracil and triamcinolone showed > 10% activity, cyclosporin A and thalidomide no activity. Fumaric acid showed 5% activity. The results show that this model could be proposed for screening antipsoriatic drugs.

ISSN:1660-5527    

DOI:10.1159/000211314

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The in vivo model which may be the most accurate for the ability to predict hair growth in humans, and which was utilized in the preclinical development of minoxidil, is the adult stumptailed macaque. Previous reports have suggested that the enzyme activity which accounts for the activation of minoxidil, i.e., minoxidil sulfotransferase, is present in skin. We have demonstrated that scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity, and further with dissection of that scalp skin into epidermis, dermis and hair follicle, most of sulfotransferase activity was present in the follicle. Sulfotransferase activity in the hair follicle in freeze-dried scalp skin sections from 9 stumptailed macaques ranged from 47 to 84% of the total (mean 61 ± 12%). Much less minoxidil sulfotransferase activity was measured in the epidermis (mean 18 ± 11%, with a range of 2–37%) and the dermis (mean 21 ± 8%, with a range of 4–3 5%) of these scalp sections. These results indicate that the scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity and this activity is largely localized in the hair follicle which may account for its ability to stimulate hair growth in this animal model.

ISSN:1660-5527    

DOI:10.1159/000211315

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Two studies in healthy male and female volunteers (aged 18–65 years) were undertaken to determine plasma and cutaneous levels of drug following topical application of piroxicam gel. Twelve subjects applied piroxicam gel to the knee (1 g of 0.5% Feldene gel) at baseline and then after 6, 12 and 24 h. Plasma was collected after 1,2,4,6,14,24,28 and 48 h and piroxicam content determined by high-pressure liquid chromatogräphy (HPLC). For the majority of samples collected, piroxicam levels were below the limit of detection (LOD) of the assay and the maximum recorded plasma level in any subject at any time point was 75.4 ng/ml. A single application of gel was administered to the forearms of four groups each of 6 subjects, and biopsy samples of the stratum corneum (skin surface biopsy, SBB) and epidermis/dermis were taken after 0.5, 1, 2 and 4 h. The levels of piroxicam were again measured in each sample by HPLC. The highest levels of piroxicam were found in the superficial skin surface biopsy with the lowest levels recorded in the skin surface biopsies nearest the viable epidermis. The mean tissue concentrations ranged from 160 to 640 ng per sample (calculated to be 80–320 μg/g of tissue). The mean levels of piroxicam in a 4-mm punch biopsy showed an increase with time after application, rising from 60.3 to 94.6 ng per biopsy (calculated to be 2.4 to 3.8 μg/g of tissue). It may be concluded that piroxicam rapidly permeates through the stratum corneum into the epidermis/dermis after application of the gel. Low and often undetectable plasma levels of drug were observed after topical application of piroxicam gel in a manner comparable to clinical usage.

ISSN:1660-5527    

DOI:10.1159/000211316

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The metabolism of xenobiotics by the epidermis can be studied in vitro by using keratinocyte cultures. We present a simple and rapid method for determining the activity of cytochrome P450-dependent enzymes (ethoxycoumarin-O-de-ethylase, ECOD, and ethoxyresorufm-O-deethylase, EROD) in intact cultured human keratinocytes. Using this method, we studied the effect of a well-known cytochrome P450 inhibitor (proadifen) and of two inducers (phenobarbital and 3-methyl-cholanthrene). As reported in vivo some imidazole compounds (miconazole and econazole) induce ECOD activity at low concentrations and inhibit it at high concentrations. In contrast, two other imidazoles (clotrimazole and sulconazole) only had an inducing effect on ECOD activity. Imidazole itself had no apparent effect on ECOD activity. In conclusion, this model appears to be useful for studying the biotransforming activity of human skin. It allows a rapid evaluation of the inducing/inhibitory effects of xenobiotics.

ISSN:1660-5527    

DOI:10.1159/000211317

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000211318

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000211319

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000211320

出版商:S. Karger AG    

年代:1994

数据来源: Karger