摘要:

The aim of the study was to investigate the concentrations of Ro 10–1670 (acitretin) and its isomeric metabolite Ro 13–7652 (cis-acitretin) after multiple oral dosing of acitretin. We used a highly sensitive HPLC method for simultaneous determination of the 2 retinoids with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). In hairless rats receiving orally 8 mg/kg acitretin once daily during 8 days, blood and skin samples were taken at different time points between 5 and 96 h after the last dose. After 96 h, appreciable concentrations of Ro 10–1670, but not Ro 13–7652 could be measured in the skin, whereas both isomers were below the quantification limit in plasma. In psoriatic patients treated with a once daily dose of 30 mg acitretin, blood samples and biopsies were taken after 1 month of treatment (i.e. under steady state conditions). 24 h after the last drug intake, skin concentrations of acitretin were approximately 10 times higher than those observed in plasma. Ro 10–1670 concentrations in the skin were approximately 3–5 times higher than for Ro 13–7652 and concentrations of both isomers were higher in lesional compared to un

ISSN:1660-5527    

DOI:10.1159/000210818

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Several reports have demonstrated that exposure to ultraviolet light elicits increased pigmentation in the skin of the Skh:HR2 mouse. We have reexamined this model to assess its potential as a screen for compounds with skin-depigmenting activity. The application of the previously reported ultraviolet light-B (UVB) doses led to marked necrotic damage to the skin which greatly diminished the usefulness of the model for drug testing. We have modified this model by exposing the mice to a progressively increasing dose of UVB that promotes pigmentation with a marked reduction of skin irritation. Furthermore, for compound evaluation, we preselected only those mice which developed signs of increased pigmentation after the first week of UVB exposure. This was critical for any meaningful compound evaluation, since only about 50% of the mice eventually showed signs of increased pigmentation with UVB. Our modifications make it possible to use this model for evaluating new compounds with skin-depigmenting activity. The validity of this method has been examined with a number of compounds including hydroquinone, 4-hydroxyanisole, kojic acid and all-trans retinoic acid, all with known depigmenting activity.

ISSN:1660-5527    

DOI:10.1159/000210819

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

To study the influence of cutaneous blood flow upon the transdermal penetration of drugs, an original in vivo model, the bipediculated dorsal flap (BDF) of the hairless rat is described. This model is constituted by a dorsal cutaneous muff on both sides of the spinal column. The blood circulation was maintained symmetrically on both skin insertion pedicles. Two radiotracers, 86Rb and 201T1 (respective half-lives: 18 and 3 days), known to measure nutritional blood flows, are compared in this model. In the back skin, over and under the flap, mean blood flow (expressed as percentage of injected dose per gram skin) was similar with Rb (9.5 ± 3.1) ·10-2 and Tl (10.2 ± 2.1)· 10-2. Equivalent values were obtained in BDF skin (non ligated pedicle): Rb (8.4 ± 1.3) · 10-2, Tl (9.5 ± 2.7) · 10-2. In BDF skin, cutaneous blood flow was lower by 70–91 % in the ligated pedicle (compared to the nonligated) for both radioisotopes. Identical 86Rb and 201T1 distributions suggest the use of 201T1 for further experiments of cutaneous b

ISSN:1660-5527    

DOI:10.1159/000210820

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Tape stripping of normal human skin results in a hyperproliferative response brought about by a recruitment of resting (G0) cells. The effect of diprosone and hydrocortisone on this response was studied by flow cytometric techniques. Both corticosteroids were found to delay the appearance of the cohort of recruited cells in the S-phase, the more potent antipsoriatic (diprosone) giving the greatest delay. These data indicate that corticosteroids cause a temporary block in late G1 or an inhibition of the recruitment process itself. The model may serve for the evaluation of (future) antipsoriatic drugs.

ISSN:1660-5527    

DOI:10.1159/000210821

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

A double-blind, randomized, placebo-controlled comparison of the analgesic and antihistaminic effects of four commonly used antihistamines (terfenadine, antazoline, diphenhydramine and cimetidine) was performed. Wheal and flare areas after histamine skin prick and sensory and pain thresholds induced by cutaneous argon laser irradiation were determined. Terfenadine, antazoline and diphenhydramine significantly reduced wheal and flare after histamine skin pricks. Only diphenhydramine increased the pain threshold to noxious cutaneous laser stimulations (22%) with a concomitant reduction of histamine wheal (61.5%) and flare (52.8%). The sensory threshold was not affected significantly. The antihistaminic and analgesic effects were not related.

ISSN:1660-5527    

DOI:10.1159/000210822

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210823

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210824

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000210825

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000322301

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:1660-5527    

DOI:10.1159/000322302

出版商:S. Karger AG    

年代:1989

数据来源: Karger