摘要:

Mast cells are well known effector cells not only in allergic but also in diverse acute and chronic inflammatory diseases. We have shown previously that these cells produce a broad spectrum of cytokines which might contribute to mast cell-dependent pathology. In the present study, we have investigated the influence of four potent glucocorticoids, methylprednisolone-aceponate, methylprednisolone-17-propionate, prednicarbate, and betametasone valerate (105M-10-9M), on the IL-1β, IL-3, IL-8, and tumor necrosis factor α secretion of the HMC-1 mast cell line as measured by ELISA. All four glucocorticoids caused a comparable dose- and time-dependent inhibition of cytokine release from HMC-1 cells stimulated for 24 h with phorbol 12-myristate 13-acetate 25 ng/ml and calcium ionophore 2 × 10-7M. These results shed further light on the mechanisms involved in antiinflammatory effects of glucocorticoids in allergic inflammation.

ISSN:0302-3427    

DOI:10.1159/000211403

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Fumaric acid, fumaric acid dimethylester, and the dithranol derivative C4-lactone were studied in the mouse tail test to evaluate their effects on epidermal cell differentiation compared with other topical antipsoriatic drugs, such as betamethasone, calcipotriol, and dithranol. Mouse tails were treated for 2 weeks and longitudinal histological sections prepared of the tail skin. The length of the orthokeratotic regions (stratum granulosum) was measured on 10 sequential scales per tail and expressed as percentage of the full length of the scale. In addition, epidermal thickness was measured and the efficacy of the various compounds evaluated. In comparison to 2% salicylic acid ointment, all tested compounds except fumaric acid significantly (p ≤ 0.05) increased the proportion of the orthokeratotic region. C4-lactone and calcipotriol were less effective than dithranol, fumaric acid dimethylester only moderately influenced cell differentiation, and betamethasone showed the least potent effect. Dithranol was the most potent substance inducing orthokeratosis without increasing epidermal thickness.

ISSN:0302-3427    

DOI:10.1159/000211404

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Erythromycin with or without additional zinc acetate is used topically in the treatment of acne vulgaris. A potential effect of zinc on the stratum corneum penetration of erythromycin was investigated in human volunteers. Skin surface washings and tape strippings from the skin of the back were collected after drug applications in 12 subjects for quantification of erythromycin levels. Zinc acetate increased the amount remaining on the back skin at 6 h after application from 40 ± 19 to 56 ± 15% of the dose and, vice versa, reduced the amount in stratum corneum strips from 22 ± 7 to 18 ± 7%, both with statistical significance. The effect varied with body region. Zinc acetate thus provided to prolong the residence time of erythromycin on the skin.

ISSN:0302-3427    

DOI:10.1159/000211405

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Previous studies have shown that acute disruption of the cutaneous permeability barrier by acetone results in an initial rapid phase of repair followed by a later, slower phase. In the present study, we demonstrate that manipulations which disrupt the barrier by other mechanisms, such as tape stripping or detergent treatment, have a similar pattern of barrier repair. In all three models, the return of lipid to the stratum corneum parallels the normalization of barrier function, and occlusion immediately after disrupting the barrier blocks both the return of lipid and the normalization of function. Moreover, occlusion beginning 6-8 h following barrier disruption blocks the late, slower phase of repair, indicating that the late phase can be inhibited independently of the initial phase. Lastly, both severe and relatively minor perturbations of the barrier elicit a repair response with a similar kinetic pattern. In summary, the present study demonstrates that barrier repair responses are similar regardless of the etiology or extent of barrier disruption.

ISSN:0302-3427    

DOI:10.1159/000211406

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Repeated open application of clobetasol 17-propionate cream and ointment to normal skin over a period of 6 weeks induced an increase in skin surface roughness as assessed by profilometry (p < 0.05), while 6 weeks’ application of triamcinolone acetonide cream and ointment did not. The increase in skin roughness with clobetasol 17-propionate cream turned out to be greater than with ointment containing identical amounts of clobetasol 17-propionate (p < 0.05). A clear-cut correlation between increase of skin surface roughness and skin thickness as assessed by high-frequency ultrasound could be demonstrated only with clobetasol 17-propionate cream and ointment.

ISSN:0302-3427    

DOI:10.1159/000211407

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Soybean lecithin microemulsion gels offer promising features for the possible use as matrices in transdermal therapeutic systems. In order to assess the skin irritancy potential of the gel, acute and cumulative irriation tests were performed in human subjects in vivo using as comparison an unilamellar soybean lecithin liposome preparation and the solvent isopropyl palmitate (IPP). Acute irritation was tested in 151 volunteers in a 48-hour patch test, whereas cumulative irritation was assessed in a 21-day human repeated insult patch test in 20 volunteers. In the acute irritation test, discrete irritation (erythema only) developed with the gel in 2 subjects (1.3%), with the liposomes in 3 subjects (2.0%), and with IPP in 2 subjects (1.3%). For the assessment of cumulative irritation, the IT50 (irritation time of 50% of the test population) was calculated. IT50 was 13 days for the gel, 14 days for the liposomes and 17 days for IPP. This study shows a very low acute and a low cumulative irritancy potential for the soybean lecithin microemulsion gel making it a candidate matrix for transdermal therapeutic systems also under toxicological aspects.

ISSN:0302-3427    

DOI:10.1159/000211408

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The in vitro/in vivo difference in enhanced skin permeation of nicardipine hydrochloride (NC) by simultaneous use of 1-menthol and ethanol (MEW system, 1-menthol:ethanol:water = 5:40:55) was investigated in hairless rats. First, the cutaneous blood flow clearance (clearance from skin to blood flow) of NC per unit area of skin (CLCB/A), which was comparable to the permeability coefficient across skin (Pc), was calculated from intracutaneous and intravenous injection data using the deconvolution method; the value was 1.67 μ1/h/cm2. Two formulations containing NC and the MEW system, solution (SOL) and 15 % hydroxypropyl cellulose gel (GEL), were used for in vitro and in vivo permeation experiments. The in vitro Pc of NC via excised skin from SOL (23.3 μ1/h/cm2) was significantly higher than CLCB/A, and that from GEL (1.48 μ1/h/cm2) was similar to CLCB/A. Consequently, the steady-state concentration of NC in skin during in vivo application of SOL was 6.6 times higher than corresponding in vitro data. In vivo PcS from SOL and GEL were however significantly lower than CLCB/A. These results may be explained by the findings, using a laser Doppler flowmeter, that cutaneous blood flow was decreased by the application of MEW.

ISSN:0302-3427    

DOI:10.1159/000211409

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Cyclosporine A (CyA), a well established treatment of psoriasis, is a highly lipophilic cyclic undecapeptide mainly used for its immunosuppressive properties and exerting a wide spectrum of biological activities including fungicidal antiproliferative and anti-inflammatory effects. Plasminogen activators (PA), urokinase (UK, Mr 55,000) and tissue type plasminogen activators (tPA, Mr 74,000), physiologically catalyze the conversion of the plasminogen to the wide spectrum proteinase plasmin. UK and tPA are involved in cell growth, differentiation and migration. It has recently been shown that psoriatic epidermis is provided with abnormal tPA-dependent PA activity and that in lesional epidermis elevated tPA mRNA levels are present. It has been suggested that the tPA-dependent PA activity is a marker of disease activity and is reversible with different topical and systemic treatments. In this preliminary study we investigate the effect of CyA on the tPA mRNA transcription on A431 keratinocytes cell line. Sub-confluent A431 cell cultures have been treated with CyA at in vivo relevant concentrations (10, 7.5, 5 μg/ml) for 48 h. Northern blot analysis of total RNA extracted from cultured A431 cell line has been performed for detecting tPA mRNA. mRNA for tPA has been detected in the control samples whereas an evident decrease of tPA mRNA expression has been detected in the CyA-treated samples. These data suggest that CyA could have an effect in clearing psoriatic lesions also modulating the abnormal plasminogen activation i.e. tPA-dependent serinoproteinase activity.

ISSN:0302-3427    

DOI:10.1159/000211410

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000211411

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000316441

出版商:S. Karger AG    

年代:1996

数据来源: Karger