摘要:

Using cultured human keratinocytes, three bioassays for retinoic acid-like substances have been developed. They are based on the ability of these substances (1) to inhibit cross-linked envelope formation, (2) to inhibit the synthesis of the Kl keratin, and (3) to stimulate the synthesis of the K19 keratin. The data, expressed as 50% inhibitory or activating concentrations were used to rank compounds according to their activity.

ISSN:0302-3427    

DOI:10.1159/000210795

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Since mast cells have previously been shown to be potent modulators of lymphocyte function, the effect of varying concentrations of three mast cell- or basophil- as well as skin ground substance-derived glycosaminoglycans (GAG; heparin, chondroitin sulfate, hyaluronic acid) and of histamine was investigated on rat spleen cell 3H-thymidine incorporation in the absence and presence of mitogens. Modulation proved to be different for the three GAG: chondroitin sulfate was inhibitory and hyaluronic acid enhancing, while heparin exhibited a more complex pattern, with inhibition in control and phytohemagglutinin-stimulated cultures and enhancement in concanavalin A-driven cultures, in parallel to histamine. The data suggest that ground substance GAG as well as mast cell- and basophil-derived mediators in the skin can have a marked and complex modulatory effect on the function of lymphocytes.

ISSN:0302-3427    

DOI:10.1159/000210796

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The influence of the dose, as well as the application area of topically applied 3H-estradiol in a volatile solution on its systemic bioavailability was investigated in hairless rats in vivo. The bioavailability was determined by comparing the urinary and fecal excretion of radioactivity after intravenous injection and after topical application. Whatever the size of the surface of application (1, 4 or 16 cm2), the bioavailability was similar (47–65%) 4 days after the application of a single low dose (50 nmol). When the surface of application was washed 24 h after dosing, the absorption was the same for the areas of 3 and 9 cm2. In all cases average fluxes on the first day were higher for the larger area. When applied doses were increased (1,000 and 10,000 nmol), the percentage of percutaneous absorption decreased with the reduction in the areas of application. Thus, with a dose of 1,000 nmol applied on a surface of 1, 4 and 16 cm2, absorption was equal to 18.7, 21 and 37%, respectively, of the dose. There was a linear relationship between the log of the dose applied per unit of skin area and the percentage of absorption after 4 days (r = 0.99 with washing; r = 0.98 without washing). For a determined dose of estradiol (D) it is thus possible to predict the total quantity (Q) which will be absorbed depending on the application area (A) according to the relationship: Q=(-alogD/A + b)/100 ×D, where a and b are equal to 18.7 and 73.8, respectively, for an application without washing and 20.4 and 68.8 with washing. From these results it appears that when estradiol is applied in a volatile solvent at low concentration the horny layer acts as a reservoir. After evaporation of the vehicle and for a single dose the bioavailability is equivalent for a large range of application areas. Thus, with a volatile solvent it would not appear necessary to control both the dose and the surface of application in order to obtain controlled dosage for systemic effec

ISSN:0302-3427    

DOI:10.1159/000210797

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The effects of three formulations on the transdermal absorption and antihypertensive activity of 14C-viprostol were investigated in the spontaneously hypertensive rat. Single doses of 14C-viprostol were administered topically to rats in three formulations: silicone oil, petrolatum base, and triethyl citrate (TEC). Mean arterial blood pressure (MABP) and blood concentrations of radioactivity were measured over 24 h. Metabolic profiles in the skin were determined by HPLC; in vitro skin metabolism was also investigated. Following topical dosing with 14C-viprostol in petrolatum and silicone oil, substantial systemic concentrations of radioactivity and decreases in MABP were observed. In contrast, administration of 14C-viprostol in TEC led to negligible blood concentrations of radioactivity and the lowering of MABP was diminished. Metabolic profiles in skin at the application site from rats dosed with viprostol in petrolatum and silicone oil indicated rapid hydrolysis of the viprostol methyl ester to the active free acid, CL 115,129. When TEC was used as the dosing vehicle, the conversion of viprostol to the free acid appeared to be slower. TEC (an ester itself) was also found to reduce the rate of hydrolysis of viprostol in rat skin 10,000-g supernatants.

ISSN:0302-3427    

DOI:10.1159/000210798

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Ciclosporin is clinically effective in a variety of inflammatory skin diseases. We have therefore studied the effects of the drug on cutaneous inflammation in mice. Ciclosporin inhibited the inflammatory response to 12-O-tetradecanoylphorbol-13-acetate (TPA) and to the contact sensitising agent oxazolone when applied topically to mouse skin. The drug had no effect on arachidonic acid-induced inflammation. The protein synthesis inhibitor cycloheximide showed a similar profile of activity. Ciclosporin, like actinomycin D but unlike cycloheximide, was only effective in inhibiting the inflammatory response to TPA if given 0.5 h before, but not 2 h, after TPA. These results suggest that the anti-inflammatory activity of ciclosporin in the skin is due to an effect on the production of proinflammatory proteins.

ISSN:0302-3427    

DOI:10.1159/000210799

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000210800

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000210801

出版商:S. Karger AG    

年代:1989

数据来源: Karger