ISSN:1660-5527    

DOI:10.1159/000211509

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Cyclosporin A (CsA) is efficacious in many dermatoses as an oral but not as a topical form, while tacrolimus (FK506) has been shown to be effective in both forms. As inadequate skin absorption has been proposed as the reason for inefficacy of topical CsA, factors contributing to percutaneous absorption of FK506 and CsA were studied. Partitioning of FK506 and CsA between octanol and water, stratum corneum and water, and stratum corneum and isopropyl myristate was determined. Absorption of FK506 and CsA through dermatomed human cadaver skin was determined with in vitro flow-through cells. In partitioning experiments, CsA was more lipo-philic than FK506. Both drugs were seen in comparable amounts in skin layers, but FK506 permeated the skin to a greater extent than CsA.

ISSN:1660-5527    

DOI:10.1159/000211510

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Although prior morphologic studies have shown that both polar and nonpolar materials permeate across the stratum corneum (SC) via a paracellular route, the actual pathway through these heterogeneous domains is unknown. We applied hydrophilic and hydrophobic tracers in vivo to murine skin under basal conditions and/or after permeation enhancement with occlusion, vehicle enhancers, a lipid synthesis inhibitor, sonophoresis, and iontophoresis. Ruthenium tetroxide, ruthenium red plus osmium tetroxide, in situ precipitation with osmium vapor, and microwave postfixation methods were used to visualize penetration pathways. Tracers invariably localized to discrete lacunar domains, embedded within the extracellular lamellar membrane system, regardless of their polarity or the enhancement method. Moreover, while the lacunar domains remained discontinuous under basal conditions, they appeared to gain structural continuity with permeation enhancement. These results indicate that extracellular lacunar domains comprise a pore pathway for penetration of polar and nonpolar molecules across the SC.

ISSN:1660-5527    

DOI:10.1159/000211511

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

To evaluate the epidermal barrier function of in vitro reconstructed epidermis, we measured the penetration of estradiol and water across human keratinocytes cultured in defined medium (DM), in the presence of proliferative fibroblasts (pF) or conditioned medium derived from pF, at the air-liquid interface on synthetic porous membrane, noncoated or coated with laminin, fibronectin, type I collagen or type IV collagen. Ultrastructural analysis showed a well-developed stratum corneum whatever the culture conditions. The permeability of reconstructed epidermis in DM on a noncoated porous membrane was 5- to 10-fold higher than human native epidermis, with both tracers. No significant change in barrier function was observed whatever the culture conditions.

ISSN:1660-5527    

DOI:10.1159/000211512

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Background: Topical corticoids decrease de novo collagen synthesis in the human skin. Objective: We studied the effect of three corticoids, hydrocortisone (HC), methylprednisolone aceponate (MPA) and momethasone furoate (MMF) on the de novo synthesis of type I and III collagens. Methods: Fifteen healthy male volunteers treated four areas marked on their abdominal skin for 1 week. HC was applied twice a day, MPA and MMF once a day plus vehicle once a day and vehicle twice a day. After the treatment, suction blisters were induced on the treated areas, the suction blister fluid (SBF) was collected and procollagen propeptides of type I and III procollagens (PINP, PIIINP, respectively) were analyzed by radioimmunological assays. The protein concentration in SBF was determined by a colorimetric method. Results: All the corticoids studied decreased the procollagen propeptide concentrations in SBF. HC decreased PINP concentration by 66%, MPA by 68% and MMF by 72%. HC decreased PIIINP by 62%, MPA by 68% and MMF by 72%. The protein concentration in SBF was decreased by 11-15% by these topical corticoids. Conclusion: HC decreases the concentration of procollagen propeptides in human skin in males to nearly the same extent as MPA and MMF.

ISSN:1660-5527    

DOI:10.1159/000211513

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Sixteen bile acids were tested at a concentration of 50 μM for their effect on growth of preconfluent cultures of proliferating keratinocytes. Monohydroxy bile acids (3-β-hydroxy-δ5-cho-lenate and lithocholate) stopped the accumulation of protein, dramatically decreased DNA content and led to a 90% loss of cell viability. Deoxycholate (DOC) and chenodeoxycholate inhibited protein accumulation and blocked increases in DNA content, without affecting cell viability. DOC had measurable growth-retarding effects at concentrations as low as 15 μM, and lithocholate at 2 μM. The glycine and taurine conjugates of bile acids were significantly less effective inhibitors of growth, as was the sulfate conjugate of lithocholic acid. DOC and chenodeoxycholate at 25-50 μM enhanced the differentiation-specific increase in particulate transglutaminase activity by as much as 80% over 6 days. Lithocholate had a similar effect at 5 μM. Glycine and taurine conjugates of DOC had a similar effect but were less potent; tauroursodeoxycholate had no effect. The data indicate that bile acids, at levels seen in obstructive biliary disease, can lead to a down-regulation of keratinocyte growth and an up-regulation of differentiation.

ISSN:1660-5527    

DOI:10.1159/000211514

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The in vitro antifungal activity of the new hydroxypyridone antimycotic rilopirox has been evaluated against 29 separate clinical isolates of Mαlαsseziα (M.) furfur obtained from patients with pityriasis versicolor, seborrhoeic dermatitis or dandruff. Minimum inhibitory concentrations (MICs) of rilopirox were measured by the agar dilution technique and, in comparison, by a recently described microdilution method with colorimetric detection of the MIC end points. Rilopirox was found to be able to inhibit growth of all clinical yeast isolates. For the investigated M. furfur strains MIC values from 12.5 to 50 µg ml-1 with a median of 25 µg ml-1 were determined by the agar dilution method. Using the microdilution technique, MIC values between 16 and 128 µg ml-1 (median 32 µg ml-1) were found for the M. furfur isolates. It has to be taken into account that with a 0.3% solution concentrations of 300,000 µg ml-1 are applied to the skin. Furthermore, due to its extreme low penetration rilopirox is long-term available in the skin in inhibiting concentrations. In comparison with rilopirox, the in vitro susceptibility of M. furfur against the systemically applicable triazole antimycotic itraconazole and clotrimazole, an established topical antifungal, was tested. As expected, low MIC values for these azoles were found by the agar dilution method. The median of the MIC of M. furfur was 0.1 µg ml-1 for itraconazole, and 6.25 µg ml-1 for clotrimazole. The inhibitory effectivity of rilopirox against clinical isolates of M. furfur seems to justify its therapeutic evaluation in clinical trials. This new antifungal may be a useful alternative not only in pityriasis versicolor but also in seborrhoeic dermatitis due to the growth inhibition of M. f

ISSN:1660-5527    

DOI:10.1159/000211515

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Using a model of pure epidermal wounds in normal human volunteers, we have studied the effects of Biafme® emulsion firstly on inflammatory cell migration, vascular permeability and cytokine release during the first 24 h, and secondly on epidermal wound healing by measuring transepidermal water loss from day 1 to day 7. Under these conditions, Biafme does not improve epidermal healing, in contrast to what is observed with bleeding dermoepidermal wounds. Our results suggest that the effects of Biafine are essentially at the dermis level. The analysis of epidermal wound exudates leads to the same conclusion. As a matter of fact, we demonstrated that Biafine is chemotactic for macrophages and increases the IL-l/IL-6 ratio, chiefly by reducing the secretion of IL-6. This study permits to progressively clarify the mode of action of Biafine, that seems to be located at the level of granulation tissue formation and not at the epidermal level

ISSN:1660-5527    

DOI:10.1159/000211516

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The fuzzy rat, a genetic mutant between hairless and hairy albino rats, expresses androgen-dependent hypersecretion of sebum and hyperplastic sebaceous glands. Using this model for human acne, we examined the effects of inhibitors of human steroid 5α-reductase isozymes, type I (MK386) and type II (finasteride), and an androgen receptor blocker (RU58841) on regression of glandular and ductal hyperplasia. The above three agents, 1 % weight volume, were dissolved into the vehicle (propy-lene glycol, alcohol and water) and applied on the backs of peripubertal male rats for 2 months. Control and castrate groups received vehicle alone. At 8 weeks, we examined the size of the sebaceous glandular lobules and ducts in split epidermal preparations as well as in frozen sections of skin stained with osmium-potassium dichromate solution. The number of bro-modeoxyuridine (BrdU)-positive cells was counted in the glandular lobes in split-skin tissues stained with BrdU immunochemistry. The results revealed that the sizes of both lobes and ducts in castrates were 40-60% smaller than in controls. RU58841 induced glandular and ductal regression equivalent to that in castrates. Finasteride induced a moderate degree of lobular and ductal reduction, whereas MK386 caused only ductal regression. Reduction of BrdU-positive cells in the sebaceous lobes was found in the skin treated with finasteride and RU58841. Serum concentrations of testosterone and dihydrotestosterone showed no significant changes in all drug-treated rats. The weight of the prostatic lobes was reduced significantly in rats treated with finasteride but not by the other two agents. RU58841 effectively counteracted endogenous androgens resulting in a suppression of growth of the sebaceous glands but not the prostate. This rodent model for androgen-dependent hyperplasia of the sebaceous glands is useful for the study of many pharmacological aspects comprising the rate of percutaneous absorption, stability and affinity to target organs of the testing compounds, and selection of adequate vehicles for topical application

ISSN:1660-5527    

DOI:10.1159/000211517

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The hormone melatonin is produced in the pineal gland and secreted into the blood in a circadian rhythm. Due to its antiox-idative and immunomodulatory effects it might play a role as a topical drug in dermatology. In this study we investigated the penetration kinetics of melatonin applied to the skin of 6 healthy volunteers aged 26-34 years (M/F = 2/4). First the individual physiologic daytime melatonin serum levels were determined by radioimmunoassay. Then 3 of the participants were treated once topically on their scalp with 20 mg melatonin dissolved in 70% ethanol, while the other 3 individuals received 100 mg. The application was performed at 9.00 a.m., and blood samples were collected repeatedly for a total of 8 h. Physiologic daytime melatonin levels in the 6 individuals were 16.8 ± 10.0 pg/ml. The 3 individuals treated with 20 mg melatonin displayed peak serum levels of 762, 918 and 3,440 pg/ml, respectively, those treated with 100 mg melatonin showed peak levels of 1,136, 3,360 and 4,230 pg/ml lasting throughout the entire observation period of 8 h. These findings indicate that melatonin might accumulate in the stratum corneum with prolonged release into the blood system from this depot

ISSN:1660-5527    

DOI:10.1159/000211518

出版商:S. Karger AG    

年代:1997

数据来源: Karger