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1. |
Treatment Options for Photodamaged Skin |
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Science and Public Policy,
Volume 10,
Issue 1,
1997,
Page 1-11
Christopher E.M. Griffiths,
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摘要:
Photodamage of the skin can be a detriment to physical and psychological health with a consequent negative impact on both personal and professional life. Medical treatments for photodamaged skin include topical all-trans-retinoic acid (tretinoin) as well as moisturizers, chemical peels, dermabrasion, α hydroxy acids and cosmetic surgery. Of these treatment options, only tretinoin has been subjected to large-scale, controlled studies to substantiate its clinical efficacy and long-term benefits. This review summarizes the use of various therapies and presents available clinical and histologic results of systematic trials, including the few studies of retinoid compounds other than tretinoin. Among the extensive data on topical tretinoin are long-term treatment results that provide evidence of ultrastructural changes. These histologic findings suggest that fundamental cellular effects may be responsible for the clinical benefits, which are sustained even when treatment frequency is reduced. It thus appears that tretinoin therapy at least partially restores photodamaged skin to the predamaged state.
ISSN:0302-3427
DOI:10.1159/000211454
出版商:S. Karger AG
年代:1997
数据来源: Karger
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2. |
Transcriptional Activation by 1,25-Dihydroxyvitamin D3and Synthetic Vitamin D3Analogues in Transfected Cultures of Human Keratinocytes |
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Science and Public Policy,
Volume 10,
Issue 1,
1997,
Page 12-20
Linda Ø. Henriksen,
Knud Kragballe,
Thomas G. Jensen,
Karsten Fogh,
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摘要:
Analogues of vitamin D3 have recently been introduced for the topical treatment of psoriasis. Their therapeutic effects are thought to be mediated by interaction with the vitamin D3 receptor (VDR) in epidermal keratinocytes (KCs). The purpose of the present study was to investigate the trans-acting activity of the endogenous VDR in human KCs transfected with a vitamin D response element (VDRE) in response to 1,25-dihydroxývitamin D3 [1,25(OH)2D3] and the synthetic vitamin D3 analogues GS 1500, EB 1213, MC 903 (calcipotriol) and KH 1060. Cultured KCs obtained from normal human adults were transfected with a VDRE consisting of a direct repeat (DR) of 2 hexanucleotides separated by 3 nucleotides (AGGTCAaggAGGTCA) cloned as a triple copy into the chloramphenicol acetyltransferase (CAT) reporter plasmid pBLCAT2. This DR3 response element is preferentially activated by heterodimers of the VDR and the retinoid X receptor. Twenty-four hours after transfec-tion, 1,25(OH)2D3, vitamin D3 analogues or 9-cis-retinoic acid (9-cis-RA) were added, and, after an additional 24 h, cells were harvested and assayed for CAT activity. 1,25(OH)2D3 dose-dependently induced CAT activity in VDRE-transfected KCs and co-transfection with exogenous human VDR enhanced the response to 1,25(OH)2D3. Induction of CAT activity by 1,2 5 (OH) 2D3 was enhanced in the presence of the endogenous ligand for retinoid X receptor, 9-cis-RA. The synthetic vitamin D3 analogues dose-dependently stimulated CAT activity. Compared to 1,25(OH)2D3, KCs were less sensitive to stimulation with MC 903, equally sensitive to EB 1213 and more sensitive to GS 1500 and KH 1060. In conclusion, the endogenous VDR in KCs is responsive to 1,25(OH)2D3 and its synthetic analogues in stimulating gene transcription. To the extent that the biological actions of vitamin D3 are dependent on its ability to induce gene transcription through the endogenous VDR, this transfection model may be used in the screening of novel vitamin D3 analogues for biological activity.
ISSN:0302-3427
DOI:10.1159/000211455
出版商:S. Karger AG
年代:1997
数据来源: Karger
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3. |
Pharmacodynamic Measurements of 8-Methoxypsoralen in Human Skin |
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Science and Public Policy,
Volume 10,
Issue 1,
1997,
Page 21-27
Ping Liu,
John Ademola,
Smita Amin,
Howard I. Maibach,
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摘要:
The efficiency of the epicutaneous microcirculation is important to the elicitation of pharmacological effects and percutaneous absorption of drugs. Laser Doppler flowmeter, chroma-meter and measurement of transepidermal water loss (TEWL) were used to assess the extent of skin blood flow, water loss and light absorption induced after topical administration of 8-methoxypsoralen (8-MOP). TEWL monitors barrier function directly, while the chromameter measures the light reflected by the skin. Irrespective of the concentration of 8-MOP applied, there is a good correlation between chromameter and evaporimeter readings. However, different drug concentrations elicited significant differences between laser Doppler flowmetry (LDF) and TEWL readings. The response measured with LDF was faster and greater when compared with the other measurements, suggesting that 8-MOP caused a rapid and intense response in skin blood flow. Superficial responses, such as those produced by light reflectance (chromameter) and transepidermal perturbations, were weaker following topical application of 8-MOP combined with UV irradiation (PUVA). This information may be important in delineating guidelines for the clinical practice and instrumental monitoring of topical 8-MOP. These observations suggest that LDF provides a useful, noninvasive physical technique to monitor skin after PUVA. However, caution should be exercised in the interpretation of physical measurements for evaluating the degree of the clinical vasoresponse produced by PUVA treatment.
ISSN:0302-3427
DOI:10.1159/000211456
出版商:S. Karger AG
年代:1997
数据来源: Karger
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4. |
Pharmacokinetics of Topically Applied Metronidazole in Two Different Formulations |
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Science and Public Policy,
Volume 10,
Issue 1,
1997,
Page 28-33
Peter Dykes,
Stephanie Hill,
Ronald Marks,
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摘要:
Topical metronidazole is effective in the treatment of papulo-pustular rosacea, a common inflammatory disease of the face. In this study, a comparison of the bio-availability of two topical formulations (A and B) of 0.75% metronidazole has been made. Twenty-four subjects took part in a double-blind study where each was randomly allocated to four groups corresponding to 0.5, 1, 2 and 4 h of treatment. A single application was made to each forearm and after increasing times of contact, samples of stratum corneum were removed by the skin surface biopsy (SSB) technique. After SBB removal, a full-thickness skin biopsy was taken. The tissues were extracted and analysed by an HPLC method. Both formulations showed rapid percutaneous penetration. Formulation A gave the highest concentrations at the lowest levels of the stratum corneum at 4 h. Thus in SSB5, the mean drug concentrations at 4 h were as follows: A, 6.20 ± 1.16 μg cm-2; B, 1.93 ± 0.98 μg cm-2. A similar difference was observed when the levels in the punch biopsies were determined. At 4 h, the mean drug levels were: A, 6.07 ± 2.17 μgmg-1; B, 0.95 ± 1.16 μgmg-1. Formulation A clearly gives a higher rate of percutaneous penetration leading to higher tissue levels of drug. Whether this increase leads to a clinically more effective treatment has yet to be det
ISSN:0302-3427
DOI:10.1159/000211457
出版商:S. Karger AG
年代:1997
数据来源: Karger
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5. |
Vehicle-Dependent Biotin Liberation and Penetration into Human Skin |
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Science and Public Policy,
Volume 10,
Issue 1,
1997,
Page 34-39
C. Wagner,
S. Göbel,
W. Wohlrab,
R. Neubert,
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摘要:
The presence of a sufficient quantity of a drug in the epidermis is a necessary prerequisite for influencing epidermal proliferation and differentiation processes. With the aim of obtaining a high concentration of a potential active agent (biotin) at the target area after topical application, the influence of the vehicle on biotin release and penetration was investigated. Liberation studies (multi-layer membrane model) showed that over 50% of the biotin in an oil-in-water (O/W) emulsion (64.8 ± 1.9%) and a micro-emulsion (ME, 54.5 ± 2.4%) is released within 300 min, whereas the degree of release from a water-in-oil emulsion does not exceed 16%. For this latter vehicle, the influence of a controlled drug release on the penetration processes in human skin (Franz cell) results in the penetration of only small quantities of the drug into the skin layers (into the horny layer 7.9 ± 2.6%, living epidermis 0.11 ± 0.06%, dermis 0.38 ± 0.31% within 300 min). The application of an O/W emulsion or an ME appears to be more favourable. Both vehicles lead to not only a large reservoir in the horny layer (O/W 26.5 ± 3.5%, ME 26.0 ± 0.8% within 300 min) of the skin but also important epidermal and dermal concentrations (living epidermis: O/W 2.0 ± 0.9%, ME 0.3 ± 0.2%; dermis: O/W 3.4 ± 1.3%, ME 1.6 ± 0.8% within 300 min). The time-dependent concentration profiles in the skin layers suggest that the use of an ME produces an immediate effect, whereas the application of an O/W emulsion results in a delayed and/or long-t
ISSN:0302-3427
DOI:10.1159/000211458
出版商:S. Karger AG
年代:1997
数据来源: Karger
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6. |
Assessment of the Activity of Tacalcitol on Psoriatic Plaques by Means of Colorimetry and High-Frequency Ultrasound: A Double-Blind Intrasubject Half-Side Right-Left Comparison with Betamethasone Valerate and Placebo |
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Science and Public Policy,
Volume 10,
Issue 1,
1997,
Page 40-47
Stefania Seidenari,
Rita Magni,
Alberto Giannetti,
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摘要:
The aim of our study was to further investigate and to objectively assess the effects of tacalcitol on psoriasis by means of double-blind comparisons with placebo and betamethasone valerate, documented by instrumental evaluation. The study was conducted as intrasubject half-side right-left comparisons. Twelve subjects entered a double-blind placebo-controlled treatment (tacalcitol/placebo group), whereas 14 subjects received double-blind medication with tacalcitol/betamethasone valerate. Medications were applied once daily without occlusion to affected skin areas. Instrumental evaluations were carried out by means of a colorimeter and a 20-MHz B scanner. The colour co-ordinate a*, representing the colour range from green (-) to red (+), was used for assessing erythema. B scan images were processed according to segmentation procedures. A 0-10 interval, marking the hyporeflecting dermal areas, was used for assessing oedema and inflammatory infiltration at psoriatic plaque sites. Twenty-two patients (11 of the tacalcitol/betamethasone group and 11 of the tacalcitol/ placebo group) completed the treatment period. Mean a* values showed an increase in the tacalcitol/betamethasone group after the first week of therapy on both sides, followed by a slight decrease, the values of which did not reach statistical relevance for either treatment. The decrease observed at tacalcitol-treated sites in patients of the tacalcitol/placebo group was not significant either with respect to baseline values during the first weeks of therapy. The extension of 0-10 dermal areas decreased both in betamethasone- and tacalcitol-treated areas in both patient groups. No significant differences were noticeable between the two treatments at all assessment points, although both by clinical and echographic evaluation a more pronounced decrease in clinical scores and in echogenicity values was observable at betamethasone-valerate-treated sites, especially at weeks 6 and 8. According to our data, assessment of erythema does not always represent a valid method for monitoring the response to therapy in psoriatic patients. In fact, modifications of a* values did not allow a distinction between different treatments, whereas processing of echographic images by the 0-10 segmentation enabled tacalcitol to be classified as a topical drug, the activity of which approaches that of a potent steroid.
ISSN:0302-3427
DOI:10.1159/000211459
出版商:S. Karger AG
年代:1997
数据来源: Karger
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7. |
Announcements |
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Science and Public Policy,
Volume 10,
Issue 1,
1997,
Page 48-48
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ISSN:0302-3427
DOI:10.1159/000211460
出版商:S. Karger AG
年代:1997
数据来源: Karger
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