|
1. |
Effect of Inducers on the Activity of Glutathione S-Transferase and Other Enzymes of the Glutathione Pathway in Cultured Human Keratinocytes |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 241-245
Donald A. Vessey,
Kyung-Hee Lee,
Kerry L. Blacker,
Thomas D. Boyer,
Preview
|
PDF (1711KB)
|
|
摘要:
Known inducers of the hepatic glutathione (GSH) S-transferases were tested at the limits of their solubility as inducers of the enzyme in cultured human keratinocytes. Neither phenobarbital, trans-stilbene oxide, propylthiouracil, nor butylated hydroxyanisole increased GSH S-transferase activity or led to the appearance of α- or μ-forms of the enzyme, as judged by Western blotting. Only the π-form of the enzyme was found before and after all treatments. Thus, the enzyme is not indu-cible in keratinocytes. However, 4 mM propylthiouracil did lead to a 50% increase in GSH reductase activity, and phenobarbital at 4 mM completely abolished GSH peroxidase and GSH reductase activity and led to a significant loss of viabili
ISSN:0302-3427
DOI:10.1159/000211144
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
2. |
Metabolism of Ethyl 4-Aminobenzoate in the Isolated Single-Pass Perfused Rabbit Ear |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 246-252
B. Henrikus,
H.G. Kampffmeyer,
Preview
|
PDF (2357KB)
|
|
摘要:
Isolated rabbit ears were single-pass perfused with a protein-free Tris buffer solution. Ethyl 4-amino[U-ring-14C]benzoate or 4-amino[U-ring-14C]benzoic acid was applied to the epithelial surface in isopropyl myristate, or perfused arterially. Metabolites in the effusate were extracted and separated by high-performance liquid chromatography. Five metabolites were separated from ethyl aminobenzoate and identified as aminobenzoic acid, or acid-labile conjugates from either substrate. Their chemical structure has not yet been established. One metabolite, perhaps a glycolic acid N-conjugate of ethyl 4-ami-nobenzoate, was found at about 100 times higher concentration after arterial than after dermal drug application, indicating that the quantitative metabolic patterns in skin differ depending on whether the xenobiotic reaches the enzymes of the skin by cutaneous absorption or by the blood circulation. The metabolite pattern of the skin was compared with that from rabbit or rat liver cell preparations.
ISSN:0302-3427
DOI:10.1159/000211145
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
3. |
Increased Superoxide Anion Production in Dermal Fibroblasts of Psoriatic Patients |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 253-258
A. Er-raki,
M. Charveron,
J.L. Bonafé,
Preview
|
PDF (2052KB)
|
|
摘要:
We studied the superoxide anion activity of psoriatic and normal dermal fibroblasts in culture. Superoxide anion production was measured by the technique of Pick and Mizel in fibroblasts cultured from biopsies of involved and uninvolved skin of patients with psoriasis and from skin biopsies of normal controls. Our results show that the liberation of superoxide anion was sig nificantly increased (p < 0.001) in fibroblasts obtained from involved areas of skin (5.58 nmol O2-/106cells/50 min) and also from uninvolved skin (p < 0.01) (4.60 nmol O2-/106 cells/50 min) of psoriatic patients, compared to controls (2.25 nmol O2-/106 cells/50 min). The increase in superoxide anion liberation was 100 and 150% in uninvolved and involved psoriatic fibroblasts, respectively. This suggests an important role for dermal fibroblasts in the inflammatory mechanism of psoriasis.
ISSN:0302-3427
DOI:10.1159/000211146
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
4. |
Ultrastructural Localization and Quantification of Extracellular Calcium Binding Sites in Mouse Vibrissa and Human Scalp Follicles |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 259-267
Cynthia J. Mills,
Allen E. Buhl,
Roger G. Ulrich,
Arthur R. Diani,
Preview
|
PDF (3165KB)
|
|
摘要:
The purpose of these experiments was to determine if an extracellular calcium binding site gradient is evident in freshly dissected or cultured mouse vibrissa and human scalp follicles and to measure possible drug effects on this gradient. Mouse vibrissae were cultured with or without either minoxidil or pinacidil, and human scalp follicles were cultured with or without epidermal growth factor. Anagen vibrissa and scalp follicles were dissected and placed in culture for 4 h to 4 days, then fixed in a solution containing lanthanum chloride and prepared for either quantitative energy-dispersive X-ray microanalysis (X-ray) or qualitative transmission electron microscopy (TEM). Since lanthanum has a high charge density it displaces Ca2+ ions from anionic binding sites. TEM analysis revealed extensive accumulation of electron-dense lanthanum deposits in the intercellular compartment of differentiating cells in the hair shaft and inner root sheath in the apex of the follicular bulb. Sparse lanthanum precipitate was observed in the intercellular space of the proliferative cells at the base of the bulb. This gradient of lanthanum precipitate was evident in both freshly dissected and cultured vibrissa and scalp hair follicles, irrespective of treatment with drugs that grow hair or epidermal growth factor. X-ray microanalysis indicated that percent by weight of lanthanum was markedly higher in the apex compared to the base of the follicular bulb in vibrissa and scalp follicles. These qualitative and quantitative data demonstrate that an extracellular calcium binding site gradient exists in cultured vibrissa and scalp hair follicles, and that this gradient is not significantly affected by hair growth altering drugs including minoxidil or pinacidil, and epidermal growth factor.
ISSN:0302-3427
DOI:10.1159/000211147
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
5. |
Announcement |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 267-267
Preview
|
PDF (189KB)
|
|
ISSN:0302-3427
DOI:10.1159/000211148
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
6. |
Feasibility of Measuring the Bioavailability of Topical Ibuprofen in Commercial Formulations Using Drug Content in Epidermis and a Methyl Nicotinate Skin Inflammation Assay |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 268-275
P. Treffel,
B. Gabard,
Preview
|
PDF (2692KB)
|
|
摘要:
A method has been developed which simultaneously compares the inhibition of an inflammation induced by a methyl nicotinate assay with the concentration of drug in the human epidermis determined in vitro following topical application of two 10% ibuprofen formulations. The bioavailability of drug from commercial gel and emulsion was assessed after the application of various doses (3, 6 and 12 mg/cm2) and an application time of 0.5 h at two time points: 0.5 and 24 h (only with the 12 mg/cm2 dose) after the removal of the non-steroi-dal anti-inflammatory drug (NSAID) from the skin. In parallel, we assessed the epidermal concentration of the drug in vitro and evaluated the anti-inflammatory effect of the topicals in vivo. A correlation (r = 0.9603, p < 0.001) between the amount of drug in the epidermis expressed as micrograms per milligram of epidermal protein and the corresponding inhibition of the inflammation was observed. Increasing the amount of drug in the epidermis correlated with an increased inhibition of the inflammation. The gel formulation released more drug to the skin and produced a greater anti-inflammatory effect. Topical NSAID concentration in treated skin can therefore be determined and correlates well with the resulting phar-macodynamic activity. This approach will likely have utility in optimizing topical NSAIDs.
ISSN:0302-3427
DOI:10.1159/000211149
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
7. |
Does Salicylic Acid Increase the Percutaneous Absorption of Diflucortolone 21-Valerate? |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 276-281
U. Täuber,
C. Weiss,
H. Matthes,
Preview
|
PDF (1937KB)
|
|
摘要:
The percutaneous absorption of diflucortolone-21-valerate (DFV) and its effect on the pituitary adrenal system were investigated during large skin area treatment (20 g ointment twice a day for 8 days) of two groups of healthy volunteers with Nerisona® and Nerisalic® ointment, respectively. Plasma levels of diflucortolone, cortisol and dehydroepiandrosterone (DHEA) were measured in both groups whereas plasma levels of salicylic acid were measured additionally in volunteers treated with Nerisalic. No differences, neither in percutaneous absorption of DFV nor in effects on cortisol and DHEA were found between the two treatment groups. There was a slight reduction in cortisol levels under both treatments, but the circadian rhythm was not disturbed. Mean salicylic acid plasma levels under high-dose topical Nerisalic treatment were about 50-fold below levels where toxicity may be expecte
ISSN:0302-3427
DOI:10.1159/000211150
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
8. |
Evaluation of Phototoxic and Photogenotoxic Risk Associated with the Use of Photosensitizers in Suntan Preparations: Application to Tanning Preparations Containing Bergamot Oil |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 282-291
A. Moysan,
P. Morlière,
D. Averbeck,
L. Dubertret,
Preview
|
PDF (3998KB)
|
|
摘要:
Bases for the elaboration of a standardized protocol are proposed for studying phototoxic effects of skin tanning preparations containing photosensitizing agents. The experimental procedure includes in vivo phototoxicity tests, evaluation of the photogenotoxic risk and determination of the photosensitizer concentration in plasma after topical application. This procedure was carried out with tanning preparations containing a well-known photosensitizer, 5-methoxypsoralen, as a component of bergamot oil. The whole study has been performed using topical application of the commercial suntan product, i.e. containing the sunscreens and all other components. Whereas the exposure to solar simulated radiation never triggered any phototoxic response, a photosensitizing effect was observed for skin type I volunteers exposed to high doses of ultraviolet A. The transepidermal penetration resulted in a 5-methoxypsoralen concentration of 1-4 ng/ml in the suction blister fluid. The photogenotoxicity of this suction blister fluid containing 5-methoxypsoralen and also other ingredients of the tanning preparation was assayed on yeast cells and was found to be rather low. 5-Methoxypsoralen was also detected in plasma after repeated applications but at low concentrations (about 1 ng/ml) which do not present a potential risk for systemic ocular effects.
ISSN:0302-3427
DOI:10.1159/000211151
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
9. |
5-Lipoxygenase Activation in Psoriasis: A Dead Issue? |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 292-297
Anthony W. Ford-Hutchinson,
Preview
|
PDF (2350KB)
|
|
摘要:
It has been suggested in the literature that 5-lipoxygenase activation may be an important pathological event in psoriasis and that 5-lipoxygenase inhibitors may thus have some beneficial therapeutic effect in this disease. This is because (1) neutrophil activation is a prominent feature of the disease, (2) leukotriene B4 is a potent chemotactic agent for neutrophils and is present in psoriatic lesions, (3) 5-lipoxygenase is present in human epidermis, (4) inhibition of 5-lipoxygenase may affect the disease. These concepts are questioned, and in particular it is suggested that (1) the leukotriene B4-like material found in psoriatic skin has never been shown to have the correct stereochemistry to indicate that it is 5-lipoxygenase derived, (2) there is no convincing evidence for the presence of the 5-lipoxygenase enzyme in human skin, (3) drugs purported to have some benefit in psoriasis through 5-lipoxygenase inhibitory mechanisms act through other mechanisms and (4) selective leukotriene biosynthesis inhibitors have no therapeutic utility in psoriasis. It is concluded that 5-lipoxygenase activation does not play a significant role in the pathology of psoriasis and therefore selective leukotriene biosynthesis inhibitors would have no significant role in the treatment of this disease.
ISSN:0302-3427
DOI:10.1159/000211152
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
10. |
Quantitative Evaluation of Drug-Induced Erythema by Using a Tristimulus Colour Analyzer: Experimental Design and Data Analysis |
|
Science and Public Policy,
Volume 6,
Issue 4,
1993,
Page 298-312
S.Y. Chan,
A. Li Wan Po,
Preview
|
PDF (1861KB)
|
|
摘要:
Pulsed-light reflectance using the Minolta® Chroma Meter CR-200 was evaluated as a quantitative method for the non-invasive assessment of drug-induced erythema on the flexor surface of the forearm. Nicotinate esters were used as model vasodilators. Several parameters derived from the data were analysed using analysis of variance (ANOVA) and Tukey’s multiple range tests appropriate for the study designs used. The effects of varying concentrations of methylnicotinate and of different nicotinate esters were found to be statistically significant. This non-invasive technique was found to be particularly useful in ranking the cutaneous responses elicited by the topical application of increasing concentrations of methylnicotinate in a single subject, as well as in a group of 6 voluntee
ISSN:0302-3427
DOI:10.1159/000211153
出版商:S. Karger AG
年代:1993
数据来源: Karger
|
|