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Biomedical subjects

A Fourtanier

Publications and source records attributed to A Fourtanier.

31 records · Page 2Linked to original sources
PubMed1996

Hyaluronic acid and dermatan sulfate are selectively stimulated by retinoic acid in irradiated and nonirradiated hairless mouse skin.

All-trans retinoic acid (RA) has been shown to enhance subepidermal repair in photoaged hairless mice. The current study assesses the effects of RA on the glycosaminoglycan (GAG) content in irradiated and nonirradiated mouse skin. Mice were exposed to ultraviolet B (UVB) for 10 wk, after which they were treated either with 0.05% RA or with an ethanolpolyethylene glycol 400 vehicle three times a week for 10 or 20 wk. When assessed at the end of 10 wk of UVB irradiation, the GAG content had doubled, without a change in the hyaluronic acid (HA) to dermatan sulfate (DS) ratio. When irradiation was discontinued, the GAG content decreased progressively until the end of the experimental period. This decline was totally inhibited by RA treatment and could be ascribed to a marked increase in hyaluronic acid (78%), whereas no significant change in DS was observed. In nonirradiated skin, however, topical RA increased GAG levels mainly by a pronounced increase in the content (50%) and the synthesis (40%) of DS. In untreated mice, the HA/DS ratio decreased significantly with age in both irradiated and nonirradiated mice. Interestingly, RA maintained this ratio only in animals exposed to UVB. In addition, there was a marked stimulation in the heparin content, up to approximately 20-fold, after irradiation, whereas the amount of heparin in both irradiated and nonirradiated skin increased about 2- to 3-fold with RA treatment. In summary, the alterations induced in HA and DS contents in irradiated and nonirradiated skin indicate the specificity of the RA-induced effects for the various GAGs.

Animals↗
PubMed1996

Mexoryl SX protects against solar-simulated UVR-induced photocarcinogenesis in mice.

The aim of this study was to determine, for regulatory purposes, the potential of Mexoryl SX, a broad UVA absorber that also absorbs to some extent in the UVB, to modify the UV radiation (UVR)-induced murine skin tumor development and growth. Skh-hr1 mice were exposed to solar-simulated UVR 5 days per week for 40 weeks. Two control groups were irradiated without topical application, three groups received a sunscreen preparation containing either the UVA absorber, Mexoryl SX at 5 or 10% concentration, or a filter that absorbs principally in the UVB, 2-ethylhexyl-p-methoxycinnamate (2-EHMC) at 5% concentration, introduced as a comparator test article. Sunscreen application was performed before UVR exposure 3 days per week and after UVR exposure on the other 2 days (consistent with the design of a standard photocarcinogenesis safety test). Two different weekly UVR doses were administrated: the lower dose was given to one group of unprotected animals, whereas the higher dose was administrated to the other unprotected group and to the three sunscreen-treated groups. The two UVR control groups demonstrated a UVR-dependent response for cumulative tumor prevalence, tumor yield and median latent period. Neither concentration of Mexoryl SX increased the probability of tumor development; consistent with the principles for safety testing, this provides evidence in that it is safe for use in sunlight. Although this study was explicitly designed as a safety test, the results also provide some clues about the efficacy of Mexoryl SX in decreasing the probability of tumor development. Topical administration of Mexoryl SX, at both concentrations, resulted in a 6 week delay in the median latent period compared to high UVR controls, whereas 5% 2-EHMC delayed the median latent periods only by 2 weeks. Tumor prevalence and yield show the same efficacy differences between the two sunscreen ingredients. Tumor protection factors were calculated from these results and found to be equal to 2.4 for the two preparations containing Mexoryl SX and to 1.3 for the 5% 2-EHMC preparation. These findings illustrate the efficacy of Mexoryl SX in preventing UVR-induced carcinogenesis.

Animals↗
PubMed1996

Expression of intercellular adhesion molecule-1 in UVA-irradiated human skin cells in vitro and in vivo.

Ultraviolet A (UVA) radiation represents an important oxidative stress to human skin and certain forms of oxidative stress have been shown to modulate intercellular adhesion molecule-1 (ICAM-1) expression. ICAM-1 has been shown to play an important part in many immune reactions and the perturbations of this molecule by ultraviolet radiation could have implications in many inflammatory responses. An enhancement immunohistochemical method with avidin/biotin was used for analysing the early effects of UVA radiation on human cell cultures and human skin (340-400 nm). Both in vitro and in vivo data show that ICAM-1 staining in epidermal keratinocytes, which was expressed constitutively, decreased in a UVA dose-dependent manner. The decrease was most noted at 3-6 h following UVA radiation with some ICAM-1 staining returning by 48 h post-UVA. ICAM-1 positive staining in the dermis was specific for vascular structures and was increased 24 h after UVA radiation. Cultured dermal fibroblasts exhibited ICAM-1 staining which increased slightly within 6-48 h post-UVA radiation. As epidermal ICAM-1 expression is depleted following UVA radiation and dermal expression increases due to an increase in the vascular structures, ICAM-1 provides a valuable marker following UVA radiation in human skin that can be readily measured in situ.

Adult↗
PubMed1995

Chronic UVB- and all-trans retinoic-acid-induced qualitative and quantitative changes in hairless mouse skin.

Histochemical and ultrastructural studies have already demonstrated that chronic exposure to UV radiation induces profound alterations in all structural elements of the skin and that topical all-trans retinoic acid (tRA) can substantially correct much of the tissue damage. However, previous biochemical studies on dermal components of the extracellular matrix have led to contradictory results, particularly with regard to the effect of chronic UV exposure. The aim of our study was to investigate changes in collagen content and other dermal modifications induced by tRA in irradiated and non-irradiated hairless mouse skin. Hairless mice were exposed to increasing doses of UVB for 10 weeks (the cumulative total dose was 4.6 J cm-2). After the UV irradiation period the animals were treated with 0.05% tRA or with ethanol-polyethylene glycol vehicle alone three times a week for up to 10 weeks. Non-irradiated animals underwent the same treatments. The main clinical and histological changes induced by UVB exposure were erythema, wrinkling, keratosis and epidermal thickening. Following UVB exposure, tRA treatment did not improve the clinical aspect but increased the width of the dermal repair zone. Fibronectin, laminin and type I and VI collagens were detected by indirect immunofluorescence techniques in this zone. Type I and III collagens were quantitated in skin fragments after cyanogen bromide digestion and polyacrylamide gel electrophoresis. Under our experimental conditions, UVB irradiation alone induced neither changes in total collagen nor in type I and III collagen levels. tRA treatment of irradiated skin significantly increased both type I and III collagen levels by factors of 1.33 and 1.88 respectively. The ratio of type III to types I + III increased significantly. Topical tRA also increased collagen type levels in non-irradiated hairless mouse skin. Type I collagen increased proportionally to type III. This study leads to the conclusion that topical tRA exerts direct or indirect effects on collagen metabolism in irradiated as well as non-irradiated hairless mouse skin.

Animals↗
PubMed1993

Alterations of proteoglycans in ultraviolet-irradiated skin.

The effect of UVB exposure on the distribution and synthesis of dermal proteoglycans was measured in the skin of hairless mice. Two groups of mice were included: one was irradiated for 10 weeks; the other was kept as control. After intraperitoneal injection of sodium 35-S-sulfate, punch biopsies were taken for histology and proteoglycans were extracted from the remaining skin with 4 M guanidinium chloride, containing 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (0.5%, weight per volume). Following proteolytic digestion, the glycosaminoglycan constituents were isolated and analyzed by quantitative cellulose acetate electrophoresis and enzymatic digestibility. Under the influence of UVB radiation, newly synthesized proteoglycans measured by 35SO4 uptake increased as much as 60%. In addition, the irradiated skin had a higher average content of proteoglycan than had control skin (4981 micrograms vs 4134 micrograms/g dry weight). This could be ascribed to an increase in heparin (1400 vs 533 micrograms/g dry weight) and heparan sulfate (472 vs 367 micrograms/g dry weight), whereas no change in the concentration of hyaluronic acid (1243 vs 1372 micrograms/g dry weight) and dermatan sulfate (1866 vs 1863 micrograms/g dry weight) was observed. The irradiated animals also exhibited a marked increase in the synthesis of heparan sulfate and heparin (62% and 71%, respectively). These results demonstrate that chronic doses of UVB altered proteoglycan metabolism through both quantitative and qualitative changes.

Animals↗
PubMed1992

UVA- and UVB-induced changes in collagen and fibronectin biosynthesis in the skin of hairless mice.

The modifications induced in hairless mouse skin by chronic UV irradiation were investigated. Skin explant cultures were used to study UVA- and UVB-induced changes occurring in interstitial collagen (type I and type III) and fibronectin biosynthesis. To study the long-term effects, albino hairless mice were irradiated with UVA radiation alone from two sources with different spectral qualities or with UVB. UVA and UVB radiation produced a significant increase in the ratio of type III to type I collagen (more than 100% for UVA-irradiated skin and about 60% for UVB-irradiated skin) accompanied by a significantly increased fibronectin biosynthesis (50% or more in all irradiated groups). Irradiation with either UVA or UVB alone had no significant effect on the total collagen synthesis and resulted in only a slight decrease in the total collagen content of the skin determined as hydroxyproline. This decrease was significant only in the case of the group irradiated with UVA (xenon) (decrease of 25%, expressed as micrograms of hydroxyproline per milligram wet weight). A significant decrease in collagen hydroxylation (expressed as radioactive hydroxyproline/radioactive hydroxyproline plus proline in neosynthesized collagen) was observed of about 50% in skin irradiated with UVA (xenon) but not in UVB-treated skin. Several of the above modifications (increased fibronectin biosynthesis, increased collagen type III to type I ratio) correspond to the modifications observed during the aging of non-irradiated hairless mice. Therefore it appears that UV irradiation accelerates the modifications of extracellular matrix biosynthesis observed during aging.

Amino Acids↗
PubMed1992

In vivo evaluation of photoprotection against chronic ultraviolet-A irradiation by a new sunscreen Mexoryl SX.

In a previous study on the hairless mouse it was shown that sub-erythemal doses of pure UV-A enhanced the numerous changes normally observed during chronological aging. A new sunscreen (a bis-benzylidene campho sulfonic acid derivative) has been synthesized in our research laboratory (lambda max: 345 nm, epsilon: 47,000). Its photoprotective properties against UV-A induced damages were assessed in our mouse model. Three month old albino hairless mice were exposed for 1 y to suberythemal doses (35 J/cm2) of UV-A obtained from a xenon source filtered through a WG 345 filter. One group of animals was exposed untreated, the other received a formulation containing 5% of the sunscreen prior to irradiation. At the end of the study the cutaneous properties of protected mice were compared to those of unprotected animals and to 3 and 15 month old unirradiated controls. We found that the visible changes induced by UV-A irradiation were mainly sagging and wrinkling. Histological and electron microscopic alterations consisted of hyperkeratosis, increased density of elastic fibers with alteration of fiber orientation and increased glycosaminoglycan deposits. Biochemical changes consisted of decreases in total collagen and collagen hydroxylation and increases in both collagen III/I + III ratio and fibronectin biosynthesis. All these changes were reduced or abolished by the sunscreen.

Animals↗
PubMed1991

Age-dependent variations of the biosyntheses of fibronectin and fibrous collagens in mouse skin.

Skin explant cultures from hairless mice of increasing age were incubated with radioactive precursors in order to determine the age-dependent variations of the biosyntheses of fibronectin and fibrous collagens (types I and III). Total collagen synthesis expressed as a percentage of total protein synthesis did not vary with age but, if expressed as micrograms hydroxyproline per mg wet weight of skin, decreased by about 30% between 2 and 22 months of age. Hydroxylation of collagen, expressed as the ratio of 3H-hypro over 3H (pro + hypro) incorporated in freshly synthesized collagen, decreased with age by about 40% between 2 and 22 months of age. The proportion of type III collagen expressed as % of type I + type III collagens increased progressively with age by about 25% at 12 months to 60% at 22 months of age. Fibronectin biosynthesis, determined by immunoprecipitation of 35S-methionine labeled peptides in SDS-extracts of skin increased progressively with age from about 2% of total incorporated radioactivity in fibronectin at 2 months to 4% at 22 months. Plasma fibronectin, of hepatic origin, was shown already to increase with age in humans. It appears thus that the expression of genes coding for extracellular matrix macromolecules is under age-dependent regulation. This regulation appears to be different for the investigated macromolecules.

Aging↗
PubMed1989

Miniature pig as an animal model to study photoaging.

Seven miniature pigs were irradiated thrice weekly over a 14 months period with suberythematogenic doses of UVB and UVA. Another seven were not exposed, to record innate aging changes. Chronic irradiation induced the following changes: 1. Increased scaling, with thickening of the stratum corneum and decreased reactivity to acetic acid. 2. Increased minimum erythema dose, corresponding to decreased transmission of UV-radiation through isolated epidermis. 3. Increased elastic fibers, accompanied by strong deposition of glycosaminoglycans in the upper dermis. 4. Increased laxity with greater extensibility to a deforming torque. 5. Increased density of vessels. 6. More disorderly arrangement of collagen bundles with minor alterations in collagen biochemistry. These changes mimic those in photoaged human skin but are milder in degree, attributable to the low total dosage of ultraviolet radiation.

Aging↗
PubMed1978

[Clinical evaluation of a topical ethyl lactate treatment of acne vulgaris (author's transl)].

The efficacy of a lotion containing 10 p. 100 ethyl lactate was evaluated in a double-blind clinical trail during 8 weeks. Test subjects were 45 male and female patients with polymorphous juvenile acne. They were divided into three groups and received the following treatments: Group A: oral antibiotic + topical placebo lotion. Group B: oral antibiotic + topical ethyl lactate lotion. Group C: topical ethyl lactate lotion only. The lotions were applied twice daily with a swab of cotton-wool. The antibiotic doses (tetracycline hydrochloride) were decreased as the trial progressed. Patients were examined before the trial, then after 1, 2, 4, 6 and 8 weeks. At each visit, comedones, microcysts, pustules and nodules were counted on a skin surface of 9 cm2. Colour photographs were taken before and at the end of the trial and served for counting inflammatory lesions. Also, at each visit, skin lipids were sampled and analysed by I. R. spectrophotometry in order to asses the effect of the treatments on the free fatty acid/triglyceride ratio. The treatments showed similar effectiveness as regards comedones and microcysts, but only treatments A and B succeeded in reducing the number of inflamed lesions. With respect to the latter, the combined treatment B (oral antibiotic + topical ethyl lactate lotion) was more effective than treatment A (oral antibiotic + topical placebo); both treatments were more effective than treatment C (topical ethyl lactate lotion only). At the end of the trial, all three groups of patients showed significant overall improvement, but acne scores (total number of lesions) did not differ significantly between treatments. When comparing these results with literature data concerning the effects of vitamin A acid and benzoyl peroxide, it appears that ethyl lactate is slightly less effective for topical treatment of acne than vitamin A acid, but slightly more effective than benzoyl peroxide. It should be underlined that ethyl lactate is well tolerated by the skin. Analysis of sebum samples failed to yield evidence of a decrease in the free fatty acid/triglyceride ratio in skin lipids of the patients irrespective of the treatment applied.

Acne Vulgaris↗
PubMedDate not supplied

Histological evaluation of a topically applied retinol-vitamin C combination.

Two double-blind studies versus vehicle were carried out to investigate the effects of a topically applied retinol plus vitamin C combination on epidermal and dermal compartments of aged or photoaged human skin. The two studies were performed on postmenopausal women who were selected for treatment based on the mild level of elastosis of their facial skin. At completion of treatment, skin biopsies were collected and processed for classical histology and immunohistochemistry. In the first study (aged skin), 8 volunteers applied the retinol- and vitamin C-containing preparation on the ventral side of one elbow and the vehicle on the other elbow twice daily for 3 months. After the 3-month treatment we observed histological changes mainly within the epidermis. The stratum corneum was thinner with a compact pattern, whereas the epidermal proliferation increased, resulting in a thickening of the viable epidermis. Moreover, the interdigitation index was increased. In the second study (photoaged skin), 11 volunteers were divided in two groups; one applied the retinol- and vitamin C-containing preparation and the other one the vehicle on their face twice daily for 6 months. Facial skin samples presented histologic hallmarks of photoaging, i.e. accumulation of elastotic material in the papillary dermis. After the 6-month topical treatment, the observed histological changes were mainly concentrated at the dermal level. Both treated and control groups showed the same distribution pattern of type I procollagen, however, the high level of type III procollagen originally observed in photoaged skin was reduced in the retinol- and vitamin C-treated group, resulting in a lower type III-to-type I procollagen ratio. Furthermore, a wide band of eosinophilic material just beneath the epidermis, devoid of oxytalan fibers and forming the 'grenz zone', appeared more frequently and was larger in the retinol- and vitamin C-treated group. In conclusion, our results show that repeated topical application of a preparation containing both retinol and vitamin C is able to reverse, at least in part, skin changes induced by both chronologic aging and photoaging.

Administration, Cutaneous↗