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Biomedical subjects

Christian Tran

Publications and source records attributed to Christian Tran.

13 recordsLinked to original sources
PubMed2006

Production and clearance of cyclobutane dipyrimidine dimers in UV-irradiated skin pretreated with 1% pimecrolimus or 0.1% triamcinolone acetonide creams in normal and atopic patients.

BACKGROUND: Ultraviolet (UV)-induced pyrimidine dimers are an early step in skin carcinogenesis, which is accelerated in the setting of long-term immunosuppression with systemic calcineurin inhibitors. It is not known whether topical application of calcineurin inhibitors exposes to a similar risk. OBJECTIVE: To assess the formation and clearance of UV-induced dipyrimidine dimers in human epidermis treated with topical pimecrolimus as compared to topical steroid, vehicle and untreated control. METHODS: Pretreated buttock skin of 20 human volunteers with (10) or without (10) atopic dermatitis was exposed to two minimal erythema doses (MED) of simulated solar radiation. DNA was extracted from epidermis 1 and 24 h postirradiation. Pyrimidine dimers were visualized by immuno slot blots and quantified by chemoluminescence image analysis. RESULTS: One-hour postirradiation, pimecrolimus-treated epidermis contains less DNA damage as compared to untreated control, but there were no statistically significant differences between pimecrolimus, triamcinolone acetonide and vehicle. Dimer levels at 24 h postirradiation showed no significant differences between different treatments. CONCLUSION: Treatment with pimecrolimus cream, triamcinolone acetonide cream and vehicle is not associated with increased epidermal DNA damage at 1 and 24 h post-UV exposure.

Administration, Cutaneous↗
PubMed2006

Retinoic acid synergistically enhances the melanocytotoxic and depigmenting effects of monobenzylether of hydroquinone in black guinea pig skin.

Monobenzylether of hydroquinone (MBEH) has long been utilized for the depigmentation therapy of patients with extensive vitiligo. In this approach, the normally pigmented areas surrounding vitiligo lesions are depigmented to achieve a uniform skin tone. One of the important disadvantages of MBEH therapy, however, is the resistance of a considerable number of vitiligo patients against the depigmenting effect of this agent. We have previously proposed that the glutathione-dependent cytoprotection of melanocytes can be impaired through the inhibition of the enzyme glutathione S-transferase by retinoic acid (RA). The combination of RA with melanocytotoxic agents could thus lead to increased susceptibility of melanocytes to such compounds. In this study we have shown, for the first time, that the melanocytotoxic and depigmenting effects of MBEH are synergistically enhanced when it is combined with RA. The treatment of black guinea pig skin with RA (0.025%) alone induced no significant changes in the number of epidermal melanocytes and no skin depigmentation. On the other hand, MBEH (10%) produced mild to moderate skin depigmentation and reduced the average number of melanocytes from 76 (+/-5)/field (magnification: x 40) in control sites, to 42 (+/-6)/field in the depigmented skin. The RA (0.025%)-MBEH (10%) combination, however, produced a complete degree of depigmentation in the majority of treated sites after 10 days of application and reduced the average number of melanocytes to only 6 (+/-6)/field. RA-MBEH combination serves as a very potent skin depigmenting formula and now awaits future assessments of its potential use for the treatment of extensive vitiligo.

Animals↗
PubMed2006

Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism.

BACKGROUND: Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present. METHODS AND FINDINGS: Atrophic skin displays a decreased hyaluronate (HA) content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF) on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da) but not with small-size HAF (HAFs; <50,000 Da) or large-size HAF (HAFl; >400,000 Da) induced wild-type (wt) but not CD44-deficient (CD44-/-) keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF) and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3), and by tissue inhibitor of metalloproteinase-3 (TIMP-3). CONCLUSIONS: Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.

Adult↗
PubMed2005

Pharmacology of RALGA, a mixture of retinaldehyde and glycolic acid.

BACKGROUND: Retinoids and alpha-hydroxy acids (AHAs) are major compounds in topical therapy. They exert distinct but potentially complementary activities. However, their association is limited by their respective irritating potential. Recently, the first association between a retinoid and an AHA has been achieved; this formulation (RALGA) associates retinaldehyde (RAL)--a precursor of retinoic acid (RA)--and glycolic acid (GA)--an AHA. OBJECTIVE: To study the pharmacological properties of RALGA. METHODS: The bioavailability of RAL into the skin after topical RALGA was studied by HPLC, and its bioconversion to RA was analysed by measuring the enzyme activity of retinaldehyde dehydrogenase and the RA content in the epidermis and dermis. The retinoid activity of RALGA was studied on the modulation of Hhb4 keratin mRNA on the tail of C57BL/6 mice, and its comedolytic properties on the size and density of dermal cysts and the morphology of sebaceous glands in hairless mice. RESULTS: Epidermal and dermal concentrations of RAL and RA were higher after RALGA treatment, as compared to both RAL 0.1% alone and RA 0.05% alone; this indicates that the presence of GA favours the bioavailability and biotransformation of RAL into RA. The retinoid activity of RALGA (suppression of Hhb4 mRNA keratin) was similar to that of RAL alone, indicating that the presence of GA does not interfere with specific retinoid activity; GA alone had no effect in this test, which confirms the specificity of Hhb4 mRNA keratin modulation for retinoid activity. The diameter and the density of dermal cysts as well as the size of sebaceous glands were significantly decreased by RALGA. CONCLUSION: These observations indicate that the addition of an AHA such as GA to a retinoid such as RAL results in a better bioavailability of the retinoid, thus a higher delivery of RA, which potentiates the biological activities of the retinoid. This combination allows a delivery of high amounts of RA in the skin while preventing the side-effects usually observed with high concentrations of topical RA.

Aldehyde Oxidoreductases↗
PubMed2005

Topical calcineurin inhibitors decrease the production of UVB-induced thymine dimers from hairless mouse epidermis.

BACKGROUND: An increased incidence of ultraviolet-light-related skin tumours is a well-known problem in patients undergoing posttransplantation immunosuppression with systemic calcineurin inhibitors such as cyclosporine A or tacrolimus. UV-related carcinogenesis as a consequence of long-term treatment of sun-exposed sites with topical calcineurin inhibitors is therefore of theoretical concern. RESULTS: In this study, we show that tacrolimus acts as a UVB filter when incorporated into liposome membranes. In hairless mice pretreated with 1% pimecrolimus cream, 0.1% tacrolimus ointment or vehicle, the amount of epidermal thymine dimers, measured 1 h after 1 J/cm2 of UVB irradiation, was decreased by 89, 84 and 47%, respectively, as compared to untreated mice. Forty-eight hours after UVB irradiation, 97, 89 and 93% of epidermal thymine dimer levels were removed in pimecrolimus-, tacrolimus- or vehicle-treated mice, respectively. In contrast, 69% of thymine dimers, originally present in much higher amounts than in treated mice, were removed from untreated controls. UVB-induced apoptosis was less pronounced in treated mice. CONCLUSION: Taken together, these results suggest that topical calcineurin inhibitors prevent DNA photodamage due to a filter effect of both vehicle and active components, whereas they do not affect the clearance of DNA photoproducts.

Administration, Cutaneous↗
PubMed2005

Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case.

We have previously shown that the peroxidase inhibitor methimazole (1-methyl-2-mercapto imidazole; MMI) is a noncytotoxic inhibitor of melanin production in cultured B16 melanocytes. It was further demonstrated that the topical application of 5% MMI on brown guinea pig skin for 6 weeks causes a significant reduction in the amount of epidermal melanin, resulting in visually recognizable cutaneous depigmentation. Herein, we report a 27-year-old male with postinflammatory hyperpigmentation (due to acid burn), successfully treated with topical MMI as a new skin depigmenting agent. Topical 5% MMI caused a moderate to marked improvement of the hyperpigmented lesions within 6 weeks of once-daily application. Topical MMI was well tolerated by the patient and did not affect the level of serum thyroid hormones (free thyroxin, free triiodothyronine and the thyroid-stimulating hormone). Unlike most known depigmenting agents, such as hydroquinone and kojic acid, MMI is a noncytotoxic, nonmutagenic compound, and it is possible that MMI could serve as a novel agent for the treatment of hyperpigmentary disorders in human.

Administration, Cutaneous↗
PubMed2004

Topical beta-carotene is converted to retinyl esters in human skin ex vivo and mouse skin in vivo.

Human epidermis contains endogenous retinoids (retinol and retinyl esters) and carotenoids (mostly beta-carotene). Previous studies have shown that the enzymes involved in retinoid metabolism are present in human epidermis. There is still a controversy about the presence in the skin of the enzymes able to convert beta-carotene into vitamin A (retinol), although a recent study demonstrated the conversion of beta-carotene into retinol in human cultured epidermal cells. In this study, we addressed the question of the possible bioconversion of topical beta-carotene into vitamin A or derivatives by human and mouse skin. Surgically excised human abdominal skin was mounted on Franz perfusion chambers to assess the cutaneous penetration of topical beta-carotene as well as its metabolism, after a 24-h incubation period, whereas hairless mice received topical beta-carotene 24 h before assaying epidermal beta-carotene and retinoid concentrations. Epidermal retinoid and beta-carotene concentrations were determined by high-pressure liquid chromatography. Topical beta-carotene penetrated well into human and mouse epidermis and induced a 10-fold (human) and a threefold (mouse) increase of epidermal retinyl esters, which demonstrates that topical beta-carotene is converted into retinyl esters by human and mouse epidermis and thus appears as a precursor of epidermal vitamin A.

Administration, Topical↗
PubMed2003

Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet B radiation.

Retinyl esters, a storage form of vitamin A, concentrate in the epidermis, and absorb ultraviolet radiation with a maximum at 325 nm. We wondered whether these absorbing properties of retinyl esters might have a biologically relevant filter activity. We first used an in vitro model to assess the photoprotective properties of retinyl palmitate. We then applied topical retinyl palmitate on the back of hairless mice before exposing them to 1 J per cm2 ultraviolet B, and assayed the levels of thymine dimers produced in epidermal DNA 2 h following ultraviolet B exposure. Finally, we applied topical retinyl palmitate or a sunscreen on the buttocks of human volunteers before exposing them to four minimal erythema doses of ultraviolet B; we assayed the levels of thymine dimers produced 2 h following ultraviolet B exposure, and determined the intensity of erythema 24 h after ultraviolet B. In vitro, retinyl palmitate was shown to be as efficient as the commercial filter octylmethoxycinnamate in preventing ultraviolet-induced fluorescence or photobleaching of fluorescent markers. The formation of thymine dimers in mouse epidermis was significantly inhibited by topical retinyl palmitate. In human subjects, topical retinyl palmitate was as efficient as a sun protection factor 20 sunscreen in preventing sunburn erythema as well as the formation of thymine dimers. These results demonstrate that epidermal retinyl esters have a biologically relevant filter activity and suggest, besides their pleomorphic biologic actions, a new role for vitamin A that concentrates in the epidermis.

Animals↗
PubMed2002

Oxidative stress-independent depletion of epidermal vitamin A by UVA.

In hairless mice, epidermal vitamin A (retinol and retinyl esters) is strongly decreased following a single exposure to UVB. Here, using the same mouse model, we studied the effects of UVA on epidermal vitamin A content, lipid peroxidation, and CRBP-I expression, as well as the putative prevention of vitamin A depletion or lipid peroxidation by topical alpha-tocopherol. An acute exposure to UVA completely depleted epidermal vitamin A with EC50 of 0.25 and 0.5 J per cm2 for retinyl esters and retinol, respectively; these values were 0.1 J per cm2 for both retinoids under UVB exposure. CRBP-I expression was increased 2-fold 8 h following UVA exposure (10 J per cm2), and this increase persisted for at least 16 h. A single UVA exposure induced a concentration-dependent epidermal lipid peroxidation (EC50 = 3.5 J per cm2) giving rise to 55.4 +/- 4.2 nmol lipid peroxides per g at 20 J per cm2, whereas UVB, up to 1 J per cm2, did not increase the basal concentration of 6.7 +/- 0.9 nmol lipid peroxides per g. On the other hand, topical menadione induced a concentration-dependent lipid peroxidation, but did not affect vitamin A content. Pretreatment with alpha-tocopherol (i) did not inhibit UV-induced vitamin A depletion, (ii) completely inhibited the increased lipid peroxidation induced by UVA or menadione, and (iii) accelerated reconstitution of epidermal vitamin A after UVB but not UVA induced depletion. Thus acute UVA induced both epidermal vitamin A depletion and lipid peroxidation, UVB induced only vitamin A depletion, and menadione induced only a lipid peroxidation; topical alpha-tocopherol prevented lipid peroxidation but not vitamin A depletion. These observations indicate (i) that CRBP-I neither provides protection to UVB- and UVA-induced epidermal vitamin A depletion, nor interferes significantly with reconstitution, and (ii) that the UV-induced vitamin A depletion and lipid peroxidation in mouse epidermis are unrelated processes. UV light does not destroy epidermal vitamin A through an oxidative stress but probably by a photochemical reaction in which UV radiations at about 325 nm give the corresponding activation energy.

Administration, Topical↗
PubMed2002

A new model using liposomes that allow to distinguish between absorption and oxidative properties of sunscreens.

We have developed a new model using liposome-encapsulated fluorescent probes, aiming at assessing both the physical and the biological protection provided by filter molecules such as those incorporated in sunscreens. The fluorescent indicator Indo-1 or 2',7'-dichlorofluorescin (DCFH) was inside the liposomes, in the aqueous inner compartment, whereas the filter molecules octyl methoxycinnamate (OMC), benzophenone-3 (BP3) or avobenzone, widely used in sunscreens, were incorporated into liposome membranes. When liposome suspensions were placed in a fluorometer cuvette exposed to an incident UV beam, the decrease of Indo-1 fluorescence as a function of filter concentration was related to the extinction coefficient of the filters. On the other hand, when liposome suspensions were exposed to moderate UVB doses allowing Indo-1 photobleaching, the remaining intact Indo-1 was linked to the protection provided by filter-containing liposome membranes. Finally, when liposome-encapsulated DCFH was exposed to UVB, the degree of photo-oxidation of the fluorescent probe into 2',7'-dichlorofluorescein accounted for the photoprotection provided by the filter contained in liposome membranes. BP3 was more potent and slightly less efficient than the other two filters in preventing Indo-1 fluorescence; all three filters provided a similar concentration-dependent protection of Indo-1 photobleaching, whereas only OMC was able to prevent the photooxidation of DCFH. The liposome model presented here has the advantage of combining both physical and biological parameters to assess the photoprotection provided by filter molecules, and the lack of photoprotection by two sunscreen molecules having a good filter capacity highlights the need for such a biological parameter when talking about the safety of sunscreens.

Absorption↗
PubMedDate not supplied

UVA and UVB decrease the expression of CD44 and hyaluronate in mouse epidermis, which is counteracted by topical retinoids.

The transmembrane glycoprotein CD44 is currently thought to be the main cell surface receptor for the glycosaminoglycan hyaluronate. We previously showed that (1) CD44 regulate keratinocyte proliferation; (2) topical retinoids dramatically increase the expression of CD44, hyaluronate and hyaluronate synthase (HAS)s in mouse epidermis; (3) topical retinaldehyde restores the epidermal thickness and CD44 expression which are correlated with clinical improvement in lichen sclerosus et atrophicus lesions; and (4) retinaldehyde-induced proliferative response of keratinocytes is a CD44-dependent phenomenon and requires the presence of HB-EGF, erbB1 and matrix metalloproteinases. In this study, we analyzed the effect of UV irradiation on the levels of epidermal hyaluronate and CD44 in mice, as well as its potential prevention by topical retinoids. UVA (10 J/cm(2)) or UVB (1 J/cm(2)) irradiation significantly decreased the expression of CD44 and hyaluronate in the epidermis of hairless mice after 2 h. Expression of both epidermal CD44 and hyaluronate was reconstituted within 24 h. Topical application of retinaldehyde for 3 days prior to UVA or UVB irradiation prevented the decrease of CD44 and hyaluronate expression. Topical retinol and retinoic acid also increased the basal levels of epidermal CD44 and hyaluronate, although their preventive effect on UV-induced decrease of these molecules was less pronounced as compared to topical retinaldehyde. These data confirm the relationships between retinoid and CD44 pathways, although the primary target(s) of UV leading to CD44 and hyaluronate degradation remain to be elucidated.

Administration, Topical↗