Do you want to buy antibiotics online without prescription? - This is pharmacy online for you!

Back to Basics
Topical retinoids in the treatment of photoaging
Christina Stefanaki, Alexander Stratigos & Andreas Katsambas
Department of Dermatology, University of Athens, Andreas Sygros Hospital, Athens, Greece A large number of different substances comprise the family of retinoids, which are tradi-tionally described as vitamin A derivatives. By exerting their action through nuclearand cytoplasmic receptors they may improve photoaging. Tretinoin is the best studiedretinoid in the treatment of photoaging. Others such as isotretinoin, retinaldehyde, andtazarotene, although less well studied, have given promising results.
Keywords: retinaldehyde, retinoids, tazarotene, tretinoin melanocytes, reduction and alteration in collagen, twisted Introduction
and dilated microvasculature, and most of all by deposi- Since human life span has expanded, and people more tion of abnormal elastoid material in the upper dermis and more desire a youthful and attractive appearance, a tremendous public and scientific interest has been The beneficial effects of retinoids on photodamaged skin were first noted by Kligman et al.5 in postadolescent Aging of the skin can be the result of a normal process women treated with tretinoin for persistent acne, as long- that involves a lower rate of metabolic activities and is term use of tretinoin led to improvement of skin wrinkling called chronologic aging.1 Chronologically aged skin remains smooth and demonstrates only subtle changes,such as slight atrophy, loss of elasticity, fine wrinkling, and Retinoids
deepening of expression wrinkles. Those changes arealso evident histopathologically. The epidermis appears Retnoids are traditionally described as vitamin A (all- atrophic and flattened. In the dermis fibroblasts, inflam- trans retinol) derivatives. All-trans retinol is oxidized matory cells and the microvasculature are significantly through retinal to its most active metabolite all-trans reduced and the collagen bundles become thick and retinoic acid (tretinoin), which has two stereoisomers, 13-cis retinoic acid (isotretinoin) and 9-cis retinoic On the contrary, photoaging is the consequence of acid.6 Following application to the skin, 50% of topically chronic sun exposure and manifests clinically with fine applied tretinoin remains in its original form, while the and coarse wrinkling, roughness, dryness, laxity, shallow- remaining is either metabolized to hydroxyretinoic acid ness, pigmentary mottling, telangiectasia, and in some cases with preneoplastic and neoplastic changes.3 Photo- Retinoids bind with specific cytoplasmic receptors and aged skin is typified histopathologically by acanthosis, exert their action through nuclear receptors, which loss of epidermal polarity, a basket weave appearance of belong to the family of steroid-thyroid receptors, thus the epidermis, keratinocyte atypia, irregularly dispersed activating transcription and leading to the production ofretinoid-specific proteins.8 Two families of nuclear receptors have been found, Correspondence: A Katsambas, MD, Department of Dermatology, Andreas RAR and RXR, each consisting of three isotypes, Sygros Skin Hospital, University of Athens, 5 Ionos Dragoumi Street, Athens γ.9 RAR receptors bind both tretinoin and 9-cis retin-oic acid, whereas RXR binds only 9-cis retinoic acid.9 Accepted for publication April 05, 2005 2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 130–134
Topical retinoid treatment • C Stefanaki et al. RXR α is the receptor that is predominately expressed in In the first study assessing the efficacy of tretinoin the epidermis, but RAR γ is also strongly expressed.10 emollient cream on 251 subjects with mild or moderate Tretinoin, when applied to the skin, may either bind to recep- photodamage, it was found that tretinoin 0.05% emol- tors as all-trans retinoic acid or its isomer 9- cis retinoic lient cream applied for 6 months was more effective than acid and alter gene transcription, ultimately affecting cell tretinoin 0.01% in reducing wrinkles, skin roughness, growth and differentiation. Cellular retinoic acid-binding and mottled hyperpigmentation.25 Side effects such as protein (CRABP-II), a binding protein for retinoic acid, is xerosis, mild erythema, peeling, burning, and stinging a very sensitive marker of retinoid activity.11 were also dose dependent. Irritant effects decreased with The beneficial effects of retinoids include: improved ongoing use and when persistent they were effectively fine wrinkling, diminished tactile roughness, improved actinic keratoses, and reduced hyperpigmentation.
In the other study conducted by Olsen et al.26 compar- Histopathologically, after treatment with tretinoin the ing different concentrations of tretinoin emollient cream following effects are noted: epidermal hyperplasia, com- (0.05%, 0.01%, and 0.001%) to vehicle, a greater paction of the stratum corneum, thickening of the granu- response was detected in the 0.05% treated group. Over- lar layer, reduced melanocytic hypertrophy, restoration of all improvement was noted in 78% of the subjects using cell porarity, increased angiogenesis, increased new col- the 0.05% cream, whereas only 44% of the subjects in the lagen formation, and normalization of the appearance of vehicle group improved. No significant difference was found between vehicle and tretinoin 0.01% and 0.001%.
The question arises how retinoids improve photodamage.
However, in a study comparing two different concen- Epidermal thickening noted early on after the initi- trations of retinoic acid, 0.025% and 0.1%, no significant ation of therapy and followed after several months by difference was found in clinical efficacy between the two normalization of the epidermal thickness cannot fully concentrations.27 Irritancy was greater with tretinoin 0.1% cream. This study suggested that efficacy is inde- The lightening of mottled hyperpigmentation is prob- pendent to the degree of irritation, in contrast to previous ably the result of increased epidermal turnover, reduced studies that indicated that the effects of tretinoin may be transfer of melanosomes, and inhibition of tyrosinase.16 the result of a nonspecific irritant reaction.28 This issue of It has been found that in retinoic acid-treated skin irritancy and efficacy is not fully resolved. Even a very low there is a significant increase in collagen I synthesis that irritation may be required to produce the desirable clinical is reduced in photoaged skin.12 Anchoring fibrils, consist- ing mainly of collagen VII, are reduced in number in Several studies have been conducted to assess the photoaged skin but increase in number after tretinoin maintenance of the beneficial effects of tretinoin.
treatment.17,18 Furthermore, tretinoin may prevent In one study, 298 photodamaged subjects who com- photodamage by inhibiting UVR-induced matrix metallo- pleted 6 months of once-daily use of tretinoin 0.05% proteinases (e.g., collagenase), which induce collagen or 0.1% emollient cream continued to use the same strength for another 6 months.30 Improvement was Despite those findings, the precise mechanisms of re- maintained and furthered with continuous use. Subjects tinoid actions remain to be elucidated.
receiving the 0.01% formulation improved more duringthe second than the first 6 months of treatment, but stilldid not achieve the level of response of the 0.05% group.
Interestingly, some individuals responded only in the The best-studied retinoid on the treatment of photo- extended 6-month period indicating a slow or delayed damage is tretinoin. Since the first observations by response in certain subjects. Side effects declined with Kligman et al.,5 a great number of studies followed. In the continuous use. It was only after 12 months of treatment earliest controlled trials of topical tretinoin therapy that well-organized collagen fibers and normal-appearing for photodamaged skin, both clinical and histological microfibrils were detected in the majority of subjects, improvements were seen with 0.05% and 0.1% which were detectable in the initial 6-month treatment formulations.15,21–24 However, the formulations used were primarily designed for acne, so an emollient base Subjects on tretinoin 0.05% cream were then ran- for tretinoin was developed and two large 24-week domized into three groups: once weekly therapy, three multicenter, double-blind studies followed.25,26 Both times weekly therapy or no therapy.5 The clinical im- studies concluded that the beneficial effects of retinoic provement was sustained with the three times/weekly acid on photodamaged skin are dose dependent.
application regimen and, to a lesser extent, with the once 2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 130–134
Topical retinoid treatment • C Stefanaki et al.
weekly application regimen.31 Discontinuation of ther- whereas tazarotenic acid selectively binds to RARs β and apy for 6 months resulted in some reversal of the benefi- γ.6 In addition to its RARβ and RARγ binding properties, cial effects seen after 1 year on treatment, while ongoing tazarotenic acid reduces abnormal expression of epidermal treatment further enhanced the reduction of photodam- growth factor and keratinocyte transglutaminase I and down-regulates gene expression dependent on activator These results have been confirmed by other studies.
protein 1, a transcription factor associated with cell Ellis et al.15 noted a sustained clinical and histological improvement in the severity of photodamage with con- Preliminary data from a small pilot study in 10 tinuous treatment with tretinoin 0.1% and 0.05% over a patients showed that tazarotene 0.1% gel applied to phodamaged skin for 12 weeks results in a statisticallysignificant increase in epidermal thickness and a signi-ficant decrease in skin roughness.36 Isotretinoin
Tazarotene was evaluated further against photo- Although isotretinoin is less well studied than retinoic damage in two subsequent studies. The first was a double- acid, it has given promising results. Prompted by animal blind, randomized, dose-ranging study involving 349 studies that have demonstrated isotretinoin efficacy in patients.37 Tazarotene 0.1% performed better than lower reversing photoaging, Sendagorta et al.32 conducted a concentrations in reducing fine wrinkling, mottled double-blind controlled trial to assess the efficacy of the hyperpigmentation, lentigines, and elastosis. In the formulation in 776 subjects with mild to moderate second 24-week multicenter, double-blind, randomized, photodamage. Isotretinoin 0.05% applied at night for vehicle-controlled trial enrolling 563 patients, tazaro- 3 months followed by 0.1% cream for 6 months im- tene 0.1% applied once daily achieved greater than 50% proved photoaging without causing any significant global improvement and at least 1 grade improvement of fine wrinkles, mottled hyperpigmentation, lentigines,elastosis, pore size, irregular depigmentation, tactileroughness, and coarse wrinkling.38 Actinic keratoses Retinaldehyde
and telangiectasia were not significantly improved after Human keratinocytes transform retinol into retinal- 24 weeks of treatment. After the first 24 weeks, an open- dehyde and then into retinoic acid — a two-step label extension of tazarotene 0.1% cream followed for enzymatic process involving dehydrogenase. The use of another 28 weeks. Additional clinical improvement was retinaldehyde seemed appealing for two reasons. First, noted, which did not plateau after 52 weeks on treat- it would bypass the first step of retinol oxidation.
ment. Irritation was generally mild or moderate and Furthermore, because only well-differentiated epidermal declined with ongoing treatment, whereas plasma tazaro- cells are capable of oxidizing retinaldehyde to retinoic acid, tenic acid concentration did not exceed the plasma levels a controlled delivery of retinoic acid and a better tolerance would be achieved with retinaldehyde, compared to To assess the efficacy of four different concentrations retinoic acid and its synthetic analogues.33,34 of tazarotene in the treatment of facial photodamage, A study enrolling 125 photodamaged individuals dem- a multicenter, randomized, vehicle-controlled study was onstrated a significant reduction of wrinkles and skin conducted.37 Three hundred forty-nine subjects were roughness after 44 weeks of treatment in both tretinoin randomized to use either tazarotene in various formula- 0.05% and retinaldehyde-treated patients.35 Retinalde- tions (0.1%, 0.05%, 0.025%, 0.01%) or tretinoin 0.05%, hyde was shown to be well tolerated, in contrast to retinoic or vehicle. Tazarotene 0.1% had the best overall efficacy, acid, which caused more local irritation, affecting com- with significant improvement of mottled hyperpigmenta- tion occurring as early as week 8 and of fine wrinkling atweek 12.38 Increased epidermal thickness and reducedmelanin content were the only histopathological features Tazarotene
that changed significantly. Tazarotene 0.1% and tre- Tazarotene is a synthetic retinoid that has been used tinoin 0.05% cream achieved a similar degree of improve- primarily for psoriasis. Tazarotenic acid, the active ment of fine wrinkling and mottled hyperpigmentation, metabolite of tazarotene, appears not to be convertible although a trend toward a quicker response was noted to other potentially active retinoid forms.6 Tazarotene with tazarotene 0.1%. The irritation observed was gener- and tretinoin display different receptor selectivities.
ally of mild and moderate severity and was greater with Tretinoin activates directly the RARs α, β, and γ, the higher tazarotene concentrations.
2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 130–134
Topical retinoid treatment • C Stefanaki et al. hydroxyretinoic acid after topical application of retinoic acid receptor-mediated transcription in vitro. J Clin Invest Retinol has been incorporated into many skin products.
1992; 90: 1269 – 74.
It is extremely unstable and easily degradable to 8 Evans RM. The steroid and thyroid hormone receptor family. Science 1988; 240: 889 – 95.
biologically inactive forms on light exposure.39 Retinyl 9 Chambon PA. A decade of molecular biology of retinoic acid palmitate is the easiest retinoid to formulate and its receptors. FASEB J 1996; 10: 940 – 54.
activity is thought to occur after cutaneous enzymatic 10 Fisher GJ, Talwar HS, Xiao JH et al. Immunological cleavage of the ester bond and subsequent conversion of identification and functional quantification of retinoic acid and retinoid X receptor proteins in human skin. J Biol Chem Experimental data have shown that all-trans retinol 1994; 269: 20629 – 35.
application on normal human skin induces epidermal 11 Elder JT, Astrom A, Petterson U et al. Differential regulation thickening and enhances the expression of CRABP II and of retinoic acid receptors and binding proteins in human CRBP mRNAs and proteins, as does retinoic acid. In con- skin. J Invest Dermatol 1992; 98: 673 – 9.
trast to retinoic acid, it produces only trace erythema.40 12 Griffiths CEM, Russman AN, Majmudar G et al. Restoration However, a much higher concentration of retinol than of collagen formation in photodamaged human skin by
tretinoin (retinoic acid). N Engl J Med 1993; 329: 530 – 5.
retinoic acid is needed to achieve similar results. Retinol 13 Kligman AM, Graham CF. Histological changes in facial appears about 20-fold less potent than retinoic acid.40 skin after daily application of tretinoin for 5 – 6 years. The metabolism of retinol to retinoic acid is required to J Dermatol Treat 1993; 4: 113 –7.
demonstrate biologic activity.41 Other studies have also 14 Brawan J, Gonzalez–Serva A, Nehal K et al. Effects of shown that retinol can produce some of the changes of tretinoin on photodamaged skin: a histologic study. Arch retinoic acid in human skin.42,43 Retinol in stable for- Dermatol 1991; 127: 666 –72.
mulations and appropriate concentrations can produce 15 Ellis CN, Weiss JJ, Hamilton TA et al. Sustained improvement retinoid effects, but few formulations meet this stand- with prolonged topical tretinoin for photoaged skin. J Am ard.44 So far, no controlled studies exist to compare the Acad Dermatol 1990; 23: 629–37.
efficacy of retinol to retinoic acid. It is likely that much 16 Orlow SJ, Chakraborty AK, Pawalek JM. Retinoic acid is a higher concentrations would have a better activity profile.
potent inhibitor of inducible pigmentation in murine and
hamster melanoma cell lines. J Invest Dermatol 1990; 94:
461– 4.
17 Craven NM, Watson REB, Jones CJP et al. Clinical features of photodamaged human skin are associated with a reduction Among the variety of topical agents that are used to treat in collagen VII. Br J Dermatol 1997; 137: 344 –50.
photodamaged skin, certainly retinoids play a pivotal 18 Woodley DT, Zelickson AS, Briggaman RA et al. Treatment role. The cosmetic industry will certainly formulate new of photoaged skin with topical tretinoin increases retinoid products with better efficacy and a better profile epidermal–dermal anchoring fibrils: a preliminary report.
J Am Med Assoc 1990; 263: 3057–9.
19 Fisher GJ, Datta SC, Talwar HS et al. Molecular basis of sun-induced premature skin ageing and retinoid References
antagonism. Nature 1996; 379: 335–9.
1 Fenske NA, Lober CW. Structural and junctional changes in 20 Fisher GJ, Wang ZQ, Datta SC et al. Pathophysiology of aging human skin. J Am Acad Dermatol 1986; 15: 571– 85.
premature skin ageing induced by ultraviolet radiation. 2 Lavker RM, Zheng PS, Dong G. Aged skin: a study by light, N Engl J Med 1997; 337: 1419–28.
transmission electron and scanning electron microscopy. 21 Zelikson AS, Mottaz JH, Weiss JS et al. Topical tretinoin in J Invest Dermatol 1987; 88: 44s – 51s.
photoaging: an ultrastructural study. J Cutan Aging Cosmet 3 Green LJ, McCormick A, Weinstein GD. Photoaging and the Dermatol 1988; 1: 41–7.
skin: the effects of tretinoin. Dermatol Clin 1993; 11:
22 Weiss JS, Ellis CN, Headington JT et al. Topical tretinoin improves photoaged skin: a double-blind vehicle-controlled 4 Gilchrest BA. A review of skin ageing and its medical study. JAMA 1988; 259: 527–32.
therapy. Br J Dermatol 1996; 135: 867 – 75.
23 Leyden JJ, Grove GL, Grove MJ et al. Treatment of 5 Kligman AM, Grove GL, Hirose R et al. Topical tretinoin for photodamaged skin with topical tretinoin. J Am Acad photoaged skin. J Am Acad Dermatol 1986; 15: 836 – 59.
Dermatol 1989; 21: 638–44.
6 Del Rosso JQ. Retinoic acid receptors and topical acne 24 Lever L, Kumar P, Marks R. Topical retinoic acid for therapy: establishing the link between gene expression and treatment of solar damage. Br J Dermatol 1990; 122: 91– 8.
drug efficacy. Cutis 2002; 70: 127 – 9.
25 Weinstein GD, Nigra TP, Pochi PE et al. Topical tretinoin for 7 Duell EA, Astrom A, Griffiths CEM et al. Human skin treatment of photodamaged skin: a multicenter study. Arch levels of retinoic acid and cytochrome p -450 derived Dermatol 1991; 127: 659– 65.
2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 130–134
Topical retinoid treatment • C Stefanaki et al.
26 Olsen EA, Katz HI, Levine N et al. Tretinoin emollient cream: retinoic acid treatment. J Am Acad Dermatol 1998; 39:
a new therapy for therapy for photodamaged skin. J Am Acad Dermatol 1992; 26: 215–24.
36 Sefton J, Kligman AM, Kopper SC et al. Photodamage pilot 27 Griffiths CEM, Kang S, Ellis CN et al. Two concentrations of study: a double-blind, vehicle controlled study to assess the topical tretinoin (retinoic acid) cause similar imrovement of efficacy and safety of tazarotene 0.1% gel. J Am Acad photoaging but different degrees of irritation. Arch Dermatol Dermatol 2000; 43: 656 –63.
1995; 131: 1037– 44.
37 Kang S, Leyden JJ, Lowe NJ et al. Tazarotene cream for the 28 Marks R, Hill S, Barton SP. The effects of an abrasive agent treatment of facial photodamage. Arch Dermatol 2001; 137:
on normal skin and on photodamaged skin in comparison to topical tretinoin. Br J Dermatol 1990; 123: 457–66.
38 Philips TJ, Gottlieb AB, Leyden JJ et al. Efficacy of 0.1% 29 Griffiths CEM. Dowling oration delivered at the tazarotene cream for the treatment of photodamage. Arch Royal College of Physicians, London, Friday 5 June 1998.
Dermatol 2002; 138: 1486 –93.
Retinoids: renaissance and reformation. Clin Exp Dermatol 39 Draelos ZD. Therapeutic moisturizers. Derm Clin 2000; 18:
1999; 24: 329–35.
30 Olsen EA, Katz HI, Levine N et al. Tretinoin emollient cream 40 Kang S, Duell EA, Fisher GJ et al. Application of retinol to for photodamaged skin: results of 48 week, multicenter, human skin in vivo induces epidermal hyperplasia and double-blind studies. J Am Acad Dermatol 1997; 37:
cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or 31 Olsen EA, Katz HI, Levine N et al. Sustained improvement in irritation. J Invest Dermatol 1996; 105: 549–56.
photodamaged skin with reduced tretinoin emollient cream 41 Kurlandsky SB, Xiao JH, Duell EA et al. Biological activity of treatment regimen: Effect of once weekly and three times all-trans retinol requires metabolic conversion to weekly applications. J Am Acad Dermatol 1997; 37: 227–
all-trans-retinoic acid and is mediated through activation of nuclear retinoid receptors in human kertinocytes. J Biol 32 Sendagorta E, Lesiewicz J, Armstrong RB. Topical Chem 1994; 269: 32821–7.
isotretinoin for photodamaged skin. J Am Acad Dermatol 42 Duell EA, Derguini F, Kang S et al. Extraction of human 1992; 27: S15 – 8.
epidermis treated with retinol yields retroretinoids in 33 Saurat JH, Didierjean L, Masgrau E et al. Topical addition to free retinol and retinyl esters. J Invest Dermatol retinaldehyde on human skin: biological effects and 1996; 107: 178– 82.
tolerance. J Invest Dermatol 1994; 103: 770 – 4.
43 Duell EA, Kang S, Voorhes JJ et al. Unoccluded retinol 34 Didierjean L, Carraux P, Grand D et al. Topical penetrates human skin in vivo more effectively than retinaldehyde increases skin content of retinoic acid and unoccluded retinyl palmitate or retinoic acid. J Invest exerts biologic activity in mouse skin. J Invest Dermatol Dermatol 1997; 109: 301–5.
1996; 107: 714 –9.
44 Kligman AM. Cosmetics: a dermatologist looks to the 35 Creidi P, Vienne MP, Ochonisky S et al. Profilometric future: promises and problems. Derm Clin 2000; 18:
evaluation of photodamage after topical retinaldehyde and 2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 130–134


Microsoft word - capsule_sante_censeo_ang_29_2013.doc

No. 29 | 2013 The Highs and Lows of Caffeine In our overworked and sleep-deprived society caffeine has become a quick fix for many people. It wakes up the brain, improves concentration and can make us feel temporarily more alert, even happier. But, if you’re using caffeine as an energy crutch, it may be time to take a closer look at the amount you’re choosing to take in each day a

Vr3 full 2008-09 retail price list eur.xls

VR Dive Computers VR3 HD Single Colour with Multicolour Preview Upgrades Computer Level Upgrades VR Dive Computer Upgrades Open Circuit Air/Nitrox to Open & Closed Circuit Air/NitroxOpen Circuit Air/Nitrox to Open Circuit TrimixOpen Circuit Air/Nitrox to Open & Closed Circuit Air/Nitrox/TrimixOpen and Closed Circuit Air/Nitrox to Open Circuit TrimixOpen and Closed Circui

Copyright © 2010-2014 Medical Pdf Finder