Abstract: Rosacea is treated with a composition comprising an antimicrobial and at least one of an anti-inflammatory and a non-retinoid inhibitor of at least one of NF-k&bgr;, AP-1, MMPs, adhesion molecules, TLRs, and CD14. The composition may further comprise a retinoid.

Abstract: Many human conditions, often skin conditions, are treated topically or orally with a retinoid such as retinoic acid or acetretin, which treatment often has the side effect of dry, irritated, and/or peeling skin. The use of soaps, detergents, chemical irritants, and such can also cause these same side effects. These side effects can be reduced or eliminated by the topical administration of an inhibitor, especially a natural inhibitor, of the epidermal growth factor receptor (EGFR), administered concomitantly with the retinoid, separately from the retinoid (such as on an as needed basis), or both. Administration of the two together is facilitated by a composition suitable for topical application and comprising both the retinoid and a natural EGFR inhibitor. Preferred natural inhibitors are genistein and other isoflavones extracted from natural occurring substances, or simple derivatives of such substances.

Abstract: The invention is based on selective inhibition of the enzyme (MMP-1), which causes the dermal matrix damage in humans, while sparing the enzyme(s) (MMP-9 and perhaps MMP-2) which not only do not cause the damage (based on extrapolation from our in vitro collagen gel system to real skin) but actually “clear away” the damage produced by MMP-1 to restore normal function to the skin. Matrix metalloproteinase-1 (MMP-1; fibroblast collagenase) is induced by UV radiation from the sun and is naturally elevated in old age. Human fibroblasts exposed to the degradation products of MMP-1 contract collagen, but when this debris is removed from their environment, the fibroblasts behave normally. Inhibiting MMP-1 but sparing enzymes that remove the debris improves human skin after onslaught from solar UV radiation, old age, and acne.

Abstract: Compositions and methods are provided for ameliorating various effects of UVA and UVB radiation from the sun. The compositions include an ingredient that prevents photoaging from MED and subMED radiation, namely a direct acting MMP (matrix metalloproteinase) inhibitor. The compositions can include another, indirect MMP inhibitor, such as a retinoid, certain other compounds (such as N-acetylcysteine, 2-furildioxime, and vitamin C), tetracyclines, and if a retinoid is used then in addition optional compounds that inhibit the CYP-26 (chytochrome P-450) mediated metabolism of retinoids such as ketoconazole and other azole compounds. In the method, the composition is applied prior to exposure to the sun; for direct acting MMP inhibitors, application should be just prior to exposure, and if indirect inhibitors such as retinoids are used in addition, then application of the indirect inhibitor should be at least about seven hours prior to exposure.

Abstract: Compositions and methods are provided for ameliorating various effects of UVA and UVB radiation from the sun. The compositions including an ingredient that prevents photoaging from MED and subMED radiation, such as a retinoid, certain other compounds (such as N-acetylcysteine, 2-furildioxime, and vitamin C) and optionally other MMP inhibitors such as tetracyclines and/or compounds that inhibit the P-450-mediated metabolism of retinoids such as ketoconazole and other azole compounds. In the method, the composition is applied prior to exposure to the sun; depending upon the ingredients used in the composition, application should be from 7 to 48 hours prior to exposure. Compounds that prevent erythema (skin reddening, sunburn) do not necessarily protect against UV-mediated elevation of MMP levels and activity, and similarly compounds that prevent UV-mediated elevation of MMP levels and activity are not necessarily effective against UV-induced erythema.

Abstract: UVB radiation of about 300-310 nm wavelength and UVA radiation of about 380-390 nm wavelength, each of which exists in solar light, induces MMPs (matrix metalloproteinases) in human skin that degrade the collagen of the dermal matrix. This degradation contributes to photoaging of human skin, which can be prevented by blocking these wavelengths of solar radiation. In contrast, diseases that result in the overproduction of collagen can be treated by exposing the affected with to radiation having wavelengths in those regions, for these wavelengths not only induce MMPs but also inhibit collagen biosynthesis. For lighter skinned people so affected, the UVA wavelengths are preferred because of the reduced amount of erythema, whereas dark skinned people can be treated with the UVB radiation because they generally do not suffer from erythema.

Abstract: Photoaging of human skin, such as evidenced by the increased presence of matrix metalloproteinases after exposure to UV radiation, is prevented by pretreating the skin with an inhibitor of epidermal growth factor receptor (EGF-R) prior to exposure. Such inhibitor are preferably natural, an example of which is genistein. Compositions used for such purposes preferably include an EGF-R as well as another MMP inhibitor, such as a retinoid.

Abstract: The deleterious effects of the passage of time on human skin (i.e., chronological aging of human skin) can be prevented and treated with the topical application of a retinoid, preferably retinol. We have found that some of the same pathways (namely the stress-activated pathways, SAPs) activated in photoaging of human skin (i.e., sun-induced premature skin aging) are similarly elevated in the skin of elderly people. We have also found that other pathways (namely the mitogen-activated ERK pathway) is depressed in the same skin. Treatment of chronologically-aged skin with a retinoid both inhibits degradation of dermal collagen and promotes procollagen synthesis. Biopsied sections from skin of elderly (80+ years old) show that a single treatment can increase epidermal thickness, improve the dermal collagen density, and promote the formation of rete pegs and dermal papillae (see FIG. 13), and can decrease the amount of c-Jun and increase the amounts of Types I and III procollagen (see FIG. 18).

Abstract: Methods are provided for ameliorating various effects of UVA and UVB radiation from the sun, comprising administering compositions including an ingredient that prevents photoaging from MED and subMED radiation, such as a retinoid, certain other compounds (such as N-acetylcysteine, 2-furildioxime, and vitamin C) and optionally other MMP inhibitors such as tetracyclines and/or compounds that inhibit the P-450-mediated metabolism of retinoids such as ketoconazole and other azole compounds. In the method, the composition is applied prior to exposure to the sun; depending upon the ingredients used in the composition, application should be from 7 to 48 hours prior to exposure. Compounds that prevent erythema (skin reddening, sunburn) do not necessarily protect against UV-mediated elevation of MMP levels and activity, and similarly compounds that prevent UV-mediated elevation of MMP levels and activity are not necessarily effective against UV-induced erythema.

Abstract: Treatment of post-inflammatory hyperpigmentation (PIH) in black and asian skin is accelerated from natural healing by use of a composition comprising a retinoid and/or an inhibitor of cytochrome P-450 enzyme-mediated degradation of retinoids, the composition does not require a conventional depigmenting or bleaching agent (such as a hydroquinone) as is typically used. Healing of PIH lesions is accelerated about three to five times from normal healing. Additionally, these compositions are useful separately for lightening black or asian skin.

Abstract: Described are in vivo methods for testing the activity of vitamin D.sub.3 (1,25-dihydroxyvitamin D.sub.3) and analogs thereof in human skin and for testing the effect of a test compound on said activity. Also described are methods for enhancing the in vivo activity of vitamin D.sub.3 and analogs thereof by coadministering vitamin D.sub.3 or an analog thereof with an RXR ligand, a 24-hydroxylase inhibitor, or a mixture thereof. Preferred RXR ligand materials are retinoids, such as 9-cis retinoic acid, and precursors thereof, such as all trans retinoic acid. Preferred 24-hydroxylase inhibitors are imidazoles, especially those inhibiting cytochrome-P450 oxidative enzymes, such as ketoconazole. Also included is a method for determining whether a candidate compound inhibits 24-hydroxylase activity or induction thereof.

Abstract: Described are in vivo methods for testing the activity of vitamin D.sub.3 (1,25-dihydroxyvitamin D.sub.3) and analogs thereof in human skin and for testing the effect of a test compound on said activity. Also described are methods for enhancing the in vivo activity of vitamin D.sub.3 and analogs thereof by coadministering vitamin D.sub.3 or an analog thereof with an RXR ligand, a 24-hydroxylase inhibitor, or a mixture thereof. Preferred RXR ligand materials are retinoids, such as 9-cis retinoic acid, and precursors thereof, such as all trans retinoic acid. Preferred 24-hydroxylase inhibitors are imidazoles, especially those inhibiting cytochrome-P450 oxidative enzymes, such as ketoconazole. Also included is a method for determining whether a candidate compound inhibits 24-hydroxylase activity or induction thereof.

Abstract: The sequences encoding two isoforms of human cellular retinoid acid binding proteins, CRABP-I and CRABP-II, have been cloned and sequenced and are set forth with their corresponding amino acid sequences. The identification of human CRABP nucleic and amino acid sequences provides the basis for the construction of recombinant human CRABP vectors and expression constructs. Human CRABP can also be synthesized or produced ex vivo, e.g. in bacterial or other production systems. Ligand binding assays, including recombinant and chimeric receptor reporter assays, and direct and competition hybridization assays employing the human CRABP sequences herein described can be used to test drugs for retinoid induction and tissue specificity for pathologies in which retinoids are implicated. Immunoassays utilizing antibodies or binding fragments produced to human CRABP can also be used to test patient tissues for the presence and levels of CRABP for diagnosis and to monitor treatment.

Abstract: Photoaging of undamaged skin due to UVB irradiation exposure is inhibited by administering an agent that inhibits (1) the activity of UVB irradiation inducible MMPs in the skin, (2) one or both of the transcription factors AP-1 and NF-.kappa.B or (3) at least one of the GTP binding proteins or kinases involved in the activation and/or production of jun or fos proteins, which comprise AP-1, to the skin prior to such exposure.

Abstract: Hyperpigmentation of black skin may be treated by topical application of retinoic acid to the skin. Topical application of retinoic acid is also effective for lightening normal black skin.

Abstract: The sequences encoding two isoforms of human cellular retinoid acid binding proteins, CRABP-I and CRABP-II, have been cloned and sequenced and are set forth with their corresponding amino acid sequences. The identification of human CRABP nucleic and amino acid sequences provides the basis for the construction of recombinant human CRABP vectors and expression constructs. Human CRABP can also be synthesized or produced ex vivo, e.g. in bacterial or other production systems. Ligand binding assays, including recombinant and chimeric receptor reporter assays, and direct and competition hybridization assays employing the human CRABP sequences herein described can be used to test drugs for retinoid induction and tissue specificity for pathologies in which retinoids are implicated. Immunoassays utilizing antibodies or binding fragments produced to human CRABP can also be used to test patient tissues for the presence and levels of CRABP for diagnosis and to monitor treatment.

Abstract: Topical application of retinoic acid is effective for increasing the tyrosinase activity in the skin of people having light skin. Thus, topical application of retinoic acid may be used to effect a suntan in people having light skin and as a consequence protect against photodamage.

Abstract: This invention relates to a new method of therapy comprising the administration of a pro-drug to a human or animal, said pro-drug being a compound formed by a therapeutic compound chemically combined with another moiety by a photocleavable bond and irradiating the diseased area with ultraviolet radiation in an amount sufficient to cleave the bond and release the therapeutic compound in a therapeutically effective amount. Specifically disclosed are pro-drugs which are cleaved to therapeutically active medications which are anti-proliferative and anti-inflammatory compounds and the treatment of inflammatory and/or proliferative skin diseases therewith.

Abstract: This invention relates to a new method of therapy comprising the administration of a pro-drug to a human or animal, said pro-drug being a compound formed by a therapeutic compound chemically combined with another moiety by a photocleavable bond and irradiating the diseased area with ultraviolet radiation in an amount sufficient to cleave the bond and release the therapeutic compound in a therapeutically effective amount. Specifically disclosed are pro-drugs which are cleaved to therapeutically active medications which are anti-proliferative and anti-inflammatory compounds and the treatment of inflammatory and/or proliferative skin diseases therewith.

Abstract: This invention relates to a new method of therapy comprising the administration of a pro-drug to a human or animal, said pro-drug being a compound formed by a therapeutic compound chemically combined with another moiety by a photocleavable bond and irradiating the diseased area with ultraviolet radiation in an amount sufficient to cleave the bond and release the therapeutic compound in a therapeutically effective amount. Specifically disclosed are pro-drugs which are cleaved to therapeutically active medications which are anti-proliferative and anti-inflammatory compounds and the treatment of inflammatory and/or proliferative skin diseases therewith.