| 1. |
- Björntorp Mark, Elisabeth, 1964, et al.
(författare)
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Expression of genes involved in the regulation of p16 in psoriatic involved skin
- 2006
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Ingår i: Arch Dermatol Res. - : Springer Science and Business Media LLC. - 0340-3696. ; 297:10, s. 459-67
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that the up-regulation of the tumour suppressor p16 gene and induction of senescence protect the phenotype of psoriatic involved skin from malignant transformation. On the other hand, Id1, which is inversely correlated with p16 has been shown to be up-regulated in psoriatic involved skin. To test the hypothesis that there may be an altered regulation of p16 in psoriatic involved skin, we have measured genes involved in the Igf-1 receptor signalling through the Ras/MAPK cascade. Igf-1R, IGFBP3, hRas, Ets2, JunB, Egr-1, Id1, MIDA1 and p16 gene expressions were measured using quantitative real-time PCR in total RNA isolated from punch biopsies from psoriatic involved (n = 9) and uninvolved skin (n = 9) and from cutaneous squamous cell cancer (SCC) involved (n = 8) and uninvolved skin (n = 8). The IGFBP3, hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic involved skin compared with uninvolved skin. The p16, JunB and MIDA1 genes were up-regulated in SCC involved skin compared with uninvolved skin. Our results indicate that there may be a balance between the proliferation and induction of senescence in psoriasis. This balance may vary and the psoriatic involved skin represented in this study appears to be in a proliferative state rather than senescence. Furthermore, we suggest that the noted up-regulation of JunB, which has been shown to up-regulate p16, in combination with the previously reported elevation of p16 expression in psoriatic involved skin, may indicate activation of a pathway by which JunB may protect the psoriatic plaque by inducing p16 in an event of malignant stress.
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| 2. |
- Bock (Seifert), Oliver, et al.
(författare)
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Quality of life of patients with keloid and hypertrophic scarring
- 2006
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Ingår i: Archives of dermatological research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 297:10, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- Keloid and hypertrophic scarring represent chronic disfiguring dermatoses with a high resistance to therapy. The aim of our study was to assess for the first time the quality of life of patients with hypertrophic scars and keloids, because they suffer from quality of life impairment as much as patients with other chronic skin diseases. An item-pool was created modifying and supplementing the items of the Questionnaire on Experience with Skin Complaints. This questionnaire was distributed to 100 outpatients with keloids and hypertrophic scars. A factor analysis was used to identify the underlying dimensions. Two scales (psychological and physical impairment) of the questionnaire with nine and five items, respectively, were established. Test–retest reliability of the questionnaire was excellent (corr>0.9). Good validity was suggested by the correlation of physical impairment with pain (P≤0.001), pruritus (P<0.001), and the amount of restriction of mobility (P<0.001). The psychological scale was associated with pain and restriction of mobility, although the correlations were lower. This study demonstrates for the first time an impairment of quality of life in a large group of patients with keloid and hypertrophic scarring.
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| 3. |
- Buraczewska, Izabela, et al.
(författare)
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Long-term treatment with moisturizers affects the mRNA levels of genes involved in keratinocyte differentiation and desquamation
- 2009
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 301:2, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- In a recent study, we showed that long-term treatment with two different moisturizers affected TEWL in opposite directions. Therefore, we decided to examine the effect of these moisturizers on the cellular and molecular level. In a randomized controlled study on 20 volunteers, epidermal mRNA expression of genes essential for keratinocyte differentiation and desquamation after a 7-week treatment with two moisturizers was analyzed. Treatment with one test moisturizer increased gene expression of involucrin, transglutaminase 1, kallikrein 5, and kallikrein 7, while the other moisturizer affected only expression of cyclin-dependent kinase inhibitor 1A. Thus, moisturizers are able to modify the skin barrier function and change the mRNA expression of certain epidermal genes. Since the type of influence depends on the composition of the moisturizer, these should be tailored in accordance with the requirement of the barrier of each individual patient, which merits further investigations.
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| 4. |
- Buraczewska, Izabela, et al.
(författare)
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Moisturizers change the mRNA expression of enzymes synthesizing skin barrier lipids
- 2009
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 301:8, s. 587-594
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study, 7-week treatment of normal human skin with two test moisturizers, Complex cream and Hydrocarbon cream, was shown to affect mRNA expression of certain genes involved in keratinocyte differentiation. Moreover, the treatment altered transepidermal water loss (TEWL) in opposite directions. In the present study, the mRNA expression of genes important for formation of barrier lipids, i.e., cholesterol, free fatty acids and ceramides, was examined. Treatment with Hydrocarbon cream, which increased TEWL, also elevated the gene expression of GBA, SPTLC2, SMPD1, ALOX12B, ALOXE3, and HMGCS1. In addition, the expression of PPARG was decreased. On the other hand, Complex cream, which decreased TEWL, induced only the expression of PPARG, although not confirmed at the protein level. Furthermore, in the untreated skin, a correlation between the mRNA expression of PPARG and ACACB, and TEWL was found, suggesting that these genes are important for the skin barrier homeostasis. The observed changes further demonstrate that long-term treatment with certain moisturizers may induce dysfunctional skin barrier, and as a consequence several signaling pathways are altered.
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| 5. |
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| 6. |
- Faergemann, Jan, 1948, et al.
(författare)
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Pentane-1,5-diol as a percutaneous absorption enhancer
- 2005
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Ingår i: Arch Dermatol Res. - : Springer Science and Business Media LLC. ; 297:6, s. 261-5
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Tidskriftsartikel (refereegranskat)abstract
- Propylene glycol (propane-1,2-diol) is the only diol widely used in dermatology. Pentane-1,5-diol is mainly used as a plasticizer in cellulose products and adhesives, in dental composites and in brake fluid compositions and as a preservative for grain. However, pentane-1,5-diol is also an effective solvent, water-binding substance, antimicrobial agent and preservative and may therefore replace several ingredients in a skin composition. The release of tri-iodothyroacetic acid (TRIAC) and percutaneous absorption of hydrocortisone and mometasone furoate with either pentane-1,5-diol or propane-1,2-diol and 2-methyl-pentane-2,4-diol (hexylene glycol), respectively, as enhancers was compared. The release of TRIAC was 21% higher when pentane-1,5-diol was used as an enhancer instead of propane-1,2-diol. The percutaneous absorption of hydrocortisone through the skin was increased 12 times with propane-1,2-diol compared to 4.4 times with pentane-1,5-diol. However, the percutaneous absorption of hydrocortisone into the skin was 50% higher with pentane-1,5-diol compared to propane-1,2-diol. There was no significant difference, between the original mometasone furoate cream, with 2-methyl-pentane-2,4-diol, and the new cream with pentane-1,5-diol in the amount of mometasone furoate that was absorbed into the skin and through the skin. However, the cosmetic properties of the new mometasone furoate cream was superior to the original mometasone furoate cream, for examples, no bad odour, more even texture, goes better into the skin and has less greasiness. Pentane-1,5-diol can be used as a technology platform, which adds a series of desirable properties to dermatological preparations and enhances product usability. This will result in improved formulations for a series of major and commonly used dermatological drugs. When used in pharmaceutical topical preparations, pentane-1,5-diol will increase the percutaneous absorption of the active substance and it is an efficient antimicrobial agent that will act as an effective preservative in topical formulations. Pentane-1,5-diol is cosmetically attractive, has low risk for skin and eye irritation compared to other diols, low toxicity risk and no bad odour.
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| 7. |
- Forsberg, Sofi, et al.
(författare)
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Regeneration of human epidermis on acellular dermis is impeded by small-molecule inhibitors of EGF receptor tyrosine kinase
- 2008
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 300:9, s. 505-516
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Tidskriftsartikel (refereegranskat)abstract
- The family of human epidermal growth factor receptors (EGFR, HER2-4) exerts key functions in normal and malignant epithelial cells. Both EGFR and HER2 are valuable targets for anti-cancer drugs by interfering with ligand binding, receptor dimerization, or tyrosine kinase activity. A similar therapeutic strategy has been advocated for chronic psoriasis since plaque lesions overexpress EGFR and its ligands. Our aim was to characterize EGFR/HER2 protein expression in skin cultures and to evaluate the effects of tyrosine kinase inhibitors on epidermal outgrowth, morphology, and EGFR activation. Human skin explants were established on cell-free dermis and cultured at the air-liquid interface. The impact of small-molecule HER inhibitors on outgrowth was assayed by fluorescence-based image analysis and histometry. Effects of a dual EGFR/HER2 kinase inhibitor, PKI166, on neoepidermis were studied by immunohistochemistry and Western blot. Receptor immunostaining showed in vivo-like distributions with highest EGFR intensity in the proliferative layers whereas HER2 was mainly expressed by suprabasal keratinocytes. Reepithelialization was associated with EGFR autophosphorylation irrespective of exogenous ligand stimulation. PKI166 inhibited neoepidermal EGFR activation, keratinocyte proliferation, and outgrowth from normal and psoriatic skin explants. The rate of epidermalization in presence of other HER inhibitors varied suggesting that drug specificity, potency, and reversibility determine the dynamic outcome. Overall, agents predominantly targeting EGFR kinase were more efficient inhibitors of epidermal regeneration than an HER2-selective drug. The study illustrates the usefulness of a dynamic skin model and emphasizes the potential of HER-directed approaches to control epidermal growth in hyperproliferative skin disorders.
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| 8. |
- Harvima, IT, et al.
(författare)
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Is there a role for mast cells in psoriasis?
- 2008
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Ingår i: Archives of dermatological research. - : Springer Science and Business Media LLC. - 1432-069X .- 0340-3696. ; 300:9, s. 461-478
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Nordlind, Klas, et al.
(författare)
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Expression of serotonergic receptors in psoriatic skin
- 2006
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 298:3, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P < 0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HT1AR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P < 0.001 and P < 0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P < 0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis.
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| 10. |
- Pavez Loriè, Elizabeth, et al.
(författare)
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Both all-trans retinoic acid and cytochrome P450 (CYP26) inhibitors affect the expression of vitamin A metabolizing enzymes and Retinoic biomarkers in organotypic epidermis
- 2009
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 301:7, s. 475-485
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Tidskriftsartikel (refereegranskat)abstract
- The biosynthesis of retinoic acid (RA) from retinol is controlled by several enzymes, e.g. dehydrogenases (RalDH2, RoDH-4) and retinol-esterifying enzyme (LRAT), whereas its degradation mainly involves CYP26 enzymes. In keratinocytes, RA activates the nuclear retinoid-receptors inducing the transcription of many genes. Here, we examined the effects of RA and the CYP26 inhibitors, liarozole and talarozole, on retinoid metabolism and RA-regulated genes in organotypic epidermis. RA induced the expression of CYP26 enzymes already after 8 h, whereas LRAT exhibited a later response and peaked at 48 h, indicating a feedback induction of retinol esterification. In line with a reduced biosynthesis of RA from retinol after exogenous RA, the expression of RDH16 reduced 80% in response to exogenous RA. The mRNA expression of RA-regulated genes (KRT2, KRT4, CRABPII and HBEGF) was altered within 24 h after RA exposure. In contrast, the CYP26 inhibitors caused only minor effects, except for a clear-cut induction of CYP26A1 only when combined with minute amounts of exogenous RA. Cellular accumulation of exogenous [H-3]RA was higher after talarozole than after liarozole, probably indicating a greater CYP26-inhibitory potency of the former drug. The present study shows that CYP26A1 expression is extremely sensitive to both exogenous RA and increased endogenous RA levels, i.e. due to CYP26 inhibition, and thus an excellent biomarker for retinoid signalling in organotypic epidermis.
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| 11. |
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| 12. |
- Szabad, Gábor, et al.
(författare)
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Human adult epidermal melanocytes cultured without chemical mitogens express the EGF receptor and respond to EGF.
- 2007
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Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 299:4, s. 191-200
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Tidskriftsartikel (refereegranskat)abstract
- We describe a novel chemical mitogen-free in vitro culture technique for obtaining pure melanocyte cultures using normal human adult epidermis as a source. The culture medium consists equal parts of the commercially available Keratinocyte Basal and AIM-V media (both from Gibco), as basal medium, which is supplemented with fetal bovine serum, bovine pituitary extract and recombinant human epidermal growth factor (EGF). Melanocytes harvested from human adult skin proliferate extensively and can be passaged serially up to 10-15 times using this medium. We have verified the identity of the cultured cells by tyrosinase mRNA expression and TRP-1 protein staining. Moreover, we showed that autologous human serum alone, without additional supplements is able to provide sufficient growth support for the cultured cells in the basal medium, making this culture technique suitable for autologous melanocyte transplantation. In this culture system normal human adult melanocytes expressed both EGF receptor (EGFR) mRNA and protein and EGF showed a dose dependent mitogenic effect on the cells. EGF itself had no significant influence on EGFR mRNA expression.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Nyberg, F
(författare)
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SCLE in Sweden, novel findings
- 2009
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Ingår i: ARCHIVES OF DERMATOLOGICAL RESEARCH. - 0340-3696. ; 301:1, s. 40-40
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 18. |
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