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  • 1
    Language: English
    In: PLoS ONE, 01 January 2018, Vol.13(9), p.e0204318
    Description: BACKGROUND AND OBJECTIVES:Microneedling therapy is a widely used technique in dermatology. However, little is known about the underlying molecular effects of this therapy on extracellular matrix remodeling, wound healing, and inflammation. The aim of this study was to examine morphological and molecular changes caused by microneedling treatment in a standardized in vitro full-thickness 3D model of human skin. MATERIALS AND METHODS:A microneedling device was used to treat full-thickness 3D skin models. Specimens were harvested at specified time points and qRT-PCR and microarray studies were performed. Frozen sections were examined histologically. RESULTS:Microneedling treatment caused morphological changes in the skin model resulting in an almost complete recovery of the epidermis five days after treatment. Microarray analysis identified an upregulation of genes that are associated with tissue remodeling and wound healing (e.g. COL3A1, COL8A1, TIMP3), epithelial proliferation and differentiation (KRT13, IGF1), immune cell recruitment (CCL11), and a member of the heat shock protein family (HSPB6). On the other hand, we detected a downregulation of pro-inflammatory cytokines (e.g. IL1α, IL1β, IL24, IL36γ, IL36RN), and antimicrobial peptides (e.g. S100A7A, DEFB4). These data were confirmed by independent RT-PCR analyses. CONCLUSION:We present for the first time the direct molecular effects of microneedling therapy on epidermal keratinocytes and dermal fibroblasts using a standardized 3D skin model. Treatment resulted in histological alterations and changed the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling. This data suggests that skin microneedling plays a role in dermal remodeling, increases epidermal differentiation, and might also have a direct effect on collagen synthesis. These findings may increase our understanding of the molecular mechanisms of human skin repair induced by microneedling therapy and will allow comparisons with competing applications, such as ablative laser therapies.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Lasers in Medical Science, 2017, Vol.32(4), pp.805-814
    Description: The molecular changes in gene expression following ablative laser treatment of skin lesions, such as atrophic scars and UV-damaged skin, are not completely understood. A standardized in vitro model of human skin, to study the effects of laser treatment on human skin, has been recently developed. Therefore, the aim of the investigation was to examine morphological and molecular changes caused by fractional ablative erbium:YAG laser treatment on an in vitro full-thickness 3D standardized organotypic model of human skin. A fractional ablative erbium:YAG laser was used to irradiate organotypic human 3D models. Laser treatments were performed at four different settings using a variety of stacked pulses with similar cumulative total energy fluence (60 J/cm 2 ). Specimens were harvested at specified time points and real-time PCR (qRT-PCR) and microarray studies were performed. Frozen sections were examined histologically. Three days after erbium:YAG laser treatment, a significantly increased mRNA expression of matrix metalloproteinases and their inhibitors (MMP1, MMP2, MMP3, TIMP1, and TIMP2), chemokines (CXCL1, CXCL2, CXCL5, and CXCL6), and cytokines such as IL6, IL8, and IL24 could be detected. qRT-PCR studies confirmed the enhanced mRNA expression of IL6, IL8, IL24, CXCLs, and MMPs. In contrast, the mRNA expression of epidermal differentiation markers, such as keratin-associated protein 4, filaggrin, filaggrin 2, and loricrin, and antimicrobial peptides (S100A7A, S100A9, and S100A12) as well as CASP14, DSG2, IL18, and IL36β was reduced. Four different settings with similar cumulative doses have been tested (N10%, C10%, E10%, and W25%). These laser treatments resulted in different morphological changes and effects on gene regulations. Longer pulse durations (1000 μs) especially had the strongest impact on gene expression and resulted in an upregulation of genes, such as collagen-1A2, collagen-5A2, and collagen-6A2, as well as FGF2. Histologically, all treatment settings resulted in a complete regeneration of the epidermis 3 days after irradiation. Fractional ablative erbium:YAG laser treatment with a pulse stacking technique resulted in histological alterations and shifts in the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling depending on the treatment setting applied. A standardized in vitro 3D model of human skin proved to be a useful tool for exploring the effects of various laser settings both on skin morphology and gene expression during wound healing. It provides novel data on the gene expression and microscopic architecture of the exposed skin. This may enhance our understanding of laser treatment at a molecular level.
    Keywords: Fractional erbium:YAG laser ; Organotypic skin equivalents ; Wound healing ; Gene expression ; Molecular effects ; Resurfacing
    ISSN: 0268-8921
    E-ISSN: 1435-604X
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  • 3
    Language: English
    In: Oncology Research and Treatment, November 2013, Vol.36(11), pp.685-686
    Keywords: Letter to the Editors · Brief an Die Herausgeber ; Side Effects ; Melanoma ; Pulmonary Toxicity ; Braf Inhibitor ; Pneumonia ; Lung Injury ; Inflammation ; Vemurafenib ; Medicine
    ISSN: 2296-5270
    ISSN: 0378584X
    E-ISSN: 2296-5262
    E-ISSN: 14230240
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  • 4
    Language: English
    In: Case Reports in Dermatology, 18 April 2011, Vol.3(1), pp.85-88
    Description: Treatment of pityriasis rubra pilaris is still challenging. We here present a 74-year-old woman who had not experienced stable remission of her skin symptoms during prior treatments including topical and systemic corticosteroids, phototherapy, orally administered acitretin, cyclosporine, methotrexate and adalimumab. A therapy with oral alitretinoin was started and tolerated very well. After a few weeks, skin condition improved significantly and itching and scaling disappeared. The present case shows that alitretinoin might be an alternative in the treatment of recalcitrant pityriasis rubra pilaris type I. Further studies are needed to investigate the benefit of this encouraging result.
    Keywords: Published: April 2011 ; Hair Loss ; Retonoids ; Medicine
    E-ISSN: 1662-6567
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  • 5
    In: JDDG: Journal der Deutschen Dermatologischen Gesellschaft, January 2018, Vol.16(1), pp.66-69
    Description: Byline: Karolin Juliane Pauly, Galina Balakirski, Mosaad Megahed, Albert RAaAaAeA bben, Laurenz Schmi ***** No abstract is available for this article. *****
    Keywords: Medicine;
    ISSN: 1610-0379
    E-ISSN: 1610-0387
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  • 6
    In: Dermatologic Surgery, 2017, Vol.43(7), pp.928-933
    Description: BACKGROUND: Digital mucoid cysts have a tendency for recurrence after operative intervention. Several procedures are in use. OBJECTIVE: Retrospective evaluation for effectiveness, safety and patient satisfaction by using a questionnaire after treatment for digital mucoid cysts with targeted surgical excision and closure by flap-design. MATERIALS AND METHODS: All patients treated with surgical excision for digital mucoid cysts at the Dermatology Department of the Ludwigshafen City Hospital between 2007 and 2011 were evaluated using a specially designed questionnaire. RESULTS: We evaluated 31 patients. The patient group consisted of 65% women, the median age was 61 years. Seventy-eight percent of patients with nail involvement had a marked improvement or complete resolution of this complaint after surgery. A few complications (e.g., redness, pain or hematoma) were observed after treatment, but no patients required oral antibiotics. Patient evaluation of cosmetic outcome revealed high satisfaction with the procedure, nevertheless recurrence of the digital mucoid cysts was observed in 22.5% of all cases. CONCLUSION: Surgical excision in treatment of digital mucoid cysts was shown to be effective and safe. However, possible advantages and disadvantages of this treatment option should be discussed with the patients before a decision on the kind of therapy is reached.
    Keywords: Excision (Surgery) -- Usage ; Excision (Surgery) -- Safety And Security Measures ; Excision (Surgery) -- Research ; Ganglion Cysts -- Care And Treatment ; Ganglion Cysts -- Patient Outcomes ; Ganglion Cysts -- Research ; Treatment Outcome -- Analysis;
    ISSN: 1076-0512
    E-ISSN: 15244725
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  • 7
    Language: English
    In: Skin Pharmacology and Physiology, February 2017, Vol.29(6), pp.281-290
    Description: Tasisulam is a promising antitumor agent with complex pharmacology, which is used as an antiproliferative agent in patients with metastatic melanoma and other solid tumors. Phase 2 melanoma studies showed promising results but had to be stopped because of insufficient tasisulam clearance leading to toxic side effects. To reduce the negative effects of tasisulam, we synthesized a novel sulfonimidamide-based analog to evaluate its antiproliferative effects in comparison to the original compound by performing a cell proliferation assay in melanoma cell lines SKMel23 and A375. The results revealed that the analog had inhibitory effects on the proliferation comparable to tasisulam in both investigated cell lines. These results could contribute to a reduced toxicity of tasisulam and lead to further clinical trials in metastatic melanoma.
    Keywords: Original Paper ; Tasisulam ; Melanoma ; Ly573636 ; Skmel23 Cell Line ; A375 Cell Line ; Chemotherapy ; Sulfonimidamide ; Antiproliferative Effect ; Medicine
    ISSN: 1660-5527
    E-ISSN: 1660-5535
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  • 8
    Language: English
    In: Case Reports in Dermatology, 12 March 2013, Vol.5(1), pp.69-72
    Description: Background: The BRAF inhibitor vemurafenib is state of the art in therapy of patients with malignant melanoma in non-resectable stage III or stage IV and evidence of oncogenetic BRAF mutation. Multiple cutaneous side effects like rash and keratoacanthoma-like lesions have been described so far. Case Report: We report a patient who presented multiple wart-like lesions under therapy with vemurafenib. Histologically we have seen multiple melanocytic nevi with a wart-like appearance. One melanoma in situ developed on the left forearm. Conclusions: Eruptive nevi and induction of melanoma may be a further side effect in patients undergoing a therapy with BRAF inhibitors.
    Keywords: Published: March 2013 ; Melanoma ; Wart-Like Lesions ; Braf Inhibitor ; Eruptive Nevi ; Side Effects ; Vemurafenib ; Melanoma in Situ ; Zelboraf ; Medicine
    E-ISSN: 1662-6567
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  • 9
    In: Experimental Dermatology, September 2018, Vol.27(9), pp.1009-1014
    Description: Atopic dermatitis () is a chronically relapsing, pruritic inflammation of the skin with dryness and disturbed skin barrier function. Recently, we established that ‐31 treatment of human 3D skin models resulted in a disrupted skin barrier phenotype resembling . In this model, we found that ‐31 interferes with the differentiation of keratinocytes and inhibits the expression of terminal differentiation markers. In the present study, we investigated the effects of a ceramide‐containing water‐in‐oil skin care ointment on the physical skin barrier structure and function in disrupted skin barrier models, generated either by using primary normal human epidermal keratinocytes () or HaCaT cells. We observed that the physical skin barrier of the models recovered after daily topical treatment with the ceramide‐containing ointment. Topical application of the ointment prevented downregulation of filaggrin and disorganization of other differentiation markers, such as keratin 10 and β4‐integrin, as demonstrated by immunohistological analysis. The expression of Ki67 was also upregulated in response to the ointment. Furthermore, functional studies revealed that local application of the ointment diminished the increased uptake of fluorescently labelled recombinant allergens of timothy grass (phl p1) in our model. In conclusion, our data revealed that topical application of a ceramide‐containing skin care ointment reduced ‐31 induced impairments of the physical skin barrier and skin barrier function in an in vitro model of the disrupted skin barrier. This standardized model can be utilized in the future to monitor ex vivo effects of various topical therapies on skin morphology, physiology, and gene expression.
    Keywords: Atopic Eczema ; Local Therapy ; Skin Barrier ; Skin Equivalent ; Skin Physiology
    ISSN: 0906-6705
    E-ISSN: 1600-0625
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  • 10
    In: Dermatologic Surgery, 2018, Vol.44(12), pp.1525-1536
    Description: BACKGROUND: Immunosuppression is often considered as an indication for antibiotic prophylaxis to prevent surgical site infections (SSI) while performing skin surgery. However, the data on the risk of developing SSI after dermatologic surgery in immunosuppressed patients are limited. PATIENTS AND METHODS: All patients of the Department of Dermatology and Allergology at the University Hospital of RWTH Aachen in Aachen, Germany, who underwent hospitalization for a dermatologic surgery between June 2016 and January 2017 (6 months), were followed up after surgery until completion of the wound healing process. The follow-up addressed the occurrence of SSI and the need for systemic antibiotics after the operative procedure. Immunocompromised patients were compared with immunocompetent patients. The investigation was conducted as a retrospective analysis of patient records. RESULTS: The authors performed 284 dermatologic surgeries in 177 patients. Nineteen percent (54/284) of the skin surgery was performed on immunocompromised patients. The most common indications for surgical treatment were nonmelanoma skin cancer and malignant melanomas. Surgical site infections occurred in 6.7% (19/284) of the cases. In 95% (18/19), systemic antibiotic treatment was needed. Twenty-one percent of all SSI (4/19) were seen in immunosuppressed patients. CONCLUSION: According to the authorsʼ data, immunosuppression does not represent a significant risk factor for SSI after dermatologic surgery. However, larger prospective studies are needed to make specific recommendations on the use of antibiotic prophylaxis while performing skin surgery in these patients.
    Keywords: Immunocompromised Host ; Dermatologic Surgical Procedures -- Adverse Effects ; Immunosuppression -- Adverse Effects ; Skin Neoplasms -- Surgery ; Surgical Wound Infection -- Etiology;
    ISSN: 1076-0512
    E-ISSN: 15244725
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