Jürgen Lademann

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

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Publications (417)988.12 Total impact

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    ABSTRACT: Optical non-linear multimodal tomography is a powerful diagnostic imaging tool to analyse human skin based on its autofluorescence and second-harmonic generation signals. Recently, the field of clinical non-linear imaging has been extended by adding coherent anti-Stokes Raman scattering (CARS)-a further optical sectioning method for the detection of non-fluorescent molecules. However, the heterogeneity of refractive indices of different substances in complex tissues like human skin can have a strong influence on CARS image formation and requires careful clinical interpretation of the detected signals. Interestingly, very regular patterns are present in the CARS images, which have no correspondence to the morphology revealed by autofluorescence at the same depth. The purpose of this paper is to clarify this phenomenon and to sensitize users for possible artefacts. A further part of this paper is the detailed comparison of CARS and autofluorescence images of healthy human skin in vivo covering the complete epidermis and part of the upper dermis by employing the flexible medical non-linear tomograph MPTflex CARS.
    Physics in Medicine and Biology 09/2015; 60(17):6881-6899. DOI:10.1088/0031-9155/60/17/6881 · 2.92 Impact Factor
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    ABSTRACT: Organisms produce free radicals which are essential for various metabolic processes (enzymatic oxidation, cellular respiration, signaling). Antioxidants are important chemical compounds that specifically prevent the oxidation of substances by scavenging radicals, especially reactive oxygen species (ROS). Made up of one or two unpaired electrons, ROS are free radicals that are highly reactive and can attack other metabolites. By using electron paramagnetic resonance (EPR) spectroscopy, it is possible to measure paramagnetic substances such as free radicals. Therefore the dermal antioxidant activity can be determined by applying semi-stable radicals onto the skin and measuring the antioxidant-induced radical scavenging activity in the skin. In recent years, EPR has been developed as a spectroscopic method for determining the antioxidant status in vivo. Several studies have shown that an additional uptake of dietary supplements, such as carotenoids or vitamin C in physiological concentrations, provide a protective effect against free radicals. Using the EPR technique it could be demonstrated that the radical production in stress situations, such as irradiation with infrared and visible light, was reduced with time. However, not only the oral uptake of antioxidants, but also the topical application of antioxidants, e.g., a hyperforin-rich cream, is very useful against the development of oxidative stress. Regular application of a hyperforin-rich cream reduced radical formation. The skin lipids, which are very important for the barrier function of the skin, were also stabilized.
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    ABSTRACT: Three evolutionary sources create 'primary' reactive oxygen species (ROS) and 'secondary' lipid oxygen species (LOS), forming the human body's 'free radical ground state'. We present evidence for the existence of a universal free radical threshold value (FRTV), defining the borderline between advantageous and adverse effects of free radicals observed above the free radical ground state. Based on standard vitamin D doses, the calculated amount of ∼3.5 × 10(12) rad/mg ROS/LOS tissue represents the tolerated number of free radicals in skin tissue - defined as FRTV. By means of quantitative ESR x-band spectroscopy, the FRTV was experimentally verified using ex vivo human skin irradiated with ultraviolet + visible (UV + VIS), UVB + UVA and VIS light. In addition, we investigated whether this threshold is also existent in internal organs by extending our experiment to fresh porcine liver. Based on the determination of ROS/LOS below and above the FRTV, ROS > LOS was characterized as beneficial and LOS > ROS as deleterious to the organism, respectively. Results of the experiments using porcine liver confirmed the appearance of the FRTV at radical generation ∼3.5 × 10(12) rad/mg. The relation ROS/LOS before and after the FRTV was consistent with the results determined for the skin. We conclude that the FRTV, theoretically calculated and experimentally confirmed, should be considered as a new 'universal body constant'. © 2015 S. Karger AG, Basel.
    Skin pharmacology and physiology 07/2015; 28(5):264-268. DOI:10.1159/000435893 · 1.96 Impact Factor
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    ABSTRACT: Raman spectroscopy has proved its capability as an objective, non-invasive tool for the detection of various melanoma and non-melanoma skin cancers (NMSC) in a number of studies. Most publications are based on a Raman micro-spectroscopic ex vivo approach. In this in vivo clinical evaluation, we apply Raman spectroscopy using a fiber coupled probe that allows access to a multitude of affected body sites. The probe design is optimized for epithelial sensitivity, whereby a large part of the detected signal originates from within the epidermal layer's depth down to the basal membrane where early stages of skin cancer develop. Data analysis was performed on measurements of 104 subjects scheduled for excision of lesions suspected of being malignant melanoma (MM) (n=36), basal cell carcinoma (BCC) (n=39) and squamous cell carcinoma (SCC) (n=29). NMSC were discriminated from normal skin with a balanced accuracy of 73% (BCC) and 85% (SCC) using partial least squares discriminant analysis (PLS-DA). Discriminating MM and pigmented nevi (PN) resulted in a balanced accuracy of 91%. These results lie within the range of comparable in vivo studies and the accuracies achieved by trained dermatologists using dermoscopy. Discrimination proved to be unsuccessful between cancerous lesions and suspicious lesions that had been histopathologically verified as benign by dermoscopy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Experimental Dermatology 05/2015; DOI:10.1111/exd.12768 · 4.12 Impact Factor
  • ChunSik Choe · Jürgen Lademann · Maxim E Darvin
    Journal of dermatological science 05/2015; DOI:10.1016/j.jdermsci.2015.05.004 · 3.34 Impact Factor
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    ABSTRACT: In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects. The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment. Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated. The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.
    Journal of Wound Care 05/2015; 24(5):196-203. DOI:10.12968/jowc.2015.24.5.196 · 1.11 Impact Factor
  • Journal of Biomedical Optics 05/2015; 20(5):51006. DOI:10.1117/1.JBO.20.5.051006 · 2.75 Impact Factor
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    Journal of Biomedical Optics 05/2015; 20(5):51013. DOI:10.1117/1.JBO.20.5.051013 · 2.75 Impact Factor
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    ABSTRACT: The penetration of spherical and rod-like gold nanoparticles into human skin is reported. Several skin preparation techniques are applied, including cryo techniques, such as plunge freezing and freeze drying, and the use of wet cells. Their advantages and drawbacks for observing nanoparticle uptake are discussed. Independent of the particle shape no uptake into intact skin is observed by a combination of imaging approaches, including scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and scanning X-ray microscopy (STXM). These results are discussed along with suitable skin preparation approaches. Experiments on barrier-disrupted skin, i.e. mechanical lesions made by pricking, indicate, however, that gold particles can be identified deep in the dermis, as follows from STXM studies on wet skin samples. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
    Colloidal Nanoparticles for Biomedical Applications X, San Francisco; 04/2015
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    S. Jung · J. Sehouli · R. Chekerov · A. Patzelt · F. Knorr · J. Lademann
    Aktuelle Dermatologie 03/2015; 41(03):77-80. DOI:10.1055/s-0034-1377790
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    Staffan Vandersee · Marc Beyer · Juergen Lademann · Maxim E. Darvin
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    ABSTRACT: In contrast to ultraviolet and infrared irradiation, which are known to facilitate cutaneous photoaging, immunosuppression, or tumour emergence due to formation of free radicals and reactive oxygen species, potentially similar effects of visible light on the human skin are still poorly characterized. Using a blue-violet light irradiation source and aiming to characterize its potential influence on the antioxidant status of the human skin, the cutaneous carotenoid concentration was measured noninvasively in nine healthy volunteers using resonance Raman spectroscopy following irradiation. The dose-dependent significant degradation of carotenoids was measured to be 13.5% and 21.2% directly after irradiation at 50 J/cm² and 100 J/cm² (P < 0.05). The irradiation intensity was 100 mW/cm². This is above natural conditions; the achieved doses, though, are acquirable under natural conditions. The corresponding restoration lasted 2 and 24 hours, respectively. The degradation of cutaneous carotenoids indirectly shows the amount of generated free radicals and especially reactive oxygen species in human skin. In all volunteers the cutaneous carotenoid concentration dropped down in a manner similar to that caused by the infrared or ultraviolet irradiations, leading to the conclusion that also blue-violet light at high doses could represent a comparably adverse factor for human skin.
    Oxidative medicine and cellular longevity 02/2015; 2015:1-7. DOI:10.1155/2015/579675 · 3.36 Impact Factor
  • Sora Jung · Jalid Sehouli · Alexa Patzelt · Jürgen Lademann
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    ABSTRACT: Cutaneous adverse events can have an important negative influence on quality of life and compliance in affected patients. Palmoplantar erythrodysesthesia (PPE; hand-foot syndrome) is a cutaneous toxicity associated with chemotherapeutic treatment, which necessitates treatment interruption or dose reduction in severe cases. This case report of pegylated liposomal doxorubicin-induced PPE shows the influence of mechanical stress on the development of skin lesions in various locations and the importance of patient education and compliance. We present the case of a 43-year-old female patient diagnosed with ovarian cancer and having undergone surgical and chemotherapeutic treatment. The development of extensive grade 3 PPE affecting numerous areas of the body particularly exposed to mechanical pressure necessitated dermatological treatment. The combination of local application of an antioxidant-containing ointment and the patient's compliance made it possible to continue chemotherapy without interruption or dose reduction. The development of PPE often limits the use of chemotherapeutic agents, and this case report can provide a possible therapeutic and preventive strategy for affected patients. © 2015 S. Karger GmbH, Freiburg.
    Oncology Research and Treatment 02/2015; 38(1-2):42-44. DOI:10.1159/000370343
  • C. Wahrlich · S.A. Alawi · S. Batz · J.W. Fluhr · J. Lademann · M. Ulrich
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    ABSTRACT: Background Multi-beam optical coherence tomography (OCT) is a novel method of non-invasive skin imaging allowing the evaluation of tissue at high level of lateral and axial resolution. It permits the horizontal and vertical evaluation of the extent of diseases.Objective Herein, we aimed to validate diagnosing basal cell carcinoma (BCC) by OCT using a newly developed scoring system (‘Berlin Score’-BS). This was based on the predetermined criteria such as dark border underneath the tumour and ovoid structures. Their frequency and distribution in subtypes of BCC were evaluated.Methods The study was conducted in two phases, in which the experience of examiner differed. A total of 127 BCC and 50 other skin diseases were examined. In phase one, students performed the evaluation of skin lesions using the BS, while in phase two an expert performed the scoring in a different subset of patients.ResultsApplication of BS by students revealed sensitivity and specificity of 92.8% (95% CI 85.4–96.8) and 24.1% (95% CI 11.0–43.4) when reaching the lower threshold BS≥8. The most common BCC subtypes were superficial (28.7%) and nodular (22.6%) BCC. Second phase was carried out to verify collected data by a dermatological specialist and expert in using OCT. Increased sensitivity and specificity for OCT amounted to 96.6% (95% CI 80.4–99.8) and 75.2% (95% CI 52.5–90.9). Thereby 88% of all diagnoses were correctly classified confirmed by histopathology.Conclusion Multi-beam optical coherence tomography revealed to be a fast and promising device for assessing lesions by means of BS. Both students, who benefit from practice in handling OCT, and experts are able to perform this procedure. However, experience and training in the interpretation markedly increased sensitivity and specificity of the BS in our study. Moreover, redefinition and refining of the criteria seems necessary and may further increase the diagnostic value of OCT for NMSC.
    Journal of the European Academy of Dermatology and Venereology 01/2015; DOI:10.1111/jdv.12935 · 3.11 Impact Factor
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    ABSTRACT: The increasing interest and recent developments in nanotechnology pose previously unparalleled challenges in understanding the effects of nanoparticles on living tissues. Despite significant progress in in vitro cell and tissue culture technologies, observations on particle distribution and tissue responses in whole organisms are still indispensable. In addition to a thorough understanding of complex tissue responses which is the domain of expert pathologists, the localization of particles at their sites of interaction with living structures is essential to complete the picture. In this review we will describe and compare different imaging techniques for localizing inorganic as well as organic nanoparticles in tissues, cells and subcellular compartments. The visualization techniques include well-established methods, such as standard light, fluorescence, transmission electron and scanning electron microscopy as well as more recent developments, such as light and electron microscopic autoradiography, fluorescence lifetime imaging, spectral imaging and linear unmixing, superresolution structured illumination, Raman microspectroscopy and X-ray microscopy. Importantly, all methodologies described allow for the simultaneous visualization of nanoparticles and evaluation of cell and tissue changes that are of prime interest for toxicopathologic studies. However, the different approaches vary in terms of applicability for specific particles, sensitivity, optical resolution, technical requirements and thus availability, and effects of labeling on particle properties. Specific bottle necks of each technology are discussed in detail. Interpretation of particle localization data from any of these techniques should therefore respect their specific merits and limitations as no single approach combines all desired properties.
    Beilstein Journal of Nanotechnology 01/2015; 6(1):263-80. DOI:10.3762/bjnano.6.25 · 2.33 Impact Factor
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    ABSTRACT: Pregnancy and postpartum adaptation cause an increased formation of free radicals. This is associated with various perinatological diseases, e.g. necrotising enterocolitis. The human body has developed a protective system in the form of the antioxidative potential. The present study was the first to investigate the kinetics of the cutaneous antioxidative status in pregnant women and newborns using a non-invasive spectroscopic method. Eighteen pregnant women and their babies took part in the study. A light-emitting diode-based compact scanner system was used for quick non-invasive measurements of carotenoid antioxidants in human skin based on reflection spectroscopy. It could be shown that the antioxidative status of the expectant mothers significantly declined during labour (p < 0.001) and on day 1 after delivery (p < 0.01). Compared to the mothers, the newborns exhibited a significantly higher cutaneous carotenoid concentration on both day 1 (p < 0.01) and 5 (p < 0.01) after delivery. These results suggest that the oxidative stress due to postpartum adaptation is counteracted by an enhanced reservoir of carotenoid antioxidants in the subcutaneous fatty tissue. The peripartum cutaneous carotenoid level of mothers declines continuously, whereas term newborns show very high cutaneous antioxidant values. © 2015 S. Karger AG, Basel.
    Skin pharmacology and physiology 01/2015; 28(4):189-95. DOI:10.1159/000365520 · 1.96 Impact Factor
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    ABSTRACT: UV irradiation leads to formation of reactive oxygen species (ROS). An imbalance between the antioxidant system and ROS can lead to cell damage, premature skin aging or skin cancer. To counteract these processes, antioxidants such as coenzyme Q10 (CoQ10) are contained in many cosmetics. To improve and optimize cell/ tissue penetration properties of the lipophilic CoQ10, ultra-small lipid nanoparticles (usNLC) were developed. The antioxidant effectiveness of CoQ10-loaded usNLC compared to conventional nanocarriers was investigated in the human keratinocyte cell line HaCaT. Using confocal laser scanning microscopy investigations of the carriers additionally loaded with nile red showed a clear uptake into cells and their distribution within the cytoplasm. By use of the XTT cell viability test, CoQ10 concentrations of 10 to 50μg/ ml were shown to be non-toxic, and the antioxidant potential of 10 μg/ml CoQ10 loaded usNLC in the HaCaT cells was analyzed via electron paramagnetic resonance spectroscopy after cellular exposure to UVA (1J/ cm(2)) and UVB (18mJ/ cm(2)) irradiation. In comparison to the CoQ10-loaded conventional carriers, usNLC-CoQ10 demonstrated the strongest reduction of the radical formation; reaching up to 23% compared to control cells without nanocarrier treatment. Therefore, usNLC-CoQ10 are very suitable to increase the antioxidant potential of skin. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmaceutics and Biopharmaceutics 12/2014; 89. DOI:10.1016/j.ejpb.2014.12.008 · 4.25 Impact Factor
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    ABSTRACT: The investigation of nanoparticle interactions with tissues is complex. High levels of standardization, ideally testing of different material types in the same biological model, and combinations of sensitive imaging and detection methods are required. Here, we present our studies on nanoparticle interactions with skin, skin cells, and biological media. Silica, titanium dioxide and silver particles were chosen as representative examples for different types of skin exposure to nanomaterials, e.g., unintended environmental exposure (silica) versus intended exposure through application of sunscreen (titanium dioxide) or antiseptics (silver). Because each particle type exhibits specific physicochemical properties, we were able to apply different combinations of methods to examine skin penetration and cellular uptake, including optical microscopy, electron microscopy, X-ray microscopy on cells and tissue sections, flow cytometry of isolated skin cells as well as Raman microscopy on whole tissue blocks. In order to assess the biological relevance of such findings, cell viability and free radical production were monitored on cells and in whole tissue samples. The combination of technologies and the joint discussion of results enabled us to look at nanoparticle-skin interactions and the biological relevance of our findings from different angles.
    Beilstein Journal of Nanotechnology 12/2014; 5(5):2363-73. DOI:10.3762/bjnano.5.245 · 2.33 Impact Factor
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    ABSTRACT: PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of -20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles.
    Beilstein Journal of Nanotechnology 11/2014; 5:1944-65. DOI:10.3762/bjnano.5.205 · 2.33 Impact Factor
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    ABSTRACT: The cutaneous carotenoid concentration correlates with the overall antioxidant status of a person and can be seen as biomarker for nutrition and lifestyle. 50 high school students were spectroscopically measured for their cutaneous carotenoid concentrations initially in a static phase, followed by an intervention phase with biofeedback of their measured values, living a healthy lifestyle and on healthy food this time. The volunteers showed higher carotenoid concentrations than found in previous studies. A significant correlation of healthy lifestyle habits and a high antioxidant status could be determined. Subjects improved their nutritional habits and significantly increased their carotenoid concentration during intervention. Follow-up five months later showed a consolidation of the increase. The investigations show that a healthy diet and a well-balanced lifestyle correlate with a high cutaneous antioxidant concentration and that spectroscopic biofeedback measurement of cutaneous carotenoids as part of an integrated prevention program is a feasible and effective means to raise the health awareness in adolescents. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
    Journal of Biophotonics 11/2014; 7(11-12). DOI:10.1002/jbio.201300134 · 3.86 Impact Factor
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    ABSTRACT: UV irradiation is one of the most harmful exogenous factors for the human skin. In addition to the development of erythema, free radicals, i.e. reactive oxygen species (ROS), are induced under its influence and promote the development of oxidative stress in the skin. Several techniques are available for determining the effect of UV irradiation. Resonance Raman spectroscopy (RRS) measures the reduction of the carotenoid concentration, while electron paramagnetic resonance (EPR) spectroscopy enables the analysis of the production of free radicals. Depending on the method, the skin parameters are analysed in vivo or ex vivo. The present study provides a critical comparison between in vivo and ex vivo investigations on the ROS formation and carotenoid depletion caused by UV irradiation in human skin. The oxygen content of tissue was also determined. It was shown that the antioxidant status measured in the skin samples in vivo and ex vivo was different. The depletion in the carotenoid concentration in vivo exceeded the value determined ex vivo by a factor of about 1.5, and the radical formation after UV irradiation was significantly greater in vivo by a factor of 3.5 than that measured in excised human skin, which can be explained by the lack of oxygen ex vivo.This article is protected by copyright. All rights reserved.
    Experimental Dermatology 11/2014; 24(3). DOI:10.1111/exd.12605 · 4.12 Impact Factor

Publication Stats

7k Citations
988.12 Total Impact Points

Institutions

  • 2000–2015
    • Charité Universitätsmedizin Berlin
      • Department of Dermatology, Venerology and Allergology
      Berlín, Berlin, Germany
  • 2014
    • University of Greifswald
      • Institute of Hygiene and Environmental Medicine
      Griefswald, Mecklenburg-Vorpommern, Germany
  • 2003–2012
    • Freie Universität Berlin
      • • Ruminant and Swine Clinic
      • • Division of Physical and Theoretical Chemistry
      Berlín, Berlin, Germany
  • 1999–2012
    • Humboldt-Universität zu Berlin
      • Department of Chemistry
      Berlín, Berlin, Germany
  • 2011
    • Universität des Saarlandes
      • Biophotonik und Lasertechnologie
      Saarbrücken, Saarland, Germany
  • 2009
    • COTY Inc.
      New York Mills, New York, United States
  • 1997
    • Universität der Bundeswehr München
      • Institut für Physik
      Neubiberg, Bavaria, Germany