Stephan Pfeiffer

Bio: Stephan Pfeiffer is an academic researcher from University of Kiel. The author has contributed to research in topics: Stratum corneum & Filaggrin. The author has an hindex of 12, co-authored 16 publications receiving 1241 citations. Previous affiliations of Stephan Pfeiffer include Beiersdorf.

The human stratum corneum layer: an effective barrier against dermal uptake of different forms of topically applied micronised titanium dioxide.

Abstract: Electron microscopy visualisation and light microscopic investigations of three different application forms of titanium dioxide proved that neither surface characteristics, particle size nor shape of the micronised titanium dioxide result in any dermal absorption of this substance: Micronised titanium dioxide is solely deposited on the outermost surface of the stratum corneum and cannot be detected in deeper stratum corneum layers, the human epidermis and dermis.

Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis.

Abstract: Background Genetic defects leading to skin barrier dysfunction were recognized as risk factors for atopic dermatitis (AD) It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens Objectives We investigated the effect of 2 common treatments, a calcineurin inhibitor and a corticosteroid, on the skin barrier Methods In a randomized study 15 patients with AD were treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks Results Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier, improved in both groups Dye penetration, a marker of the outside-inside barrier, was also reduced in both drugs Electron microscopic evaluation of barrier structure displayed prevalently ordered stratum corneum lipid layers and regular lamellar body extrusion in pimecrolimus-treated skin but inconsistent extracellular lipid bilayers and only partially filled lamellar bodies after betamethasone treatment Both drugs normalized epidermal differentiation and reduced epidermal hyperproliferation Betamethasone was superior in reducing clinical symptoms and epidermal proliferation; however, it led to epidermal thinning Conclusion The present study demonstrates that both betamethasone and pimecrolimus improve clinical and biophysical parameters and epidermal differentiation Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD

Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation.

Abstract: We previously demonstrated that the aspartate protease cathepsin D is activated by ceramide derived from acid sphingomyelinase. Increased expression of cathepsin D in the skin has been reported in wound healing, psoriasis and skin tumors. We explored specific functions of cathepsin D during epidermal differentiation. Protein expression and enzymatic activity of cathepsin D increased in differentiated keratinocytes in both stratified organotypic cultures and in mouse skin during epidermal barrier repair. Treatment of cultured keratinocytes with exogenous cathepsin D increased the activity of transglutaminase 1, known to cross-link the cornified envelope proteins involucrin and loricrin during epidermal differentiation. Inhibition of cathepsin D by pepstatin A suppressed the activity of transglutaminase 1. Cathepsin D-deficient mice revealed reduced transglutaminase 1 activity and reduced protein levels of the cornified envelope proteins involucrin and loricrin. Also, amount and distribution of cornified envelope proteins involucrin, loricrin, filaggrin, and of the keratins K1 and K5 were significantly altered in cathepsin D-deficient mice. Stratum corneum morphology in cathepsin D-deficient mice was impaired, with increased numbers of corneocyte layers and faint staining of the cornified envelope only, which is similar to the human skin disease lamellar ichthyosis. Our findings suggest a functional link between cathepsin D activation, transglutaminase 1 activity and protein expression of cornified envelope proteins during epidermal differentiation.

The potential environmental impact of engineered nanomaterials

Abstract: With the increased presence of nanomaterials in commercial products, a growing public debate is emerging on whether the environmental and social costs of nanotechnology outweigh its many benefits. To date, few studies have investigated the toxicological and environmental effects of direct and indirect exposure to nanomaterials and no clear guidelines exist to quantify these effects.

Review article: Polymer-matrix Nanocomposites, Processing, Manufacturing, and Application: An Overview

Abstract: This review is designed to be a comprehensive source for polymer nanocomposite research, including fundamental structure/property relationships, manufacturing techniques, and applications of polymer nanocomposite materials. In addition to presenting the scientific framework for the advances in polymer nanocomposite research, this review focuses on the scientific principles and mechanisms in relation to the methods of processing and manufacturing with a discussion on commercial applications and health/safety concerns (a critical issue for production and scale-up). Hence, this review offers a comprehensive discussion on technology, modeling, characterization, processing, manufacturing, applications, and health/safety concerns for polymer nanocomposites.

The cornified envelope: a model of cell death in the skin

Abstract: The epidermis functions as a barrier against the environment by means of several layers of terminally differentiated, dead keratinocytes - the cornified layer, which forms the endpoint of epidermal differentiation and death. The cornified envelope replaces the plasma membrane of differentiating keratinocytes and consists of keratins that are enclosed within an insoluble amalgam of proteins, which are crosslinked by transglutaminases and surrounded by a lipid envelope. New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing our understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.

The skin: an indispensable barrier

Abstract: The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis

The potential risks of nanomaterials: a review carried out for ECETOC

Abstract: During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.