Search PubMed⌕ Search

Biomedical subjects

E Proksch

Publications and source records attributed to E Proksch.

At least 19 recordsLinked to original sources
PubMed2006

[Therapy of atopic dermatitis].

Atopic eczema is one of the most common diseases in dermatology. Patients suffer from both the chronic relapsing skin disease and the associated emotional stress. Itching and visible lesions on the face and hands are the most unpleasant features for many often young patients, seriously reducing their quality of life. New therapeutic approaches have changed the management of atopic eczema in recent years. Relatively potent new drugs with fewer side effects than corticosteroids help to control the disease. This review focuses on the basic principles of modern atopic eczema treatment, emphasizing basic emollient therapy and topical therapy with calcineurin inhibitors.

Adolescent↗
PubMed2006

Intraoral lesions associated with sebaceous nevus syndrome.

The sebaceous nevus syndrome describes the rare association of a sebaceous nevus with systemic features such as mental retardation, seizures and colobomas (among others). It is thought to be a cutaneous mosaic inherited as a paradominant trait. Three cases are provided illustrating the intraoral manifestations of the syndrome. The first histological comparison of contiguous mucosal and cutaneous lesions is provided. We also describe the possible association of SFM syndrome with a benign fibrous histiocytic lesion of the mandible. This and other mandibular tumors associated with the sebaceous nevus syndrome may have significant implications for patients. Awareness of the potential presence or development of significant intraoral lesions in association with the sebaceous nevus syndrome is important for those involved in the care of patients with this syndrome.

Abnormalities, Multiple↗
PubMed2005

Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration.

In this study we analyzed the proteolytic activity of MMP-19 and its impact on keratinocyte migration. In the HaCaT keratinocyte cell line overexpressing wild-type MMP-19 (HaCaT-WT), transmigration through fibrin and type IV collagen matrices was significantly increased compared to cells harboring a catalytically inactive mutant (HaCaT-EA). Studying the expression of MMP-19 in early stages of squamous cell cancer (SCC), we found co-localization of MMP-19 and laminin 5 at the invading tumor front but not in suprabasal epidermis of the tumor. Examination of laminin 5 processing revealed increased processing of the gamma2 chain in the medium and matrix of HaCaT-WT cells and degradation by recombinant human MMP-19 to 105-kDa and 80-kDa fragments. Parental HaCaT grown on the matrix of HaCaT-WT and HaCaT-EA cells displayed differential tyrosine phosphorylation. Using integrin blocking and stimulating antibodies we could attribute these differences to a shift from beta4-integrin-dependent signaling on the HaCaT-EA matrix toward alpha3-integrin-dependent signaling on the HaCaT-WT matrix. As a consequence, parental HaCaT showed increased migration on the matrix of HaCaT-WT cells. These data suggest that the MMP-19-dependent processing of the gamma2 chains leads to the integrin switch favoring epithelial migration and that MMP-19 actively participates in the early stages of SCC invasion.

Cell Movement↗
PubMed2001

Toxicological evaluation of nitrosamines in condoms.

Volatile N-nitrosamines have been found in rubber products including gloves, balloons, toys, baby bottle teats, soothers, and condoms. N-Nitrosamines are potent carcinogens, and therefore, European legislation has limited the release of N-nitrosamines and N-nitrosatable compounds in teats and soothers to 0.01-0.1 mg/kg rubber, respectively. Previously, endogenous nitrosamine formation in the vagina has been suggested as a cause of cervical cancer. It was speculated that exogenous N-nitrosamines and N-nitrosatable compounds from condoms may also lead to genital cancer. Therefore, we reviewed the literature and calculated the risk for the induction of tumors by nitrosamines from condoms. In vitro Biaudet et al. (1997) found up to 88 ng nitrosatable compounds migrating from condoms to cervical mucous within 24 hrs. During sexual intercourse about 0.6 ng may migrate in the female genital mucous membranes because of the short contact to the condom, e.g. 10 min. Comparable amounts of nitrosamines may also migrate in the penile skin. Estimating 1500 contacts to condoms during lifetime (50 condoms/year for 30 years) this may result in the adsorption of up to 0.9 microgram nitrosamines in total. Animal studies in Syrian hamsters showed the induction of local and/or systemic tumors, in particular liver tumors, after topical application of nitrosamines to the skin or mucous membrane at a total dose of about 1 g. This dose exceeds the dose to be expected from contact with condoms by more than 1 million. Also, epidemiological studies do not support a role for condoms in the induction of cancer. The incidence of cervical cancer and liver tumors is high in developing countries, where condoms are seldom used. In addition, humans are regularly exposed to nitrosamines from food and tobacco smoke at a dose which is 1,000 to 10,000 fold higher than expected from condom use. In summary, the risk for the induction of tumors from nitrosamines in condoms is very low.

Animals↗
PubMed2000

Iontophoresis of nickel elicits a delayed cutaneous response in sensitized individuals that is similar to an allergic patch test reaction.

Wearing of patch test chambers for 1-2 days is uncomfortable for patients. Allergen application by iontophoresis avoids this, but it is unknown so far whether iontophoresis itself interferes with the delayed immune response. We compared the effects occurring 48 h after iontophoresis with distilled water, 0.9% NaCl, and 0.01 M NiSO4 in normal volunteers and in nickel-sensitized patients (total n=36). Visual assessment was performed and transepidermal water loss (TEWL), stratum corneum hydration, cutaneous blood flow, and immunohistopathology were determined. After iontophoresis with nickel sulfate, only individuals sensitized to nickel reacted with a positive clinical response, increase in cutaneous blood flow, decline in epidermal CD-1a-positive cells, increase in epidermal proliferation (Ki-67-positive cells), pronounced infiltration of cells positive for CD4, CD11, or CLA, and cellular activation (expression of ICAM1, HLA-DR). Iontophoresis with distilled water or saline did not result in such reactions in volunteers with or without nickel sensitization, and the latter also tolerated nickel iontophoresis without significant skin reactions. We conclude that the delayed cutaneous response to nickel induced via iontophoresis is specific and similar to a positive patch test reaction. Iontophoresis may therefore be considered as an alternative to patch testing.

Adult↗
PubMed2000

Impaired cutaneous permeability barrier function, skin hydration, and sphingomyelinase activity in keratin 10 deficient mice.

Point mutations in the suprabasal cytokeratins 1 (K1) or 10 (K10) in humans have been shown to be the cause of the congenital ichthyosis epidermolytic hyperkeratosis. Recently, a K10 deficient mouse model was established serving as a model for epidermolytic hyperkeratosis. Homozygotes suffered from severe skin fragility and died shortly after birth. Heterozygotes developed hyperkeratosis with age. To see whether phenotypic abnormalities in the mouse model were associated with changes in skin barrier function and skin water content we studied basal transepidermal water loss and capacity for barrier repair after experimental barrier disruption as well as stratum corneum hydration. Also, we determined the activities of acid and neutral sphingomyelinase key enzymes of the tumor necrosis factor and interleukin-1 signal transduction pathways generating the ceramides most important for epidermal permeability barrier homeostasis. Neonatal homozygotes showed an 8-fold increase in basal transepidermal water loss compared with wild type controls. Adult heterozygotes exhibited delayed barrier repair after experimental barrier disruption. Stratum corneum hydration was reduced in homozygous and heterozygous mice. Acid sphingomyelinase activity, which is localized in the epidermal lamellar bodies and generates ceramides for extracellular lipid lamellae in the stratum corneum permeability barrier, was reduced in homozygous as well as heterozygous animals. Neutral sphingomyelinase activity, which has a different location and generates ceramides involved in cell signaling, was increased. The reduction in acid sphingomyelinase activity may explain the recently described decreased ratio of ceramides to total lipids in K10 deficient mice. In summary, our results demonstrate the crucial role of the keratin filament for permeability barrier function and stratum corneum hydration.

Animals↗
PubMed2000

Barrier characteristics of different human skin types investigated with X-ray diffraction, lipid analysis, and electron microscopy imaging.

The stratum corneum requires ceramides, cholesterol, and fatty acids to provide the cutaneous permeability barrier. The lipids are organized in intercellular membranes exhibiting short- and long-periodicity lamellar phases. In recent years, the phase behavior of barrier lipid mixtures has been studied in vitro. The relationship of human stratum corneum lipid composition to membrane organization in vivo, however, has not been clearly established. Furthermore, the special function of the different ceramide species in the stratum corneum is largely unknown. We examined lipid organization and composition of stratum corneum sheets from different subtypes of healthy human skin (normal, dry, and aged skin). Lipid organization was investigated using X-ray diffraction and demonstrated that the 4.4 nm peak attributed to the long periodicity phase was frequently missing for skin with a low Cer(EOS)/Cer(total) ratio, indicating an important part for Cer(EOS), which contains omega-hydroxy fatty acid (O) ester-linked to linoleic acid (E) and amide-linked to sphingosine (S). A deficiency in the 4. 4 nm peak was predominantly observed in young dry skin. In one case of aged skin, however, and less often in young normal skin this peak was also missing. Furthermore, the ceramide composition of samples without the 4.4 nm peak showed a deficiency of Cer(EOH), which contains 6-hydroxy-4-sphingenine (H), and an increase in Cer(NS) and Cer(AS), which contain nonhydroxy (N) or alpha-hydroxy fatty acids (A). In addition, a 3.4 nm peak attributed to crystalline cholesterol occurred in most cases of aged and dry skin, but was not observed in young normal skin. Our results do not indicate a definite pattern of correlation between lipid organization and types of human skin. They demonstrate, however, that Cer(EOS) and Cer(EOH) are key elements for the molecular organization of the long periodicity lamellar phase in the human stratum corneum.

Adult↗
PubMed1999

Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice.

The WD-40 repeat protein FAN binds to a distinct domain of the p55 receptor for tumor necrosis factor (TNF) and signals the activation of neutral sphingomyelinase (N-SMase). To analyze the physiological role of FAN in vivo, we generated FAN-deficient mice by targeted gene disruption. Mice lacking a functional FAN protein do not show any overt phenotypic abnormalities; in particular, the architecture and cellular composition of lymphoid organs appeared to be unaltered. An essential role of FAN in the TNF-induced activation of N-SMase was demonstrated using thymocytes from FAN knockout mice. Activation of extracellular signal-regulated kinases in response to TNF treatment, however, was not impaired by the absence of the FAN protein. FAN-deficient mice show delayed kinetics of recovery after cutaneous barrier disruption suggesting a physiological role of FAN in epidermal barrier repair. Although FAN exhibits striking structural homologies with the CHS/Beige proteins, FAN-deficient mice did not reproduce the phenotype of beige mice.

Amino Acid Sequence↗
PubMed1999

Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier.

Epidermal TNF expression increases in response to cutaneous permeability barrier disruption and wound healing. TNF signaling is mediated by acid and neutral sphingomyelinases (A- and N-SMase), which generate ceramide, an important regulator of proliferation, differentiation, and apoptosis. In the epidermis, ceramide is known to be an integral part of the extracellular stratum corneum (SC) lipid bilayers that constitute the permeability barrier of the skin. We show here that topical application of TNF after experimental injury to the SC of hairless mice (hr(-/-)) enhances barrier repair. In TNF receptor p55-deficient (TNF-R55-deficient) mice (hr(+/+)), cutaneous barrier repair was delayed compared with wild-type (hr(+/+)) or TNF-R75-deficient (hr(+/+)) animals. After barrier disruption in hairless (hr(-/-)) and wild-type (hr(+/+)), but not in TNF-R55-deficient (hr(+/+)) mice, the enzymatic activities of both A-SMase and N-SMase were significantly enhanced. Stimulation of SMase activities was accompanied by an increase in C(24)-ceramide levels. Most A-SMase activity in hairless mice (hr(-/-)) was found in the outer epidermal cell layers and colocalized in the lamellar bodies with A-SMase and sphingomyelin. Reduction of epidermal A-SMase activity by the inhibitor imipramine resulted in delayed permeability barrier repair after SC injury. Together, these results suggest that TNF-R55 signaling pathways contribute to cutaneous permeability barrier repair through SMase-mediated generation of ceramide.

Animals↗
PubMed1998

Expression of epidermal keratins and the cornified envelope protein involucrin is influenced by permeability barrier disruption.

In previous studies we have shown that experimental permeability barrier disruption leads to an increase in epidermal lipid and DNA synthesis. Here we investigate whether barrier disruption also influences keratins and cornified envelope proteins as major structural keratinocyte proteins. Cutaneous barrier disruption was achieved in hairless mouse skin by treatments with acetone +/- occlusion, sodium dodecyl sulfate, or tape-stripping. As a chronic model for barrier disruption, we used essential fatty acid deficient mice. Epidermal keratins were determined by one- and two-dimensional gel electrophoresis, immunoblots, and anti-keratin antibodies in biopsy samples. In addition, the expression of the cornified envelope proteins loricrin and involucrin after barrier disruption was determined by specific antibodies in human skin. Acute as well as chronic barrier disruption resulted in the induction of the expression of keratins K6, K16, and K17. Occlusion after acute disruption led to a slight reduction of keratin K6 and K16 expression. Expression of basal keratins K5 and K14 was reduced after both methods of barrier disruption. Suprabasal keratin K10 expression was increased after acute barrier disruption and K1 as well as K10 expression was increased after chronic barrier disruption. Loricrin expression in mouse and in human skin was unchanged after barrier disruption. In contrast, involucrin expression, which was restricted to the granular and upper spinous layers in normal human skin, showed an extension to the lower spinous layers 24 h after acetone treatment. In summary, our results document that acute or chronic barrier disruption leads to expression of keratins K6, K16, and K17 and to a premature expression of involucrin. We suggest that the coordinated regulation of lipid, DNA, keratin, and involucrin synthesis is critical for epidermal permeability barrier function.

Animals↗
PubMed1997

Effects of xerosis and ageing on epidermal proliferation and differentiation.

The hallmarks of dry skin (xerosis) are scaliness and loss of elasticity. Decreased hydration and a disturbed lipid content of the stratum corneum are also well-known features. The frequency of dry skin increases with ageing. The aim of this study was to examine if these known features of dry skin are related to changes in epidermal proliferation and differentiation. In addition, age-related changes in normal and in dry skin were examined: 62 volunteers were divided by clinical grading and biophysical measurements into groups with young/normal, young/dry, aged/normal and aged/dry skin. Biopsy samples from the lower legs (most severe dryness) were examined by two-dimensional gel electrophoresis and by immunohistochemistry for epidermal proliferation, epidermal keratins and cornified envelope proteins. There was a slight increase in proliferation in both groups with dry skin compared with normal skin of the corresponding age. In aged/normal compared with young/normal skin there was a significant decrease in proliferation. However, epidermal proliferation was the same in aged/dry skin as in young/normal skin. For epidermal differentiation, an age-independent decrease of keratins K1 and K10 and an associated increase in the basal keratins K5 and K14 was detected in dry skin. There was also an age-independent premature expression of the cornified envelope protein involucrin. In contrast, loricrin expression was not influenced by dry skin conditions. In summary, epidermal proliferation was significantly decreased in aged/normal compared with young/normal skin. Dry skin showed significant changes in the epidermal expression of basal and differentiation-related keratins, and a premature expression of involucrin irrespective of age.

Adult↗
PubMed1997

Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria pigmentosa and systemic mastocytosis.

BACKGROUND: Previous studies have shown that oral PUVA is effective in urticaria pigmentosa. Long-term results, however, are unknown. OBJECTIVE: We studied the long-term effectiveness of oral PUVA treatment in urticaria pigmentosa as well as in systemic mastocytosis. In addition, the success of bath PUVA was examined in these diseases. METHODS: Twenty patients with urticaria pigmentosa and systemic mastocytosis treated by oral PUVA were examined retrospectively for a time period of up to 18 years. We studied the duration of improvement and correlated these results with the total PUVA dose, the skin type and the age of onset. Four patients were treated by bath PUVA therapy. RESULTS: In oral PUVA therapy an improvement was seen in 14 out of 20 patients (70%). There was no difference in the response rate between urticaria pigmentosa and systemic mastocytosis and there was no correlation with the total PUVA dosage. The duration of the treatment's success ranged from a few weeks to more than 10 years. 25% of the patients showed an improvement for more than 5 years. Patients with onset during childhood and early adolescence and patients with skin types I and II responded favourably to the treatment. Bath PUVA therapy was without effect in our 4 patients. CONCLUSION: Oral PUVA is very effective for the long-term treatment of urticaria pigmentosa as well as systemic mastocytosis.

Administration, Cutaneous↗
PubMed1997

Topical vitamin D3 derivatives impair the epidermal permeability barrier in normal mouse skin.

BACKGROUND: Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 are potent drugs for the treatment of psoriasis. It has recently been published that these compounds induce epidermal hyperproliferation in hairless mouse skin. OBJECTIVE: The aim of our study was to examine the effect of vitamin D3 derivatives on epidermal growth, keratinization and permeability barrier function in vivo. METHODS: Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 in isopropanol or in an ointment formula were applied to normal hairless mouse skin. Transepidermal water loss (TEWL), a marker of cutaneous barrier function, and epidermal proliferation were determined at different time points 0-264 h after treatment. In addition, light and electron microscopy studies were performed. RESULTS: A single treatment in solution led to a transient (2- to 3-fold) increase in TEWL after application of calcipotriol or 1,25(OH)2D3 and to a 3- to 6-fold increase in epidermal proliferation after application of each of the compounds. Repeated applications also resulted in an up to 3-fold increase in TEWL which persisted for 3 days after the end of the treatment. By light microscopy an increase in epidermal thickness was observed. There was no sign of inflammation. Electron microscopy studies showed the formation of a transitional cell zone as a sign of a premature keratinization. CONCLUSION: These results demonstrate that in normal mouse skin vitamin D3 and its analogues disrupt the epidermal permeability barrier by induction of epidermal proliferation and premature keratinization but without morphological signs of inflammation.

1-Propanol↗
PubMed1997

Influence of epidermal permeability barrier disruption and Langerhans' cell density on allergic contact dermatitis.

Previously, we have showed that artificial epidermal permeability barrier disruption leads to an increase in epidermal Langerhans' cell (LC) density within 24 h. We now asked if this is accompanied by an enhancement of allergic contact dermatitis. Barrier disruption was induced by acetone on the upper arms in 6 volunteers with known sensitization to nickel, fragrance mix, or p-phenylenediamine. Twenty-four hours after this treatment the relevant allergen was applied without occlusion or with Finn chambers. Twenty-four hours after application of the allergen, clinical grading and transepidermal water loss (TEWL) measurements were performed and biopsies were taken. Immunohistochemical stainings for LCs (anti-CD1a, Leu6) and for epidermal proliferation (Ki-S3) were performed. Open applications of the allergens after acetone pretreatment resulted in strong allergic test reactions. TEWL, which showed a 70% recovery 24 h after acetone treatment, was increased again 4-fold by the allergic test reactions. LC density, which was increased by 80% 24 h after acetone-induced barrier disruption, was further enhanced 2.4-fold in total. Epidermal proliferation showed a 6-fold increase after open application of the allergens. Under patch test conditions after acetone pretreatment very strong bullous reactions were observed. We conclude that the increase in epidermal LC density induced by epidermal permeability barrier disruption is accompanied by an enhanced response in allergic contact dermatitis.

Acetone↗