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Biomedical subjects

E Proksch

Publications and source records attributed to E Proksch.

At least 37 records · Page 2Linked to original sources
PubMed1997

Epidemiological features of Adamantiades-Behçet's disease in Germany and in Europe.

The German Registry of Adamantiades-Behçet's disease was founded in 1990 in Berlin and it provides current data on the epidemiology, the clinical manifestations and the course of the disease in Germany on a continuous basis. A total of 218 patients, including 89 German and 100 Turkish patients, had been reported to the German Registry until October 1997. One hundred and ninety-six patients fulfilled the criteria of the Behçet's disease classification tree. The prevalence of the disease evaluated in Berlin-West was 1.68/100,000 in 1989 and had risen to 2.26/100,000 by 1994. The median age of onset was 25 years (range 5 to 66 years; German-Turks, ns). Juvenile disease was recorded in 6.9% of patients. The complete clinical picture according to the criteria of the International Study Group of Behçet's Disease developed in 15.5 months. The interval between onset of the disease and diagnosis was 35 months, which was significantly longer than the duration of the development of the complete clinical picture (p < 0.0001). The disease was diagnosed later in German (48.5 months) than in Turkish patients (25.5 months, p = 0.003). While German patients presented an equal male-to-female ratio, a male predominance was shown in Turkish patients (M:F 2.1:1, p = 0.022). Familial occurrence was detected in 2.0% of German and 15.9% of Turkish patients (p = 0.013). The frequencies of major clinical manifestations were: oral ulcers 99%, skin lesions 76%, genital ulcers 75%, ocular manifestations 59%, arthritis 59%, and positive pathergy test 52%. Clinical differences between German and Turkish patients were only found in the frequency of ocular lesions (48% vs. 66%, p = 0.025). Oral ulcers were with 72% the most common onset symptom of the disease followed by erythema nodosum (9%), uveitis (7%), arthritis (7%), genital ulcers (3%), superficial thrombophlebitis (2%) and papules/sterile pustules (2%). Uveitis and erythema nodosum as onset symptoms shortened the median interval to diagnosis to 1.5 and 15 months, respectively, while arthritis delayed diagnosis (43.5 months; p = 0.029). A severe course developed in 25% of the patients; irreversible retinal vasculitis to blindness in 15%, sterile meningoencephalitis in 8%, severe arthritis in 5%, hemoptysis in 2%, lethal outcome in 2% and bowel perforation in 1%. The relative risk of HLA-B5 positive German natives developing the disease. HLA-B5 was confirmed as a marker of severe prognosis. Cardiolipin autoantibodies were associated with cutaneous vasculitis and superficial thrombophlebitis was correlated with systemic vessel involvement.

Adolescent↗
PubMed1996

Topical treatment by urea reduces epidermal hyperproliferation and induces differentiation in psoriasis.

The mechanisms of action of urea-containing ointments in the treatment of eczema, ichthyosis and psoriasis are only partly known and related to proteolysis and keratinolysis. In this study, we have examined the effects of topical urea on epidermal proliferation and differentiation in 10 patients with psoriasis. Plaque type lesions were treated for 2 weeks with an ointment containing 10% urea, with the vehicle alone, or left untreated. Clinical score, hydration of the stratum corneum, transepidermal water loss (TEWL), and immunohistochemical studies were performed. Epidermal proliferation was assessed using the Ki-S3 proliferation-associated nuclear antigen. For epidermal differentiation antibodies against involucrin and against keratins CK 5, 6, 17 and CK 1, 5, 10, 14 were used. The patients showed a reduction of the clinical score (> 50%), a 2-fold increase in stratum corneum hydration (p < 0.01), and a small decrease in TEWL (N.S.) on the urea- treated compared to the untreated site. Light microscopy studies revealed a 29% reduction in epidermal thickness (p < 0.01); epidermal proliferation was decreased by 51% (p < 0.005). The altered expression of involucrin and of cytokeratins (reduction of CK 5, 1 and 10 and induction of CK 6 and 17) was partially reversed. The ointment base also improved psoriasis, but urea was significantly better than the vehicle (urea: 40% reduction in epidermal proliferation vs. vehicle). In summary, these studies show that urea influences epidermal proliferation and differentiation in psoriasis.

Administration, Topical↗
PubMed1996

Integrity of the permeability barrier regulates epidermal Langerhans cell density.

Previous studies have shown that barrier requirements regulate epidermal liquid and DNA synthesis. In the present study, we examined the possibility that the integrity of the permeability barrier influences epidermal Langerhans cells involved with the immune response. Barrier disruption was achieved by treatment of human skin with acetone, sodium dodecylsulphate (SDS), or tape stripping, until a 10-20-fold increase in transepidermal water loss was achieved. Serial biopsies were performed 6-168 h after treatment, and Langerhans cells were complexed with anti-CD1a (Leu6) or S-100 antibodies, and visualized with an immunoperoxidase technique. Acetone treatment resulted in an increase in epidermal Langerhans cell density, reaching a maximum of 94% over control (P < 0.01) by 24 and 48 h post-treatment. Following SDS treatment or tape stripping, epidermal Langerhans cell density was increased by 100 and 175% (P < 0.01), respectively. There was a linear correlation between the degree of barrier disruption and the increase in epidermal Langerhans cell density. Studies with the Ki-S3 proliferation-associated nuclear antigen revealed a two- to threefold increase in epidermal proliferation after barrier disruption. The time curves of the increase in Langerhans cell density and the increase in epidermal proliferation were similar, suggesting that there was a coordinate regulation. In contrast with our previous studies employing patch test reactions to allergens or irritants, disruption of barrier function neither resulted in an increased dermal Langerhans cell density, nor influenced T lymphocytes (CD3+, Leu4+), macrophages (KiM8+), ICAM-1 or ELAM-1 expression in the skin. In addition, barrier disruption did not result in either dermal inflammation or epidermal spongiosis. In summary, these findings support our hypothesis that the permeability barrier influences epidermal Langerhans cell density, which is involved in maintaining an immunological barrier.

Acetone↗
PubMed1995

[Antilipemic drug-induced skin manifestations].

Systemically administered lipid-lowering drugs can induce eczema, ichthyosis, or psoriasis as side effects. Common abnormalities in these diseases are a rough, scaly skin, a disturbed permeability barrier and disturbed epidermal proliferation and differentiation. The disturbed epidermal differentiation is accompanied by changes in the keratin composition and the cornified envelope proteins as well as by changes in the lipid composition. Lipid-lowering drugs do not necessarily all cause the same diseases, because they inhibit different steps in the cholesterol synthetic pathway. The lipid-lowering drugs lovastatin (Mevacor), simvastatin (Zocor) and pravastatin (Selipram) can cause eczema; these drugs inhibit an early step of cholesterol biosynthesis, viz. HMG CoA reductase activity. The lipid-lowering drugs triparanol and diazacholesterol inhibit a late step in cholesterol biosynthesis, delta-24-sterol reductase, and they can induce ichthyosis or palmoplantar hyperkeratosis. In contrast, systemically applied gemfibrozil, which mainly lowers triglycerides, can cause an exacerbation of psoriasis. These observations show the importance of the lipid metabolism in the pathogenesis of eczema, ichthyosis, and psoriasis.

Cholesterol↗
PubMed1995

[Von Recklinghausen neurofibromatosis and dermal melanocytic nevi].

Neurofibromas, café au lait macules and freckles in the axillary or inguinal regions are common manifestations of von Recklinghausen's neurofibromatosis (NF-1). Less known is the simultaneous appearance of dermal melanocytic naevi. We describe the case of a 21-year-old Vietnamese woman who showed generalized, multiple neurofibromas, a solitary plexiform neurofibroma in the left gluteal region and Lisch nodules. In addition, there were several large grey-blue macules histologically characterized by fusiform pigment-bearing cells in the dermis, which we diagnosed as persistent aberrant mongolian spots. In the right zygomatic region she presented a grey-blue, hair-bearing macule, which we saw as a variant of Ota's naevus. A genetic background for this coincidence of a systemic with a local phakomatosis can be supposed, as both Schwann's cells and melanocytes are derived from the neural crest. Such pathologic rearrangement in the embryogenesis of the cellular elements could be important for the pathogenesis of NF-1 and dermal melanocytic nevi.

Adult↗
PubMed1993

Barrier function regulates epidermal lipid and DNA synthesis.

The stratum corneum, the permeability barrier between the internal milieu and the environment, is composed of fibrous protein-enriched corneocytes and a lipid-enriched intercellular matrix. The lipids are a mixture of sphingolipids, cholesterol and free fatty acids, which form intercellular membrane bilayers. Lipid synthesis occurs in the keratinocytes in all nucleated layers of the epidermis, and the newly synthesized lipids are delivered by lamellar bodies to the interstices of the stratum corneum during epidermal differentiation. Disruption of barrier function by topical acetone treatment results in an increase in the synthesis of free fatty acids, sphingolipids and cholesterol in the living layers of the epidermis, leading to barrier repair. Cholesterol and sphingolipid synthesis are regulated by the rate-limiting enzymes HMG CoA reductase and serine palmitoyl transferase (SPT), respectively. Acute barrier disruption leads to an increase in both enzymes, but with a different time curve: increase in HMG CoA reductase activity begins at 1.5 h, whereas the increase in SPT activity occurs 6 h after barrier impairment. Topical application of HMG CoA reductase or SPT inhibitors after acetone treatment delays barrier repair, providing further evidence for a role of cholesterol and sphingolipids in epidermal barrier function. Repeated application of lovastatin to untreated skin results in disturbed barrier function accompanied by increased DNA synthesis and epidermal hyperplasia. Therefore, we have examined the specific relationship between barrier function and epidermal DNA synthesis. After acute and chronic disturbances not only lipid, but also DNA synthesis, is stimulated. Thus, stimulation of DNA synthesis leading to epidermal hyperplasia may be a second mechanism by which the epidermis repairs defects in barrier function. The link between barrier function and both lipid and DNA synthesis is supported further by occlusion studies. Artificial barrier repair by latex occlusion prevents an increase in both lipid and DNA synthesis. In addition, increased epidermal lipid and DNA synthesis in essential fatty-acid deficiency can be reversed by topical applications of the n-6 unsaturated fatty acids, linoleic or columbinic acid. These studies may be of relevance in understanding the pathogenesis of hyperproliferative skin diseases, such as ichthyosis, psoriasis, atopic dermatitis, and irritant contact dermatitis.

Animals↗
PubMed1992

Remediation of groundwater polluted with chlorinated ethylenes by ozone-electron beam irradiation treatment.

OH radicals formed in water radiolysis may be effectively used for the oxidative decomposition of trichloroethylene and perchloroethylene contained as micropollutants in groundwater. Addition of ozone to the water before irradiation causes the reducing species of the water radiolysis to be converted into OH radicals. Moreover, this eliminates the dose rate effect observed with irradiation alone. By the ozone-electron beam treatment greater than 95% of the organic chlorine content are mineralized, only negligible amounts of organic chlorine containing by-products are formed. AMES test has shown no mutagenic activity at all.

Electrons↗
PubMed1992

Epidermal HMG CoA reductase activity in essential fatty acid deficiency: barrier requirements rather than eicosanoid generation regulate cholesterol synthesis.

We showed previously that the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol biosynthesis, increases after both barrier disruption with organic solvents and in essential fatty acid deficiency (EFAD). Here, we treated EFAD hairless mice with linoleic acid, columbinic acid (C18: 3, n-6, trans; not metabolizable to known regulatory eicosanoids), prostaglandin E2 (PGE2), or latex occlusion, and determined transepidermal water loss (TEWL), epidermal protein content, and epidermal HMG CoA reductase activity. Increased TEWL rates in EFAD were accompanied by increased HMG CoA reductase activity (+130%, n = 6, p less than 0.01) and protein content (+69%; n = 6, p less than 0.025). Artificial restoration of the barrier by occlusion reduced the increase in enzyme activity and protein content toward normal, but barrier function, measured immediately after removal of the latex wrap, deteriorated further (TEWL: two-fold greater than EFAD unoccluded; p less than 0.01). Topical applications of either linoleate or columbinate (but not PGE2), normalized barrier function, HMG CoA reductase activity, and protein content. These results show that a) barrier function modulates HMG CoA reductase activity; b) reduction of cholesterol synthesis with occlusion results in a further deterioration in barrier function, suggesting that increased synthesis is a protective homeostatic response; and c) the barrier abnormality reflects a requirement for specific fatty acids for the barrier rather than resulting from epidermal hyperplasia or decreased prostaglandin generation.

Animals↗
PubMed1992

Calcium and potassium are important regulators of barrier homeostasis in murine epidermis.

Topical solvent treatment removes lipids from the stratum corneum leading to a marked increase in transepidermal water loss (TEWL). This disturbance stimulates a variety of metabolic changes in the epidermis leading to rapid repair of the barrier defect. Using an immersion system we explored the nature of the signal leading to barrier repair in intact mice. Initial experiments using hypotonic to hypertonic solutions showed that water transit per se was not the crucial signal. However, addition of calcium at concentrations as low as 0.01 mM inhibited barrier repair. Moreover, both verapamil and nifedipine, which block calcium transport into cells, prevented the calcium-induced inhibition of TEWL recovery. Additionally, trifluoroperazine or N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide, which inhibit calmodulin, prevented the calcium-induced inhibition of TEWL recovery. Although these results suggest an important role for calcium in barrier homeostasis, calcium alone was only modestly effective in inhibiting TEWL recovery. Potassium alone (10 mM) and phosphate alone (5 mM) also produced a modest inhibition of barrier repair. Together, however, calcium and potassium produced a synergistic inhibition of barrier repair (control 50% recovery vs. calcium + potassium 0-11% recovery in 2.5 h). Furthermore, in addition to inhibiting TEWL recovery, calcium and potassium also prevented the characteristic increase in 3-hydroxy-3-glutaryl CoA reductase activity that occurs after barrier disruption. Finally, the return of lipids to the stratum corneum was also blocked by calcium and potassium. These results demonstrate that the repair of the epidermal permeability barrier after solvent disruption can be prevented by calcium, potassium, and phosphate. The repair process may be signalled by a decrease in the concentrations of these ions in the upper epidermis resulting from increased water flux leading to passive loss of these ions.

Animals↗
PubMed1992

[Regulation of the epidermal permeability barrier by lipids and hyperproliferation].

The stratum corneum, the permeability barrier between the internal and external milieu, is composed of protein-enriched cells and lipid-enriched intercellular domains. Lipid synthesis is localized in the keratinocytes. The lamellar bodies located in the keratinocytes secrete lipids (sphingolipids, free fatty acids and cholesterol) into in the intercellular spaces of the stratum corneum. A disturbance of barrier function results in an increase in the synthesis of free fatty acids, non-saponified lipids and cholesterol in all nucleated layers of the epidermis. Cholesterol synthesis is regulated by the enzyme HMG-CoA reductase. After acute disturbance of barrier function by acetone treatment the increase in cholesterol synthesis occurs mainly in the lower epidermis (stratum basale/stratum spinosum), while after chronic disturbance by a diet deficient in essential fatty acids the increase shifts to the upper epidermis (stratum granulosum). After barrier disturbance not only lipid but also DNA synthesis is stimulated. Stimulation of DNA synthesis leading to epidermal hyperplasia may be a second mechanism by which the epidermis tries to correct defects in barrier function. Artificial barrier repair with latex occlusion prevents an increase in lipid and in DNA synthesis. Chronic barrier impairment by topical application of lovastatin, an inhibitor of cholesterol synthesis, or by a diet deficient in essential fatty acid also leads to an increase in lipid and DNA synthesis and to epidermal hyperplasia. Epidermal lipid and DNA synthesis in essential fatty acid deficiency is independent of prostaglandin E2, but depends on n-6-unsaturated fatty acids such as linoleic and columbinic acid.

Animals↗
PubMed1991

Localization and regulation of epidermal 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity by barrier requirements.

Recent studies have shown that epidermal cholesterol synthesis is regulated by HMG CoA reductase activity and that this activity is modulated by changes in the cutaneous permeability barrier. Here, we quantitated HMG CoA reductase activity after acute and chronic barrier disruption in the upper and lower layers of murine epidermis. In unperturbed epidermis, 13 and 87% of enzyme activity localized to the upper and lower epidermis, respectively, with the majority of activity in the stratum basale. Acute barrier disruption with either acetone or sodium dodecylsulfate provoked an increase in HMG CoA reductase activity (54% and 30%) in the lower layers, but only a small change in the upper layers. However, the activation state of the enzyme was increased 50% in the upper epidermis. Correction of barrier function by occlusion with an impermeable Latex wrap prevented the increase both in enzyme activity and activation state. After chronic barrier disruption; i.e., essential fatty acid deficient (EFAD) diet, HMG CoA reductase activity was increased in the upper epidermis (161%); a change prevented by occlusion. These results show: (1) that HMG CoA reductase activity is present in both the upper and lower cell layers; (2) that acute insults to barrier integrity stimulate enzyme activity in both the upper and lower epidermis; and (3) that chronic insults provoke an increase in enzyme activity in the upper layers. These studies provide further insights into the linkage of the permeability barrier with epidermal cholesterol metabolism.

Animals↗
PubMed1991

The lovastatin-treated rodent: a new model of barrier disruption and epidermal hyperplasia.

Recent studies have linked epidermal cholesterol synthesis with maintenance of the permeability barrier. To assess directly the importance of cholesterol synthesis, we applied lovastatin, a potent inhibitor of cholesterol synthesis, to hairless mouse skin. Transepidermal water loss (TEWL) began to increase after four to six daily applications. Co-application of cholesterol blocked the expected increase in TEWL, demonstrating the importance of cholesterol for development of the lesion. The histology of lovastatin-treated skin revealed epidermal hyperplasia, accompanied by accelerated DNA synthesis. Whereas cholesterol synthesis initially was reduced in lovastatin-treated epidermis, with further treatment cholesterol synthesis normalized, while fatty acid synthesis accelerated greatly. Although the total free sterol content of lovastatin-treated epidermis remained normal, the fatty acid content increased coincident with barrier disruption. Finally, morphologic abnormalities of both lamellar body structure and their deposited, intercellular contents occurred coincident with the emerging biochemical abnormalities. Thus, the abnormal barrier function in this model can be ascribed to an initial inhibition of epidermal sterol synthesis followed by an alteration in cholesterol and fatty acid synthesis, leading to an imbalance in stratum corneum lipid composition and abnormal membrane bilayer structure.

Animals↗
PubMed1991

Barrier function regulates epidermal DNA synthesis.

We examined the possibility that the cutaneous permeability barrier regulates epidermal DNA synthesis in two acute and two chronic models of barrier perturbation. In animals treated topically with acetone, DNA synthesis is increased 102%, in tape-stripped animals 127%, in essential fatty acid deficient animals 50%, and in animals chronically treated with topical lovastatin 64%. This linkage between disturbances in barrier function and increased DNA synthesis is further supported by specific and correlative observations: (a) in these disparate models, artificial replacement of the barrier with a water-impermeable membrane inhibits the expected increase in DNA synthesis; (b) the extent of the burst in DNA synthesis is proportional to the degree of barrier abrogation; (c) the inhibition of DNA synthesis by membranes is directly related to the degree of permeability of these occlusive membranes, i.e., the more impermeable the greater the degree of inhibition; (d) topical treatment with lipids that restore barrier function corrects the increase in DNA synthesis; and (e) barrier abrogation with acetone produces an increase in epidermal DNA synthesis without altering bulk protein synthetic rates in contrast to events known to follow injury or cell replacement. Autoradiographic studies show that the increase in DNA synthesis after acetone treatment is limited to the epidermal basal layer. This constellation of findings strongly suggests that cutaneous barrier function is one factor that regulates epidermal DNA synthesis.

Animals↗
PubMed1990

Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements.

Epidermal cholesterol biosynthesis is regulated by barrier function. We quantitated the amount and activation state (phosphorylation-dephosphorylation) of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, in epidermis before and after barrier disruption. In murine epidermis we found high enzyme activity (1.75 +/- 0.02 nmol/min per mg protein). After acute barrier disruption, enzyme activity began to increase after 1.5 h, reaching a maximum increase by 2.5 h, and returned to normal by 15 h. Chronic barrier disruption increased total enzyme activity by 83%. In normal epidermis, measurement of HMG CoA reductase activity in microsomes isolated in NaF- vs. NaCl-containing buffers demonstrated that 46 +/- 2% of the enzyme was in the active form. After acute or chronic barrier disruption, a marked increase in the percentage of HMG CoA reductase in the active form was observed. Acute disruption increased enzyme activation state as early as 15 min, reaching a maximum after 2.5 h, with an increase still present at 15 h, indicating that changes in activation state had a close temporal relationship with barrier function. Increases in total HMG CoA reductase activity occurred only after profound barrier disruption, whereas changes in activation state occur with lesser degrees of barrier disruption. Artificial correction of barrier function prevented the increase in total HMG CoA reductase activity, and partially prevented the increase in enzyme activation. These results show that barrier requirements regulate epidermal cholesterol synthesis by modulating both the HMG CoA reductase amount and activation state.

Acetone↗
PubMed1990

[The epidermis as metabolically active tissue: regulation of lipid synthesis by the barrier function].

Numerous investigations have shown that the lipids of the horny layer play an important role in the epidermal barrier function. These lipids consist of sphingolipids, cholesterol, and free fatty acids in nearly equimolar proportions. If the barrier function is disturbed--i.e. in case of lipid extraction or a diet deficient of essential fatty acids--we find an increased synthesis of free fatty acids, cholesterol, and non-saponifiable lipides in the epidermis. Covering the skin with a Latex wrap prevents an increased lipid synthesis. The synthesis of cholesterol depending on the barrier function is regulated by the enzyme HMG CoA reductase. The regulation process involves both the quantity and the activity (phosphorylation) of the enzyme. Acute disruption of the permeability barrier results in an increased synthesis of cholesterol in the lower epidermis, whereas in case of chronic barrier disorders, the specific increase takes place in the upper dermis. A reduction of the cholesterol synthesis by the HMG CoA reductase inhibitor Lovastatin leads to a disturbed permeability barrier and epidermal hyperplasia.

Animals↗
PubMed1989

Radiation-induced decomposition of small amounts of trichloroethylene in drinking water.

Solutions of 10 ppm trichloroethylene in air-saturated drinking waters are decomposed by gamma radiation with initial G-values, G0, around 3-5 molecules per 100 eV. At lower concentrations, the G0-values decrease with decreasing trichloroethylene concentration and with increasing amounts of inorganic (especially HCO3- and NO3-) and organic solutes. From the results, a semi-empirical formula is derived which allows an estimation of G0-values for the trichloroethylene decomposition in drinking waters of given composition.

Trichloroethylene↗