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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 13 (2004), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Circulating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulation with other stimuli like N-formyl-methionyl-leucyl-phenylalanine (FMLP), interleukin-8 (IL-8), leukotriene B4 (LTB4), or platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). In this study, we raised the question whether factors released from polymorphonuclear leukocytes (PMNs) can specifically down-regulate C5a-dependent neutrophil functions.When neutrophils were preincubated with either neutrophil lysates or neutrophil degranulation supernatants, a complete inhibition of C5a-stimulated β-glucuronidase release and chemotaxis could be observed, whereas FMLP-, IL-8-, LTB4- or PAF-dependent functions were not affected. Serine protease inhibitors like phenylmethylsulfonyl fluoride, antileukoprotease, or elafin abolished this effect. High-performance liquid chromatography of neutrophil degranulation supernatants revealed pronounced inhibition of C5a-dependent neutrophil functions in fractions exerting elastase or cathepsin G activity, but not in fractions exerting proteinase 3 activity. Using purified human leukocyte elastase (HLE), C5a responses like intracellular calcium influx, β-glucuronidase release, and chemotaxis were also specifically inhibited.Our experiments show that the release of HLE or cathepsin G from neutrophils specifically down-regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin G may therefore play an important role in the down-regulation of acute inflammation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 13 (2004), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Human keratinocytes are known to express the protease-activated receptors, PAR-1 and PAR-2. Activation of PAR-1 results in increased proliferation, whereas PAR-2 activation results in decreased keratinocyte proliferation. Trypsin activates PAR-1 and in higher concentrations, PAR-2. The aim of this study was to evaluate the overall effect of trypsin on keratinocyte proliferation in a mouse in vivo and in vitro model. Daily topical application of 0.3–300 pmol trypsin/cm2 on hairless mouse skin induced dose-dependent epidermal hyperproliferation as determined by an increase in 5-bromo-2′-deoxyuridine incorporation of up to eight-fold in basal keratinocytes and an up to three-fold increase in keratinocyte layers. This was accompanied by an increased transepidermal water loss. These effects of trypsin were abolished by the addition of the trypsin inhibitor n-p-tosyl-l-lysine-chloromethyl ketone. Histological analysis revealed acanthosis, hypergranulosis, and spongiosis in the epidermis as well as vasodilatation and an inflammatory infiltrate in the upper dermis. In the murine keratinocyte cell line PAM-212 activation of PAR-1 with specific activating peptides resulted in a calcium influx and an increase of proliferation, whereas activation of PAR-2 caused a diminished proliferation. Incubation with trypsin, PAR-1-, and PAR-2-activating peptides induced cytokine-induced neutrophil chemoattractant (KC) mRNA expression as a marker for inflammation in PAM-212 in a dose-dependent manner. In conclusion, our results suggest that trypsin induces in vivo epidermal proliferation and inflammation. Proliferation seems not to be signaled by PAR activation, but PAR-2-induced KC chemokine expression may contribute in part to trypsin-induced inflammation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Experimental dermatology 12 (2003), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Elafin is a skin-derived serine-protease inhibitor. It is thought to be important to prevent human leukocyte elastase-mediated tissue damage and might play an important role in maintaining the integrity of the human epidermis. Recent studies have provided evidence for an antimicrobial activity of elafin against P. aeruginosa. As gram-negative infections typically occur in barrier-disrupted skin we were interested to determine whether supernatants of the gram-negative bacteria P. aeruginosa and Escherichia coli were capable of inducing elafin expression.Supernatants of various P. aeruginosa strains stimulated elafin mRNA-expression and protein release, whereas supernatants of E. coli did not induce elafin expression. In non-differentiated cells the relative increase of elafin mRNA was much higher (100-fold) than in differentiated cells (sixfold), although the latter exhibited higher constitutive mRNA-expression (150-fold). However, concentrations of secreted elafin were similar in differentiated and non-differentiated cells after stimulation. We could not confirm a bactericidal effect against P. aeruginosa as described previously but observed that its growth was inhibited as demonstrated for different strains in liquid cultures. Growth of E. coli was not affected by elafin.In conclusion, the data presented in this paper suggest that elafin represents an innate immune response factor induced by secreted products of P. aeruginosa. Besides its elastase inhibitory potency elafin is an antimicrobial agent against P. aeruginosa.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Der Hautarzt 47 (1996), S. 901-908 
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Arzneimittel-Intoleranz ; Arzneimittel-Allergie ; Analgetika ; Scratch-Test ; Expositionstest ; Key words Drug allergy ; Drug intolerance ; Analgesics ; Scratch test ; Oral challenge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Although intolerance reactions to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987–1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verfied by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acetaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects.
    Notes: Zusammenfassung Obwohl Intoleranzreaktionen gegenüber Analgetika nicht ungewöhnlich sind, gibt es zur Zeit kein einheitliches und allgemein anerkanntes Vorgehen bei der Diagnostik von Analgetikaintoleranzreaktionen. Wir führten daher eine retrospektive Analyse der an unserer Klinik durchgeführten scratch- und Expositionstestungen mit Analgetika (Acetylsalicylsäure ausgenommen) durch, um die Aussagekraft und Risiken dieser Testverfahren zu überprüfen. Im Zeitraum von 1987–1992 haben wir 650 Expositions-Testungen bei anamnestisch begründetem Verdacht auf Arzneimittelintoleranz durchgeführt. In 98 Fällen bestand eine positive Anamnese für eine Intoleranz gegenüber Analgetika (ohne Acetylsalizylsäure), die in 56 Fällen durch positive Expositionstestrestultate verifiziert werden konnte. Dabei konnten, in der Reihenfolge abnehmender Häufigkeit, Propyphenazon, Diclofenac, Metamizol, Ibuprofen, Carbamazepin, Indometacin, Phenazon und Paracetamol als Auslöser von Intoleranzreaktionen verifiziert werden. Bei diesen Testungen zeigten sich eindeutige Dosis-Wirkungsbeziehungen zwischen Provokationsdosis und Provokationserfolg. Für Propyphenazon waren die halbeffektiven Provokationsdosen unabhängig von der Art der Reaktion (kutan, nasal, bronchial, anaphylaktoid). Scratch-Testungen mit Analgetika erscheinen für die Diagnostik von Analgetikaintoleranzen unzureichend. Bei der Durchführung von oralen Expositionstestungen mit Analgetika sind standardisierte Dosierungsschemata mit ansteigenden Dosierungen sinnvoll, um die Provokationsnebenwirkungen zu minimieren.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Der Hautarzt 45 (1994), S. 140-144 
    ISSN: 1432-1173
    Keywords: Schlüsselwörter: Psoriasis – Bade-PUVA-Solebäder – 8-Methoxypsoralen ; Key words: Psoriasis – Bath – PUVA – Salt bath – 8-methoxypsoralen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract. Balneo-phototherapy, in which salt baths are followed by UV-B irradiation, has proved successful in the treatment of psoriasis. Because of practical problems, the major one of which is the large turnover of bath solution volumes, balneotherapy has so far been limited to specialized treatment centres. With the aid of a polyethylene foil the volume of bathing solutions needed can be reduced to a total of 4 l per bath. Balneotherapy using small bath solution volumes for total body treatment can now be applied as an outpatient regimen for salt bath and bath-PUVA therapy. The methods for establishing balneotherapy with restricted water volumes and the advantages of bath-PUVA over conventional oral psoralen therapy are described.
    Notes: Zusammenfassung. Balneo-Phototherapie in Form von Solebädern und UV-B-Bestrahlung hat sich bei Patienten mit Psoriasis bewährt. Jedoch standen bislang praktische Schwierigkeiten, insbesondere die beim Einsatz von Wannenbädern pro Patient auftretenden großen Badevolumina einer weiten Verbreitung entgegen. Mit Hilfe einer Polyethylenfolie läßt sich die einzusetzende Badelösung (z. B. hypertonische Salzlösungen, Psoralen-Lösung) auf ein Volumen bis zu 4 l reduzieren und ermöglicht eine unter Kosten/Nutzen-Gesichtspunkten günstige Balneotherapie auch im ambulanten Bereich. Als Einsatzbereiche dieser ,,Folienbäder'' kommt die Soletherapie und Bade-PUVA-Therapie in Betracht. Das methodische Vorgehen sowie die geringeren Nebenwirkungen der Bade-PUVA-Therapie im Vergleich zur konventionellen peroralen Psoralen-Gabe werden dargestellt.
    Type of Medium: Electronic Resource
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