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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 27 (2002), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Expression of a variety of surface epitopes is a characteristic feature of immune cells. Receptors and adhesion molecules are the most predominant ones. It is also characteristic that epitope expression is modulated during cellular activation. In inflammatory skin diseases these structures can be used to define not only the type of cell but also their activity status. The availability of monoclonal antibodies and fusion proteins enabled to target cellular surface epitopes in order to modulate the cellular function as a principle of treatment.In psoriasis receptor-targeted therapy has been developed and tested in a considerable number of clinical trials. However, these approaches revealed that not all the strategies are equally effective.In this review the development of receptor-targeted treatment for skin disorders, mainly psoriasis, is described. Clinical as well as experimental data obtained with the various compounds employed are discussed with regard to clinical efficacy, safety and tolerability.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 136 (1997), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Anthralin is a most widely used compound for topical treatment of psoriasis. Whereas numerous studies have ascertained anthralin as a safe and effective drug its mode of action still remains unclear. Previous studies demonstrated dose-dependent inhibition of a number of pro-inflammatory functions in human enutrophils and monocytes (MO). The aim of the present study was to investigate in stimulated MO the effect of anthralin on the secretion of cytokines which are of known importance for the psoriatic tissue reaction.Highly purifies MO were incubated with anthralin (0·01–1·0μg/ml), its clinically inactive derivative danthrone (0·1 and 10 μg/ml), the solvent acetone, or medium alone. Culture supernatants were analysed for immunoreactivity for interleuking-1β, and -8 (IL-1β, IL-8), and tumour necrosis factor β (TNF-β) by specific ILISA. IL-6 bioactivity was determined using the B9-bioassay. Additionally, IL-1 bioactivity was measured by the D10[N4]M-bioassay.The results show a dose-dependent inhibition of MO IL-6, IL-8, and TNF-α release with a half- maximal inhibitory concentration of 0.25–0.6μ/ml of anthralin. There was no effect of danthrone or acetone on the secretion of these cytokines from MO. Secretion of IL-1β immunoreactivity measured by ELISA as determination of biological activity of IL-1 using the D10[N4]M- bioassay revealed a slight increase in IL-1 secretion with a maximum at an anthralin concentration of 0.1 μg/ml. Danthrone at a concentration of 10μg/ml and acetone (0.1%) similarly enhanced IL-1 secretion from human MO measured by both methods.Our results demonstrate a differential, dose-dependent inhibition of cytokine secretion from human MO by anthralin. The present data provide evidence that the anti-inflammatory and anti- proliferative activity of anthralin may at least in part be due to its inhibitory effect on pro-inflammatory cytokine secretion by MO.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 35 (1992), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In this study we report on functional characteristics of pustule as well as blood polymorphonuclear neutrophils (PMN) in patient suffering from relapsing bullous staphyloderma. Large numbers of viable PMN from newly formed pustules as well as from the peripheral blood were investigated. During the course of disease chemotactic migration, enzyme degranulation, superoxide-anion generation and leukotriene B4 production were determined simultaneously.The results revealed C5a- and NAP-1/IL-8-specific dysfunction of pustule PMN as compared with blood PMN. In contrast, FMLP-elicited functional activities of pustule PMN were only slightly affected.Our findings provide evidence that in inflamed tissue invading PMN are regulated by in situ generated mediators. C5a produced by staph. aureus-induced activation of the alternative pathway of the complement cascade represents predominant regulatory factor in situ. Furthermore, the results substantiate previous observations concerning different modulation of C5a and f-met-peptide receptors on human PMN.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 5 (1996), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract Involvement of T-lymphocytes in the pathogenesis of psoriasis and atopic dermatitis is well established. The question arises as to whether not only tissue infiltrating but also circulating T-lymphocytes are involved in the disease process. Therefore we sought to determine whether T-lymphocytes from patients with psoriasis and atopic dermatitis show abnormal biological behavior to the proinflammatory chemokine interleukin 8 (IL-8) in vitro as studied by their chemotactic activity. In addition, the expression of T-cell activation markers such as HLA-DR and interleukin 2 receptor (IL-2R) were analysed with FACS-technique. In all, 25 patients with psoriasis (13 patients with severe psoriasis and 12 patients with mild psoriasis) and 11 patients with atopic dermatitis were investigated. For comparison, T-lymphocytes from 14 healthy controls were tested equally. The results show that T-cell chemotactic responses to IL-8 were significantly decreased in patients with severe psoriasis as compared to healthy controls. T-cells from patients with atopic dermatitis demonstrated an even more pronounced decrease in chemotactic response as compared to T-cells from psoriasis patients or healthy controls. In contrast, increased expression of activation markers HLA-DR and IL-2R were demonstrated in circulating T-cells from patients with severe psoriasis and atopic dermatitis in comparison to healthy controls. It can be concluded that circulating T-cells in patients with severe psoriasis and atopic dermatitis show a decreased in vitro chemotactic response to IL-8. Furthermore, the in vivo phenotypic activation state of T-lymphocytes in these patients seemed to be associated with their decreased in vitro functional capacity.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 10 (2001), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: T cells play a major role in inflammatory skin disorders such as psoriasis vulgaris and atopic dermatitis. They are both active on the level of cell-to-cell interaction and by the secretion of pro-inflammatory mediators. CD26 is a lymphocyte membrane-associated dipeptidyl peptidase IV (DPP IV), which is able to inactivate chemokines such as RANTES or eotaxin by cleaving dipeptides from the NH2−terminus of proteins. We investigated the expression of CD26 on CD4+ and CD8+ peripheral blood T cells in patients with psoriasis and atopic dermatitis. In addition PASI and SCORAD as a measure of disease severity were determined in each patient at the time of blood drawing. Thirty patients with psoriasis, 15 with atopic dermatitis and 17 age- and sex-matched healthy persons were investigated by two-colour flow cytometry using epitope-specific monoclonal antibodies. Our results revealed, that there is a significant decrease (P〈0.05) of CD26 expression on CD8+ T cells in both psoriasis (7.7%±3.3, mean and SD, n=30) and atopic dermatitis patients (7.9%±3.7, mean and SD, n=15) compared to the control population (11.58%±5.0, mean and SD, n=17). However, there was no correlation to disease severity as determined by PASI and SCORAD, respectively. Since CD26 can be regarded as an anti-inflammatory principle the decreased expression in psoriasis and atopic dermatitis patients may lead to a dysbalance in favour of pro-inflammatory mediators in both clinical conditions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 10 (2001), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Dendritic cells seem to be of major importance for the pathogenesis of psoriasis. They are increased in number in lesional psoriatic skin which is thought to be due to an increased influx from the peripheral blood regulated by chemotaxins. Using a biological/biochemical approach we have addressed the question whether psoriasis scale extracts contain proteinaceous chemotaxins for dendritic cells. Human monocytes differentiated into dendritic cells by culture with GM-CSF and IL-4 (MoDC) served as responder cells. Chemotactic activity for MoDC was purified by several HPLC-steps. The results of our study show that C5a/C5adesarg is the major chemotactic peptide for MoDC in psoriasis scale extracts. In comparison to other stimuli such as fMLP or monocyte chemotactic peptide 1 (MCP-1) C5a proved to be a most potent and efficient chemotaxin for MoDC. C5a co-eluted with MRP14/calgranulin B which is present in large amounts in psoriasis scale extracts as identified by amino acid sequencing. However, MRP14/calgranulin B did not possess any chemotactic activity for MoDC. Our results provide evidence that C5a/C5adesarg although not specific for dendritic cells seems to be the major chemoattractant for these cells in lesional psoriasis skin.
    Type of Medium: Electronic Resource
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  • 7
    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:  Keloid disease (KD) is an abnormal form of scarring with a familial predisposition. Genetic studies have yet to identify the genes involved in KD. Transforming growth factor β (TGF-β) has multiple cellular activities including cellular proliferation, differentiation and extracellular matrix production. TGF-β family members such as TGF-β1 and TGF-β2 are known to be involved in KD formation. However, we previously demonstrated a lack of association between common TGF-β1 and TGF-β2 polymorphisms and KD. Other studies have implicated TGF-β receptors in KD pathogenesis. TGF-β receptors were therefore selected as candidate-susceptibility genes for this condition. Single-nucleotide polymorphisms (SNPs) in TGF-β receptors I, II and III (TGF-βRI, TGF-βRII and TGF-βRIII) were identified and investigated for association with the risk of developing KD. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping novel and known TGF-β receptor polymorphisms. DNA samples from 92 KD cases and 181 controls were examined. There were no statistically significant differences in genotype or allele frequency distributions between cases and controls for the TGF-β receptor SNPs. Therefore, these TGF-β receptor polymorphisms are unlikely to be associated with keloid scarring. It is possible that other SNPs in other TGF-β family members are associated with KD. To our knowledge, this is the first report of a case-control association study with KD and TGF-β receptor gene polymorphisms.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Copenhagen : Blackwell Publishing Ltd
    Allergy 54 (1999), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 127 (1992), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Anthralin is a well-established and widely used compound for topical treatment of psoriasis. In recent years attention has been focused on the anti-inflammatory properties of anthralin, with particular reference to psoriasis. In this study the effect of anthralin on human monocyte chemotaxis, superoxide-anion generation, and enzyme degranulation, were investigated. For comparison, the effect of the clinically inactive anthralin derivative danthrone and the solvent (acetone) were also studied. The results show that anthralin potently inhibits stimulated human monocyte superoxide-anion generation and enzyme degranulation, with a half-maximal inhibitory concentration (IC50) of as low as 0.02 μg/ml. Chemotactic migration of monocytes, however, was only affected when very high doses of anthralin (10 μg/ml) were used for pretreatment of the cells. Danthrone, up to a concentration of 10 μg/ml, or acetone alone (0.1%, v/v), did not inhibit the monocyte functions tested. Our results indicate that anthralin at pharmacological concentrations is a potent and selective inhibitor of human monocyte pro-inflammatory activities, by inhibiting respiratory burst activity (e.g. superoxide-anion generation) and enzyme degranulation, without affecting chemotactic migration.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 150 (2004), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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