摘要:

Since the majority of itching skin diseases are inflammatory or allergic, it has been assumed that release or activation of inflammatory mediators, stimulating the itch receptors, play an essential role in the pathophysiology of itch. In this review some of the possible mediators are discussed. Histamine induces itch upon intradermal injection, but urticaria is the only itching dermatosis which is significantly relieved by antihistamines. Serotonin is much weaker than histamine in provoking itch upon intradermal injection. Serotonin acting in synergism with prostaglandins may cause itch in polycythaemia vera. Neuropeptides release histamine from skin mast cells, but it remains to be determined whether neurogenic peptides are resopnsible for clinical pruritus. Prostaglandins enhance pruritus induced by intradermal histamine (and serotonin) but are weak pruritogens per se. Lymphocytes are present in many itching skin diseases and it could be assumed that lymphokines are involved in the pathogenesis of itch. Supporting this theory is the finding that ciclosporin A, an inhibitor of lymphokine production, reduces itch in atopic dermatitis. Central mechanisms are essentially unknown, but there are indications that opioid peptides might be involved in the central transmission of itch.

ISSN:1660-5527    

DOI:10.1159/000211009

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Capsaicin selectively excites C-polymodal nociceptors in mammalian skin. In the rat, the only species so far studied in detail, a long-term desensitization of a subpopulation of C-polymodal nociceptors occurs after the initial excitation. After nerve treatment, permanent loss of some C-polymodal nociceptors is found in the rat. It is argued that capsaicin must act primarily on C fibres involved in signalling about pain and not itch, although there may be overlap between the C afferents involved in these two nociceptive sensations. The possibility is raised that C mechanoreceptors, with their good histamine sensitivity, are also involved in itch.

ISSN:1660-5527    

DOI:10.1159/000211010

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Despite advances in dialysis treatment, pruritus remains a common and distressing manifestation of chronic renal failure. Two-thirds of patients on maintenance hemodialysis experience persistent itching, however, the etiology of this condition is unknown. Although pruritic patients have higher serum levels of parathyroid hormone (PTH) than nonpruritic patients, subsequent studies do not support a role for PTH as a peripheral itch mediator. Experimental itching induced by intracutaneous histamine injections is significantly stronger in patients with uremic itching, indicating an enhanced sensitivity to pruritogens in these patients. Immunohistochemistry of skin nerve fibers has shown conflicting results and the innervation pattern of uremic skin clearly needs further elucidation. The possibility of uremic itching being a neuropathic manifestation awaits future investigations.

ISSN:1660-5527    

DOI:10.1159/000211011

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This article reviews the effect of H1 antihistamines on the pruritus of urticaria, from articles in which their therapeutic effect on chronic idiopathic and physical urticaria is assessed. In limited studies available pruritus improved concomitantly with wealing by an average of two thirds, though the response in individual patients was variable. In some physical urticarias the pruritus and wealing showed disproportionate improvement compared to erythema. The minimally sedating H1 antihistamines were as effective or more effective than classical H1 antihistamines. The dose of antihistamines that totally abolished a histamine weal only partly reduced urticarial weals (therefore by inference also of the associated pruritus). Additional therapy aimed at pruritogenic mediators other than histamine would be expected to improve urticarial pruritus.

ISSN:1660-5527    

DOI:10.1159/000211012

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effect of terfenadine, an H1 0.05). This study shows that H1-receptor blockade does not inhibit anthralin inflammatio

ISSN:1660-5527    

DOI:10.1159/000211013

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This randomised double-blind, placebo-controlled, cross-over study compared the effects of single oral doses of terfenadine 120 mg, cetirizine 10 mg, and loratadine 10 mg on experimentally induced weal and flare reactions. The areas of weal and flare induced by intracutaneous injections of histamine were measured using planimetry, weal thickness by A-scan pulsed ultrasound and erythema index by a device which measures the relative reflectance of red and green light. All three antihistamines suppressed the weal and flare area and weal thickness 3, 6, 12 and 24 h after dosing. At the usual currently recommended doses terfenadine and cetririzine were most effective after 6 h and were more potent than loratadine for the first 6 h of the study.

ISSN:1660-5527    

DOI:10.1159/000211014

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Although dithranol has been used for 75 years in the treatment of psoriasis, its working mechanism is still not resolved. In order to further define the mode of action of dithranol, the interference with normal skin was studied. The effect of dithranol on epidermal proliferation, keratinization and inflammation was examined using immunohistochemistry. Punch biopsies from 6 volunteers who applied dithranol 0.5% in petrolatum were taken before application, after 48 and 96 h. Biopsies were processed for assessing epidermal proliferation by Ki67 binding (cycling cells), for keratinization by Ks8.12 binding (keratin 13 and 16, keratin 16 is expressed by hyperproliferative keratinocytes) and RKSE60 binding (keratin 10). For assessing inflammation the antibodies antielastase (polymorphonuclear leukocytes (PMN)), T11 (T lymphocytes, CD2), T6 (Langerhans cells, CD1a) and WT14 (monocytes/macrophages, CD 14) were used. Ki-67 staining started to increase between 48 and 96h whereas Ks8.12 binding had increased already between 0 and 48 h. RKSE60 staining showed a decline between 48 and 96 h. Inflammation in the dermis showed an increase after 48 h, and continued to increase. In the inflammatory infiltrate, the accumulation of PMN was limited compared to the pronounced infiltration of T lymphocytes. Langerhans cell shape and epidermal position altered in 4 volunteers. Application of dithranol on normal skin produces analogies and discrepancies compared to application of dithranol on psoriatic lesions. Direct interference with epidermal growth and differentiation seems less likely as the antipsoriatic principle.

ISSN:1660-5527    

DOI:10.1159/000211015

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Topical treatment of the mouse tail with antipsoriatic drugs enhances orthokeratotic cell differentiation in the epidermal scales. We developed a new evaluation system for this test which allows quantification of drug efficacy. Drugs were applied topically, once daily, 5 times a week, for 2 weeks. Two hours after the last treatment the animals were sacrificed, longitudinal sections of the tail skin were made and prepared for histological examination (hematoxylineosin staining). As indicator of orthokeratosis (OK), the length of the granular layer per scale was measured microscopically with a semiautomatic image evaluation unit and related to the total scale length(= % OK per scale). Drug activity was defined by the increase in the total length of orthokeratotic regions, 100% activity corresponds to a granular layer extending over the whole scale length. In this model dithranol and retinoic acid dose-dependently increased orthokeratosis up to 75 and 79%, respectively. Beech tar, in a concentration of 5 % induced a 19 % increase in orthokeratosis. Morphometric quantification by image analysis of the conversion of parakeratotic into orthokeratotic regions in mouse tail scales induced by topical drug treatment seems to be a suitable and reliable procedure to investigate new drugs from which antipsoriatic acitivity may be expected.

ISSN:1660-5527    

DOI:10.1159/000211016

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In previous studies, we have shown that architecture and differentiation of human epidermis reconstructed by culturing dissociated keratinocytes on deepidermized dermis at the air-liquid interface resembles very much those of epidermis in vivo. The various types of epidermal layers are present with the appropriate differentiation markers, such as the bullous pemphigoid antigen, suprabasal keratins, involucrin, membrane-bound transglutaminase and filaggrin, positioned almost like in normal epidermis. At the ultrastructural level, heterogeneous keratohyalin granules and intra- and extracellular membrane-coating granules are observed. After 7 days of culture, a compact stratum corneum covers the reconstructed epidermis. In the present work, the barrier function of the reconstructed epidermis was evaluated by measuring fluxes of 3H-water. Our results show that under the various culture conditions tested, the presence of the reconstructed epidermis reduces dramatically the permeability of the deepidermized dermis although the skin equivalent exhibits a higher permeability than normal skin. Conditions that favor terminal differentiation of the keratinocytes such as maintaining the cultures in delipidized serum improve the barrier function. Reduction of the relative humidity has a similar effect, whereas the age of the culture is of no influence. Experiments are in progress to reconstruct human epidermis with a barrier function as efficient as in normal skin.

ISSN:1660-5527    

DOI:10.1159/000211017

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

From a series of naphthalene and benzoic acid derivatives we have identified synthetic retinoic acid analogues exhibiting high selectivity for the nuclear retinoic acid receptors RARα (Am 580), RARβ (CD 2019) and RARγ (CD 437) as well as ligands sharing high affinities for all RAR subtypes (CD 367). The compounds were evaluated in two complementary screening systems: (1) binding to nuclear proteins extracted from COS-7 cells after transfection with the appropriate expression vectors, and (2) induction of plasminogen activator in the embryonic mouse teratocarcinoma cell line F9. All compounds behaved as retinoic acid agonists in the F9 te

ISSN:1660-5527    

DOI:10.1159/000211018

出版商:S. Karger AG    

年代:1992

数据来源: Karger