The British journal of dermatology
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Randomized Controlled Trial Clinical Trial
Effects of H1 antagonists on the cutaneous vascular response to histamine and bradykinin: a study using scanning laser Doppler imaging.
Histamine plays an important part in the cutaneous weal and flare response which underlies many allergic skin conditions. It has a direct effect on the local vasculature to promote vasodilatation and increase microvascular permeability and may also initiate the more widely spread neurogenic flare. Quantification of these responses and studies of the mediator mechanisms underlying them have been limited by the lack of appropriate techniques to investigate them. ⋯ The histamine concentration in dialysate from unprovoked skin was 4.19 +/- 0.75 nmol/L. These data reveal differences in the dermal responses to different mediators when assessed using scanning LDI. They confirm that histamine is released within the weal but not the flare response to the intradermal injection of both histamine and bradykinin and that its effects on the local vasculature to cause the oedematous weal and the axon reflex-mediated flare are significantly attenuated by the H1 antagonist cetirizine and to a lesser extent by the H1 antagonist loratadine.
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Tripe palms are thickened, moss-like or velvety textured exaggerations of the normal dermatoglyphics. The disease belongs to the spectrum of papulosquamous paraneoplastic syndromes. Although suspected, the role of transforming growth factor-alpha (TGF-alpha) has not been clearly established. ⋯ The TGF-alpha probe reacted strongly with the mast cells that also reacted with the antitryptase monoclonal antibody. Elevated tryptase, histamine and TGF-alpha levels prior to interferon-alfa administration decreased under treatment. The demonstration of TGF-alpha in infiltrating mast cells, the clinical regression of tripe palms and the lowering of the serum level and the mast cell molecular signal of the cytokine when systemic mastocytosis was controlled by interferon-alfa, suggest a key role for TGF-alpha in this cutaneous paraneoplastic syndrome.
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A questionnaire survey of dermatologists practising in Scotland was carried out to assess strategies for the management of women prescribed isotretinoin for acne. The results of the study suggested that the prevention of pregnancy during treatment is of considerable concern to dermatologists: over 90% routinely asked women about sexual activity and 97% routinely gave both verbal and written advice on the need to avoid pregnancy during treatment. ⋯ Additionally, there was an apparent lack of recognition of the possibility of sexual activity in girls aged under 16 years. Suggestions for the management of women prescribed isotretinoin include taking a sexual history from all women; providing clear information on the need to avoid pregnancy during treatment; obtaining informed consent prior to treatment; recommending the use of effective contraceptive measures; and exclusion of pregnancy prior to treatment by means of a suitably timed blood or urine sample and sensitive assay technique.
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Randomized Controlled Trial Clinical Trial
Granulocyte/macrophage colony-stimulating factor increases wound-fluid interleukin 8 in normal subjects but does not accelerate wound healing.
Granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to play an important part under conditions of impaired wound healing. This is not confirmed and it is also unknown whether GM-CSF affects wound healing in healthy subjects. We conducted a randomized, double-blind, placebo-controlled pilot study in 10 healthy volunteers. ⋯ Transforming growth factor (TGF) beta 1 and beta 2, epidermal growth factor (EGF), and beta-fibroblast growth factor (beta-FGF) were not measurable in any wound fluid. The lack of efficacy of exogenously delivered GM-CSF on wound healing in healthy subjects is probably based on the failure of GM-CSF to induce 'wound-healing cytokines' like PDGF, FGF, TGF, EGF or VEGF. However, GM-CSF increases IL-8 release, which is a potent chemotactic cytokine, indicating that GM-CSF might be of therapeutic value under conditions of impaired chemotaxis.
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Plasminogen activation is observed in the human epidermis during re-epithelialization of epidermal defects. The activation reaction depends on plasminogen activators (PAs) associated with re-epithelializing keratinocytes. PA inhibitor type 2 (PAI-2) is thought to be a major epidermal PA inhibitor in keratinocytes. ⋯ In organotypic cocultures, in which the transition from a re-epithelializing to a sedentary phenotype can be studied, PAI-2 was most strongly expressed in early cultures prior to formation of a differentiated epidermis-like structure. We found a strong expression of PAI-2 in keratinocytes that re-epithelialized dermal burn wounds or lesions caused by the autoimmune blistering disease pemphigus vulgaris. Our results suggest that not only PAs, but also a major PA inhibitor, PAI-2, are expressed in keratinocytes that are actively involved in re-epithelialization.