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Biomedical subjects

G Wozel

Publications and source records attributed to G Wozel.

At least 37 records · Page 2Linked to original sources

Croconazole: an inhibitor of eicosanoid synthesis in A23187-stimulated human polymorphonuclear leukocytes and human whole blood.

The aim of this investigation was to ascertain possible inhibitory effects of the antimycotic agent croconazole on eicosanoid biosynthesis. Human polymorphonuclear leukocytes (PMN) and whole blood of healthy donors were pretreated with croconazole in different concentrations (0.8-100 microM) for 5 min followed by the addition of Ca ionophore A23187 (10 microM) and subsequent incubation for 10 min (PMN) and 30 min (whole blood), respectively. Thereupon the eicosanoids were determined by reversed-phase high-performance liquid chromatography. Croconazole exhibited dose-dependent inhibitory activity on the 5-lipoxygenase (5-LOX) of neutrophils. The mean half maximum inhibition concentration (IC50) of croconazole for synthesis of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) was determined as 7.8 +/- 1.7 and 7.6 +/- 0.3 microM, respectively. The mean IC50 value for LTB4 estimated in whole blood was distinctly higher (27.0 +/- 3.1 microM) compared with that determined in PMN. Additionally, an inhibitory effect (IC50 9.8 +/- 2.0 microM) on the production of the cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (HHT) was demonstrated, whereas the production and/or releasing of 12-hydroxyeicosatetraenoic acid (12-HETE) was not attenuated by the azole. Our results in the cell-free 5-LOX system favor a direct inhibitory action of croconazole on 5-LOX, with a relatively high portion (45-77%) of reversibility. In spite of distinctly lower inhibitory potency compared with reference inhibitors such as nordihydroguaiaretic acid and indomethacin, croconazole is an effective inhibitor of arachidonic acid metabolism. Our results suggest that croconazole may be of some benefit in anti-inflammatory therapy.

Antifungal Agents↗

The effect of topical retinoids on the leukotriene-B4-induced migration of polymorphonuclear leukocytes into human skin.

Systemic retinoids are effective in a variety of inflammatory dermatoses. Disorders in which polymorphonuclear leukocytes (PMN) are involved, such as psoriasis and acne, respond particularly well to various retinoids. However, side-effects restrict the use of systemic retinoids to severe manifestations. Topical application might provide the possibility of avoiding the systemic side-effects of these compounds. In this communication we report on the modulation of transepidermal migration of PMN by topical application of all-trans-retinoic acid, 13-cis-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone. Test areas of healthy volunteers were pretreated with these retinoids in a cream base and with corresponding placebo creams, and intraepidermal accumulation of PMN was quantified 24 h after epicutaneous challenge with leukotriene B4 (LTB4), using elastase as a marker enzyme. Topical treatment with 13-cis-retinoic acid resulted in a marked and statistically significant inhibition of the LTB4-induced migration of PMN. All-trans-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone reduced the accumulation of PMN slightly, but not statistically significantly. Topical treatment with arotinoid methyl sulphone had no effect.

Administration, Topical↗

[Effectiveness of combination treatment with H1-(Tavegyl) and H2-antagonists (Altramet) in chronic/chronically-recurrent urticaria].

Histamine H1 receptor antagonists are a mainstay in the management of chronic/chronic recurrent urticaria (c./c.r.U.). Since experimental studies have confirmed the presence of cutaneous H2 receptors partially conflicting results have been reported on the use of H2 antagonists in c./c.r.U. 20 patients with c./c.r.U. of idiopathic type were treated with cimetidine plus clemastine or placebo plus clemastine in a double-blind crossover study. Before this treatment traditional H1 antagonists alone failed to show any satisfying therapeutic effect. The results reveal that combined therapy is statistically more effective than corresponding H1 antagonists alone (P = 0.001). The addition of cimetidine is proposed in patients with c./c.r.U. if conventional therapy has been tried and proven ineffective.

Adult↗

[The REM syndrome--alternative therapeutic possibilities].

Chloroquine and chloroquine derivatives have proved successful in the therapy of REM syndrome (REMS). Alternative treatment schedules have not been described so far. In a female Patient, chloroquine therapy had to be discontinued because of ophthalmologic contraindication. PUVA therapy induced complete remission, whereas dapsone alone only led to incomplete improvement. Additional UV radiation--mainly UV-A--had a positive effect. Chloroquine contraindication justifies the use of these alternative therapeutic approaches to REMS.

Adult↗

[Urticaria vasculitis and sulfone, a case report].

Systemic corticosteroids play a predominant role in the treatment of urticarial vasculitis (U.V.). If steroids are contraindicated, there may be applied a variety of pharmacologically different compounds. A female patient suffering from U.V. and metabolic syndrome, who had not shown any positive response to indomethacin, H1 and H2 antagonists, or colchicine, was treated with dapsone. As a result, the clinical symptoms improved within a few days and her hypocomplementemia normalized. We discuss the possible mechanisms of action of sulphones in U.V.

Aged↗