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T Ruzicka

Publications and source records attributed to T Ruzicka.

At least 307 records · Page 17Linked to original sources
PubMed1991

Inhibition of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] binding to epidermal cells by ultraviolet-B.

12-hydroxyeicosatetraenoic acid (12-HETE), the main eicosanoid in skin, is assumed to have both pathophysiologic effects in inflammatory skin diseases such as psoriasis and atopic eczema and a physiologic role in the biology of cutaneous reparative processes. Because 12-HETE exerts its effects via specific high-affinity epidermal receptors, and ultraviolet-B (UV-B) is capable of modulating various cell-surface molecules, the effects of single and repeated UV-B irradiations on the 12(S)-HETE binding sites in a human epidermal cell line, SCL-II, were studied. UV-B (100-300 J/m2) induced a large decrease in 12(S)-HETE binding in a dose-dependent manner. The inhibition occurred after a latency period of 6 h, reached its maximum at 18 h and slowly declined thereafter. A single UV-B dose of 300 J/m2 or repeated irradiation with 50 J/m2 of UV-B resulted in a 70% decrease in the number of binding sites (Bmax), whereas receptor affinity remained unaffected. The modulation of epidermal 12-HETE receptors by UV-B may partly explain the therapeutic effects of UV-B, but possibly also contribute to photodamage to skin.

Cell Count↗
PubMed1991

Blood rheology in lupus erythematosus.

Blood rheology is one of the determinants of perfusion and might therefore have an impact on the thromboembolic complications of lupus erythematosus. This study aimed at defining the flow properties of blood in patients with various types of lupus erythematosus. Results for 51 patients were compared with those for 20 controls matched for sex. The patients were divided into subgroups--chronic discoid, subacute cutaneous, and systemic lupus erythematosus--according to their clinical or laboratory characteristics. Blood and plasma viscosity, packed cell volume, red cell aggregation, and red cell deformability were used as parameters of blood rheology. Blood and plasma viscosity and red cell aggregation were significantly different in patients compared with controls, indicating reduced blood fluidity in lupus erythematosus. There were no marked sex differences. The rheological effects were greater in those with systemic lupus erythematosus than in those with chronic discoid or subacute cutaneous lupus erythematosus. The presence of a positive antinuclear antibody titre or methods of treatment (systemic steroids or retinoids) had no apparent effect on the parameters tested. It is suggested that a complex haemorheological deficit exists in lupus patients.

Acute Disease↗
PubMed1991

Effect of ciclosporin on epidermal 12(S)-hydroxyeicosatetraenoic acid binding sites.

12-Hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in the pathogenesis of inflammatory skin diseases. Recently, high-affinity binding sites for this eicosanoid have been identified on human keratinocytes by our group. Since ciclosporin exerts therapeutic effects in chronic inflammatory dermatoses such as psoriasis or atopic eczema, the influence of the drug on 12(S)-HETE binding to human keratinocytes was studied. No competitive inhibition of 12(S)-HETE binding was observed in ciclosporin concentrations between 10(-10) and 10(-6) M. In contrast, pretreatment of epidermal cells for 24 h resulted in a dose-dependent decrease of specific 12(S)-HETE binding. The analysis of saturation curves showed that the inhibition of 12(S)-HETE binding by ciclosporin was due to the decrease of 12-HETE binding sites, while receptor affinity remained unchanged. In addition, ciclosporin blocked the interferon-gamma-induced increase in epidermal 12(S)-HETE binding. These findings suggest that the effects of ciclosporin in cutaneous disorders could be partly mediated via an influence on epidermal 12(S)-HETE binding.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

[Benign symmetric Launois-Bensaude type III lipomatosis and Bureau-Barrière syndrome].

We report on a patient with an unusual distribution of benign symmetric Launois-Bensaude lipomatosis. In addition, the patient presented with Bureau-Barrière syndrome. With regard to our own observations and those reported in the literature, we propose a new classification of the disease referred to the distribution of the fatty tissue.

Amputation, Surgical↗
PubMed1991

Preparation, metabolic stability and biological properties of omega-trifluorinated analog of 12-hydroxyeicosatetraenoic acid.

12-Hydroxyeicosatetraenoic acid (HETE) is associated with a variety of inflammatory conditions. For studies on pathophysiological function of 12-HETE, metabolically more stable analogs of 12-HETE would be useful. We biologically synthesized 20,20,20-trifluoro-12-HETE (20-F3-12-HETE) by incubating enantioselectively synthesized 20,20,20-trifluoro-arachidonic acid with human platelets. The product was identified by UV absorption spectrophotometry and gas chromatography-mass spectrometry. When 1 microgram 20-F3-12-HETE was incubated with 5 X 10(6) human neutrophils for 45 min, only 5% of the analog was metabolized while 66% of 12-HETE was metabolized in the same incubation condition. With 2 X 10(7) neutrophils, 37% of the analog was metabolized at the same incubation condition while 87% of 12-HETE was metabolized. Thus, by blocking omega-oxidation of 12-HETE with fluorine atoms, the stability of 12-HETE was greatly increased. This result indicates that the omega-oxidation is a major pathway for 12-HETE metabolism. The analog demonstrated as much chemotactic activity on human neutrophils as 12-HETE, and binding affinity of the analog for 12-HETE receptor in human epidermal cell was equal to that of 12-HETE. An analog of 12-HETE, which has extended metabolic stability without alteration of neutrophil chemotactic activity and binding affinity, would be a useful tool for studies on pathophysiological role of 12-HETE in inflammatory conditions.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Regulation of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) binding sites on human epidermal cells by interferon-gamma.

We recently detected specific high-affinity binding sites for 12(S)-HETE, the main arachidonic acid metabolite in skin, on epidermal cells. The putative receptor is involved in keratinocyte chemotaxis toward 12(S)-HETE, which points to its participation in wound healing. In an effort to further characterize the 12(S)-HETE receptor, we investigated its regulation by various cytokines. Of the tested cytokines, only interferon (IFN)-gamma led to a massive induction of the 12(S)-HETE receptors. The effect was dose and time dependent and blocked by cycloheximide. The up-regulation of 12(S)-HETE receptors by IFN-gamma may represent an amplification mechanism of the assumed role of 12(S)-HETE in skin wound repair.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Influence of eicosanoids on fibroblast chemotaxis and protein synthesis in vitro.

Metabolism of fibroblasts plays a key role in wound healing, fibrosis, rheumatoid arthritis, and similar physiological and pathological processes. The regulatory influence of eicosanoids, an important class of inflammatory mediators, on fibroblast metabolism, in these processes is, to date, unclear. The aim of this study was to investigate the effect of some eicosanoids on chemotaxis and protein synthesis of fibroblasts in vitro. Of twelve eicosanoids tested, only 5(S)-HETE, LTB4, and 12(S)-HETE were active as chemo-attractants for fibroblasts. 5(S)-HETE was the most potent attractant. It exerted its maximal activity at 10(-10) mol/l. 12(S)-HETE and LTB4 caused similar dose dependent fibroblast chemotaxis with a maximum of activity at 10(-7) M and 5 x 10(-8) M, respectively. Hydroxylation of LTB4 on C20 or methylation of the carboxy group of 12(S)-HETE decreased reactivity of the parent compounds only slightly. Eicosanoid induced chemotaxis could be antagonized by 12(S)-HETE but not by the proteinaceous chemoattractants fibronectin, PDGF, or EGF. Receptors for peptide and eicosanoid mediated chemotaxis are thus different. Inhibition of collagen synthesis was observed in the presence of 5(S)-HETE and 12(S)-HETE while total protein synthesis was unaffected by 12(S)-HETE and augmented by 5(S)-HETE. These data suggest that certain eicosanoids specifically regulate fibroblast activities in wound healing and similar events of connective tissue reorganization.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

High-affinity binding and lack of growth-promoting activity of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) in a human epidermal cell line.

The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in skin physiology and pathophysiology. Specifically, it has recently been discussed as a growth promoting agent in keratinocytes. Our aim was to find out whether epidermal cells possess specific receptors for 12-HETE which would mediate the effects of this eicosanoid in skin, including the putative growth stimulating activity. We could identify specific binding sites for 12(S)-HETE on the human epidermal cell line SCL-II. The analysis of binding data revealed a single class of binding sites with a Kd of 2,6 nM and a Bmax of 216,000 sites per cell. The binding was saturable, readily reversible, and specific for 12(S)-HETE with lower affinities for other monoHETE. We failed to detect any significant proliferative activity of 12(S)-HETE in the same epidermal cell line, although we applied three independent methods for evaluation of cell growth and used a concentration of 12(S)-HETE which should enable an optimal receptor occupancy. Thus, epidermal cells possess high-affinity 12(S)-HETE binding sites which are likely to be involved in the effects of this eicosanoid in epidermis. However, biologic effects other than direct growth stimulation seem to be transduced by 12(S)-HETE receptors in epidermal cells which need further investigation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Dithranol: a review of the mechanism of action in the treatment of psoriasis vulgaris.

Dithranol is highly effective in the treatment of psoriasis. The drug inhibits keratinocyte hyperproliferation, granulocyte function and, in addition, may exert an immunosuppressive effect. Free radicals, histamine, eicosanoids and platelet-activating factor have been shown to be involved in dithranol-induced dermatitis, and the oxidation products of the drug are responsible for the staining. Our experimental data suggest that extracellularly generated oxygen free radicals are responsible for both the antipsoriatic and irritative effect of the drug. Furthermore, we could recently provide evidence that extracellularly generated superoxide anion radical also induces an active adaptation mechanism resulting in increased tolerance to dithranol upon repeated application. This adaptive process may explain the requirement for increasing dithranol concentrations to maintain the antipsoriatic efficacy, and also the beneficial effect of other antipsoriatic modalities such as UV-B on dithranol-induced dermatitis. The recognition of this adaptive mechanism may open future prospects to overcome some limitations concerning the practical use of dithranol.

Anthralin↗
PubMed1990

Efficiency of acitretin in combination with UV-B in the treatment of severe psoriasis.

Compared with the antipsoriatic retinoid etretinate, the new aromatic retinoid acitretin represents an important advance due to its rapid elimination kinetics. Since in psoriasis vulgaris retinoids are used predominantly in combination regimens, we investigated the therapeutic efficacy of acitretin and UV-B compared with placebo and UV-B in a double-blind, randomized multicenter trial in 82 patients with severe psoriasis. They were treated with 35 mg of the study medication during the first 4 weeks of therapy and 25 mg thereafter, concomitantly with UV-B irradiation in increasing energy doses. Forty patients who underwent therapy with acitretin and UV-B and 38 patients who underwent therapy with placebo and UV-B were evaluated for efficacy. The target variables--psoriasis severity index and total UV-B dose--were reported at intervals of 2 weeks over a maximum period of 8 weeks. At the end of treatment, the psoriasis severity index decrease was 79% in the acitretin and UV-B group and 35% in the placebo and UV-B group. The response rate, defined as greater than or equal to a 75% decrease of the psoriasis severity index, was 60% for the combination treatment and only 24% for the control treatment. This treatment response was achieved with markedly lower cumulative UV-B energy. The median cumulative UV-B energy applied to reach 75% clinical improvement was 11.8 J/cm2 vs 6.9 J/cm2. Side effects showed a similar pattern in both groups. Our data show that the acitretin dramatically improves the results of UV-B treatment in patients with severe psoriasis. In addition, it markedly decreases the effective cumulative UV-B dose, thereby reducing the potential long-term hazards of UV irradiation. We conclude that the acitretin plus UV-B combination treatment represents a highly effective therapeutic regimen in severe psoriasis.

Acitretin↗
PubMed1990

[Cutaneous amyloidoses].

Significant advances in basic research in biochemistry and immunology has tremendously increased our understanding of amyloidoses. The chemical structure of several amyloid proteins has been partly characterized. Specific antibodies may provide new methods for immunohistological diagnosis of amyloidoses. Cutaneous manifestations can affect the skin only or develop during the course of systemic amyloidoses. Although these conditions are so rare, dermatologists should be aware of the changing clinical manifestations of cutaneous amyloidoses if they wish to avoid diagnostic failures.

Amyloid↗
PubMed1990

[Cyclosporin A treatment of Behçet's disease].

We report on an Italian patient with severe mucocutaneous and arthritic manifestations of Behçet's disease. Monotherapy with cyclosporin A led to a complete remission. The therapeutic efficiency could be verified by relapse after discontinuation of treatment and a second remission after its reintroduction.

Administration, Oral↗