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T Ruzicka

Publications and source records attributed to T Ruzicka.

At least 19 recordsLinked to original sources
PubMed1992

Interleukin-8 receptor-mediated chemotaxis of normal human epidermal cells.

Normal human keratinocytes show chemotactic behavior towards interleukin-8 (IL-8). Under physiological conditions this cytokine seems to be present in an equilibrium between monomeric and dimeric forms, as indicated by Western blotting data. Radioligand binding studies suggest that keratinocyte chemotaxis is mediated by receptors specific for IL-8 dimers. IL-8 receptor-specific mRNA can be detected in a keratinocyte cell line by polymerase chain reaction.

3T3 Cells↗
PubMed1992

Langerhans cells of the human skin possess high-affinity 12(S)-hydroxyeicosa tetraenoic acid receptors.

The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) is the main eicosanoid formed by epidermal cells and is assumed to play an important role in skin physiology and pathophysiology. Our aim was to find out whether epidermal Langerhans cells possess specific receptors for 12-HETE which would mediate the effects of this eicosanoid in their skin microenvironment. By radioligand binding studies on isolated human Langerhans cells, we could identify specific binding sites for 12(S)-HETE. The analysis of binding data revealed a single class of binding sites with a Kd of 3.32 +/- 0.45 nM and a Bmax of 691,000 +/- 58,000 receptors per cell. The binding was saturable, readily reversible, and specific for 12(S)-HETE. The receptor is likely to mediate the potent chemotactic response of human Langerhans cells towards 12(S)-HETE, which we previously described. Our results strongly suggest that extremely low concentrations of 12-HETE which is formed by epidermal keratinocytes may dramatically influence the biology of Langerhans cells by receptor-mediated effects.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Treatment of cutaneous lupus erythematosus with acitretin and hydroxychloroquine.

A randomized, double-blind, multicentre study was performed to compare the efficacy of acitretin (50 mg/day) with hydroxychloroquine (400 mg/day) in 28 and 30 patients, respectively, suffering from cutaneous lupus erythematosus (LE). The study was carried out over an 8-week period. Improvement of facial LE lesions after treatment with acitretin and hydroxychloroquine was assessed using several clinical parameters. In the acitretin group there was marked improvement or clearing of erythema in 10/24 patients (42%), of infiltration in 15/24 (63%) and of scaling/hyperkeratosis in 12/20 (60%). In the hydroxychloroquine group there was complete clearing or marked improvement of erythema in 17/25 patients (68%), of infiltration in 17/25 (68%) and of scaling/hyperkeratosis in 15/23 (65%). Overall improvement occurred in 13/28 patients (46%) treated with acitretin and in 15/30 patients (50%) with hydroxychloroquine. The incidence of side-effects was higher in the acitretin group, and necessitated discontinuation of treatment in four patients. The present results demonstrate that both acitretin and hydroxychloroquine provide effective treatment in approximately 50% of cases of cutaneous LE.

Acitretin↗
PubMed1992

Defect of epidermal 12(S)-hydroxyeicosatetraenoic acid receptors in psoriasis.

12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play a central role in the pathophysiology of psoriasis. Since its effects in skin are mediated by specific high-affinity receptors, we studied the receptor characteristics in cultured epidermal cells from involved and apparently healthy skin of psoriasis patients by radioligand binding assay. Involved and uninvolved psoriatic epidermal cells showed a fourfold decrease in the number of 12-HETE binding sites as compared with normal healthy individuals and patients with atopic dermatitis, while receptor affinity remained unchanged. The decrease in receptor number was evident in psoriatic cells even in long-term culture and was not due to receptor down-regulation, defective response to interferon gamma or to protease degradation of receptor protein. The decrease in the number of 12-HETE receptors detectable even in clinically normal psoriatic skin functionally leads to diminished 12-HETE uptake and may thus represent a primary central molecular defect in the pathophysiology of the disease.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Interleukin-8 receptors in normal and psoriatic polymorphonuclear leukocytes.

Polymorphonuclear leukocyte (PMNL) infiltration is an important characteristic in psoriatic lesions. The proinflammatory 8-kD peptide interleukin-8 (IL-8) is present in psoriatic scales and possesses a high chemotactic activity on human neutrophils, which may relate to its role in psoriasis. Its chemotactic activity is mediated via specific receptors on PMNL. The goal of our work was to ascertain whether PMNL infiltration in psoriasis can be accounted for by functional abnormalities of the circulating PMNL due to alterations in the IL-8 receptor density or affinity (or both). Results of radioligand binding studies performed in 10 psoriatic patients, 10 patients with atopic eczema and 11 normal controls showed no difference in receptor affinity (Kd) between the groups. However, a slight but significant elevation in IL-8 receptor density was seen on PMNL from psoriatic individuals (31,230 +/- 3,237 binding sites per cell) compared to those from normal volunteers (24,152 +/- 2,643) and atopic eczema patients (24,092 +/- 2,743). Increased number of IL-8 receptors may, besides elevated cutaneous IL-8 concentrations, contribute to the intraepidermal accumulation of PMNL in psoriasis.

Adult↗
PubMed1992

Red lunulae in severe alopecia areata.

The development of red nail lunulae has been extremely rarely described in alopecia areata. We observed 2 patients, a 30-year-old woman and a 61-year-old man, both suffering from severe alopecia areata, and having red lunulae. The colour changes, which developed a few weeks after the acute onset of hair loss, disappeared slowly, leaving horizontal fissures (Beau's lines).

Adult↗
PubMed1992

The role of the epidermal 12-hydroxyeicosatetraenoic acid receptor in the skin.

The epidermal layer of the skin is the site of active arachidonic acid metabolism. The main product of epidermal keratinocytes is the 12-lipoxygenase derivative 12(S)-hydroxy-eicosatetraenoic acid (12(S)-HETE). Its biological effects in skin are mediated via specific, high affinity binding sites present on both keratinocytes and epidermal antigen presenting Langerhans cells. The main biological effect is chemotaxis of keratinocytes suggesting a physiological role of 12-HETE in cutaneous wound healing. Analysis of 12-HETE receptors in various cutaneous disease states revealed a dramatic defect in lesional and uninvolved psoriatic skin which may represent a central molecular defect in the pathophysiology of the disease.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

[Multiple angiolipomas--analgesics therapy with doxepin].

Angiolipomas are rare benign tumours of the subcutaneous fat; they are sometimes solitary but their occurrence is more frequently multiple. Angiolipomas can be differentiated from lipomas clinically by their pronounced tenderness and histologically by their variable vascularization. The disease occurs mostly in young adults, the sites of predilection being the trunk and proximal extremities. Multiple angiolipomas have to be differentiated from other lipomatoses, especially from adiposis dolorosa (Dercum's disease). The case reported in this paper was characterized by typical clinical and histological findings. The systemic administration of acetylsalicylic acid, diclofenac, ketotifen, ranitidine, tramadol, tilidine combined with naloxone did not provide adequate pain relief. In contrast, the therapeutic efficiency of the antidepressant doxepin, which also displays antihistaminic effects, suggests a possible role of mediators in the development of pain in angiolipomas.

Biopsy↗
PubMed1992

[Cyclosporin A in the therapy of inflammatory dermatoses].

The experience reported in the literature with cyclosporin A (CyA) in the treatment of various inflammatory and autoimmune dermatological diseases is reviewed and compared with the authors' own experience of treating 36 patients presenting with psoriatic arthritis [8], generalized pustular psoriasis [2], palmoplantar pustular psoriasis [12], Behçet's disease [2], disseminated circumscribed scleroderma [2], acrodermatitis continua suppurativa [2], pemphigus vulgaris [1], lupus erythematosus [3], pyoderma gangrenosum [1], severe atopic eczema [2], and actinic reticuloid [1]. On the basis of the authors' own experience and the reported results, treatment with CyA appears to be primarily indicated in pyoderma gangrenosum, circumscribed scleroderma, psoriatic arthritis and acrodermatitis continua suppurativa. In diseases such as actinic reticuloid, Behçet's disease, localized and generalized pustular psoriasis, treatment with CyA leads to good results with an acceptable risk-benefit ratio. In our view, it is doubtful whether treatment with CyA alone is indicated in alopecia areata, lichen ruber, dermatomyositis, atopic eczema, systemic scleroderma, bullous diseases, and lupus erythematosus, and in the last two it should be given only in combination with systemic steroids. Literature reports provide no support for the use of CyA in ichthyosis vulgaris, pityriasis rubra pilaris, and cutaneous T-cell lymphomas. The risk-benefit ratio of CyA treatment should be carefully considered, especially in diseases that are not life-threatening.

Behcet Syndrome↗
PubMed1991

Dithranol-induced down-regulation of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] receptors in a human epidermal cell line.

The effects of dithranol and its therapeutically inactive oxidation product, danthrone, on 12(S)-HETE binding to the human epidermal cell line SCL-II were studied. Dithranol (0.25-1 microgram/ml), in contrast to danthrone, induced a substantial 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 18-24 h and slowly declined thereafter. At a concentration of 1 microgram/ml, the drug led to an approximately 50% decrease in the number of specific high-affinity 12(S)-HEFE receptors (Bmax), whereas receptor affinity (Kd) showed no change. The down-regulation of 12(S)-HETE receptors on epidermal cells by dithranol may contribute to its antipsoriatic action.

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

SC-41930, a leukotriene B4 receptor antagonist, inhibits 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) binding to epidermal cells.

SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxyl]-3, 4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid, a potent leukotriene-B4 (LTB4) receptor antagonist, inhibits in vivo 12-hydroxyeicosatetraenoic acid (12-HETE)-induced neutrophil infiltration, suggesting a potential 12-HETE receptor antagonist effect, as well. Since 12-HETE is assumed to have a pathophysiological role in inflammatory skin diseases, and epidermal cells possess high affinity binding sites for 12(S)-HETE, we studied the effect of SC-41930 on 12(S)-HETE binding to the human epidermal cell line, SCL-II. SC-41930 antagonized the 12(S)-HETE binding to SCL-II cells with a Ki of 480 nM. This Ki value is similar to that obtained for the inhibition of LTB4 binding to human neutrophils. Our results show that SC-41930, in addition to its LTB4 receptor antagonist effect, exhibits 12-HETE receptor antagonist effect as well, and therefore may be of benefit in skin diseases with elevated 12-HETE levels.

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

Annular erythema associated with Sjögren's syndrome: a variant of systemic lupus erythematosus.

We present a Burmese patient with widespread annular erythema associated with Sjögren's syndrome. Unlike previously described cases, the disease occurred in the setting of systemic lupus erythematosus. Photoprovocation testing revealed light sensitivity in the UVA range with elicitation of subacute cutaneous lupus erythematosus-like lesions. The presence of an erythema annulare centrifugum-like eruption should initiate the search for Sjögren's syndrome and systemic lupus erythematosus.

Adult↗
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↗