Biomedical subjects
Publications and source records attributed to B Sebök.
A 73-year-old female patient presented with asymmetric herpes zoster. She was treated successfully with systemic immunostimulants, vitamin B1 tablets and topical etheric acetyl-salicylic acid solution. No underlying malignancy, immunodeficiency or other systemic diseases could be detected.
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The authors describe the case of a 38-year-old female patient suffering from angiolymphoid hyperplasia with eosinophilia. The symptoms, histopathology, differential diagnostic relations and the therapeutic modalities of this disease are discussed.
Fumaric acid, fumaric acid dimethylester, and the dithranol derivative C4-lactone were studied in the mouse tail test to evaluate their effects on epidermal cell differentiation compared with other topical antipsoriatic drugs, such as betamethasone, calcipotriol, and dithranol. Mouse tails were treated for 2 weeks and longitudinal histological sections prepared of the tail skin. The length of the orthokeratotic regions (stratum granulosum) was measured on 10 sequential scales per tail and expressed as percentage of the full length of the scale. In addition, epidermal thickness was measured and the efficacy of the various compounds evaluated. In comparison to 2% salicylic acid ointment, all tested compounds except fumaric acid significantly (p < or = 0.05) increased the proportion of the orthokeratotic region. C4-lactone and calcipotriol were less effective than dithranol, fumaric acid dimethylester only moderately influenced cell differentiation, and betamethasone showed the least potent effect. Dithranol was the most potent substance inducing orthokeratosis without increasing epidermal thickness.
The immortalized human keratinocyte cell line HaCaT was used to assess the effect of interferon-gamma (IFN-gamma) on expression of keratin K17. Both IFN-gamma and K17 have been implicated in the pathophysiology of psoriasis. Western and quantitative enzyme-linked immunosorbent assay analyses demonstrated increasing induction of K17 protein by 48 h exposure to IFN-gamma at concentrations of 10, 50, and 250 U/ml. At 50 U/ml IFN-gamma, immunohistochemical analysis revealed numerous K17-positive foci, whereas in situ hybridization demonstrated K17 message in the majority of cells. In addition, at low (5 U/ml) concentrations of IFN-gamma, cell proliferation and protein synthesis decreased, as determined by 3H-thymidine labeling and 14C-amino acid uptake. These data suggest that aberrant K17 expression observed in psoriatic lesions may be a consequence of IFN-gamma overexpression, and that the HaCaT cell line may be a useful in vitro model system to elucidate the underlying mechanisms.
Oral administration with complex mixtures of fumaric acid derivatives is known to have antipsoriatic efficacy. The present studies aimed to clarify the mode of action and toxicity of the individual compounds. Hyperproliferative HaCaT keratinocytes in monolayer cultures were exposed to fumaric acid, dimethylfumarate, zinc monoethylfumarate, calcium monoethylfumarate and magnesium monoethylfumarate at concentrations between 0.4 microM and 960 microM for 48 h. Cell proliferation was studied by [3H]thymidine incorporation. In addition 14C-labelled amino acid uptake and total protein content were measured. Direct cytotoxicity was determined by the release of cytoplasmic lactate dehydrogenase (LDH) into the culture medium. The corresponding 50% inhibition concentrations (IC50) were calculated for DNA/protein synthesis: 2.3/2.5 microM (dimethylfumarate), 133/145 microM (zinc monoethylfumarate), 215/230 microM (calcium monoethylfumarate), 275/270 microM (magnesium monoethylfumarate), > 960/> 960 microM (fumaric acid). The total protein content was less sensitive. Antiproliferative activity was found for dimethylfumarate and to a lesser degree for calcium monoethylfumarate already at the subtoxic concentrations of 1.3 and 4 microM, respectively. In the case of magnesium monoethylfumarate, zinc monoethylfumarate and fumaric acid there was no such dissociation between their cytotoxic and antiproliferative potential. These data indicate that most of the antipsoriatic potential of fumaric therapies is due to the dimethylfumarate compound.
BACKGROUND: In the psoriatic plaque both IL-1 dysregulation and ICAM-1 expression on keratinocytes have been previously described. Furthermore systemic administration of fumarates has been reported to be effective in psoriasis. We, therefore, studied the effect of dimethyl-fumarate ester (DMF) on the putative IL-1-induced ICAM-1 expression. METHODS: Hyperproliferative human keratinocytes (HaCaT cell line) were incubated in 10 to 100 U/mL IL-1 alpha for 24 h with and without preincubation with 0.4-12.0 microM DMF: Expression of ICAM-1 was measured by a special ELISA-APAAP technique. RESULTS: The exposure to IL-1 led to a significant dose-dependent induction of ICAM-1 expression of from 124 +/- 17 to 194 +/- 22% (control 100 +/- 12%), while proliferation remained unaltered. Pretreatment with > or = 4 microM DMF resulted in a distinct suppression of ICAM-1 expression and a slight decrease in proliferation. CONCLUSIONS: The present results show that ICAM-1 expression on hyperproliferative keratinocytes may be triggered by IL-1 alpha and serve as a molecular target for antipsoriatic DMF.
The authors describe the case of a 40-year old female patient. Since her childhood she realised of her urine the black discoloration of the underwear. For about a year, without subjective complaints, blue-black color of the skin involved the axillae and pinnae. For a year appeared the increased pain of thoracal and lumbal spine column and the limitation of motion of these parts. The examination of urine, histological and electron microscopical findings, the X-ray photograph of the spinal column confirmed the diagnosis of alkaptonuria or rather congenital ochronosis.
The authors describe the case of a 40-year-old female patient. Since childhood her urine had caused black discoloration on her underwear. For about a year the skin of the axillae and pinnae had been bluish-black without subjective complaints. One year before admission, pain in the thoracic and lumbar spine began, with limitation of motion. Examination of the urine, histological and electron microscopical findings, and X-ray examination of the spinal column confirmed the diagnosis of alkaptonuria and congenital ochronosis.
The authors completed the surgical removal of tattoos with epithelization using epidermal cell suspension. The cells were separated from the removed tattood skin. The advantages of this method that there is no need for separate donor skin, the procedure is cheap and good epithelization can be achieved.
The authors describe the case of a 12 year-old boy suffering from acne fulminans. Typical clinical findings were observed. The disease responded to treatment with prednisolon and antibiotics.
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There is good evidence indicating that hyoscine-resistant contractions of the guinea-pig ileum evoked by stimulation of the intramural nerves are mediated by substance P (SP). In the present experiments, non-cholinergic neurogenic ileum contractions to field stimulation (100 imp., 5-50 Hz) were inhibited by the opiate agonists morphine and [D-Met2,Pro5]enkephalinamide (10(-6) M) in a naloxone-reversible manner. Neither morphine nor naloxone influenced the musculodirect contracting effect of histamine. Capsaicin, a drug that has been shown to deplete SP from primary afferent neurones, exerted no long-lasting effect on non-cholinergic contractions to field stimulation. Repeated administration of long trains of stimuli (900 impulses) resulted in a progressive decrease of the contractions evoked. Addition of naloxone (3 X 10(-7) M) restored the original height of the responses. The above inhibitory action of opiate agonists and of repeated long-train stimulation was 3-6 times greater at 5 Hz than at 50 Hz. It is concluded that opiate agonists inhibit the release of SP from intramural neurones of the guinea-pit ileum. The decrease in responses to repeated long-train stimulations is mediated, at least in part, by the release of endogenous opioid substance(s).
Disturbed epidermal proliferation and keratinization are major features of psoriatic skin lesions. The so-called mouse tail test is known as an animal model to evaluate the antipsoriatic efficacy of topical drugs with regard to the induction of orthokeratosis. The purpose of the present study was to investigate the effect of tazarotene, a novel, receptor-specific retinoid, by the mouse tail test in a direct comparison to dithranol representing a classical topical antipsoriatic compound. The tails of CFLP mice were treated with tazarotene gel (0.1%, 0.05%), dithranol ointment (1.0%), tretinoin cream (0.05%) and methylcellulose (5%) hydrogel (vehicle control) for 2 weeks. Longitudinal histological sections were prepared from the tail skin, and the degree of orthokeratosis was determined by measuring the horizontal length of the fully developed granular layer within an individual scale in relation to its total length according to a method originally described by Bosman and co-authors. The degree of orthokeratosis was significantly (p < or = 0.05) increased by 0.1% tazarotene (87+/-20%), 1.0% dithranol (75+/-26%), 0.05% tazarotene (59+/-27%), and 0.05% tretinoin (23+/-13%) as compared to untreated (11+/-6%) and methylcellulose hydrogel-treated (13+/-6%) controls. Under the conditions of the mouse tail test, tazarotene showed a strong potency to induce orthokeratosis. With regard to clinically relevant concentrations this effect was even more pronounced than that observed for dithranol.
In order to test the advantage of vitamin D(3) preparations in liposomal form, calcitriol, the natural activated form of vitamin D(3), and tacalcitol, a vitamin D(3) analogue, were employed in various concentrations and using different vehicles in the mouse tail test, an animal model for testing the antiparakeratotic efficacy of topical medications. The optimal concentration in petrolatum turned out to be similar to that in commercial preparations. The liposomal preparations were superior to those in petrolatum and to those in nonliposomal phospholipids. The antiparakeratotic potency (drug activity) of liposomal tacalcitol in a concentration of 2 microg/g was twice that of the commercial preparation with a higher concentration of 4 microg/g. These results suggest that the use of liposomal vitamin D(3) preparations can achieve a given antipsoriatic effect with a reduced concentration of the active substance thereby reducing the risk of skin irritation and of hypercalcemia.