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Biomedical subjects

V Steinkraus

Publications and source records attributed to V Steinkraus.

At least 37 records · Page 2Linked to original sources
PubMed1993

Beta-adrenergic receptors in psoriasis: evidence for down-regulation in lesional skin.

Lesional psoriatic skin displays reduced responsiveness to beta-adrenergic stimulating agents. To elucidate whether the receptor protein itself is responsible for this, lesional and non-lesional psoriatic skin was investigated ex vivo for maximal beta-adrenergic binding density (Bmax) and beta-adrenergic binding affinity (KD). Epidermal crude membrane homogenates (ECMH) were prepared from split-thickness skin biopsies and saturated with the lipophilic beta-adrenergic antagonist (-)-125I-iodocyanopindolol (ICYP) as radioligand. Specific binding was saturable and Scatchard transformation of the binding data revealed a homogeneous class of beta-adrenergic receptors in all nine experiments. The maximal beta-adrenergic binding density was significantly less in lesional than in non-lesional psoriatic skin (Bmax = 49.7 +/- 7.2 fmol/mg protein vs. 67.1 +/- 2.2 fmol/mg protein, n = 9, P < 0.05). The binding affinity was similar in lesional and in non-lesional skin (KD = 9.0 +/- 1.5 pmol/l vs. 8.0 +/- 0.9 pmol/l). These results could at least partially explain the reduced responsiveness of the beta-adrenergic system in lesional psoriatic skin seen after stimulation with beta-adrenergic agonists.

Adult↗
PubMed1993

Increased in vitro expression of beta 2-adrenoceptors in differentiating lesional keratinocytes of vitiligo patients.

Keratinocytes were established in serum-free culture medium from lesional and nonlesional skin of a patient with vitiligo (skin type III) and from an age-matched healthy control subject. Both differentiating and undifferentiated cells were examined for the presence of beta 2-adrenoceptors in culture medium containing either low (0.1 x 10(-3) M) or high (1.5 x 10(-3) M) calcium concentrations. Binding experiments were performed with saturating levels of radiolabeled (--)-[3H] CGP 12177, a nonselective beta-adrenergic antagonist. Controls for nonspecific binding were determined by the addition of the beta-adrenergic antagonist, propranolol (5 mumol), before the introduction of (--)-[3H] CGP 12177 to cell cultures. Undifferentiated keratinocytes yielded the highest expression of beta 2-adrenoceptors, whereas differentiating keratinocytes grown in medium with a low calcium concentration (0.1 x 10(-3) M) had a significantly lower expression of receptors with the exception of vitiliginous cells, which retained high densities of receptors, similar to undifferentiated cells. In addition, these vitiliginous keratinocytes showed a defect in 45calcium uptake. In contrast, differentiated keratinocytes from all three cell strains, grown in medium containing a high calcium concentration (1.5 x 10(-3) M) revealed a significantly lower receptor density compared to undifferentiated cells. This finding identified the importance of the extracellular calcium concentration in the expression of beta 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Chronic urticaria due to nickel intake.

A case of chronic urticaria is presented. The case of the disease was traced back to nickel intake by food as judged from type I and IV sensitization to nickel, a positive oral challenge test and long-standing, complete healing under a nickel-restrictive diet.

Adult↗
PubMed1992

Binding of beta-adrenergic receptors in human skin.

Radioligand-binding experiments were performed with crude membrane homogenates (CMH) from human skin in order to investigate the epidermal beta-adrenergic receptor (beta AR) density. CMH were prepared from leftovers of split-thickness skin grafts by sequential homogenization and centrifugation procedures to yield essentially epidermal fragments. Saturation experiments with the non-selective beta-adrenoceptor antagonist (-)-[125I]-iodocyanopindolol (ICYP) as radioligand showed saturable specific binding isotherms. Scatchard transformation of the data demonstrated high-affinity binding of ICYP to a single class of beta AR (Bmax = 80 +/- 10 fmol/mg protein; KD = 8 pM +/- 0.9; n = 8). beta AR antagonists displaced ICYP in a monophasic displacement pattern. The IC50 values were (nmol/1) propranolol (non-selective) 24.8; ICI 118,551 (beta 2 selective) 14.7; CGP-12177 (non-selective) 28.9; bisoprolol (beta 1 selective) 1500; CGP-20712A (beta 1 selective) 8990. beta AR agonists displaced ICYP with a potency ranking isoprenaline greater than adrenaline greater than noradrenaline. We conclude that epidermal crude membrane homogenates prepared from human split-thickness skin contain a high population of beta 2-adrenergic receptors. These receptors may be studied to further investigate the nature of human epidermal beta-adrenergic mechanisms.

Adult↗
PubMed1992

[Psoriasis and beta-blockade].

Psoriasiform skin eruptions during treatment with beta-adrenergic blocking drugs have recently attracted increasing attention and led the Bundesgesundheitsamt [German Office of Public Health] to publish general information on this issue. Today's knowledge on the clinical picture, pharmacology, and the pathogenesis is discussed, with reference to the latest experimental data. The blockade of keratinocyte beta-adrenergic receptors may play a key role in the aetiopathology of this unwanted side-effect.

Adrenergic beta-Antagonists↗
PubMed1992

[Eosinophilia-myalgia syndrome. Clinical aspects and follow-up of 10 patients].

A retrospective study (1985-1989) of patients suffering from diffuse fasciitis with eosinophilia revealed that five of eight patients had taken L-tryptophan-containing drugs before the onset of the disease. In addition, since this drug-disease association was first described five patients have been diagnosed during the year 1990. All ten patients developed peripheral eosinophilia, myalgia and deep skin involvement indistinguishable from eosinophilic fasciitis. Corticosteroids were able to reduce the pain and inflammatory parameters, but did not prophylactically improve the long-standing sclerodermalike skin thickening. In 2/5 patients with symptoms longer than 1 year, low-dose corticosteroid maintenance therapy has been continuously required to control joint and muscle pain.

Adult↗
PubMed1991

High density of beta 2-adrenoceptors in a human keratinocyte cell line with complete epidermal differentiation capacity (HaCaT).

A non-tumorigenic keratinocyte cell line with complete epidermal differentiation capacity (HaCaT) was used in radioligand binding experiments to determine the number of beta-adrenoceptors. Intact cells were saturated with 3H-labelled (-)CGP-12177 (CGP), a hydrophilic non-selective beta-adrenergic antagonist as radioligand. In order to investigate the beta-adrenergic subtype selectivity, displacement experiments were performed with different antagonists and agonists. Binding of CGP to keratinocytes has been shown to be reversible and saturable and to have high affinity (Bmax = 114.0 +/- 8.8 fmol/10(7) cells with 6866 receptors/cell, KD = 0.095 +/- 0.017 nmol/l; n = 11). Beta-adrenergic antagonists inhibited binding yielding monophasic displacement curves. IC50-values (nmol/l) were: propranolol (non-selective) 1.68; CGP-12177 (non-selective) 1.08; ICI 118,551 (beta 2-selective) 2.92; bisoprolol (beta 1-selective) 1230; and CGP-20712 (beta 1-selective) 24,980. Agonists displaced CGP in the order isoprenaline greater than adrenaline greater than noradrenaline. We conclude that HaCaT cells express a high density of beta2-adrenoceptors providing a good model system to study adrenergic receptor mechanisms under reproducible experimental conditions in keratinocytes.

Binding, Competitive↗
PubMed1991

[Blunt aortic injury/choosing appropriate time for surgery].

Based on our experience in a cohort of 39 patients and also on the results of post-mortem findings obtained from the department of forensic medicine in Hamburg, we prefer to perform emergency surgery only in cases of aortic aneurysms over 6 cm in diameter, in cases of hemorrhage, or in coarctation syndrome. Because of the high incidence of concomitant multiorgan injuries, surgery for aortic lesions with only radiologic symptoms is not performed until a period of 2-8 weeks has elapsed since the injury, according to the degree of stabilisation. With this strategy, the mortality in surgical management of aortic injuries in our department is about 15%.

Aortic Aneurysm↗
PubMed1990

Radioligand binding characteristics of beta 2-adrenoceptors of cultured melanoma cells.

The existence of beta-adrenoceptors on intact cells of the human malignant melanoma cell line A-375 was investigated using the binding properties of the tritiated radioligand (-)-[3H]CGP-12177, a hydrophilic non-selective beta-adrenoceptor antagonist. Displacement experiments of the radioligand from its binding site were performed with antagonists and agonists to determine the beta-adrenoceptor subtype selectivity. The binding of (-)-[3H]CGP-12177 was saturable, of high affinity (KD = 0.025 nmol/l, n = 12) and was rapid and readily reversible. The maximal number of binding sites (Bmax) was 33.5 +/- 1.9 fmol/10(7) cells or 2018 +/- 114 receptors per cell. beta-adrenoceptor antagonists inhibited binding of the radioligand with monophasic displacement curves. IC50 values were (nmol/l): propranolol (non-selective) 2.82, alprenolol (non-selective) 2.0, ICI 118,551 (beta 2-selective) 3.5 and bisoprolol (beta 1-selective) 2200. Agonists inhibited binding in the order of potency of isoprenaline greater than adrenaline greater than noradrenaline. It is concluded that cells of the melanoma cell line A-375 contain a homogeneous population of beta 2-adrenoceptors.

4-Chloro-7-nitrobenzofurazan↗
PubMed1989

Time course and extent of alpha 1-adrenoceptor density changes in rat heart after beta-adrenoceptor blockade.

1. It has been suggested that impaired beta-adrenoceptor stimulation is a condition under which the functional role of cardiac alpha 1-adrenoceptors is enhanced. We therefore investigated the extent and time course of changes in alpha 1-adrenoceptor characteristics after chronic treatment with the beta-adrenoceptor blocker propranolol in rat heart. For comparison beta-adrenoceptors were also studied. The mechanism of the changes in adrenoceptor density was investigated with cycloheximide, an inhibitor of protein synthesis. The functional significance of an increased alpha 1-adrenoceptor density was tested by measuring isometric force of contraction in the presence of phenylephrine or isoprenaline in right ventricular papillary muscles. 2. Rats were treated with propranolol (9.9 mg kg-1 daily) or 0.9% NaCl, applied with osmotic minipumps for 1, 2, 3 or 7 days. Propranolol treatment resulted in a maximally 28% increase of alpha 1-adrenoceptor density after 3 days (NaCl 95.9 +/- 3.5 vs. propranolol 123.0 +/- 1.6 fmol mg-1 protein, n = 6, P less than 0.01). This up regulation reached significant levels after 2 days of treatment and was reversible after cessation of treatment within two days. KD-values were the same for NaCl- and propranolol-treated rats. Changes of Bmax and KD in beta-adrenoceptor binding assays did not reach significant levels. 3. Cycloheximide (1.5 mg kg-1 i.p. daily for 3 days) inhibited the propranolol-induced increase in Bmax of alpha 1-adrenoceptors completely. In addition, cycloheximide also decreased the density of alpha 1- and beta-adrenoceptors also under control conditions. 4. pD2-values for the positive inotropic effect of phenylephrine and isoprenaline in isolated electrically driven papillary muscle were similar in NaCl- and propranolol-treated rats (phenylephrine: 5.41 + 0.11 vs. 5.41 + 0.19, n = 7; isoprenaline: 6.31 + 0.18 vs. 6.65 + 0.19, n = 7). The observed increase in alpha-adrenoceptor density in healthy rat heart may therefore not be high enough to enhance the phenylephrine-induced increase in force of contraction. 5. In conclusion, time course and effects of cycloheximide indicate that the increase in B,,,, of myocardial alpha 1-adrenoceptors is due to de novo synthesis of receptors. However, at least for the rat heart model, a functional significance of this increase could not be demonstrated.

Adrenergic beta-Antagonists↗
PubMed1984

Metabolic and hormonal responses to exhaustive supramaximal running with and without beta-adrenergic blockade.

The metabolic and hormonal responses to exhaustive short-term supramaximal exercise were studied in 10 male physical education students. The exercise task was a single bout of running on the treadmill at 22 km X h-1 and 7.5% slope. It was performed with single oral doses of 100 mg Bupranolol (non-selective beta-blockade), 100 mg Metoprolol (beta-1-selective blockade), and placebo. Arterialized capillary and venous blood were sampled until 30 min post exercise. Time to exhaustion was 52.0 +/- 2.6, 47.6 +/- 2.0, and 46.0 +/- 1.9 s in the control, Metroprolol, and Bupranolol experiments. At cessation of exercise, adrenaline and noradrenaline were grossly elevated in all three conditions. Lactate and glucose increased markedly, this being accompanied by increasing insulin in the control and Metoprolol, but not the Bupranolol trials. Glycerol increased moderately, while FFA were depressed. Growth hormone showed a delayed increase at 15 and 30 min post exercise. Cortisol was unaffected by exercise. beta-blockade reduced the increases of lactate, glucose, glycerol, insulin, and growth hormone, exaggerated the depression of FFA and had no effect on cortisol. The results demonstrate that the strong sympatho-adrenal response to exercise of this nature is a major determinant of the increase of glucose at cessation of exercise. The hyperglycemia in concert with beta-2-adrenergic stimulation leads to elevation of insulin. Furthermore, lipolysis is controlled by beta-adrenergic stimulation. The delayed increase of growth hormone seems to be triggered by the declining glucose level during recovery.

Adrenergic beta-Antagonists↗