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Biomedical subjects

B Staberg

Publications and source records attributed to B Staberg.

At least 19 recordsLinked to original sources

Efficacy of topical treatment in psoriasis with MC903, a new vitamin D analogue.

In 10 in-patients with chronic plaque psoriasis, the antipsoriatic effect of MC903, a new synthetic analogue of vitamin D was evaluated. In each patient two symmetrical located psoriatic plaques were selected for the study. Topical treatment with MC903 cream (containing 1.2 mg MC903 per g cream) was compared with placebo cream in a double-blind, controlled, left-right, randomized way during 6 weeks of therapy. Compared with baseline, the clinical (erythema, scaling and infiltration) improvement was significant after 1 week of therapy with MC903 cream, while lateral comparison showed MC903 cream significantly better than cream base after 4 weeks of therapy (p less than 0.05). Measurements of skin blood flow by the laser Doppler technique in evaluating the disease activity was not superior to the clinical assessments. In 3 patients the psoriatic lesions treated with MC903 cream cleared completely during 6 weeks of therapy. No essential adverse reactions were observed. MC903 has a potent effect on cell proliferation and cell differentiation, but has minimal effect on calcium metabolism. It is concluded that this synthetic vitamin D analogue is potentially useful in the treatment of psoriasis.

Administration, Topical

Interleukin-6 in the epidermis of patients with psoriasis before and during PUVA treatment.

Biopsies from lesional and unaffected skin of 6 patients with psoriasis, taken before and during treatment with psoralen plus UVA (PUVA) were examined immunohistologically, using partially purified polyclonal antibodies to crude supernatants of activated human blood monocytes. By absorption with recombinant derived human monokines, we were able to demonstrate that interleukin-6 (IL-6) (but not IL-1 alpha or IL-1 beta) was located in a laminar and granular pattern in stratum corneum, and on epidermal cell membranes in the viable cellular epidermis. Before PUVA treatment, the intensity and the extension of staining for IL-6 were both markedly increased in lesional skin compared with uninvolved skin. A weaker staining for IL-6 was observed in lesional skin, simultaneous with the clinical improvement of psoriasis. The staining patterns for IL-6 in biopsies from cleared lesional skin and uninvolved psoriatic skin were identical at the conclusion of therapy.

Adult

Expression of interleukin-6-like molecules and tumour necrosis factor after topical treatment of psoriasis with a new vitamin D analogue (MC 903).

Skin biopsies from 5 patients with chronic plaque psoriasis were examined to test the effect of topical treatment with a new synthetic vitamin D3 analogue, MC 903, on epidermal interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF alpha). Skin biopsies, taken before therapy and after one and 2 weeks of therapy were examined immunohistologically. IL-6 was visualized using a partially purified polyclonal antiserum to crude supernatants of activated human blood monocytes before and after absorption with recombinant human IL-6. TNF alpha was demonstrated using a specific polyclonal antiserum to human recombinant TNF alpha. Both the intensity and extension of staining for IL-6, but not for TNF alpha, were increased in lesions compared with unaffected skin. During therapy with MC 903 a decline in the staining intensity for IL-6, but not for TNF alpha, was observed in both lesional and unaffected skin. Placebo-treated lesions, however, remained unchanged.

Adult

Decreased retinyl ester concentrations in UV-induced murine squamous cell carcinomas.

Squamous cell carcinomas were induced in hairless mice by repeated irradiations with UVB (280-320 nm, total dose 30 J/cm2) plus UVA (320-400 nm, total dose 168 J/cm2). The irradiated animals and non-irradiated controls were fed on diets with or without vitamin A supplementation (20,000 IU/kg). At the appearance of tumours, 30 to 43 weeks after the last irradiation, the vitamin A (retinol plus retinyl ester) concentrations in the serum, liver, epidermis and tumours and the retinol esterifying activities in microsomes from epidermis and tumours were measured. The liver and epidermal vitamin A concentrations were 2-3 times higher in vitamin A supplemented than in unsupplemented animals, but did not differ between tumour-bearing animals and non-irradiated controls receiving identical diets. The vitamin A concentration in the tumours was significantly lower than in perilesional epidermis. The largest difference (p less than 0.001) between the tumour and epidermal values was observed in the vitamin A supplemented group. The low vitamin A content of the tumours was entirely due to a marked (2 to 6-fold) reduction in the retinyl ester fraction. In contrast, the retinol content of the tumours was increased to twice that of normal epidermis. The activity of the esterifying enzyme, acyl-CoA:retinol acyltransferase (EC 2.3.1.76), was unchanged. The reason for the reduced retinyl ester concentration thus remains unclear. Still, it is possible that a disturbed interconversion of retinol to retinyl esters plays a role in murine photo-carcinogenesis.

Acyltransferases

Immunohistological detection of interleukin I-like molecules and tumour necrosis factor in human epidermis before and after UVB-irradiation in vivo.

Skin biopsies from five healthy subjects, taken before and after UVB irradiation, were examined using immunohistological techniques for the cytokines interleukin-I (IL-I) and tumour necrosis factor (TNF). Using polyclonal specific antibodies against IL-I and TNF, the two cytokines appeared identically located on the epidermal cell membranes of the stratum granulosum and stratum spinosum in unexposed skin. After UVB-exposure, the staining intensity for both IL-I/epidermal cell derived thymocyte-activating factor (ETAF) and TNF was markedly increased, and the epidermal staining included the basal cell layer. Immunohistological investigation of tissue-bound epidermal cytokines may be valuable in the study of skin diseases.

Adult

Allergic and irritant skin reactions evaluated by laser Doppler flowmetry.

Skin blood flow (SBF) in allergic and irritant reactions was determined by laser Doppler flowmetry (LDF) in an attempt to differentiate these reactions in an objective way. 12 subjects with known allergy to nickel were patch tested with nickel sulphate, nickel chloride, and with sodium lauryl sulphate (SLS) 1, 2, 5 and 10%. A positive correlation between the concentration of SLS and SBF was found. Compared with control sites, SBF in weak (+) and strong (++) positive allergic and irritant reactions was increased approximately 5-10 fold 1 and 2 days after application, and decreased towards normal 7 days after application. At day 7, the mean SBF was higher in allergic reactions than in irritant reactions. However, no consistent differences were found. It is concluded that although LDF can be used to quantify the strength of allergic and irritant skin reactions, this method cannot be used solely to separate these 2 types of reaction.

Adult

Effects of dynamic leg exercise on subcutaneous blood flow rate in the lower limb of man.

Subcutaneous blood flow (SBF) was studied simultaneously in the upper arm at heart level and in the lower limb during positional changes and during leg exercise in seven healthy males. SBF was estimated by local clearance of 133Xenon registered by portable cadmium telluride detectors. Venous pressure was recorded directly on dorsum on the foot. Changing the position from supine to head-up tilt, SBF decreased by 43% (P less than 0.01) at the arm level, 40% at the thigh (P less than 0.01), 47% at the calf (P less than 0.01) and decreased by 51% at the ankle level (P less than 0.01). Performing 20 heel-raisings per min in nearly erect posture, SBF increased by 96% at the thigh (P less than 0.01), 25% at the calf (P greater than 0.1) and increased by 18% at the ankle level (P greater than 0.01). At 40 heel-raisings per min SBF increased by 99% at the thigh (P less than 0.01), 121% at the calf (P less than 0.01), but only 44% at the ankle level (P greater than 0.1). During leg exercise subcutaneous vascular resistance was significantly increased at arm and ankle levels. In contrast, a vasodilatory response was noticed at the thigh and calf levels and seemed associated with a decrease in local venous pressure to below the trigger level of the sympathetic veno-arteriolar reflex mechanism. In conclusion, SBF in the lower limb of man was increased during exercise. The increase in SBF could only partly be ascribed to the concomitant increase in perfusion pressure. The local blood flow response seemed modified by changes in sympathetic nervous activity and metabolic rate.

Adult

Is the effect of phototherapy in psoriasis partly due to an impact on vitamin D metabolism?

To elucidate the effect of phototherapy on vitamin D metabolism in psoriatics, the serum concentrations of the major vitamin D metabolites (25-hydroxy-vitamin D (25(OH)D), 1,25-dihydroxy-vitamin D (1,25(OH)2D), and 24,25-dihydroxy-vitamin D (24,25(OH)2D)) were studied in 10 patients with disseminated psoriasis, both before and after phototherapy. Some 3-4 weeks of Goeckerman therapy induced significantly increased serum levels of 25(OH)D (mean: 24.6 ng/ml versus 54.4 ng/ml; (p less than 0.001] and 24,25(OH)2D (mean: 2.01 ng/ml versus 3.49 ng/ml; (p less than 0.001)). After phototherapy the mean serum level of 1,25(OH)2D increased nearly to the level found in healthy controls (mean: 23.8 vs. 32.2 pg/ml). However, this increase was not significant. It is shown that conventional phototherapy does have an impact on vitamin D metabolism in psoriatics. Since previous investigations have indicated an abnormal vitamin D metabolism in patients with psoriasis, it is possible that the beneficial effect of phototherapy in this disease might be due partly to an impact on vitamin D metabolism.

Adult

Differentiation of allergic and irritant reactions by transepidermal water loss.

12 patients with known allergy to nickel were patch tested with nickel sulphate, nickel chloride, and sodium lauryl sulphate 1, 2, 5 and 10%. 2 parallel series were performed, i.e., one with 24-h and one with 48-h application time. Reactions were followed by measurement of transepidermal water loss (TEWL). Allergic reactions showed a normal TEWL after 24-h application, and after 48 h, only strong reactions resulted in increased TEWL. In contrast, irritant reactions showed increased TEWL in both series, irrespective of the strength of the reaction. The deficient water barrier of allergic reactions is secondary, probably resulting from the underlying inflammatory process. Consequently, if TEWL measurements are used for the purpose of differentiating allergic and irritant skin reactions, a short application period, i.e., in this study 24 h, is preferable, with recordings performed shortly after removal of test chambers.

Adolescent

Ultrasound for assessment of allergic and irritant patch test reactions.

The oedema formation of patch test reactions was quantified by high-frequency ultrasound measurement of skin thickness. Patch testing with nickel sulphate, nickel chloride and sodium lauryl sulphate 1, 2, 5 and 10% was performed in 12 individuals with known nickel allergy. Oedema was greater in allergic than in irritant reactions similar in strength according to the clinical reading. In allergic reactions, the oedema appeared more transcutaneous, while in irritant reactions, more superficial. For differentiation of the 2 types of reaction, application of substances for a 24-h period with measurements the following day is preferable. For rating of allergic and irritant reactions, 48 h of application is preferable with measurements performed on the day patches are removed.

Adolescent

Abnormal vitamin D metabolism in patients with psoriasis.

To elucidate if psoriatic skin involvement induces changes in vitamin D metabolism, the serum concentrations of the major vitamin D metabolites (25-hydroxy-vitamin D(2+3) (25OHD), 1,25-dihydroxyvitamin D(2+3) (1,25(OH)2D), and 24,25-dihydroxyvitamin D(2+3) (24,25(OH)2D)) were studied in a group of patients with psoriasis, who had not been exposed to ultraviolet radiation at least three months before the investigation. Serum concentrations of 1,25(OH)2D were significantly reduced in 17 patients with disseminated psoriasis compared to healthy age and sex matched controls (22.3 pg/ml versus 35.0 pg/ml (p less than 0.001)) and compared to 15 patients with moderate extended psoriasis (22.3 pg/ml versus 38.3 pg/ml (p less than 0.005)). Serum concentrations of the two other metabolites were not significantly decreased. In patients with moderate psoriatic skin manifestations, the values of the three vitamin D metabolites were normal. It is concluded that patients with disseminated psoriasis demonstrate decreased serum concentrations of the vitamin D metabolite 1,25(OH)2D. Since 1,25(OH)2D plays a role in differentiation and proliferation of epidermal cells, the abnormal low serum level of 1,25(OH)2D might be of importance for the abnormalities in cell maturation and proliferation found in psoriatic skin.

Adult

Reduced density of T6-positive epidermal Langerhans' cells in uninvolved skin of patients with psoriasis.

The Langerhans' cell (LC) density is known to be reduced in skin lesions as compared to uninvolved skin in patients with psoriasis. It is, however, still unsettled whether the LC density in uninvolved psoriatic skin differs from the density in normal skin. We have enumerated epidermal LC in uninvolved skin from 15 patients with stable psoriasis and in 15 healthy subjects. Punch biopsies from non-sunexposed skin from the buttock were taken. Epidermal sheets were separated by EDTA and LC then stained with an indirect immunoperoxidase technique using the mouse monoclonal antibody OKT6. The LC density was significantly reduced in uninvolved skin of patients with psoriasis (mean +/- SD: 375 +/- 37/mm2) as compared to healthy controls (544 +/- 168/mm2) (p less than 0.01). A reduced number of LC in uninvolved psoriatic skin is in accordance with previous reports demonstrating an impaired DNCB reactivity in patients with psoriasis. Whether the reduction in LC density is of pathogenic importance for psoriasis is unknown.

Cell Count

Cutaneous and subcutaneous blood flow in non-lesional skin of patients with minimal psoriatic skin manifestations.

Cutaneous and subcutaneous blood flow (CBF, SBF) were studied in non-lesional psoriatic skin (NLS) of 10 patients with only minimal psoriatic skin manifestations, using the local 133Xe washout method. Measurements of the CBF and SBF in the NLS of the patients and 10 normal individuals yielded no statistically significant differences. The results of the present study indicate that the activity of psoriasis can be monitored by the CBF measurements in the NLS, since previously published values for CBF of NLS have shown increasing values with increasing psoriatic activity. The significance of these findings may be more evidence of humoral factors playing a role in the pathogenesis of the disease. The tissue-to-blood partition coefficient for 133Xe was calculated on the basis of biochemical estimations of the relative content of lipids, proteins, and water in skin biopsies from non-lesional skin sites of 8 psoriatic patients. The relative content of lipids, proteins, and water was normal. Thus, the normal 133Xe partition coefficient of 0.7 ml/g should be used for measurements of the CBF in NLS.

Adult

The effects of antipsoriatic treatment on cutaneous blood flow in psoriasis measured by 133Xe washout method and laser Doppler velocimetry.

In 8 patients with psoriasis vulgaris, the cutaneous blood flow (CBF) was measured simultaneously in both involved and uninvolved psoriatic skin before (i.e., on the first day of hospitalization) and on the 3rd, 7th, 14th, and 28th days of treatment with tar. The 133Xe washout method was used after epicutaneous labeling and compared to the laser Doppler velocimetry (LDV) technique. Control experiments were performed in 10 normal individuals. Before treatment the mean CBF in involved psoriatic skin was 62.6 +/- 18.7 SD ml X (100 g X min)-1, which is significantly higher than CBF of uninvolved skin in psoriatic patients, 9.5 +/- 4.0 SD ml X (100 g X min)-1, (p less than 0.01) and is 13.6 times higher than CBF in the normal individuals (p less than 0.01). Fifty hours following onset of treatment (i.e., after only 2 applications of tar), mean CBF of the involved psoriatic skin had decreased significantly to 35.0 +/- 13.9 SD ml X (100 g X min)-1, (p less than 0.01), which was not statistically different from the CBF on the 7th day. During the following weeks, the CBF in involved psoriatic skin decreased at a more moderate rate than that observed during the first week and was 15.0 +/- 6.1 SD ml X (100 g X min)-1 on the 28th day. This value is not significantly different from the CBF of uninvolved skin in these patients. At the end of treatment, the CBF of the uninvolved skin had decreased significantly (p less than 0.05) in all the patients to values similar to those observed in the skin of normal individuals. A parallel decline was observed in a clinical psoriatic score index; however, it is not known whether the observed decrease in CBF was preceded or succeeded by the clinical improvement. A comparison of the 133Xe measurements and LDV measurements in the normal individuals by linear regression analysis yielded a correlation coefficient of -0.24 (N = 20, p greater than 0.05). In the skin of psoriatic patients the correlation coefficient was 0.01, (N = 47, p greater than 0.05) for unaffected skin, and 0.61 (N = 47, p less than 0.001) in the involved psoriatic skin sites. The LDV measurements did not reflect changes in the uninvolved skin in psoriatic patients during treatment and resulted in a remarkably high C.V. in the bilateral measurements of skin in normal individuals (43.8%) compared to the C.V. of 133Xe flow measurements (14.8%). It is concluded that while the LDV method gives a rough estimate of blood flow in cutaneous tissue with a high capillary perfusion rate, inaccurate measurements are made in skin areas with normal to twice the normal CBF range.

Adolescent

Quantification of weal reactions with laser Doppler flowmetry. Comparative blood flow measurements of the oedematous centre and the perilesional flare of skin-prick histamine weals.

Skin-prick experiments with different concentrations of histamine (0.1 mg/ml, 1.0 mg/ml, 10.0 mg/ml) and isotonic NaCl solution for control were performed on the forearms of 10 healthy volunteers. Regular recordings of the cutaneous blood flow by laser Doppler flowmetry were performed in the centre of the weals and 5, 10, 15 and 20 mm from the centre representing the zone of perilesional flare. In the weal centre the blood flow was increased but neither different concentrations of histamine nor the control reaction could be differentiated. Recordings performed 5 and 10 mm from the centre showed, however, significant differences between the different solutions of histamine tested as well as the control reaction. The better differentiation was obtained 5 and 10 min after skin-prick. In conclusion, laser Doppler flowmetry with recordings of the perilesional flare is found useful for quantification of weal reactions.

Adult

Interaction between 8-methoxypsoralen and phenytoin. Consequence for PUVA therapy.

A patient with epilepsy and psoriasis in phenytoin therapy was treated with PUVA with no effect at all. The PUVA treatment failure was demonstrated as being due to abnormally low serum levels of 8-methoxypsoralen (8-MOP) during phenytoin therapy, while normal serum levels of 8-MOP were observed after phenytoin was discontinued. The effect is probably due to an induction of the hepatic enzyme system by phenytoin, leading to an increased metabolism of 8-MOP. Other drugs with hepatic enzyme inducing properties might possibly also interfere with psoralen metabolism with further consequences for PUVA therapy.

Drug Interactions