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Biomedical subjects

J Serup

Publications and source records attributed to J Serup.

At least 19 recordsLinked to original sources

Stimulation of epidermal proliferation in mice with 1 alpha, 25-dihydroxyvitamin D3 and receptor-active 20-EPI analogues of 1 alpha, 25-dihydroxyvitamin D3.

The effects of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) and receptor-active 20-epi vitamin D analogues (MC 1288, 20-epi-1 alpha, 25-(OH)2D3; MC 1301, 20-epi-24a-homo-26,27-dimethyl-1 alpha, 25-(OH)2D3, and KH 1060: 20-epi-22-oxa-24a-homo-26,27-dimethyl-1 alpha, 25-(OH)2D3) on epidermal proliferation in mice were studied in vivo. Single topical applications of all compounds induced epidermal proliferation in a dose-dependent manner. The relative potencies in vivo (KH 1060 > MC1301 > MC1288 > 1 alpha, 25-(OH)2D3) correlated well with the known activities of these compounds to inhibit U 937 cell proliferation in vitro. Vitamin D3 and 1 beta, 25-(OH)2D3, two compounds that do not bind the vitamin D receptor, did not affect epidermal proliferation. Our study shows that vitamin D3 compounds that bind to the vitamin D receptor stimulate epidermal proliferation in mice.

Administration, Cutaneous

The effects of KH 1060, a potent 20-epi analogue of the vitamin D3 hormone, on hairless mouse skin in vivo.

Dermal effects of KH 1060, a novel, highly potent 20-epi analogue of 1 alpha,25-dihyroxyvitamin D3, were investigated in a hairless mouse model. During daily topical applications of a 0.4 microM solution of KH 1060 for 4 weeks, epidermal hyperplasia and an increase of dermal thickness and mass were observed. KH 1060 upregulated glycosaminoglycan and collagen synthesis in the skin, and increased glycosaminoglycan deposition in the subepidermal region. Reverse transcription-polymerase chain reaction amplification of the transforming growth factor (TGF) beta 1-specific mRNA revealed that KH 1060 stimulated expression of this growth factor in the epidermis, but not in the dermis. Changes observed after application of 1 alpha,25-dihydroxyvitamin D3 were much less pronounced but qualitatively similar to the effects of KH 1060, whereas structurally related but receptor inactive compounds, vitamin D3 and 1 beta,25-dihydroxyvitamin D3, did not produce any effects. Furthermore, we were unable to demonstrate the involvement of the non-genomic, receptor-independent vitamin D signalling in the skin, using a specific stimulator (Ro 24-2090) and a blocker (1 beta,25-dihydroxyvitamin D3) of this pathway. Our findings provide the first evidence that a strong vitamin D3 analogue triggers synthesis of skin connective tissue, possibly via vitamin D receptor activation and the paracrine action of epidermis-derived TGF-beta 1.

Animals

Ultrastructure of murine epidermis treated with the vitamin D3 analogue KH-1060.

A new highly potent analogue (KH-1060) of vitamin D3 has been recently shown to stimulate the growth and differentiation of keratinocytes. This study was intended to determine the effects of this new analogue on epidermis at the ultrastructural level. KH-1060 was applied topically on the backs of hairless mice for 4 weeks; the skin was then studied by routine electron microscopy. The effects were compared with those of betamethasone-17-valerate and with concomitant treatment of KH-1060 following betamethasone. KH-1060 stimulated normal function of keratinocytes and formed a thick epidermis. The ultrastructure of the thick epidermis represents an enhanced normal process of keratinization and proliferation. Moreover, KH-1060 diminished the atrophogenic effects of betamethasone.

Administration, Cutaneous

Age-related diurnal changes of dermal oedema: evaluation by high-frequency ultrasound.

Using high-frequency ultrasound, we measured the influence of gravitational stress on skin echogenicity in 22 young (age range 17-27; median 19) and 22 elderly (age range 75-100; median 87) healthy adults. B-mode ultrasound images were obtained from the medial malleolus, lateral calf, anterior thigh, volar forearm and the medial aspect of the arm three times daily: in the morning, immediately before rising, and 2 and 12 h later. The echogenicity was measured by counting the number of low echogenic pixels in the image. Pronounced changes of low echogenic pixel numbers were seen in the areas exposed to high gravitational stress, i.e. the ankle and calf. In the young age-group echogenicity of the skin increased steadily during the day, whereas in the elderly population echogenicity decreased 2 h after getting up in the morning, and subsequently returned to the baseline level. In a control group of 10 people (aged 17-83; median 18), who remained in the supine position throughout the day, the echogenicity of the skin remained unchanged. As the echogenicity of the dermis is inversely related to the amount of fluid it contains, our results indicate that young skin responds to gravitational stress by fluid depletion. In the skin of the elderly, the mechanism of fluid removal appears to be defective. The impaired protection against the development of intradermal oedema in the elderly may predispose to the development of lipodermatosclerosis and leg ulceration.

Adolescent

Inhibition of glucocorticoid-induced epidermal and dermal atrophy with KH 1060--a potent 20-epi analogue of 1,25-dihydroxyvitamin D3.

1. The possibility of preventing and treating glucocorticoid-induced skin atrophy with KH 1060 (the potent 20-epi-22-oxa-24a-homo-26,27-dimethyl analogue of 1,25-dihydroxyvitamin D3) was examined in a hairless mouse model. 2. KH 1060 (0.625-6.25 pmol cm-2 of skin) applied topically for 7 days together with 2.5 nmol cm-2 betamethasone-17-valerate prevented, in a concentration-dependent manner, the development of epidermal, dermal and total skin thinning caused by the glucocorticoid. The effect of KH 1060 on the epidermis occurred at a lower dose than on the dermis, and at doses above 1.25 pmol cm-2 KH 1060 caused epidermal hyperplasia. 3. KH 1060 (2.5 pmol cm-2) prevented the development of betamethasone-associated skin atrophy in mice during a long-term (4 weeks) treatment, and reversed established cutaneous glucocorticoid atrophy. 4. Radiolabelling experiments with [35S]-sulphate and [3H]-proline in vivo revealed that KH 1060 stimulated the synthesis of sulphated glycosaminoglycans and hydroxyproline in skin treated with betamethasone. 5. These findings strongly suggest that KH 1060 prevents and reverses glucocorticoid-induced skin atrophy by stimulating epidermal proliferation and enhancing synthesis of extracellular matrix in the dermis.

Animals

Alterations in skin properties during rapid and slow tissue expansion for breast reconstruction.

This study comprises 23 women who had had mastectomies because of breast cancer. They were randomly divided into two groups when they were admitted for breast reconstruction by tissue expansion. The first group was expanded rapidly, i.e., every day, and the other group was expanded slowly, i.e., every week. There were no other differences in the treatment between the two groups. Three months after completion of expansion, the expander was replaced by a permanent prosthesis. The follow-up time was up to 6 months after the second operation. Three different parameters--distensibility, elasticity, and hysteresis--were measured noninvasively on the breast skin and at a control site on several occasions throughout the treatment. During the treatment period there were no differences in skin properties between rapidly and slowly expanded patients. Of the three parameters, distensibility showed the most prominent changes: decreasing during the expansion period, increasing after the expander had been replaced by a permanent prosthesis, and decreasing during the following 6 months. Elasticity did not change significantly, except decreasing after insertion of the permanent prosthesis, and the hysteresis increased at the same time. These findings indicate that tissue expansion alters breast skin only to a small extent and that the mechanical resistance sometimes encountered during tissue expansion is due to deeper structures such as underlying muscles or capsule formation.

Body Water

Scaling, dry skin and gender. A bioengineering study of dry skin.

Dry skin and scaling was studied in a group of 72 healthy volunteers by using subjective self-assessment and by clinical assessment by a dermatologist, as well as application of noninvasive bioengineering techniques to measure scaling and epidermal hydration. The study revealed that 67% of the volunteers had subjective complaints, while only 5.6% had definite clinical signs of dry skin at the time of examination. Subjective complaints were more common in women than in men (p < 0.001), though neither clinical nor objective measurements showed any sex difference, which suggests that other factors may play a role in the way men and women perceive dry skin. Subjective and clinical scores were correlated (p < 0.02), though neither was significantly correlated to objective measurements. Grading of skin scaling on D-squame tapes correlated with densitometry of the tapes (p < 0.001), as did the electrical capacitance (p < 0.001). Both clinical and objective methods can identify dry skin. However, the study showed that in healthy persons a number of irrational factors play a role in the use of moisturizers, and while these factors cannot be measured, they must be taken into account. Healthy, but dry skin is a vaguely defined clinical entity, which may explain the generally poor correlation between the two methods. This underlines the need for several methods to be used simultaneously in order to elicit complementary information.

Adult

A double-blind comparison of acitretin and etretinate in the treatment of Darier's disease.

The objective of this double-blind study was to compare the therapeutic effects of acitretin with those of etretinate in patients with Darier's disease. Twenty-six patients (10 males and 16 females) were included in the study. Patients were treated with 30 mg daily for the first 4 weeks and with an individually adjusted dose (10-50 mg/day) for the subsequent 12 weeks. Remission or marked improvement was obtained in 10 of the 13 acitretin-treated patients and in 8 of the 11 etretinate-treated patients who completed the 16-week treatment. The usual mucocutaneous adverse reactions of retinoids were observed in all but one patient. There were no significant differences between treatment groups with regard to the incidence of these reactions.

Acitretin

Alterations of skin microcirculatory rhythmic oscillations in different positions of the lower extremity.

Microcirculatory vasomotion is considered to be an important mechanism promoting and facilitating the transfer of blood cells through skin capillaries. Since skin vulnerability of the leg is closely associated with gravitational factors and skin micro-circulation, we investigated by a laser Doppler apparatus influence of postural changes on skin blood flow oscillations in lower limbs of healthy volunteers. Our data show a marked decrease in microcirculatory oscillation amplitudes at a frequency 7.6 (+/- 0.6) min-1 after lowering the leg. This could be reversed by the application of compressive bandage. Our study points toward a potentially important mechanism of microcirculatory impairment during orthostasis.

Adult

Characterization of contact dermatitis and atopy using bioengineering techniques. A survey.

Bioengineering techniques useful in the characterization of contact dermatitis and atopy are surveyed, including non-invasive techniques for the measurement of skin colour, blood flow, skin surface temperature, skin surface contour, water barrier, and skin surface hydration. Ultrasound measurement of skin thickness and edema formation, and ultrasound cross-sectional imaging are also included. Structural and pathophysiological findings in the different types of dermatitis are outlined. Weal or hive formation is covered additionally.

Chronic Disease

A three-hour test for rapid comparison of effects of moisturizers and active constituents (urea). Measurement of hydration, scaling and skin surface lipidization by noninvasive techniques.

An in vivo skin test for rapid comparison of the efficacy of moisturizers is introduced. Test substances were applied to flexor side forearm skin, and measurements by non-invasive techniques were performed after 3 h. As indicators of epidermal hydration, the electrical conductance and capacitance were measured. To quantify the effects on scale pattern, D-Squame tapes were scored and the optical transmission measured. Moreover, skin surface lipids resulting from lotion lipids were measured. Lotions and different concentrations of urea could be ranked in a consistent way, viz. untreated skin < vehicle < 3% urea lotion < 10% urea lotion. Urea was concluded to be very potent as a skin humidifier and as a descaling agent, particularly in 10% concentration. Humidity characteristics correlated much better with the concentration of urea than with lipidization of the skin surface due to lotion lipids. A 3-hour test period was sufficient for the evaluation of the effects of moisturizers on both epidermal hydration and scale pattern. With a rapid test method, sources of variation such as diurnal and day-to-day variations, dosage and non-compliance are easily controlled. Further, by using non-invasive methods, the assessment has been rendered objective.

Adult

A double-blind comparison of two creams containing urea as the active ingredient. Assessment of efficacy and side-effects by non-invasive techniques and a clinical scoring scheme.

From a group of 72 healthy individuals, 47 with evidence of dry skin according to measurements by non-invasive techniques were enrolled for a 3-week study with double-blind and randomized treatment of one forearm, using either 3% urea cream (HTH lotion 'light') or 10% urea cream (HTH lotion 'Original'). The contralateral forearm served as an untreated control. Two volunteers had to be excluded because measurements of skin surface lipids gave evidence of vehicle components on the skin surface at the time of final evaluations. Evaluations took place not less than 12 h after the last application. According to questionnaire replies, the two creams were equally effective. This was confirmed by "blind" evaluation of the skin hydration state by a dermatologist, measurements of electrical capacitance and conductance indicating epidermal and skin surface hydration, and by D-Squame tape assessments including optical transmission of tapes with stratum corneum and scales from adhering skin, as well as visual scoring of the tapes. The methods showed a high degree of correlation, i.a. a definite relation between increase in electrical hydration parameters, reduced scaling according to the D-Squame tape evaluations, and clinical improvement of dryness. In skin treated with 10% urea cream the transepidermal water loss (TEWL) decreased, indicating an improved water barrier function. Skin colour measurement according to the CIE colour system showed that skin treated with the 3% urea cream turned in the direction of yellow, and there was generally a tendency for the brightness to decrease. Thus, the 3% urea cream gave the skin a more golden colour. There was no change in redness with any of the creams. Neither data from the questionnaire, the clinical examination, nor results of TEWL and colour measurements indicated any local irritant effect of urea causing water barrier damage or inflammation. In conclusion, the 3% and 10% urea creams were both found efficient, resulting in improvement of hydration and reduction of scaling. Both were non-toxic. However, specific differences did appear, viz. the 3% urea cream turned the skin colour golden, while the 10% urea cream improved the skin's water barrier function.

Adult

Treatment of lichen planus with acitretin. A double-blind, placebo-controlled study in 65 patients.

Sixty-five patients with lichen planus were included in a multicenter trial of acitretin. At the end of an 8-week placebo-controlled, double-blind phase, a significantly higher number of patients treated with 30 mg/day acitretin (64%) showed remission or marked improvement compared with placebo (13%). Furthermore, during the subsequent 8-week open phase, 83% of previously placebo-treated patients responded favorably to acitretin therapy. Typical retinoid adverse reactions were present in all patients on active drug. Laboratory studies did not show any clinically significant changes. This study shows that acitretin is an effective and acceptable therapy for severe cases of lichen planus.

Acitretin

Formation of oiliness and sebum output--comparison of a lipid-absorbant and occlusive-tape method with photometry.

Sebum output and the development of oiliness formation were studied in 24 acne-prone volunteers. Sebutape and photometric measurement by the Sebumeter were compared. Tapes were taken 1, 2 and 3 h after degreasing. Tapes were scored, and light transmission was measured by a special densitometric device. Sebumeter recordings were performed after 3 h. Densitometric evaluation of tapes was accurate with a high correlation to scoring. Sebutape and Sebumeter assessments correlated. However, in some individuals the tape method overestimated the sebum output. Right-left comparison indicated that the tape method was less reproducible, particularly after longer sampling periods. It is suggested that Sebutape, due to water occlusion and temperature insulation during the sampling period, interferes with sebum droplet formation and spreading. However, such systematic interference may be advantageous since sweating and heat are important clinical prerequisites in the formation of oiliness. Thus, it is suggested that the Sebutape is a specialized method for the determination of 'oiliness', the very last phase of sebum output, in which sebum droplets spread over the skin surface. The tape is not automatically comparable to other methods for determining sebum output from the follicular reservoir.

Acne Vulgaris