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S Pavel

Publications and source records attributed to S Pavel.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Tanning beds: effect on skin cancer risk unclear].

Recent estimations show that over 25% of the Dutch population make regular use of tanning equipment. This use is still increasing, in spite of improving knowledge on the potential hazards of ultraviolet radiation. There are different motivations to use the tanning equipment. Younger women are largely represented in the group of sunbed users. Recent studies have brought the testimony that intermittent sun exposure (e.g. during holidays) is an important risk factor for skin cancer (notably basal cell carcinoma and melanoma). The investigations have not provided convincing evidence on the relation between the use of artificial devices and the development of skin cancer. This is partly caused by the fact that sunbed users are generally very motivated to get a tan. It is therefore difficult to distinguish between the effect of natural sun and of artificial UV radiation. In the Netherlands, the analyses of scientific data provide the basis for recommendations concerning sun exposure and use of sunbeds. There is an effort to provide the general public with qualified, professional information on the responsible way of tanning.

Basal Cell Carcinoma↗
PubMed2000

Efficacy, tolerability, and safety of a long-pulsed ruby laser system in the removal of unwanted hair.

BACKGROUND: Unwanted hair growth is a common, usually physiologic phenomenon. OBJECTIVE: In this study the efficacy and tolerability of a long-pulsed ruby laser system was compared with needle electrolysis and hot wax on three parts of the body. METHODS: Thirty volunteers were treated three times on the forearm (n = 10), on the face (n = 10), or in the pubic area (n = 10) with 25 J/cm2 laser, 40 J/cm2 laser, needle electrolysis, and hot wax therapy. RESULTS: The 25 J/cm2 and 40 J/cm2 laser treated sites showed a statistically significant decrease (38% and 49%, respectively) in the number of hairs at the first visit after the last treatment compared to the pretreatment hair counts. No significant decrease was observed in the needle electrolysis and hot wax treated sites. Laser therapy yielded better results on the forearm than on the face or pubic area and was scored as the least painful. CONCLUSION: The long-pulsed ruby laser is a promising, well-tolerated method of epilation.

Adult↗
PubMed1999

[Ultraviolet A-I phototherapy for skin diseases].

Favourable effects of sunlight on various skin diseases include inhibition of rapid proliferation of cells (psoriasis), modulation of cells in an inflammatory infiltrate (atopic eczema) and stimulation of proteolytic enzymes (scleroderma). The ultraviolet (UV) fraction of the solar spectrum is the most biologically active because it is almost completely absorbed by the skin. UVB and the combination of psoralens with UVA (PUVA) have become important therapeutic modalities, especially for psoriasis and eczema. Lamps producing long wave UV radiation are available: UVA-I light. Owing to its longer wavelength it penetrates more deeply into the skin and gives less risk of development of skin cancer than other forms of UV radiation. Good results are reported of application of UVA-I in patients suffering from atopic dermatitis, scleroderma, urticaria pigmentosa, and systemic lupus erythematosus.

Dermatitis, Atopic↗
PubMed1999

Study of DT-diaphorase in pigment-producing cells.

DT-diaphorase is an FAD-containing enzyme capable of a two-electron reduction of ortho- and paraquinones. Nicotinamide coenzymes (NADH + H+ and NADPH + H+) serve as hydrogen sources in these reactions. The role of DT-diaphorase has been thoroughly investigated in situations when the enzyme is able to reduce exogenous and endogenous quinones, hence protecting the cells against these reactive intermediates. The enzyme has also been studied in connection with its ability to activate some quinoid cytostatics. It is surprising that DT-diaphorase has never been investigated in pigment-producing cells that are known to generate considerable amounts of ortho-quinones. Using a spectrophotometric method we could readily measure the activity of DT-diaphorase in epidermis and various cultured pigment cells. The melanocytes isolated from dark skin showed generally higher DT-diaphorase activity than those from fair skin samples. Also, darkly pigmented congenital naevus cells exhibited higher activity of this enzyme. The most striking was the high DT-diaphorase activity in melanoma cell cultures. In these cells DT-diaphorase activity could be induced by incubation of the cells with 4-hydroxyanisole. A similar effect was seen when a catechol-O-methyltransferase (COMT) inhibitor (3-(3,4-dihydroxy-5-nitrobenzylidene)-2,4-pentanedione (OR-462) was utilised. The induction was inhibited by cyclohexidine.

Anisoles↗
PubMed1998

The role of EDTA in provoking allergic reactions to subcutaneous infusion of apomorphine in patients with Parkinson's disease: a histologic study.

One of the formulations of apomorphine, used in clinical practice, contains sodium edetate (EDTA). EDTA is a chelator which indirectly prevents oxidation of apomorphine. A clinical and histologic study in four patients revealed that apomorphine with EDTA caused severe subcutaneous nodules, histologically characterized by an inflammatory infiltrate with a large amount of eosinophils, indicating a cell-mediated allergic reaction. After withdrawal of EDTA, this allergic component completely disappeared, which was accompanied clinically by less extensive nodule formation with a softer consistency. It is therefore recommended that EDTA be excluded from apomorphine formulations.

Abdominal Muscles↗
PubMed1998

Variations in melanin formation by cultured melanocytes from different skin types.

In many laboratories, culturing skin melanocytes has become a routine research activity. However, recent investigations have revealed that the quality and quantity of the pigment formed in the cultured cells may differ significantly from those of the original skin pigment cells. To shed more light on this issue, we examined the influence of different culture media on pigment production. We showed that there were notable passage-to-passage variations in the synthesis of melanin. This was particularly true for phaeomelanin. It is therefore advisable to analyse the melanin in the cells before the start of experiments. In spite of the variations, basic differences in the pigmentation pattern between melanocytes isolated from light-skinned and dark-skinned individuals remained preserved in the corresponding cultures as observed by electron microscopy. Also, the total melanin content was higher in a skin type VI melanocyte culture than in skin type I and II melanocyte cultures. In contrast to total melanin, the phaeomelanin concentration of skin type VI cells was similar to that of the skin type I melanocytes. With higher L-tyrosine concentrations in the medium, as well as increased eumelanin synthesis, phaeomelanogenesis was also stimulated in all cultures tested. This stimulation was particularly prominent in skin type I melanocytes. Our preliminary experiments also showed that a melanocyte culture from atypical naevus cells exhibited a similar preference for phaeomelanogenesis when pigmentation was stimulated.

Culture Media↗
PubMed1998

(Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes.

The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by culturing at two different concentrations, basic (0.01 mM) or high (0.2 mM), of L-tyrosine, the main precursor of melanin. In parallel, pheo- and total melanin contents of the cells were determined. Identical experiments were performed with two melanocyte cultures derived from a skin type I and a skin type VI individual. For the first time the correlation between UVA-induced genotoxicity and pheo-/total melanin content has been investigated. We observed that cultured in basic medium, the skin type VI melanocytes contained 10 times more total melanin and about seven times more pheomelanin than the skin type I melanocytes. Elevation of tyrosine level in the culture medium resulted in an increase of both pheo- and total melanin levels in both melanocyte cultures; however, the melanin composition of skin type I melanocytes became more pheomelanogenic, whereas that of skin type VI melanocytes remained the same. The skin type VI melanocytes cultured in basic medium demonstrated a very high sensitivity (1.18 ssb per 10(10) Da per kJ per m2) toward UVA that is probably related to their high pheo- and total melanin content. Their UVA sensitivity, however, did not change after increasing their melanin content by culturing at high tyrosine concentration. In contrast, the skin type I melanocytes demonstrated a low sensitivity (0.04 ssb per 10(10) Da per kJ per m2) toward UVA when cultured in basic medium, but increasing their melanin content resulted in a 3-fold increase in their UVA sensitivity (0.13 ssb per 10(10) Da per kJ per m2). These results demonstrate that UVA-irradiated cultured human melanocytes are photosensitized by their own synthesized chromophores, most likely pheomelanin and/or melanin intermediates.

Cells, Cultured↗
PubMed1998

Effect of topical tretinoin under occlusion on atypical naevi.

Atypical naevi are potential precursors of melanoma and markers of increased melanoma risk. To examine the possibility of chemoprevention of melanoma by retinoids, we studied the effect of topical tretinoin 0.1% (all-transretinoic acid; vitamin A acid) and tretinoin 0.1% with hydrocortisone on atypical naevi. Thirty patients with atypical naevi were enrolled in a prospective randomized double blind study. For each patient three comparable naevi were selected and randomized to receive tretinoin 0.1% (T), tretinoin 0.1% with hydrocortisone 1% (C) or a placebo cream (P) once a week under Actiderm occlusion for 4 months. Baseline views of the naevi, taken with a videomicroscope (magnification 20 x), were assessed for morphological changes compared with views taken 2 months after the beginning of treatment, 1 week after completion of treatment and 6 months later. After completion of the study all naevi in the T and C groups and six naevi in the P group were removed and evaluated histologically for the presence of atypia. The number of naevi that had changed in colour or size was significantly higher in the T and C groups compared with the placebo group. A size reduction took place in 42.9% (T) and 40.0% (C) of the naevi and the colour changed in 75.0% (T) and 66.7% (C). The effect of treatment, in general subtle, did not differ significantly between groups T and C, but naevi treated with C became significantly less irritated. Histologically, 75.0% of the naevi treated with T and 69.6% of the naevi treated with C were atypical. Therefore, no major change was seen in the clinical aspect of atypical naevi after treatment with tretinoin 0.1% or tretinoin with hydrocortisone 1%, and most of the treated naevi still met the histological criteria for atypia after the treatment period. The current management of follow-up of atypical naevi and excision when change to melanoma is suspected is therefore still recommended. Nevertheless, some response was seen, which may justify a further exploration of tretinoin and hydrocortisone 1% therapy for a longer treatment period in combination with research to clarify its mechanism.

Adult↗
PubMed1998

Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly.

The objective of this study was to compare the effect of ultraviolet radiation (UV) and oral vitamin D3 on the vitamin D status and parathyroid hormone (PTH) concentration in elderly nursing home patients. The design of the study was a randomized clinical trial. The setting was a psychogeriatric nursing home. Subjects included 45 female psychogeriatric patients with a mean age of 85 years. Exclusion criteria were going outdoors more than once a week and the presence of actinic or cancer skin lesions. Intervention was random allocation of UV-B irradiation at half the minimal erythemal dose of the lower back, three times per week during 12 weeks (UV-B), or oral vitamin D3 400 IU/day during 12 weeks (VIT-D), or no treatment (CONTR). Main outcome measures were change in fasting serum levels of vitamin D metabolites at 0, 2, 4, 8, and 12 weeks in the treatment groups, compared with the control group. PTH(1-84) was measured at 0 and 12 weeks. Baseline serum 25-hydroxyvitamin D (25(OH)D) was lower than 30 nmol/l in 95% of the participants. It increased to a median value of around 60 nmol/l after 12 weeks both in the UV-B and VIT-D groups, whereas there was no change in the CONTR group. Serum 1,25-dihydroxyvitamin D increased significantly in the UV-B group. Serum calcium increased significantly in both treatment groups. Serum PTH decreased more than 30% in both treatment groups (p < 0.001), whereas there was no significant change in the control group. Irradiation with UV-B in the very elderly for a few minutes per day leads to adequate improvement of the vitamin D status. It is as effective as oral vitamin D3 in increasing serum 25(OH)D and suppressing secondary hyperparathyroidism.

Administration, Oral↗
PubMed1997

Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase.

Tyrosinase (EC 1.14.18.1) exhibits unusual kinetic properties in the oxidation of monohydric phenol substrates consisting of a lag period that increases with increasing substrate concentration. The cause of this is an autocatalytic process dependent on the generation of a dihydric phenol substrate, which acts as an activator of the enzyme. Experiments with N-substituted dihydric phenol substrates (N-methyldopamine, N-acetyldopamine) demonstrate that oxygen consumption is retarded in the N-acetyl substituted material due to a diminished rate of cyclization. The oxygen uptake exhibited a similar pattern when N-acetyltyramine was oxidized, and this was reflected by a prolongation of the lag period. N,N-Dipropyldopamine was oxidized with normal kinetics but with an oxygen stoichiometry of 0.5 mol of oxygen/mol of substrate. We show that this is the result of the formation of a stable indoliumolate product with oxidation-reduction properties that prevent the formation of dopaminochrome, thus blocking further stages in the tyrosinase-catalyzed oxidation. Evidence that the indoliumolate product is formed by cyclization of the ortho-quinone is presented by pulse radiolysis studies, which demonstrate the formation of the ortho-quinone (by disproportionation of the corresponding semiquinones), which cyclizes to give the indoliumolate. The rate constant for cyclization was shown to be 48 s-1 (at pH 6.0). Tyrosinase-catalyzed oxidation of the monohydric phenol analogue, N, N-dimethyltyramine, was shown to require the addition of a dihydric phenol. Oxygen utilization then exhibited a stoichiometry of 1.0, indicating that the reactions proceed only as far as the cyclization. The analogous stable cyclic indoliumolate product was shown to be formed, with UV absorption and NMR spectra closely similar to the indoliumolate derived from N,N-dipropyldopamine. This material was methylated by catechol O-methyltransferase but was unreactive to redox reagents. The formation of the cyclic product accounts for the indefinite lag when N,N-dimethyltyramine is used as the substrate for tyrosinase in the absence of a dihydric phenol cofactor.

Catechols↗
PubMed1997

Determination of pheomelanin by measurement of aminohydroxyphenylalanine isomers with high-performance liquid chromatography.

We describe an improved method for the analysis of pheomelanin in biological samples. The method is based on a chemical degradation of the melanin polymer and HPLC analysis of specific degradation products. Hydriodic hydrolysis provides 4-amino-3-hydroxyphenylalanine (AHP) and 3-amino-l-tyrosine (AT) which are detected with an electrochemical detector. We have examined each step of the analysis and the results are presented in this paper. First the samples are hydrolyzed for 16 h. AT and AHP are then isolated from the hydrolysates by ion-exchange chromatography and then separated and quantitated by HPLC and electrochemical detection. The method shows good reproducibility with a total imprecision below 5.6%. The linearity of the method was shown from 0 to 490 ng AT and 0 to 850 ng AHP per sample, using a melanoma cell suspension (27 mg protein/ml) with up to 24-fold dilutions of the original sample. For cultured "normal" human melanocytes a minimal amount of 0.1 mg protein is sufficient for analysis of pheomelanin in the samples. This method provides the opportunity to study the composition of the formed melanin in cell lines, cultured in different growth media.

3T3 Cells↗
PubMed1997

Melanogenesis in transfected fibroblasts induces lysosomal activation.

Normal melanosome biogenesis requires the association of structural proteins with tyrosinase. 3T3 Swiss fibroblasts transfected with mouse tyrosinase cDNA (line 13.4, clone c) are a unique system in which melanogenesis takes place in the absence of melanosomal structural proteins. Our study confirmed that transfected fibroblasts displayed tyrosinase activity and some of them produced pigment granules. In the absence of melanosomal structural proteins the granules failed both to show a typical ultrastructure and to undergo the usual melanosome ontogenesis. The differentiating agent--dimethyl sulfoxide--increased phaeomelanin production. Pigment was localized in membrane-bound vesicles which were identified as lysosomes by means of immunogold electron microscopy. Cell line 13.4 had higher levels of lysosomal enzymes (beta-hexosaminidase, alpha-mannosidase) than both parental 3T3 cells and clone pKG4 (fibroblasts transfected with the G418 resistance plasmid). Melanosomal proteins act as scavengers of toxic products of melanogenesis, and our results suggest that in their absence cells may employ an alternative mechanism to sequester injurious products.

3T3 Cells↗
PubMed1997

Cytotoxic interactions of Zn2+ in vitro: melanoma cells are more susceptible than melanocytes.

Previous studies have shown that sensitivity to high extracellular levels of Zn2+ is a general feature of cells in vitro and that a prerequisite of the toxic action of zinc is entry into cells via channels that are shared with iron or calcium. As the biochemical and toxicological behaviour of zinc chelate complexes could be different from that of free Zn2+, the effect of chelating agents on zinc transport into human melanoma cell lines was tested. EDTAcal and tetracycline reduced the toxic action of zinc ions in vitro, whereas phenytoin and diethyldithiocarbamate potentiated its effects. D-penicillamine, an effective chelator of zinc in vivo, also exerted a protective action in vitro. Comparison of sensitivity to Zn2+ in vitro between human melanoma lines and several lines of pigment cells from skin of various origins demonstrated that melanoma cells are killed by zinc ions at concentrations which are only partially toxic for normal pigment cells. This is consistent with the repeatedly observed high uptake of 65Zn by melanoma cells.

Chelating Agents↗
PubMed1997

Melanogenesis in cultured melanocytes can be substantially influenced by L-tyrosine and L-cysteine.

We investigated the effect of varying concentration of 1-tyrosine and 1-cysteine in culture medium on melanin production by human skin melanocytes (skin phototype II/III). In addition to the analyses of dopa oxidase activity and total melanin, pheomelanin production in the cells was assessed by high-performance liquid chromatography determinations of pheomelanin degradation products, 3-aminotyrosine and 4-amino-3-hydroxyphenylalanine. As another marker for pheomelanin, melanosomal sulfur was determined by the use of X-ray microanalysis. With varying concentration of both amino acids, profound changes in the pigmentation patterns of the melanocytes were observed. A high concentration of 1-tyrosine (0.2 mM) was always connected with increased pigmentation. In combination with a low 1-cysteine content we saw an increase in tyrosinase activity and the highest melanin content. At high concentrations of both 1-tyrosine and 1-cysteine, the melanocytes showed reduced tyrosinase activity and they produced notably more pheomelanin. In case of the pheomelanin measurements by high-performance liquid chromatography and the sulfur detection with X-ray microanalysis, strongly increased concentrations were found when cells were maintained in high 1-tyrosine medium as compared with those grown with low 1-tyrosine. This was especially true for the combination with low 1-cysteine showing that the 1-tyrosine content of the medium strongly influences not only the eumelanin but also the pheomelanin production in the cultured melanocyte. It can be concluded that variations in the concentrations of 1-tyrosine and 1-cysteine in culture medium can be used to regulate the melanogenetic phenotype under in vitro conditions.

Cells, Cultured↗
PubMed1997

Prolonged increase of cis-urocanic acid levels in human skin and urine after single total-body ultraviolet exposures.

Cis-urocanic acid (cis-UCA), a mediator of immunosuppression, is formed from trans-UCA upon UV-exposure of the skin. This study describes a liquid chromatographic method for the simultaneous quantification of cis- and trans-UCA in skin, urine and plasma of nonirradiated volunteers. It also describes cis- and trans-UCA kinetics in UV-irradiated volunteers. New procedures to remove interfering substances from urine and plasma are reported. Normal levels of cis-UCA in skin, urine and plasma of nonirradiated volunteers were 0.5 nmol/cm2, 0.03 mumol/mmol creatinine (median 0.00) and undetectable and those of trans-UCA were 17.1 nmol/cm2, 1.36 mumol/ mmol creatinine and 0.5 microM, respectively. Upon single total body UVB (290-320 nm) exposures of 250 J/m2, epidermal cis-UCA levels immediately reached a maximum and returned to basic levels 3 weeks later. The cis-UCA levels in urine reached a maximum in 5-12 h postirradiation and reached baseline values in 8-12 days. Additionally, a single total body UVA (320-400 nm) irradiation of 200 kJ/m2 yielded a similar pattern. The kinetics of cis-UCA in plasma could not be followed due to low concentrations; however, that of skin and urine was informative in relation to solar exposures and phototherapy.

Adolescent↗
PubMed1996

Comet assay demonstrates a higher ultraviolet B sensitivity to DNA damage in dysplastic nevus cells than in common melanocytic nevus cells and foreskin melanocytes.

We used the single cell gel electrophoresis assay (comet assay) to study ultraviolet B (UVB)-induced DNA damage in pigment cells. This assay detects DNA damage, mainly DNA strand breaks and alkali labile sites in the DNA molecule. We studied the effect of biologically relevant doses (comparable to 2-3 MED (minimal erythemal dose) for in vivo irradiated full-thickness skin) of monochromatic UVB light of 302 nm on cultured melanocytes derived from foreskin, common melanocytic nevi, and dysplastic nevi. We were able to demonstrate a linear dose-response relationship between UV dose and the migration coefficient of the comet tail in all three types of pigment cells. Nevus cells originating from dysplastic nevi showed the highest sensitivity to UVB irradiation: 65% higher induction of DNA damage compared to the induction in foreskin melanocytes. Common melanocytic nevus cells were most resistant and showed a 30% lower induction of DNA damage in comparison to foreskin melanocytes. Differences in chromatin structure and cell cycle profile may influence the results of the comet assay. Control experiments with x-ray irradiation, which is well known to produce direct DNA strand breaks via radical formation, revealed only small differences between the three types of melanocytic cells. It is unlikely, therefore, that intrinsic nuclear characteristics may account for the observed differences.

Cell Movement↗
PubMed1996

Metabolic interference of melanogenesis in pigment cells.

Biosynthesis of pigment melanin in pigment cells (melanocytes, nevus cells, melanoma cells) constitutes a distinctive but integrated part of intracellular metabolism. Although the melanin formation takes place in specialized compartments (melanosomes), these structures are not fully "leak-proof" and, as a consequence, the reaction products of melanogenesis have an opportunity to interact with different metabolic processes. This can be of particular importance when the melanogenesis is stimulated (e.g. by UV radiation) and when the integrity of melanosomes and/or their limited membranes is disturbed. From the toxicologic viewpoint melanogenesis represents an unique metabolic burden for the cell and this fact can have consequences for cellular defence systems. For instance, the conjugation of melanogenic precursors present in cytoplasm with glutathione or cysteine may reduce the availability of the thiocompounds for other necessary protective reactions. For the same reason, in melanin-producing cells there is an increased need for detoxification of the reactive intermediates by O-methylation. This reaction catalyzed by catechol-O-methyl-transferase may lead to concentration changes of methyl donor S-adenosylmethionine and the reaction product S-adenosylhomocysteine. As a consequence, decreased S-adenosylmethionine/S-adenosylhomocysteine ratio (so-called "methylation ratio") is known to have profound inhibitory effect on methylation processes inclusive DNA methylation. Although still very speculative, this situation might very well lead to the generation of CpG mutations and (due to DNA hypomethylation) to activation of silent (onco)genes.

Animals↗