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S Pavel

Publications and source records attributed to S Pavel.

At least 19 recordsLinked to original sources
PubMed1992

Preparation of monoclonal mouse antibodies against two specific eu-melanin related compounds.

Two eu-melanin precursors, 6-hydroxy-5-methoxyindole-2-carboxylic acid (HMI2C) and 5,6-dihydroxyindole-2-carboxylic acid (DHI2C) were synthesized and coupled to bovine serum albumin, hemocyanin and polylysine by the combined action of carbodiimide and succinimide. These indole-carrier conjugates served as antigens for the production of specific antibodies against DHI2C and HMI2C in BALB/c mice. The specificity of these antibodies was tested using a combination of affinity chromatography and ELISA procedures. Polyclonal mouse antibodies reacted with the indole-carrier conjugates, but not with the unbound indole compounds. Monoclonal antibodies from two hybridoma cell lines were obtained from a HMI2C-immunized mouse after a fusion with four subclonings. They reacted with free HMI2C and to a lesser extent with unbound DHI2C. One monoclonal showed 50% inhibition in the ELISA test at concentrations of 0.6 mumol.l-1 and 5 mumol.l-1 for HMI2C and DHI2C, respectively. These antibodies did not show any cross-reactivity with nine structurally related compounds and should be valuable reagents for the detection and quantification of HMI2C and other eu-melanin related compounds.

Animals↗
PubMed1992

[Exogenous ochronosis, a little-known side effect of hydroquinone-containing ointments].

Two patients with exogenous ochronosis, an unfamiliar side effect of hydroquinone-containing bleaching creams, are presented. This disorder is characterized by progressive darkening of the area to which the cream is applied. Histologically there is deposition of yellow-brown pigment in the dermis, in addition to degeneration of collagen and elastic fibres. The chemical composition of the ochronotic material and the pathogenesis of this paradoxical effect of hydroquinone are unknown. Hydroquinone containing creams should not be used for longer than two years. If there is no improvement within six months, application should be discontinued.

Adult↗
PubMed1992

Cytotoxicity of a selected series of substituted phenols towards cultured melanoma cells.

Substituted phenolic compounds were previously shown to exhibit cytotoxicity towards epithelial cells in the presence of the enzyme tyrosinase as a result of the formation of their quinone products. Seventeen of these compounds were tested for cytotoxic properties towards three different melanoma cell lines. The compounds were split into four groups of phenol derivatives, A; alkoxyethers, including 4-hydroxyanisole (4HA), B; oxyethers derivatized at the acyl side chain, C; oxyethers derivatized at the phenol, and D; acyl thioethers. Toxicity was determined by total cell counts after 3 days exposure to the compounds. Large reductions in cell numbers were observed with 4HA (the methoxy-), ethoxy-, propoxy and iso-butoxyethers of group A and the methyl- and propyl thioethers of phenol of group D. Derivatization of the ethoxy- and propoxy side chains (group B) did not seem to increase the cytotoxic effects, as determined by cell counts. Compounds of group C, which need intracellular esterase activity to release the phenols, showed moderate toxicities. Toxicity of certain compounds was confirmed by LDH release into the culture medium and by increased trypan blue uptake of cells exposed to the compounds. Flow cytometric investigations of cells after exposure for 24 h revealed that most compounds caused an increase in the proportion of cells in G1 phase. A complete accumulation of cells in S-phase was observed after exposure to 4-ethoxyphenol. Inhibition of DNA synthesis was also shown by inhibition of bromodeoxyuridine incorporation. The results presented show that phenolic compounds exhibit cytotoxic properties towards melanoma cells some of which may be mediated by tyrosinase activity. Toxicity of the compounds was shown to be exerted during DNA replication but their toxic action may also be due to membrane damage and inhibition of cell metabolism.

Antineoplastic Agents↗
PubMed1992

Fair, and still a sun lover: risk of gallstone formation.

STUDY OBJECTIVE: The aim was to evaluate the hypothesis that sunlight exposure leads to the development of gallstones in people with a sun sensitive skin. DESIGN AND SETTING: This was a case-control study among 206 white patients referred for an ultrasound examination of the gallbladder. Sunlight exposure and skin sensitivity were retrospectively assessed by a structured questionnaire. The questionnaire was taken before the outcome of the ultrasound examination was known, so that the patients and the interviewers were blind to the outcome. The main outcome measure was gallstones in the gallbladder detected by ultrasound. MAIN RESULTS: 87 patients had gallstones (cases), 119 had none (controls). In subjects with a skin sensitive for sun (Fitzpatrick skin type I) a positive attitude to sunbathing was associated with a higher risk of gallstones than a negative attitude. In subjects with an insensitive skin (skin type IV) no association was found. CONCLUSIONS: This study confirms a hypothesis which was based upon metabolic research. However it is too early to upgrade the first "F" in the traditional adage that gallstone patients are "fair, fat, female, fertile and forty". Since both epidemiological and pathobiological evidence is scarce, the role of sun and/or (ultraviolet) light exposure and skin sensitivity in the aetiology of gallstones should be confirmed by further research.

Adolescent↗
PubMed1990

Determination of catechol O-methyltransferase activity in relation to melanin metabolism using high-performance liquid chromatography with fluorimetric detection.

A new sensitive method for the determination of catechol O-methyltransferase activity has been developed. The method is based on the O-methylation of the indolic intermediates of melanin metabolism. The substrate, 5,6-dihydroxyindole-2-carboxylic acid, is converted by the enzyme to two O-methylated products, which can be separated by high-performance liquid chromatography and measured with fluorimetric detection. The physiological presence of both substrate and products could be detected in crude melanoma cell extracts. The limit of sensitivity for detection of the O-methylated products is less than 0.5 pmol per injection. The method was compared with an earlier described HPLC method which makes use of uv detection of O-methylated products of 3,4-dihydroxybenzoic acid. The described method will be used to study the importance of catechol O-methyltransferase as a protective enzyme in (malignant) melanocytes.

Catechol O-Methyltransferase↗
PubMed1989

Increased anthralin irritation response in vitiliginous skin.

The irritation response to anthralin was studied using the chamber-testing technique in 17 patients with vitiligo. Anthralin concentrations of 0.1%, 0.5%, 1%, and 5% in lanette wax were applied to both vitiliginous and adjacent pigmented skin for 24 h. The extent of the erythematous reaction was evaluated on the 2nd day after application. The visual assessment of the paired anthralin patches indicated that the erythema was more intense in pigmented skin than in vitiliginous skin in 15 out of 17 patients. Chromometer readings, however, clearly indicated that the erythematous response was stronger in the vitiliginous skin than in the pigmented skin, confirming the known fact that the human eye is not accurate in the quantitative assessment of complex colors. Immunophenotypification of cellular infiltrates, using the combination of different monoclonal antibodies and the peroxidase technique, showed that inflammatory cell infiltrates caused by the anthralin exposure contained increased numbers of granulocytes and monocytes in vitiliginous skin when compared with normal skin. The percentage of T-cell subsets, Langerhans cells, and mast cells in the same infiltrates of both types of skin were similar. Our results are discussed in accordance with the view that anthralin-induced radical species of the pigmented skin can be neutralized by the scavenging properties of melanin.

Adult↗
PubMed1989

Vasotocin increases quiet sleep and suppresses active sleep in newborn cats. Opposite effects after vasotocin immunoneutralization.

One picogram of synthetic arginine vasotocin (AVT) administered into the lateral ventricle of newborn cats aged 7-9 days, increased the amount of quiet sleep and markedly decreased the amount of active sleep. Ten pg AVT completely suppressed active sleep during the recording time of 3 hr. The increase in the quiet sleep occurred within 5-7 min and lasted for the entire recording time of 3 hr. An undiluted specific AVT antiserum (10 microliters) administered into the lateral ventricle, induced opposite effects suppressing quiet sleep and increasing active sleep. It is concluded that in newborn cats both AVT and the AVT antiserum induce the same hypnogenic effects as in the adult cats.

Animals↗
PubMed1989

Large-scale cultivation of human melanocytes using collagen-coated Sephadex beads (cytodex 3).

Pure melanocytes were obtained from the epidermis of human foreskin by a modification of a previously described method in which geneticin was added for selective killing of fibroblasts. Purity of the culture was confirmed by light and electron microscopy and by the use of a monoclonal antibody NKI-beteb, which is specific for a vesicular membrane antigen present on melanocytes. Melanocytes were tested for their affinity to several microcarriers. They attached to cytodex 1 and 3 and dorma cell, but they did not attach to glass and gelatin beads. The best results were obtained with cytodex 3. After an almost immediate and total attachment of melanocytes a fourfold to fivefold increase in cell number was achieved on this microcarrier within 3 weeks. With the results obtained, it seems that the collagen-coated cytodex 3 microcarrier surface supports the growth of melanocytes. Preliminary results obtained with a microcarrier cell culture fermenter clearly indicate that the large-scale cultivation of normal human melanocytes in such an automated system is possible.

Cell Adhesion↗
PubMed1987

Melanin-related metabolites as markers of the skin pigmentary system.

Three different groups of chemical intermediates are known to be formed during the synthesis of melanin in melanocytes: phenolic compounds, phenolic thio-conjugates, and indolic compounds. All these substances and their metabolites can be detected in urine. We measured the urinary excretion of 3,4-dihydroxyphenylalanine (dopa), 5-S-cysteinyldopa (5-S-CD), and 2 indolic compounds, namely 5-hydroxy-6-methoxyindole (5H6MI) and 5-hydroxy-6-methoxyindole-2-carboxylic acid (5H6MI2C) in urine samples of 4 groups of people with different contents of cutaneous melanin: Asian group, white group, and 2 groups of whites 1 with vitiligo and 1 with tyrosinase-negative oculocutaneous albinism. Dopa and 5-S-CD were determined with the method using high-performance liquid chromatography with an electrochemical detection. Indolic substances were measured by mass fragmentography with deuterium-labeled internal standards. Comparison of the melanin-related metabolites excreted in urine of people with different capacities for melanin biosynthesis indicates that, of all measured substances, 5H6MI2C is the best urinary marker of melanin formation in the skin pigmentary system.

Adolescent↗
PubMed1986

Intranasal vasotocin decreases cerebrospinal fluid 5-HIAA levels in man.

A single dose (10 ng/kg) of the nonapeptide arginine vasotocin (AVT) administered intranasally to healthy young men, significantly decreased 5-HIAA levels in the lumbar cerebrospinal fluid (CSF) 8 hr after its administration. So far, this represents the smallest amount of an active substance able to alter CSF 5-HIAA levels in man. It is suggested that the decrease of CSF 5-HIAA levels after AVT administration reflects an AVT-induced reduction of the brain 5-HT turnover.

Administration, Intranasal↗
PubMed1986

Eumelanin-related indolic compounds in the urine of treated melanoma patients.

A method was developed for the quantitation of six eumelanin-related indolic compounds in urine. The procedure employs methane ionization of the hexafluoroisopropyl and/or pentafluoropropionyl derivatives of 5,6-dihydroxyindole, 5-hydroxy-6-methoxyindole, 6-hydroxy-5-methoxyindole, 5-hydroxy-6-methoxyindolyl-2-carboxylic acid, 6-hydroxy-5-methoxyindolyl-2-carboxylic acid and 5,6-dimethoxyindolyl-2-carboxylic acid together with their deuterated analogues, and selected ion-monitoring. Deuterated analogues are added as internal standards to enzymatically hydrolysed urine before diethyl ether extraction. The method was used for monitoring urinary excretion in patients with malignant melanoma treated with cytostatics. In several cases, a decrease of the excretion of the eumelanin-related substances was recorded after the therapy. The usefulness of the individual indolic compounds for such follow-up studies is discussed.

Gas Chromatography-Mass Spectrometry↗