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Biomedical subjects

A Suchak

Publications and source records attributed to A Suchak.

4 recordsLinked to original sources
PubMed2003

Effects of alkaline phosphatase and its inhibitor levamisole on the modulation of androgen metabolism by nicotine and minocycline in human gingival and oral periosteal fibroblasts.

UNLABELLED: The aim of this investigation was to establish the implications of nicotine, minocycline, alkaline phosphatase (AP) and its inhibitor levamisole (L) on tissue turnover in human gingival and periosteal fibroblasts (HGF, HPF) using [14C]-testosterone as substrate. Monolayer cultures of HGF and HPF established from four patients were incubated in duplicate with serial and optimal concentrations of nicotine and minocycline, alone and in combination, for 24h in Eagle's MEM, with the substrate [14C]-testosterone. Further experiments were carried out on HPF only, to investigate the effects of alkaline phosphatase (AP) and its inhibitor levamisole (L) on the metabolism of [14C]-testosterone, followed by the effects of L on the modulatory actions of nicotine. The cell-conditioned medium was then solvent-extracted, analysed and quantified for steroid metabolites using a radioisotope scanner. At low concentrations, nicotine stimulated the synthesis of the physiologically active androgen 5alpha-dihydrotestosterone (DHT) from [14C]-testosterone, with inhibition at higher concentrations (n=4; P<0.01). Minocycline stimulated the synthesis of DHT, with decreased yields in the presence of nicotine (n=4; P<0.01), but greater than with nicotine alone. Alkaline phosphatase significantly enhanced the synthesis of androgen metabolites by HPF (n=4; P<0.01), with inhibition in response to L alone and in combination with AP, to less than control values (n=4; P<0.01). L also caused further inhibition in the yields of androgen metabolites when incubated with nicotine, implying that some of the inhibitory effects of nicotine could be due to inhibition of AP activity. CONCLUSION: This investigation has shown that nicotine can inhibit the formation of matrix-stimulatory steroid metabolites in fibroblasts, partly due to inhibition of AP activity. Minocycline is a useful adjunct, in reducing the inhibition of androgen metabolism caused by nicotine.

Adult↗
PubMed2002

Phenytoin-mediated androgen metabolism in gingival fibroblasts. Effects of the antiandrogen finasteride and the alkaline phosphatase inhibitor levamisole.

OBJECTIVES: This investigation attempts to identify the role of the alkaline phosphatase inhibitor levamisole (L) and the antiandrogen finasteride (F) on 5alpha-reductase activity in gingival fibroblasts, to elucidate mechanisms for phenytoin-induced gingival overgrowth. MATERIAL AND METHODS: Human gingival fibroblasts were incubated with Eagle's MEM and 14C-testosterone/14C-4-androstenedione as substrates; effective concentrations of phenytoin (Ph), levamisole (L) and finasteride (F), alone and in combinations of (Ph + F) (Ph + L) were added to the incubate. After 24 h, the medium was analysed for steroid metabolites and quantified using a radioisotope scanner. RESULTS: The metabolites isolated were 5alpha-dihydrotestosterone (DHT), 4-androstenedione (4-A) or testosterone (T) from each substrate. With 14C-T as substrate, Ph stimulated DHT synthesis by 1.7-fold, while F and L inhibited this activity by 1.8-fold and 34%, respectively (n = 6; P < 0.001). The combination of Ph + F reduced yields by 2.7-fold compared with Ph alone and Ph + L reduced DHT synthesis by 2.4-fold compared with Ph alone (n = 6; P < 0.001). When 14C-4-androstenedione was used as substrate, similar trends were identified. CONCLUSION: These results suggest that the alkaline phosphatase inhibitor levamisole and the 5alpha-reductase inhibitor finasteride can substantially decrease the yields of DHT in fibroblasts, stimulated by phenytoin. This could be a potential target for reducing the gingival overgrowth caused by phenytoin.

5-alpha Reductase Inhibitors↗
PubMed2001

The effects of human mast-cell products and of phenytoin on androgen 5alpha-reductase expression in human gingival fibroblasts.

The aim was to elucidate mechanisms for phenytoin-induced gingival overgrowth, using effects of type 1 human mast cell (HMC-1) supernatant and histamine on the expression of 5alpha-reductase in human gingival fibroblasts (HGF), and the effects of phenytoin on this activity. Duplicate incubations of HGF in Eagle's minimum essential medium (MEM) were performed with [14C] testosterone and serial concentrations of mast-cell histamine (1-100 microgram/ml)/HMC-1 culture supernatant at serial dilutions of 1-100 microl/ml for 24 h. Other experiments employed optimal concentrations of HMC-1 supernatant (10 microl/ml) or histamine (8 microgram/ml) and phenytoin (1 and 5 microgram/ml), alone and in combination, using two androgen substrates, [14C] testosterone and [14C] 4-androstenedione. At the end of a 24-h incubation the medium was solvent-extracted for steroid metabolites, analysed and quantified in a radioisotope scanner. HMC-1, histamine (n=3) and phenytoin (n=6) significantly increased the synthesis of dihydrotestosterone and 4-androstenedione by up to 80% (P<0.01); the combination of HMC-1 and phenytoin caused two-fold increases (n=6; P<0.01). The incubations with histamine alone and in combination with phenytoin showed significant stimulation of dihydroxytestosterone and the diols alone and in combination, which was less pronounced in combination. This investigation demonstrates significant stimulation of 5alpha-reductase activity in human gingival fibroblasts by mast-cell supernatant and a specific product histamine, alone and in combination with phenytoin. Androgen 5alpha-reductase-mediated anabolic actions in connective tissue are well documented. The findings suggest a novel hypothesis that mast-cell mediated androgen action in the gingiva in response to phenytoin could contribute to gingival overgrowth.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗