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Biomedical subjects

S Shuster

Publications and source records attributed to S Shuster.

At least 91 records · Page 5Linked to original sources
PubMed1985

Phase 1 and Phase 2 drug metabolism in isolated epidermal cells from adult hairless mice and in whole human hair follicles.

A sensitive fluorimetric assay to determine both Phase 1 (oxidation) and Phase 2 (conjugation) drug metabolism in epidermal cells isolated from hairless mice, using ethoxycoumarin as a model substrate, is described. Ethoxycoumarin was metabolized by isolated epidermal cells via dealkylation to 7-hydroxycoumarin (7-OHC) and subsequent conjugation. Phase 1 metabolites were extracted in ether from the aqueous incubation media, back extracted into sodium hydroxide and determined fluorimetrically. Conjugated metabolites remaining in the aqueous phase were hydrolysed by the action of beta-glucuronidase and extracted and determined in a similar manner. The production of free 7-OHC by isolated epidermal cells was biphasic at all substrate concentrations tested, exhibiting an initial linear increase followed by a plateau phase. The plateau phase was attributable to the conjugation of 7-OHC produced in situ. Metabolism was inhibited by SKF 525A, carbon monoxide, and alpha-naphthoflavone. Endogenous supplies of reducing equivalents in the form of NADPH were adequate to attain maximal rates of metabolism. With human hair follicles both Phase 1 and Phase 2 activity was detectable in 7 out of 11 subjects. The assay has the advantages of being sensitive, producing single defined metabolites from both Phase 1 and Phase 2 metabolism; is readily adaptable to human skin samples.

Animals↗
PubMed1985

Surgery for psoriasis.

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Dermatologic Surgical Procedures↗
PubMed1985

The stimulatory effects of prostaglandins on the melanophores of the lizard, Anolis carolinensis.

The melanosome dispersing activity of prostaglandins PGE1, PGE2, PGF1 alpha, PGF2 alpha, PGI2 and 6 beta PGI, was tested on the melanophores of Anolis carolinensis. Only PGE2 and PGE1 were active and while PGE2 was the most potent and acted synergistically with alpha-MSH, PGE1 was additive with alpha-MSH. Arachidonic acid also stimulated melanosome dispersion but its effect was blocked by indomethacin suggesting an action through its conversion to PGE1 or PGE2. The effect of alpha-MSH, on the other hand, was unaltered by indomethacin which suggests that alpha-MSH stimulated melanosome dispersion does not depend upon prostaglandin synthesis. Thus, while some prostaglandins may interact with alpha-MSH to stimulate melanosome dispersion they are unlikely to mediate its action.

Animals↗
PubMed1985

Drug acetylation and expression of lupus erythematosus.

Acetylator phenotype was measure in 58 patients presenting to a skin clinic with discoid lupus erythematosus (DLE) and in 51 normal healthy subjects. Twenty seven of the patients with DLE were found to have evidence of systemic lupus erythematosus (D+SLE). Frequency of slow acetylator phenotype was 58% in all DLE patients, 52% in those with D+SLE and was no different from the 57% in controls. The distribution of acetylator phenotypes within the groups with DLE and those with D+SLE was similar to controls. Severity of DLE was assessed as number of skin lesions and median lesion count was 11.5 in slow acetylators and 10 in fast acetylators but in D+SLE median lesion count was 22 in slow acetylators and 12 in fast acetylators, and there was a significant inverse relationship between lesion count and rate of acetylation; scores for systemic involvement showed no relationship. We conclude that there is no difference in the frequency or distribution of slow acetylator phenotype between normal subjects and patients with DLE with or without SLE but that actual rate of acetylation may determine severity of expression of the disease in slow acetylators.

Acetylation↗
PubMed1985

Strain differences in the induction of mono-oxygenase activity in mouse skin by topical clobetasol propionate: evidence of a role for the hr locus.

The effect of the topical application of clobetasol propionate on cutaneous ethoxycoumarin O'dealkylation (EOD) has been studied in various strains of mice. Clobetasol propionate markedly increased cutaneous EOD activity in adult hairless mice only. Similar treatment of adult haired C57BL/6J mice, or adult haired DBA/2J mice had no significant effect on cutaneous EOD activity. In contrast 3 methylcholanthrene induced cutaneous EOD activity in both hairless and C57 strains to a far greater extent than in the DBA strain. EOD activity in hairless mice non-responsive to polycyclic hydrocarbons, derived by selective breeding of hairless and DBA strains was induced by clobetasol propionate to a similar extent to that observed in responsive hairless strains. Hepatic EOD activity was not induced by clobetasol propionate in any of the strains tested. Strain differences in the induction of EOD by clobetasol propionate were not related to differences in either the concentration of cytosolic glucocorticoid receptor in the skin, the dissociation constant of the cytosolic receptor, or differences in percutaneous absorption. Polycyclic hydrocarbons did not compete with triaminolone acetonide for binding to the cytosolic glucocorticoid receptor. Strain differences in the induction of EOD activity by clobetasol propionate appear therefore not to be related to strain differences in either the Ah receptor of the glucocorticoid receptor, but to be regulated by the hr locus.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1985

Immunofluorescent localization of intermediate filament subunits for the differential diagnosis of malignant melanoma.

Intermediate filament subunits in normal cells and in their malignant derivatives can be used as specific markers for their histogenetic origins. We have studied five neoplasms of the skin in which positive identification of vimentin containing intermediate filaments by indirect immunofluorescence microscopy helped to establish the diagnosis of malignant melanoma. All of the neoplasms included in this study posed problems in differential diagnosis by conventional light microscopy and yielded equivocal results by conventional histochemistry. Thus, definitive distinction between poorly differentiated carcinoma and poorly differentiated melanoma could not be made by conventional microscopy. In all of the neoplasms described here, immunolabeling with antibodies against different intermediate filaments demonstrated positive staining for vimentin only. This intermediate filament subunit is present in melanocytes (as well as in many mesenchymal cells) but not in epithelial cells. Our study indicates that this technique may be valuable in differential diagnosis of malignant melanoma, particularly in instances where cells lack melanin or show other atypical morphologic features.

Aged↗
PubMed1985

Enhanced weal and flare response to histamine in chronic idiopathic urticaria.

Weal and flare histamine dose-responses were measured in 30 normal subjects and 15 patients with chronic idiopathic urticaria. The log dose-response curves were shifted to the left corresponding to an increase in histamine potency of 2.5 for weal and 3.1 for flare. An enhanced response to histamine may be important in chronic idiopathic urticaria and comparison of potency of antihistamines in different subjects may be unreliable where initial weal response is abnormal.

Adult↗
PubMed1985

Comparison of ultrasound and caliper measurements of normal and inflamed skin thickness.

We have compared ultrasound and Harpenden calipers for the measurement of thickness of non-inflamed and anthralin-inflamed skin. In non-inflamed skin ultrasound gave consistently and significantly lower values (0.87 mm +/- 2.3% s.e.) than calipers (1.1 mm +/- 2.7% s.e.) and the ultrasound/caliper ratio was 0.89 +/- 1.3%. In anthralin-inflamed skin the ultrasound/caliper ratio was not significantly different from unity (1.02 +/- 1.3%), but ultrasound was unable to measure inflamed skin thickness in 18% of cases because the echo could not detect the dermis-subcutaneous fat interface. The proportion of unreadable ultrasound results increased linearly with increase in skin thickness and the variance of ultrasound readings increased as inflammatory skin thickness increased; by contrast caliper variance remained constant. Harpenden calipers cannot be used in all subjects or in skin sites in which skin folds cannot be raised, but if the patient and site to be studied can be selected, Harpenden calipers have a greater precision, reproducibility and reliability than ultrasound for measurement of the thickness of inflamed skin.

Anthralin↗
PubMed1985

Mechanism of anthralin inflammation. I. Dissociation of response to clobetasol and indomethacin.

The effect of topical clobetasol propionate and a 1% topical indomethacin gel which could inhibit UV erythema was measured on anthralin inflammation by change in skin-fold thickness and erythema. The time course of the inflammatory oedema and erythema were different, as was their response to the drugs studied. The oedema of anthralin inflammation was completely inhibited by clobetasol propionate but the erythemal response showed a small and non-significant reduction. Indomethacin had no effect on anthralin oedema but produced a small but significant reduction in erythema in the first 24 h after anthralin application. These results suggest that either anthralin inflammation is not due to production of prostenoids, or that if it is, it occurs by other than the classical enzymic pathway.

Adult↗
PubMed1985

Mechanism of anthralin inflammation. 2. Effect of pretreatment with glucocorticoids, anthralin and removal of stratum corneum.

The inflammatory dose-response to anthralin was measured in human skin 24 h after pretreatment with topical corticosteroids and anthralin, and 48 h after removal of the stratum corneum with adhesive tape. Anthralin inflammation was increased after 1% hydrocortisone application and decreased by 0.1% betamethasone valerate and 0.05% clobetasol propionate; although the difference between these effects was not significant, the difference between the effect of hydrocortisone and clobetasol propionate was. Anthralin inflammation was not significantly affected by pretreatment with anthralin and was reduced, although not significantly by removal of the stratum corneum. The finding that anthralin inflammation is not altered in skin in which aryl hydrocarbon hydroxylase (AHH) activity is increased and that anthralin inflammation may be altered in situations in which AHH activity is unchanged, excludes a direct relationship between anthralin inflammation and AHH activity.

Administration, Topical↗
PubMed1985

A comparison of astemizole and chlorpheniramine in dermographic urticaria.

The effects of the H I receptor antagonists astemizole and chlorpheniramine on dermographism were compared in a double-blind study in sixteen patients. Both drugs resulted in a parallel and significant depression of the dermographic force-response curve and an elevation of the weal-force threshold, but the changes were greater in the patients receiving astemizole (a maximal potency shift of 74% for astemizole and 37% for chlorpheniramine). Subjective itch (10 cm line) and frequency of dermographic episodes were also reduced more by astemizole than by chlorpheniramine. The effect of astemizole was greater at 4 weeks than at 2 weeks, whereas the effect of chlorpheniramine had decreased at 4 weeks. The effect of astemizole but not chlorpheniramine was still apparent 4 weeks after treatment had been stopped. Since the degree of residual dermographism was comparable despite great differences in histamine weal inhibition a vasoactive mechanism in addition to that mediated by histamine must be involved in dermographic urticaria.

Adolescent↗
PubMed1985

Etretinate in pustular psoriasis of palms and soles.

In a double-blind controlled study of patients with pustular psoriasis of palms and soles who were allocated at random to etretinate or placebo, we found that etretinate improved the condition as assessed by pustule count and overall clinical response. Side-effects occurred but were accepted by the patients in the short-term. The clinical usefulness of etretinate in this condition will depend on time to relapse, and whether this can be prevented or postponed by continuous treatment. Toxicity in the long-term will also be important.

Adult↗
PubMed1985

Distribution and sub-cellular localization of drug metabolizing enzymes in the skin.

The distribution and sub-cellular localization of cytochrome P-450-dependent mono-oxygenase activity in the skin of adult hairless mice has been investigated using ethoxycoumarin, ethoxyresorufin and benzpyrene as substrates. Highest levels of mono-oxygenase activity per unit area of skin were found in the dermis, both before and after induction with benzanthracene. Subcellularly, mono-oxygenase activity was predominantly microsomal and, prior to induction, located entirely in the smooth microsomal fraction.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1985

Antipyrine clearance and alpha 1-acid glycoprotein levels after isotretinoin.

Eight male subjects aged 18-24 years were treated with 0.5 mg of isotretinoin day-1 kg-1. After 4 weeks levels of cholesterol (P less than 0.05) and triglyceride (P less than 0.05) were increased and levels of high-density lipoprotein (HDL)-cholesterol were decreased (P less than 0.05). Concentrations of aspartate aminotransferase (P less than 0.01) and gamma-glutamyltranspeptidase (P less than 0.01) were higher after treatment; increased alkaline phosphatase and a reduction in bilirubin levels did not reach statistical significance. Values for thyroxine were reduced after isotretinoin and free thyroxine index was lower (P less than 0.01). Measurements of salivary clearance of antipyrine and levels of alpha 1-acid glycoprotein were lower after treatment but these differences did not reach statistical significance. The findings suggest that there is a small decrease in hepatic microsomal-enzyme activity after isotretinoin and that the unwanted effects on lipids, liver and thyroid function are unlikely to be due to hepatic microsomal-enzyme induction.

Acne Vulgaris↗
PubMed1985

Minimal effect of complete H1 receptor blockade on urticaria pigmentosa.

The effect of complete H1 receptor blockade on urticaria pigmentosa was studied in 6 patients. Astemizole 10 mg tds was given for 6 weeks to achieve complete H1 receptor blockade and the response measured by change in force-weal response measurements using two different forces on a dermographic stylus and measuring response as weal diameter. Weal and flare reactions to 8 micrograms histamine were completely abolished by the astemizole but dermographic weal-force responses were reduced only by 12-15% indicating that histamine acting at the H1 receptor plays only a small part in the wealing of urticaria pigmentosa.

Adult↗