The mechanism of ultraviolet erythema.
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Biomedical subjects
Publications and source records attributed to S Shuster.
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An attempt has been made to purify factors present in aqueous extracts of pig epidermis which inhibit epidermal cell proliferation. A lipophilic factor of low molecular weight (less than 10,000), has been shown to inhibit DNA synthesis as measured by the uptake of tritiated thymidine in mouse ear epidermis. Purification by alcohol precipitation, ethyl acetate extraction and silicic acid column chromatography produced a fifteen-fold increase in the specific activity of the inhibitory action. It seems likely that aggregation or absorption of this low molecular weight factor may explain the high molecular weight of epidermal cell proliferation inhibitors previously studied, as well as the difficulty in their characterization.
1 The primary effect of catecholamines was to lighten Anolis skin previously darkened by alpha-melanocyte-stimulating hormone (alpha-MSH). In concentrations above 10(-7) M noradrenaline, 10(-6) M adrenaline and 10(-5) dopamine, darkening of subpopulations of melanophores occurred. Subsequent experiments were concerned with the effect of low catecholamine concentrations on alpha-MSH action. 2 The relationship between MSH receptors and alpha-adrenoceptors on the Anolis melanophore was studied by a kinetic approach using the rate bioassay method and by use of alpha-adrenoceptor agonists and antagonists. 3 alpha-MSH dose-response curves were shifted, in parallel, to the right in the presence of the catecholamines, noradrenaline, adrenaline and dopamine, and Lineweaver-Burke plots and Arunlakshana-Schild plots indicated that the catecholamines antagonized MSH action by a competitive mechanism. 4 Phentolamine had an inhibitory effect on the action of adrenaline but not on the action of MSH. Therefore MSH and catecholamine actions were mediated by separate receptors. 5 The classical kinetics of competition are not confined to competition at a single receptor. 6 The alpha-adrenoceptor was defined as the alpha 2-subtype since (a) the alpha 2-selective agonist, clonidine, was found to mimic catecholamine action. (b) The alpha 2-selective antagonist, yohimbine, blocked the actions of clonidine and adrenaline. (c) The alpha 1-selective antagonist, prazosin, had negligible blocking effects on adrenaline and clonidine. 7 We conclude that a close association exists between the separate MSH receptor and alpha 2-adrenoceptor on the Anolis melanophore. The competition that takes place between MSH and catecholamines must occur after hormone-receptor interaction, possibly through a common adenylate cyclase moiety oppositely controlled by the two receptors involved.
The metabolism of testosterone and 5 alpha-dihydrotestosterone has been studied in vitro in preputial glands of posterior hypophysectomized, totally hypophysectomized and control sham-operated rats. The level of C19 steroid 5 alpha-reductase activity/unit of preputial gland DNA did not fall after removal of the neurointermediate lobe and rose after total hypophysectomy. It was concluded from this that the androgen unresponsiveness of the preputial glands of hypophysectomized rats was not due to a near-total lack of 5 alpha-reductase and hence that the combined synergistic action of testosterone and alpha-melanocyte-stimulating hormone (alpha-MSH) on preputial gland activity was unlikely to be due to an alpha-MSH-mediated restoration of 5 alpha-reductase levels in hypophysectomized rats. Levels of 3 alpha and 3 beta-hydroxysteroid dehydrogenase but not of 17 beta-hydroxysteroid dehydrogenase appeared to be altered by hypophysectomy.
A new wax formulation of anthralin was compared with anthralin as used in the Ingram regimen for the treatment of chronic discoid psoriasis. In 16 out-patients 12 of the 13 who responded to the Ingram regimen also showed a satisfactory response to the wax preparation. The latter could be applied more rapidly and simply and may thus have a useful place in the domestic management of chronic psoriasis.
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The relapse rate of plaque psoriasis after initial clearing with the "Ingram" dithranol regimen or photochemotherapy was comparable when no maintenance treatment was given. It was estimated that psoriasis recurs to half of its pretreatment extent after about six months in half the patients. Maintenance treatment with photochemotherapy once a week or once every three weeks was useful in reducing the relapse rate. This study failed to show any statistical difference in relapse rates between these two maintenance schedules. If this finding turns out to be true over longer periods of study the maintenance schedule entailing treatment once every three weeks with its lower cumulative dose of long-wave ultraviolet light will clearly be preferable. The psoriasis in most patients was under better overall control with maintenance treatment than with intermittant clearing courses given when the extent of the psoriasis had become unacceptable to them. There was, however, a group of roughly one-fifth of patients who remained in satisfactory remission for over 16 months after initial clearing. Regular maintenance treatment was unnecessary in them. Much more information is needed on response to treatment in subgroups of patients to permit recognition from the start of which patients are likely to have long remission and which are not.
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Melanotrophin-potentiating factor (MPF) is a fragment of human beta-lipotrophin (LPH 88-91) which potentiates the action of alpha-MSH on Anolis skin. In the present study, we investigated the effect of MPF on MSH-induced melanogenesis. Pooled hair follicle scrapings from Siberian hamsters (Phodopus sungorus) were incubated for 48 hours with or without alpha-MSH and/or MPF. Melanogenesis was monitored by measuring tyrosinase activity and melanin accumulation. 10-8 M MPF potentiated the effect of no effect on melanogenesis, but 10-9 to 10-7 M alpha-MSH caused a dose-related increase. 10-8 M MPF potentiated the effect of each dose of alpha-MSH. Thus MPF potentiated MSH action on mammalian melanogenesis as well as on reptilian melanosome dispersion. Although each of these processes involve different intracellular responses the receptor mechanisms involved in each may therefore be the same.
Sexually experienced male rats were used to test the attractiveness of odors of hypophysectomized females the male rats showed a clear preference for 4 days failed to alter the attractiveness of odors of hypophysectomized females and male rats showed a clear preference for the odors of females that had received 10 micrograms EB. Daily administration of 50 micrograms alpha-MSH failed to increase the attractiveness of odors of hypophysectomized females the male rats showed a clear preference for the odors of females that had received 10 micrograms EB. Daily administration of 50 micrograms alpha-MSH failed to increase the attractiveness of odors from females that received 2 microgram EB but was effective in females that had received 10 micrograms EB. However, no effect was seen in female rats that had been preputialectomized. alpha-MSH also increased the attractiveness of odors of posterior hypophysectomized rats in proestrus. Moreover, the reduction in odor attractiveness found after posterior hypophysectomy in female rats in proestrus was almost restored by alpha-MSH treatment. On the other hand, when the alpha-MSH treated posterior hypophysectomized females were in diestrus their odors were less attractive to male rats than those of the untreated controls. A similar reduction in odor attractiveness occurred in alpha-MSH treated posterior hypophysectomized females in proestrus after a single injection of progesterone. These results suggest that in the female rat alpha-MSH has a physiological role in controlling sexual odors from the preputial glands and by interacting with estrogen and progesterone can either enhance or reduce the attractiveness of these odors to male rats.
1. To study the difference in sweat rate between men and women the rates of cholinergic-induced sweating were measured in normal people before and after puberty and in response to androgens and anti-androgens. 2. Sweat rate in men was more than double that in women. 3. This difference did not occur in prepubertal boys and girls in whom the rate, corrected for surface area, was comparable with that in women. 4. Application or injection of androgen locally did not stimulate sweat production in the adult female. 5. Anti-androgen topically or systemically did not decrease sweat rate in men. 6. It is concluded that the rate of sweat rate in men is caused by androgen-induced gene expression at puberty and not by androgen modulation in adult life.
17 alpha Propyltestosterone produced a mean inhibition of sebum excretion of 20% when it was applied topically for four weeks to the forehead skin of patients with acne.
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