Ethel Tur

Are there age and racial differences to methyl nicotinate—induced vasodilatation in human skin?

Preliminary experiments have been performed to determine whether there are age and racial differences in the response of human skin to the topically applied vasodilator methyl nicotinate. With the use of a constant stimulus (a 15-second exposure to a 100 mM aqueous solution of drug), the subsequent time-course of the vasodilatation response was followed noninvasively and objectively with the optical technics of laser Doppler velocimetry (LDV) and photoplethysmography (PPG). Three groups of subjects were considered: young white subjects (20 to 30 years of age), elderly white subjects (63 to 80 years old), and young black subjects (20 to 30 years old). Analysis of the results shows that the time to peak response, the area under the response-time curve, and the time for the response to decay to 75% of its maximum value are statistically indistinguishable for all three groups at the p = 0.05 level of significance. Only the magnitude of the peak response revealed some significant differences between the cohorts (young greater than black, determined by PPG; young greater than old, determined by LDV). The data suggest, therefore, a remarkable similarity in response across a wide range of skin types. The origin of this consistency may, however, be complex and is not revealed by these experiments.

Percutaneous penetration of methyl nicotinate at three anatomic sites: evidence for an appendageal contribution to transport?

Percutaneous absorption of the vasodilator methyl nicotinate (MN) was evaluated in human volunteers at three anatomic sites (forehead, forearm and palm) using the technique of laser Doppler flowmetry (LDF). The experiments were designed to test the hypothesis that the kinetics and extent of skin penetration are dependent upon the appendageal density at the site of application. The LDF technique measured the increase in skin blood flow elicited by topically applied MN once the chemical had penetrated to the microvasculature. Significant differences in the measured LDF responses at the three sites were found, and further analysis of the data suggested that MN penetration was greatest through forehead skin, least through the palm and intermediate across the skin of the forearm. A correlation therefore existed between apparent MN absorption and appendageal density.

Dorfman-Chanarin syndrome: A case report and a review

Dorfman-Chanarin syndrome in two sisters of Jewish Iraqi origin is reported. This heritable disorder of the metabolism of neutral lipids was manifested by congenital ichthyosis, vacuoles in the leukocytes, and variable involvement of liver, muscle, central nervous system, and the auditory system. In two asymptomatic members of the family leukocyte vacuoles were found as the only sign of the syndrome. Clinical, pathologic, ultrastructural, and biochemical findings are described. Previous reported cases are reviewed.

Cutaneous responses to topical methyl nicotinate in black, oriental, and caucasian subjects

SummaryThe response of human skin to topical methyl nicotinate (MN) has been monitored in black, oriental, and caucasian subjects. The study aimed to address the question: “Do racial differences in percutaneous absorption and microcirculatory sensitivity exist?” MN-induced vasodilation was assessed visually and by laser Doppler velocimetry (LDV). At three dose levels, in the three subject populations, four parameters were compared: (a) the diameter of the maximum visually perceptible erythematous area (Emx); (b) the area under the erythematous diameter versus time curve (AUE); (c) the maximum LDV response (Lmx); and (d) the area under the LDV response versus time curve (AUL). At p<0.05, AUL (black)>AUL (caucasian) for all MN concentrations; AUL (oriental)>AUL (caucasian) for the higher dose levels. Emx, AUE and Lmx showed no significant differences between races within concentrations. For all subjects, Emx AUE, and AUL were significantly dependent on MN dose whereas Lmx was not. The results suggest that some racial differences in response to topical MN exist and that perception of these distinctions may depend upon the method of measurement.

Pharmacodynamic measurements of methyl nicotinate percutaneous absorption.

The local kinetics of percutaneous absorption provide information of relevance to the treatment of skin diseases and to the potential efficacy of transdermally delivered chemotherapy for systemic effect. This paper describes two non-invasive procedures (laser Doppler velocimetry and photopulse plethysmography) which permit pharmacodynamic measurements of methyl nicotinate skin penetration to be made in vivo in man. The methods are sensitive to the local vasodilative action elicited by the nicotinic acid ester. Dose-response behavior as a function of time has been monitored (1) over the concentration range 5–100 mM, and (2) by variation of drug application time and administration area. At the higher concentrations used, the magnitude of the erythemal response is saturable, and the effect is then progressively prolonged by further increasing the applied dose. Analysis of the data permits assessment of (a) the kinetics of drug delivery to and depletion from the site of action, and (b) the hypothetical level of steady state drug input necessary to sustain 50 % of the maximum detected response. Measurements of the type described here may prove useful, therefore, for elucidating otherwise inaccessible aspects of transcutaneous kinetics in vivo.

Blood flow in psoriatic skin lesions: the effect of treatment.

Laser Doppler velocimetry (LDV) was used to assess the effect of treatment upon cutaneous blood flow in psoriatic skin lesions. The resolution of two separate plaques in each of seven subjects was followed. Six of the subjects received the Goeckerman regimen, the seventh was reated with psoralen‐ultraviolet A (PUVA) therapy. Control LDV readings were taken from uninvolved skin sites during the treatment period. Cutaneous blood flow in the psoriatic lesions of the Goeckerman‐treated patients decreased to levels comparable to those in uninvolved skin early in the course of treatment and significantly preceeded the observed clinical resolution from 4 to 8 days after initiation of therapy (P < 0.05). Visible flare‐ups sometimes appeared when patients were untreated (over a weekend, for example) and these eruptions were accompanied by a transient elevation of LDV readings. Perfusion of the lesions of the PUVA‐treated patient remained consistently higher than perfusion of uninvolved skin despite clinical healing. In a separate series of experiments, blood flow at the extensor surface of the forearm was measured in the skin of normal subjects, the uninvolved skin of psoriatic patients and the untreated lesional skin of psoriatic patients. While the lesional skin had significantly higher perfusion levels than uninvolved psoriatic or normal control skin (P < 0.01), there was no significant difference between blood flow to the uninvolved psoriatic skin of psoriatics and that to the skin of healthy controls.

Spatial variability of vasodilatation in human forearm skin

Vasodilatation elicited by topical application of methyl nicotinate was measured by photoplethysmography at various positions on human ventral forearm skin. The time‐to‐peak response, the magnitude of the peak response, the area under the response‐time curve and the time for the response to decay to 75% of the maximum value, were recorded at six positions on the left and right forearms of eight subjects. There was no significant difference between response on the right and left forearm sites and no difference in response between the lateral and medial sites on the forearms. In a second experiment, the vasodilatation was measured at proximal and distal positions on the forearm. The magnitude of the peak response at the proximal position was significantly higher than that found distally (P<0.01) as was the area under the response‐time curve (P<0.05). These results suggest a possible cause for the variation observed in vasoconstrictor assays of corticosteroids.

Early treatment of pemphigus does not improve the prognosis A review of 53 patients

Background With the introduction of systemic steroids to control pemphigus vulgaris the prognosis and survival of these patients has changed dramatically. However, in contrast to their beneficial effects, in a once almost inevitably fatal disease, the steroid therapy has created other problems, including cases of mortality.

Regional Variations of Human Skin Blood Flow Response to Histamine

The aim ofthe present study was to assess age-related regional variations in skin function, by measuring the cutaneous microvascular response to histamine. Histamine was topically applied to the back and forearm of young and aged volunteers, and the response was quantified utilizing laser Doppler flowmetry. Each group comprised of 14 volunteers. The cutaneous vascular response to histamine was significantly greater on the back than on the forearm ofyoung healthy volunteers, whereas in aged ones the response over these two sites did not significantly differ. These observations indicate anatomical or functional differences between old and young skin as relates to regional variations. They may underlie some ofthe differences in the manifestations ofdisease processes in various age groups.

Regional variations of skin blood flow response to histamine: evaluation by spectrophotometry and laser Doppler flowmetry

To study inherent differences in skin function related to regional variation, we tested the hypothesis that different reactivities of small blood vessels via their direct and indirect activation by histamine play an important role in the observed regional variation of processes. Histamine was administered to three cutaneous regions in 20 volunteers, and the induced response was quantified utilizing spectrophotometry and laser Doppler flowmetry. The back exhibited the greatest response, followed by the forearm and ankle in decreasing order of responsiveness. We suggest that the intensity of the wheal and flare response may partly be related to the local reactivity of the blood vessels once the histamine actually reached them, and to their indirect dilatation via the axonal reflex. These blood vessel response observations may provide initial insight into inherent functional differences influencing cutaneous manifestations of endogenous and exogenous diseases.