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Biomedical subjects

H Maibach

Publications and source records attributed to H Maibach.

At least 19 recordsLinked to original sources
PubMed1997

Effect of percutaneous absorption of fluocinolone acetonide on the activity of superoxide dismutase and total antioxidant status in patients with psoriasis.

This study defines a modification of antioxidant systems by percutaneous absorption of fluocinolone acetonide. Total antioxidant status (TAS) provides an overall indication of antioxidant status. Superoxide dismutase (SOD), a primary antioxidant, accelerates the dismutation of the toxic superoxide radical produced during the oxidative energy processes into the less harmful molecules, hydrogen peroxide and molecular oxygen. We monitored the level of SOD and TAS in 7 males with psoriasis and 6 control subjects before and after a single application of fluocinolone acetonide 0.025% ointment to 90% of the body. The results showed that the plasma level of TAS was significantly increased (p < 0.02) at 24 h posttreatment. The erythrocytic level of SOD was significantly decreased (p < 0.01) only at 12 h after glucocorticosteroid application. The level of TAS and SOD in patients with psoriasis was also significantly increased (p < 0.01 for both situations) as compared to healthy controls. Our study suggests that fluocinolone acetonide as a therapeutic agent may play a role in the oxidative stress in skin diseases.

Administration, Cutaneous↗
PubMed1997

Basic demographic and professional characteristics of US women physicians.

Women physicians are a rapidly growing percentage of the physician population in the United States; yet, their fundamental characteristics and largely unknown. The Women Physicians' Health Study is the first large, national study of US women physicians, comprising a random sample (n = 4,501 respondents) of women physicians aged 30 to 70. Data from the Women Physicians' Health Study showed that African-American and Latina or Hispanic physicians were underrepresented, and Asian-American and foreign-born physicians were overrepresented in proportion to their prevalence in the US female population. Women physicians were more likely to be married and less likely to have never married and less likely to have never married or to be divorced or widowed than other US women. Younger physicians were more likely to be residency trained and board-certified and to work more hours per week than older physicians. Younger physicians were also less likely to be in solo practice, government work, or inactive; they tended to be concentrated in group or hospital-based practices. We found that although US women physicians have some common characteristics that differentiate them from other US women, their practice and other characteristics vary substantially by age and specialty in ways that have not previously been reported.

Adult↗
PubMed1996

The effect of saline iontophoresis on skin integrity in human volunteers. I. Methodology and reproducibility.

This study, conducted in 36 human volunteers, was an evaluation of the effects of saline iontophoresis on skin temperature, irritation, and barrier function. The major objectives were to assess the effects of low-level ionic currents, to validate the proposed methodology of assessment, and to establish reproducibility in repeated saline iontophoresis applications. This was the first of a multistage study designed to assess the safety of 24-hr saline iontophoresis episodes at selected currents and current densities. Since an iontophoresis patch challenges the skin barrier both by occluding the skin surface and by passing ionic current through the skin, the experimental protocol was designed to permit measurement of the contribution of each of these processes to the overall response. In this first stage we investigated the effect of 10 min of current delivery, at 0.1 mA/cm2 on a 1-cm2 area patch and 0.2 mA/cm2 on a 6.5-cm2 area patch compared to unpowered control patches. Twelve subjects were tested under each condition on two separate occasions to examine reproducibility of the response variable measurements. A further 12 subjects were tested once under the 0.2 mA/cm2, 6.5-cm2 condition. Skin irritation was evaluated via repeated measurements of transepidermal water loss, capacitance, skin temperature, skin color, and a visual scoring system, before the iontophoresis episode and after patch removal. No damage to skin barrier function in terms of skin-water loss or skin-water content was detected. Slight, subclinical, short-lasting erythema was observed for both conditions. Assessment of correlation coefficients showed highly statistically significant indications of reproducibility for all five response variables measured. The experimental design, in combination with a repeated measures analysis, provided clear separation of the occlusion and ionic current components of the iontophoretic patch challenge. Further, the repeated measures analysis gave a highly sensitive assessment of skin irritation and resolution after patch removal. We conclude that the experimental methodology is appropriate for assessing possible changes in skin integrity resulting from saline iontophoresis under similar operating conditions for longer durations and for other skin challenges from which a subclinical response is expected.

Body Temperature↗
PubMed1996

Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin.

The effect of menthol and alcohol as its vehicle on thermal sensations, pain, experimental itch and irritation were studied in 18 subjects, using a computerized thermal sensory analyzer, laser Doppler flowmetry and an evaporimeter for transepidermal water loss (TEWL). Menthol had a subjective cooling effect lasting up to 70 min in 12/18 subjects; however, it did not affect cold and heat threshold, nor did it affect cold and heat pain threshold. Alcohol produced an immediate cold sensation lasting up to 5 min in 4/18 subjects and lowered the sensitivity of cold sensation threshold (P < 0.05). Histamine injection did not change thermal and pain thresholds. Menthol did not alleviate histamine-induced itch magnitude, nor its duration. Following histamine injection, cold sensation median threshold decreased by 1.2 degrees C from (29.9 degrees C to 28.7 degrees C) on the site treated with menthol (P < 0.01) with similar changes in thresholds at the alcohol-treated site (P < 0.05). Warm sensation and pain threshold in subjects receiving histamine injections, measured after menthol and alcohol application, did not differ from their baseline values with histamine alone. TEWL at the site treated with menthol was significantly higher (P < 0.05) than at the alcohol-treated and the control site (P < 0.01), suggesting that menthol has a higher skin irritating effect, or at least alters the stratum corneum water permeability. Our results suggest that menthol fulfills the definition of a counterirritant, but does not affect histamine-induced itch, nor does it affect pain sensation.

Administration, Topical↗
PubMed1996

Racial differences in skin pathophysiology.

Racial differences in skin function occur and may be responsible for differences in skin reactivity in physiologic and pathologic conditions. This article reviews the main racial anatomic and physiologic differences as well as mechanisms of irritation, sensitization, and drug absorption reported in the recent literature. Racial differences in transcutaneous penetration of chemicals and drug absorption have been described. Decreased transcutaneous penetration has been reported in black persons. In contrast, conflicting findings have been reported concerning some aspects of irritation and sensitization. Decreased erythematous reactions have been found in pigmented skin, whereas white persons have a stronger resistance to water barrier damage. Regional variation in skin function is more evident in fair skin because of the modifying effects of long-term UV exposure.

Asian People↗
PubMed1996

Epidermal enzymes as penetration enhancers in transdermal drug delivery?

Epidermal enzymes play an important role in the process of differentiation of keratinocytes. The present preliminary in vitro study was undertaken to observe if topical enzyme treatment influenced permeation of compounds across the skin. Due to the noted function and importance of phosphatidylcholine metabolism during maturation of the barrier lipids, the effects of topical application of the phosphatidylcholine dependent phospholipase C enzyme (not present in epidermis) on skin penetration of three model drugs, viz. benzoic acid, mannitol and testosterone, were studied. Similar studies were also carried out using epidermal enzymes like triacylglycerol hydrolase, acid phosphatase, and phospholipase A2 (present in epidermis). Pretreatment of skin with phospholipase C significantly enhanced permeation of benzoic acid, mannitol, and testosterone relative to untreated skin. Triacylglycerol hydrolase (neutral) increased the penetration of mannitol 3-fold and had no effect on benzoic acid penetration. Topical application of acid phosphatase did not alter the permeation of any of these compounds. Phospholipase A2 significantly enhanced permeation of benzoic acid and mannitol while it did not have any effect on the penetration of testosterone. These results for the first time demonstrate that enzymes may remarkably affect and/or regulate the permeation of topically applied compounds.

Drug Delivery Systems↗
PubMed1995

Quantification of sodium lauryl sulfate penetration into the skin and underlying tissue after topical application--pharmacological and toxicological implications.

Sodium lauryl sulfate (SLS) is known to penetrate skin and cause cutaneous irritation. Some of these effects have been well-defined using bioengineering techniques. In this study, the ability of SLS to penetrate skin was quantified in a hairless rat model. In addition, local deep tissue penetration and systemic exposure to SLS were also evaluated to assess the toxic potential of topically applied SLS. SLS was observed to penetrate directly to a depth of about 5-6 mm below the applied site. Systemic redistribution was predominantly responsible in determining concentrations of SLS in tissues deeper than 5-6 mm. Epidermal concentrations of SLS after application of 1% (34 mM) aqueous SLS solution for 24 h were above the threshold levels which are known to evoke typical skin irritation responses. Deeper underlying tissues including dermis, subcutaneous, and muscle may also be exposed to high levels of SLS. Topically applied SLS was also observed in blood and contralateral tissues but the observed levels were not likely to elicit any systemic side effects at these doses. Traces of SLS were observed in tissues 7 days after single 24 h application of SLS, which supports the prolonged barrier disruption data generated using conventional bioengineering techniques. Cumulative treatment of SLS significantly increased the concentration of this compound in the underlying epidermis. The known preferential affinity of SLS for skin lipids and proteins was further confirmed by both in vitro and in vivo results. However, in vitro studies failed to predict the underlying tissue toxicity of SLS under the patch site when compared to the in vivo results. Such quantitative pharmacokinetic-pharmacodynamic correlations may be useful predictors for effective use of surfactants as penetration enhancers in cosmetic, pharmaceutical, and industrial applications.

Administration, Topical↗
PubMed1995

Radial spread of sodium lauryl sulfate after topical application.

PURPOSE: Since topical application of sodium lauryl sulfate (SLS) has been reported to elevate transepidermal water loss and decrease skin capacitance in areas immediately adjacent to the applied site, studies were carried out to quantify the extent of radial spread of SLS below a topically exposed site in a hairless rat model. METHODS: Fixed sites were demarcated and the levels of SLS measured around the applied site in the epidermis, dermis and the subcutaneous tissues. Underlying deep tissue penetration and radial spread of SLS in the presence and absence of a vasoconstrictor, phenylephrine, was also quantified. RESULTS: In a typical 24 hour study, the radial spread of SLS was observed to a distance of approximately 0.75 cm from the applied site. The use of phenylephrine (1:20000), did not significantly enhance either the local underlying tissue (apart from underlying epidermis) concentration or radial spread of SLS relative to no vasoconstrictor treatment. CONCLUSIONS: Given that SLS impairs barrier function of the skin, its radial spread could be explained by a passive diffusion process. Vasoconstrictor did not remarkably alter SLS penetration and radial spread possibly due to the competing effects of vasodilation (caused by SLS) and vasoconstriction (caused by phenylephrine).

Administration, Topical↗
PubMed1995

A time correlation study between reflectance spectroscopic cutaneous vasoconstriction and plasma corticosteroid concentration.

Although cutaneous vasoconstriction assays are used as a primary screen for ranking the in vivo efficacy of new corticosteroids and in vivo human drug delivery studies, little is known about the relationship between the blanching reaction and corticosteroid tissue or plasma concentrations. We measured cutaneous vascular reactions in five volunteers, using an improved reflectance spectroscopic method, and a sensitive radioimmunoassay technique was employed to measure plasma betamethasone concentrations. Using a specially developed betamethasone-17-valerate patch prepared in BIO-PSA, constant corticosteroid release was ensured, and correlations between cutaneous blanching and plasma corticosteroid concentrations were calculated. Maximal skin blanching was documented 12 h post-application, whereas plasma corticosteroid concentrations peaked later, at 32 h post-application, when a paradoxical telangiectatic vasodilatation occurred. At 72 h post-application, when the plasma corticosteroid concentration was still above the 12 h level, this paradoxical vasodilatation was maximal. The corticosteroid-induced vascular reactions were mainly due to arterial haemoglobin (Oxy Haem), and both vasoconstriction and vasodilatation were related to changes in Oxy Haem. Our results suggest a dual, probably both time and concentration related, interaction between corticosteroids and dermal vessels in which lower concentrations at 6-12 h exposure caused vasoconstriction, but as the exposure time increased (> or = 24 h) paradoxical vasodilatation was induced, although plasma corticosteroid concentrations were still rising.

Adult↗
PubMed1994

Contact urticaria and its mechanisms.

This paper reviews the syndrome of contact urticaria in terms of current knowledge regarding pathophysiological mechanisms. The three mechanistic categories into which contact urticants are grouped include: (1) immunological contact urticaria, (2) non-immunological contact urticaria and (3) uncertain-mechanism-mediated contact urticaria. Within this schema, the clinical manifestations, diagnosis and therapy of contact urticaria are presented.

Adult↗
PubMed1993

Influence of skin irritants on percutaneous absorption.

The effects of the application of skin irritants on the in vitro percutaneous absorption of three model compounds of diverse physico-chemical properties, caffeine, indomethacin, and hydrocortisone, were investigated. Norephedrine and imipramine, basic drugs with a known skin irritation potential, were employed to damage the skin. Treatment with norephedrine increased the permeation of caffeine and hydrocortisone by two- to fourfold, while absorption of indomethacin declined an order of magnitude. A similar result was obtained for the effect of treatment with imipramine on transport of caffeine. Pretreatment with imipramine promoted hydrocortisone absorption 10-fold but, unlike norephedrine, did not alter indomethacin permeation. While both treatments in vivo caused an increase (norephedrine > imipramine) in the pH on the surface of skin and after tape-stripping the skin, only norephedrine caused changes in transepidermal water loss in vivo in man. Since imipramine was the more severe irritant as judged by erythema, alterations by irritants of barrier function appeared rather complex.

Adult↗
PubMed1993

Effect of organic solvents on in vitro human skin water barrier function.

Skin barrier disruption caused by organic solvents to human cadaver dermatomed skin was evaluated using an in vitro model system. Resultant changes in transepidermal water loss (TEWL), as measured with an evaporimeter, were recorded after topical application of either acetone, chloroform:methanol 2:1, hexane, hexane:methanol 2:3, or the control, water, for exposure times of 1, 3, 6, and 12 min. The resultant lipid/solvent mixture was removed and analyzed for its lipid content. The ability of the different solvents to induce changes in the skin's barrier function was assessed by comparing pre- to post-solvent exposure TEWL (delta TEWL). When compared to the controls, water and unexposed skin, chloroform:methanol 2:1 caused the greatest significant increase in TEWL, followed by hexane:methanol 2:3. Acetone and hexane showed no difference in TEWL from the controls. Besides solvent, exposure time was a significant independent variable for predicting delta TEWL, and the interaction of the two (exposure time and solvent type together) was the strongest predictor. Lipid analysis of the extracts revealed that all the solvents removed comparable quantities of the surface lipids (triglycerides, wax esters, squalene, cholesterol esters). Stratum lipids--ceramides, free fatty acids, and cholesterol--extracted by chloroform:methanol 2:1 and hexane:methanol 2:3 were comparable and significantly greater than those extracted by acetone and hexane. These two solvents failed, however, to induce comparable changes in TEWL, as chloroform:methanol 2:1 induced a significantly greater delta TEWL than hexane:methanol 2:3. Additionally, no individual lipid class extracted by either chloroform:methanol 2:1 or hexane:methanol 2:3 proved to be a significant or accurate variable for predicting delta TEWL. This suggests that the mechanism by which topical chloroform:methanol 2:1 and hexane:methanol 2:3 exposure induce a delta TEWL involves more than pure lipid extraction.

Adolescent↗
PubMed1993

The cutaneous corticosteroid vasoconstriction assay: a reflectance spectroscopic and laser-Doppler flowmetric study.

Cutaneous vasoconstriction induced by topical corticosteroids was investigated using non-invasive bioengineering techniques. Corticosteroids of different potency in alcoholic solution were applied topically, under occlusion, and cutaneous blanching was investigated using visual scoring, reflectance spectroscopy (RS) and laser-Doppler flowmetry (LDF). The RS technique allowed separation of cutaneous haemoglobin content into arterial oxygenated (OH) and venous deoxygenated haemoglobin (DOH) components. Application of alcohol decreased total haemoglobin by 10%, with a corresponding 8% increase in blood flow (BF). Clobetasol propionate was the most potent vasoconstrictor, inducing significant visible blanching and decreasing DOH (30%), OH (33%) and BF (18%) (P < 0.01). Fluocinolone acetonide, betamethasone-17-valerate and dexamethasone also caused visible blanching (P < 0.01). There was no significant decrease in BF, but reflectance spectroscopy showed a decrease in DOH (P < 0.01). Tixocortol, CMJ and hydrocortisone acetate did not produce significant blanching, although DOH was decreased compared with the alcohol control. Measured by reflectance spectroscopy, corticosteroid-induced blanching was predominantly venoconstriction and only the most potent corticosteroid caused a significant decrease in OH and blood flow. This may explain why previous attempts to improve cutaneous vasoconstriction assays using laser-Doppler flowmetry have been unsuccessful.

Adrenal Cortex Hormones↗
PubMed1993

A corticosteroid, a non-steroidal anti-inflammatory drug and an antihistamine modulate in vivo vascular reactions before and during post-occlusive hyperaemia.

Post-occlusive reactive hyperaemia is the temporary increase of blood flow in a tissue following transient vascular obstruction, and has recently been proposed as an in vivo method for ranking topical corticosteroid potency. We investigated in vivo vascular reactions before and during post-occlusive hyperaemia using laser-Doppler flowmetry and reflectance spectroscopy (RS). RS enables resolution of in vivo erythema into deoxygenated (venous) [DOH] and oxygenated (arterial) haemoglobin (OH) components (expressed in arbitrary units, AU). Using a randomized 24-h occlusive exposure in 10 healthy volunteers the effects of a corticosteroid (betamethasone-17-valerate), a non-steroidal anti-inflammatory drug (NSAID) [indomethacin], an antihistamine (diphenhydramine), or vehicle, were studied before and during post-occlusive hyperaemia. The 24-h vehicle exposure decreased total haemoglobin (composed of a small increase in OH [P < 0.001] and a greater decrease in DOH [P < 0.005], [OH, 0.23 +/- 0.18 AU; DOH, 0.28 +/- 0.12 AU]). The blood flow increased 7.1% to 28 +/- 8 AU (P > 0.05). Betamethasone-17-valerate exposure decreased total haemoglobin further (OH, 0.10 +/- 0.09 AU [P < 0.005]; DOH, 0.18 +/- 0.08 AU [P < 0.05]), which corresponded to a 15% blood flow decrease (P < 0.05). Indomethacin reduced OH to 0.18 +/- 0.12 AU (P < 0.02) and increased DOH slightly, with a trend towards decreased blood flow (P > 0.05). Diphenhydramine caused no significant changes in RS or laser-Doppler flowmetry readings before post-occlusive hyperaemia. Post-occlusive hyperaemia increased total haemoglobin maximally at the first observation time (OH, 0.63 +/- 0.13 AU; DOH, 0.31 +/- 0.11 AU [P < 0.001]).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Plastic occlusion stress test as a model to investigate the effects of skin delipidization on the stratum corneum water holding capacity in vivo.

The purpose of the study was to develop an in vivo model to study the effects of lipid removal on skin barrier. 16 subjects (age 41 +/- 8) were delipidized in vivo on the volar forearm using respectively ether/acetone (EA; 1:1) and chloroform/methanol (CM; 2:1). A third site served as control. Water holding capacity (WHC) was measured according to the plastic occlusion stress test (POST) procedure: the water desorption curve after removal of the occlusion was recorded in terms of skin surface water loss (SSWL) using an evaporimeter for 30 min. In the central part of the evaporation curve (bound water) the CM-treated site is significantly different from control and EA-treated sites (p < 0.01). The SSWL decay constants reflecting the desorption rate of water from SC are higher in the CM-treated site (p < 0.01). The data are consistent with the effect of CM delipidization (polar lipids) on bound water. No differences are recorded in the evaporation of free water. We conclude that polar lipids have a key role in modulating barrier function and WHC of the stratum corneum. The POST can represent a useful in vivo model to study the effects of lipid extraction on skin function.

Administration, Cutaneous↗
PubMed1993

Transcutaneous CO2 and O2 diffusion.

Transcutaneous gas measurements offer a useful tool for non-invasive monitoring of skin function, but are affected by several variables that restrict their use in clinical and investigative dermatology. Skin thickness, stratum corneum and barrier function damage, blood vessel reactivity, arterial-gas concentration, skin and environmental temperature are important factors influencing transcutaneous gas flux. Improvement of techniques and standardization of methods with guidelines for operators should improve this interesting research approach.

Blood Gas Monitoring, Transcutaneous↗