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Biomedical subjects

H Maibach

Publications and source records attributed to H Maibach.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1992

Effect of occlusive dressings on the stratum corneum water holding capacity.

Occlusion of the skin is used in clinical dermatology to promote wound healing and to increase the transcutaneous penetration of topically applied drugs. These effects are related to the degree of occlusion exerted and depend on the physicochemical nature of the dressing. We have evaluated the effects of four different materials on the skin barrier and the stratum corneum water holding capacity (WHC) using the Plastic Occlusion Stress Test (POST). The following materials were compared: hydrocolloid dressing, polyurethane film, polyethylene film, and a plastic chamber. These devices were applied on the volar forearm for 24 hours in 10 healthy volunteers (mean age 32 +/- 4 years). Upon their removal, the stratum corneum WHC, measured as skin surface water loss (SSWL), was recorded continuously for 25 minutes using an Evaporimeter. SSWL decay curves showed significant differences between the occlusive materials (analysis of variance, p less than 0.01). Higher SSWL values were recorded in sites occluded with the plastic chamber, whereas the polyurethane film resulted in poor occlusive capacity. Hydrocolloid dressing and polyethylene gave similar responses with higher WHC values compared to polyurethane (p less than 0.05). The relevance of these findings to clinical dermatology in terms of wound healing and drug absorption is discussed.

Adult↗
PubMed1992

Ultraviolet B dose-dependent inflammation in humans: a reflectance spectroscopic and laser Doppler flowmetric study using topical pharmacologic antagonists on irradiated skin.

Normal skin responds acutely to ultraviolet (UV) light exposure with complex inflammatory mechanisms. In the present study UVB irradiation ranging from subclinical erythema doses to twice the minimal erythema dose (24 mJ/cm2 to 96 mJ/cm2) was delivered to the skin of 8 volunteers. Pre-irradiated sites were immediately afterwards exposed to a 24-h occlusive patch containing 1 of 4 anti-inflammatory agents or vehicle control. The resultant change in erythema (vascular reaction) was measured objectively using laser Doppler flowmetry (LDF) and reflectance spectroscopy (RS). The 4 anti-inflammatory compounds reduced the UVB-induced vascular reactions in different and dose-dependent ways. Betamethasone-17-valerate and diphenhydramine were most effective at the 24 mJ/cm2 dose site and indomethacin and acetylsalicylic acid were more effective at sites > or = 48 mJ/cm2. Ranking the reduction in oxygenized hemoglobin (OH) content was as follows: betamethasone-17-valerate (OH reduction = 37.4%) > indomethacin (OH reduction = 21.5%) > acetylsalicylic acid (ASA) (OH decrease = 21.0%) > diphenhydramine (OH reduction = 18.4%). Using LDF, the total ranking of the cutaneous blood flow (BF) reduction was: indomethacin (BF reduction = 39.7%) > betamethasone-17-valerate (BF reduction = 32.7%) > acetylsalicylic acid (BF decrease = 17.5%) > diphenhydramine (BF reduction = 12.3%). Diphenhydramine significantly reduced erythema only at the lowest irradiation dose (24 mJ/cm2) and the decrease in OH was associated with an increased amount of deoxygenized hemoglobin (DOH). A similar slight venous dilatation was present at acetylsalicylic acid-exposed sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1991

Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy.

Skin absorption of benzoyl peroxide from a topical lotion containing freely dispersed drug was compared with that from the same lotion in which the drug was entrapped in a controlled-release styrene-divinylbenzene polymer system. In an in vitro diffusion system, statistically significant (p = 0.01) differences were found in the content of benzoyl peroxide in excised human skin and in percutaneous absorption. In vivo, significantly (p = 0.002) less benzoyl peroxide was absorbed through rhesus monkey skin from the polymeric system. This controlled release of benzoyl peroxide to skin can alter the dose relation that exists between efficacy and skin irritation. Corresponding studies showed reduced skin irritation in cumulative irritancy studies in rabbits and human beings, whereas in vivo human antimicrobial efficacy studies showed that application of the formulations containing entrapped benzoyl peroxide significantly reduced counts of Propionibacterium acnes (p less than 0.001) and aerobic bacteria (p less than 0.001) and the free fatty acid/triglyceride ratio in skin lipids. These findings support the hypothesis that, at least for this drug, controlled topical delivery can enhance safety without sacrificing efficacy.

Administration, Cutaneous↗