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Biomedical subjects

Howard I Maibach

Publications and source records attributed to Howard I Maibach.

At least 19 recordsLinked to original sources
PubMed2006

Percutaneous penetration of methyl nicotinate from ointments using the laser Doppler technique: bioequivalence and enhancer effects.

Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increased cutaneous microcirculation induced by methyl nicotinate (MN). Bioequivalence of a test and a standard preparation (vehicles: light mineral oil and medium chain triglycerides, respectively) was confirmed according to the pilot study of the FDA Guidance for Industry "Topical dermatologic corticosteroids: In Vivo bioequivalence" applying the staggered application and synchronized removal method for one defined concentration. Furthermore, the influence of penetration enhancers (5% w/w Dimethylsulfoxide (DMSO) and 10% w/w diethylene glycol monoethyl ether) on MN penetration was investigated. It was shown that DMSO and diethylene glycol monoethyl ether altered cutaneous microcirculation and thus MN penetration in comparison to the standard formulation. However, true penetration enhancement could only be proved with diethylene glycol monoethyl ether resulting from an improved drug solubility in the skin which was confirmed by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR). Increased MN penetration by DMSO was only caused by thermodynamic effects, i.e. a decreased drug solubility in the vehicle.

Adolescent↗
PubMed2006

In vivo human transfer of topical bioactive drug between individuals: estradiol.

This study determined the in vivo human bioavailability of topical estradiol, and the transfer of drug between dosed subject and naive recipient. In vivo bioavailability was determined in human volunteers by (14)C urinary excretion following topical [(14)C]-estradiol (0.06%) dose administration and were adjusted by intravenous human excretion amounts to give absolute bioavailability amounts. Drug transfer was determined by volunteer skin contact/rubbing for 15 minutes, 1 hour after topical dosing. [(14)C]-estradiol bioavailability as percent dose absorbed (n=6) was 7.5+/-4.1 from protected dose site, 8.2+/-6.3 from non-protected dose site, 6.6+/-7.6 from dosed volunteers subjected to skin contact/rub and 4.3+/-3.8 from non-dosed volunteers subjected to skin contact/rub. Between these small groups, the values were not statistically different. Under experimental conditions, a measurable dose of radioactive 17beta-estradiol dose was delivered to naive recipient volunteers through skin contact/rub with other volunteers previously topically dosed. Any residual topical bioactive chemical which resides on the open skin surface can transfer by skin contact to another individual. It is important for prescribing physicians and patients to understand that clinically significant transfer of topical bioactive drugs can occur. This may be particularly important for substances which may produce inadvertent effects.

Administration, Topical↗
PubMed2006

Skin decontamination: Importance of the wash-in effect.

That skin washing/decontamination may increase percutaneous absorption is commonly referred to as the 'wash-in' (W-I) effect. This article traces the development of the W-I effect both in vivo and more recently in vitro. The mechanism(s) responsible for this effect are examined particularly in relation to the laboratory method used in vitro. The importance of the W-I effect is presented and it is recommended that caution be practiced when skin is washed as the W-I effect may increase both local cutaneous and general systemic toxicity. Experimental data on a wide variety of chemicals are urgently needed.

Animals↗
PubMed2006

Human stratum corneum penetration by copper: in vivo study after occlusive and semi-occlusive application of the metal as powder.

Aim of the study was to shed light on the long-standing controversy whether wearing copper bangles benefits patients suffering from inflammatory conditions such as arthritis. Sequential tape stripping was implemented on healthy volunteers to examine the diffusion of copper through human stratum corneum in vivo following application of the metal as powder on the volar forearm for periods of up to 72 h. Exposure sites were stripped 20 times and the strips analyzed for metal content by inductively coupled plasma-mass spectroscopy with a detection limit for copper of 0.5 ppb. Untreated skin was stripped in the same fashion, to determine baseline copper levels for comparison with exposure values resulting from exposure in respective volunteers. Under occlusion with exclusion of air, up to 72 h copper values decreased from the superficial to the deeper layers of the stratum corneum with gradients increasing commensurately with occlusion time, characteristic of passive diffusion processes. From the tenth strip on, however, levels reverted to background values. Under semi-occlusion allowing access of air by covering the skin with "breathable" tape, initial copper values lay significantly above baseline values and concentration gradients increased proportionally with occlusion time. At 72 h, from the tenth to the twentieth strip reaching the glistening epidermal layer, copper values continued at constant levels, significantly above baseline values. The results indicate that, in contact with skin, copper will oxidize and may penetrate the stratum corneum after forming an ion pair with skin exudates. The rate of reaction seems to depend on contact time and availability of oxygen. A marked inter-individual difference was observed in baseline values and amounts copper absorbed.

Adult↗
PubMed2006

Deep percutaneous penetration into muscles and joints.

The transdermal absorption of drugs and its subsequent deep tissue delivery is a complex process, with many factors influencing the penetration mechanisms. Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the treatment of joint and muscle diseases. However, the dangers associated with oral medications highlight the need for alternative methods of targeting and retaining drugs; one such means is through topical delivery. The drug's lipophilicity, permeability, and fraction unbound found in the viable skin are some physiochemical factors influencing the delivery mechanism after transdermal absorption. These and other variables play a role in determining whether the drug reaches the deep tissues via direct penetration or from systemic redistribution. Pharmacokinetic models have been developed to help elucidate the penetration routes and efficacy for various drugs. While there are still uncertainties regarding the deep tissue penetration kinetics, improvements to current research methodologies may bring about a greater understanding of percutaneous absorption into the deep muscle and joints.

Administration, Topical↗
PubMed2006

Textiles and human skin, microclimate, cutaneous reactions: an overview.

This article overviews research in the interdisciplinary area of textile/skin interaction and related cutaneous intolerance. Microclimate in the skin/clothing system and especially the skin responses relates to the moisture and heat transfer within this system and plays a critical role in skin irritation from textiles. A discussion is then given on skin irritation reactions to textiles, including intolerance caused by chemicals (dyes and finishes) and physical contact/friction. Finally, two skin injuries, blisters and pressure ulcers, which are caused by physical contact, pressure, and friction, are documented. Despite the prevalent problems caused by ill textile/skin interactions, minimal efforts have been devoted to this field. In addition, the in vivo experimental studies infrequently lead to a solid conclusion. The cause may lie in the dramatic variation of skin conditions among individuals as well as among different anatomic sites of the same person. Another reason might be the lack of communications between researchers in the areas of textiles and dermatology.

Blister↗
PubMed2006

Water decontamination of chemical skin/eye splashes: a critical review.

Skin/eye chemical splashes are a significant workplace problem. Initial water decontamination is usually recommended, but there are few well-conducted experimental animal and human studies of efficacy. An extensive review of the literature and other available information sources was performed to define the scope of the problem and critically review the evidence for water decontamination efficacy. Although water decontamination can decrease the severity of chemical skin/eye burns, it cannot completely prevent them. An ideal replacement decontamination solution would be sterile, nontoxic, chelating, polyvalent, amphoteric, and slightly hypertonic to retard skin or corneal penetration of the chemical.

Animals↗
PubMed2006

Gender: a possible determinant in dosing of dermatologic drugs--an overview.

The role of gender in pharmacokinetics could play a significant role in tailoring HIV and other drug regimens. Here we investigate sex as a factor in saquinavir pharmacokinetics. The HIV-positive women who use saquinavir in combination with other protease inhibitors frequently demonstrate higher saquinavir concentrations than their male counterparts. The majority of the data indicates that the root of women's higher saquinavir concentrations is not inherent to their gender. Rather, extenuating factors associated with HIV play a prominent role in the observed difference between men and women's pharmacokinetic parameters. The source of observed differences in saquinavir pharmacokinetics could not be definitively traced to CYP3A, the enzyme responsible for saquinavir's metabolism or drug transporters. Hormonal changes associated with HIV infection together with concurrent use of other protease inhibitors could help explain development of sex differences. These findings can be used to further investigate when and why gender-based differences in saquinavir pharmacokinetics exist and possible future dosage and therapy considerations. Our knowledge of gender-related pharmacokinetics should be extended for other systemic drugs in dermatology.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Sensory, clinical and physiological factors in sensitive skin: a review.

Certain individuals experience more intense and frequent adverse sensory effects than the normal population after topical use of personal care products, a phenomenon known in popular usage as sensitive skin. Consumer reports of sensitive skin are self-diagnosed and often not verifiable by objective signs of physical irritation. Companies who manufacture cosmetic and personal care products are challenged to provide safe products to an audience with tremendous differences in skin type, culture and habits. This review examines the still incomplete understanding of this phenomenon with respect to aetiology, diagnosis, appropriate testing methods, possible contributing host factors such as, sex, ethnicity, age, anatomical site, cultural and environmental factors, and the future directions needed for research.

Age Factors↗
PubMed2006

Moisturizer effect on irritant dermatitis: an overview.

Moisturizers are empirically used as prevention and treatment of surfactant and irritant dermatitis. Some products state they not only improve barrier function by providing moisturization but also create an environment optimal for healing. Yet, moisturizer clinical efficacy remains a topic of controversy. We reviewed publication from 1992 to 2006 that quantitatively examines moisturizer effectiveness, as an update of our prior overview, Zhai and Maibach in 1998 (2). We intuitively (in a testimonial sense) believe that moisturizers are sometimes effective for preventing and treating irritant dermatitis. However, moisturizer may not be broadly effective (8, 12) and may be relatively specific against certain acids, bases, hydrophilics, and lipophilics. We need to develop principles of what is formulated in moisturizers to improve efficacy; for this purpose, there is a need for experimental moisturizer models for comparative studies.

Dermatitis, Irritant↗
PubMed2006

Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure.

BACKGROUND/PURPOSE: The aging process has been studied with fervor recently, given our shifting demographics. As age's effects are so manifest in the skin's appearance, structure, mechanics, and barrier function, it is not surprising that much effort has been made in research to better understand them. Quantitative measurements permitted by bioengineering have allowed us to objectively and precisely study aging skin. These overviews piece together the immense amounts of information that have emerged from recent technological advances in dermatological research in order to develop a unified understanding of the quantitative effects of age on skin. METHODS: We performed a literature search on age-related changes in protein, glycosaminoglycan (GAG), water, and lipid content and structure, searching Pub-med, Em-Base, Science Citation Index, and the UCSF dermatological library's collection of books on the topic of aging skin. RESULTS: Collagen becomes sparser and less soluble in intrinsically aged skin, but is thickened and more soluble in extrinsically aged areas. Elastin is degraded slowly and accumulates damage with intrinsic aging; also, increased synthesis of abnormally structured elastin occurs in photoexposed areas. This leads to an age-related accumulation of aberrant elastoic material, clumped in the papillary dermis. Generally, age leads to increased folding and decreased interaction of proteins with water. Also, despite increased GAGs in aged skin, these are abnormally deposited on the elastoic material and cannot interact properly with water. Hence, in aged skin, water is found in the tetrahedron form, bound to itself rather than other molecules. Lipid content appears to decrease with age, although the proportion of different lipid classes seems to remain fairly constant. CONCLUSION: Much work remains to be carried out to reach a consensus on the effects of age on skin structure and function. Future studies would be benefited by increased standardization of skin sites tested, methodology, and increased sample sizes.

Body Water↗
PubMed2006

Functional map and age-related differences in the human face: nonimmunologic contact urticaria induced by hexyl nicotinate.

Variation in human skin reactivity to various irritants in association with age and body region has been reported. Hexyl nicotinate (HN), a lipophilic nicotinate ester, was used to induce nonimmunologic contact urticaria in human volunteers of 2 age groups: 10 young subjects [24-34 years, mean +/- standard deviation (SD) 29.8 +/- 3.9 years] and 10 older volunteers (66-83 years, mean +/- SD 73.6 +/- 17.4 years); and to define skin function and potential age-related differences in various facial areas. About 5 mM of HN in ethanol was applied to 8 locations on the face, neck, and volar forearm. A laser Doppler flowmeter was used to determine baseline blood flow and to monitor the skin blood flow changes after HN application. In the contralateral areas, stratum corneum turnover was determined using 5% dansyl chloride in petrolatum. In the young group, the perioral area exhibited the strongest reaction to HN. In the older group, the chin was the most sensitive site. In both the groups, the forearm was the least responsive. The older group demonstrated a stronger reaction than the younger group in 3 sites (forehead, cheek, and nasolabial area). Stratum corneum turnover was slower in the nasolabial area and in the forearm in both age groups, whereas the fastest was in the perioral area and the chin in the younger group and in the chin and the forehead in the older group. Compared to the older group, the younger group showed a slower stratum corneum turnover in the nose and the neck. This study demonstrates the regional and the age-related variability of the stratum corneum turnover and the skin reactions to HN. These observations may help explain some aspects of the cutaneous intolerance in skin care of the face.

Adult↗
PubMed2006

Current understanding of contrast media reactions and implications for clinical management.

Iodinated contrast media (CM) are an integral part of modern diagnostic medicine. Although these agents are considered to be relatively safe, adverse effects in the form of allergy-like reactions occur in a significant number of exposed patients. These reactions may be divided into immediate and delayed responses. Immediate (within 1 hour of administration) anaphylactic reactions range from urticaria and angioedema to laryngeal oedema, hypotension and even death. Delayed reactions to CM occur from 1 hour to 1 week after administration and usually have mostly cutaneous manifestations. History of prior CM reactions and atopy predispose patients to CM reactions. Despite intense research into the pathogenesis of the immediate anaphylactoid responses, new evidence shows that true IgE type I hypersensitivity mediation occurs only in rare, severe cases. The aetiology appears to be multifactorial in most individuals. There is strong evidence to conclude that type IV hypersensitivity is responsible for the delayed reactions to CM. Although switching to non-ionic agents significantly reduces the incidence of immediate reactions to CM, there is little consensus regarding corticosteroid prophylaxis in high-risk individuals. Skin testing and provocative challenges also provide little security. Therefore, physicians must be better prepared to treat immediate anaphylactoid responses. Preventing delayed CM reactions is best performed with patch and delayed intradermal testing in those with a history of prior reactions, although false-negative results have been reported. Corticosteroids and antihistamines may be required for treatment. Until newer agents are developed that negate these issues, healthcare providers must strive to better understand the risk factors associated with CM reactions, as well as the available prophylactic and treatment options.

Anaphylaxis↗
PubMed2006

Hydroxychloroquine-induced retinopathy: a dermatologic perspective.

Dermatologists use antimalarials to treat conditions such as cutaneous lupus erythematosus. One potentially serious adverse effect of these agents is irreversible maculopathy. Although there is some evidence that hydroxychloroquine and chloroquine have similarly narrow therapeutic indices with regard to retinal toxicity, the former is thought to be less damaging to the retina and is thus more widely employed by dermatologists. The current recommended maximal dose for hydroxychloroquine is 6.5 mg/kg/day, with the weight in kilograms used for this calculation being the ideal bodyweight rather than actual bodyweight. Ophthalmologic follow-up is an important component of monitoring patients taking antimalarials. Recommendations for follow-up frequency have varied, and we present the recent guidelines from the American Academy of Ophthalmology. Despite dose limitations and ophthalmologic monitoring, irreversible retinal damage can occur. Among the reported cases, there does not seem to be any obvious predictor of the development of maculopathy. The idiosyncratic nature of this adverse effect may be related to interindividual differences in drug metabolism. To understand why only some patients develop retinopathy, better pharmacokinetic models need to be developed, and further elucidation of the precise mechanism of retinal damage is required.

Antimalarials↗
PubMed2006

Pharmionics in dermatology: a review of topical medication adherence.

The objective of this article was to review patient adherence to topical medications and its relationship to health outcomes in dermatologic disease. To this end, MEDLINE searches from January 1966 through June 2006 and EMBASE searches from January 1974 through June 2006 were conducted. Relevant human efficacy studies, including randomized controlled trials, observational studies, and case-control studies, were selected on the basis of the key words 'compliance,' 'adherence,' 'pharmionics,' 'topical,' 'medication,' or 'dermatology.' Studies were included and reviewed on the basis of their experimental design, controls, and statistical analysis. Analysis revealed that suboptimal adherence to topical medications is a common cause of minimal response or lack of response to drugs and is linked with poor dermatologic outcomes in diseases such as psoriasis, atopic dermatitis, and acne. It is concluded that non-adherence to topical medications is as common as non-adherence to oral medications, and its relationship to poor health outcomes is clear. Several barriers to topical medication adherence and predictors of non-adherence are similar to those for oral medications, while other barriers and predictors are unique to topical medications and the nature of dermatologic disease. Further studies of effective interventions to increase adherence are necessary to improve health outcomes in dermatology.

Administration, Cutaneous↗
PubMed2006

Topical DNA vaccination with DNA/Lipid based complex.

Topical DNA vaccines have been shown to elicit both broad humoral and cellular immune response in vivo. The skin is an attractive site for the delivery DNA antigens for DNA vaccination. However, due to skin's barrier properties, the penetration of DNA and the applications of topical vaccination are limited. To improve permeability of stratum corneum and the potency of topical DNA vaccines, efficient delivery systems are needed. Topical vaccination has been achieved using topical application of naked DNA with or without tape stripping and DNA/lipid based complex such as liposomes, niosomes, Transfersomes, or microemulsion. All methods resulted in significant enhancement in humoral and cellular immune response over naked DNA alone. To develop more cost-effective and needle free vaccines, skin targeted immunizations are required. This overview focuses on the comparison of the potency of topical DNA vaccine between naked DNA and DNA-lipid based complex.

AIDS Vaccines↗