Carcinogenic consequences of coal-tar shampoo?
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Animals↗
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Results for “Skin Absorption”
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Structure of the skin barrier and its modulation by vesicular formulations.
The natural function of the skin is to protect the body from unwanted influences from the environment. The main barrier of the skin is located in the outermost layer of the skin, the stratum corneum. Since the lipids regions in the stratum corneum form the only continuous structure, substances applied onto the skin always have to pass these regions. For this reason the organization in the lipid domains is considered to be very important for the skin barrier function. Due to the exceptional stratum corneum lipid composition, with long chain ceramides, free fatty acids and cholesterol as main lipid classes, the lipid phase behavior is different from that of other biological membranes. In stratum corneum crystalline phases are predominantly present, but most probably a subpopulation of lipids forms a liquid phase. Both the crystalline nature and the presence of a 13 nm lamellar phase are considered to be crucial for the skin barrier function. Since it is impossible to selectively extract individual lipid classes from the stratum corneum, the lipid organization has been studied in vitro using isolated lipid mixtures. These studies revealed that mixtures prepared with isolated stratum corneum lipids mimic to a high extent stratum corneum lipid phase behavior. This indicates that proteins do not play an important role in the stratum corneum lipid phase behavior. Furthermore, it was noticed that mixtures prepared only with ceramides and cholesterol already form the 13 nm lamellar phase. In the presence of free fatty acids the lattice density of the structure increases. In stratum corneum the ceramide fraction consists of various ceramide subclasses and the formation of the 13 nm lamellar phase is also affected by the ceramide composition. Particularly the presence of ceramide 1 is crucial. Based on these findings a molecular model has recently been proposed for the organization of the 13 nm lamellar phase, referred to as "the sandwich model", in which crystalline and liquid domains coexist. The major problem for topical drug delivery is the low diffusion rate of drugs across the stratum corneum. Therefore, several methods have been assessed to increase the permeation rate of drugs temporarily and locally. One of the approaches is the application of drugs in formulations containing vesicles. In order to unravel the mechanisms involved in increasing the drug transport across the skin, information on the effect of vesicles on drug permeation rate, the permeation pathway and perturbations of the skin ultrastructure is of importance. In the second part of this paper the possible interactions between vesicles and skin are described, focusing on differences between the effects of gel-state vesicles, liquid-state vesicles and elastic vesicles.
Administration, Cutaneous↗
Cutaneously applied acyclovir acts systemically in the treatment of herpetic infection in the hairless mouse.
Using the SKH-1 hairless mouse (HM) we have addressed the issue as to whether topically applied acyclovir (ACV) may mediate some of its antiviral actions by a systemic effect. When topically applied in a formulation consisting of polyvinyl alcohol (25% w/v):DMSO:cremophor EL:linoleic acid (63:16:16:5, v/v/v/v), ACV penetrated hairless mouse skin in a concentration-dependent manner and dose-dependently reduced cutaneous herpes simplex virus 1 (HSV-1) KOS infection. Topically applied ACV also effectively reduced the mortality associated with disseminated HSV-2 HG-52 infection. At 1 h following topical application of 1.7% w/v ACV the plasma and skin concentrations of ACV were 5.5 nmoles/ml and 120 nmoles/g. At 1 h following an oral dose of ACV with antiviral efficacy comparable to topically applied ACV (1.7% w/v) the plasma and skin concentrations of ACV were 21.3 nmoles/ml and 51 nmoles/g. These findings imply that when applied topically to the HM, ACV can mediate a portion of its antiviral activity through a systemic mode of action.
Acyclovir↗
Effect of the different factors on the iontophoretic delivery of calcium ions from bentonite.
The calcium content of mud patches used for therapy is very small. Several mineral clays originating from Hungary served as a base material for experiments in order to find a suitable drug for transdermal introduction of calcium ions into the body. The Ca++ transport through the pig skin has been investigated in vitro in diffusion cells applying iontophoresis. Studies of electrical and physicochemical factors acting on the permeation kinetics of in vitro experiments were performed. The utilization of direct current has intensified the Ca++ transport through the pig skin (129.78+/-26. 15 microgram Ca/cm2). On using pulsate currents the amount of the Ca++ penetrating through the skin was 5-10 times higher (283.18+/-16.89 microgram Ca/cm2, 388.71+/-19.90 microgram Ca/cm2) than that of the passive transport (36.22+/-14.20 microgram Ca/cm2). The amount of Ca++ cumulated in the receptor compartment was directly proportional to the amount of bentonite (a natural mineral clay with a large cation exchange capacity) in the donor compartment and to the concentration of Ca++ in the lattice of the applied mineral clay. Therefore, the experiments were carried out on a bentonite previously enriched in Ca++ in its lattice (50 mg Ca/g bentonite). The results of the in vitro studies could open a new field of application in the therapy of osteoporosis or in the use of mineral substances.
Administration, Cutaneous↗
A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivo protoporphyrin IX accumulation determined by confocal microscopy.
Topical application of 5-aminolevulinic acid (5-ALA) followed by light irradiation is a new concept of photodynamic therapy (PDT) of skin cancers. 5-ALA is a prodrug that can be converted by the heme biosynthetic pathway into protoporphyrin IX, an effective photosensitizer. In the present work we propose the enhancement of 5-ALA-induced protoporphyrin IX accumulation by dimethylsulphoxide (DMSO) and ethylenediamine-tetraacetic acid disodium salt (EDTA). The presence of 20% DMSO (w/w) in oil-in-water emulsions increased the in vitro permeation of 5-ALA through hairless mouse skin. In vivo studies demonstrated a significant increase in the amount of protoporphyrin IX extracted from healthy hairless mouse skin after 3 h treatment with an oil-in-water emulsion containing 10% 5-ALA (w/w), 3% EDTA (w/w) and 20% DMSO (w/w). By confocal scanning laser microscopy imaging, an observed increase in red fluorescence, at 476 nm excitation and emission detected longer than 590 nm, in skin that had received this treatment, was attributed to protoporphyrin IX accumulation. Although no effect of EDTA on short-term protoporphyrin IX accumulation in skin was detected, this chelator could protect 5-ALA from decomposition during prolonged topical administration. The results obtained indicate that association of 5-ALA, EDTA and 20% DMSO may enhance the delivery of 5-ALA to the skin in the topical PDT.
Aminolevulinic Acid↗
Drug delivery routes in skin: a novel approach.
The role of hair follicles in transdermal delivery remains difficult to elucidate due partly to animal model complications. This paper explores a novel technique employing two human skin membranes to differentiate shunt route delivery from bulk transepidermal input. The method monitors penetration through epidermal membranes and compares this with delivery through a sandwich of stratum corneum and epidermis, with the corneum forming a top membrane. As orifices of shunts occupy only 0.1% of the area, there is negligible chance that shunts in the membranes will superimpose. The top layer blocks shunts available in the bottom layer. If shunts are important, delivery through sandwiches will be much reduced compared with that through epidermis, allowing for increased double membrane thickness. Experiments with penetrants under passive, iontophoretic and electroporation conditions illustrated the value of the method. A Monte Carlo simulation suggested that any failure of membrane adherence would not affect conclusions drawn.
Administration, Cutaneous↗
Multicenter evaluation of sunscreen UVA protectiveness with the protection factor test method.
BACKGROUND: Currently there is no consensus on a test method to determine the protectiveness of sunscreens in the UVA region alone. OBJECTIVE: The protection factor in UVA (PFA) test method was evaluated to determine its ability to detect dose-response, specificity for UVA protection only, and repeatability between laboratories, and to detect whether the protection factors depended on the skin response observed (erythema or tanning). METHODS: Sunscreens containing 0%, 2%, or 5% oxybenzone, or 7% octyl dimethyl para-aminobenzoic acid were tested by the PFA protocol in five laboratories. RESULTS: The test method demonstrated ability to distinguish differences between the protection in the oxybenzone formulations but not between the placebo (0%) and the 7% octyl dimethyl para-aminobenzoic acid formula. The protection factors were independent of the type of skin response. CONCLUSION: These data support the utility and validity of the PFA method for determining the UVA protection provided by sunscreen products.
4-Aminobenzoic Acid↗
Black and white human skin differences.
This review of black and white human skin differences emphasizes the alleged importance of factors other than the obvious, i.e., skin color. Physicochemical differences and differences in susceptibility to irritants and allergens suggest a more resistant black than white skin. Differences appear to exist in the frequency of which several skin diseases occur among blacks and whites. A striking feature in this literature is the disagreement between authors. Common for much of this information is difficulty of interpretation, because of socioeconomic influences and other environmental factors.
Africa↗
Topical chemotherapy with 5-fluorouracil. A review.
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Administration, Topical↗
Hazards of therapy.
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Dinitrochlorobenzene↗
Anthralin: historical and current perspectives.
Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.
Anthracenes↗
Dermatologic needs in drugs and instrumentation.
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Administration, Topical↗
Environmental reactions to chemical, physical, and biologic agents.
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Animals↗
Cutaneous signs of systemic toxicity due to dioxins and related chemicals.
The controversy about dioxin effects on human health received a great deal of attention recently when the State of Missouri was declared to have a dioxin crisis. However, dioxin and several related chemicals are widespread throughout the world. Cutaneous signs play an important part in evaluating toxicity of dioxin and similar chemicals. Chloracne is the most sensitive indicator of significant dioxin exposure. Porphyria cutanea tarda and hyperpigmentation are other known cutaneous effects, and malignant fibrous histiocytomas of the skin may possibly be associated, although data are inconclusive on this point. The AMC Council on Scientific Affairs recommended that all physicians become familiar with chloracne and other toxic effects of dioxin. Dermatologists, especially, should be aware of the problem and may discover early cases of previously unsuspected exposure to this group of chemicals.
Abnormalities, Drug-Induced↗
Pseudomonic acid, a new antibiotic for topical therapy.
Pseudomonic acid, a new wide-spectrum antimicrobial agent, was evaluated as a 2% formulation in a cream. Animal studies showed that this formulation was just capable of penetrating the skin. When administered parenterally to animals, pseudomonic acid was converted to inactive metabolites that were quickly eliminated from the body. When pseudomonic acid was applied as a cream to human skin, no sensitization was observed. In an open clinical study, sixty-eight patients with skin infections (mostly superficial conditions such as impetigo, infected eczema, folliculitis, or balanitis) applied pseudomonic acid cream three times a day for 5 days. In fifty patients the infections completely cleared within 2 days of the end of therapy, and considerable clinical improvement was noted in sixteen more. One patient stopped the treatment prematurely due to local burning pain, and one patient could not be evaluated clinically.
Administration, Topical↗
Calcinosis cutis resulting from percutaneous penetration and deposition of calcium.
A case of localized calcinosis cutis of the hands and fingers is described in an oil field worker with normal serum calcium and phosphorus levels. The proposed mechanism consists of percutaneous penetration and subsequent deposition of calcium from the daily exposure to industrial drilling fluids containing calcium salts.
Adult↗
Structural and functional changes of normal aging skin.
Solar-induced cutaneous changes are more prevalent and profound in older persons and, thus, are often inappropriately attributed to the aging process, per se. Structural and functional alterations caused by intrinsic aging and independent of environmental insults are now recognized in the skin of elderly individuals. Structurally the aged epidermis likely becomes thinner, the corneocytes become less adherent to one another, and there is flattening of the dermoepidermal interface. The number of melanocytes and Langerhans cells is decreased. The dermis becomes atrophic and it is relatively acellular and avascular. Dermal collagen, elastin, and glycosaminoglycans are altered. The subcutaneous tissue is diminished in some areas, especially the face, shins, hands, and feet, while in others, particularly the abdomen in men and the thighs in women, it is increased. The number of eccrine glands is reduced and both the eccrine and apocrine glands undergo attenuation. Sebaceous glands tend to increase in size but paradoxically their secretory output is lessened. The nail plate is generally thinned, the surface ridged and lusterless, and the lunula decreased in size. There is a progressive reduction in the density of hair follicles per unit area on the face and scalp, independent of male-pattern alopecia. The hair shaft diameter is generally reduced but in some areas, especially the ears, nose, and eyebrows of men and the upper lip and chin in women, it is increased as vellus hairs convert to cosmetically compromising terminal hairs. Functional alterations noted in the skin of elderly persons include a decreased growth rate of the epidermis, hair, and nails, delayed wound healing, reduced dermal clearance of fluids and foreign materials, and compromised vascular responsiveness. Eccrine and apocrine secretions are diminished. The cutaneous immune and inflammatory responses are impaired, particularly cell-mediated immunity. Clinical correlates of these intrinsic aging changes of the skin include alopecia, pallor, xerosis, an increased number of benign and malignant epidermal neoplasms, increased susceptibility to blister formation, predisposition to injury of the dermis and underlying tissues, delayed onset and resolution of blisters and wheals, persistent contact dermatitis, impaired tanning response to ultraviolet light, increased risk for wound infections, prolongation of therapy necessary for onychomycosis, and thermoregulatory disturbances.
Adult↗
Proallergens of formaldehyde applied in patch testing of formaldehyde contact allergy.
The ability of the nonliquid, nonvolatile proallergen of formaldehyde, N-hydroxymethylsuccinimide, to test for contact allergy to formaldehyde has been investigated by in vitro penetration studies in human epidermis. Compared with the standard test, 1% formaldehyde in water, N-hydroxymethylsuccinimide equal to 0.8 mg formaldehyde gave a similar penetration profile. This is explained by cleavage of N-hydroxymethylsuccinimide into formaldehyde and carrier (succinimide) by transepidermal water on the surface of the skin. Results were confirmed by a guinea pig maximazation test on animals sensitized to formaldehyde and in a preliminary clinical study on nine patients with known allergy to formaldehyde.
Administration, Cutaneous↗