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Biomedical subjects

J J Hostýnek

Publications and source records attributed to J J Hostýnek.

11 recordsLinked to original sources

Allergic contact dermatitis elicitation thresholds of potent allergens in humans.

Literature scoured for human allergenicity to individual chemicals yields a limited number of potent sensitizers, which can be classified in four categories: metals, botanicals, biocides and miscellany. Potency is defined as strong for substances eliciting eczematous reactions to patch concentrations of 500 ppm (parts per million) or less in sensitized individuals. Most data encountered stem from studies conducted on dermatology patients tested routinely for hypersensitivity; only few data have been generated by systematic serial dilution testing.

Adrenal Cortex Hormones↗

Human stratum corneum penetration by nickel. In vivo study of depth distribution after occlusive application of the metal as powder.

Sequential tape stripping was implemented on three healthy volunteers to examine the surface distribution of nickel through human stratum corneum in vivo following occlusive application of the metal as powder on the volar forearm. Exposure sites were stripped 20 times at intervals from 5 min to 96 h post-dosing and the strips analyzed for metal content by Inductively Coupled Plasma-Mass Spectroscopy with a detection limit for nickel of 0.5 ppb. The gradients of nickel distribution profiles increased proportionally with occlusion time, but after the 10th strip to the 20th strip continued at constant levels. Total nickel removed with 20 stratum corneum strips to the level of the glistening layer after maximum occlusion of 96 h was 41.6 micrograms/cm2 (+/- 12.2; average n = 3). In order to normalize the nickel depth distribution profiles, stratum corneum removed by stripping of untreated skin after occlusion was determined by weighing. Following application of nickel dust over 24 h, analysis of the 20th strip still indicated nickel present at 1.42 micrograms/cm2 (+/- 0.68; average n = 3). These data indicate that, in contact with skin, nickel metal is oxidized to form soluble, stratum corneum-diffusible compounds which may penetrate the intact stratum corneum, presumably by the intercellular route, and have the potential to elicit allergic reactions.

Adult↗

Human stratum corneum adsorption of nickel salts. Investigation of depth profiles by tape stripping in vivo.

Sequential adhesive tape stripping was implemented to characterize the penetration of nickel salts in human stratum corneum. Exposure areas of the salts in methanol applied open on arm and back skin in low volume were stripped 20 times to the level of the glistening layer at intervals of 30 min to 24 h post-dosing, and the strips analyzed for metal content by inductively coupled plasma-atomic emission spectroscopy. In the case of nickel chloride, sulfate, nitrate and acetate, material left on the skin surface, the depth-penetration profiles in the stratum corneum, and the dosage unaccounted for suggest the following conclusions: (a) Up to 24 h, most of the nickel dose applied remains on the skin surface or is adsorbed in the uppermost layers of the stratum corneum. (b) At higher concentrations, incomplete material recovery becomes discernible; within 24 h, nickel salts thus appear to penetrate beyond the stratum corneum to a minor degree, possibly via the skin shunts. (c) While the concentration gradients of nickel adsorbed vary with counter ion, anatomical site, dose and exposure time, for all variables tested the depth profiles converge to non-detectable levels (< 20 ppb) towards the level of the glistening layer. A notable exception is nickel as nitrate, for which levels continue at low but constant levels (1% of dose) beyond the third stratum corneum strip, indicative of intercellular diffusion. (d) Differences in material recovered suggest that the stratum corneum on the arm is more penetrable to nickel than stratum corneum on the back. (e) The counter ion in nickel salts plays a major part in their diffusion into the stratum corneum, suggestive of ion pairing. Overall, the data point to all three avenues of skin penetration by nickel: intracellular, intercellular, and transappendageal.

Adult↗

In vitro permeation of nickel salts through human stratum corneum.

Allergic contact dermatitis due to nickel salts is common. It is therefore important to measure the permeation of these salts through the stratum corneum (SC), the primary rate-limiting domain in skin. An advanced diffusion system and analytical techniques now enable better measurement of the flux than was possible in earlier experiments. Human SC was prepared by trypsinization of dermatomed cadaver leg skin. The diffusion system included diffusion cells with a spiral line. Aqueous solutions of nickel salts (Ni(NO3)2, NiSO4, NiCl2 and Ni(-OOCCH3)2 at 1% Ni2+ concentration) were used as the donor solution (400 microL/cell). The receptor fluid, pure water, was collected up to 96 h after application of the donor solutions. Nickel concentrations in the donor and receptor fluid, as well as in the SC, were analysed using inductively coupled plasma mass spectrometry (ICP-MS) with a confidence limit of 0.5 ppb. Based on the total recovery of nickel from the experiments, about 98% of the dose remained in the donor solution, whereas 1% or less was retained in SC and less than 1% was found in the receptor fluid. Following an early surge, nickel permeates slowly across SC. The steady-state permeability coefficients of nickel were calculated from the flux data (approximately 5.2-8.5 x 10(-7) cm/h) with no significant difference among the salts. The results concur in principle with earlier studies conducted using the full-thickness human skin in vitro, and suggest that in vivo nickel ions may permeate simultaneously by routes of diffusion such as the shunt pathway, apart from slow transcellular/intercellular diffusion alone.

Acetates↗

Colorimetric method for quantifying human Stratum corneum removed by adhesive-tape stripping.

Tape-stripping of the skin is a useful method for removing the stratum corneum and obtaining more information about the function of this skill layer as the main barrier for skin penetration. The amount of stratum corneum removed is of relevance in establishing the concentration profile of chemicals within the stratum corneum after topical application. Weighing is the preferred method for measuring the amount stripped, but because it is often subject to artifacts, alternative methods are sought. We present a simple, colorimetric method for determining the amount stratum corneum removed by sequential adhesive-tape-stripping of human skin in vivo. The method is based on quantification of the sodium hydroxide soluble protein fraction using a commercially available protein assay similar to the Lowry assay. The method is shown to be an accurate and reproducible alternative to weighing, also demonstrating uniform removal of stratum corneum layers following the very initial strips.

Adhesives↗

Nickel content of standard patch test materials.

The nickel sulfate content in standard patch test materials currently used in the US, Europe and Japan was determined by inductively-coupled plasma atomic emission spectroscopy, a state-of-the-art microanalytical method which allows nickel detection to levels of 7 ppb (microg/l). In 2 materials with a nominal concentration of 5% nickel sulfate hexahydrate in pet., the range (calculated averages of triplicate analyses of 3 different batches) was from 4.72 to 4.87% and 4.97 to 5.39%, respectively. In 1 material with a 2.5% nominal concentration in pet., the values ranged from 2.41 to 2.48%. The range seen in a 5% NiSO4 hexahydrate aq. material was 4.95 to 5.03%. The range for 2.5% NiSO4 anh. in pet. was 2.39 to 2.49%. This data suggest a significant improvement in quality control compared to our previously published data.

Allergens↗

Gold: an allergen of growing significance.

Gold moved into the limelight of medical literature thanks to the anti-inflammatory activity and effectiveness of gold compounds in the treatment of rheumatoid arthritis, but more recently also because of the growing incidence of hypersensitivity induced by it which is expressed in cutaneous and mucosal reactions. This review discusses dermatotoxicity associated with gold. In some countries gold has moved into second place as allergen, following nickel. Such recognition is mainly due to improved diagnostic methods and to its inclusion in routine dermal patch testing. Some unconventional manifestations of hypersensitivity are associated with use patterns which involve intimate contact with the metal as a component of jewelry. In-depth analysis of the growing number of cases of allergy has revealed various immunological idiosyncrasies as being characteristic of this metal. These include late reactions to challenge, extraordinary persistence of clinical effects, formation of intracutaneous nodules and immunogenic granuloma unresponsive to conventional steroid therapy, the occurrence of eczema at sites distant from the site of contact, and flare-ups of eczema upon systemic provocation with allergen which are characteristic of drug induced allergy. These manifestations demand investigations at the molecular level of the unusual mechanisms of action involved.

Allergens↗

A local lymph-node assay validation study of a structure-activity relationship model for contact allergens.

A structure-activity relationship model for prediction of contact allergenic potential of chemicals had previously been developed. The model had been shown to be able to classify known allergens and nonallergens using data on physicochemical and reactivity parameters of functional groups by discriminant two-value multiple regression analysis. To investigate the model, six selected chemicals which had not been previously investigated for allergenicity were studied with both the model and a murine local lymph-node assay. The same compounds were predicted to be allergens (3-bromo-2-coumaranone, 1-nitrocyclohexene and alpha-acryloyloxy-beta, beta-dimethyl-beta-butyrolactone) and nonallergens (1-carbethoxy-4-piperidone, 6,7-dimethoxy-2-tetralone and 9-acetylanthracene) by both the model and the local lymph-node assay.

Allergens↗

Metals and the skin.

Certain metals, and many metal-based compounds, are inherently toxic, and their presence in occupational and environmental settings raises appropriate questions concerning human exposure. Contact of these materials with the skin represents an important route of exposure, which is not well characterized. The purpose of this review, therefore, is to assemble the available, useful information pertinent to risk assessment following dermal contact. Specifically, we summarize here: (1) data relevant to the qualitative and (where possible) quantitative evaluation of metal compound permeation through the skin; (2) the role of each metal in metabolism, particularly with respect to the skin, and the potentially toxic effects that may result from dermal contact; and (3) the immunological characteristics (including allergenicity) of the metals and their derivatives. In total, information on 31 metals has been reviewed. It is clear that many diverse factors determine the ability of metal-based species to permeate biological membranes, not all of which have been fully defined. Therefore, considerably more experimentation, targeted at the development of high-quality transport data, will be required before the specification of practically useful structure-activity relationships are possible.

Animals↗