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Biomedical subjects

A Kydonieus

Publications and source records attributed to A Kydonieus.

6 recordsLinked to original sources
PubMed1996

Sensitization of mice to topically applied drugs: albuterol, chlorpheniramine, clonidine and nadolol.

Allergic contact dermatitis from drugs is a significant obstacle to the development of transdermal drug delivery systems. Protocols for the sensitization of mice to drugs are needed to test methods for the prevention of allergic contact dermatitis. CBA/J female mice were sensitized to the drugs albuterol, chlorpheniramine, clonidine and nadolol by topical application. Sensitization was achieved by application of drug at 5% (w/v) to shaven dorsal skin for 5 days in a hydroxyethylcellulose vehicle. Contact sensitization was determined by measuring the ear swelling response to application of 1% drug in vehicle. Control mice treated by application of vehicle alone did not exhibit an ear swelling response to drug. Supplementation of the mice with vitamin A boosted the ear swelling response, as did application of drug to dorsal versus abdominal skin. Although plasma amounts of retinol were higher in vitamin A supplemented versus control mice, the rate of drug (albuterol and nadolol) permeation was not significantly different between vitamin A supplemented and control mice. Permeability of dorsal skin for nadolol was twice that of ventral skin, which may explain the differences in sensitization at these sites. This sensitization protocol should be useful in the development of hypoallergenic transdermal drug delivery systems.

Administration, Cutaneous↗
PubMed1993

Analysis of the extractive and hydrolytic behavior of microthane poly(ester-urethane) foam by high pressure liquid chromatography.

Microthane foam, a poly(ester-urethane) (PU) used in the manufacture of Meme/Replicon breast implants, was analyzed by an HPLC method to determine whether 2,4- and 2,6-toluenediamine (TDA) were formed under a variety of physiological and nonphysiological extraction and hydrolytic conditions. At our detection limit of 20 ppb, no 2,4- or 2,6-TDA was observed in either methyl tert-butyl ether (MTBE), or aqueous buffer extracts of PU foam. The predominant extractable components identified by HPLC UV-analysis, were mixture of nonaromatic and aromatic PU fragments. Moreover, no detectable amounts of TDA were found in foam or MTBE extract of foam incubated in phosphate buffer, pH 7.4, at 37 degrees C for 5 days. By contrast, 2,4- and 2,6-TDA were found in foam and foam extracts exposed to low concentrations of either strong mineral acid or base; higher levels were found at higher acidity, treatment temperature, or durations of incubation. Moreover, 2,4- and 2,6-TDA were found in oligomers isolated by preparative HPLC and exposed to alkaline conditions. Finally, 1-2 ppm of 2,4-TDA was detected when PU foam extracts were prepared by the Snyder-Breder method, which employs acidic and alkaline conditions in the work-up procedure. Based on these findings, we suggest that published observations of 2,4-TDA formation from in vitro and ex vivo extractions of PU foam are artifacts resulting from pH effects on oligomeric PU fragments present in or extracted from the foam.

Biocompatible Materials↗
PubMedDate not supplied

Several different ion channel modulators abrogate contact hypersensitivity in mice.

A major obstacle in transdermal delivery of drugs is the development of adverse skin sensitization reactions. We tested the concept that ion channel modulators as a class of agents suppress contact hypersensitivity in a mouse model. Mice were sensitized to several contact sensitizing chemicals including dinitrochlorobenzene (DNCB) and a sensitizing drug, nadolol. We report our successful use of several ion channel modulators in suppressing contact hypersensitivity, including amiloride, ethacrynic acid (ECA), nifedipine and verapamil. For this purpose, Balb/c female mice were sensitized with DNCB, and abrogation of induction of contact hypersensitivity reaction (CHR) was examined by topical pretreatment of the target-sensitized skin with amiloride, nifedipine and pairwise combinations of these agents with ECA, a potassium ion channel blocker. Abrogation of induction of CHR was observed in all cases. In addition, suppression of contact hypersensitivity was observed in nadolol-sensitized mice pretreated with either verapamil or nifedipine. The results indicate that ion channel inhibitors are broadly effective inhibitors of allergic contact dermatitis and may be useful for facilitating the transdermal delivery of therapeutic drugs that have sensitization potential.

Amiloride↗
PubMedDate not supplied

Inhibition of irritation and contact hypersensitivity by phenoxyacetic acid methyl ester in mice.

New anti-irritant treatments are required to prevent irritation and sensitization reactions to consumer medicines and dermatological drugs. We report here that phenoxyacetic acid methyl ester (PAME) is an effective agent to prevent and treat irritant and allergic contact dermatitis. Balb/c mice skin-treated with 1% PAME do not lose weight relative to vehicle-treated mice, nor is it irritating to mouse skin. Topical PAME prevents skin irritation to a wide variety of irritants including: arachidonic acid, capsaicin, sodium lauryl sulfate (SLS), disodium laureth sulfosuccinate and tetradecanoylphorbol-13-acetate. Histological studies showed that 1% PAME greatly diminished dermal neutrophilic infiltration and dermal capillary vessel dilation, and prevented epidermal hyperproliferation and hyperkeratosis that accompanies detergent (SLS)-induced skin irritation. Topical PAME inhibited ear swelling following ear challenge during the elicitation phase of contact hypersensitivity in mice sensitized with 1-chloro-2, 4-dinitrochlorobenzene (DNCB), oxazolone and the hair coloring dye rho-phenylenediamine (PPD). Finally, topical administration of 1% PAME prior to PPD or DNCB sensitization prevented the induction phase of contact hypersensitivity. These results indicate that PAME represents a potential new category of potent topical anti-inflammatory agents.

Administration, Topical↗
PubMedDate not supplied

Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria.

The percent lipid composition of pooled human sebum analyzed by thin-layer chromatography was: ceramides (13%), fatty acid (47%), cholesterol (7%), cholesterol esters (2%), squalene (11%), triglycerides (3%), and wax esters (17%). Total sebum lipids (2- 4 mg/ml), sonicated into bacterial culture medium, caused 4- to 5-fold log reduction in growth of gram-positive bacteria, Staphylococcus aureus, Streptococcus salivarius and the anaerobe Fusobacterium nucleatum, but was ineffective against most gram-negative bacteria. Fractionation of the sebum lipids showed that both saturated and unsaturated fatty acids contained the bulk of the antimicrobial activity. Lauric acid (C12:0) was the most active saturated fatty acid. The unsaturated fatty acid, palmitoleic acid (C16:1delta6, cPA) was both the most predominant monoene and the most active antimicrobial fatty acid. Purified cPA (>99%) yielded typical minimal inhibitory concentration (MIC) values of 10-20 microg/ml against gram-positive bacteria. Organically synthesized cPA isomer gave MIC values comparable to the natural material. Both natural and synthetic cPA were found to be the most active sebum lipid fraction in blocking the adherence of a pathogenic strain of Candida albicans to porcine stratum corneum. Ethanol in combination with cPA exerts a synergistic bactericidal activity against gram-negative pathogenic bacteria, including Pseudomonas aeruginosa, Propionibacterium acnes, Escherichia coli, and several methacillin-resistant strains of S. aureus. Palmitoleic acid may be useful in topical formulations for treatment of secondary gram-positive bacterial infections, as a gram-positive bacteria antimicrobial in wound dressings, and as a natural gram-positive antimicrobial preservative in skin and hair care products.

Animals↗