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Background: Allergic symptoms can be induced by behavioral conditioning. However, the conditionability of antiallergic effects has not yet been studied. Thus, we investigated whether the effects of a histamine 1 (H(1)) receptor antagonist are inducible in patients suffering from house-dust mite allergy using a behavioral conditioning procedure., Methods: During the association phase, 30 patients with allergic house-dust mite rhinitis received a novel-tasting drink once daily, followed by a standard dose of the H(1) receptor antagonist, desloratadine, on 5 consecutive days. After 9 days of drug washout, the evocation trial commenced: 10 patients received water together with an identically looking placebo pill (water group), 11 patients were re-exposed to the novel-tasting drink and received a placebo pill [conditioned stimulus (CS); CS group] and 9 patients received water and desloratadine (drug group)., Results: During the association phase, desloratadine treatment decreased the subjective total symptom scores, attenuated the effects of the skin prick test for histamine and reduced basophil activation ex vivo in all groups. During the evocation trial, the water group, in which subjects were not re-exposed to the gustatory stimulus, showed a reduction in subjective total symptom scores and skin prick test results, but no inhibition of basophil activation. In contrast, re-exposure to the novel-tasting drink decreased basophil activation, the skin prick test result and the subjective symptom score in the CS group to a degree that was similar to the effects of desloratadine in the drug group., Conclusions: These data show that behaviorally conditioned effects are not only able to relieve subjective rhinitis symptoms and allergic skin reactions, but also to induce changes in effector immune functions., ((c) 2008 S. Karger AG, Basel.)

Gene expression following direct injection of naked plasmid DNA into the skin has been demonstrated in the past. Topical application of plasmid DNA represents an attractive route of gene delivery. If successful, it would have great prospects in skin gene therapy since it is painless and easy to apply. In this study, we analyzed the expression of plasmid DNA in vivo and in vitro following topical application of plasmid DNA in various liposomal spray formulations. Therefore, different concentrations of plasmid DNA expressing enhanced green fluorescent protein (pEGFP-N1) were sprayed onto mouse or human skin once daily for three consecutive days and compared with direct injection. Gene expression was assessed 24 h after the final topical application of various liposomal DNA formulations. The results showed that EGFP mRNA and protein were detectable by RT-PCR and Western blot, respectively. However, epicutaneously applied EGFP plasmid DNA did not lead to microscopically detectable EGFP protein, when assessed by confocal laser microscopy or fluorescence-activated cell sorting in contrast to about 4% of fluorescent keratinocytes following intradermal injection. In an in vivo mouse model, the application of pEGFP-N1 DNA led to the generation of GFP-specific antibodies. These results indicate that topical spray application of pEGFP-N1 liposomal DNA formulations is a suitable method for plasmid DNA delivery to the skin, yielding limited gene expression. This spray method may thus be useful for DNA vaccination. To increase its attractiveness for skin gene therapy, the improvement of topical formulations with enhanced DNA absorption is desirable.

Background: The penetration of topically applied substances into the stratum corneum can non-invasively be studied using the tape stripping procedure. This method was applied to investigate in vivo the penetration of a fragrance, vanillin, applied in ethanol and a w/o emulsion., Methods: Twenty tape strips were removed from each skin area treated with vanillin in ethanol or w/o emulsion, respectively. The concentration of vanillin was determined for each tape strip. In addition, the pseudo-absorption of the corneocytes was determined to calculate the SC profile., Results: The vanillin concentration was correlated both with the tape number and with the stratum corneum profile. Depending on whether the tape number or the profile of the stratum corneum were correlated with the vanillin concentration, different distributions within the stratum corneum were obtained. Different amounts of stratum corneum were removed with 20 tape strips dependent on the vehicle applied previously. The application of the w/o emulsion led to the removal of nearly the half the amount of corneocytes stripped from the ethanol-treated area., Conclusions: The results obtained underline the general necessity to correlate the amount of stratum corneum with the amount of substance in penetration studies.