pulmicort and Dermatitis--Contact

There is a major clinical need for new therapies for the treatment of chronic itch. Many of the molecular components involved in itch neurotransmission are known, including the neuropeptide NPPB, a transmitter required for normal itch responses to multiple pruritogens in mice. Here, we investigated the potential for a novel strategy for the treatment of itch that involves the inhibition of the NPPB receptor NPR1 (natriuretic peptide receptor 1). Because there are no available effective human NPR1 (hNPR1) antagonists, we performed a high-throughput cell-based screen and identified 15 small-molecule hNPR1 inhibitors. Using in vitro assays, we demonstrated that these compounds specifically inhibit hNPR1 and murine NPR1 (mNPR1). In vivo, NPR1 antagonism attenuated behavioral responses to both acute itch- and chronic itch-challenged mice. Together, our results suggest that inhibiting NPR1 might be an effective strategy for treating acute and chronic itch.

Topics: Animals; Behavior, Animal; Cell-Free System; Dermatitis, Contact; Disease Models, Animal; Ganglia, Spinal; Humans; Mice, Inbred C57BL; Mice, Knockout; Neurons; Pruritus; Receptors, Atrial Natriuretic Factor; Reproducibility of Results; Signal Transduction; Small Molecule Libraries

In order to map the frequency of contact hypersensitivity (CH) to epoxy resin, methyldibromoglutaronitrile (MDBGN), tixocortol pivalate (TP) and budesonide patch tests were carried out.. The tests were performed in 1448 patients. Most patients belong to the allergic and irritative contact dermatitis groups. The tests were administered with the allergens epoxy resin 1%, MDBGN 0.3%, TP 1% and budesonide 0.1%, applied on the back. Reactions were evaluated at 40 min, on day 2 (D2), day 3 (D3) and day 4 (D4). In the patients of the Dept. of Dermatology, Venerology and Dermatooncology of Semmelweis University (patients number =1073) reactions were evaluated on day 7 as well.. Epoxy resin elicited immediate reactions in 1 patient at 40 min. Further evaluations showed no difference on D3, D4 and D7 with a frequency of CH of 1.03%. Patch testing for MDBGN did not provoke immediate reactions, evaluations showed an increasing hypersensitivity rate (D2: 0.93%; D7:1.77%). Patch tests with TP yielded no immediate reactions, the frequency of CH increased from 0.47% (D2) to 2.01% (D7). No immediate reactions were observed by budesonide; an increase was seen in frequency of CH (D2:0.93% to D7:3.84%). CH to the studied allergens was observed mostly in allergic contact dermatitis group, to budesonide in irritative contact dermatitis and in atopic dermatitis groups as well.. The data of the present study are the first results about this four allergens in Hungary and to our knowledge from our region as well.

Topics: Allergens; Budesonide; Dermatitis, Allergic Contact; Dermatitis, Contact; Dermatitis, Irritant; Epoxy Resins; Humans; Hungary; Hydrocortisone; Hypersensitivity, Immediate; Nitriles; Patch Tests; Preservatives, Pharmaceutical; Urticaria

Topics: Administration, Topical; Budesonide; Child; Dermatitis, Contact; Erythema Multiforme; Female; Glucocorticoids; Humans

The effects of a topically applied corticosteroid and its acetone vehicle on experimental allergic, toxic and irritant reactions are presented. The corticosteroid budesonide in acetone or acetone alone was applied to reactions immediately after and at different time intervals within the 1st h after provocation. Classical naked eye observation was performed and the dermal cellular infiltrate was differentiated and counted using a previously well-characterized method. "Treatment", whether with the steroid in acetone or acetone alone, had anti-inflammatory effects. For all reaction types, erythema and oedema diminished and a significant decrease in mononuclear cells was seen, when application occurred within the first 5 min after provocation. The effects were most marked for the toxic reaction to croton oil, the steroid and the vehicle being anti-inflammatory to the same extent. Application up to 60 min after provocation had anti-inflammatory effects for this reaction type. The mechanisms of acetone's anti-inflammatory effects are at present unclear. One possible explanation is that intercellular lipid organisation and, by extension, cellular membrane lipid organisation, are altered, influencing membrane receptor function. Possible anti-inflammatory effects of acetone should be considered in experimental and perhaps even clinical situations. Further investigation of the therapeutic possibilities of the finding seems warranted.

Topics: Acetone; Administration, Topical; Animals; Anti-Inflammatory Agents; Budesonide; Dermatitis, Contact; Disease Models, Animal; Drug Therapy, Combination; Female; Glucocorticoids; Guinea Pigs; Pilot Projects; Reference Values; Skin; Skin Tests

Ear edema models are regularly used for topical testing of antiinflammatory compounds. However, test compounds are usually applied simultaneously with proinflammatory agents at the same site which may result in mutual interactions. In order to avoid the occurrence of false antiinflammatory effects, a model of oxazolone-induced contact hypersensitivity has been described in which the hapten and test compound are each applied separately to only one side of the ear. By splitting and weighing the dorsal and ventral cutis of the ears, it was shown that the edemateous response of the control nonhapten side was comparable with the hapten-treated side. Some agents with antiinflammatory properties, as for example, dapsone, cimetidine, cyclosporine A, and budesonide, were tested simultaneously with oxazolone on both sides of the ear or applied separately on the dorsal and ventral ear sides, respectively. When dissolving the compounds in solutions of oxazolone, marked colorations of the test solutions were noted, indicating the occurrence of a chemical interaction. On simultaneous application at the same area, almost complete inhibition of the edemateous response was obtained for all compounds tested. In contrast, when applied separately, only budesonide appeared to exhibit antiinflammatory activity. The results indicate that the proposed model can be used to avoid the occurrence of interactions between oxazolone, and possibly other sensitizers, and substances that are being evaluated for topical antiinflammatory activity. By use of this model spurious antiinflammatory activity can be detected.

Topics: Adjuvants, Immunologic; Animals; Artifacts; Budesonide; Dermatitis, Contact; Disease Models, Animal; Drug Interactions; Ear; Edema; False Positive Reactions; Female; Haptens; Mice; Mice, Inbred BALB C; Organ Size; Oxazolone; Toxicity Tests

Contact hypersensitivity to corticosteroids is increasingly reported and has been identified as a problem of considerable clinical relevance. The prevalence of positive patch tests to corticosteroids ranges from 0.2 up to 5%.. The prevalence of positive patch tests to corticosteroids in Switzerland was determined in a multi-centre study of patients undergoing routine patch tests.. As representatives of corticosteroid groups, the following substances were used for screening: tixocortol pivalate and hydrocortisone for group A (hydrocortisone type), hydrocortisone butyrate for group D (hydrocortisone butyrate type) and budesonide for both groups B (triamcinolone type) and D. Patients positive for at least one corticosteroid were retested with the screening series and 12 corticosteroids commonly used in Switzerland.. Among 3,016 consecutive patients, 65 individuals (2.2%) with a total of 106 positive reactions were found. Retesting showed a concordance of 70-98%, depending on the corticosteroid and the score of the positive reaction. In the subsequently tested corticosteroid series including 12 substances, 19 out of 56 screening-positive patients had a positive result to one or several corticosteroids. There were only few evident cross-reactive patterns in between the corticosteroids tested.. Corticosteroids should be included in routine patch testing, because contact sensitization to a corticosteroid is of considerable practical importance. We confirm that as markers of corticosteroid sensitization tixocortol pivalate, budesonide and hydrocortisone butyrate may be suited, because there is no single corticosteroid which is a marker for all four corticosteroid groups. Patch test reactions of 2+ or higher have a better reproducibility than 1+ reactions.

Topics: Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Budesonide; Child; Cross Reactions; Dermatitis, Contact; Drug Eruptions; Female; Humans; Hydrocortisone; Male; Middle Aged; Patch Tests; Pregnenediones; Prevalence; Switzerland

Topics: Adult; Aerosols; Bronchodilator Agents; Budesonide; Dermatitis, Contact; Drug Hypersensitivity; Female; Humans; Nasal Mucosa; Nasopharyngitis; Pregnenediones; Rhinitis; Skin Tests

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Budesonide; Dermatitis, Contact; Drug Eruptions; Female; Glucocorticoids; Humans; Pregnenediones

Topics: Administration, Cutaneous; Adult; Anti-Inflammatory Agents; Budesonide; Dermatitis, Contact; Drug Eruptions; Glucocorticoids; Humans; Male; Pregnenediones

Topics: Administration, Topical; Adult; Aerosols; Anti-Inflammatory Agents; Budesonide; Cross Reactions; Dermatitis, Contact; Drug Eruptions; Female; Glucocorticoids; Humans; Pregnenediones; Triamcinolone

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Budesonide; Dermatitis, Contact; Drug Eruptions; Eczema; Glucocorticoids; Humans; Male; Pregnenediones

Topics: Aerosols; Bronchodilator Agents; Budesonide; Dermatitis, Contact; Female; Humans; Middle Aged; Patch Tests; Pregnenediones

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Budesonide; Dermatitis, Contact; Desonide; Female; Glucocorticoids; Humans; Pregnenediones

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Budesonide; Dermatitis, Contact; Drug Eruptions; Female; Glucocorticoids; Humans; Pregnenediones

The systemic and topical antiinflammatory activities of budesonide (B) were studied in rats and mice and compared with those of commercially available steroids. Betamethasone 17-valerate (BV) was used as the main reference compound, and fluosinolone acetonide (FA), hydrocortisone 17-butyrate (HB) and hydrocortisone 21-acetate (HA) were also used. B given systemically had stronger antiinflammatory effect than BV on carrageenin edema, cotton pellet granuloma, adjuvant arthritis, croton oil edema, PCA reaction, Arthus reaction, contact hypersensitivity and histamine or serotonin skin reaction. The potency of antiinflammatory activity of the 5 compounds in carrageenin edema, croton oil edema and contact hypersensitivity tests was in the order of FA, B, BV, HB and HA. B given locally also produced stronger antiinflammatory effects than BV on carrageenin edema, cotton pellet granuloma, croton oil edema and contact hypersensitivity. The order of potency of the 5 compounds in carrageenin edema, croton oil edema and contact hypersensitivity tests was the same as by systemic application. In general, the ratio of the dose required to cause atrophy of the thymus and adrenals to the dose required to produce the antiinflammatory effect was the greatest with B by both systemic and local application. The results suggest that B has a stronger antiinflammatory activity with fewer systemic side effects than conventional steroid compounds.

Topics: Adrenal Gland Diseases; Animals; Anti-Inflammatory Agents; Budesonide; Dermatitis; Dermatitis, Contact; Drug Evaluation, Preclinical; Lymphatic Diseases; Mice; Mice, Inbred ICR; Pregnenediones; Rats; Rats, Inbred Strains; Thymus Gland

The antiinflammatory effect of topically applied budesonide ointment on carrageenin induced paw edema in rats, croton oil induced ear edema in rats, passive cutaneous anaphylaxis (PCA) in rats and picrylchloride induced contact hypersensitivity in mice was studied and compared with those of commercially available ointments containing betamethasone 17-valerate, hydrocortisone 21-acetate, hydrocortisone 17-butyrate or fluocinonide. The five ointments had almost the same degree of activity against the carrageenin induced paw edema. Budesonide ointment was strongest in inhibiting the croton oil induced ear edema. Budesonide and fluocinonide ointments were stronger than the other 3 ointments in inhibiting PCA and picrylchloride induced hypersensitivity. No clear atrophic effect on the thymus or adrenal was observed with any of the ointments at the doses tested. When the effect of budesonide ointment was compared with that of budesonide cream, there were no differences in activity between the two formulations. The results suggest that budesonide is a useful drug with a superior topical antiinflammatory activity.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Budesonide; Dermatitis; Dermatitis, Contact; Edema; Emulsions; Mice; Mice, Inbred ICR; Ointments; Passive Cutaneous Anaphylaxis; Pregnenediones; Rats; Rats, Inbred Strains

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Budesonide; Dermatitis, Contact; Female; Glucocorticoids; Humans; Methylprednisolone; Pregnenediones; Psoriasis; Triamcinolone Acetonide