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- Identification and characterization of triamcinolone acetonide, a microglial-activation inhibitor. [Journal Article, Research Support, Non-U.S. Gov't]
- Immunopharmacol Immunotoxicol 2012 Dec; 34(6):912-8.
Recent studies show that necrotic neuronal cells (NNC) activate microglia, thereby leading to neuronal cell death. This suggests that chemicals that inhibit microglia activation may be used as neuroprotective drugs. In this context, we screened a chemical library for inhibitors of microglia activation. Using a screening system based on a nitrite assay, we isolated two chemicals that inhibit nitric oxide (NO) release from activated microglia: triamcinolone acetonide (TA) and amcinonide. The half-maximal inhibitory concentrations (IC50) of TA and amcinonide for NO release inhibition were 1.78 nM and 3.38 nM, respectively. These chemicals also inhibited NNC-induced expression of the proinflammatory genes iNOS, TNF-α, and IL-1β in glial cells. A study based on a luciferase assay revealed that TA attenuated NNC-induced microglia activation by blocking the NF-κB signaling pathway. In addition, TA protected cortical neurons in coculture with microglia from LPS/IFN-γ-induced neuronal cell death. In conclusion, TA may inhibit microglia activation and may protect neuronal cells from death induced by microglial activation.
- Contact allergy to topical corticosteroids--results from the IVDK and epidemiological risk assessment. [Journal Article, Multicenter Study]
- J Dtsch Dermatol Ges 2009 Jan; 7(1):34-41, 34-42.
Contact allergy (CA) to topical corticosteroids (CS) is relatively rare; however, current data from Germany are not available. Furthermore, valid risk assessment needs to take into account of the actual exposure to CS in the population.The reaction profile of 9 CS included in a "CS test battery" of the German Contact Dermatitis Research Group (DKG) in patients seen in German clinics belonging to the Information Network of Departments of Dermatology (IVDK; http://www.ivdk.org) between 01/1995 and 12/2004 was analyzed. Applying the "Clinical Epidemiology/Drug Utilization Research" approach, annual incidences of CA to CS in Germany were extrapolated. These estimates were used as numerator for a relative incidence (RI) estimate which used exposure in terms of "defined daily doses" (DDD) to the respective CS as denominator, the latter information collected by the AOK Research Institute (WIdO).On average, 7.4% of all patients were patch tested with the CS series, mostly yielding < 1% positive reactions. Exceptions included hydrocortisone 17-butyrate (1.5%), amcinonide (1.6%) and budesonide (2.6%). With a RI of 10.7, 23.6 and 4.9 per 100,000 DDD, respectively, the three CS mentioned classify as moderate topical drug allergens. Clobetasol 17-propionate and triamcinolone acetonide both yielded a RI of 1.4/100,000 DDD, indicating low sensitization risk. For hydrocortisone, betamethasone, prednisolone and dexamethasone (RI < 1/100,000 DDD) the risk of sensitization appears minute.The results support and extend previous evidence on the CA risk of CS, adding to a therapeutic index and risk assessment.
- Allergic contact dermatitis to topical drugs--epidemiological risk assessment. [Journal Article]
- Pharmacoepidemiol Drug Saf 2008 Aug; 17(8):813-21.
Estimation of the population-based relative incidence (RI) of contact sensitization to a set of topical drug allergens (cases/100,000 defined daily doses (DDDs) per year) (1995-2004) and comparison of the RI for drugs with a similar therapeutic scope.Clinical data regarding the frequency of contact sensitization to important topical drug allergens in Germany were obtained from the Information Network of Departments of Dermatology (IVDK). This was extrapolated to the general population level using the 'clinical epidemiology and drug utilization research' (CE-DUR) approach. As denominator of exposure, national prescription data (DDDs of topical drug specialties) provided by the WIdO Research Institute (Bonn) were aggregated per substance.The probable RIs of contact sensitization to topical 'skin' corticosteroids ranged from 0.3 (dexamethasone phosphate disodium salt) to 23.3 (amcinonide) cases/100,000 DDDs per year. Concerning topical aminoglycoside antibiotics, the RI of framycetin sulphate was about threefold higher than that of gentamicin sulphate. Regarding topical ophthalmic use, the RI of kanamycin sulphate was higher compared to gentamicin sulphate. Active principles marketed over-the-counter (OTC) had, in general, lower RIs, with the exception of bufexamac, benzocaine, clioquinol and phenylephrine.The population-based risk assessment--quantitatively considering exposure in the RI estimation--revealed a ranking of contact sensitization risk to topical drugs which partly differed from the respective frequencies in the clinical patch test population. Some drugs available OTC carry non-negligible risk, too. The current findings should contribute to differential therapeutic considerations regarding topical drug use.
- Angioedema and dysphagia caused by contact allergy to inhaled budesonide. [Case Reports, Journal Article]
- Contact Dermatitis 2003 Aug; 49(2):77-9.
Inhaled corticosteroids may cause various adverse effects ranging from irritation to severe anaphylactic reactions and systemic contact dermatitis. We report a 43-year-old woman who developed sore throat, swelling of the lips and oral cavity and dysphagia, 2 weeks after the use of budesonide spray (Budefat) for treatment of bronchial asthma. The symptoms occurred with a delay of 3-4 h after the treatment x2 daily. There were no immediate reactions on prick and intracutaneous testing with the commercial product used by the patient. However, marked pruritic infiltration developed within 24 h, progressing to coalescing eczematous lesions over the following 2 days. In addition, severe oedema of the right upper eyelid was observed. On patch testing, budesonide was strongly positive at day 2 and 3 in a concentration ranging from 1% to 10 p.p.m. (in petrolatum). Other corticosteroids of group A, B, C and D were completely negative. Repeated open application tests with amcinonide and triamcinolone acetonide cream on the ventral aspect of the upper arm were negative. Bronchial exposure to alternative sprays containing beclomethasone dipropionate (group D), fluticasone-17- propionate (D) and dexamethasone-21-isonicotinate (C) was well tolerated. In conclusion, this case is instructive, because the symptoms which developed after a short period of corticosteroid inhalation suggested a type I allergy. Testing proved a severe type IV contact allergy restricted to budesonide (group B), without cross-reactions to major corticosteroids of other groups.
- Selective corticosteroid injection into the extensor pollicis brevis tenosynovium for de Quervain's disease. [Journal Article]
- Orthopedics 2002 Jan; 25(1):68-70.
Selective corticosteroid injection into the extensor pollicis brevis tenosynovium was performed in 50 patients (7 men and 43 women; 53 hands) with de Quervain's disease. Mean patient age was 32.4 years and mean follow-up was 4.1 years. Before selective injection into the extensor pollicis brevis tenosynovium, the extensor pollicis brevis tendon was palpated at the distal ulnar side of the first compartment, with dorsal and volar flexion of the first metacarpophalangeal joint. A 27-gauge needle was placed along the extensor pollicis brevis tendon and into the distal entrance of the extensor pollicis brevis tenosynovium selectively, and 10 mg of 40 mg/mL triamcinolone acetonide and 0.25 mL of 1% xylocaine were combined and injected. Forty-six hands had relief of pain following a single injection. Six hands required a second injection and 1 hand required a third injection. Ultimately, all 53 hands had satisfactory results by selective extensor pollicis brevis injection alone, and no patients required surgical treatment.
- Exacerbation of allergic contact dermatitis from amcinonide triggered by patch testing. [Case Reports, Journal Article]
- Contact Dermatitis 2001 Oct; 45(4):232-3.
- Patch testing with serial dilutions of budesonide, its R and S diastereomers, and potentially cross-reacting substances. [Journal Article, Research Support, Non-U.S. Gov't]
- Am J Contact Dermat 2001 Sep; 12(3):170-6.
Budesonide, a marker for corticosteroid allergy, is a 1:1 mixture of 2 diastereomers, the R and S, present in all commercial formulations. Budesonide is said to cross-react with group B substances through the R and S diastereomer and some group D substances only through the S diastereomer.To investigate the cross-reactivity pattern between the R and S diastereomers and 4 potentially cross-reacting substances, 2 from group B and 2 from group D.By patch testing 10 patients hypersensitive to budesonide with a serial dilution of budesonide, the R and S diastereomer, triamcinolone acetonide, amcinonide, prednicarbate, and hydrocortisone-17-butyrate.Nine of 10 patients reacted to budesonide and the S diastereomer. Seven of 9 to the R diastereomer. Each of the 9 patients with S diastereomer allergy reacted to the group B and/or group D substances. Five patients reacted to triamcinolone acetonide, not to 1.0% but only to 0.0010% and 0.00010%.The R and S diastereomers can induce positive patch test reactions in budesonide-hypersensitive individuals. The potential of budesonide to cross-react with substances from group B and D might be explained by the presence of the 2 diastereomers. When patch testing with triamcinolone acetonide, much lower concentrations than recommended should be used.
- Tixocortol pivalate contact allergy in the GPMT: frequency and cross-reactivity. [Comparative Study, Journal Article, Research Support, Non-U.S. Gov't]
- Contact Dermatitis 2001 Jan; 44(1):18-22.
In spite of their intrinsic anti-inflammatory properties, corticosteroids can induce contact allergy. When studying the allergenic properties of corticosteroids it has to be considered that both the allergenic and anti-inflammatory effect may influence the induction phase as well as the elicitation phase and that such effects may be dose-dependent. A multiple dose guinea pig maximization test (GPMT) was therefore used to study the dose-response relationship of tixocortol pivalate. The GPMT was conducted according to OECD guideline #406, using a multiple-dose design and test results were analysed with logistic regression analysis. There was a significant tixocortol pivalate sensitization of the test animals compared to the control group (p<0.05), after both challenge and re-challenge. The challenge with 1% tixocortol pivalate gave more positive reactions than the challenge with 3%. The highest frequency of positive animals was observed when the animals were treated with low to intermediate induction concentrations and intermediate to high challenge concentrations with tixocortol pivalate in the TRUE Test. Cross-reactivity was found between tixocortol pivalate and hydrocortisone, which was expected from their close molecular resemblance, whereas no cross-reactivity was seen between tixocortol pivalate and the 3 other corticosteroids: amcinonide, budesonide, and hydrocortisone-17-butyrate.
- Delayed generalized allergic reactions to corticosteroids. [Case Reports, Journal Article]
- Dermatology 2000; 200(4):349-51.
A 37-year-old patient presented with a severe allergic local reaction upon inhalation of budesonide for asthma. Skin tests were positive for budesonide and amcinonide (group B) and elicited a strong local reaction and a disseminated macular exanthema. Corticosteroids from other groups were well tolerated. A 38-year-old male patient had first an allergic contact dermatitis to topically applied prednisolone acetate and then a disseminated eczematous exanthema upon oral intake of prednisone. A delayed-type sensitization to corticosteroids from group A such as hydrocortisone, prednisone and tixocortol pivalate was identified. A detailed diagnosis in patients with allergic reactions to corticosteroids is crucial with regard to their use in emergency therapy.
- Pemphigoid and pemphigus foliaceus successfully treated with topical corticosteroids. [Case Reports, Journal Article]
- J Dermatol 1996 Oct; 23(10):683-8.
Six patients with pemphigoid and three patients with pemphigus foliaceus were successfully treated with topical corticosteroids. This was especially effective in cases of pretibial localized pemphigoid and in mild cases of bullous pemphigoid and pemphigus foliaceus with negative or low-titer circulating autoantibodies.