Amcinonide has not been studied during breastfeeding. Since only extensive application of the most potent corticosteroids may cause systemic effects in the mother, it is unlikely that short-term application of topical corticosteroids would pose a risk to the breastfed infant by passage into breastmilk. However, it would be prudent to use the least potent drug on the smallest area of skin possible. It is particularly important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only the lower potency corticosteroids should be used on the nipple or areola where the infant could directly ingest the drugs from the skin. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[1] Any topical corticosteroid should be wiped off thoroughly prior to nursing if it is being applied to the breast or nipple area.

Emission of compounds with biological activities from waste water treatment plant (WWTP) effluents into surface waters is a topic of concern for ecology and drinking water quality. We investigated the occurrence of hormone-like activities in waste water sample extracts from four Dutch WWTPs and pursued to identify compounds responsible for them. To this aim, in vitro reporter gene bioassays for androgenic, anti-androgenic, estrogenic, glucocorticoid and progestogenic activity and a UPLC-tQ-MS target analysis method for 25 steroid hormones used in high volumes in pharmacy were applied. Principal component analysis of the data was performed to further characterize the detected activities and compounds. All five types of activities tested were observed in the WWTP samples. Androgenic and estrogenic activities were almost completely removed during WW treatment, anti-androgenic activity was only found in treated WW. Glucocorticoid and progestogenic activities persisted throughout the treatment. The androgenic activity in both influent could predominantly be attributed to the presence of androstenedione and testosterone. Anti-androgenic activity was explained by the presence of cyproterone acetate. The glucocorticoid activity in influent was fully explained by prednicarbate, triamcinolone acetonide, dexamethasone and amcinonide. In effluent however, detected hormones could only explain 10-32% of the activity, indicating the presence of unknown glucocorticoids or their metabolites in effluent. Progesterone and levonorgestrel could explain the observed progestogenic activity. The principle component analysis confirmed the way in which hormones fit in the spectrum of other emerging contaminants concerning occurrence and fate in WWTPs.

The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort (n = 115; p = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression (p = 0.002) and overall survival (p = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

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.

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 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.

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.

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.

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.

Annexin 1 (named p35, lipocortin I or calpactin II), initially described as a glucocorticoid induced protein, belongs to a new characterized family of intracellular proteins. In the skin, the role of annexins has still not been elucidated. In a previous study, we reported the localization of annexin 1 in both freshly isolated human epidermal cells and in cultured keratinocytes using immunofluorescence, FACS analysis and immunoblotting techniques. The protein was characterized by Western blot and immunoprecipitation as a 35 kDa protein. Results from in vivo studies confirmed the presence of annexin 1 in basal and suprabasal layers of normal human skin with modified reactivity patterns in hyperproliferative lesions. In the present study, the role of glucocorticoids in annexin 1 regulation was investigated in epidermal cells by Western blot and immunoprecipation assays. In contrast to other studies, we found that glucocorticoid treatment of epidermal cells led to a decrease in annexin 1 content in the cytoplasm and the membranes of cells. As annexin 1 was not detected in the nucleus of cells, we conclude that there was a down regulation of annexin 1 after glucocorticoid treatments rather than a translocation of the protein to the nucleus. Despite the absence of the signal peptide sequence necessary for protein secretion, annexin 1 was released in the keratinocyte culture medium. We found that the protein was secreted only in low Ca2+ medium (0.15 mM), this process required an active metabolism.

5 cases of allergic contact dermatitis due to budesonide are described. We studied the antigen determinant structures in these cases by applying patch tests with several substances related to budesonide. 2 cases showed cross-reactions to both amcinonide and prednisolone acetate. The antigen determinant structure is also discussed.

The patient, a 34-year-old Japanese woman who noticed worsening of her rash after using topical corticosteroid preparations on her neck, was patch tested for both commercial preparations and corticosteroids themselves. The patch test results revealed that she had a contact allergy to gold, oxytetracycline, and 2 types of corticosteroid (acetonides and esters) in 7 compounds (betamethasone valerate and dipropionate, hydrocortisone butyrate and hydrocortisone butyrate propionate, amcinonide, budesonide, and fluocinonide).

Three women with suspected contact allergies to topical corticosteroids had positive patch test reactions to amcinonide, triamcinolone acetonide and budesonide, two of them also reacted to tixocortol pivalate. Doubtful patch test results were seen on hydrocortisone and Alfasone cream. On performing a ROAT (repeated open application test) with amcinonide in all women we saw massive erythematous reactions and spreading urticaria. ROAT with Betnesol-V cream was negative. Two of the women, who were older, had multiple sensitization owing to long-term treatment of venous ulcers over many years. The third woman was young and had acquired the allergy through short-term treatment of prurigo with various topical corticosteroids. Contact allergy to topical corticosteroids is frequent and should be borne in mind in daily practice. Especially when chronic dermatitis is difficult to manage, cross reactions between chemically related corticosteroids should be considered.

Patients who noticed worsening of their skin disease after using topical corticosteroid preparations were patch tested both with the commercial preparation and the corticosteroid itself. Between 1987 and 1989, 10 cases of contact dermatitis due to topical corticosteroids were detected in this way. The corticosteroids wee amcinonide (2 patients), hydrocortisone butyrate, clobetasol propionate (2), betamethasone valerate (2), prednicarbate and fluocortolone (2). Patch tests with the commercial preparations and the corticosteroids themselves elicited reactions almost identical in time course and severity. Individual sensitivity seems to be more important for test results than test conditions. 9 of the 10 patients underwent further patch testing with a corticosteroid series. In 2 patients, a true cross-reaction between budesonide and hydrocortisone butyrate was found. All 9 patients showed further sensitivities to other corticosteroids. Most of the cross or concomitant reactions could be categorized into recently defined corticosteroid classes. To improve our understanding of corticosteroid sensitization, and to help the patient avoid reactions to other topical corticosteroids, a corticosteroid series should be patch tested in every case of corticosteroid sensitivity.

Topical applications of monobenzylether of hydroquinone (MBEH) or intraperitoneal injections of phenol induced graying of hair in eumelanic mice but had little effect on hair color in pheomelanic mice. Amcinonide, an anti-inflammatory agent, elicited whitening of a few hairs in both pheomelanic and eumelanic mice. In phenol-treated eumelanic mice, damaged follicular melanocytes were uprooted from hair bulbs and incorporated into the developing hair. The fate of follicular melanocytes in MBEH- or amcinonide-treated mice was not determined since hair growth and graying were more variable than in phenol-treated mice. In contrast to the susceptibility of eumelanic hair follicles to depigmentation by phenol or MBEH, the tail skin of eumelanic or pheomelanic mice was not depigmented by these agents. Overall, during the 3 week period of treatment that was sufficient for phenol or MBEH to elicit graying of hair, epidermal melanocytes of the tails of eumelanic or pheomelanic mice either failed to respond (phenol) or were stimulated in their "proliferative" and melanogenic activity (MBEH). In contrast, amcinonide brought about a marked reduction in the numbers of DOPA-positive epidermal melanocytes inhabiting the tails of eumelanic or pheomelanic mice. Amcinonide exerted a deleterious influence on the structure and function of tail epidermis. Its actions were partly reversed by simultaneous treatment with MBEH but not with prostaglandin (PGE2).

22 cases of allergic contact dermatitis from topical corticosteroids were observed in Strasbourg and previously published. 7 further cases are reported here and the vehicle and concentration of corticosteroids for patch tests are discussed. A 0.1% concentration in petrolatum seemed adequate for testing the 4 molecules (triamcinolone acetonide, dexamethasone, desonide and amcinonide) responsible for the 7 new cases. In 1 case, several cross-reactions were seen. A corticosteroid screening series permits patch testing of the suspected molecule(s) in a selective way. Without this series, long delays are required to make the correct diagnosis by patch testing. We have reviewed more than 60 papers on corticosteroid allergy published up to now.

Serine protease inhibitors with a specificity for trypsin inhibit interferon-gamma (INF-gamma)-induced HLA-DR expression on a hybrid human epidermal cell line (H12), dermal fibroblasts, and primary keratinocytes. Protease inhibitors with a specificity for chymotrypsin or papain fail to inhibit IFN-gamma. The inhibitory effect of the trypsin inhibitors is similar to that of glucocorticoids in that it is a transient event, fading with length of exposure to IFN-gamma, and is reversed by the addition of dibutyryl cyclic AMP (dbcAMP) and phospholipase C(PLC) from Clostridium perfringens. In H12 cells, dbcAMP and PLC enhance the IFN-gamma induction of HLA-DR, but do not induce in the absence of INF-gamma. Evidence suggests that the protease inhibitors, as well as dbcAMP and PLC, may modulate HLA-DR expression at a post-translational site as well as during IFN-gamma signal transduction. These results suggest that trypsin-like protease activity may be required for cellular HLA-DR antigen expression following exposure to IFN-gamma.

In 15 subjects 6 different parts of the body were treated with the potent topical corticosteroid (CS) amcinonide once a day for 21 days. The skin thickness of the treated areas was measured sonographically at intervals of 2 days. After completion of the CS application the regression of the CS-induced reduction in skin thickness was measured for a further 14 days. A clear thinning of the skin could be measured after only 4 days and continued up to the 21st day of treatment. This thinning regressed completely in all areas after 10-12 days. The thinning and regression curves were very similar for all body areas. Differences in intensity of thinning were evident. No tachyphylaxis was detected.

In order to classify the new topical preparations amcinonide cream and prednicarbate cream according to the order of potency laid down by the EEC commission, we performed a number of test series in healthy young persons. Betamethasone valerate cream, clobestasol propionate cream, flumethasone pivalate cream, hydrocortisone butyrate cream, and hydrocortisone cream were comparatively tested. In addition, we included a cream base without any active substances in every test series. By means of the vasoconstriction test we were able to establish the order of rank according to potency starting from clobetasol propionate to hydrocortisone. Thus amcinonide was classified as a very strong corticoid preparation, whereas prednicarbate turned out to be moderately strong. The differences in potency between clobetasol propionate and amcinonide on the one hand and prednicarbate, flumethasone pivalate and hydrocortisone on the other hand were definitely proved (p less than 0.01). Further comparative studies were conducted on the basis of the kerosene test, the sorbic acid test, the prick test with codeine, and the anthralin inflammatory test. Moreover, the preparations underwent the formic acid test. The rank orders displayed in the individual tests largely agreed with that obtained by the vasoconstriction test. The exact differences in potency, however, were not as easy to define with the inflammatory tests. Thus the vasoconstriction test must still be considered an excellent screening technique with regard to the selection of corticoid preparations. Subsequently, these preparations should be investigated by means of clinical tests according to their ascertained potencies.

In this investigation skin fold thinning was determined after topical application of several potent corticosteroids in hairless mice using a simple mechanical measuring device. The skin thinning effect of prednicarbate was compared with other corticosteroids (amcinonide, beta-methasone-17-valerate, clobetasol-17-propionate, diflorasone-17,21-diacetate, hydrocortisone-21-acetate). Prednicarbate produced a clear thinning of skin. Like other tested dermatocorticoids prednicarbate caused a significant atrophy of the mouse tail epidermis. By prednicarbate the 3H-thymidine triphosphate incorporation into epidermal DNA was inhibited.