- Steroid hormonal bioactivities, culprit natural and synthetic hormones and other emerging contaminants in waste water measured using bioassays and UPLC-tQ-MS. [Journal Article]
- STSci Total Environ 2018 Jul 15; 630:1492-1501
- 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 th...
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.
- DAPK1 as an independent prognostic marker in liver cancer. [Journal Article]
- PPeerJ 2017; 5:e3568
- 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 progno...
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.
- Identification and characterization of triamcinolone acetonide, a microglial-activation inhibitor. [Journal Article]
- IIImmunopharmacol Immunotoxicol 2012; 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 neurop...
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. [Multicenter Study]
- JDJ Dtsch Dermatol Ges 2009; 7(1):34-41, 34-42
- CONCLUSIONS: 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]
- PDPharmacoepidemiol Drug Saf 2008; 17(8):813-21
- CONCLUSIONS: 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]
- CDContact Dermatitis 2003; 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 th...
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]
- OOrthopedics 2002; 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 yea...
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]
- CDContact Dermatitis 2001; 45(4):232-3
- Patch testing with serial dilutions of budesonide, its R and S diastereomers, and potentially cross-reacting substances. [Journal Article]
- AJAm J Contact Dermat 2001; 12(3):170-6
- CONCLUSIONS: 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.
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- Tixocortol pivalate contact allergy in the GPMT: frequency and cross-reactivity. [Journal Article]
- CDContact Dermatitis 2001; 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 ...
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.