Physiological and transcriptional effects in the male western mosquitofish (Gambusia affinis) following exposure to dexamethasone.

Dexamethasone (DEX) is a synthetic glucocorticoid widely found in a variety of aquatic environments and has potential adverse effects on aquatic organisms. This study was to assess the toxic effects of exposure to different concentrations (0, 5 and 50 µg/L) of DEX for 60 days on adult male mosquitofish (Gambusia affinis). Morphological analyses of skeleton and anal fin, histological effects of testes and livers, and transcriptional expression levels of genes related to reproductive and immune system were determined. The results showed that exposure to DEX significantly increased 14L and 14D values of hemal spines, which suggested DEX could affect skeleton development and result in more masculine characteristics in male fish. In addition, the damage to testis and liver tissue was observed after DEX treatment. It also enhanced mRNA expression of Erß gene in the brain and Hsd11b1 gene in the testis. The findings of this study reveal physiological and transcriptional effects of DEX on male mosquitofish.

Screening for drugs potentially interfering with MCT8-mediated T3 transport in vitro identifies dexamethasone and some commonly used drugs as inhibitors of MCT8 activity.

BACKGROUND: Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity. AIM: This study aimed at investigating whether some common drugs having a structural similarity with TH and/or whose treatment is associated with thyroid function test abnormalities, or which behave as antagonists of TH action can inhibit MCT8-mediated T3 transport. METHODS: [125I]T3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of hydrocortisone, dexamethasone, prednisone, prednisolone, amiodarone, desethylamiodarone, dronedarone, buspirone, carbamazepine, valproic acid, and L-carnitine. The mode of inhibition was also determined. RESULTS: Dexamethasone significantly inhibited T3 uptake at 10 µM; hydrocortisone reduced T3 uptake only at high concentrations, i.e. at 500 and 1000 µM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T3 uptake by MCT8 only at the highest concentrations used (44% at 50 µM and 68% at 100 µM), and this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T3 uptake at 0.1-10 µM. L-Carnitine inhibited T3 uptake only at 500 mM and 1 M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T3 uptake did not affect T3 release. CONCLUSION: This study shows a novel effect of some common drugs, which is inhibition of T3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, and dronedarone behave as potent inhibitors of MCT8.

Stability of dexamethasone sodium phosphate over a 28 day period when added to commercial veterinary wipe and pad products.

Background - Topical glucocorticoids commonly are used in the management of canine atopic dermatitis to control and prevent allergy flares. Compounding commercial veterinary wipe/pad products to include dexamethasone sodium phosphate (Dex SP) can simplify treatment protocols for owners. Dex SP has not been evaluated for stability when added to wipes/pads. Hypothesis/objective - To evaluate the stability of Dex SP when compounded in three commercial veterinary wipe/pad products containing chlorhexidine. Methods and materials - Dex SP (Dexium, Bimeda; Oakbrook Terrace, IL, USA) was added to TrizCHLOR 4 wipes (TCL; Dechra Veterinary Products; Overland Park, KS, USA), KetoHex wipes (KH; VetOne; Boise, ID, USA), and DOUXO Chlorhexidine Pads (DCP; Ceva Animal Health; Lenexa, KS, USA), creating a 0.04% Dex SP solution. The concentration of Dex SP was measured in µg/mL/wipe or pad in triplicate at Day (D)0, D14 and D28 using liquid chromatography with tandem mass spectrometry. The amount of Dex SP at baseline (D0) was compared to the amount recovered at D14 and D28. Results - The amount of Dex SP in TCL and KH was unchanged between D0, D14 and D28. The amount of Dex SP recovered from DCP on D0 (mean 89.40 µg/mL/pad), D14 (mean 65.58 µg/mL/pad) and D28 (mean 68.09 µg/mL/pad) revealed a significant decline from D0 to D14 (P = 0.004). Conclusions and clinical importance - These data provide evidence that Dex SP is stable for 28 days in TCL and KH, and not in DCP from D0 to D14 or D28 days.

Contexte - Les glucocorticoïdes topiques sont couramment utilisés dans la prise en charge de la dermatite atopique canine pour contrôler et prévenir les poussées allergiques. La composition de produits commerciaux de lingettes / tampons vétérinaires pour inclure du phosphate de dexaméthasone sodique (Dex SP) peut simplifier les protocoles de traitement pour les propriétaires. Dex SP n'a pas été évalué pour la stabilité lorsqu'il est ajouté aux lingettes/tampons. Hypothèse/objectif - Évaluer la stabilité de Dex SP lorsqu'il est mélangé dans trois produits commerciaux de lingettes/tampons vétérinaires contenant de la chlorhexidine. Matériels et méthodes - Dex SP (Dexium, Bimeda; Oakbrook Terrace, IL, États-Unis) a été ajouté aux lingettes TrizCHLOR 4 (TCL; Dechra Veterinary Products; Overland Park, KS, États-Unis), aux lingettes KetoHex (KH; VetOne; Boise, ID, États-Unis) et DOUXO Chlorhexidine Pads (DCP ; Ceva Animal Health ; Lenexa, KS, États-Unis), créant une solution de Dex SP à 0,04 %. La concentration de Dex SP a été mesurée en µg/mL/lingette ou tampon en triple exemplaire aux jours (J)0, J14 et J28 par chromatographie liquide avec spectrométrie de masse en tandem. La quantité de Dex SP à l'inclusion (J0) a été comparée à la quantité récupérée à J14 et J28. Résultats - La quantité de Dex SP dans le TCL et le KH était inchangée entre J0, J14 et J28. La quantité de Dex SP récupérée du DCP à J0 (moyenne 89,40 µg/mL/pad), J14 (moyenne 65,58 µg/mL/pad) et J28 (moyenne 68,09 µg/mL/pad) a révélé une baisse significative de J0 à J14 (P = 0,004). Conclusions et importance clinique - Ces données fournissent des preuves que Dex SP est stable pendant 28 jours en TCL et KH, et non en DCP de J0 à J14 ou J28 jours.

Introducción- los glucocorticoides tópicos se usan comúnmente en el tratamiento de la dermatitis atópica canina para controlar y prevenir los brotes de alergia. La combinación de productos comerciales de toallitas/apósitos veterinarios para incluir fosfato sódico de dexametasona (Dex SP) puede simplificar los protocolos de tratamiento para los propietarios. No se ha evaluado la estabilidad de Dex SP cuando se agrega a toallitas/apósitos. Hipótesis/objetivo- evaluar la estabilidad de Dex SP cuando se mezcla en tres productos comerciales de toallitas/apósitos veterinarios que contienen clorhexidina. Métodos y materiales- se agregó Dex SP (Dexium, Bimeda; Oakbrook Terrace, IL, EE. UU.) a las toallitas TrizCHLOR 4 (TCL; Dechra Veterinary Products; Overland Park, KS, EE. UU.), toallitas KetoHex (KH; VetOne; Boise, ID, EE. UU.) y los apósitos de clorhexidina DOUXO (DCP; Ceva Animal Health; Lenexa, KS, EE. UU.), creando una solución de Dex SP al 0,04 %. La concentración de Dex SP se midió en µg/mL/toallita o apósito por triplicado en el día (D)0, D14 y D28 usando cromatografía líquida con espectrometría de masas en tándem. La cantidad de Dex SP al inicio (D0) se comparó con la cantidad recuperada en D14 y D28. Resultados- la cantidad de Dex SP en TCL y KH no cambió entre D0, D14 y D28. La cantidad de Dex SP recuperada de DCP en D0 (media de 89,40 µg/ml/almohadilla), D14 (media de 65,58 µg/ml/almohadilla) y D28 (media de 68,09 µg/ml/almohadilla) reveló una disminución significativa de D0 a D14 (P = 0,004). Conclusiones e importancia clínica- estos datos proporcionan evidencia de que Dex SP es estable durante 28 días en TCL y KH, y no en DCP de D0 a D14 o D28 días.

Contexto - Os glicocorticoides tópicos são comumente usados no manejo da dermatite atópica canina para controlar e prevenir crises alérgicas. A inclusão de incluir fosfato sódico de dexametasona (Dex SP) na fórmula de produtos comerciais em lenços/toalhas veterinárias pode simplificar os protocolos de tratamento para os proprietários. Dex SP não foi avaliado quanto à estabilidade quando adicionado a lenços/toalhas. Hipótese/objetivo - Avaliar a estabilidade do Dex SP quando formulado em três lenços/almofadas veterinárias comerciais contendo clorexidina. Métodos e materiais - Dex SP (Dexium, Bimeda; Oakbrook Terrace, IL, EUA) foi adicionado aos lenços TrizCHLOR 4 (TCL; Dechra Veterinary Products; Overland Park, KS, EUA), lenços KetoHex (KH; VetOne; Boise, ID, EUA) e DOUXO Chlorhexidine Pads (DCP; Ceva Animal Health; Lenexa, KS, EUA), criando uma solução de Dex SP a 0,04%. A concentração de Dex SP foi medida em µg/mL/lenço ou almofada em triplicata no Dia (D)0, D14 e D28 utilizando cromatografia líquida com espectrometria de massa em tandem. A quantidade de Dex SP no dia zero (D0) foi comparada com a quantidade recuperada em D14 e D28. Resultados - A quantidade de Dex SP em TCL e KH permaneceu inalterada entre D0, D14 e D28. A quantidade de Dex SP mensurada no DCP em D0 (média de 89,40 µg/mL/lenço), D14 (média de 65,58 µg/mL/lenço) e D28 (média de 68,09 µg/mL/lenço) revelou uma redução significativa de D0 para D14 (P=0,004) Conclusões e importância clínica - Esses dados fornecem evidências de que Dex SP é estável por 28 dias em TCL e KH, e não em DCP de D0 a D14 ou D28 dias.

Determination of dexamethasone acetate in CETETH 20-based in liquid crystalline systems using HPLC.

Dexamethasone acetate (DEX), a potent anti-inflammatory, is used primarily in the treatment of inflammatory and autoimmune diseases. It was incorporated in CETETH 20 (polyoxyethylene 20 cetyl alcohol)-based liquid crystalline systems to enhance the purpose of the drug. Concomitant with the pharmaceutical technology performed, a HPLC method was developed and validated for the quantification of dexamethasone acetate in CETETH 20-based liquid crystalline systems for the evaluation of the drug in the new matrix. The method was performed using a C18 column with acetonitrile:methanol:water (35:35:30, v/v/v) as the mobile phase at a flow rate of 0.8 mL min-1 at 239 nm. The method was linear in the range of 1-25 µg mL-1 ; the limit of quantification and limit of detection were 0.05 and 0.16 µg mL-1 , respectively; the accuracy of the method was 99.92% (relative standard deviation < 1%), and it presented intra-day and inter-day precision with deviations less than 1%. In this context, the method was successfully used to determine the incorporation efficiency of DEX in CETETH 20-based liquid crystalline systems and can be easily used by pharmaceutical companies and laboratories around the world.

Semiquantitative immunochromatographic colorimetric biosensor for the detection of dexamethasone based on up-conversion fluorescent nanoparticles.

A low-cost bifunctional immunochromatographic colorimetric biosensor was developed that can be read visually or by using an optical density scanner. Five test lines (T lines) coated with different antigens were set on a nitrocellulose (NC) membrane to indicate the concentration of analyte. This method was applied for the detection of dexamethasone. The corresponding detection range was 0.1-9 ng mL-1, and the detection limit for dexamethasone in food supplements and cosmetic samples was 2.0 µg kg-1. For visual inspection of the colour the quantitative relative error range between the proposed method and liquid chromatography was -62 to -25%, with a detection time of only 10 min. More accurate assay results were obtained by using an optical density scanner with the relative error range of -31 to 20%. The results indicated that the proposed method has the potential of application for rapid and efficient screening of dexamethasone in cosmetics and food supplements. Graphical abstract.

Qualifying X-ray and Stimulated Raman Spectromicroscopy for Mapping Cutaneous Drug Penetration.

Research on topical drug delivery relies on reconstructed human skin (RHS) in addition to ex vivo human and animal skin, each with specific physiological features. Here, we compared the penetration of dexamethasone from an ethanolic hydroxyethyl cellulose gel into ex vivo human skin, murine skin, and RHS. For comprehensive insights into skin morphology and penetration enhancing mechanisms, scanning transmission X-ray microscopy (STXM), liquid chromatography tandem-mass spectrometry (LC-MS/MS), and stimulated Raman spectromicroscopy (SRS) were combined. STXM offers high spatial resolution with label-free drug detection and is therefore sensitive to tissue damage. Despite differences in sample preparation and data analysis, the amounts of dexamethasone in RHS, detected and quantified by STXM and LC-MS/MS, were very similar and increased during the first 100 min of exposure. SRS revealed interactions between the gel and the stratum corneum or, more specifically, its protein and lipid structures. Similar to both types of ex vivo skin, higher protein-to-lipid ratios within the stratum corneum of RHS indicated reduced lipid amounts after 30 min of ethanol exposure. Extended ethanol exposure led to a continued reduction of lipids in the ex vivo matrixes, while protein integrity appeared to be compromised in RHS, which led to declining protein signals. In conclusion, LC-MS/MS proved the predictive capability of STXM for label-free drug detection. Combining STXM with SRS precisely dissected the penetration enhancing effects of ethanol. Further studies on topical drug delivery should consider the potential of these complementary techniques.

The application of a lateral flow immunographic assay to rapidly test for dexamethasone in commercial facial masks.

Dexamethasone (DE) is a synthetic glucocorticoid that is frequently added to cosmetic products for its good short-term effects, especially in facial masks, but long-term use is hazardous to the health. The abuse of DE in whitening and acne cosmetic products is currently a serious problem in China. It is necessary to establish a rapid method of detecting illegal DE addition in cosmetics. In the present study, a monoclonal antibody (mAb) against DE, 2D5-3D12, was developed that displayed cross-reactivities of 124.5%, 38.8%, 6.7%, 0.9%, 1.1%, 1.82%, and 2.39% with prednisolone, betamethasone, prednisone, beclomethasone, hydrocortisone, triamcinolone, and flumetasone, respectively. A colloidal gold-based lateral flow immunographic assay based on mAb 2D5-3D12 was established and used to determine the DE contents of commercial facial masks. The indicator range of the immunographic assay for DE was 100-200 ng/mL, and the results were consistent with those afforded by LC-MS. This novel method provides the advantages of simple sample treatment, a user-friendly procedure, and rapid detection. Graphical abstract.

The efficiency of UV/S2O8 2- photo-oxidation process in the presence of Al2O3 for the removal of dexamethasone from aqueous solution: kinetic studies.

This study aimed to investigate the efficiency of the UV/S2O8 2- photocatalytic process in the presence of Al2O3 nanoparticles for the removal of dexamethasone from aqueous solution. In this experimental study, the variables pH, persulfate concentration, initial concentration of dexamethasone, the catalyst dose were studied in order to investigate the process efficiency. Furthermore, the efficiency of UV/S2O8 2- in the presence and absence of catalyst was investigated. The Al2O3 nanoparticle catalyst was characterized using X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses and scanning electron microscopy (SEM) image. The results showed that a decrease in pH and the initial concentration of dexamethasone increased the process efficiency. Given the increased concentrations of the persulfate and Al2O3, the removal efficiency was partially increased. In UV/S2O8 2-/Al2O3 under optimum conditions (pH = 3, t = 30 minutes, dexamethasone concentration = 20 mg/L, 0.5 mM of persulfate, and UV radiation = 55 watts), 94% of the dexamethasone was removed. The kinetic response showed that the reaction data corresponded to the pseudo-first-order kinetic model. The results showed that the UV/S2O8 2- photochemical process can efficiently remove dexamethasone from aqueous solution in the presence of Al2O3 catalyst and the mineralization efficiency reached about 98%. Therefore, this process is recommended due to its high efficiency and availability for the removal of pharmaceutical compounds.

HPLC-UV method for simultaneous determination of sparfloxacin and dexamethasone sodium phosphate in eye drops.

A simple, sensitive liquid chromatographic method was developed and validated for the simultaneous estimation of sparfloxacin and dexamethasone sodium phosphate in bulk and pharmaceutical formulations. Optimum separation was achieved in less than 10 min using a C18 column (250 mmx4.6 mm i.d, 5µ particle size) by isocratic elution. The mobile phase consisting of a mixture of mixed phosphate buffer (pH 6.8) and acetonitrile (50:50, v/v) was used. Column effluents were monitored at 224nm at a flow rate of 1ml/min. Retention times of sparfloxacin and dexamethasone sodium phosphate were 3.01 and 6.47 min respectively. The linearity of sparfloxacin and dexamethasone sodium phosphate was in the range of 3-18µg/ml and 1-6µg/ml respectively. Developed method was economical because, the time taken and amount of solvent consumed for each analysis was less. The method was validated and was applied to the simultaneous determination of sparfloxacin and dexamethasone sodium phosphate in bulk and pharmaceutical formulations.

Facile preparation of magnetic molecularly imprinted polymers for the selective extraction and determination of dexamethasone in skincare cosmetics using HPLC.

Dexamethasone-imprinted polymers were fabricated by reversible addition-fragmentation chain transfer polymerization on the surface of magnetic nanoparticles under mild polymerization conditions, which exhibited a narrow polydispersity and high selectivity for dexamethasone extraction. The dexamethasone-imprinted polymers were characterized by scanning electron microscopy, transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive spectrometry, and vibrating sample magnetometry. The adsorption performance was evaluated by static adsorption, kinetic adsorption and selectivity tests. The results confirmed the successful construction of an imprinted polymer layer on the surface of the magnetic nanoparticles, which benefits the characteristics of high adsorption capacity, fast mass transfer, specific molecular recognition, and simple magnetic separation. Combined with high-performance liquid chromatography, molecularly imprinted polymers as magnetic extraction sorbents were used for the rapid and selective extraction and determination of dexamethasone in skincare cosmetic samples, with the accuracies of the spiked samples ranging from 93.8 to 97.6%. The relative standard deviations were less than 2.7%. The limit of detection and limit of quantification were 0.05 and 0.20 µg/mL, respectively. The developed method was simple, fast and highly selective and could be a promising method for dexamethasone monitoring in cosmetic products.

Long-term stability of dexamethasone and alizapride or ondansetron in sodium chloride 0.9% polyolefin bag at 5±3°C.

INTRODUCTION: The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C. METHOD: Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend. RESULTS: The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r2) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days. CONCLUSION: The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.

Clinical application of DEX/CRH test and multi-channel NIRS in patients with depression.

BACKGROUND: To reduce the number of patients with depression, biomarkers for clarifying psychiatric disorders are warranted. Numerous candidates have been proposed; however, near-infrared spectroscopy (NIRS) with multi-channel probes and a dexamethasone/corticotropin-releasing hormone (DEX/CRH) test are still surviving for practical demand. Thirty-one outpatients with depressed moods were analyzed using both biological tests. RESULTS: The non-suppressors, as indicated by the DEX/CRH test, exhibited a high severity on the Hamilton Depression Scale and severe anxiety on the State Trait Anxiety Scale. In addition, a unique response was identified via NIRS in the same group suggested by the DEX/CRH assessment. CONCLUSIONS: The results obtained from these biological tests did not fit well with the category defined by operative diagnostic criteria, such as the Diagnostic and Statistical Manual of Mental Disorders or The International Classification of Diseases. Thus, it is critical that the utility evaluations of candidate biomarkers not be assessed by comparisons with the categorized criteria for a specific psychiatric disorder. Trial registration UMIN000013214, Registered 21 February 2014.

SALDI-TOF-MS analyses of small molecules (citric acid, dexasone, vitamins E and A) using TiO2 nanocrystals as substrates.

Surface-assisted laser desorption/ionisation time-of-flight mass spectrometry (SALDI-TOF-MS) might be the method of choice for the analysis of low mass molecules (less than m/z 500). Titanium dioxide (TiO2) nanocrystals as a substrate for SALDI-TOF-MS improve the reproducibility of the signal intensities and prevent the fragmentation of some molecules upon laser irradiation, as we have previously shown. In addition, variously shaped and sized TiO2 nanocrystals/substrates for SALDI-MS could be used for quantification of small molecules, which are otherwise difficult to detect with the assistance of organic matrices. TiO2-assisted LDI-MS spectra could be acquired with excellent reproducibility and repeatability and with low detection limit. In the current study, we analysed the spectra of dexasone, citric acid, vitamin E and vitamin A acquired with TiO2 nanocrystals of various shapes and dimensions, i.e. the colloidal TiO2 nanoparticles (TiO2 NPs), TiO2 prolate nanospheroids (TiO2 PNSs) and TiO2 nanotubes (TiO2 NTs). Various shapes and dimensions of substrates were used since these factors determine desorption and ionisation processes. The homogeneity on the target plate was compared based on signal-to-noise values of peaks of interest of analysed molecules as well as the within-day and day-to-day repeatability. In summary, the obtained results show that the applicability of individual TiO2 nanocrystals depends on the analyte. Signals which are acquired with the assistance of TiO2 PNSs have the highest sensitivity and reproducibility (the smallest standard deviation), even compared with those in the LDI mode. This implies that TiO2 PNSs could also be suitable for quantitative analyses of small molecules.

Effects of trophic exposure to dexamethasone and diclofenac in freshwater fish.

Steroidal and non-steroidalanti-inflammatories are pharmaceutical prescribed in human medicine and have the potential to contaminate water and sediments via inputs from sewage treatment plants. Their impacts on humans and ecosystems are emerging issues in environmental health. The aim of the present work was to evaluate the effects of diclofenac and dexamethasone in male fish Hoplias malabaricus after trophic exposure. Fish were fed twice every week with Astyanax sp. submitted to intraperitoneal inoculation with diclofenac (0; 0.2; 2.0 or 20.0 µg/kg) or dexamethasone (0; 0.03; 0.3 or 3.0 µg/kg). After 12 doses, blood was collected for testosterone dosage. The gonad and liver were collected to calculate gonadosomatic (GSI) and hepatosomatic index (HSI). Antioxidants enzymes activity and biotransformation were also evaluated in liver and gonads. In liver, diclofenac caused oxidative stress with increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and lipoperoxidation (LPO). The GST activity was reduced by diclofenac in liver. Trophic exposure of H. malabaricus to dexamethasone caused an increase in antioxidant system (GPx, CAT, GST, and GSH) and LPO in liver. However, it reduced antioxidant system (GPX and GST activities and GSH) in gonads. Both diclofenac and dexamethasone reduced the levels of testosterone, causing impairment to reproduction. Diclofenac reduced HSI at the 0.2 µg/kg, but not GSI. Our results suggest that the anti-inflammatory drugs diclofenac and dexamethasone caused oxidative stress and reduced testosterone levels that can have a negative impact in aquatic organisms.

Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem.

OBJECTIVES: To investigate adulteration of proprietary Chinese medicines with corticosteroids in Hong Kong. DESIGN: Case series with cross-sectional analysis. SETTING: A tertiary clinical toxicology laboratory in Hong Kong. PATIENTS: All patients using proprietary Chinese medicines adulterated with corticosteroids and referred to the authors' centre from 1 January 2008 to 31 December 2012. MAIN OUTCOME MEASURES: Patients' demographic data, clinical presentation, medical history, drug history, laboratory investigations, and analytical findings of the proprietary Chinese medicines were analysed. RESULTS: The records of 61 patients who consumed corticosteroid-adulterated proprietary Chinese medicines were reviewed. The most common corticosteroid implicated was dexamethasone. Co-adulterants such as non-steroidal anti-inflammatory drugs and histamine H1-receptor antagonists were detected in the proprietary Chinese medicine specimens. Among the patients, seven (11.5%) required intensive care, two (3.3%) died within 30 days of presentation, and 38 (62.3%) had one or more complications that were potentially attributable to exogenous corticosteroids. Of 22 (36.1%) patients who had provocative adrenal function testing performed, 17 (77.3% of those tested) had adrenal insufficiency. CONCLUSION: The present case series is the largest series of patients taking proprietary Chinese medicines adulterated with corticosteroids. Patients taking these illicit products are at risk of severe adverse effects, including potentially fatal complications. Adrenal insufficiency was very common in this series of patients. Assessment of adrenal function in these patients, however, has been inadequate and routine rather than discretionary testing of adrenal function is indicated in this group of patients. The continuing emergence of proprietary Chinese medicines adulterated with western medication indicates a persistent threat to public health.

Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery.

OBJECTIVE: This study deals with the preparation and evaluation of a pluronic lecithin organogel (PLO gel) containing ricinoleic acid for the transdermal eyelid delivery of dexamethasone and tobramycin. METHODS: Five different PLO gel formulations (F1, F2, F3, F4 and F5) containing tobramycin (0.3%) and dexamethasone (0.1%) were prepared and compared to a conventional PLO gel (light mineral oil PLO gel, F6) with respect to physical appearance and viscosity. The optimized ricinoleic acid PLO gel formulation (F2) was further characterized for pH, gelation temperature, morphology and drug content. Ex vivo permeability of dexamethasone and bactericidal activity of tobramycin from formulation F2 was tested, and values were compared to the marketed Tobradex® eye ointment. RESULTS: No apparent changes in the physical appearance and consistency were observed when ricinoleic acid was used as the oil phase. The pH of the optimized ricinoleic acid PLO gel (formulation F2) was found to be 6.54 with a gelation temperature of 31 °C. The drug content of tobramycin and dexamethasone were found to be 102.8% and 100.14%, respectively. The penetration profile of dexamethasone from formulation F2 was found to be much higher than the marketed Tobradex® eye ointment. F2 showed a better antimicrobial activity and higher zones of inhibition when compared to the marketed Tobradex® eye ointment. CONCLUSION: The findings of this investigation indicate that the ricinoleic acid PLO gel has the potential for use as a transdermal eyelid delivery system.

Development of a broad-spectrum one-step immunoassay for detection of glucocorticoids in milk using magnetosome-based immunomagnetic beads.

Immunomagnetic beads provide novel tools for high-throughput immunoassay techniques. In this study, protein G (PG) was immobilized onto bacterial magentic particles (BMPs) using an additional cysteine residue at the C-terminus. A broad-spectrum monoclonal antibody against glucocorticoids (GCs) was attached to BMPs through PG-Fc interaction, generating BMP-PG-mIgG immunomagentic beads. A sensitive one-step immunoassay was developed for GCs based on combination of BMP-PG-mIgG and dexamethasone-horseradish peroxidase tracer (DMS-HRP). The developed assay exhibited half inhibitory concentrations (IC50) for dexamethasone (DMS), betamethasone (BMS), prednisolone (PNS), hydrocortisone (HCS), beclomethasone (BCMS), cortisone (CS), 6-α-methylprednisone (6-α-MPNS), fludrocortisone acetate (HFCS) of 0.98, 1.49, 2.42, 9.29, 1.63, 6.13, 7.3, and 4.89 ng/mL, respectively. The method showed recoveries ranging rates from 86.5 % to 117 % with a coefficient of variation less than 12.3 % in milk sample, which showed a good correlation with LC-MS/MS. Thus, the proposed assay offers a rapid and broad-spectrum screening tool for simultaneous detection of GCs in milk.

Feasibility of 1H-high resolution-magic angle spinning NMR spectroscopy in the analysis of viscous cosmetic and pharmaceutical formulations.

The feasibility of (1)H-High Resolution-Magic Angle Spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy for the direct analysis of viscous cosmetic and pharmaceutical formulations such as creams, gels, and pastes is presented. Three examples are described: (i) the detection of chitosan in toothpaste, (ii) the analysis of dexamethasone acetate (DMA) in a cream, and (iii) the analysis of the local anesthetics, lidocaine and prilocaine, in a gel and a cream. All active components could be directly detected in their original commercial formulations without the need for laborious sample preparation steps. In addition, the possibility for HR-MAS-based quantifications and the analysis of dynamic properties of active components in different formulations applying HR-MAS diffusion-ordered NMR spectroscopy are shown.

Use of potentially harmful skin-lightening products among immigrant women in Rome, Italy: a pilot study.

BACKGROUND: Skin-lightening products are increasingly common in European cities. These products may contain substances that are banned under EU regulations as they can induce adverse effects, including cutaneous and systemic reactions (e.g., mercury, hydroquinone and topical corticosteroids). OBJECTIVES: To assess the knowledge, attitudes and practices of women regarding skin-lightening products and to quantify the potentially harmful substances in the products used. METHODS: We performed a cross-sectional study among 82 non-Italian women visiting an outpatient facility in Rome, Italy. The women completed a questionnaire on product use, side effects and risk awareness. We performed patch tests among a subgroup of 48 women who presented with contact dermatitis. We also quantified the allergenic and toxic substances in the 14 products reported, using dynamic reaction cell inductively coupled plasma mass spectrometry for metals and high-performance liquid chromatography for hydroquinone and topical corticosteroids. RESULTS: Out of the 82 women, 33 used skin-lightening products; about one fourth of these women were aware of potential risks. Three cosmetic creams and two soaps contained high concentrations of metals (Cr, Ni and Pb); hydroquinone was found in three creams and one oil. The only topical corticosteroid detected was dexamethasone, in one product. More than half of the women in the clinical evaluation had irritant contact dermatitis (i.e., negative response to patch test). CONCLUSIONS: Among immigrant women in Rome, the use of skin-lightening products seems to be fairly common, and some of these products contain potentially hazardous substances. Consumers must be informed of the potential risks, and EU regulations must be more strictly enforced.

[Dexamethasone and diclofenac by LC-MS-MS as herbal product adulterants]. / Confirmación de dexametasona y diclofenaco por LC-MS-MS como adulterantes en un producto herbolario.

OBJECTIVE: To confirm the presence of dexamethasone and diclofenac as adulterants of an herbal product. MATERIALS AND METHODS: For identificaction and confirmation of drugs a method of instrumental analysis by liquid chromatography coupled with high pressure tandem mass spectrometry was used. RESULTS: The presence of dexamethasone and diclofenac was confirmed in samples of 11 bottles of Reumofan Plus obtained from patients and/or physicians. The methodology used, allowed separation of stereoisomers dexamethasone and betamethasone, the relative abundances of product ions 237.2 and 279.2 m / z spectrally differentiate the compounds. CONCLUSIONS: The presence of dexamethasone and diclofenac was confirmed in samples of a product marketed as "100% natural" obtained from patients and / or physicians in a period from January to December, 2011.