Comparison of phosphodiesterase type V inhibitors use in eight European cities through analysis of urban wastewater

In this work a step forward in investigating the use of prescription drugs, namely erectile dysfunction products, at European level was taken by applying the wastewater-based epidemiology approach. 24-h composite samples of untreated wastewater were collected at the entrance of eight wastewater treatment plants serving the catchment within the cities of Bristol, Brussels, Castellón, Copenhagen, Milan, Oslo, Utrecht and Zurich. A validated analytical procedure with direct injection of filtered aliquots by liquid chromatography-tandem mass spectrometry was applied. The target list included the three active pharmaceutical ingredients (sildenafil, tadalafil and vardenafil) together with (bio)transformation products and other analogues. Only sildenafil and its two human urinary metabolites desmethyl- and desethylsildenafil were detected in the samples with concentrations reaching 60 ng L−1. The concentrations were transformed into normalized measured loads and the estimated actual consumption of sildenafil was back-calculated from these loads. In addition, national prescription data from five countries was gathered in the form of the number of prescribed daily doses and transformed into predicted loads for comparison. This comparison resulted in the evidence of a different spatial trend across Europe. In Utrecht and Brussels, prescription data could only partly explain the total amount found in wastewater; whereas in Bristol, the comparison was in agreement; and in Milan and Oslo a lower amount was found in wastewater than expected from the prescription data. This study illustrates the potential of wastewater-based epidemiology to investigate the use of counterfeit medication and rogue online pharmacy sales

Multi-year interlaboratory exercises for the analysis of illicit drugs and metabolites in wastewater:development of a quality control system

Thirty-seven laboratories from 25 countries present the development of an inter-laboratory testing scheme for the analysis of seven illicit drug residues in standard solutions, tap- and wastewater. Almost 10 000 concentration values were evaluated: triplicates of up to five samples and 26 laboratories per year. The setup was substantially improved with experiences gained across the six repetitions (e.g. matrix type, sample conditions, spiking levels). From this, (pre-)analytical issues (e.g. pH adjustment, filtration) were revealed for specific analytes which resulted in formulation of best-practice protocols for inter-laboratory setup and analytical procedures. The results illustrate the effectiveness of the inter-laboratory setup to assess laboratory performance in the framework of wastewater-based epidemiology. The exercise proved that measurements of laboratories were of high quality (>80% satisfactory results for six out of seven analytes) and that analytical follow-up is important to assist laboratories in improving robustness of wastewater-based epidemiology results

Potential interplay between NFκB and PPARγ in human dermal microvascular endothelial cells cultured in low magnesium

Dermal microvascular endothelial cells contribute to cutaneous inflammation by secreting proinflammatory cytokines and chemokines. We show here that low extracellular magnesium stimulates the secretion of interleukin 8 and monocyte chemoattractant protein-1 in dermal microvascular endothelial cells. This secretory pattern might result from interplay between NF\u3baB, the master regulator of inflammation, and PPAR, a transcription factor that has emerged as an inhibitor of inflammation. Indeed, both NF\u3baB and PPAR\u3b3 are activated in dermal microvascular endothelial cells cultured in low magnesiumcontaining medium. In conclusion, we hypothesize that PPAR\u3b3 and NF\u3baB might contribute to the response of these cells to low Mg