RESUMO
BACKGROUND: Studies have shown that contamination of surfaces by illicit drugs frequently occurs in forensic laboratories when manipulating seized samples as well as in pharmacies and hospitals when preparing medicinal drugs. In this project, we extended these studies to a Drug Consumption Room to investigate drug levels and possible exposure of the staff members. METHODS: We investigated pre and post cleaning contamination by heroin and cocaine and their degradation products 6-monoacetylmorphine and benzoylecgonine on different surfaces (tables, counters, computers and door handles) and in the ambient air. We also collected urine and hair samples from staff members to check for potential short and long term contaminations. RESULTS: Medium to heavy contamination has been detected on most surfaces and door handles; as expected, air contamination was particularly high in the smoking room. Drug levels were < LOD to very low in the urine and the hair samples of staff members tested. CONCLUSION: The cleaning efficiency of the surfaces, carried out by staff and drug users after drug consumption, was often not satisfactory. The very low drug levels in hair indicate that acute health risks for staff members are low.
Assuntos
Cocaína , Cabelo , Exposição Ocupacional , Humanos , Cabelo/química , Cocaína/urina , Cocaína/análise , Cocaína/análogos & derivados , Exposição Ocupacional/análise , Drogas Ilícitas/análise , Derivados da Morfina/análise , Derivados da Morfina/urina , Contaminação de Equipamentos , Pessoal de SaúdeRESUMO
Nickel is a food contaminant of natural or anthropogenic origin. Monitoring of contaminants in food in general allows obtaining an overview on the presence of substances that are undesirable to health. The aim of this study was to analyse nickel content in food of non-animal origin and beverages sold in Luxembourg to determine the exposure of the population to this contaminant. In total, 660 samples were analysed in the timeframe from 2017 to 2021. The results demonstrate high concentrations of nickel in cashew nuts, walnuts, hemp and sunflower seeds, dried peas, oregano, and cocoa powder. Surveillance of contaminants in food allows identifying contributors to the chronic and acute exposure of nickel in order to potentially set official maximum levels in European legislation in the future, allowing for better enforcement actions in case of contaminated products and increasing consumer protection.
Assuntos
Contaminação de Alimentos , Níquel , Humanos , Níquel/análise , Luxemburgo , Contaminação de Alimentos/análise , Bebidas/análise , Ingestão de AlimentosRESUMO
We describe here the evaluation of the cytotoxic efficacy of two platinum (II) complexes bearing an N-heterocyclic carbene (NHC) ligand, a pyridine ligand and bromide or iodide ligands on a panel of human metastatic cutaneous melanoma cell lines representing different genetic subsets including BRAF-inhibitor-resistant cell lines, namely A375, SK-MEL-28, MeWo, HMCB, A375-R, SK-MEL-5-R and 501MEL-R. Cisplatin and dacarbazine were also studied for comparison purposes. Remarkably, the iodine-labelled Pt-NHC complex strongly inhibited proliferation of all tested melanoma cells after 1-h exposure, likely due to its rapid uptake by melanoma cells. The mechanism of this inhibitory activity involves the formation of DNA double-strand breaks and apoptosis. Considering the intrinsic chemoresistance of metastatic melanoma cells of current systemic treatments, these findings are promising and could give research opportunities in the future to improve the prognosis of patients suffering from unresectable metastatic melanoma that are not eligible or that do not respond to the most effective drugs available to date, namely BRAF inhibitors and the anti-PD-1 monoclonal antibody (mAb).
Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Melanoma/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacocinética , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Humanos , Melanoma/patologia , Metano/análogos & derivados , Metano/química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacocinética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/patologia , Proteína bcl-X/metabolismo , Melanoma Maligno CutâneoRESUMO
A platinum (II) complex stabilized by a pyridine and an N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC50 ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the N-heterocyclic carbene (NHC) Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase atomic force microscopy (AFM). The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behavior was quantified from the different experiments due to contour length variations. At 24 h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands.
Assuntos
Antineoplásicos/química , DNA/química , Compostos Organoplatínicos/química , Antracenos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , DNA/metabolismo , Células HCT116 , Humanos , Células MCF-7 , Pinças Ópticas , Compostos Organoplatínicos/farmacologia , Células PC-3RESUMO
The high interest in N-Heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed on 8 different types of cells that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. Using HCT116 cells, the conjugates displayed an effective activity after only 45 min of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives.
Assuntos
Portadores de Fármacos/química , Compostos Organoplatínicos/farmacologia , Polietilenoimina/farmacologia , Morte Celular/efeitos dos fármacos , Endocitose , Fluorescência , Corantes Fluorescentes/química , Células HCT116 , Humanos , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Polietilenoimina/síntese química , Polietilenoimina/químicaRESUMO
The current interest for platinum N-heterocyclic carbene complexes in cancer research stems from their impressive toxicity reported against a range of different human cancer cells. To date, the demonstration of their in vivo efficacy relative to that of established platinum-based drugs has not been specifically addressed. Here, we introduce an innovative approach to increase the NHC-Pt complex potency whereby multiple NHC-Pt(II) complexes are coordinated along a polyethylenimine polymer (PEI) chain. We show that such NHC-Pt(II)-PEI conjugates induce human cancer cell death in vitro and in vivo in a xenograft mouse model with no observable side effects in contrast to oxaliplatin. Additional studies indicate nucleus and mitochondria targeting and suggest various mechanisms of action compared to classical platinum-based anticancer drugs.