Biomedical subjects

Sara Castiglioni

Publications and source records attributed to Sara Castiglioni.

14 recordsLinked to original sources

PubMed2026

Assessing the potential of wastewater-based epidemiology to evaluate the impact of COVID-19 policy changes on stimulant use across 17 countries.

BACKGROUND AND AIMS: A limited number of studies have employed wastewater-based epidemiology (WBE) to assess the impact of specific COVID-19 public health directives on stimulant consumption. This study investigates the potential of WBE as a complementary information source to support decision-making, by examining drug use changes during the pandemic. METHODS: WBE data on stimulant use from 2019 through 2022 was obtained from 17 countries covering a total of 47 wastewater treatment plants worldwide. The Oxford Coronavirus Government Response Tracker stringency index was used to standardize the severity of the COVID-19 interventions across different countries. A multiple linear regression model was fitted for the population-normalized mass loads of amphetamine, cocaine (through its metabolite benzoylecgonine), MDMA, and methamphetamine to investigate whether changes in COVID-19 restrictions influenced stimulant use, controlling for possible week-weekend and spatial effects. RESULTS: In most locations, WBE suggests that stimulant use was not significantly affected by the COVID-19 interventions, or even increased under the stricter measures. Methamphetamine use showed the largest decrease with increasing policy stringency, with a negative linear relationship found in 19% of cities, followed by MDMA (18%), cocaine (15%) and amphetamine (6%). Social gathering restrictions mainly impacted cocaine and MDMA use, while methamphetamine consumption declined most under stringent travel restrictions. CONCLUSIONS: This study highlights the heterogeneous effects of the COVID-19 policy changes on stimulant use, even within countries. The ability of WBE to compile consecutive daily estimates proves to be particularly useful to assess the direct effect of specific policy changes on the consumption of different stimulants.

COVID-19 interventions↗

PubMed2006

Identification and measurement of illicit drugs and their metabolites in urban wastewater by liquid chromatography-tandem mass spectrometry.

Residues of illicit drugs and their metabolites that are excreted by humans may flow into and through wastewater treatment plants. The aim of this study was to develop a method for the determination of cocaine, amphetamines, morphine, cannabinoids, methadone, and some of their metabolites in wastewater. Composite 24-h samples from urban treatment plants were enriched with deuterated internal standards before solid-phase extraction. High-pressure liquid chromatography tandem mass spectrometry with multiple reaction monitoring was used for quantitation. Recoveries were generally higher than 80%, and limits of quantifications were in the low nanograms-per-liter range for untreated and treated wastewater. The overall variability of the method was lower than 10% for untreated and 5% for treated wastewater. The method was applied to wastewater samples coming from two treatment plants in Italy and Switzerland. Quantification ranges were found to be 0.2-1 microg/L for cocaine and its metabolite benzoylecgonine, 80-200 ng/L for morphine, 10 ng/L for 6-acetylmorphine, 60-90 ng/L for 11-nor-9-carboxy-Delta9-tetrahydrocannabinol, 10-90 ng/L for methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, and lower than 20 ng/L for amphetamines. As previously reported for cocaine, this method could be useful to estimate and monitor drug consumption in the population in real time, helping social scientists and authorities to combat drug abuse.

Chromatography, Liquid↗

PubMed2006

The tyrosine phosphatase HD-PTP is regulated by FGF-2 through proteasome degradation.

Angiogenesis is essential in development and wound healing and contributes to the pathogenesis of many diseases. The signalling pathways activated in angiogenesis are, in part ,known and the overall tyrosine phosphorylation of cellular proteins plays a relevant role. By RNA fingerprinting, we isolated a tyrosine phosphatase, HD-PTP, modulated in human endothelial cells exposed to human immunodeficiency virus type 1 Tat, a viral protein known to be angiogenic. For the first time, we describe HD-PTP at the protein level. HD-PTP, a 185 kDa cytosolic protein which is expressed in endothelial cells of different origin. We show that HD-PTP is upregulated by Tat at the mRNA but not at the protein level. HD-PTP protein is differentially modulated by two angiogenic growth factors. While Vascular Endothelial Growth Factor does not affect protein levels, Fibroblast Growth Factor-2 induces HD-PTP degradation via the proteasome system.

Cell Culture Techniques↗

PubMed2006

Expression analysis and modulation by HIV-Tat of the tyrosine phosphatase HD-PTP.

The human immunodeficiency virus type 1 Tat transactivates viral proteins and also affects the expression of eukaryotic genes. Since Tat is angiogenic, we assumed that the isolation of differentially expressed genes in Tat-treated endothelial cells would yield insights into the molecular mechanisms of the angiogenic process. By RNA fingerprinting, we found that Tat upregulates the tyrosine phosphatase HD-PTP mRNA in a human endothelial cell line. At the moment, little is known about HD-PTP. We here show that HD-PTP is highly conserved through evolution from yeast to man, and is ubiquitously distributed in adult and fetal tissues. HD-PTP is expressed in human cell lines derived from different tumors, but the mRNA levels do not appear to correlate with the malignant phenotype of the cells. HD-PTP mRNA was also detected in cell lines derived from tumors that develop in BKV/Tat-transgenic mice. Interestingly, a relation exists between the amounts of secreted Tat and the levels of HD-PTP mRNA. HD-PTP encodes a 185-kDa protein which is expressed in human endothelial from the umbilical cord and in human Kaposi-spindle cells. Tat-induction of HD-PTP mRNA parallels only with a slight increase of the protein, which occurs after 24 and 48 h of incubation in the presence of Tat. These results suggest that HD-PTP amounts might be regulated both at the transcriptional and post-transcriptional levels.

Adult↗

PubMed2006

Interleukin 1 alpha is a marker of endothelial cellular senescent.

BACKGROUND: The functional changes associated with endothelial senescence may be involved in human aging and age-related vascular disorders. Since the inflammatory cytokine interleukin (IL-)1 inhibits endothelial growth, we evaluated the expression of IL-1alpha, IL-1beta and their antagonist, the IL-1 receptor antagonist (IL-1ra), in endothelial in vitro senescence and quiescence. We also examined the expression of IL-1alpha in human senescent and progeric fibroblasts. RESULTS: We found that the overexpression of IL-1alpha specifically characterizes endothelial senescence. No modulation of this cytokine was observed in endothelial quiescence and in senescent or progeric human fibroblasts. The expression of IL-1beta and IL-1ra was also assessed and found not to be affected by senescence. CONCLUSION: Our results indicate that a dysfunction of the cytokine network associates with aging and point to a specific role of IL-1alpha in endothelial senescence.

Journal Article↗

PubMed2006

Effects of a complex mixture of therapeutic drugs at environmental levels on human embryonic cells.

The potential risk associated with the presence of low levels of pharmaceuticals in aquatic environments is currently under debate. In this study we investigated the effects of 13 drugs merged to mimic both the association and low concentration (ng/L) profiles detected in the environment. The mixture comprised atenolol, bezafibrate, carbamazepine, cyclophosphamide, ciprofloxacin, furosemide, hydrochlorothiazide, ibuprofen, lincomycin, ofloxacin, ranitidine, salbutamol, and sulfamethoxazole. At environmental exposure levels, the drug mix inhibited the growth of human embryonic cells HEK293, with the highest effect observed as a 30% decrease in cell proliferation compared to controls. Pharmaceuticals activated stress-response signaling protein kinases (ERK1/2), and induced overexpression of glutathione-S-transferase P1 gene. No evidence was found for apoptosis or necrosis in HEK293 cells, although morphological changes were observed. The drug mixture effectively stimulated the expression of cell-cycle progression-mediating genes p16 and p21, with a slight accumulation of cells in the G2/M phase of the cell-cycle. Our results suggest that a mixture of drugs at ng/L levels can inhibit cells proliferation by affecting their physiology and morphology. This also suggests that water-borne pharmaceuticals can be potential effectors on aquatic life.

Cell Cycle↗

PubMed2006

Removal of pharmaceuticals in sewage treatment plants in Italy.

A listing of "priority pharmaceuticals" for human use in Italy resulted in the selection of 26 pharmaceuticals, belonging to 11 therapeutic classes. They were analyzed by liquid chromatography-tandem mass spectrometry, their occurrence was assessed in six sewage treatment plants (STPs), and the loads and the removal rates (RR) were studied. Total loads ranged from 1.5 to 4.5 g/day/1000 inhabitants in influents and 1.0 and 3.0 g/day/1000 inhabitants in effluents. Total RR in STPs were mostly lower than 40%. Pharmaceuticals could be divided into three groups according to their behavior in STPs: one group with RR higher in summer than in winter, one group with RR similar in summer and winter, and a last group not removed. Last, we studied the distribution and fate of residual pharmaceuticals in the surface waters receiving the effluents of the STPs and identified degradation and sorption as the major factors affecting attenuation. Ciprofloxacin, ofloxacin, sulfamethoxazole (antibiotics), atenolol (cardiovascular drug), ibuprofen (antiinflammatory), furosemide, hydrochlorothiazide (diuretics), ranitidine (gastrointestinal drug), and bezafibrate (lipid regulator) were the most abundant residual drugs, thus those of environmental concern.

Drug Residues↗

PubMed2006

Pharmaceuticals in the environment in Italy: causes, occurrence, effects and control.

BACKGROUND, AIM AND SCOPE: Environmental contamination by pharmaceuticals is an emerging issue. Until recently, information on medicinal substances released into the environment was scant, but several studies have now been published. Data are, however, usually scattered and a systematic approach to this subject is generally lacking. Moreover, because of differences in the prevalence of diseases, treatment habits and options, or simply for market reasons, the pollution profile can differ significantly in different countries. The aim of this work is to review the papers dealing with environmental contamination by pharmaceuticals in Italy, with the aim of providing a comprehensive view on a national scale. METHODS: Papers related to environmental contamination by pharmaceuticals in Italy were reviewed, in order to offer a comprehensive view of this subject. Topics included analysis, occurrence, monitoring, modelling, treatment, control of the emissions, and ecotoxicological effects of pharmaceuticals in the environment. RESULTS AND CONCLUSION: The literature suggests that pharmaceuticals are widespread contaminants, entering the environment from a myriad of scattered points. Patients, in case of drugs for human use, or animals for veterinary drugs, are the main sources of contamination. Pharmaceuticals can be ranked according to environmental loads, predicted by multiplying sales figures by the rate of metabolism in man or animals. Priority pharmaceuticals, i.e. the molecules of concern for the environment, can be measured in waste and surface water by liquid chromatography-tandem mass spectrometry, and the loads detected are generally comparable to the predicted ones. Pharmaceuticals are designed to stimulate a response in humans and animals at low doses, with a very specific target, so the implications for human health and the environment need to be assessed. In vitro and in vivo studies suggest that pharmaceutical principles, taken singularly or in combinations, and concentrations close to those detected in the environment, may have ecotoxicological effects. The sewage system is an important point in the control of contamination, but sewage treatment plants are not able efficiently to abate a substantial part of water-borne pharmaceuticals. Several variables play a role, however, in the processes of waste water treatment, and could be specifically adjusted to improve the efficiency of drug abatement, mitigating the potential environmental hazards. RECOMMENDATION AND PERSPECTIVE: Pharmaceuticals in the environment are becoming a subject of global concern, with potential environmental consequences. Further knowledge of the causes, occurrence and effects of drugs as environmental pollutants is necessary for a better understanding of this ecological issue, as well as to improve abatement strategies, and to mitigate subtle environmental consequences.

Animals↗

PubMed2005

A multiresidue analytical method using solid-phase extraction and high-pressure liquid chromatography tandem mass spectrometry to measure pharmaceuticals of different therapeutic classes in urban wastewaters.

An analytical method with two extraction steps has been developed and validated for the simultaneous determination of 30 pharmaceuticals belonging to various therapeutic categories in urban wastewater. The aim was to boost the little available information on drugs' fates in sewage treatment plants (STPs) and in the receiving surface water. Aqueous samples were divided into two aliquots, each extracted by a different solid-phase extraction (SPE) method and analysed by reversed-phase liquid chromatography tandem mass spectrometry (HPLC-MS-MS). Recoveries of the pharmaceuticals were mostly greater than 70% and the overall variability of the method was below 8%. The instrumental quantification limit (IQL) varied between 30 and 400 pg injected, and the limits of quantification (LOQ) were in the low ng/L range. Nineteen pharmaceuticals were detected in concentrations between 0.5 and 2000 ng/L in effluents collected from several STPs in Italy. Atenolol, ciprofloxacin, furosemide, hydrochlorothiazide, ofloxacin, ranitidine and sulphamethoxazole were the most abundant compounds. The present analytical method was useful to check for pharmaceuticals in various Italian STPs and to identify the most abundant compounds.

Chromatography, High Pressure Liquid↗

PubMed2005

Cocaine in surface waters: a new evidence-based tool to monitor community drug abuse.

BACKGROUND: Cocaine use seems to be increasing in some urban areas worldwide, but it is not straightforward to determine the real extent of this phenomenon. Trends in drug abuse are currently estimated indirectly, mainly by large-scale social, medical, and crime statistics that may be biased or too generic. We thus tested a more direct approach based on 'field' evidence of cocaine use by the general population. METHODS: Cocaine and its main urinary metabolite (benzoylecgonine, BE) were measured by mass spectrometry in water samples collected from the River Po and urban waste water treatment plants of medium-size Italian cities. Drug concentration, water flow rate, and population at each site were used to estimate local cocaine consumption. RESULTS: We showed that cocaine and BE are present, and measurable, in surface waters of populated areas. The largest Italian river, the Po, with a five-million people catchment basin, steadily carried the equivalent of about 4 kg cocaine per day. This would imply an average daily use of at least 27 +/- 5 doses (100 mg each) for every 1000 young adults, an estimate that greatly exceeds official national figures. Data from waste water treatment plants serving medium-size Italian cities were consistent with this figure. CONCLUSION: This paper shows for the first time that an illicit drug, cocaine, is present in the aquatic environment, namely untreated urban waste water and a major river. We used environmental cocaine levels for estimating collective consumption of the drug, an approach with the unique potential ability to monitor local drug abuse trends in real time, while preserving the anonymity of individuals. The method tested here--in principle extendable to other drugs of abuse--might be further refined to become a standardized, objective tool for monitoring drug abuse.

Adult↗

PubMed2005

Identification of the pharmaceuticals for human use contaminating the Italian aquatic environment.

A predictive approach seems useful to identify pharmaceuticals in the environment and give an idea of overall levels of contamination, so as to restrict monitoring to those molecules most likely to be contaminants. We propose an approach based on two parts. The first is to rank the molecules according to the predicted environmental loads; the second is to refine the list by analysing the pharmaceuticals in sewage treatment plants (STPs) and comparing the concentrations with levels previously measured in surface water. This approach identified a restricted group of priority pollutants (ofloxacin, furosemide, atenolol, hydrochlorothiazide, carbamazepine, ibuprofen, spiramycin, bezafibrate, erythromycin, lincomycin and clarithromycin) in the aquatic environment in Italy, for further studies and monitoring.

Adrenergic beta-Antagonists↗

PubMed2004

Preliminary investigation on the environmental occurrence and effects of antibiotics used in aquaculture in Italy.

A preliminary investigation has been carried out on the occurrence and effects of antibiotics used in Italian aquaculture with the objective of identifying priorities for monitoring programmes. According to the information available on the most pertinent and diffuse fish diseases and their related therapies, the presence of flumequine and oxytetracycline in sediments sampled from two trout farms and three sea-bass farms and in their surrounding environments was selected for an analytical investigation. The concentrations of oxytetracycline and flumequine varied up to a maximum of 246.3 and 578.8 microg/kg d.w., respectively. Flumequine was seen to have the highest toxicity in a bioluminescence assay with EC50 values varying within the range of 12-15 mg/l, while the EC50 values for oxytetracycline were within the range of 121-139 mg/l. The results of the present study indicate flumequine and oxytetracycline as priority chemicals to be monitored for possible environmental side effects of aquaculture in Italy. Apart from peak concentrations the chronic presence of flumequine and oxytetracycline in sediments both inside and outside farms should also be considered. In spite of the potential risks related to the use of antibiotics, the concentrations found in the sediments of the studied fish farms are significantly lower than those found in other areas.

Aquaculture↗

PubMed2004

Screening the leaching tendency of pesticides applied in the Amu Darya Basin (Uzbekistan).

The Amu Darya River, one of the most important water resources for Uzbekistan and Turkmenistan, was declared a World Disaster Zone in 1991. The great increase in irrigation and the use of pesticides has led to both a lack of water and drinking water contamination. The aim of the present study, part of an EU project on water management guidelines, was to evaluate the leachability of 71 organic pesticides commonly employed in the area, and to assess compounds that could potentially contaminate the river and impair drinking water quality. A multivariate approach is proposed for the pesticide screening, condensing information from different environmental partition indexes (GUS, "modified LEACH", LIN) into a single ranking, the Global Leachability Index (GLI). For a selected data set in water medium this super-index identifies three classes with a risk potential for pesticide leachability, and allows the selection of a small number of chemicals for an analytical survey.

Environmental Monitoring↗

PubMed2004

Methodological approaches for studying pharmaceuticals in the environment by comparing predicted and measured concentrations in River Po, Italy.

A predictive approach seems useful to study human and veterinary pharmaceuticals in the environment and provide an idea of overall levels of contamination, so as to restrict monitoring to those molecules which are most likely to represent possible environmental contaminants. Predicted environmental concentrations (PECs) can be calculated by a mass balance approach, while a recent proposal from the European Agency for the Evaluation of Medicinal Products (EMEA) suggests an alternative method for calculating PEC for each pharmaceutical and then focusing further work on molecules with high PEC values. We used the results of monitoring campaigns on the River Po, in Northern Italy, to assess the accuracy of predictive models with measured environmental concentrations (MECs). The comparison indicated that in some cases a refined PEC value can provide a good approximation of the MEC. In other cases PECs substantially differed from the MECs, particularly when there were not enough data to estimate the environmental fate of the molecule. Predictive models might therefore be useful for studying pharmaceuticals in the environment, providing enough experimental data is available on the environmental fate of the molecules.

Environmental Monitoring↗