The study reported in this paper is focused on occupational exposure to potential toxic compounds... more The study reported in this paper is focused on occupational exposure to potential toxic compounds for employees working in dynamic olfactometry, following EN 13725:2003 standard procedures. Municipal solid waste (MSW) incineration plants, typically, have authorized stack emissions for primary pollutants (like CO, NOx, particulate), for selected trace organics (polycyclic aromatic hydrocarbons (PAHs) or dioxins), metals or for total organic compounds (TOC). Odour control is limited on recommendations of good practices for the waste receiving areas and storage, generally on the air management systems. In Italy there is an increasingly number of requests, to environmental inspection authorities, Agenzia Regionale per la Protezione Ambientale (ARPA), Regional Environment Agency, to quantitatively describe possible odour annoyance effects from different industrial plants, including MSW incineration plants. Recently ARPA Piemonte has been asked to perform one odour survey for the newly incinerator for the city of Torino, that burns 500,000 t/y of MSW recovering energy through cogeneration. The plant is equipped with a pollutant's automated measuring system (AMS) to assess the compliance with the emission limit values, but not to measure odour emissions. For this reason, it is necessary to assess odour emissions as well, in order to prepare an exhaustive environmental odour scenario for the whole area. We recently presented a risk assessment approach, to evaluate non-carcinogenic and carcinogenic compounds for different sample types, based on STEL or TWA data, or EPA slope factors values respectively. It has been decide to follow this approach to define potential sample toxicity (PT), using the different risk occupational scenarios proposed, before odour concentration analysis of stack emissions samples. Using emission limit values that are set in the permit, PT has been defined. Since samples are presented to assessors in an ascending concentration series, workers exposure has been limited to acceptable levels defining the specific minimum dilution value to be used in the ARPA Piemonte olfactometric laboratory standard procedures.
IntroductionMore than a decade after electronic cigarettes (e-cigarette) hit the European market,... more IntroductionMore than a decade after electronic cigarettes (e-cigarette) hit the European market, we are still debating whether they may help or hinder tobacco control. It is therefore useful to explore the potential net effect of e-cigarette use in the general population.MethodsWe annually conduct a face-to-face survey on smoking in Italy on a representative sample of the general population aged 15 years or over (52.4 million). A total of 15 406 subjects were interviewed in 2014–2018. We investigated the consequences of using e-cigarettes on tobacco smoking behaviour among ever and regular e-cigarette users.ResultsIn all, 5.7% of our sample reported ever e-cigarette use. Multivariate analyses showed more use by men, ex-smokers and current smokers. E-cigarette use decreased with age and increased with education and calendar year. Only 1.1% of subjects were regular e-cigarette users. This prevalence rose from 0.4% in 2014–2015 to 1.8% in 2016–2017 and was 1.3% in 2018. Among 522 ever users, 13.2% stopped smoking after trying e-cigarettes and 22.2% started smoking or relapsed after using e-cigarettes. The corresponding estimates among regular users were 24.7% and 28.0%, respectively.ConclusionsAmong Italian e-cigarette users, those (re)starting smoking after using e-cigarettes outnumber those who stop smoking after using e-cigarettes. From a public health point of view, e-cigarettes may have an unfavourable net effect. Consequently, if we are not able to prevent sales of e-cigarettes to non-smokers, this product will more likely stimulate smoking tobacco than reduce harm.
There is no shortage of information about the average benzene concentrations in urban air, but th... more There is no shortage of information about the average benzene concentrations in urban air, but there is very little about microenvironmental exposure, such as in-vehicle concentrations while driving in various traffic conditions, while refuelling, or while in a parking garage The main reason for this lack of data is that no analytical instrumentation has been available to measure on-line trace amounts of benzene in such situations We have recently proposed a highly accurate, high-speed cryofocusing gas chromatography/mass spectrometry (GC/MS) system for monitoring benzene concentrations in air Accuracy of the analytical data is achieved by enrichment of the air sample before trapping, with a stable isotope permeation tube system The same principles have been applied to a new instrument, specifically designed for operation on an electric vehicle (Ducato Elettra, Fiat) The zero emission vehicle and the fully transportable, battery-operated GC/MS system provide a unique possibility of monitoring benzene exposure in real everyday situations such as while driving, refuelling, or repairing a car All power consumptions have been reduced so as to achieve a batteryoperated GC/MS system Liquid nitrogen cryofocusing has been replaced by a packed, inductively heated, graphitized charcoal microtrap The instrument has been mounted on shock absorbers and installed in the van The whole system has been tested in both fixed and mobile conditions The maximum monitoring period without external power supply is 6 h The full analytical cycle is 4 min, allowing close to real-time monitoring, and the minimum detectable level is 1 g/m 3 for benzene In-vehicle monitoring showed that, when recirculation was off and ventilation on, i e ,
The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all c... more The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice.
The antitumor activity of angiogenesis inhibitors is reinforced in combination with chemotherapy.... more The antitumor activity of angiogenesis inhibitors is reinforced in combination with chemotherapy. It is debated whether this potentiation is related to a better drug delivery to the tumor due to the antiangiogenic effects on tumor vessel phenotype and functionality. We addressed this question by combining bevacizumab with paclitaxel on A2780-1A9 ovarian carcinoma and HT-29 colon carcinoma transplanted ectopically in the subcutis of nude mice and on A2780-1A9 and IGROV1 ovarian carcinoma transplanted orthotopically in the bursa of the mouse ovary. Paclitaxel concentrations together with its distribution by MALDI mass spectrometry imaging (MALDI MSI) were measured to determine the drug in different areas of the tumor, which was immunostained to depict vessel morphology and tumor proliferation. Bevacizumab modified the vessel bed, assessed by CD31 staining and dynamic contrast enhanced MRI (DCE-MRI), and potentiated the antitumor activity of paclitaxel in all the models. Although tumor paclitaxel concentrations were lower after bevacizumab, the drug distributed more homogeneously, particularly in vascularized, nonnecrotic areas, and was cleared more slowly than controls. This happened specifically in tumor tissue, as there was no change in paclitaxel pharmacokinetics or drug distribution in normal tissues. In addition, the drug concentration and distribution were not influenced by the site of tumor growth, as A2780-1A9 and IGROV1 growing in the ovary gave results similar to the tumor growing subcutaneously. We suggest that the changes in the tumor microenvironment architecture induced by bevacizumab, together with the better distribution of paclitaxel, may explain the significant antitumor potentiation by the combination. Mol Cancer Ther; 15(1); 125-35. Ó2015 AACR.
Abstract The analytical difficulties in odor measurements are related to the well-known complexit... more Abstract The analytical difficulties in odor measurements are related to the well-known complexity of our olfactory sensory perception. Still, the importance of such an analysis in environmental pollution is of primary importance in certain fields and there is a strong need for instrumental analytical technologies to describe odor pollution to define objective odor policy criteria. There is a lack of actual legislation in specific odor control procedures, and in this chapter, we discuss the possibility of using instrumental analysis, in conjunction with sensorial analysis, to characterize odor emissions in order to detect malfunctions in facilities and to prevent air pollution and olfactory nuisance in the environment. A gas chromatographic-based approach to study environmental problems related to olfactory pollution is presented, and the results are discussed.
Imidacloprid is an insecticide belonging to neonicotinoids, a class of agonists of the nicotinic ... more Imidacloprid is an insecticide belonging to neonicotinoids, a class of agonists of the nicotinic acetylcholine receptors that shows higher affinities in insects compared to mammals. However, recent evidence show that neonicotinoids can bind to the mammalian receptors, leading to detrimental responses in cultured neurons. We developed an analytical strategy which uses mass spectrometry with multiple reaction monitoring (targeted approach) and high-resolution acquisitions (untargeted approach), which were applied to quantify imidacloprid and to identify its metabolites in biological tissues after oral treatments of mice. Mouse dams were treated with doses from 0.118 mg/kg bw day up to 41 mg/kg day between gestational days 6-9. Results showed quantifiable levels of imidacloprid in plasma (from 30.48 to 5705 ng/mL) and brain (from 20.48 to 5852 ng/g) of treated mice, proving the passage through the mammalian blood-brain barrier with a high correspondence between doses and measured concentrations. Untargeted analyses allowed the identification of eight metabolites including imidacloprid-olefin, hydroxy-imidacloprid dihydroxy-imidacloprid, imidacloprid-nitrosimine, desnitro-imidacloprid, 6-chloronicotinic acid, 5-(methylsulfanyl)pyridine-2-carboxylic acid and N-imidazolidin-2-ylidenenitramide in plasma and brain. Moreover, analysis of embryonic tissues after oral treatment of mouse dams showed detectable levels of imidacloprid (816.6 ng/g after a dose of 4.1 mg/Kg bw day and 5646 ng/g after a dose of 41 mg/Kg bw day) and its metabolites, proving the permeability of the placenta barrier. Although many studies have been reported on the neurotoxicity of neonicotinoids, our study paves the way for a risk assessment in neurodevelopmental toxicity, demostrating the capability of imidacloprid and its metabolites to pass the biological barriers.
Journal of the National Cancer Institute, Aug 21, 1991
(18) READ LD, SNIDER CE, MILLER JS, ET AL: Ligand-modulated regulation of progesterone receptor m... more (18) READ LD, SNIDER CE, MILLER JS, ET AL: Ligand-modulated regulation of progesterone receptor messenger ribonucleic acid and protein in human breast cancer cell lines. Mol Endocrinol 2:263-271, 1988 (19) WFJ LL, KRETT NL, FRANCIS MD, ET AL: Mul-tiple human ...
MALDI MSI images from the tumor models described in Fig. 4 and 5 of the Results and Discussion, w... more MALDI MSI images from the tumor models described in Fig. 4 and 5 of the Results and Discussion, were quantified for ion signal distribution.
The study reported in this paper is focused on occupational exposure to potential toxic compounds... more The study reported in this paper is focused on occupational exposure to potential toxic compounds for employees working in dynamic olfactometry, following EN 13725:2003 standard procedures. Municipal solid waste (MSW) incineration plants, typically, have authorized stack emissions for primary pollutants (like CO, NOx, particulate), for selected trace organics (polycyclic aromatic hydrocarbons (PAHs) or dioxins), metals or for total organic compounds (TOC). Odour control is limited on recommendations of good practices for the waste receiving areas and storage, generally on the air management systems. In Italy there is an increasingly number of requests, to environmental inspection authorities, Agenzia Regionale per la Protezione Ambientale (ARPA), Regional Environment Agency, to quantitatively describe possible odour annoyance effects from different industrial plants, including MSW incineration plants. Recently ARPA Piemonte has been asked to perform one odour survey for the newly incinerator for the city of Torino, that burns 500,000 t/y of MSW recovering energy through cogeneration. The plant is equipped with a pollutant's automated measuring system (AMS) to assess the compliance with the emission limit values, but not to measure odour emissions. For this reason, it is necessary to assess odour emissions as well, in order to prepare an exhaustive environmental odour scenario for the whole area. We recently presented a risk assessment approach, to evaluate non-carcinogenic and carcinogenic compounds for different sample types, based on STEL or TWA data, or EPA slope factors values respectively. It has been decide to follow this approach to define potential sample toxicity (PT), using the different risk occupational scenarios proposed, before odour concentration analysis of stack emissions samples. Using emission limit values that are set in the permit, PT has been defined. Since samples are presented to assessors in an ascending concentration series, workers exposure has been limited to acceptable levels defining the specific minimum dilution value to be used in the ARPA Piemonte olfactometric laboratory standard procedures.
IntroductionMore than a decade after electronic cigarettes (e-cigarette) hit the European market,... more IntroductionMore than a decade after electronic cigarettes (e-cigarette) hit the European market, we are still debating whether they may help or hinder tobacco control. It is therefore useful to explore the potential net effect of e-cigarette use in the general population.MethodsWe annually conduct a face-to-face survey on smoking in Italy on a representative sample of the general population aged 15 years or over (52.4 million). A total of 15 406 subjects were interviewed in 2014–2018. We investigated the consequences of using e-cigarettes on tobacco smoking behaviour among ever and regular e-cigarette users.ResultsIn all, 5.7% of our sample reported ever e-cigarette use. Multivariate analyses showed more use by men, ex-smokers and current smokers. E-cigarette use decreased with age and increased with education and calendar year. Only 1.1% of subjects were regular e-cigarette users. This prevalence rose from 0.4% in 2014–2015 to 1.8% in 2016–2017 and was 1.3% in 2018. Among 522 ever users, 13.2% stopped smoking after trying e-cigarettes and 22.2% started smoking or relapsed after using e-cigarettes. The corresponding estimates among regular users were 24.7% and 28.0%, respectively.ConclusionsAmong Italian e-cigarette users, those (re)starting smoking after using e-cigarettes outnumber those who stop smoking after using e-cigarettes. From a public health point of view, e-cigarettes may have an unfavourable net effect. Consequently, if we are not able to prevent sales of e-cigarettes to non-smokers, this product will more likely stimulate smoking tobacco than reduce harm.
There is no shortage of information about the average benzene concentrations in urban air, but th... more There is no shortage of information about the average benzene concentrations in urban air, but there is very little about microenvironmental exposure, such as in-vehicle concentrations while driving in various traffic conditions, while refuelling, or while in a parking garage The main reason for this lack of data is that no analytical instrumentation has been available to measure on-line trace amounts of benzene in such situations We have recently proposed a highly accurate, high-speed cryofocusing gas chromatography/mass spectrometry (GC/MS) system for monitoring benzene concentrations in air Accuracy of the analytical data is achieved by enrichment of the air sample before trapping, with a stable isotope permeation tube system The same principles have been applied to a new instrument, specifically designed for operation on an electric vehicle (Ducato Elettra, Fiat) The zero emission vehicle and the fully transportable, battery-operated GC/MS system provide a unique possibility of monitoring benzene exposure in real everyday situations such as while driving, refuelling, or repairing a car All power consumptions have been reduced so as to achieve a batteryoperated GC/MS system Liquid nitrogen cryofocusing has been replaced by a packed, inductively heated, graphitized charcoal microtrap The instrument has been mounted on shock absorbers and installed in the van The whole system has been tested in both fixed and mobile conditions The maximum monitoring period without external power supply is 6 h The full analytical cycle is 4 min, allowing close to real-time monitoring, and the minimum detectable level is 1 g/m 3 for benzene In-vehicle monitoring showed that, when recirculation was off and ventilation on, i e ,
The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all c... more The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice.
The antitumor activity of angiogenesis inhibitors is reinforced in combination with chemotherapy.... more The antitumor activity of angiogenesis inhibitors is reinforced in combination with chemotherapy. It is debated whether this potentiation is related to a better drug delivery to the tumor due to the antiangiogenic effects on tumor vessel phenotype and functionality. We addressed this question by combining bevacizumab with paclitaxel on A2780-1A9 ovarian carcinoma and HT-29 colon carcinoma transplanted ectopically in the subcutis of nude mice and on A2780-1A9 and IGROV1 ovarian carcinoma transplanted orthotopically in the bursa of the mouse ovary. Paclitaxel concentrations together with its distribution by MALDI mass spectrometry imaging (MALDI MSI) were measured to determine the drug in different areas of the tumor, which was immunostained to depict vessel morphology and tumor proliferation. Bevacizumab modified the vessel bed, assessed by CD31 staining and dynamic contrast enhanced MRI (DCE-MRI), and potentiated the antitumor activity of paclitaxel in all the models. Although tumor paclitaxel concentrations were lower after bevacizumab, the drug distributed more homogeneously, particularly in vascularized, nonnecrotic areas, and was cleared more slowly than controls. This happened specifically in tumor tissue, as there was no change in paclitaxel pharmacokinetics or drug distribution in normal tissues. In addition, the drug concentration and distribution were not influenced by the site of tumor growth, as A2780-1A9 and IGROV1 growing in the ovary gave results similar to the tumor growing subcutaneously. We suggest that the changes in the tumor microenvironment architecture induced by bevacizumab, together with the better distribution of paclitaxel, may explain the significant antitumor potentiation by the combination. Mol Cancer Ther; 15(1); 125-35. Ó2015 AACR.
Abstract The analytical difficulties in odor measurements are related to the well-known complexit... more Abstract The analytical difficulties in odor measurements are related to the well-known complexity of our olfactory sensory perception. Still, the importance of such an analysis in environmental pollution is of primary importance in certain fields and there is a strong need for instrumental analytical technologies to describe odor pollution to define objective odor policy criteria. There is a lack of actual legislation in specific odor control procedures, and in this chapter, we discuss the possibility of using instrumental analysis, in conjunction with sensorial analysis, to characterize odor emissions in order to detect malfunctions in facilities and to prevent air pollution and olfactory nuisance in the environment. A gas chromatographic-based approach to study environmental problems related to olfactory pollution is presented, and the results are discussed.
Imidacloprid is an insecticide belonging to neonicotinoids, a class of agonists of the nicotinic ... more Imidacloprid is an insecticide belonging to neonicotinoids, a class of agonists of the nicotinic acetylcholine receptors that shows higher affinities in insects compared to mammals. However, recent evidence show that neonicotinoids can bind to the mammalian receptors, leading to detrimental responses in cultured neurons. We developed an analytical strategy which uses mass spectrometry with multiple reaction monitoring (targeted approach) and high-resolution acquisitions (untargeted approach), which were applied to quantify imidacloprid and to identify its metabolites in biological tissues after oral treatments of mice. Mouse dams were treated with doses from 0.118 mg/kg bw day up to 41 mg/kg day between gestational days 6-9. Results showed quantifiable levels of imidacloprid in plasma (from 30.48 to 5705 ng/mL) and brain (from 20.48 to 5852 ng/g) of treated mice, proving the passage through the mammalian blood-brain barrier with a high correspondence between doses and measured concentrations. Untargeted analyses allowed the identification of eight metabolites including imidacloprid-olefin, hydroxy-imidacloprid dihydroxy-imidacloprid, imidacloprid-nitrosimine, desnitro-imidacloprid, 6-chloronicotinic acid, 5-(methylsulfanyl)pyridine-2-carboxylic acid and N-imidazolidin-2-ylidenenitramide in plasma and brain. Moreover, analysis of embryonic tissues after oral treatment of mouse dams showed detectable levels of imidacloprid (816.6 ng/g after a dose of 4.1 mg/Kg bw day and 5646 ng/g after a dose of 41 mg/Kg bw day) and its metabolites, proving the permeability of the placenta barrier. Although many studies have been reported on the neurotoxicity of neonicotinoids, our study paves the way for a risk assessment in neurodevelopmental toxicity, demostrating the capability of imidacloprid and its metabolites to pass the biological barriers.
Journal of the National Cancer Institute, Aug 21, 1991
(18) READ LD, SNIDER CE, MILLER JS, ET AL: Ligand-modulated regulation of progesterone receptor m... more (18) READ LD, SNIDER CE, MILLER JS, ET AL: Ligand-modulated regulation of progesterone receptor messenger ribonucleic acid and protein in human breast cancer cell lines. Mol Endocrinol 2:263-271, 1988 (19) WFJ LL, KRETT NL, FRANCIS MD, ET AL: Mul-tiple human ...
MALDI MSI images from the tumor models described in Fig. 4 and 5 of the Results and Discussion, w... more MALDI MSI images from the tumor models described in Fig. 4 and 5 of the Results and Discussion, were quantified for ion signal distribution.
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