Silvia Fustinoni

• PhD
• Professor (Associate) at University of Milan

Acute intermittent porphyria (AIP) is a rare metabolic disorder characterized by acute attacks often triggered by porphyrinogenic drugs and a low-glucose diet. According to recent findings, chronic symptoms persist in AIP patients. To avoid the symptoms, patients often adopt preventive strategies such as increasing glucose intake, suggesting that n...

Background Glioblastoma (GBM) is a lethal brain tumor characterized by the glioma stem cell (GSC) niche. The V-ATPase proton pump has been described as a crucial factor in sustaining GSC viability and tumorigenicity. Here we studied how patients-derived GSCs rely on V-ATPase activity to sustain mitochondrial bioenergetics and cell growth. Methods...

Acute intermittent porphyria (AIP) is a rare metabolic disorder characterized by acute attacks often triggered by porphyrinogenic drugs and a low-glucose diet. According to recent findings, chronic symptoms persist in AIP patients. To avoid the symptoms, patients often adopt preventive strategies such as increasing glucose intake , suggesting that...

Background The rapid growth of the digital economy has transformed various labor markets, including the food sector. The transient nature and the peculiar work environments of food delivery workers raise concerns about occupational safety and health (OSH). This study aims to better understand these issues by conducting a comprehensive exploratory s...

Traffic-related air pollutants inside vehicle cabins are often extremely high compared to background pollution concentrations. The study of the determinants of these concentrations is particularly important for professional drivers and commuters who spend long periods in vehicles. This study is aimed at identifying and quantifying the effect of sev...

Erythropoietic ProtoPorphyria (EPP) is an autosomal recessive disorder caused by the deficiency of the ferrochelatase (FECH) enzyme resulting in the systemic accumulation of protoporphyrin IX (PPIX) in blood, erythrocytes and tissues. EPP is characterized by acute, painful and non-blistering phototoxicity on sun exposure and, in a small proportion...

Oxytocin and cortisol (OXY and CORT) are hormones related to stress, cognitive, and social behaviors. Their detection is relevant to epidemiological studies aimed at investigating the effects of stressor factors on human life. The aim of this study was to develop and validate an assay for the measurement of OXY and CORT in saliva samples using liqu...

Glyphosate, an herbicide largely used in various contexts, can have adverse effects on human health. Although it is currently the most applied pesticide worldwide, few studies evaluated the extent of human exposure via biomonitoring. To expand such information, biological monitoring of exposure to glyphosate was conducted. The study has a before-an...

Introduction Working as a rider for digital food delivery companies has become a widespread opportunity nowadays. According to the main Italian platforms, there are around 60.000 riders in Italy, of which 8.000 in Milan only. This exploratory survey aims at examining health and safety issues of riders operating in the Milan area. Methods The surve...

Introduction Perfluoroalkyl acid surfactants PFOA (from the sixties to 2013) and ADV (since 1996) were historically used in two Italian fluoropolymer plants; cC6O4 was introduced in 2012 as a PFOA substitute. This work reports biomonitoring results in the years 2004-2021. Methods Workers surveyed from 2004, measuring serum concentrations of perflu...

Background In the regeneration of waste oil, a strategical technological process for the European Union circular economy action plan, exhausted oils are regenerated to produce high performing oil bases. Aim of this work was to assess the exposure to benzene in plant workers during ordinary activities. Methods 59 workers, potentially exposed to ben...

Introduction Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-contro...

Cardiogenic shock (CS) portends a dismal prognosis if hypoperfusion triggers uncontrolled inflammatory and metabolic derangements. We sought to investigate metabolomic profiles and temporal changes in IL6, Ang-2, and markers of glycocalyx perturbation from admission to discharge in eighteen patients with heart failure complicated by CS (HF-CS). Bio...

Glyphosate-based herbicides are the most widely used pesticides in the world; however, the toxicity of glyphosate (GlyP) toward humans, especially its carcinogenicity, is controversial. The aim of this work was to validate a rapid assay for measuring GlyP and its metabolite aminomethylphosphonic acid (AMPA) in urine for human biomonitoring. The ana...

Background Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors. Objective The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. Methods The search was perform...

In recent years, there has been growing interest in exploring alternative and innovative delivery systems to improve the efficacy of iron supplements, satisfying iron needs and lowering side effects. To address this issue, this study aimed at demonstrating the advantages of Ferro Supremo formulation (composed of encapsulated iron, vitamins, and mic...

Purpose Random start protocols are commonly used for oocyte cryopreservation in women with cancer. However, albeit generally reassuring, available evidence is still insufficient to rule out a sub-optimal cycle outcome. This study aimed to compare follicular steroidogenesis between women initiating the random start protocol in the luteal phase and t...

Background In women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatment...

cC6O4 is a new-generation perfluoroalkyl surfactant used in the chemical industry for the synthesis of perfluoroalkyl polymers. It was introduced as a less biopersistent substitute of traditional perfluoroalkyl surfactants such as PFOA, but its kinetics in humans was never investigated. This work is aimed to investigate the kinetics of elimination...

Background and aim Shift work, especially including night shifts, has been found associated with several diseases, including obesity, diabetes, cancers, and cardiovascular, mental, gastrointestinal and sleep disorders. Metabolomics (an omics-based methodology) may shed light on early biological alterations underlying these associations. We thus aim...

Objectives Perfluoroalkyl acid surfactants are used in the chemical industry for the synthesis of perfluoroalkyl polymers. In one Italian fluoropolymer plant and in the research and innovation center, two major perfluoroalkyl surfactants have been historically used: PFOA and ADV and a third, cC6O4 substituted PFOA from mid-2013. This work is summar...

Objective Patients with adrenal insufficiency (AI) may be exposed to supraphysiological glucocorticoids levels during standard treatment with cortisone acetate (CA) or immediate-release hydrocortisone (IR-HC). Recent studies, predominantly including patients in IR-HC treatment, suggested that modified-release hydrocortisone (MRH) provide a more phy...

Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the generation of reactive oxygen species. 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, and a sensitive biomarker of oxidative stress and genotoxi...

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese co...

Background Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disrupters. Objective The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. Methods The search was perform...

Objective During the induction of gaseous anaesthesia, waste anaesthetic gases (WAGs) can be released into workplace air. Occupational exposure to high levels of halogenated WAGs may lead to adverse health effects; hence, it is important to measure WAGs concentration levels to perform risk assessment and for health protection purposes. Methods A sy...

An ever-growing burden of scientific evidence links air pollution to different aspects of human health even at very low concentrations; the impact increases for those living in urban environments, especially the youngest and the elderly. This study investigated the exposure to air pollution of urban school children of Milan, Italy, by personal and...

Background: College campuses and universities are valuable settings for smoking prevention programs targeting young adults. Aim: To investigate smoking habits, electronic cigarette (e-cig) and heated tobacco product (HTP) use, exposure to passive smoke, compliance with smoking bans on campus, attitudes toward the anti-smoking policies, and educa...

Diet has long been identified as a major determinant of cardiovascular and other chronic diseases. In this study, we assess the relation between adherence to different dietary patterns and biochemical and metabolic parameters as well as the 10-year risk of major cardiovascular diseases (CVDs) in a community of blood donors in Northern Italy. We ass...

Background: The heme biosynthesis (HB) involves eight subsequent enzymatic steps. Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in the ferrochelatase (FECH) gene, which in the last HB step inserts ferrous iron into protoporphyrin IX (PPIX) to form heme. Aim and method: The aim of this work was to for the first time ana...

Objective The best approach to patients with adrenal incidentaloma (AI) and possible autonomous cortisol secretion (PACS) is debated. The aim of this study was to assess the metabolic effect of adrenalectomy in AI patients with PACS in relation to cortisol secretion parameters, peripheral activation, and glucocorticoid sensitivity. Design This is...

Purpose To investigate the impact of letrozole administration on follicular steroid hormones during controlled ovarian hyperstimulation for fertility preservation. Methods One hundred and nineteen women with cancer undergoing oocytes retrieval for fertility preservation were recruited. All women underwent ovarian hyperstimulation according to a ra...

Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as compounds present at low levels only in exposed subje...

Cadmium is a heavy metal with established adverse effects on human health, namely on bone, liver and kidney function and the cardiovascular system. We assessed cadmium exposure and its correlation with biomarkers of toxicity. We recruited 137 non-smoking blood donors without a history of chronic disease or cancer who resided in the Northern Italy p...

Implanted metallic medical devices release many of the same metals (e.g., aluminum, nickel, cobalt, chromium) that individuals are exposed to from environmental or occupational sources. At sufficiently high doses, these metals can produce adverse effects at the site of implantation, in target tissues distant to the implant site, or both. As a resul...

Per- and polyfluoroalkyl substances (PFASs) include persistent organic pollutants whose spread is still ubiquitous. Efforts to substitute substances of high concern with fluorinated alternatives, such as HFPO-DA (GenX), DONA (ADONA), and cC6O4, have been made. The aim of this work was to develop and validate an isotopic dilution liquid chromatograp...

In Italy, smoking is still widespread among a relatively high percentage of young people. This study aimed to develop and validate a questionnaire to assess smoking habits, passive smoke exposure, electronic cigarette (e-cig) and heated tobacco product (HTP) use, attitudes, knowledge, and needs among undergraduates. A questionnaire consisting of 84...

The trace element selenium is of considerable interest due to its toxic and nutritional properties, which markedly differ according to the dose and the chemical form. It has been shown that excess selenium intake increases the risk of type 2 diabetes and, possibly, other metabolic diseases like hyperlipidemia and non-alcoholic fatty liver disease (...

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these int...

Selenium is both an essential nutrient and a highly toxic element, depending on its dose and chemical forms. We aimed to quantify urinary selenium excretion and dietary selenium intake in 137 healthy non-smoking blood donors living in the northern Italian province of Reggio Emilia. We assessed selenium status by determining urinary selenium levels...

Pesticides used to protect agricultural crops may contaminate groundwater. This work aimed to identify the pesticides used in Lombardy, Italy, in 2016, their concentration in the groundwater and the risk for health associated with the intake of drinkable water in the adult population. The risk was evaluated for the presence of single and multiple a...

It is known that air pollution affects human health and commuting environments are significant contributors to the total daily personal exposure to air pollution. With this study we aim at assessing and comparing personal exposure to traffic-related air pollution and related estimated inhaled dose of different typical commuter profiles in real-worl...

Introduction Children with smoking parents are potentially exposed to Environmental Tobacco Smoke (ETS). The aims of this study were: 1) to assess ETS exposure in Milan schoolchildren, by measuring urinary cotinine (COTU), 2) to compare the parents' perception of children ETS exposure, with the actual ETS exposure measured by COTU, 3) to explore th...

Background: Formaldehyde and xylene are two hazardous chemicals widely used in pathology laboratories all over the world. The aim of this work was to survey a large volume pathology lab, measuring exposure of workers and residents to formaldehyde and xylene, and verify the efficacy of the undertaken preventive actions and the accomplishment with oc...

The aim of the present work was the application of hair biomonitoring to investigate exposure to pesticides in children and their parents residing in a vineyard area. Thirty-three children and 16 parents were involved in the study. Hair samples were self-collected before and after the application season (PRE- and POST-EXP samples). Information on s...

Overweight and obesity have high prevalence worldwide and assessing the metabolomic profile is a useful approach to study their related metabolic processes. In this study, we assessed the metabolomic profile of 1391 subjects affected by overweight and obesity, enrolled in the frame of the SPHERE study, using a validated LC–MS/MS targeted metabolomi...

The homeostasis of tissues in a chronic disease is an essential function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells with a consequent aggravation of symptoms. The protoporphyria (PP) is a rare chronic disease that causes phototoxicity in visible light with l...

Human biological monitoring is a powerful tool for scientists, policy makers, and occupational health‐care professionals, such as physicians and occupational hygienists, to assess and manage health risks associated with chemical exposures among the general population as well as at the workplace. This chapter will focus on using biological monitorin...

Background Human exposure to air pollutants, and specifically to particulate matter (PM) and volatile organic compounds (VOCs), may pose a relevant risk on human health. Aim To evaluate the personal exposure of adults living and working in Milan (Italy) by environmental and biological monitoring. Methods Personal exposure of 51 volunteer adults to...

Air pollution is a global threat to public health, especially when considering susceptible populations, such as children. A better understanding of determinants of exposure could help epidemiologists in refining exposure assessment methods, and policy makers in identifying effective mitigation interventions. Through a participatory approach, 73 and...

In the last two decades, hair, breast milk, meconium, and oral fluid have been investigated as specimens for biomonitoring pesticide exposure in alternative to urine and blood. The main feature of hair is the possibility to investigate exposure over a few months preceding sampling and to take into account cumulative and multiple exposure to pestici...

The identification of hyperandrogenism in polycystic ovary syndrome (PCOS) is concerning because of the poor accuracy of the androgen immunoassays (IA) and controversies regarding which androgens should be measured. The aim of our study was to evaluate the impact of the assessment of testosterone (T) and androstenedione (A) by liquid chromatography...

STUDY QUESTION Does oral Vitamin D supplementation alter the hormonal milieu of follicular fluid (FF) and the transcriptomic profile of luteinised granulosa cells (GCs) in women with Vitamin D deficiency undergoing IVF? SUMMARY ANSWER A transcriptomic signature relevant to oral Vitamin D supplementation in luteinised GCs was demonstrated, although...

Pesticides are chemicals widely applied in agriculture and proven environmental contaminants; their hazards include harmful effects on human health, therefore the evaluation of exposure is relevant to risk assessment. Hair is a non-invasive specimen that incorporates pollutants allowing an extended exposure window to be surveyed. Aim of this work w...

Background: Erythropoietic Protoporphyria (EPP) is a rare inherited hematological disorder resulting from reduced activity of the ferrochelatase (FECH), which catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme, in the last step of the biosynthetic pathway. FECH reduced activity leads to significantly elevated PPIX levels mai...

The homeostasis of tissues in chronic disease is an important function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells. Protoporphyria (PP) is a rare disease that causes photosensitivity at the visible light due to the accumulation of Protoporphyrin-IX in the der...

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement. Objective: To provide epidemiological data of EPP in Italy. Materials & methods: Prospective/retrospective data of EPP patients were collected by an Italian netwo...

Introduction: Bisphenol A (BPA) is the most used colour developer in thermal paper products such as cashiers' receipts, followed by Bisphenol S (BPS), Wincon 8 (D-8), and Pergafast 201® (PF201). These chemicals can migrate from the paper onto the skin and possibly be absorbed and metabolised. Until now, D-8 and PF201 have not been analysed in biol...

This study reports the development of a method based on headspace (HS)-solid-phase microextraction (SPME)-gas chromatography (GC)-triple quadrupole tandem mass spectrometry (MS/MS) for the quantification of 2- to 4-ring polycyclic aromatic hydrocarbons (PAHs) in saliva samples. Eight unmetabolized compounds (naphthalene, acenaphthylene, acenaphthen...

Purpose. Cortisol secretion, peripheral activation and sensitivity seem to be associated with hypertension (HY), type-2 diabetes (T2D) and fragility fractures (FX) even in eucortisolemic subjects. The aim of the present study was to determine the cut-off(s) of the parameters of cortisol secretion and peripheral activation for predicting the presenc...

PurposeCortisol secretion, peripheral activation, and sensitivity seem to be associated with hypertension (HY), type 2 diabetes (T2D), and fragility fractures (FX) even in eucortisolemic subjects. The aim of the present study was to determine the cutoff(s) of the parameters of cortisol secretion and peripheral activation for predicting the presence...

Background. Although thousands of different chemicals have been identified in cigarette smoke, the characterization of their urinary metabolites still requires significant research. The aim of this work was to perform an untargeted metabolomic approach to a pilot cross-sectional study conducted on subjects with different smoking habits and to compa...

Rationale Several phthalates and bisphenol A are endocrine‐disrupting chemicals (EDCs). Recently, their use has been partially restricted, and less toxic compounds, such as di‐2‐ethylhexyl terephthalate (DEHTP), have been placed on the market. The aim of this work was to develop and validate a method for the simultaneous quantitation of bisphenol A...

Background While tobacco smoke contains thousands of chemicals, some of which are carcinogenic to humans, the content of electronic cigarette smoke is less known. This work aimed to assess and compare the exposure associated with different smoking habits by profiling urinary mercapturic acids as biomarkers of toxic compounds. Methods In this pilot...

PurposeThe current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure...

In this study, the urinary concentrations of selected metals in workers from an electric steel foundry in Tunisia were assessed and compared with existing biological limit values and general population reference values. Moreover, the association between oxidative DNA damage, measured as urinary 8-oxo-7,8-dihydro-2’deoxyguanosine (8-oxodG) and co-ex...

Coke production was classified as carcinogenic to humans by the International Agency for Research on Cancer. Besides polycyclic aromatic hydrocarbons, coke oven workers may be exposed to benzene and other volatile organic compounds (VOCs). The aim of this study was to assess the exposure to several VOCs in 49 coke oven workers and 49 individuals li...

Introduction: The Clinica del Lavoro, the first clinic for occupational diseases of the world, was inaugurated in Milan on 20 March 1910; its first director was Luigi Devoto, who was in charge until 1935. The purpose of this work is to review the activities of industrial hygiene and toxicology carried out at the Clinica del Lavoro under the guidan...

Background: The Clinica del Lavoro of Milan provided several contributions to industrial hygiene and occupational toxicology during the twentieth century. Objectives: Describe the first years of the laboratory of industrial hygiene of Milan through three figures who played a leading role: Enrico Carlo Vigliani, Nicola Zurlo and Gianmario Cavagna...

Introduction: Environmental tobacco smoke (ETS) has been classified as carcinogenic to humans by the International Agency on Research on Cancer. Children with smoking parents are potentially exposed to ETS. The aim of the present study was the assessment of exposure to ETS in Milan schoolchildren, using biological monitoring. Methods: Eighty-two th...

The phototoxic reaction is a known feature of EPP at least in part triggered by the oxidative status, complement system activation, and mast cell response. The aim of this study was to verify some aspects involved in phototoxic reaction during a season. The complement system was evaluated by C3 assay, alternative pathway by factor-B, and classical...

Background: Solid waste incinerators (SWI) emit several pollutants among which polychlorodibenzodioxins and furans (PCDD/Fs), polychlorobiphenyls, metals, monocyclic and polycyclic aromatic hydrocarbons (PAHs). Aim of the study: To present a systematic review of peer-reviewed literature on human biological monitoring of exposure and effect followin...

Land Use Regression (LUR) modeling is a widely used technique to model the spatial variability of air pollutants in epidemiology. In this study, we explore whether a LUR model can predict home-to-school commuting exposure to black carbon (BC). During January and February 2019, 43 children walking to school were involved in a personal monitoring cam...