Paolo Mocarelli

• Prof
• Università degli Studi di Milano-Bicocca

STUDY QUESTION Is there an association between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and fecundability and infertility among Seveso women and their daughters? SUMMARY ANSWER TCDD exposure is associated with a decrease in fecundability and increased risk of infertility in women, as well as their daughters. WHAT IS KNOWN ALREADY In an...

Type 2 diabetes (T2DM) is a disease with heterogenous phenotypic manifestations.¹ Distinct subgroups, each with salient metabolic characteristics, risk of complications, and response to treatments, have been identified.²,³ An accurate phenotyping could improve outcome prediction and prevention strategies. However, which phenotyping parameters may e...

In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with delayed pubertal development in animal studies. No epidemiologic study has investigated this association. We examined the relationship of in utero exposure to TCDD with reported age at onset of menarche in female children born to a unique cohort of TCDD-exposed women...

Background In animal studies, perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters thyroid homoeostasis and thyroid hormone concentrations; epidemiologic evidence is limited. Objectives We aimed to determine the association of prenatal exposure to TCDD with thyroid hormone concentrations in the Seveso Second Generation Study, a...

Background: Exposure to endocrine disrupting compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during susceptible developmental windows may alter risk of metabolic disease later in life. Animal studies of in utero and lactational TCDD exposure report associations with alterations in insulin sensitivity and energy homeostasis, but epidem...

Background/objectives In utero exposure to endocrine-disrupting compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may alter risk of obesity and related metabolic disease later in life. We examined the relationship of prenatal exposure to TCDD with obesity and metabolic syndrome (MetS) in children born to a unique cohort of TCDD-exposed w...

Context Hypoglycemic drugs with proven cardiovascular benefits are recommended for patients with type 2 diabetes and cardiovascular disease, whether the beneficial effects extend to those at lower risk remains unclear. Aim We investigate the long-term cardiovascular effects of pioglitazone or sulphonylureas across the spectrum of pretreatment card...

Background: Prenatal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure has been shown to alter sexual differentiation of the brain in animal models, impacting pubertal development, behavior, cortical dominance, and cognition. The effects of early life exposure to dioxin-like compounds on human neurodevelopment, however, are less clear and warran...

Background: Exposure to endocrine-disrupting chemicals (EDCs) during sensitive developmental windows, such as in utero, may influence disease later in life but direct measurement of fetal hormones is not feasible. The ratio of the length of the second finger digit to the fourth digit (2D:4D), a sexually dimorphic trait, is a biomarker of androgen...

Background: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is proposed to interfere with fetal growth via altered activity of the aryl hydrocarbon receptor (protein: AHR; gene: AHR) pathway which regulates diverse biological and developmental processes including xenobiotic metabolism. Genetic variation in AHR is an important driver of susceptibilit...

Background: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant that can bioaccumulate in humans, cross the placenta, and cause immunological effects in children, including altering their risk of developing allergies. On July 10, 1976, a chemical explosion in Seveso, Italy, exposed nearby residents to a high amount of T...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is neurotoxic in animals but few studies have investigated its effects on the human brain. Related dioxin-like compounds have been linked to poorer cognitive and motor function in older adults, with effects more pronounced in women, perhaps due to the loss of neuro-protective estrogen in menopause. On 10 J...

Background: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods:...

Background The disasters at Seveso, Three Mile Island, Bhopal, Chernobyl, the World Trade Center (WTC) and Fukushima had historic health and economic sequelae for large populations of workers, responders and community members. Methods Comparative data from these events were collected to derive indications for future preparedness. Information from...

On July 10, 1976, an explosion at a chemical plant in Seveso, Italy, released up to 30kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-the most potent dioxin congener. Twenty years later, the Seveso Women's Health Study (SWHS) initiated a follow-up assessment of a cohort of female Seveso residents. Researchers collected serial blood, measured for T...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Although experimental evidence suggests that TCDD alters thyroid hormone levels in rodents, human data are inconsistent. In 1976, a trichlorophenol plant exploded in Seveso, Italy. Women living in highly exposed areas were followed through the Seveso Women's Healt...

Animal evidence suggests an association between exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and adverse pregnancy outcomes. Epidemiologic studies report inconsistent results, but are limited by narrow range of exposure, small sample size, and lack of a biologic measure of highest lifetime exposure. On July 10, 1976, a chemical explosion...

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association. On July 10, 1976, a chemical explosion in Seveso, Italy resulted in the highe...

The Seveso Women's Health Study (SWHS) is a historical cohort study of the female population residing near Seveso, Italy, on 10 July 1976, when a chemical explosion resulted in the highest known residential exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Individual TCDD concentration was measured in serum collected near the time of the expl...

Background: In animal studies, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters glucose transport and increases serum lipid levels and blood pressure. Epidemiologic evidence suggests an association between TCDD and metabolic disease. Objectives: On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential expos...

BACKGROUND AND AIMS: Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovasc...

Background and aims: Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovas...

The 1976 trichlorophenol reactor explosion led to the most massive acute airborne release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into a densely populated area that has been documented to date. This industrial accident caused a persistent skin disease, chloracne, in nearly 200 individuals and led to some of the highest body doses of TCDD ever...

2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD), a widespread environmental contaminant, disrupts multiple endocrine pathways. The International Agency for Research on Cancer classified TCDD as a known human carcinogen, based on predominantly male occupational studies of increased mortality from all cancers combined. After a chemical explosion on 10...

From may 2008 to June 2010 we have analyzed faecal samples of 2306 subjects: in the subjects was performed the coproparassitological standard examination and in 523 of them was performed scotch test. Of the 2306 subjects examined, 101 resulted positive, 59 to the coproparasitological exam, 43 to scotch test, and 1 to both of them (Taenia spp.). In...

To investigate the association of normal fasting plasma glucose (FPG) and the risk for type 2 diabetes. Data concerning 13,845 subjects, aged 40-69 years, who had their FPG measured at least three times between 1992 and 2008 were extracted from a database. Three FPG groups were defined (51-82, 83-90, and 91-99 mg/dL). A Cox proportional hazards ana...

In recent decades, young men in some industrialized areas have reportedly experienced a decrease in semen quality. We examined effects of perinatal dioxin exposure on sperm quality and reproductive hormones. We investigated sperm quality and hormone concentrations in 39 sons (mean age, 22.5 years) born between 1977 and 1984 to mothers exposed to di...

Introduction: Urinary tract infections are one of the most common diseases found in medical practice and are diagnosed with traditional methods of cultivation on plates. In this study we evaluated an automated instrumentation for screening of the urinocultures that can provide results quickly and guarantee traceability. The comparison of results ob...

An important prognostic factor in patients with chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy chain variable region genes (IgVH), whose determination depends on the comparison between the nucleotide sequence of IgVH expressed by the leukemic clone of the patient and the germ line of the concerned family. If the...

Pollution may play a role in population trends of declining semen quality and regional differences in time to pregnancy (TTP) in industrialized societies. Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been suspected. In 1976, an explosion near Seveso, Italy resulted in the highest TCDD exposure known in residential populations....

Primary cell cultures from renal cell carcinoma (RCC) and normal renal cortex tissue of 60 patients have been established, with high efficiency (more than 70%) and reproducibility, and extensively characterized. These cultures composed of more than 90% of normal or tumor tubular cells have been instrumental for molecular characterization of Annexin...

To investigate the possibility of using the ClinProt technique to find serum cancer related diagnostic markers that are able to better discriminate healthy subjects from patients affected by renal cell carcinoma (ccRCC). Renal cell carcinoma is the most common malignancy of the kidney. Biomarkers for early detection, prognosis, follow-up, and diffe...

Renal cell carcinoma (RCC) is one of the major causes of cancer death and is radio- and chemoresistant. Urine of 29 healthy subjects and 39 clear cell RCC patients were analyzed using the ClinProt technique to search for possible biomarkers for early RCC diagnosis. A cluster of three signals (marker A= at m/z 1827 ± 8 Da, marker B = 1914 ± 8 Da and...

We verified the feasibility of plasma bound method for detecting renal cell carcinoma (RCC) combining the study of plasma DNA concentration and microsatellite alterations (LOH). Plasma DNA concentration was evaluated with real-time PCR in 54 patients with renal neoplasm before surgery and in 20 of these patients during a 26-64 month follow-up. Micr...

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) are products and byproducts of industrial or combustion processes. These compounds have been identified in almost all animal species, including humans. Some of these chemicals can disrupt multiple endocrine pathways and induce a lar...

MODULAR ANALYTICS Serum Work Area (in USA Integrated MODULAR ANALYTICS, MODULAR ANALYTICS is a trademark of a member of the Roche Group) represents a further approach to automation in the laboratory medicine. This instrument combines previously introduced modular systems for the clinical chemistry and immunochemistry laboratory and allows customis...

Aquaporin (AQP)1 belongs to a ubiquitous family of water channel proteins characterized by sequence similarity and the presence of two NPA (Asp-Pro-Ala) motifs existing in almost all organs and tissues. Currently, 13 human AQPs are known and they are divided into two subgroups according to their ability to transport only water molecules, such as AQ...

Clear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approa...

MODULAR ANALYTICS Serum Work Area (in USA Integrated MODULAR ANALYTICS, MODULAR ANALYTICS is a trademark of a member of the Roche Group) represents a further approach to automation in the laboratory medicine. This instrument combines previously introduced modular systems for the clinical chemistry and immunochemistry laboratory and allows customise...

Genes mapping in regions harbouring recurrent DNA copy number alterations or significant LOH events. Genes are listed in order of chromosome and genomic start position. Using UCSC genome browser a complete gene annotation was retrieved including Entrez Gene ID, Gene symbol, Gene name, chromosome, cytoband and genomic start and end positions. In add...

Complete description about methods used to prepare biological samples for microarray experiments and about statistical procedures implemented to analyse data.

Chromosomal maps of LOH regions and DNA copy number alterations in the 27 RCC samples. Each map represents one single chromosome (from 1 to 22). For each tumor sample compared to corresponding normal control, probability of LOH events as calculated by dChip2006 was displayed along the entire chromosome, from p to q arm, according to the following c...

Complete list of differentially expressed genes (DEGs) in RCC tissues as compared to normal cortical samples. GeneChip® HG-U133 Plus 2.0 array probesets were annotated using an updated custom chip description file and metaprobes corresponding to unique Entrez Gene IDs having differential expression levels in tumor samples as compared to normal samp...

Differentially expressed genes (DEGs) mapping in aberrant chromosomal regions. For each gene (reported as Entrez Gene ID, Gene symbol and Gene name), genomic position (in terms of chromosome, cytoband and start and end positions) and type of DNA alteration (labelled as CN gain, CN loss, LOH+CN loss and LOH+CN neutral) occurring in the corresponding...

Clear cell renal carcinoma samples analyzed in this study and corresponding clinical data. Cases are listed in order of increasing tumor size, stage and grade classes. For each case, patient's gender, tumor size at the time of surgery, tumor stage and nuclear grade classifications and time elapsed from surgery are reported. These samples were analy...

Several efforts are today focused on studying the most wide form of tumor affecting human kidney, renal cell carcinoma (RCC), because of our inability to diagnose and treat this very aggressive neoplasia. Different complementary approaches based on genomic and proteomic tools are used to highlight its altered molecular processes, and new developed...

Environmental toxicants are allegedly involved in decreasing semen quality in recent decades; however, definitive proof is not yet available. In 1976 an accident exposed residents in Seveso, Italy, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The purpose of this study was to investigate reproductive hormones and sperm quality in exposed males. We...

Surface-activated chemical ionization (SACI) was employed for the analysis of cocaine and its metabolite, benzoylecgonine, extracted from hair. Following decontamination and acid hydrolysis procedures on the hair sample, the sample solution was diluted (1:10) and directly analyzed by liquid chromatography/surface-activated chemical ionization multi...

Uterine leiomyomata (fibroids), benign neoplasms of the smooth muscle, are a major cause of hysterectomy. Exposure to hormonally active chemicals may play an etiologic role. The authors investigated the risk of uterine leiomyoma associated with exposure to 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) for women who resided near Seveso, Italy, in 1976...

The application of genome-wide approaches to the molecular characterization of cancer was investigated, identifying footprints that can potentially assist in the subclassification of tumors in order to contribute to diagnosis and clinical management of patients. High resolution DNA copy number analysis by single nucleotide polymorphism mapping arra...

Human aquaporin-1 (AQP1) is the most studied member of the aquaporin family, acting as molecular water channel. It is also considered a differentiation marker for proximal renal tubular cells, from which clear cells renal cell carcinoma (RCC) originates, playing an important role in urine formation. We therefore studied AQP1 expression at the prote...

Introduction: Antimicrobial resistance among nosocomial pathogens is steadily increasing, causing complications to patients and raising health care costs.To prevent the diffusion of antimicrobial-resistant organisms, a surveillance program was conducted at Desio Hospital.The aim of this work was to evaluate the prevalence of alert organisms in pati...

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with alterations in ovarian function and hormones in animals, it has not been studied in humans. On 10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later, we initiated the Seveso Women's Health Study to...

The course of early stage CLL patients may be very different with patients who never need therapy and other who need therapy at different times. The presence or absence of somatic mutations in the immunoglobulin heavy-chain gene of the CLL cell (mutational status) was recently identified as one of the most predictive factors for the time from diagn...

Pharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents. We used blood concentrations to calculate TCDD elimination half-life. Variables examined by statistical analysis include age, latency from exposure, sex, TCDD concentration an...

Aquaporins (AQPs) are an ubiquitous family of proteins characterized by sequence similarity and the presence of two NPA (Asp-Pro-Ala) motifs. At present, 13 human AQPs are known and they are divided into two subgroups according to their ability to transport only water molecules (AQP0, AQP1, AQP2, AQP4, AQP5, AQP6, and AQP8), or also glycerol and ot...

Introduction: Antimicrobial resistance among nosocomial pathogens is steadily increasing, causing complications to patients and raising health care costs.To prevent the diffusion of antimicrobial-resistant organisms, a surveillance program was conducted at Desio Hospital.The aim of this work was to evaluate the prevalence of alert organisms in pati...

The new atmospheric pressure chemical ionization source, named surface-activated chemical ionization (SACI), has been used in conjunction with high-flow gradient chromatography to reduce the matrix effect. This high-flow gradient chromatography approach avoids the co-elution of analyte and biological matrix compounds that leads to a reduction in qu...

The new ionization method, called surface-activated chemical ionization (SACI), was employed for the analysis of fives drugs (morphine, codeine, 6-monoacetylmorphine (6-MAM), benzoylecgonine and cocaine) by ion trap mass spectrometry. The results so obtained have been compared with those achieved by using atmospheric pressure chemical ionization (A...

The role of C-reactive protein (CRP) in heart failure is not well studied. We assessed the prognostic value of CRP in patients randomized in Val-HeFT (Valsartan Heart Failure Trial) and studied changes in CRP that were associated with valsartan. Characteristics of patients with baseline CRP levels above and below the median value were compared. Uni...

Renal cell carcinoma (RCC) tissue is composed of a mixture of neoplastic and normal cells, which complicate proteome analysis. The aim of our study was to investigate whether it is feasible to establish primary cell cultures of RCC and of renal cortex maintaining the tissue phenotype along with a more homogeneous and enriched cytological material....

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residi...

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are widespread environmental contaminants that exist as complex mixtures and are frequently detected at part-per-trillion (ppt) levels in humans. Using isotope dilution high-resolution gas chromatography/ high-resolution mass spect...

This epidemiological study in a group of Italian children was undertaken in order to increase our knowledge of the prevalence of Molar Incisor Hypomineralisation (MIH) in different European countries. A population of school children aged 7.3 - 8.3 years, living in Lissone, Northern Italy, was examined for the presence and severity of MIH. Of a tota...