Urinary profiles to assess polycyclic aromatic hydrocarbons exposure in coke-oven workers.

Aim of the study was the assessment of exposure of coke-oven workers to polycyclic aromatic hydrocarbons (PAHs) by determination of urinary profiles of hydroxylated and unmetabolized PAHs. Fifty-five Polish coke-oven workers were investigated by measurement of 12 hydroxylated metabolites of PAHs (OHPAHs) (1-, 2-hydroxynaphthalene; 2-, 9-hydroxyfluorene; 1-, 2-, 3-, 4-, 9-hydroxyphenanthrene; 1-hydroxyypyrene, 6-hydroxychrysene and 3-hydroxybenzo[a]pyrene) and 13 unmetabolized PAHs (U-PAHs) (from naphthalene to benzo[a]pyrene), in spot urine samples collected at the end of the workshift. U-PAHs with four or less rings were detected in all samples.

Assessing variability and comparing short-term biomarkers of styrene exposure using a repeated measurements approach.

The aim of this work is to compare several short-term biomarkers of styrene exposure, namely urinary styrene (StyU), mercapturic acids (M1+M2), mandelic acid (MA), phenylglyoxylic acid (PGA), phenylglycine (PHG), and 4-vinylphenol conjugates (VP), for use as biomarkers of exposure in epidemiologic studies. A repeated measurements protocol (typically 4 measurements per worker over 6 weeks) was applied to measure airborne styrene (StyA) and urinary biomarkers in 10 varnish and 8 fiberglass reinforced plastic workers. Estimated geometric mean personal exposures to StyA were 2.

Methodological issues in the biological monitoring of urinary benzene and S-phenylmercapturic acid at low exposure levels.

Biological monitoring of low level exposure to pollutants is a very challenging analytical activity, and the quality of results is difficult to assess, especially when a certified reference material is unavailable. The aim of this work was to evaluate the reliability of the assays used to measure urinary benzene (Benz-U) and S-phenylmercapturic acid (SPMA), by applying an internal quality control protocol. Urine spot samples from 705 subjects who were either members of the general urban population, gasoline station attendants, or refinery plant workers were assayed for Benz-U and SPMA, using GC/MS and LC/MS/MS, with quantification limits of 15 ng/L and 0.

Dermal exposure to polycyclic aromatic hydrocarbons in asphalt workers.

Objectives: To assess dermal exposure to 16 polycyclic aromatic hydrocarbons (PAHs) in asphalt workers by applying polypropylene pads to six body sites (neck, shoulder, upper arm, wrist, groin, ankle), to identify the compounds and exposure sites most representative, and to integrate dermal exposure results with environmental and biological data.

Methods: Twenty-four asphalt workers were recruited. Dermal exposure was assessed during a single work shift.

A novel headspace solid-phase microextraction method using in situ derivatization and a diethoxydiphenylsilane fibre for the gas chromatography-mass spectrometry determination of urinary hydroxy polycyclic aromatic hydrocarbons.

An innovative and simple headspace solid-phase microextraction method using a novel diethoxydiphenylsilane fibre based on in situ derivatization with acetic anhydride was optimized and validated for the gas chromatography-mass spectrometry determination of some monohydroxy metabolites of polycyclic aromatic hydrocarbons, namely 1-hydroxynaphthalene, 2-hydroxynaphtalene, 9-hydroxyfluorene, 2-hydroxyfluorene and 1-hydroxypyrene at trace levels in human urine. Enzymatic hydrolysis was applied before derivatization, whereas extraction conditions, i.e.

Hypertension alters the function of nitrergic and sensory innervation in mesenteric arteries from female rats.

Objectives: To investigate whether hypertension could modify the function of adrenergic, nitrergic, and sensory innervations involved in the electrical field stimulation-induced response in mesenteric arteries from female rats.

Methods: Vascular reactivity experiments were performed in endothelium-denuded mesenteric arteries from normotensive, Wistar-Kyoto and spontaneously hypertensive female rats; protein expression was measured by western blot; nitric oxide release was measured by fluorometry; calcitonin gene-related peptide and noradrenaline release were determined by enzyme immunoassay.

Results: The electrical field stimulation-induced contractions were significantly lower in segments from spontaneously hypertensive rats than those of Wistar-Kyoto rats.

Accuracy of computed tomographic colonography for the detection of polyps and colorectal tumors: a systematic review and meta-analysis.

Background: The real accuracy of computed tomographic colonography (CTC) is still unknown.

Objective: To perform a meta-analysis of the diagnostic accuracy of CTC for the detection of polyps and colorectal tumors.

Selection Of Studies: Studiesassessing the accuracy of CTC for the detection of colorectal polyps and tumors were selected.

Urinary polycyclic aromatic hydrocarbons and monohydroxy metabolites as biomarkers of exposure in coke oven workers.

Objectives: To assess exposure to polycyclic aromatic hydrocarbons (PAHs) using 13 unmetabolised PAHs (U-PAHs) and 12 monohydroxy metabolites (OHPAHs) in urine, and to compare the utility of these biomarkers.

Methods: 55 male Polish coke oven workers collected urine spot samples after a workshift. U-PAHs (naphthalene, acenaphtylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[k]fluoranthene, benzo[b]fluoranthene, benzo[a]pyrene) were determined by automatic solid phase micro-extraction followed by gas chromatography/mass spectrometry (GC/MS).

Immunomodulation of FOXP3+ regulatory T cells by the aromatase inhibitor letrozole in breast cancer patients.

Purpose: We have shown previously that tumor infiltration by FOXP3+ regulatory T cells (Treg) is associated with increased relapse and shorter survival of patients with both in situ and invasive breast cancer. Because estrogen regulates Treg numbers in mice and promotes the proliferation of human Tregs, we hypothesized that blocking estrogen receptor-alpha signaling would abrogate Tregs and be associated with response to hormonal therapy and increased survival.

Experimental Design: FOXP3+ Tregs were quantified in tumor samples collected at baseline by incisional biopsy and after 6 months at definitive surgery in 83 elderly breast cancer patients (T2-4 N0-1) enrolled in a randomized phase II trial based on 6 months of primary letrozole (2.

The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy.

Basal-like tumours account for 15% of invasive breast carcinomas and are associated with a poorer prognosis and resistance to therapy. We hypothesised that this aggressive phenotype is because of an intrinsically elevated hypoxic response. Microarrayed tumours from 188 patients were stained for hypoxia-inducible factor (HIF)-1alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast tumours.

Self-collected urine sampling to study the kinetics of urinary toluene (and o-cresol) and define the best sampling time for biomonitoring.

Purpose: To study the excretion kinetics of urinary toluene, TOL-U, and o-cresol, o-C, following occupational exposure to toluene in order to define the best time for sample collection, to apply a non-invasive approach based on self-collected urine sampling.

Methods: Five rotogravure printing workers exposed to uncontrolled levels of toluene collected spot urine samples over three consecutive working days and the following day of rest. In each sample TOL-U and o-C were measured and kinetics of excretion evaluated.

Quantification of 13 priority polycyclic aromatic hydrocarbons in human urine by headspace solid-phase microextraction gas chromatography-isotope dilution mass spectrometry.

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants in both living and working environments. The aim of this study was the development of a headspace solid-phase microextraction gas chromatography-isotope dilution mass spectrometry (HS-SPME/GC-IDMS) method for the simultaneous quantification of 13 PAHs in urine samples. Different parameters affecting PAHs extraction by HS-SPME were considered and optimized: type/thickness of fiber coatings, extraction temperature/time, desorption temperature/time, ionic strength and sample agitation.

Phosphorylated ERalpha, HIF-1alpha, and MAPK signaling as predictors of primary endocrine treatment response and resistance in patients with breast cancer.

Purpose: We aimed to identify signaling pathways involved in the response and resistance to aromatase inhibitor therapy in patients with breast cancer.

Patients And Methods: One hundred fourteen women with T2-4 N0-1, estrogen receptor (ER) alpha-positive tumors were randomly assigned to neoadjuvant letrozole or letrozole plus metronomic cyclophosphamide. Twenty-four tumor proteins involved in apoptosis, cell survival, hypoxia, angiogenesis, growth factor, and hormone signaling were assessed by immunohistochemistry in pretreatment samples (eg, caspase 3, phospho- mammalian target of rapamycin, hypoxia-inducible factor 1alpha [HIF-1alpha], vascular endothelial growth factor, mitogen-activated protein kinase [MAPK], phosphorylated epidermal growth factor receptor, phosphorylated ERalpha [pERalpha]).

Asthmatic symptoms after exposure to ethylenebisdithiocarbamates and other pesticides in the Europit field studies.

We conducted a multicenter prospective study to assess the effects of occupational exposure to ethylenebisdithiocarbamate fungicides and/or other pesticides on self-reported asthma and asthmatic symptoms. This multicenter study was conducted among 248 workers exposed to pesticides and 231 non-exposed workers from five field studies. The five field studies were carried out in The Netherlands, Italy, Finland, and two studies in Bulgaria.

Biological monitoring and questionnaire for assessing exposure to ethylenebisdithiocarbamates in a multicenter European field study.

This study deals with pesticide exposure profile in some European countries with a specific focus on ethylenebisdithiocarbamates (EBDC). In all, 55 Bulgarian greenhouse workers, 51 Finnish potato farmers, 48 Italian vineyard workers, 42 Dutch floriculture farmers, and 52 Bulgarian zineb producers entered the study. Each group was matched with a group of not occupationally exposed subjects.

Development of a gas chromatography/mass spectrometry method to quantify several urinary monohydroxy metabolites of polycyclic aromatic hydrocarbons in occupationally exposed subjects.

The aim of this study was the development of a method for the determination of 12 urinary monohydroxy metabolites of PAHs, namely 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene. Analytes were determined in the presence of deuterated analogues as internal standards, by GC/MS operating in the electron impact mode. Sample preparation was performed by enzymatic hydrolysis of glucoronate and sulphate conjugates of hydroxy metabolites of PAHs, liquid-liquid extraction with n-hexane, and derivatization with a silylating reagent.

An integrated approach to biomonitoring exposure to styrene and styrene-(7,8)-oxide using a repeated measurements sampling design.

The aim of this work was to investigate urinary analytes and haemoglobin and albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers. We obtained three or four air and urine samples from each exposed worker (eight reinforced plastics workers and 13 varnish workers), one air and urine samples from 22 control workers (automobile mechanics) and one blood sample from all subjects. Median levels of exposure to Sty and StyOX, respectively, were 18.

Aldosterone induces endothelial dysfunction in resistance arteries from normotensive and hypertensive rats by increasing thromboxane A2 and prostacyclin.

Background And Purpose: The present study was designed to assess whether cyclooxygenase-2 (COX-2) activation is involved in the effects of chronic aldosterone treatment on endothelial function of mesenteric resistance arteries (MRA) from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR).

Experimental Approach: Relaxation to acetylcholine was measured in MRA from both untreated and aldosterone-treated strains. Vasomotor responses to prostacyclin and U46619 were also analysed.

Down-regulation of phosphatidylinositol 3'-kinase/AKT/molecular target of rapamycin metabolic pathway by primary letrozole-based therapy in human breast cancer.

Purpose: The phosphatidylinositol 3'-kinase (PI3K)/AKT/molecular target of rapamycin (mTOR) pathway is involved in the development of tumor resistance to endocrine therapy in breast cancer cell lines and represents an attractive target for pharmacologic intervention. However, the effects of endocrine therapy with aromatase inhibitors on in vivo expression of this signaling cascade, and its relation to tumor response and patient outcome, is unknown.

Experimental Design: PI3K, phospho-AKT (pAKT) and phospho-mTOR were assessed by immunohistochemistry on tumor specimens collected at baseline and after 6 months of treatment in 113 elderly breast cancer patients consecutively enrolled in a randomized phase II trial of primary letrozole therapy and letrozole associated with metronomic cyclophosphamide.

Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery.

The aim of this study was to analyze whether endogenous male sex hormones influence the release of thromboxane A2(TXA2) and its role in the electrical field stimulation (EFS)-induced response, as well as the mechanism involved. For this purpose, endothelium-denuded mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used to measure TXA2 release; EFS-induced response, nitric oxide (NO), norepinephrine (NA), and prostaglandin (PG) I2 release were also measured in the presence of the TXA2 synthesis inhibitor furegrelate. Orchidectomy increased basal and EFS-induced TXA2 release.

[Biological monitoring in the molding of plastics and rubbers].

This survey was carried out in the molding of plastics and rubbers, in the "Professional Cancer Prevention Project" sponsored by the Lombardy region with the objective of developing and implementing protocols for evaluating exposure to carcinogens through the biological monitoring. The realities of molding the thermoplastic polymer ABS, rubber, and thermosetting plastics containing formaldehyde were examined. The carcinogenic substances identified in these processes were: 1,3-butadiene, acrylonitrile and styrene in molding ABS, polycyclic aromatic hydrocarbons (PAH) in molding rubber, and formaldehyde in molding the thermosetting plastics.

[Exposure to polycyclic aromatic hydrocarbons (PAH) in rubber forming industry].

Among various chemical agents present at the workplaces in the rubber industry, a particular attention was adressed to the Polycyclic Aromatic Hydrocarbons (PAH) contained in oil and carbon black, but some questions regarding level of exposure are also controversially discussed. The literature reports that PAH may have irritant effects; moreover some of these have been recognized as probably or possibly carcinogenic to human by the International Agency for Research on Cancer, the European Union, and other institutions. In Lombardy, a study aimed to evaluate the occupational exposure in Benzo[b]fluorantene the rubber forming industry was planned during last two years.

Expression of BNIP3 correlates with hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha and the androgen receptor in prostate cancer and is regulated directly by hypoxia but not androgens in cell lines.

Background: BNIP3 is a hypoxia-induced protein involved in cell death and survival but its role in human tumors is unclear. This study investigated the role of BNIP3 in prostate cancer.

Methods: The expression of BNIP3, the androgen receptor (AR), hypoxia inducible factor (HIF)-1alpha, HIF-2alpha and the hypoxia regulated gene GLUT1 were assessed in tissue microarrays constructed from 149 radical prostatectomy specimens.

Cytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer.

Introduction: Hypoxia-inducible factor (HIF)-1alpha levels in invasive breast carcinoma have been shown to be an adverse prognostic indicator. Cellular HIF-1alpha activity is regulated by factor-inhibiting hypoxia-inducible factor 1 (FIH-1). In hypoxia, FIH-1 hydroxylation of Asn803 within the C-terminal transactivation domain does not occur and HIF-1alpha forms a fully active transcriptional complex.

Prognostic significance of microvessel density and other variables in Japanese and British patients with primary invasive breast cancer.

The purpose of this study is to investigate the associations of microvessel density (MVD) and other pathological variables with survival, and whether they accounted for survival differences between Japanese and British patients. One hundred seventy-three Japanese and 184 British patients were included in the study. British patients were significantly older (56.