157 research outputs found
Vinyl chloride: still a cause for concern.
Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL
of Environmental Health Sciences
ABSTRACT: The stereoselectivity of cytosolic glutathione S-transferases (GS-T) in rat tissues was determined using (Β±)-benzo(a)pyrene 4,5-oxid
Workgroup Report: Biomonitoring Study Design, Interpretation, and CommunicationβLessons Learned and Path Forward
Human biomonitoring investigations have provided data on a wide array of chemicals in blood and urine and in other tissues and fluids such as hair and human milk. These data have prompted questions such as a) What is the relationship between levels of environmental chemicals in humans and external exposures? b) What is the baseline or βbackgroundβ level against which individual levels should be compared? and c) How can internal levels be used to draw conclusions about individual and/or population health? An interdisciplinary panel was convened for a 1-day workshop in November 2004 with the charge of focusing on three specific aspects of biomonitoring: characteristics of scientifically robust biomonitoring studies, interpretation of human biomonitoring data for potential risks to human health, and communication of results, uncertainties, and limitations of biomonitoring studies. In this report we describe the recommendations of the panel
Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort
Background: Prenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth;
however, previous findings are inconsistent and based on few studies.
Objectives: We assessed whether prenatal exposure to BPA and phthalates was associated with
fetal growth in a Spanish birth cohort of 488 motherβchild pairs.
Methods: We measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites
(DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites
(LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy.
We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference
(AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy
(weeks 12β20 and 20β34), and for birth weight, birth length, head circumference at birth, and
placental weight.
Results: Overall, results did not support associations of exposure to BPA or DEHPm during
pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with
FL at 20β34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per
doubling of MBzP concentration. MBzP was positively associated with birth weight among boys
(48 g; 95% CI: 6, 90) but not in girls (β27 g; 95% CI: β79, 25) (interaction p-value = 0.04). The
LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12β20 pregnancy
weeks [β4.88% of HC average (95% CI: β8.36, β1.36%)].
Conclusions: This study, one of the first to combine repeat exposure biomarker measurements
and multiple growth measures during pregnancy, finds little evidence of associations of BPA or
phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated
with some fetal growth parameters, but these findings require replication
N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial
AIMS/HYPOTHESIS: The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces plateletβmonocyte conjugation in blood from patients with type 2 diabetes. METHODS: In this placebo-controlled randomised crossover study, the effect of oral NAC dosing on plateletβmonocyte conjugation and intraplatelet GSH was investigated in patients with type 2 diabetes (eligibility criteria: men or post-menopausal women with well-controlled diabetes (HbA(1c)β<β10%), not on aspirin or statins). Patients (nβ=β14; age range 43β79Β years, HbA(1c)β=β6.9βΒ±β0.9% [52.3βΒ±β10.3Β mmol/mol]) visited the Highland Clinical Research Facility, Inverness, UK on dayΒ 0 and dayΒ 7 for each arm of the study. Blood was sampled before and 2Β h after oral administration of placebo or NAC (1,200Β mg) on dayΒ 0 and dayΒ 7. Patients received placebo or NAC capsules for once-daily dosing on the intervening days. The order of administration of NAC and placebo was allocated by a central office and all patients and research staff involved in the study were blinded to the allocation until after the study was complete and the data fully analysed. The primary outcome for the study was plateletβmonocyte conjugation. RESULTS: Oral NAC reduced plateletβmonocyte conjugation (from 53.1βΒ±β4.5% to 42.5βΒ±β3.9%) at 2Β h after administration and the effect was maintained after 7Β days of dosing. Intraplatelet GSH was raised in individuals with depleted GSH and there was a negative correlation between baseline intraplatelet GSH and plateletβmonocyte conjugation. There were no adverse events. CONCLUSIONS/INTERPRETATION: The NAC-induced normalisation of intraplatelet GSH, coupled with a reduction in plateletβmonocyte conjugation, suggests that NAC might help to reduce atherothrombotic risk in type 2 diabetes. FUNDING: Chief Scientist Office (CZB/4/622), Scottish Funding Council, Highlands & Islands Enterprise and European Regional Development Fund. TRIAL REGISTRATION: isrctn.org ISRCTN89304265 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-012-2685-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users
The N-glycome of human embryonic stem cells
<p>Abstract</p> <p>Background</p> <p>Complex carbohydrate structures, glycans, are essential components of glycoproteins, glycolipids, and proteoglycans. While individual glycan structures including the SSEA and Tra antigens are already used to define undifferentiated human embryonic stem cells (hESC), the whole spectrum of stem cell glycans has remained unknown. We undertook a global study of the asparagine-linked glycoprotein glycans (N-glycans) of hESC and their differentiated progeny using MALDI-TOF mass spectrometric and NMR spectroscopic profiling. Structural analyses were performed by specific glycosidase enzymes and mass spectrometric fragmentation analyses.</p> <p>Results</p> <p>The data demonstrated that hESC have a characteristic N-glycome which consists of both a constant part and a variable part that changes during hESC differentiation. hESC-associated N-glycans were downregulated and new structures emerged in the differentiated cells. Previously mouse embryonic stem cells have been associated with complex fucosylation by use of SSEA-1 antibody. In the present study we found that complex fucosylation was the most characteristic glycosylation feature also in undifferentiated hESC. The most abundant complex fucosylated structures were Le<sup>x </sup>and H type 2 antennae in sialylated complex-type N-glycans.</p> <p>Conclusion</p> <p>The N-glycan phenotype of hESC was shown to reflect their differentiation stage. During differentiation, hESC-associated N-glycan features were replaced by differentiated cell-associated structures. The results indicated that hESC differentiation stage can be determined by direct analysis of the N-glycan profile. These results provide the first overview of the N-glycan profile of hESC and form the basis for future strategies to target stem cell glycans.</p
Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity
Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production
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