Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air.

Background: Several classifications of adult asthma patients using cluster analyses based on clinical and demographic information has resulted in clinical phenotypic clusters that do not address molecular mechanisms. Volatile organic compounds (VOC) in exhaled air are released during inflammation in response to oxidative stress as a result of activated leukocytes. VOC profiles in exhaled air could distinguish between asthma patients and healthy subjects.

Redox and epigenetic regulation of the APE1 gene in the hippocampus of piglets: The effect of early life exposures.

Oxidative stress via redox reactions can regulate DNA repair pathways. The base excision repair (BER) enzyme apurinic/apyrimidinic endonuclease 1 (APE1) is a key player in the redox regulation of DNA repair. Environmental factors can alter the methylation of DNA repair genes, change their expression and thus modulate BER activity and susceptibility to oxidative DNA damage.

Profiling of volatile organic compounds in exhaled breath as a strategy to find early predictive signatures of asthma in children.

Wheezing is one of the most common respiratory symptoms in preschool children under six years old. Currently, no tests are available that predict at early stage who will develop asthma and who will be a transient wheezer. Diagnostic tests of asthma are reliable in adults but the same tests are difficult to use in children, because they are invasive and require active cooperation of the patient.

Profile of volatile organic compounds in exhaled breath changes as a result of gluten-free diet.

In the present longitudinal study, we followed volatile organic compounds (VOCs) excreted in exhaled breath of 20 healthy individuals over time, while adhering to a gluten-free diet for 4 weeks prior to adherence to a normal diet. We used gas chromatography coupled with mass spectrometry (TD-GC-tof-MS) in combination with chemometric analysis to detect an array of VOCs in exhaled breath. Multivariate analysis was applied to extract the maximal information from the obtained data.

Non-alcoholic steatohepatitis: a non-invasive diagnosis by analysis of exhaled breath.

Background & Aims: Histological evaluation of a liver biopsy is the current gold standard to diagnose non-alcoholic steatohepatitis (NASH), but the procedure to obtain biopsies is associated with morbidity and high costs. Hence, only subjects at high risk are biopsied, leading to underestimation of NASH prevalence, and undertreatment. Since analysis of volatile organic compounds in breath has been shown to accurately identify subjects with other chronic inflammatory diseases, we investigated its potential as a non-invasive tool to diagnose NASH.

Whole-genome gene expression modifications associated with nitrosamine exposure and micronucleus frequency in human blood cells.

N-nitroso compounds (NOCs) are suspected human carcinogens and relevant in human exposure. NOCs also induce micronuclei (MN) formation in vivo. Since lymphocytic MN represent a validated biomarker of human cancer risk, establishing a link between NOC exposure and MN frequency in humans and concurrently investigating associated transcriptomic responses may provide crucial information on underlying molecular mechanisms that predispose to carcinogenicity.

Discriminative protection against hydroxyl and superoxide anion radicals by quercetin in human leucocytes in vitro.

Antioxidants play a vital role in the cellular protection against oxidative damage. Quercetin is a well-investigated antioxidant and known to be able to protect against cellular oxidative DNA damage. In this study, we tried to relate the protection by quercetin pre-treatment against oxidative DNA damage in human leucocytes in vitro to the interaction of quercetin in solution with hydroxyl and superoxide anion radicals as measured by electron spin resonance (ESR) spectrometry, using DMPO as a spin trap.

Comparison of coumarin-induced toxicity between sandwich-cultured primary rat hepatocytes and rats in vivo: a toxicogenomics approach.

Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro system with improved metabolic competence enhances the predictability for coumarin-induced in vivo toxicity by using a toxicogenomics approach.

Development and application of an electron spin resonance spectrometry method for the determination of oxygen free radical formation by particulate matter.

Exposure to increased levels of ambient particulate matter (PM) are associated with several health effects, including cardiopulmonary diseases. The formation of reactive oxygen species (ROS) is thought to play an important role in the induction of these health effects. To quantify the ROS generating capacityof PM,we developed an improved electron spin resonance (ESR) spectrometry-based method.

Genotoxicity and physicochemical characteristics of traffic-related ambient particulate matter.

Exposure to ambient particulate matter (PM) has been linked to several adverse health effects. Since vehicular traffic is a PM source of growing importance, we sampled total suspended particulate (TSP), PM(10), and PM(2.5) at six urban locations with pronounced differences in traffic intensity.

Differential gene expression in human peripheral blood mononuclear cells induced by cigarette smoke and its constituents.

In current molecular epidemiology studies, a wide range of methods are used to monitor early biological effects after exposure to xenobiotic agents. Gene expression profiling is considered a promising tool that may provide more sensitive, mechanism-based biomarkers. As a first step toward obtaining information on the applicability of gene expression profiles as a biomarker for early biological effects of carcinogen exposure, we conducted in vitro studies on human peripheral blood mononuclear cells (PBMC).

Neutrophil-mediated formation of carcinogenic N-nitroso compounds in an in vitro model for intestinal inflammation.

In order to study neutrophil-mediated formation of carcinogenic N-nitroso compounds as a mechanism of inflammation-related colon carcinogenesis, we designed an in vitro model for intestinal inflammation, consisting of a coincubation system with human colon cells (Caco-2 cells) and activated human neutrophils (PMN), as important immunoreactive cells. We investigated whether nitrosamines and nitrosamides could be formed upon addition of dimethylamine, morpholine and methylurea to the coincubations as nitrosatable precursors, which are known to produce carcinogenic N-nitroso compounds. Incubations of pure nitric oxide with dimethylamine and morpholine showed that NO-mediated formation of nitrosodimethylamine and nitrosomorpholine is possible under the incubation conditions.

Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls.

The evidence from epidemiological and experimental studies that vegetables reduce the risk of colorectal cancer is convincing. However, the involved genes and genetic pathways are not clear. The aim of this study was to identify genes that are modulated in vivo in colorectal mucosa by vegetables, and to investigate whether colon adenoma patients respond differently compared with healthy controls.

CYP1A2 and NAT2 genotype/phenotype relations and urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a human dietary intervention study.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking, and is subsequently metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). Respective genes encoding for these enzymes, display polymorphic distribution in the human population and are thus believed to cause interindividual differences in cancer risk susceptibility. The present study investigated the influence of dietary exposure and CYP1A2 and NAT2 genotypes and phenotypes on differential urinary PhIP excretion levels in 71 human volunteers after consumption of either a high (7.

Decreased human semen quality and organochlorine compounds in blood.

Background: Various studies have been performed in which potential effects of xenoestrogens on fertility or sperm parameters were investigated by comparing groups of subjects exposed to different levels of these chemicals.

Methods: In our study we used an alternative approach, as we selected one group of men with very poor semen quality and another group with normal semen quality and determined the blood organochlorine contents in order to determine whether a difference in these levels could be established. Organochlorine compounds, including polychlorinated biphenyls (PCB) and PCB metabolites, were detected using gas chromatography.