Multichannel gas-uptake/evolution reactor for monitoring liquid-phase chemical reactions.

The design of a headspace pressure-monitoring reactor for measuring the uptake/evolution of gas in gas-liquid chemical transformations is described. The reactor features a parallel setup with ten-reactor cells, each featuring a low working volume of 0.2-2 ml, a pressure capacity from 0 to 150 PSIa, and a high sensitivity pressure transducer. The reactor cells are composed of commercially available disposable thick-walled glassware and compact monolithic weld assemblies. The software interface controls the reactor temperature while monitoring pressure in each of the parallel reactor cells. Reactions are easy to set up and yield high-density gas uptake/evolution data. This instrument is especially well suited to acquire quantitative time-course data for reactions with small quantities of gas consumed or produced.

Molecular changes in the esophageal epithelium after a subchronic exposure to cigarette smoke in the presence of bile-acid reflux.

BACKGROUND: Gastroesophageal reflux of bile acids plays an important role in the development of Barrett's esophagus (BE)-associated esophageal adenocarcinoma (EAC). Cigarette smoke has been demonstrated to exacerbate the effects of reflux and thus the initial stages of EAC carcinogenesis. To date, no in vivo studies have been conducted to look at the concomitant effects of cigarette smoke and bile acids on EAC incidence. METHODS: In this pilot study, rats that underwent esophagoduodenal anastomosis (EDA) surgery to induce reflux were exposed to whole-body cigarette smoke 3 weeks after surgery. Smoke exposure (135 mg/m³/day) was done for 4 h/day for 5 consecutive days and animals were euthanized after a 48-h recovery period. RESULTS: Exposure to EDA-smoke accelerated the development of BE when compared to EDA-air. The presence of reflux caused a significant 3.5-fold increase in nuclear factor-κB-inducing kinase (NIK) staining (1.47 ± 0.6; p = 0.01). Animals with both reflux and smoking had the highest (10-fold; 4 ± 0.9) induction of cyclooxygenase-2 (COX-2) expression (p < 0.05). Similarly, there was a 10-fold increase in 4-aminobiphenyl (4-ABP) protein adducts identified in all smoke-exposed animals (p < 0.01). CONCLUSION: Cigarette smoke aggravates reflux-induced BE and potentially accelerates the progression of BE to EAC through the loss of manganese superoxide dismutase (MnSOD), and overexpression of NF-κB- and COX-2-mediated factors.

Human exposure to selected animal neurocarcinogens: a biomarker-based assessment and implications for brain tumor epidemiology.

This review is based on the proceedings from the Second Lebow Conference, held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the four most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types.

Haemoglobin adducts as biomarkers of exposure to tobacco-related nitrosamines.

A sensitive gas chromatography/mass spectrometry (GC/MS) method was developed to measure nitrosamine-haemoglobin adducts (HPB-Hb) (4-hydroxy-3-pyridinyl-1-butanone) at trace levels in red blood cells of smoking and non-smoking mothers and their newborn babies. GC/MS methods with chemical ionization (CI) of methane reagent gas in both positive and negative ion mode as well as electron ionization (EI) were studied to determine differences in sensitivity among the various ionization methods. Detection limits using both positive and negative chemical ionization modes were found to be 30 fmol HPB, whereas detection using electron impact modes yielded a detection limit of 80 fmol HBP. In order to apply the various methods of detection to tobacco-exposed samples from human populations, we characterized adduct levels in maternal as well as paired fetal samples obtained from mothers exposed to tobacco smoke during pregnancy. Maternal samples were characterized using serum cotinine levels and were classified as non-smokers, passively smoke-exposed women, less than one pack per day smokers and greater than one pack per day smokers. Paired maternal and fetal blood samples were obtained at delivery for qualitative and qualitative analysis of nitrosamine adducts. Comparative derivatization of HPB released under alkaline hydrolysis conditions was performed using O-bis(trimethylsilyl)-trifluoroacetamide (BSTFA) and 2,3,4,5,6-pentafluorobenzoylchloride (PFBC). Both negative CI and positive CI modes of analysis were compared to the more widely accepted EI modes of mass spectrometric analysis. These results suggest that both NICI and PICI modes of detection offer a greater sensitivity of adduct characterization when compared with EI ionization techniques and that either NICI or PICI modes are preferably applicable towards the detection of human biomarker assessment of tobacco-related nitrosamines.

Rapid effects of diesel exhaust particulate extracts on intracellular signaling in human endothelial cells.

Inhalation of ultrafine particulate matter (PM) in air pollution increases cardiovascular mortality by passing into systemic circulation and possibly affecting endothelial cell (EC) function. This study identified the chemical constituents, including polycyclic aromatic hydrocarbons (PAHs), in diesel exhaust particulate extracts (DEPEs) prepared from a truck run at different speeds and engine loads. The short-term effects of DEPEs alone or in combination with estradiol (E(2)) on MAPK (ERK1/2), AKT, and eNOS activation and nitric oxide (NO) production in human umbilical vein EC (HUVEC) were evaluated. Notably, DEPE from a truck run under increasing loads (L) stimulated phosphorylation of MAPK, AKT, and eNOS whereas DEPE from the truck run at increasing speeds (S) did not affect MAPK alone, but inhibited E(2)-induced MAPK and eNOS phosphorylation. Higher PAH concentrations in the DEPE L versus DEPE S samples correlate with the observed differences in cellular activities. Like E(2), DEPEs rapidly increased NO with the DEPE L sample acting additively with E(2) and then inhibiting E(2)-induced NO with longer treatment time. Like E(2), DEPEs increased trans-endothelial electrical resistance (TEER) across a monolayer of HUVEC. These data are the first characterization of rapid effects of DEPE in human EC and may indicate mechanisms for diesel exhaust in vascular function.

Determination of tobacco specific hemoglobin adducts in smoking mothers and new born babies by mass spectrometry.

Biological markers for assessment of exposure to a variety of environmental carcinogens has been widely applied in both basic as well as clinical research. Exposure to tobacco smoke presents an ideal environment with which to develop, characterize, and refine biological markers, especially of those carcinogens found in tobacco. In the present study, a sensitive gas chromatography/mass spectrometry (GC/MS) method was developed to measure nitrosamine- hemoglobin adducts (HPB-Hb (4-Hydroxy-3-pyridinyl-1-butanone) at trace levels in red blood cells of both African-American and Caucasian smoking and nonsmoking mothers and their infants. Gas chromatographic and mass spectrometric methods with chemical ionization (CI) of methane reagent gas in both positive and negative ion mode as well as electron ionization (EI) were studied to determine differences in sensitivity of detection among the various ionization methods. Detection limits using both positive and negative chemical ionization modes were found to be 30 femtomoles of HPB, whereas detection using electron impact modes yielded a detection limit of 80 femtomoles of HBP. Comparative derivatization of HPB was performed using O-bis(Trimethylsilyl)-trifluoroacetamide (BSTFA) and 2, 3, 4, 5, 6-Pentafluorobenzoylchloride (PFBC). Both Negative CI and Positive CI modes of analysis were compared to the more widely accepted EI modes of mass spectrometric analysis.

Elevation of serum endothelins and cardiotoxicity induced by particulate matter (PM2.5) in rats with acute myocardial infarction.

Epidemiological studies have defined a significant positive association of acute exposure to ambient concentrations of particulate matter (PM) with increased daily mortality and hospital admission for cardiovascular diseases. Experimental studies have shown that animals with pre-existing cardiovascular diseases are more susceptible to the cardiac effect of PM exposure. The present study was undertaken to investigate possible involvement of upregulation of the endothelin system in PM exposure-induced cardiotoxicity in rats with acute myocardial infarction (MI). Adult male Sprague Dawley rats were subjected to occlusion of the left coronary artery and displayed myocardial infarction 12 h after the surgery. The heart rate significantly decreased and premature ventricular complexes of the electrocardiogram occurred in the myocardial infarct animals. Exposure to PM(2.5) via intratracheal instillation with 2.0 mg in 0.3 mL normal saline significantly worsened the ventricular arrhythmia along with a further decrease in heart rate. The same PM exposure only caused slight cardiac changes in the sham-operated animals. Serum total endothelin concentrations were significantly elevated in both myocardial infarct rats and shamoperated controls in response to PM exposure. However, increased numbers of the endothelin receptor type A on the cardiomyocytes were observed only in the infarct myocardium. This study thus suggests that upregulation of the endothelin system in rats with MI is likely involved in the PM exposure-induced cardiotoxicity.