Traffic-related air pollution and respiratory health during the first 2 yrs of life.

As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 microm (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GINI) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 microg m(-3), 1.38-4.39 x 10(-5) m(-1), and 19.5-66.9 microg x m3, respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI)): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75), respectively) and dry cough at night (OR (95% CI): 1.31 (1.07-1.60), 1.27 (1.04-1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.     

Establishment of a novel in vitro system for studying the interaction of xenobiotic metabolism of liver and intestinal microflora

We developed a new two-chamber system for the coculture of hepatocytes and fecal microflora under aerobic and anaerobic conditions, respectively, to investigate the sequential metabolism of chemicals by the liver and microflora in vitro. The culture device consisted of two chambers separated by a permeable polycarbonate membrane. In the aerobic compartment, hepatocytes were cultivated as a monolayer on the membrane and in the anaerobic compartment fecal microflora as a suspension. To characterize the metabolic capacity of the microflora and hepatocytes, various marker enzymes were studied. Azoreductase, nitroductase, beta-glucuronidase, beta-glucosidase and sulphatase were tested in the microflora of the feces from three volunteers who had had significantly different eating habits for years (daily meat, mixed diet, vegetarian). The microflora exhibited significant activities and the various enzymes differed only moderately in the samples from the three volunteers. For rat hepatocytes the activities of various cytochrome P450 forms and conjugating enzymes served as markers. The enzyme activities were tested in the coculture system during a 4-h culture period intended for the test protocol. Deethylation of ethoxycoumarin and 2alpha-, 6beta- and 16alpha-hydroxylation of testosterone decreased by about 30%, 25%, 40% and 20%, respectively, while there was no loss of glucuronidation and sulphonation of 3-OH-benzo(a)pyrene nor of glutathione conjugation of 1-chloro-2,4-dinitrobenzene during the 4-h culture period. The activities of the tested hepatic phase I and II enzymes were not changed after coculture of the hepatocytes with the microflora for 4 h. The applicability of the in vitro system for studying the metabolic interaction of liver and microflora was demonstrated using 7-ethoxycoumarin and the developmental drug EMD 57033, a thiadiazinon derivative from Merck KGaA, as model compounds. Both compounds were oxidized and conjugated by liver cells. In the coculture of hepatocytes and fecal microflora the resulting glucuronides and sulphoconjugates were split by hydrolytic enzymes of the intestinal microflora.     

Trichlorfon induces spindle disturbances in V79 cells and aneuploidy in male mouse germ cells

In order to assess the effects of trichlorfon on cell division and on aneuploidy induction, we conducted an in vitro assay for spindle disturbances using V79 cells and an in vivo assay for aneuploidy induction in meiosis of male mice using multicolour fluorescence in situ hybridization (FISH) with epididymal sperm. In the in vitro assay, the chemical caused a concentration-dependent increase in the incidence of initial and full c-mitoses in the dose range 40-120 microg/ml trichlorfon. The mitotic index (MI) was decreased between 40 and 100 microg/ml trichlorfon, whereas at 120 microg/ml the MI was back to the control level, coinciding with the dramatic increase in c-mitoses. The results confirm that trichlorfon is a potent spindle poison in V79 cells. In the in vivo multicolour FISH assay, administration of trichlorfon to male mice at single doses of 200, 300 and 405 mg/kg caused a dose-dependent increase of the frequencies of disomic sperm (0.068, 0.074 and 0.134%, respectively) compared with the corresponding controls (0.046, 0.042 and 0.056%, respectively). The prevalence of X-X-8 and Y-Y-8 sperm suggests that trichlorfon affected chromosome segregation predominantly during the second meiotic division. Diploid sperm were not induced by trichlorfon treatment, indicating that no meiotic block occurred. It is concluded that trichlorfon is a potent spindle poison in V79 cells and induces aneuploidy in mouse spermatocytes during meiosis.     

Relation between stressful life events,neuropeptides and cytokines: results from the LISA birth cohort study

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-γ (IFN-γ) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-γ concentrations in children’s blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation.     

Methods for assessing gastrointestinal absorption of strontium in humans by stable tracer techniques

Intestinal absorption of strontium from an oral test dose was studied in 13 healthy human volunteers using double tracer techniques with two stable strontium isotopes as tracers. Defined amounts of one isotope were administered orally, while tracer amounts of the second isotope were injected intravenously. Two different methods were used to assess the total fraction absorbed (f1 value). Fractional intestinal strontium absorption can be calculated from the ratio of the two isotopes in plasma or urine samples (in this paper called the double-isotope method) or the convolution integral technique, since both methods provide an accurate estimate of fractional absorption and yield comparable results. The latter additionally provides information on the absorption kinetics in the gastrointestinal tract. The absorption varies with respect to the chemical form and to the amount administered. Absorption patterns are characteristically different for uptake from solutions or from whole meals.     

Effects of particulate air pollution on blood pressure and heart rate in subjects with cardiovascular disease: a multicenter approach

Given the hypothesis that air pollution is associated with elevated blood pressure and heart rate, the effect of daily concentrations of air pollution on blood pressure and heart rate was assessed in 131 adults with coronary heart disease in Helsinki, Finland; Erfurt, Germany; and Amsterdam, the Netherlands. Blood pressure was measured by a digital monitor, and heart rate was calculated as beats per minute from an electrocardiogram recording with the patient in supine position. Particle concentrations were measured at central measuring sites. Linear regression was used to model the association between 24-hr mean concentrations of particles and blood pressure and heart rate. Estimates were adjusted for trend, day of week, temperature, barometric pressure, relative humidity, and medication use. Pooled effect estimates showed a small significant decrease in diastolic and systolic blood pressure in association with particulate air pollution; a slight decrease in heart rate was found. Of the three centers, Erfurt revealed the most consistent particle effects. The results do not support findings from previous studies that had shown an increase in blood pressure and heart rate in healthy individuals in association with particles. However, particle effects might differ in cardiac patients because of medication intake and disease status, both affecting the autonomic control of the heart.     

Determinants of health policy impact: comparative results of a European policymaker study

Summary Objectives: This article will use a new theoretical framework for the analysis of health policy impact introduced by Rütten et al. (2003). In particular, it will report on a comparative European study of policymakers perception and evaluation of specific determinants of the policy impact, both in terms of output (implemented measures) and outcome (health behaviour change). Policy determinants investigated are goals, resources, obligations and opportunities as related to the policymaking process. Methods: Theory is applied to a comparative analysis of prevention and health promotion policy in Belgium, Finland, Germany, The Netherlands, Spain and Switzerland. The study is MED2-part of a project that has developed a Methodology for the Analysis of the Rationality and Effectiveness of Prevention and Health Promotion Strategies (MAREPS) within the EU-BIOprogram. A mail survey of 719 policymakers on the executive and administrative level selected by a focused sample procedure was conducted. This survey used policymakers experience and evaluative expertise to analyse determinants of policy output and outcome. Results: Regression analyses reveal differential predictive power of policy goals, resources, obligations, as well as of political, organisational and public opportunities. For instance, whereas resources, concreteness of goals, and public opportunities have significant importance for health outcome of policy, obligations and organisational opportunities significantly predict policy output. Conclusions: Results are discussed in terms of rationality and effectiveness of health policy. They indicate that six sensitising constructs derived from the theoretical framework represent equivalent structures across nations. They comprise a validated instrument that can be used for further comparative health policy research.