No abstract

The impact of the insecticide chlorpyrifos (CPF) on the mammalian digestive system has been poorly described. The present study aimed at evaluating the effect of chronic, low-dose exposure to CPF on the composition of the gut microbiota in a Simulator of the Human Intestinal Microbial Ecosystem: the SHIME and in rats. The SHIME comprises six reactor vessels (stomach to colon). The colonic segments were inoculated with feces from healthy humans. Then, the simulator was exposed to a daily dose of 1 mg of CPF for 30 days. The changes over time in the populations of bacteria were examined at different time points: prior to pesticide exposure (as a control) and after exposure. In parallel, pregnant rats were gavaged daily with 1 mg/kg of CPF (or vehicle) until the pups were weaned. Next, the rats were gavaged with same dose of CPF until 60 days of age (adulthood). Then, samples of different parts of the digestive tract were collected under sterile conditions for microbiological assessment. Chronic, low-dose exposure to CPF in the SHIME and in the rat was found to induce dysbiosis in the microbial community with, in particular, proliferation of subpopulations of some strains and a decrease in the numbers of others bacteria. In compliance with European guidelines, the use of the SHIME in vitro tool would help to (1) elucidate the final health effect of toxic agents and (2) minimize (though not fully replace) animal testing. Indeed, certain parameters would still have to be studied further in vivo.

The epithelium's barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs), multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier) during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC)-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR) and localization (using immunofluorescence) of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs). In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning) but not at day 60 (adulthood). At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal epithelium may be a risk factor for digestive inflammatory diseases.

Placenta constitutes a vital organ of exchange between mother and foetus. In addition to this favourable effect for foetal development, placenta indirectly may allow trans fer of several maternal blood xenobiotics. Human placenta and umbilical cord blood are interesting models for investigating maternal environment and the metabolism, the bioactivation and the transfer of carcinogens such as polycyclic aromatic hydrocarbons. We used them to assess the effect of a woman's smoking on the foetus. Few studies cover this subject. In pregnant women who have continued to smoke, benzo[a]pyrene compound of cigar ette smoke is metabolically activated to diol-epoxide derivative: benzo[a]pyrene-trans-7,8-dihydrodiol-9,10- epoxide, ultimate carcinogen (BPDE-I). This derivative is covalently fixed on DNA and gives BPDE-I-DNA adducts. By a competitive immunoassay technique, we determined BDPE-I-DNA adducts in 20 samples of placenta and umbilical cord blood from women who smoked (n=15) and who did not (n=10). Tobacco consumption was checked by urinary cotinine determination. In the group of smokers levels of adducts were found in 13 specimens of placenta (from 10 to 60 finol/50 μg of DNA) and 12 umbilical cord blood (from 10 to 22.15 fmol/50 μg of DNA) samples. These results indicate that a mother's tobacco consumption is linked to the accumulation of BPDE-I-DNA adducts in the placenta, which are seen in smaller quantities in the umbilical cord blood, probably because of the metabolic capacity of the placenta and the transfer of B[a]P from the mother to the foetus.

No abstract

549 IN NEONATES, THE INCIDENCE OF APNEA DEPENDS ON A VARIETY OF FACTORS, SUCH AS BIRTH WEIGHT, 1 SEX, 2 GESTATIONAL AGE, 3 AND POSTNATAL AGE. 3,4 Central apnea is generally reported as occurring more frequently during active sleep than during quiet sleep. 2,3,[5][6][7] Many authors have pointed out that apnea incidence is also closely related to ambient temperature in both full-term [8][9][10] and preterm neonates 9,11,12 and that the rate of apneic events is increased by warm exposure (i.e., thermal drive). Although preterm neonates are more often exposed to cool stress than to warm stress, little is known about the influence of cool exposure on the incidence of apnea in the different sleep states. Bader et al 11 reported a lower rate of central apnea during transient decreases in incubator temperature from warm (29°C) to thermoneutral conditions (24°C) over 30 minutes, although this was only seen during quiet sleep for preterm infants and during active sleep for term infants.The mechanism linking thermal stress and apnea is unknown and thus warrants further investigation. On the basis of the above-cited studies, it can be supposed that suprapontine influences modify respiratory control, which must be considered as a multiple-interaction system. Abnormal functional interaction among the respiratory system, thermoregulatory system, and sleep processes may alter compensatory responses to autonomic cardiovascular or respiratory challenge and increase the likelihood of life-threatening events later in life. 13 The effect of thermal stress is usually assessed by monitoring the body's internal temperature (generally esophageal or rectal temperatures, which supposedly represent the core temperature) and/or mean skin temperature. 14 However, the central controller of the thermoregulatory system receives thermal inputs from thermosensitive structures distributed throughout the body. The regulated variable therefore results from a weighted sum of different body temperatures. 15 Hence, to fully understand the thermal influence on apnea incidence in cool environments, it is essential to quantify the magnitude of body cooling that is proportional to the radiant, convective, conductive, and evaporative heat losses (i.e., body heat loss) on the other. Any failure to maintain thermal balance stimulates the body's thermal control mechanisms and thus triggers regulatory adjustments. This approach may help clarify a hypothesis raised by Perlstein et al, 9 whereby apnea is not specifically induced by changes in air temperature but, rather, through processes controlling the overall body heat loss (BHL). Hence, in the present study, the role of thermal drive in the mechanisms underlying the genesis of central apnea in the sleeping neonate was assessed by taking into account BHL during mild warm and cool thermal exposures.Central apneic events were monitored in a group of 22 nearterm neonates. Indeed, there are few published studies on these infants, who are generally considered to be physiologically similar to term infants, even t...

Wrapping low-birth-weight neonates in a plastic bag prevents body heat loss. A bonnet can also be used, since large amounts of heat can be lost from the head region, but may provide too much thermal insulation, thus increasing the risk of overheating. We assessed the time required to reach warning body temperature (t38 degrees C), heat stroke (t40 degrees C), or extreme value (t43 degrees C) in a mathematical model that involved calculating various local body heat losses. Simulated heat exchanges were based on body surface temperature distribution measured in preterm neonates exposed to 33 degrees C air temperature (relative air humidity: 35%; air velocity: <0.1 m/s) and covered (torso and limbs) or not with a transparent plastic bag. We also compared metabolic heat production with body heat losses when a bonnet (2 or 3.5 mm thick) covered 10%, 40%, or 100% of the head. Wrapping neonates in a bag (combined or not with a bonnet) does not induce a critical situation as long as metabolic heat production does not increase. When endogenous heat production rises, t38 degrees C ranged between 75 and 287, t40 degrees C between 185 and 549, and t43 degrees C between 287 and 702 min. When this increase was accompanied by a fall in skin temperature, overheating risk was accentuated (37

The present investigation was aimed at assessing the effect of home-based training on cardiorespiratory responses in children surgically corrected for congenital heart impairment using dyspnea threshold (DT) as training intensity. A group of 23 children aged 15 +/- 1.4 years who had undergone surgical correction for congenital heart disease (CHD group) and 12 healthy children used as a control group performed an exercise protocol during which aerobic capacity, ventilatory threshold (VT), and DT were assessed. Afterwards, the CHD group was divided into two subgroups: trained and untrained subjects. Training sessions over a period of 2 months were performed at an intensity corresponding to DT by the CHD trained group. Dyspnea was scored according to a visual analog scale during the warm up, at each exercise stage, and during the recovery period. DT was located on the oxygen uptake/dyspnea curve when a sudden increase in the dyspnea score occured, while VT was defined according to the methodology previously employed by Beaver and colleagues. The results showed that children who had undergone surgery for CHD had reduced aerobic capacity. No significant difference was observed between VT and DT in children corrected for CHD. These two thresholds were highly related. Home-based training at DT did not strongly improve aerobic capacity nor did it influence the relationship between VT and DT. Further studies should be conducted to confirm these preliminary findings, particularly when aerobic capacity is improved by training.