In vitro evidence of the influence of complexation of Pu and Am on uptake by human lung epithelial cells Calu-3.

Understanding the mechanisms involved in retention and clearance of actinides from the lungs after accidental intake is essential for the evaluation of the associated radiological risks. Although the absorption of radioelements has been shown in vivo to depend on their nature and physico-chemical properties, their mechanisms of translocation remain unknown. In this study, we have evaluated in vitro the binding and uptake by bronchial epithelial cells Calu-3 of 2 transuranic actinides, plutonium (Pu) and americium (Am), as the first steps of translocation across the pulmonary barrier. For this purpose, Calu-3 cells grown to confluence in 24-well plates were exposed to the radioelements for 24 h under various culture conditions. Two compartments were identified for the association of actinides to cells, corresponding to the membrane bound and internalized fractions. Binding of Pu was slightly higher than of Am, and depended on its initial chemical form (nitrate, citrate, colloids). Uptake of Pu and Am nitrate was higher in serum-free conditions than in supplemented medium, with an active mechanism involved in Pu internalization. Overall, our results suggest that complexation of actinides to bioligands may have an influence on their uptake by pulmonary epithelial cells, and therefore possibly on their subsequent absorption into blood.

Evidence for a differential translocation of actinides across human lung epithelial cell monolayer in vitro according to their physicochemical properties and the presence of a chelating agent.

The epithelial cell plays a key role in the transfer of radionuclides from lungs to blood following pulmonary exposure. The present study was designed to evaluate the transfer across human lung epithelial cells of various actinides (plutonium, americium and uranium), the influence of the physicochemical properties of plutonium compounds and of the chelating agent diethylene triamine pentaacetic acid (DTPA). To address this question, Calu-3 cells grown in a bicameral culture system were used. The integrity of the epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER) and the passage of a fluorescent marker, lucifer yellow. Activity measurement in basal compartment following periodic collection of culture medium was made from 2 h to seven days. To facilitate data handling and analysis, the statistical tool STATBIODIS was used. The results indicate differences in transfer for the different elements, and according to Pu physicochemical properties. Though to various extents, the chelating agent DTPA always increased the transfer of Pu and Am across the epithelial cells, without altering the integrity of the epithelial barrier. This in vitro cell culture model, by mimicking translocation of actinides from lungs to blood, can represent a valuable tool to further understand the underlying mechanisms and properties controlling this process.

[Accidental ingestion of paracetamol in the for of the pediatric syrup EFFERALGAN: case studies during the six months following the institution of the child-proof top]. / Ingestions accidentelles de paracétamol sous la forme de sirop EFFERALGAN pédiatrique: étude des observations au cours des six mois qui ont suivi la mise en place d'un bouchon de sécurité.

During the 6 months following the child-proof top commercialisation for the paediatric syrup EFFERALGAN in France, 51 cases of accidental ingestion were collected by the Marseilles Poison Centre. For 21 pour cent of them, the alleged dose taken was greater than the toxic dose. For 2 cases only, the responsible bottle had a child-proof top and was open on the table. For all other cases, it was simple-opening bottles (old bottles still present in houses, or bottles without a special top but sold in order to get rid of stocks). This study proves that such a preventive measure (modification of the top of the syrup bottles) is only fully effective if additional measures are undertaken such as return of unsold stocks or the provision of information to pharmacists and physicians.

The management of extreme hypernatraemia secondary to salt poisoning in an infant.

We describe a five-week-old boy who had seizures and extreme hypernatraemia secondary to ingesting an improper home-made formula. Initial sodium concentration was 211 mmol.l-1. Other clinical and biological features were moderate dehydration and renal insufficiency with generous urine output and high urinary sodium concentration. Fluid therapy with hypotonic dextrose solution corrected the volume deficit in 48 h and progressively decreased the serum sodium concentration. During ICU stay the patient developed recurrent episodes of seizures and pulmonary oedema requiring mechanical ventilation for five days. Recovery was complete with no abnormal sequelae after a ten-month follow-up. Salt poisoning is in unusual cause of extreme hypernatraemia. It can be safely managed with fluid therapy alone if urine output is preserved, with progressive decrease of serum sodium as target. If this condition is recognized, outcome should be favourable.

[Accidental ingestions of paracetamol in the form of EFFERALGAN pediatric syrup: experience of the Marseille Anti-poison Center during 1998]. / Ingestions accidentelles de paracétamol sous la forme de sirop EFFERALGAN pédiatrique: expérience du Centre Antipoison de Marseille au cours de l'année 1998.

In 1998, 77 cases of accidental ingestion of paracetamol paediatric syrup (Efferalgan) in children were notified to the Marseille Poison Centre. In a quarter of them, the alleged dose taken was greater than the toxic dose. Ingestion was mainly due to the child opening the bottle. The proximate marketing of a product with a child-proof top, which should allow the number of accidents to be reduced. Doctors and pharmacists should be informed rapidly, so that they can warn the families who still have the old type of bottle.