Cadmium Transport in a Model of Neonatal Intestinal Cells Correlates to MRP1 and Not DMT1 or FPN1

Newborns have a higher gastrointestinal uptake of cadmium than adults. In adults, the iron transporters DMT1 and FPN1 are involved in the intestinal absorption of cadmium, while in neonates, the mechanisms for cadmium absorption are unknown. We have investigated possible cadmium transporters in the neonatal intestine by applying a model of immature human intestinal epithelial Caco-2 cells. To mimic the continuous cadmium exposure via diet in neonates, cells were allowed to differentiate for 7 days in medium containing 1 μM CdCl2. A dramatic upregulation of the MT1 gene expression followed cadmium pretreatment, indicating a high sensitivity of the immature cells to cadmium. Cadmium pretreatment increased the basolateral efflux of 109Cd, without causing any effects on the passive diffusion of mannitol or the transepithelial electrical resistance. The augmented transport of cadmium was correlated to an upregulation of MRP1 gene expression and increased activity of the efflux protein MRP1. No effects were observed on gene expression of the efflux proteins MRP2 and P-gp or the iron transporters DMT1, DMT1-IRE and FPN1. In conclusion, our data indicate that continuous cadmium exposure increases the absorption of the metal in immature intestinal cells and that MRP1 is involved in the intestinal cadmium absorption in newborns.

Treatment of hypothyroidism

Treatment of primary hypothyroidism is usually both gratifying and simple and, in most cases, lifelong. Thyroxine, as l-thyroxine sodium, is the therapy of choice and is available in the UK as tablets of 25, 50, and 100 μ‎g. A greater variety of tablet strength is marketed in other parts of Europe and North America. Thyroxine has a half-life of some 7 days and should be given as a single daily dose which improves compliance. Thyroxine, taken at bedtime, is associated with higher thyroid hormone concentrations and lower thyroid-stimulating hormone (TSH) concentrations compared to the same dose taken in the morning, probably due to greater gastrointestinal uptake of thyroxine during the night (1). Omitting the occasional tablet is of no consequence and those who forget to take their medication, e.g. on vacation, will experience little in the way of symptoms for the first 2 weeks.