These data suggest that antibiotic prophylaxis does not reduce the overall incidence of urinary tract infection in children with low grade vesicoureteral reflux. However, such a strategy may prevent further urinary tract infection in boys with grade III reflux.

Retinoids are vitamin A (retinol) derivatives essential for normal embryo development and epithelial differentiation. These compounds are also involved in chemoprevention and differentiation therapy of some cancers, with particularly impressive results in the management of acute promyelocytic leukemia (APL). Although highly effective in APL therapy, resistance to retinoic acid (RA) develops rapidly. The causes of this resistance are not completely understood and the following factors have been involved: increased metabolism, increased expression of RA binding proteins, P-glycoprotein expression, and mutations in the ligand binding domain of RARalpha. RA exerts its molecular actions mainly through RAR and RXR nuclear receptors. In addition to the nuclear receptor based mechanism of RA action, covalent binding of RA to cell macromolecules has been reported. RA derives from retinol by oxidation through retinol and retinal dehydrogenases, and several cytochrome p450s (CYPs). RA is thereafter oxidized to several metabolites by a panel of CYPs that differs for the different RA isomers. Phase II metabolism, mainly glucuronidation, is also observed. The role RA metabolism plays in the expression of its biological actions is not completely understood: in several systems, metabolism decreases RA activity, whereas in other systems metabolism appears involved in its action. In addition, several RA metabolites have shown activity and cannot be classified as only catabolites. Therapy of cancer with retinoids is still in its infancy, but the use of new analogues with improved pharmacological properties, along with combination with other drugs, could undoubtedly improve the management of several cancers in the future.

. By comparing the -fold induction of luciferase activity, all retinoids tested were equipotent at transactivating RARE-tk-Luc whatever the RAR considered. However, the best induction of the transcription was obtained for RAR␣, which was 5-fold higher than for RAR␤ and 10-fold higher than for RAR␥. In conclusion, these data show that ATRA metabolites can bind to and activate the three RARs with variable relative affinity but with similar efficacy. These results suggest that ATRA metabolites may activate several signaling pathways and probably play an important role in cellular physiology and cancer therapy.Vitamin A and its derivatives (retinoids) are natural compounds that play central roles in several physiological processes such as embryonic development, proliferation, differentiation, and apoptosis (reviewed in Ref. 1). Beside their role in the physiology of normal cells, retinoids possess pharmacological properties used in dermatology and in cancer therapy, including epithelial cancers, precancerous lesions (2), and acute promyelocytic leukemia (3).All-trans-retinoic acid (ATRA 1 ) (see Fig. 1), which is considered as one of the most active retinoid, is metabolized by several cytochrome P450s (CYPs) (4). CYPs are heme proteins catalyzing the oxidation of several endobiotics and xenobiotics such as environmental pollutants and drugs. The CYP-mediated metabolism may transform some substrates into inactive compounds but can also lead to the formation of biologically active metabolites. ATRA is metabolized into several oxidized metabolites, including 4-oxo-RA, 4-OH-RA, 18-OH-RA, and 5,6-epoxy-RA (Fig. 1) (reviewed in Ref. 5). All of these metabolites have shown biological activity, e.g. 4-oxo-RA is a highly active modulator in embryogenesis (6). It has also been shown that 4-oxo-RA, 4-OH-RA, and 5,6-epoxy-RA can inhibit the growth of several breast cancer cell lines (7,8). Some of these metabolites can inhibit growth and induce differentiation of rhabdomyosarcoma cells (9) and regulate the expression of several genes involved in differentiation and embryogenesis (6, 10). We have recently shown that ATRA metabolites, including 4-oxo-, 4-OH-, 18-OH-, and 5,6-epoxy-RA, can induce granulocytic differentiation of NB4 acute promyelocytic leukemia cells, elicit nuclear bodies reorganization, and induce the degradation of the chimeric protein PML-RAR␣ (11).The retinoid signal is transduced by two families of nuclear receptors, the retinoic acid receptor (RAR) family comprising three isotypes, RAR␣, RAR␤, and RAR␥, and the retinoid X receptor (RXR) family comprising also three isotypes, RXR␣, RXR␤, and RXR␥ (12). Each RAR and RXR isotype includes several isoforms. These receptors belong to the superfamily of nuclear hormone receptors and act as ligand-activated transcription factors (reviewed in Refs. 12 and 13). RARs function as a heterodimer together with RXR. The ligand-receptor complexes act as inducible transcription regulators of several genes by binding to specific retinoic acid response elements (RARE). Two type...