[Dent's disease: hereditary nephrolithiasis related to defective tubular endocytosis processes]. / La malattia di Dent: una nefrolitiasi ereditaria da difetti dei processi di endocitosi tubulare.

Dent's disease, a X-linked hypercalciuric nephrolithiasis, is caused by mutations of the CLCN5 gene. The disease is characterised by low molecular weight proteinuria with variable presence of hypercalciuria, hyperphosphaturia, nephrocalcinosis, and kidney stones. CLCN5 encodes a chloride channel belonging to the voltage-gated chloride channel family, which is predominantly expressed in the endosomes of proximal tubular cells. By shunting the current of electrogenic H+-ATPase, ClC-5 is crucial for efficient acidification of renal endosomes. As shown in knock-out mouse models, the ClC-5 loss of function causes severe impairment of receptor-mediated endocytosis, as well as the endocytotic retrieval of plasma membrane proteins including megalin. In a minority of patients with classical Dent's disease, the analysis of CLCN5 coding sequences failed to identify causative mutations. It is conceivable that mutations in the 5' upstream regulatory regions could impair the correct processing and translation of CLCN5. The complexity of its promoter region seems to support this hypothesis. Molecular diagnosis of Dent's disease is now available; since the risk of developing renal insufficiency in adult life is elevated for this type of nephrolithiasis, the correct diagnosis could potentially modify the natural history of the disease by preventing the evolution towards uraemia.

Experimental zinc depletion and altered taste perception for NaCl in young adult males.

Taste perception for saltiness and bitterness was tested in five young men while fed a basal (15 mg Zn/day) and zinc depletion (0.25 mg Zn/day)) diet and in three young men during zinc repletion. The perceived intensity of five NaCl solutions ranging from 0 to 600 mM and five urea solutions also ranging from 0 to 600 mM were rated on a 17-point scale. The intensity ratings for the 75 and 150 mM NaCl solutions were significantly lower (p less than 0.05) during depletion than during the basal period; intensity ratings for 300 and 600 mM NaCl solutions did not change significantly. Bitterness perception was not altered with zinc depletion. The changes in perceived intensity that occurred were not related to parotid salivary zinc concentration, percentage change in plasma zinc with depletion, or the length of time required for depletion. The results suggest that zinc depletion may alter the taste perception of some moderately salty solutions.

Behavioral responses to artificial food colors.

Twenty-two young children, maintained on a diet that excluded certain foods, were challenged intermittently with a blend of seven artificial colors in a double-blind trial. Parents' observations provided the criteria of response. One child that responded mildly to the challenge and one that responded dramatically were detected. The latter, a 34-month-old female, showed a significant increase in aversive behaviors. These results further confirm previous controlled studies.