“
“Background: A recent

epidemic of melamine contamination of baby formula in China has been associated with the development of urinary tract stones, though the clinical manifestations and predisposing factors are incompletely delineated.

Methods: We administered a questionnaire to the parents of children 36 months of age or younger who were being screened for a history of exposure to melamine and symptoms of, and possible NU7441 supplier predisposing factors for, urinary tract stones. In addition, we performed urinalysis, renal-function and liver-function tests, urinary tests for biochemical markers and the calcium:creatinine ratio, and ultrasonography. Powdered-milk infant formulas were classified as having a high melamine content (>500 ppm), a moderate melamine content (<150 ppm), or no melamine (0 ppm); no formulas contained between 150 and 500 ppm of melamine.

Results: Contaminated formula was ingested by 421 of 589 children. Fifty had urinary stones, including 8 who had not received melamine-contaminated formula;

112 were suspected selleck compound to have stones; and 427 had no stones. Among children with stones, 5.9% had hematuria and 2.9% had leukocyturia, percentages that did not differ significantly from those among children who were suspected to have stones or those who did not have stones. Serum creatinine, urea nitrogen, and alanine aminotransferase levels were normal in the 22 children with stones who were tested. Four of the 41 children (9.8%) who had stones and in whom urinary markers of glomerular function were measured had evidence of abnormalities; none had tubular dysfunction. Children exposed to high-melamine formula were 7.0 times as likely to have stones as those exposed to no-melamine formula. Preterm infants were 4.5 times as likely to have stones as term infants.

Conclusions: Prematurity

and exposure to melamine-contaminated formula were associated with urinary stones. Affected children lacked typical VE 822 signs and symptoms of urolithiasis.

N Engl J Med 2009;360:1067-74.”
“The N-terminal region of the native human prion protein encompasses four highly conserved octarepeats that each contain a single His, Pro, Gln, and Trp residue as well as several Gly residues. At neutral pH these repeats are capable of individually binding copper (Cu2+) ions, involving the His side chain and the backbone amide of the Gly residues. In addition, the two His residues at positions 96 and 111 are also capable of binding Cu2+. At low concentrations of the metal ion or at low pH, one Cu2+ may be bound by multiple His residues of the four octarepeats. This complex is known to be redox active, while none of the other Cu2+-bound complexes are. Using density functional theory and molecular dynamics calculations data demonstrated how this form of the protein could reduce Cu2+, through a process involving electron transfer from the Trp side chain.