A short PNA targeting coxsackievirus B3 5'-nontranslated region prevents virus-induced cytolysis.

Targeting regulatory RNA regions to interfere with the biosynthesis of a protein is an intriguing alternative to targeting a protein itself. Regulatory regions are often unique in sequence and/or structure and, thus, ideally suited for specific recognition with a low risk of undesired side effects. Targeting regulatory RNA elements, however, is complicated by their complex three-dimensional structure, which poses kinetic and thermodynamic constraints to the recognition by a complementary oligonucleotide. Oligonucleotide mimics, which shift the thermodynamic equilibrium towards complex formation and yield stable complexes with a target RNA, can overcome this problem. Peptide nucleic acids (PNA) represent such a promising class of molecules. PNA are very stable, non-ionic compounds and they are not sensitive to enzymatic degradation. Yet, PNA form specific base pairs with a target sequence. We have designed, synthesised and characterised PNA able to enter infected cells and to bind specifically to a control region of the genomic RNA of coxsackievirus B3 (CVB3), which is an important human pathogen. The results obtained by studying the interaction of such PNA with their RNA target, the entrance into the cell and the viral inhibition are herein presented.     

Tubular function by lithium clearance, plasma amino acids and hormones following a meat meal in childhood.

Tubular function was measured by lithium clearance (CLi) and by its derived formulae before and after the transient increase (lasting 90 min) in glomerular filtration rate (GFR) following a meat meal (2g protein/kg body weight) in 12 normal children. Three baseline and 4 clearances after the meal were obtained, each lasting 30 min. The mean baseline CLi was 23.1 +/- 1.64 ml/min/1.73 m2. At peak GFR response (60 min from starting the meal), CLi averaged 27.6 +/- 2.4 ml/min/1.73 m2 (p less than 0.025 vs. baseline) and it was further increased (32.2 +/- 5.04 ml/min/1.73 m2, p less than 0.01 vs. baseline) 120 min after starting the meal, while GFR returned to baseline values. Fractional lithium excretion averaged 0.23 +/- 0.04 at baseline and increased continuously after the meat meal and, at completion of the study, it averaged 0.38 +/- 0.07 (p less than 0.025 vs. baseline). The distal absolute and fractional sodium reabsorption increased throughout the studies following the meal and peaked at 120 min. The functional changes were associated with a statistically significant increase in the plasma concentration of insulin, glucagon, and total amino acids after the meal. The latter at the end of the study was almost doubled (5,600 +/- 780 versus 3,200 microM at baseline, p less than 0.01). The data indicate that the tubulo glomerular feedback mechanism operates normally after a meat meal. The finding on increased distal sodium reabsorption might point to the existence of an insulin-dependent mechanism.