Tetrahydrobiopterin therapy vs phenylalanine-restricted diet: impact on growth in PKU.

BACKGROUND: Treatment of phenylketonuria based upon strict vegetarian diets, with very low phenylalanine intake and supplemented by phenylalanine-free formula, has proven to be effective in preventing the development of long-term neurological sequelae due to phenylalanine accumulation. On the other hand, such diets have occasionally been reported to hinder normal development, some individuals presenting with growth retardation. Tetrahydrobiopterin therapy has opened up new treatment options for a significant proportion of phenylketonuric patients, enabling them to eat normal diets and be freed from the need to take synthetic supplements. However, little is known about how this therapy affects their physical development. METHODS: We conducted a retrospective longitudinal study examining anthropometric characteristics (height, weight, body mass index and growth speed Z-scores) in a cohort of phenylketonuric patients on tetrahydrobiopterin therapy (38 subjects) comparing their characteristics with those of a group of phenylketonuric patients on phenylalanine-restricted diets (76 subjects). Nutritional issues were also considered, to further explore the possibility of higher natural protein intake being associated with better physical development. Data were collected every six months over two different periods of time (two or five years). RESULTS: No improvement was observed in the aforementioned anthropometric variables in the cohort on tetrahydrobiopterin therapy, from prior to starting treatment to when they had been taking the drug for two or five years. Rather, in almost all cases there was a fall in the mean Z-score for the variables during these periods, although the changes were not significant in any case. Further, we found no statistically differences between the two groups at any considered time point. Growth impairment was also noted in the phenylketonuric patients on low-phenylalanine diets. Individuals on tetrahydrobiopterin therapy increased their natural protein intake and, in some instances, this treatment enabled individuals to eat normal diets, with protein intake meeting RDAs. No association was found, however, between higher protein intake and growth. CONCLUSION: Our study identified growth impairment in patients with phenylketonuria on tetrahydrobiopterin, despite higher intakes of natural proteins. In fact, individuals undergoing long-term tetrahydrobiopterin treatment seemed to achieve similar developmental outcomes to those attained by individuals on more restricted diets.

Changes in pectins and MAPKs related to cell development during early microspore embryogenesis in Quercus suber L.

The occurrence and significance of changes in cell wall components and signalling molecules has been investigated during early microspore embryogenesis in cork oak (Quercus suber L.) in relation to cell proliferation and cell differentiation. Microspore embryogenesis has been induced in in vitro anther cultures of Q. suber by the application of a stress treatment of 33 degrees C. After the treatment, microspores at the responsive developmental stage of vacuolate microspore switched towards proliferation and the embryogenesis pathway to further produce haploid plantlets. Ultrastructural and immunocytochemical analysis revealed changes in cell organisation after induction at different developmental stages, the cellular features displayed being in relation to the activation of proliferative activity and the beginning of differentiation in young and late proembryos. Immunogold labelling with JIM5 and JIM7 antibodies showed a different presence of pectin and level of its esterification in cell walls at different developmental stages. Non-esterified pectins were found in higher proportions in cells of late proembryos, suggesting that pectin de-esterification could be related to the beginning of differentiation. The presence and subcellular distribution of Erk 1/2 MAPK homologues have been investigated by immunoblotting, immunofluorescence and immunogold labelling. The results showed an increase in the expression of these proteins with a high presence in the nucleus, during early microspore proembryos development. The reported changes during early microspore embryogenesis are modulated in relation to proliferation and differentiation events. These findings provided new evidences for a role of MAPK signalling pathways in early microspore embryogenesis, specifically in proliferation, and would confer information for the cell fate and the direction of the cell development.