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Alsweiler J.M.,Child and Youth Health | Harding J.E.,University of Auckland | Bloomfield F.H.,Child and Youth Health | Bloomfield F.H.,University of Auckland | Bloomfield F.H.,National Research Center for Growth and Development
Neonatology | Year: 2013

Background: Hyperglycaemic preterm babies suffer increased mortality and morbidity, but it is not known if these associations are causal or if treatment with insulin improves outcome. Objectives: We aimed to investigate the effect of neonatal hyperglycaemia, and its treatment with insulin, on mortality and morbidity in preterm lambs. Methods: Preterm lambs (137 days' gestation; term = 148 days) were randomised to a 12-day intravenous infusion of saline (PremC; n = 39), 50% dextrose (HYPER; n = 47), or 50% dextrose + insulin (INS; n = 21). Term controls (TermC; n = 19) received saline. Dextrose and insulin infusions were titrated to maintain blood glucose concentrations (BGC) at 10-12 mmol·l-1 (HYPER) or 4-6 mmol·l-1 (INS). Results: HYPER lambs had higher BGC (mean (SEM); TermC: 5.6 (0.1), PremC: 5.5 (0.1), HYPER: 10.8 (0.6), INS: 6.2 (0.3) mmol·l-1; p < 0.0001), higher mortality (n (%); TermC: 0, PremC: 2 (5), HYPER: 11 (23), INS: 0; p < 0.001), higher incidence of fever (n (%); TermC: 3 (16), PremC: 13 (33), HYPER: 26 (55), INS: 6 (29); p = 0.01) and lower weight gain (mean (SEM); TermC: 45.9 (2.9), PremC: 44.2 (2.1), HYPER: 28.4 (1.9), INS: 28.7 (2.8) g·kg-1·day-1; p < 0.0001). Conclusions: Neonatal hyperglycaemia in preterm lambs causes increased mortality and morbidity, and decreases growth. Insulin treatment to restore euglycaemia attenuated the increased mortality and morbidity, but not the decreased growth. Copyright © 2012 S. Karger AG, Basel.

Laskar A.,CSIR - Central Electrochemical Research Institute | Rodger E.J.,University of Otago | Chatterjee A.,University of Otago | Chatterjee A.,National Research Center for Growth and Development | Mandal C.,CSIR - Central Electrochemical Research Institute
BMC Research Notes | Year: 2012

Background: Serine proteases account for over a third of all known proteolytic enzymes; they are involved in a variety of physiological processes and are classified into clans sharing structural homology. The PA clan of endopeptidases is the most abundant and over two thirds of this clan is comprised of the S1 family of serine proteases, which bear the archetypal trypsin fold and have a catalytic triad in the order Histidine, Aspartate, Serine. These proteases have been studied in depth and many three dimensional structures have been experimentally determined. However, these structures mostly consist of bacterial and animal proteases, with a small number of plant and fungal proteases and as yet no structures have been determined for protozoa or archaea. The core structure and active site geometry of these proteases is of interest for many applications. This study investigated the structural properties of different S1 family serine proteases from a diverse range of taxa using molecular modeling techniques. Results: Our predicted models from protozoa, archaea, fungi and plants were combined with the experimentally determined structures of 16 S1 family members and used for analysis of the catalytic core. Amino acid sequences were submitted to SWISS-MODEL for homology-based structure prediction or the LOOPP server for threading-based structure prediction. Predicted models were refined using INSIGHT II and SCRWL and validated against experimental structures. Investigation of secondary structures and electrostatic surface potential was performed using MOLMOL. The structural geometry of the catalytic core shows clear deviations between taxa, but the relative positions of the catalytic triad residues were conserved. Some highly conserved residues potentially contributing to the stability of the structural core were identified. Evolutionary divergence was also exhibited by large variation in secondary structure features outside the core, differences in overall amino acid distribution, and unique surface electrostatic potential patterns between species. Conclusions: Encompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on S1 family serine proteases. Focusing on the common core containing the catalytic site of the enzyme, this analysisis beneficial for future molecular modeling strategies and structural analysis of serine protease models. © 2012 Laskar et al.; licensee BioMed Central Ltd.

Bloomfield F.H.,University of Auckland | Bloomfield F.H.,National Research Center for Growth and Development
Annual Review of Nutrition | Year: 2011

The incidence of preterm birth in developed countries is increasing, and in some countries, including the United States, it is almost as high as in developing countries. Demographic changes in women becoming pregnant can account for only a relatively small proportion of the increase. A significant proportion of spontaneous preterm birth continues to be of unknown cause. Experimental data from animal studies suggesting that maternal undernutrition may play a role in spontaneous, noninfectious, preterm birth are supported by observational data in human populations, which support a role for maternal prepregnancy nutritional status in determining gestation length. In addition, intakes or lack of specific nutrients during pregnancy may influence gestation length and thus the risk of preterm birth. As yet, the role of paternal nutrition in contributing to gestation length is unexplored. Copyright © 2011 by Annual Reviews. All rights reserved.

Nicholson C.L.,Massey University | Firth E.C.,Massey University | Firth E.C.,National Research Center for Growth and Development
Journal of Musculoskeletal Neuronal Interactions | Year: 2010

Objectives: To assess the effect of conditioning exercise on bone parameters at multiple sites in the radius and tibia of young Thoroughbred horses. Methods: The left and right radius and tibia were obtained from twelve horses, six of which had received conditioning exercise and six which formed the control group. Each bone was scanned at 5% intervals along its entire length using pQCT. Results: Bone strength, bone area and periosteal circumference were significantly greater for the group of conditioned horses in both the radius and tibia. Volumetric bone mineral density was lower while bone mineral content, endocortical circumference and polar moment of inertia were higher in the conditioned group of horses but the significance of these differences varied between the two bones. Cortical thickness was not significantly different between the groups in either bone. Conclusions: Conditioning exercise stimulated a significant increase in the strength of both bones that could be attributed mainly to an increase in bone size, rather than differences in bone mineral content or density. The radius and tibia exhibited differences in the significance of changes in several bone parameters suggesting that not all bones respond in an identical fashion to imposed exercise.

Bloomfield F.H.,University of Auckland | Bloomfield F.H.,National Research Center for Growth and Development
Journal of Neurodevelopmental Disorders | Year: 2011

Many aspects of postnatal development are influenced by events before birth, including cognitive and language development. An adverse intrauterine environment, for example secondary to poor maternal nutritional status, multiple pregnancy, or late preterm birth, is associated with increased risks of delayed or impaired childhood development and altered physiology in adulthood that may predispose to increased risk of adult disease. Maternal periconceptional undernutrition and twin conception can both result in late preterm birth, but it is less clear whether cases of late preterm birth not following a recognized early pregnancy event may still have their origin in the periconceptional period. Thus, the very earliest periods of pregnancy, and perhaps even the prepregnancy period, may be an important period determining the developmental trajectory of the fetus, and thus both pregnancy and later health outcomes. Profound epigenetic modifications to the genome occur in the early embryo as a normal part of development. Recent evidence suggests that environmental signals acting during early development may also result in epigenetic changes which may play a role in mediating the association between early life exposures and later phenotype. © 2011 Springer Science+Business Media, LLC.

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