Cord blood calcium, phosphate, magnesium, and alkaline phosphatase gestational age-specific reference intervals for preterm infants

<p>Abstract</p> <p>Background</p> <p>The objective was to determine the influence of gestational age, maternal, and neonatal variables on reference intervals for cord blood bone minerals (calcium, phosphate, magnesium) and related laboratory tests (alkaline phosphatase, and albumin-adjusted calcium), and to develop gestational age specific reference intervals based on infants without influential pathological conditions.</p> <p>Methods</p> <p>Cross-sectional study. 702 babies were identified as candidates for this study in a regional referral neonatal unit. After exclusions (for anomalies, asphyxia, maternal magnesium sulfate administration, and death), relationships were examined between cord blood serum laboratory analytes (calcium, phosphate, magnesium, alkaline phosphatase, and albumin-adjusted calcium) with gestation age and also with maternal and neonatal variables using multiple linear regression. Infants with influential pathological conditions were omitted from the development of gestational age specific reference intervals for the following categories: 23-27, 28-31, 32-34, 35-36 and > 36 weeks.</p> <p>Results</p> <p>Among the 506 preterm and 54 terms infants included in the sample. Phosphate, magnesium, and alkaline phosphatase in cord blood serum decreased with gestational age, calcium increased with gestational age. Those who were triplets, small for gestational age, and those whose mother had pregnancy-induced hypertension were influential for most of the analytes. The reference ranges for the preterm infants ≥ 36 weeks were: phosphate 1.5 to 2.6 mmol/L (4.5 to 8.0 mg/dL), calcium: 2.1 to 3.1 mmol/L (8.3 to 12.4 mg/dL); albumin-adjusted calcium: 2.3 to 3.2 mmol/L (9.1 to 12.9 mg/dL); magnesium 0.6 to 1.0 mmol/L (1.4 to 2.3 mg/dL), and alkaline phosphatase 60 to 301 units/L.</p> <p>Conclusions</p> <p>These data suggest that gestational age, as well as potentially pathogenic maternal and neonatal variables should be considered in the development of reference intervals for preterm infants.</p

Hypoxia Disruption of Vertebrate CNS Pathfinding through EphrinB2 Is Rescued by Magnesium

The mechanisms of hypoxic injury to the developing human brain are poorly understood, despite being a major cause of chronic neurodevelopmental impairments. Recent work in the invertebrate Caenorhabditis elegans has shown that hypoxia causes discrete axon pathfinding errors in certain interneurons and motorneurons. However, it is unknown whether developmental hypoxia would have similar effects in a vertebrate nervous system. We have found that developmental hypoxic injury disrupts pathfinding of forebrain neurons in zebrafish (Danio rerio), leading to errors in which commissural axons fail to cross the midline. The pathfinding defects result from activation of the hypoxia-inducible transcription factor (hif1) pathway and are mimicked by chemical inducers of the hif1 pathway or by expression of constitutively active hif1α. Further, we found that blocking transcriptional activation by hif1α helped prevent the guidance defects. We identified ephrinB2a as a target of hif1 pathway activation, showed that knock-down of ephrinB2a rescued the guidance errors, and showed that the receptor ephA4a is expressed in a pattern complementary to the misrouting axons. By targeting a constitutively active form of ephrinB2a to specific neurons, we found that ephrinB2a mediates the pathfinding errors via a reverse-signaling mechanism. Finally, magnesium sulfate, used to improve neurodevelopmental outcomes in preterm births, protects against pathfinding errors by preventing upregulation of ephrinB2a. These results demonstrate that evolutionarily conserved genetic pathways regulate connectivity changes in the CNS in response to hypoxia, and they support a potential neuroprotective role for magnesium

Regioselectivity in aromatic Claisen rearrangements

Theoretical calculations and the isomeric product composition for a series of eight meta-substituted allyl aryl ethers confirm the reliability of a new H-1 NMR methodology used to predict aromatic Claisen regioselectivity from ground-state conformational preference of the reactant allyloxy group. Frontier HOMO-LUMO intramolecular orbital interactions, a classical approach in predicting reactivity and selectivity for Claisen rearrangements of allyl vinyl ethers, is shown to fail to mimic transition-state orbital interactions for aromatic Claisen rearrangements of meta-substituted allyl aryl ethers. B3LYP/6-31G(d,p) calculations on reactants and transition states are shown, however, to correctly predict the outcome of such aromatic Claisen rearrangements from either the preferential reactant ground-state conformation (theoretical predictions that agree with the NMR measurements) or the less energetic transition state, or both.68145493549

Tomato treatment with chemical inducers reduces the performance of Spodoptera littoralis (Lepidoptera: Noctuidae)

The evolving understanding of plant signaling pathways has promoted the possibility of using chemical inducers as an effective tactic for crop protection. In this study, under greenhouse conditions, we conducted a growth assay of Spodoptera littoralis (Boisduval) larvae on tomato plants treated with BTH (S-methyl benzo [1, 2, 3] thiadiazole 7 carbothioate) as a salicylic acid mimic, PDJ (propyl [1RS, 2RS]-[3-oxo-2-pentylcyclopentyl] acetate) as a jasmonic acid-mimic or both chemicals as a combined treatment. The larval body weight of S. littoralis was drastically reduced with each chemical compared to control plants, and there was a significant synergistic interaction. Overall, the total weight gain of surviving larvae fed on treated plants was distinctly tenfold less than for those fed on control plants. Moreover, incorporating the chemical inducers in artificial diets had no direct or toxic impact on the larval body weight of S. littoralis under laboratory conditions. Larval survival rates were significantly lower (35–40 %) on treated plants with either combined or independent inducers’ treatments compared with control plants after 15-day feeding. In contrast, incorporating the chemical inducers in artificial diets had no direct effect on larval survival rates under laboratory conditions. The applied concentrations of BTH and PDJ had no detectable phytotoxicity to tomato plants. Our results demonstrate that BTH and PDJ can act synergistically when applied to tomato to reduce the performance of S. littoralis. These findings stress that the application of chemical inducers could provide an environment-friendly tactic to help manage insect pests and thereby play multiple roles in improving the overall plant resistance to herbivore pests

Crystal Structure of Crataeva tapia Bark Protein (CrataBL) and Its Effect in Human Prostate Cancer Cell Lines

A protein isolated from the bark of Crataeva tapia (CrataBL) is both a Kunitz-type plant protease inhibitor and a lectin. We have determined the amino acid sequence and three-dimensional structure of CrataBL, as well as characterized its selected biochemical and biological properties. We found two different isoforms of CrataBL isolated from the original source, differing in positions 31 (Pro/Leu); 92 (Ser/Leu); 93 (Ile/Thr); 95 (Arg/Gly) and 97 (Leu/Ser). CrataBL showed relatively weak inhibitory activity against trypsin (K(iapp) = 43 µM) and was more potent against Factor Xa (K(iapp) = 8.6 µM), but was not active against a number of other proteases. We have confirmed that CrataBL contains two glycosylation sites and forms a dimer at high concentration. The high-resolution crystal structures of two different crystal forms of isoform II verified the β-trefoil fold of CrataBL and have shown the presence of dimers consisting of two almost identical molecules making extensive contacts (∼645 Å(2)). The structure differs from those of the most closely related proteins by the lack of the N-terminal β-hairpin. In experiments aimed at investigating the biological properties of CrataBL, we have shown that addition of 40 µM of the protein for 48 h caused maximum growth inhibition in MTT assay (47% of DU145 cells and 43% of PC3 cells). The apoptosis of DU145 and PC3 cell lines was confirmed by flow cytometry using Annexin V/FITC and propidium iodide staining. Treatment with CrataBL resulted in the release of mitochondrial cytochrome c and in the activation of caspase-3 in DU145 and PC3 cells