Vitamin D and maternal and child health: Overview and implications for dietary requirements

The essentiality of vitamin D for normal growth and development has been recognized for over 80 years, and vitamin D fortification programs have been in place in the United States for more than 70 years. Despite the above, vitamin D deficiency continues to be a common finding in certain population groups. Vitamin D deficiency has been suggested as a potential risk factor for the development of preeclampsia, and vitamin D deficiency during infancy and early childhood is associated with an increased risk for numerous skeletal disorders, as well as immunological and vascular abnormalities. Vitamin D deficiency can occur through multiple mechanisms including the consumption of diets low in this vitamin and inadequate exposure to environmental ultraviolet B rays. The potential value of vitamin D supplementation in high‐risk pregnancies and during infancy and early childhood is discussed. Currently, there is vigorous debate concerning what constitutes appropriate vitamin D intakes during early development as exemplified by differing recommendations from the Institute of Medicine Dietary Reference Intake report and recent recommendations by the Endocrine Society. As is discussed, a major issue that needs to be resolved is what key biological endpoint should be used when making vitamin D recommendations for the pregnant woman and her offspring. Birth Defects Research (Part C) 99:24–44, 2013. © 2013 Wiley Periodicals, Inc.     

M13 endopeptidases: New conserved motifs correlated with structure,and simultaneous phylogenetic occurrence of PHEX and the bony fish

M13 endopeptidase alignments have focused mainly on mammalian sequences and on the active site region defining the catalytic sequence signatures. Aligning all available M13 from bacteria to human on a full-length basis, we have performed a sequence analysis. This enabled us to highlight the origin and function of the M13 PHEX subtype family endopeptidase (phosphate regulating gene with homologies to endopeptidases on the X chromosome). New evolutionary conserved regions in both prokaryotes and eukaryotes have been detected and eukaryotic-specific regions clearly delineated. Using the recently solved neprilysin structure, we have observed that all new motifs, except one, localize in the spatial vicinity of the previously reported catalytic signatures. Interestingly, a highly hydrophobic pocket containing three newly reported motifs is centered by the C-terminal tryptophan residue. Extensive M13 searches in complete and in progress higher eukaryotic genomes have lead to the identification of Danio rerio as the simplest organism having PHEX. Finally, the human PHEX substrate, the parathyroid hormone-related peptide, PTHrP(107-139), is absent in bony fish: this suggests the existence of further PHEX substrates common to both bony fishes and higher vertebrates.     

Life and death in a civitas capital: Metabolic disease and trauma in the children from late Roman Dorchester,Dorset

The impact that “Romanization” and the development of urban centers had on the health of the Romano‐British population is little understood. A re‐examination of the skeletal remains of 364 nonadults from the civitas capital at Roman Dorchester (Durnovaria) in Dorset was carried out to measure the health of the children living in this small urban area. The cemetery population was divided into two groups; the first buried their dead organized within an east–west alignment with possible Christian‐style graves, and the second with more varied “pagan” graves, aligned north–south. A higher prevalence of malnutrition and trauma was evident in the children from Dorchester than in any other published Romano‐British group, with levels similar to those seen in postmedieval industrial communities. Cribra orbitalia was present in 38.5% of the children, with rickets and/or scurvy at 11.2%. Twelve children displayed fractures of the ribs, with 50% of cases associated with rickets and/or scurvy, suggesting that rib fractures should be considered during the diagnosis of these conditions. The high prevalence of anemia, rickets, and scurvy in the Poundbury children, and especially the infants, indicates that this community may have adopted child‐rearing practices that involved fasting the newborn, a poor quality weaning diet, and swaddling, leading to general malnutrition and inadequate exposure to sunlight. The Pagan group showed no evidence of scurvy or rib fractures, indicating difference in religious and child‐rearing practices but that both burial groups were equally susceptible to rickets and anemia suggests a shared poor standard of living in this urban environment. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.     

An ill child among mid-Holocene foragers of Southern Africa

The skeletal remains of an infant from a southwest South African rock shelter at Byneskranskop show pervasive abnormalities that are consistent with the effects of hypertrophic (hyperplastic) rickets. Diagnostic features include beading of the costochondral junctions of the ribs, flaring and tilting of the metaphyses, and cupping of the distal ulna, as well as general skeletal hypertrophy. With an uncalibrated accelerator mass spectrometry (AMS) radiocarbon date of 4820 +/- 90 BP (TO-9531), this is a very early instance of the condition, among foragers whose environment and diet make dietary shortages of active vitamin D or dietary calcium improbable. Carbon and nitrogen stable isotope ratios indicate a mixed diet, including marine as well as terrestrial protein. Solicitous care maintained the sick infant to an estimated age of 3.5-5 months; it was buried in a manner like that of other deceased group members. This case suggests that if infanticide was practiced, it was an option only during the immediate perinatal period, when this infant would have appeared normal. This is consistent with documentation of infanticide practices among historic foragers from southern Africa.     

Effect of consumption of food cooked in aluminium or stainless-steel pots on Bangladeshi children with calcium-deficient rickets: an eight month trial

The putative role of aluminium intake in young Bangladeshi children (1.5 to 4 years of age) with calcium-deficient rickets was evaluated in a non randomised controlled eight month trial. The effects of aluminium or stain-less-steel cooking pots on bone metabolism were assessed by measuring blood calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 1,25 dihydroxy vitamin D, aminoterminal propeptide of type 1 collagen (PINP), cross-linked carboxyterminal telopeptide of type 1 collagen (ICTP), aluminium and albumin, and by analysis of wrist radiographs. In both groups, blood alkaline phosphatase, 1,25 dihydroxy vitamin D and aluminium decreased significantly, while serum albumin increased (p < 0.01). These results suggest that the nutrition may well be of major importance, whereas the role of aluminium appears to be insignificant.     

Evidence against a role for alkaline phosphatase in the dephosphorylation of plasma membrane proteins: Hypophosphatasia fibroblast study

A major impasse to understanding the physiologic role(s) of alkaline phosphatase (ALP) is uncertainty as to its natural substrates. Various in vitro studies have led other investigators to suggest that ALP functions as a plasma membrane phosphoprotein phosphatase, consistent with our demonstration of ecto-topography of ALP in a variety of cell types. Thus, we compared the phosphorylation of plasma membrane proteins from control fibroblasts to those from profoundly ALP-deficient fibroblasts of hypophosphatasia patients. Fibroblasts from 3 controls and 3 hypophosphatasia patients (ALP activity < 4% of control) were biosynthetically labeled with ³²P_i for 2 h. ³²P incorporation into total trichloracetic acid (TCA)-precipitable material was not significantly different in control and patient cells. Plasma membranes were prepared from these cells by hypotonic shock, solubilized, and subjected to two-dimensional (2-D) gel electrophoretic separation. Video densitometric analysis of silver-stained 2-D gels failed to reveal any consistent difference in the protein profile between patient vs. control fibroblasts (i.e., unique species, altered pls, or increased abundance). Autoradiography of individual 2-D gels demonstrated 63 plasma membrane phosphoproteins with molecular weights ranging from 15 to 152 kDa and predominantly acidic pls. Although several of these phosphoproteins appeared to have had donor-specific labeling, none was unique or especially abundant in the hypophosphatasia group. Thus, in ALP-deficient fibroblasts, normal incorporation of ³²P into total cellular protein and into all identifiable plasma membrane phosphoproteins indicates that ALP does not modulate the phosphorylation of plasma membrane proteins.