Prevalence of vitamin D insufficiency in African American children with forearm fractures: a preliminary study.

OBJECTIVES: Forearm fractures account for a significant proportion of childhood injuries and seem to be increasing in incidence. Poor vitamin D status increases overall fracture risk in infants with rickets and adults with osteoporosis. Children with vitamin D insufficiency (serum 25-hydroxy vitamin D level <20 ng/mL) have decreased bone mineral density (BMD) compared with children having normal vitamin D status. The relationship between vitamin D status and childhood forearm fracture has not been investigated. METHODS: This prospective study enrolled African American children, aged 5 to 9 years, with a forearm fracture. Bone health evaluation included measurement of serum 25-hydroxy vitamin D level and BMD by dual energy x-ray absorptiometry scan. Univariable analyses were used to test the associations between fracture status and the independent variables, serum vitamin D level and BMD. RESULTS: Vitamin D levels were available for 17 cases. The mean (+/-SD) 25-hydroxy vitamin D level was 20.1 (+/-7.3) ng/mL with a range of 10 to 38 ng/mL. The mean of this group was at the cut point for vitamin D insufficiency. Ten cases (59%) were vitamin D insufficient. Dual energy x-ray absorptiometry scan results for these patients were consistent with normal bony mineralization for age. CONCLUSIONS: A significant proportion of African American children with fractures in our study have vitamin D insufficiency. Analysis of serum 25-hydroxy vitamin D levels and BMD in additional cases and controls will determine the significance of these findings. CLINICAL RELEVANCE: Vitamin D insufficiency may play a previously unrecognized role in childhood fractures. Strong consideration should be given to routine vitamin D testing in African American children with forearm fractures.

Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element.

A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3' untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this region controls BMP2 synthesis by post-transcriptional mechanisms. A common A to C single nucleotide polymorphism (SNP) in the BMP2 gene (rs15705, +A1123C) disrupts a putative post-transcriptional regulatory motif within the human ultra-conserved sequence. In vitro studies indicate that RNAs bearing the A or C alleles have different protein binding characteristics in extracts from mesenchymal cells. Reporter genes with the C allele of the ultra-conserved sequence were differentially expressed in mesenchymal cells. Finally, we analyzed MRI data from the upper arm of 517 healthy individuals aged 18-41 years. Individuals with the C/C genotype were associated with lower baseline subcutaneous fat volumes (P = 0.0030) and an increased gain in skeletal muscle volume (P = 0.0060) following resistance training in a cohort of young males. The rs15705 SNP explained 2-4% of inter-individual variability in the measured parameters. The rs15705 variant is one of the first genetic markers that may be exploited to facilitate early diagnosis, treatment, and/or prevention of diseases associated with poor fitness. Furthermore, understanding the mechanisms by which regulatory polymorphisms influence BMP2 synthesis will reveal novel pharmaceutical targets for these disabling conditions.

Negative pressure wound therapy with reticulated open cell foam in children: an overview.

This article summarizes the results of a comprehensive review of the literature on the use of negative pressure wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by V.A.C.(R) Therapy (KCI, San Antonio, TX) in pediatric patients. A review of the literature revealed 20 articles that discussed the use of NPWT/ROCF in exclusively pediatric patients. Nine articles were retrospective reviews, and 11 were case studies. This review discusses the insights from these articles. This review discusses the versatility of NPWT/ROCF for use with pediatric patients with infected wounds; full-thickness burns; open fractures; large soft tissue wounds; surgical wounds of the chest, abdomen, and spine; pilonidal disease; and pressure ulcers. NPWT/ROCF has been used in children as young as a few weeks of age, and in children with comorbidities such as congenital heart disease, immunosuppression, and spina bifida. Wound healing in children can be delayed by impaired perfusion, infection, edema, and poor nutrition. Clinical considerations for using NPWT/ROCF in children can include differences in healing due to higher granulation rates requiring more frequent dressing changes, poor nutritional status, small size, and low weight. With pediatric patients, there is no consensus on foam (white or black) selection, optimum amount of negative pressure, frequency of NPWT/ROCF dressing changes, and interposing contact layer selection. Randomized prospective studies are needed to make recommendations for safe and efficacious clinical practice. Research regarding the effects of dressing types, adjunctive treatment, and wound healing in neonates and children is needed.

PPARalpha L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males.

BACKGROUND: Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50-80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome. METHODS: We studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training. RESULTS: We found the PPARalpha L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 +/- 11 mg/dL, LV = 208 +/- 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 +/- 1 mg/dL, LV = 34 +/- 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 +/- 21 mm3, LV = 17,617 +/- 58 mm3 ; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARalpha L162V is on serum triglycerides, with downstream effects on adiposity and response to training. CONCLUSION: Our results on association of PPARalpha and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).

The nitrosteroid NCX 1015, a prednisolone derivative, improves recovery of function in rats after spinal cord injury.

Glucocorticoids, given at high-doses, improve recovery of function after spinal cord injury (SCI) in animals. However, side effects combined with a limited efficacy in clinical trials have restricted their usefulness for treatment of SCI patients. Recent studies have shown that incorporation of the nitric oxide releasing moiety into the glucocorticoid structure enhances anti-inflammatory properties and reduces side effects. One compound, a derivative of prednisolone (PRE), (NCX 1015, prednisolone 21 [(4'nitrooxymethyl)benzoate]), has interesting pharmacological properties. Therefore, we investigated its effects on apoptosis and recovery of function in rats after SCI. Rats received subcutaneously vehicle, NCX 1015 or PRE (37 micromol/kg, each) 3.5 h after a standardized thoracic lesion. The treatment was continued once a day for 3 days and the effect of both steroids on apoptosis was examined by immunohistochemistry 24 h after the last injection. NCX 1015 but not PRE reduced TUNEL and activated caspase 3 in both white and ventral gray matter as well as tumor necrosis factor immunoreactivity in ventral horn motorneurons, suggesting that NCX 1015 reduces SCI-induced apoptosis. The effect of NCX 1015 on motor function was then examined by a standard locomotion rating scale (BBB) starting at 1 day after injury and continuing up to 14 days. NCX 1015 improved significantly locomotor activity by 4 days after injury, whereas PRE had an effect equivalent to that of vehicle, thus providing a correlation between the antiapoptotic effect of NCX1015 and its ability to improve recovery of function. The data suggest that NCX 1015 might be a novel experimental therapeutic compound for recovery of function in SCI patients.

Gene profiling in spinal cord injury shows role of cell cycle in neuronal death.

Spinal cord injury causes secondary biochemical changes leading to neuronal cell death. To clarify the molecular basis of this delayed injury, we subjected rats to spinal cord injury and identified gene expression patterns by high-density oligonucleotide arrays (8,800 genes studied) at 30 minutes, 4 hours, 24 hours, or 7 days after injury (total of 26 U34A profiles). Detailed analyses were limited to 4,300 genes consistently expressed above background. Temporal clustering showed rapid expression of immediate early genes (30 minutes), followed by genes associated with inflammation, oxidative stress, DNA damage, and cell cycle (4 and 24 hours). Functional clustering showed a novel pattern of cell cycle mRNAs at 4 and 24 hours after trauma. Quantitative reverse transcription polymerase chain reaction verified mRNA changes in this group, which included gadd45a, c-myc, cyclin D1 and cdk4, pcna, cyclin G, Rb, and E2F5. Changes in their protein products were quantified by Western blot, and cell-specific expression was determined by immunocytochemistry. Cell cycle proteins showed an increased expression 24 hours after injury and were, in part, colocalized in neurons showing morphological evidence of apoptosis. These findings suggest that cell cycle-related genes, induced after spinal cord injury, are involved in neuronal damage and subsequent cell death.