DNA methylation of hepatic iron sensing genes and the regulation of hepcidin expression.

Production of the iron regulatory peptide hepcidin is tightly controlled by a network of proteins in hepatocytes that sense levels of iron in the circulation (as diferric-transferrin) and in tissues (in ferritin). Human studies show high variability in the normal range of serum hepcidin levels. We have postulated that this may, in part, be related to inter-individual variability in the expression of genes in the iron sensing pathway, potentially governed by epigenetic factors. Here, we have investigated whether genes encoding hepatic iron sensing proteins and hepcidin are regulated by DNA methylation. Experiments were performed on two human hepatoma cell lines, HepG2 cells and Huh7 cells. Basal expression of TFR2 and HAMP was significantly lower in Huh7 cells compared with HepG2 cells. Analysis of bisulphite-converted DNA from Huh7 cells revealed partial methylation of TFR2 (alpha transcript), which could result in gene silencing. Demethylation using 5-aza-2'-deoxycitidine (AZA) increased TFR2 mRNA expression in Huh7. PCR analysis of bisulphite-converted HAMP promoter DNA, using methylation-specific primers, revealed no differences between cell lines. However, HAMP mRNA expression in Huh7 was increased by AZA treatment, suggesting that methylation of one or more iron sensing genes may indirectly influence HAMP expression. Our study provides evidence that DNA methylation might control expression of HAMP and other hepatic iron sensing genes, and indicates that epigenetic influences on iron homeostasis warrant further investigation.

The use of foot pumps compression devices in the perioperative management of ankle fractures: Systematic review of the current literature.

BACKGROUND: Ankle fractures account for 9% of all fractures seen in the United Kingdom. 15,000 of these fractures undergo operative fixation each year. Soft tissue swelling impacts on timing of fixation due to fears of infection and wound dehiscence. The use of arterio-venous foot pumps (AVFP) is increasing in this population although the evidence for their efficacy is unclear. In order to address this, we present an overview of the evidence for AVFP device use following ankle fracture. METHODS: In September 2015 an electronic literature search was undertaken of studies comparing two or more methods of swelling reduction in patients with ankle fractures. Of 326 screened, 5 papers ultimately were included. RESULTS: Two studies reported a statistically significant reduction in swelling (p=0.03) and (p=0.03 at 24 hours, p=0.05 at 48 hours) after using AVFP devices compared to the controls (leg elevation +/ ice therapy). Stockle et al. reported a greater reduction in the preoperative ankle, midfoot and forefoot circumference at 24 hours in their AVFP group (53% versus 32% and 10% in their continuous cryotherapy and cool pack cryotherapy groups respectively). Whereas, Rohner-Spengler et al. observed improved preoperative swelling reduction in patients treated with a multilayer compression bandage when compared to their AVFP group. Keehan et al. reported that time to surgery was considerably reduced in patients treated with an AVFP device, (2.3 days) compared to those treated with leg elevation (4.6 days) (p=0.02). Length of stay (LOS) was not influenced by any of the tested interventions. CONCLUSIONS: AVFP devices have been shown to reduce time to surgery and degree of swelling before operative intervention better than other methods but the strength of evidence to support this remains poor.