A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism

The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elderly, these mutations might be associated with increased morbidity because of the lifelong accumulation of iron. In a population-based sample of the elderly, we determined the value of genotyping for HFE mutations to screen for subclinical hemochromatosis. HFE genotype frequencies were determined in a random group of 2095 subjects (55 years and over). In this random group, we selected within the six genotype groups a total of 342 individuals and measured their serum transferrin saturation, iron and ferritin levels. We also estimated the heritability and parameters needed to evaluate screening, including the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of HFE genotypes. Iron parameters were significantly increased in subjects homozygous, heterozygous or compound heterozygous. The effect of the mutations was more pronounced in men than in women. For the H63D mutation, an allele dose effect was observed. The HFE gene explained about 5% of the variability in serum iron indices. The PPV for hemochromatosis for the C282Y homozygous was 100% in men and 67% in women. The NPV of the wild-type allele was 97% for both men and women. The sensitivity of both mutations was 70% for men and 52% for women and the specificity was 62% for men and 64% for women. Our study shows that the HFE C282Y and H63D are determinants of iron parameters in the elderly and will be effective in detecting individuals at high risk of hemochromatosis. However, when screening based on these two mutations, some individuals with subclinical hemochromatosis will be missed.

Effect of NbC and TiC precipitation on shape memory in an iron-based alloy

This paper examines the effects of TiC and NbC precipitation and prior cold rolling on the shape memory behaviour of an iron-based alloy. A precipitate-free alloy was used as a reference to investigate the relative contributions of prior-deformation and precipitation on shape memory. Heat treatment of the Nb- and Ti-containing alloys at 700 °C and 800 °C resulted in carbide precipitates between 120 nm and 220 nm in diameter. Bend testing of these samples showed a marginal increase in shape memory compared to the precipitate-free alloy. Under these conditions TiC precipitation exhibited slightly better shape memory than for NbC. However, this small increase was over-shadowed by the marked increase in shape memory that can be produced by subjecting the alloys to cold rolling followed by recovery annealing. When processed in this way, fine carbides are formed in the Ti- and Nb-containing alloys during the heat treatment. For particles >25 nm in diameter the shape memory is unaffected, but, it was found that small <5 nm particles have a detrimental effect on shape memory due to pinning of the martensite plates, thereby inhibiting their reversion to austenite. The optimum shape memory was observed in the precipitate-free alloy after cold rolling and recovery annealing.

Turbulent filling of iron castings

This thesis explores the fluid flow aspects of the casting filling process. The work shows that, if the filling process is understood, its effect on the quality of the castings can be accounted for during the design of the casting and the runner system, thereby minimising defect formation.

Relationship between inflammatory cytokines and self-report measures of training overload

It has been purported that inflammatory cytokines may be responsible for the aetiology of overtraining. The aim of the present study was to investigate the relationship between self-reported measures of overtraining and inflammatory cytokines. Eight elite male rowers were monitored in their natural training environment for 8 weeks prior to the 2007 Rowing World Championships. During this period of intense endurance training, self-report measures of overtraining and inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, and Tumor Necrosis Factor (TNF)-) were assessed fortnightly. Consistent with previous findings, proinflammatory cytokines IL-1β and TNF- were significantly associated (p ≤ 0.05) with measures of depressed mood, sleep disturbances, and stress. Similarly, IL-6 was significantly associated (p ≤ 0.01) with measures of depressed mood, sleep disturbances, and fatigue. These results are consistent with previous hypotheses describing how overtraining may be caused by excessive cytokine release, and lend further support for a cytokine hypothesis of overtraining.

Assessment of machining characteristics of austempered ductile iron

Austempered Ductile Iron (ADI) is a modified Spheroidal Graphite Iron (SGI) produced by applying a two-stage heat treatment cycle of austenitising and austempering. The microstructure of ADI also known as "ausferrite" consists of ferrite, austenite and graphite nodules. Machining ADI using conventional techniques is often problematic due to the microstructural phase transformation from austenite to martensite. Machining trials consisted of drilling ADI-Grades900, 1050, 1200 and 1400 using inserted (TiAlN PVD coated) type drills. The cutting parameters selected were; cutting speeds [m/min] of 30 and 40; penetration rates [mm/rev] of 0.1 and 0.2; to a constant depth of 20mm. The machining characteristics of ADI are evaluated through surface texture analysis and microhardness analysis. These results indicate that microhardness is modified during machining and surface texture is improved using a cutting fluid.

Machinability assessment and surface integrity characteristics of Austempered Ductile Iron (ADI) using ultra-hard cutting tools

The application of austempered ductile iron (ADI) is gaining an ever greater share of the worldwide ferrous product market, specifically centering on the aerospace, automotive and shipping industries. ADI is a heat treated cast iron, which exhibits remarkable mechanical properties and provides an attractive material for designers and engineers to displace conventional materials. Previous attempts, however, to machine ADI using carbide or ceramic cutting tools produced poor tool life characteristics due to the relatively poor machinability of the workpiece. This paper presents a research study that has applied the advanced technology of modern ultrahard cutting tools, in an attempt to achieve enhanced machinability performance. This performance was evaluated through the analysis of cutting forces, tool wear, surface finish and roundness.

A comparative assessment of austempered ductile iron as a substitute in weight reduction applications

Manufacturing engineering has had to undergo drastic changes in the approach to material selection in order to meet new design challenges. In the automotive industry, researchers in their effort to reduce emissions and satisfy environmental regulations, have shifted their focus to new emerging materials such as high-strength aluminium alloys, metal matrix composites, plastics, polymers and of late, Austempered Ductile Iron (ADI). ADI is a good choice for design where the criterion is high performance at reduced weight and cost. The unique, ausferrite microstructure gives the material desirable material properties and an edge over other materials. A comparative study of ADI in terms of materials properties and machining characteristics with other materials is desirable to highlight the potential of the material. This paper focuses on a comparative assessment of material and machining characteristics of ADI for different applications. The properties under consideration are machinability, weight and cost savings and versatility. ADI has a higher strength-to-weight ratio than aluminium making it a ready alternative for material selection. In terms of machinability, there are some problems associated with machining of ADI due to its work hardening nature. This paper attempts to identify the possible potential applications of ADI, by critically reviewing specific applications such as machinability, overall economics and service.

Structure effect on the oxygen permeation properties of barium bismuth iron oxide membranes

In this work, we investigated the oxygen permeation properties of barium bismuth iron oxide within the family of [Ba_2−3xBi_3x−1][Fe_2xBi_1−2x]O_2+3x/2 for x = 0.17–0.60. The structure changed progressively from cubic to tetragonal and then to hexagonal as function of x in accordance with the different relative amounts of bismuth on A-site and B-site of ABO_3−δ perovskite lattices. We found that the oxygen flux and electrical conductivity correlated strongly, and it was prevalent for the cubic structure (x = 0.33–0.40) which conferred the highest oxygen flux of 0.59 ml min⁻¹ cm⁻² at 950 °C for a disk membrane x = 0.33 with a thickness of 1.2 mm. By reducing the thickness of the disk membrane to 0.8 mm, the oxygen flux increased to 0.77 ml min⁻¹ cm⁻², suggesting both surface kinetics and ion diffusion controlled oxygen flux, though the former was more prominent at higher temperatures. For disk membranes x = 0.45–0.60, the perovskite structure changed to tetragonal and hexagonal, and the oxygen flux was insignificant below 900 °C, clearly indicating electron conduction properties only. However, for two compositions with relatively high bismuth content, e.g. x = 0.55 and 0.60, there was a sudden and significant rise of oxygen permeability above 900 °C, by more than one order of magnitude. These materials changed conduction behavior from metallic to semiconductor at around 900 °C. These results suggest the advent of mixed ionic electronic conducting properties caused by the structure transition as bismuth ions changed their valence states to compensate for the oxygen vacancies formed within the perovskite lattices.

An improved process for the N-demethylation of opiate alkaloids using an iron(II) catalyst in acetate buffer

An improved process to N-demethylate opiate alkaloids utilising a solution of the ferrous porphyrin, tetrasodium 5,10,15,20-tetra(4-sulfophenyl)porphyrinatoiron(II) [=Fe(II)-TPPS (8)], in acetate buffer is described. This method provided the corresponding N-demethylated opiates in good yield with high reproducibility.

Antioxidant enzyme activities of iron-saturated bovine lactoferrin (Fe-bLf) in human gut epithelial cells under oxidative stress

Chemoprevention by dietary constituents in the form of functional food has emerged as a novel approach to control inflammatory diseases and cancers. Recently we reported for the first time that iron content is a critical determinant in the anti-tumour activity of bovine milk lactoferrin (bLf). We therefore wanted to evaluate the chemo-preventative efficacy of Apo-bLF and 100% iron-saturated bLF (Fe-bLF) on hydrogen peroxide (H2O 2)-induced colon carcinogenesis, and their influence on antioxidant enzyme activities within colon carcinogenesis. This was undertaken through observing how oxidative stress induced by H2O2 alters antioxidant enzyme activity within HT29 colon cancer cells, and then observing changes in this activity by treatments with the different antioxidants ascorbic acid (AA), Apo-bLF and Fe-bLF. All antioxidant enzymes (catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GsT) and superoxide dismutase (SOD)) appeared to be increased within HT29 cells, even prior to H2O2 exposure, and all enzymes showed significant decreased activity when cells were treated with the antioxidants AA, Apo-bLF or Fe-bLF, with or without H2O2 exposure. The results indicate that all three antioxidants have the ability to scavenge ROS, lower antioxidant enzyme activities within already excited states, and possibly allow colon cancer cells to be overcome by oxidative stress that would normally be prevented, perhaps leading to damage and potential apoptosis of the cancer cells. In conclusion, the anti-oxidative effects of Apo-bLF and Fe-bLf studied for the first time, show dynamic changes that may allow for necessary protection from imbalanced oxidative conditions, and potential at reducing the ability of cancer cells to protect themselves from oxidative stress states.

The ΔF508-CFTR mutation results in increased biofilm formation by Pseodomonas aeruginosa by increasing iron availability

Enhanced antibiotic resistance of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung is thought to be due to the formation of biofilms. However, there is no information on the antibiotic resistance of P. aeruginosa biofilms grown on human airway epithelial cells or on the effects of airway cells on biofilm formation by P. aeruginosa. Thus we developed a coculture model and report that airway cells increase the resistance of P. aeruginosa to tobramycin (Tb) by >25-fold compared with P. aeruginosa grown on abiotic surfaces. Therefore, the concentration of Tb required to kill P. aeruginosa biofilms on airway cells is 10-fold higher than the concentration achievable in the lungs of CF patients. In addition, CF airway cells expressing ΔF508-CFTR significantly enhanced P. aeruginosa biofilm formation, and ΔF508 rescue with wild-type CFTR reduced biofilm formation. Iron (Fe) content of the airway in CF is elevated, and Fe is known to enhance P. aeruginosa growth. Thus we investigated whether enhanced biofilm formation on ΔF508-CFTR cells was due to increased Fe release by airway cells. We found that airway cells expressing ΔF508-CFTR released more Fe than cells rescued with WT-CFTR. Moreover, Fe chelation reduced biofilm formation on airway cells, whereas Fe supplementation enhanced biofilm formation on airway cells expressing WT-CFTR. These data demonstrate that human airway epithelial cells promote the formation of P. aeruginosa biofilms with a dramatically increased antibiotic resistance. The ΔF508-CFTR mutation enhances biofilm formation, in part, by increasing Fe release into the apical medium.