Daniel Rodrigues

Frequency of Fabry disease in male and female haemodialysis patients in Spain

BackgroundFabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme α-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression.MethodsA combined enzymatic and genetic strategy was used, measuring the activity of α-galactosidase A and genotyping the α-galactosidase A gene (GLA) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain.ResultsGLA alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with GLA causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients.ConclusionsExcluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy.

A model relating remanence and microstructure of SmCo5 magnets

Abstract The question of remanence in SmCo5 sintered magnets is reviewed, giving special attention to the influence of microstructure. In SmCo5 magnets, the microstructural constituents are the matrix phase SmCo5, another ferromagnetic phase (Sm2Co7), oxides (Sm2O3), a recently reported carbide SmCoC2 and pores. A method to estimate alignment via the ratio Jr/Js from remanence measurements and microstructural analysis is proposed. The results agree very well with the degree of alignment calculated from Schulz pole figures. During sintering it was observed that the nucleation of SmCo5 on the Sm2Co7 phase is epitaxial. Hexagonal Sm2Co7 is present in our sintered magnets but rhombohedral Sm2Co7 may also be present. The effect of chemical composition (Sm content and oxygen content) on remanence and on the ratio Jr/Js was evaluated. In the sintering step, the densification occurs more slowly for compositions with higher samarium content (or higher Sm2Co7 volume fraction). A model able to calculate the best chemical composition to maximize coercivity and remanence is presented and discussed.

Effect of Calcium Phosphate Addition to Alginate Microspheres: Modulation of Enzyme Release Kinetics and Improvement of Cell Adhesion

In this study, the addition of calcium phosphate powders to an alginate matrix was evaluated as a strategy to modulate enzyme release-kinetics from alginate microspheres and, simultaneously, to improve cell adhesion to the polymer. Pre-adsorption of the enzyme to the ceramic powders resulted in a more adequate release pattern. The ratio of ceramic-to-polymer had a pronounced effect on osteoblast adhesion to microspheres. Cells were only able to spread on microspheres with the highest percentage of ceramic (0.4 w/w using a 1.5% w/v alginate solution).

Effect of Calcination Conditions on the Magnetic Properties of MnZn Ferrites Powders Produced by Co Precipitation

MnZn ferrites are conventionally produced by the ceramic method that involves the solid state reaction of metallic oxides or carbonates at high temperatures. The particles obtained by this method are rather large and non-uniform in size. In order to overcome the difficulties arising out of the ceramic process, the coprecipitation method has been used as an alternative route to produce chemically homogeneous powders with fine particle size. In this work MnZn ferrites powders were produced by the coprecipitation method. The calcination conditions, such as temperature (900oC to 1100oC) and atmosphere (air and nitrogen), were investigated. X ray diffractometry, scanning electron microscopy, thermomagnetic analysis and vibration sample magnetometry were used to characterize the obtained samples. The results indicated that when the samples were calcined in nitrogen atmosphere, the ferrite formation occurred at low calcination temperatures and presented better magnetic properties than those calcined in air.

Combining Mager and Steinmetz: The Effect of Grain Size and Maximum Induction on Hysteresis Energy Loss

Twelve samples with different grain sizes were prepared by normal grain growth and by primary recrystallization, and the hysteresis dissipated energy was measured by a quasi-static method. Results showed a linear relation between hysteresis energy loss and the inverse of grain size, which is here called Magers law, for maximum inductions from 0.6 to 1.5 T, and a Steinmetz power law relation between hysteresis loss and maximum induction for all samples. The combined effect is better described by a Magers law where the coefficients follow Steinmetz law.

Estimative of the Stacking Fault Energy for a FeNi(50/50) Alloy and a 316L Stainless Steel

The effect of high energy milling on powders of a FeNi (50/50) alloy and a 316L stainless steel has been evaluated by means of X-Ray Diffraction (XRD). The average microstrain as function of the milling time (1/2h, 1h and 8h) was determined from XRD data. The displacement and broadening of the (XRD) peaks were used for estimate the stacking fault energy (SFE), using the method of Reed and Schramm. It was estimated SFE=79 mJ/m2 for the FeNi (50/50) alloy and SFE=14 mJ/m2 for the 316L stainless steel. The better experimental conditions for determining the SFE by XRD are discussed.

Excess Loss Localization on the Hysteresis Curve

Two alloys of nonoriented electrical steel, with 2.45 and 3.3%Si, respectively, had their magnetic properties characterized in an Epstein frame. Hysteresis curves for total, quasi-static, and parasitic losses were plotted and overlapped to identify the region where the anomalous loss happens. It was observed that most anomalous loss is from the domain wall movements region and a smaller contribution from nucleation and annihilation regions.

Reduced glucosylceramide in the mouse model of Fabry disease: Correction by successful enzyme replacement therapy

Fabry disease is an X-linked lysosomal storage disease (LSD) caused by deficient activity of α-Galactosidase A (α-Gal A). As a result, glycosphingolipids, mainly globotriaosylceramide (Gb3), progressively accumulate in body fluids and tissues. Studies aiming at the identification of secondary lipid alterations in Fabry disease may be potentially useful for the monitorization of the response to enzyme replacement therapy (ERT) and development of future therapies. The focus of this study was to evaluate if α-Gal A deficiency has an effect on two key groups of molecules of sphingolipids metabolism: glucosylceramides (GlucCers) and ceramides (Cers). Studies performed in a mouse model of Fabry disease showed reduced level of GlucCer and normal level of Cer in plasma, liver, spleen, kidney and heart. Moreover, analysis of GlucCer isoforms in Fabry knockout mice showed that GlucCer isoforms are unequally reduced in different tissues of these animals. ERT had a specific effect on the livers GlucCer levels of Fabry knockout mice, increasing hepatic GlucCer to the levels observed in wild type mice. In contrast to Fabry knockout mice, plasma of Fabry patients had normal GlucCer and Cer but an increased GlucCer/Cer ratio. This alteration showed a positive correlation with plasma globotriaosylsphingosine (lyso-Gb3) concentration. In conclusion, this work reveals novel secondary lipid imbalances caused by α-Gal A deficiency.

Study of Soft Magnetic Nickel-Iron Based Alloys Processed by Powder Injection Molding

Ni-Fe based soft-magnetic alloys, processed via Metal Injection Molding (MIM), were investigated regarding the influence of processing route on final magnetic properties and compared to fully dense cast materials. The process variations included high and low temperature debinding, different sintering routes and the application of hot isostatic pressing (HIP). The different densities resulting from the process variations were related to maximum magnetic permeability. Results have shown that density, in the range between 7,5g/cm³ and 8,0g/cm³, does not have significant influence on the maximum permeability, allowing cost-effective process routes. It was also verified that fullydense cast alloys still exhibits superior properties, with lower coercive fields and higher permeability, but results achieved after HIP process overcame even the values of these commercial grade alloys.

Curie Temperature Determination of Pr14Fe79.9-xCoxB6Nb0.1 Permanent Magnet Alloys

This paper reports the results of investigations carried out to determine the Curie temperature (Tc) of some annealed praseodymium-based alloys represented by the formula Pr14Fe79.9-xCoxB6Nb0.1. The Curie temperature of these permanent magnet alloys increase linearly with the cobalt content at about (10.2±0.3) oC/at%. Pr14Fe80B6 and Pr14Fe79.9B6Nb0.1 magnetic alloys with a Tc of 290oC have been used as a standard reference. Magnets were prepared from the alloys using the hydrogenation, disproportionation, desorption and recombination (HDDR) process.