Fabry Disease and the Heart: A Comprehensive Review

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.     

Two new aluminophosphates, IST-1 and IST-2: First examples of a dual templating role of water and methylamine in generating microporous structures

This study is aimed at exploring the ability of very small sized N-bearing molecules to generate and stabilize microporous aluminophosphates. Two new AlPO₄-n materials, called IST-1 and IST-2, have been obtained in aqueous media using, as main template, methylamine (MA), directly added, or generated in situ from methylformamide (MF) degradation. While IST-1 topology proved to be novel, IST-2 appears structurally related to AlPO₄-53(A). The obtained materials were characterized by powder XRD, TG/DSC, SEM and solid-state NMR. Tetraalkylammonium (TEA) cations were used as potential co-templates but only MA and water were found incorporated in the pore volumes of both structures, which argues for their true templating role. In IST-1, ¹³C solid-state NMR studies showed that half of MA species, presumably protonated, is H-bonded to framework oxygens while the other half surprisingly bonds directly to framework Al atoms. ¹³C NMR showed that only protonated MA occurs in IST-2 channels. TEA⁺ cations definitely do not play any specific template role. They indirectly favor the crystallization of IST-1 or IST-2 devoid from other crystalline or amorphous side phases, by interacting with part of the Al and P in solution and forming soluble [AlPO₄(OH)]–[TEA,HMA] complexes, substantially modifying the compositions of gels precursors to each phase during nucleation and/or growth steps. While both IST-1 and IST-2 crystallize from gels of similar initial compositions, it was demonstrated that the new MA/T ratio (T = Al or P) obtained after in situ complexation was the key parameter that specifically governs the crystallization of each phase.     

Intra- and interspecific mineral composition variability of commercial instant coffees and coffee substitutes: Contribution to mineral intake

The present paper reports the amount and estimated daily mineral intake of nine elements (Ca, Mg, K, Na, P, Fe, Mn, Cr and Ni) in commercial instant coffees and coffee substitutes (n = 49). Elements were quantified by high-resolution continuum source flame (HR-CS-FAAS) and graphite furnace (HR-CS-GFAAS) atomic absorption spectrometry, while phosphorous was evaluated by a standard vanadomolybdophosphoric acid colorimetric method.Instant coffees and coffee substitutes are rich in K, Mg and P (>100 mg/100 g dw), contain Na, Ca and Fe in moderate amounts (>1 mg/100 g), and trace levels of Cr and Ni. Among the samples analysed, plain instant coffees are richer in minerals (p < 0.001), except for Na and Cr. Blends of coffee substitutes (barley, malt, chicory and rye) with coffee (20–66%) present intermediate amounts, while lower quantities are found in substitutes without coffee, particularly in barley.From a nutritional point of view the results indicate that the mean ingestion of two instant beverages per day (total of 4 g instant powder), either with or without coffee, cannot be regarded as important sources of minerals to the human diet, although providing a supplementation of some minerals, particularly Mg and Mn in instant coffees. Additionally, and for authentication purposes, the correlations observed between some elements and the coffee percentage in the blends, with particular significance for Mg amounts, provides a potential tool for the estimation of coffee in substitute blends.     

In vitro intestinal absorption of amino acid mixtures extracted from codfish (Gadus morhua L.) salting wastewater

This study reports on the intestinal permeability of salt‐containing mixtures of amino acids extracted from codfish salting wastewater. Permeability was evaluated in vitro using the Caco‐2 cell line model; cell integrity during exposure to mixtures of amino acids was estimated by measuring the transepithelial electrical resistance (TEER). The effect of salt (NaCl) on the permeability and on the intestinal cell's integrity was also examined. Permeation rate (i.e. transport) was ≥95% for all amino acids except for creatine, for which it was 6%. Values for apparent permeability coefficients, P_app > 10^?5 cm s^?1, for mixture with isotonic concentration of NaCl suggest that amino acids are very likely to be absorbed in humans. Mixture with a hypertonic level of NaCl exerts a cytotoxic effect in intestinal cells resulting in a loss of epithelium integrity. Results show that isotonic mixture of amino acids extracted from codfish salting wastewater could be used in food, feed, cosmetic and pharmaceutical formulations. These applications could contribute to the fish industry sustainability.     

Preparation and properties of polyamide‐6‐based thermoplastic laminate composites by a novel in‐mold polymerization technique

In this work, a method for preparation of polyamide‐6 (PA6) based laminates reinforced by glass fiber‐ (GFL) or polyamide‐66 (PA66) textile structures (PL) via reactive injection molding is disclosed. It is based on in‐mold anionic polymerization of ε‐caprolactam carried out at 165°C in the presence of the respective reinforcements performed in newly developed prototype equipment whose design concept and operation are described. Both composite types were produced for reaction times of 20 min, with conversion degrees of 97–99%. Initial mechanical tests in tension of GFL samples displayed almost twofold increase of the Young's modulus and stress at break values when compared with the neat anionic PA6. The improvement was proportional to the volume fraction V_f of glass fiber fabric that was varied in the 0.16–0.25 range. A 300% growth of the impact strength was registered in PL composites with V_f of PA66 textile of 0.1. Removing the surface finish of the latter was found to be a factor for improving the adhesion at the matrix–fiber interface. The mechanical behavior of GFL and PL composites was discussed in conjunction with the morphology of the samples studied by optical and electron microscopy and the matrix crystalline structure as revealed by synchrotron X‐ray diffraction. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40083.     

The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines

Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays. At the molecular level, an array of gene expressions encompassing several molecular pathways were used to explore the impact of treatment on gene expression. Although both quinoxalines and the ionic liquid [C2OHMIM][Amp] did not show any effect on the BrCa and PCa cell lines, [C16Pyr][Amp] significantly decreased cell viability and colony formation ability, while it increased the apoptosis levels of all cell lines. Importantly, [C16Pyr][Amp] was found to be more selective for cancer cells and less toxic than cisplatin. At the molecular level, this ionic liquid was also associated with reduced expression levels of CPT2, LDHA, MCM2, and SKP2, in both BrCa and PCa cell lines. Hence, [C16Pyr][Amp] was shown to be a promising anticancer therapeutic agent for BrCa and PCa cell lines.     

Physical examination of arteriovenous fistula: The influence of professional experience in the detection of complications

Vascular access is one of the leading causes of mobilization of financial resources in health systems for people with chronic kidney disease on hemodialysis. Physical examination of the arteriovenous fistula (AVF) has demonstrated its effectiveness in identifying complications. We decided to evaluate the influence of nurses' professional experience in the detection of complications of the AVF (venous stenosis and steal syndrome). The study took place in eight hemodialysis centers between May and September of 2011 in the north of Portugal. Sample was constituted by registered nurses. The nurses involved in the experiment were divided in two groups: those who had more than 5 years of experience and those who had less than 5 years of experience. Ninety‐two nurses participated in the study: 34 nurses had less than 5 years of professional experience and 58 had more than 5 years of professional experience. In the practices considered by nurses in the detection of venous stenosis, there were no differences observed between the groups (P > 0.05). In steal syndrome, there were no differences observed between the groups in the practices of the nurses in the detection of this complication of the AVF (P > 0.05). We concluded that professional experience does not influence the detection of venous stenosis and steal syndrome.     

Alicyclobacillus acidoterrestris spores as a target for Cupuaçu (Theobroma grandiflorum) nectar thermal processing: kinetic parameters and experimental methods

The kinetic parameters of thermal inactivation of a spore former, Alicyclobacillus acidoterrestris, in a tropical fruit nectar [25% of Cupua?u (Theobroma grandiflorum) pulp and 15% sugar] were determined by the isothermal method (IM), under batch heating, and by the paired equivalent isothermal exposures (PEIE) method, under non-isothermal continuous conditions. The isothermal experiments were repeated three times, every 4 months, with the same spore suspension kept frozen between experiments. The aging of spores, under frozen storage, seemed to produce a notorious increase in the z-value from experiment to experiment: Experiment 1 (z = 7.8 +/- 2.6 degrees C, D(95 degrees C) = 5.29 +/- 0.96 min), Experiment 2 (z = 22 +/- 5 degrees C, D(95 degrees C) = 5.99 +/- 0.63 min), and Experiment 3 (z =29 +/- 10 degrees C, D(95 degrees C) = 3.82 +/- 0.48 min). The evaluation of the kinetic parameters by the PEIE method was carried out in parallel with Experiment 3, with the same aged spores, and the results (z = 31 +/- 6 degrees C, D(95 degrees C) = 5.5 +/- 1.2 min) were close to the ones obtained in this experiment. From this work, it seems that the PEIE method can also be applied to evaluate the reduction parameters of a spore-forming microorganism, and in a more realistic way, since the continuous system eliminates the errors caused by come-up and cool-down times (CUT and CDT) that are unavoidable in isothermal experiments. Therefore, when designing a thermal process for a continuous system, the PEIE method should be used, or the chances are that the process would be underdesigned, risking that the desired level of spore inactivation would not be achieved. An optimization of the thermal processing conditions was next performed for Cupua?u nectar, considering a 5D reduction in A. acidoterrestris spores. If a pasteurization process is considered, the conditions that ensure safety (9 min at 98 degrees C) only allow a 55% retention of ascorbic acid (AA). If sterilization is considered, 8 s at 115 degrees C will ensure a safe product and retain 98.5% of the original ascorbic acid. Therefore, if A. acidoterrestris is considered as the target microorganism, the nectar should undergo an aseptic high temperature short time principle (HTST) process to achieve a 5D reduction in this acidophilus spore former. However, if the hot-fill-and-hold pasteurization process is preferred, the product should be fortified with ascorbic acid.