Improved T2* assessment in liver iron overload by magnetic resonance imaging

In the clinical MRI practice, it is common to assess liver iron overload by T2* multi-echo gradient-echo images. However, there is no full consensus about the best image analysis approach for the T2* measurements. The currently used methods involve manual drawing of a region of interest (ROI) within MR images of the liver. Evaluation of a representative liver T2* value is done by fitting an appropriate model to the signal decay within the ROIs vs. the echo time. The resulting T2* value may depend on both ROI placement and choice of the signal decay model. The aim of this study was to understand how the choice of the analysis methodology may affect the accuracy of T2* measurements. A software model of the iron overloaded liver was inferred from MR images acquired from 40 thalassemia major patients. Different image analysis methods were compared exploiting the developed software model. Moreover, a method for global semiautomatic T2* measurement involving the whole liver was developed. The global method included automatic segmentation of parenchyma by an adaptive fuzzy-clustering algorithm able to compensate for signal inhomogeneities. Global liver T2* value was evaluated using a pixel-wise technique and an optimized signal decay model. The global approach was compared with the ROI-based approach used in the clinical practice. For the ROI-based approach, the intra-observer and inter-observer coefficients of variation (CoVs) were 3.7% and 5.6%, respectively. For the global analysis, the CoVs for intra-observers and inter-observers reproducibility were 0.85% and 2.87%, respectively. The variability shown by the ROI-based approach was acceptable for use in the clinical practice; however, the developed global method increased the accuracy in T2* assessment and significantly reduced the operator dependence and sampling errors. This global approach could be useful in the clinical arena for patients with borderline liver iron overload and/or requiring follow-up studies.     

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.     

Effect of pH and Pea Protein: Xanthan Gum Ratio on Emulsions with High Oil Content and High Internal Phase Emulsion Formation

Electrostatic interaction between protein and polysaccharides could influence structured liquid oil stability when emulsification is used for this purpose. The objective of this work was to structure sunflower oil forming emulsions and High Internal Phase Emulsions (HIPEs) using pea protein (PP) and xanthan gum (XG) as a stabilizer, promoting or not their electrostatic attraction. The 60/40 oil-in-water emulsions were made varying the pH (3, 5, and 7) and PP:XG ratio (4:1, 8:1, and 12:1). To form HIPEs, samples were oven-dried and homogenized. The higher the pH, the smaller the droplet size (Emulsions: 15.60–43.96 µm and HIPEs: 8.74–20.38 µm) and the oil release after 9 weeks of storage at 5 °C and 25 °C (oil loss < 8%). All systems had weak gel-like behavior, however, the values of viscoelastic properties (G′ and G″) increased with the increment of PP:XG ratio. Stable emulsions were obtained at pHs 5 and 7 in all PP:XG ratios, and at pH 3 in the ratio 4:1. Stable HIPEs were obtained at pH 7 in the ratios PP:XG 4:1, 8:1, and 12:1, and at pH 5 at PP:XG ratio 4:1. All these systems presented different characteristics that could be exploited for their application as fat substitutes.     

Physicochemical properties of mixed micellar aggregates containing CCK peptides and Gd complexes designed as tumor specific contrast agents in MRI

New amphiphilic molecules containing a bioactive peptide or a claw moiety have been prepared in order to obtain mixed micelles as target-specific contrast agents in magnetic resonance imaging. The first molecule, C(18)H(37)CONH(AdOO)(2)-G-CCK8 (C18CCK8), contains a C18 hydrophobic moiety bound to the C-terminal cholecystokinin octapeptide amide (CCK 26-33 or CCK8). The second amphiphilic compound, C(18)H(37)CONHLys(DTPAGlu)CONH(2) (C18DTPAGlu) or its gadolinium complex, (C18DTPAGlu(Gd)), contains the same C18 hydrophobic moiety bound, through a lysine residue, to the DTPAGlu chelating agent. The mixed aggregates as well as the pure C18DTPAGlu aggregate, in the presence and absence of Gd, have been fully characterized by surface tension measurements, FT-PGSE-NMR, fluorescence quenching, and small-angle neutron scattering measurements. The structural characterization of the mixed aggregates C18DTPAGlu(Gd)-C18CCK8 indicates a spherical arrangement of the micelles with an external shell of approximately 21 A and an inner core of approximately 20 A. Both the DTPAGlu(Gd) complexes and the CCK8 peptides point toward the external surface. The measured values for relaxivity in saline medium at 20 MHz proton Larmor frequency and 25 degrees C are 18.7 mM(-)(1) s(-)(1). These values show a large enhancement in comparison with the isolated DTPAGlu(Gd) complex.     

Highly luminescent Eu(3+) and Tb(3+) macrocyclic complexes bearing an appended phenanthroline chromophore

A two-component ligand system (1) containing 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) as the hosting unit for the lanthanide cations and an appended asymmetrically functionalized 1,10-phenanthroline (phen) as the chromophore was synthesized. The 1:1 complexes with Eu(3+), Gd(3+), Tb(3+), and Yb(3+) have been prepared and studied in aqueous solution. For Gd.1, a relaxivity value of 2.4 mM(-1) s(-1) has been measured at 20 MHz and 25 degrees C, which indicates that there are no water molecules in the first coordination sphere of the metal ion. The analysis of high resolution (1)H NMR spectra of Yb.1 supports this view and suggests the direct involvement of the phen moiety in the coordination of the metal ion. For Eu.1 and Tb.1, the absorption and luminescence spectra, the overall luminescence efficiencies, and the metal-centered (MC) lifetimes were obtained; coordination features were also determined by comparing luminescence properties in water and deuterated water. For Eu.1 and Tb.1, the overall emission sensitization (se) process in air-equilibrated water was found to be notably effective with phi(se) = 0.21 and 0.11, respectively. A detailed study of the steps originating from light absorption at the phen unit and leading to MC sensitized emission was performed.     

High-relaxivity magnetic resonance imaging (MRI) contrast agent based on supramolecular assembly between a gadolinium chelate, a modified dextran, and poly-beta-cyclodextrin

Nanosized contrast agents have great potential in magnetic resonance molecular imaging applications for clinical diagnosis. This study proposes new nanoparticles spontaneously formed under mild conditions and composed of a noncovalent adduct between a gadolinium complex, a polymer of beta-cyclodextrin (pbetaCD: MW 1.5 x 10(6) g mol(-1)) and a dextran grafted with alkyl chains (MD). The formation of this supramolecular nanoassembly is based upon a "lock-and-key" recognition process in which the hydrophobic alkyl chains of MD and the adamantyl moieties of macrocyclic Gd(III) chelates are included in the cavities of pbetaCD. The large number of betaCDs contained in the pbetaCD resulted in the formation of 200 nm diameter nanoparticles, each entrapping 1.8 x 10(5) molecules of a low-molecular-weight Gd complex. This system, which exhibits a great relaxivity enhancement (48.4 mM(-1) s(-1), at 20 MHz and 37 degrees C) compared to the Gd(III) chelate itself (5.2 mM(-1) s(-1)), appears to be a promising strategy for the in vivo targeted delivery of Gd(III) complexes. The mechanisms of particle formation, conjugation strategies, and relaxometric characterizations in the field of contrast-enhanced magnetic resonance imaging are discussed.     

Low-temperature clean-up method for the determination of pyrethroids in milk using gas chromatography with electron capture detection

This paper describes a new gas-chrormatography with electron capture detection (GC-ECD) method for determination of some pyrethroids in milk samples. The extraction of the pyrethroids was carried out by liquid–liquid extraction with clean-up by precipitation at low temperature, without additional stages for removal of fat interferences. The method was efficient with recoveries of 93.0 ± 0.1% for cipermethrin and 84.0 ± 0.3% for deltamethrin. The quantification limits were 0.75 μg L⁻¹ for both pyrethroids. The method was simple, of easy execution, and used only small quantities of organic solvent. After optimization and validation, the method was used for the determination of residues of the pyrethroids cipermethrin and deltamethrin in milk and in lactea drink commercialized in Viçosa (MG, Brazil). Some samples presented contamination with deltamethrin at levels below the maximum contamination limits established by the FAO.