A Preformulation Study of a New Medicine for Chagas Disease Treatment: Physicochemical Characterization,Thermal Stability,and Compatibility of Benznidazole

This work aimed the studies of physicochemical characterization, thermal stability, and compatibility of benznidazole (BNZ) drug by spectroscopy (NMR, IR), thermoanalytical (differential thermal analysis, differential scanning calorimetry, and thermogravimetry), and chromatographic (HPLC) techniques, beyond the analytical tools of Van’t Hoff equation and Ozawa model. The compatibility study was conducted by binary mixtures (1:1, w/w) of the drug with microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch glycolate. The physicochemical characterization confirmed data reported in scientific literature, guaranteeing authenticity of the analyzed raw material. The drug melts at 191.68°C (∆H, 119.71 J g⁻¹), characteristic of a non-polymorphic raw material, and a main stage decomposition at 233.76–319.35°C (∆m, 43.32%) occurred, ending the study with almost all mass volatilized. The quantification of drug purity demonstrated a correlation of 99.63% between the data obtained by chromatographic (99.20%) and thermoanalytical technique (99.56%). The Arrhenius equation and Ozawa model showed a zero-order kinetic behavior for the drug decomposition, and a calculated provisional validity time was 2.37 years at 25°C. The compatibility study evidenced two possible chemical incompatibilities between BNZ and the tested excipients, both associated by the authors to the reaction of the BNZ’s amine and a polymer carbohydrate’s carbonile, being maillard reactions. The BNZ reaction with anhydrous lactose is more pronounced than with the sodium starch glycolate because the lactose has more free hydroxyl groups to undergo reduction by the drug. In this sense, this work guides the development of a new solid pharmaceutical product for Chagas disease treatment, with defined quality control parameters and physicochemical stability.     

Unique Properties of Human β-Defensin 6 (hBD6) and Glycosaminoglycan Complex: SANDWICH-LIKE DIMERIZATION AND COMPETITION WITH THE CHEMOKINE RECEPTOR 2 (CCR2) BINDING SITE*

Defensins are components of the innate immune system that promote the directional migration and activation of dendritic cells, thereby modulating the adaptive immune response. Because matrix glycosaminoglycan (GAG) is known to be important for these functions, we characterized the structural features of human β-defensin 6 (hBD6) and GAG interaction using a combination of structural and in silico analyses. Our results showed that GAG model compounds, a pentasaccharide (fondaparinux, FX) and an octasaccharide heparin derivative (dp8) bind to the α-helix and in the loops between the β2 and β3 strands, inducing the formation of a ternary complex with a 2:1 hBD6:FX stoichiometry. Competition experiments indicated an overlap of GAG and chemokine receptor CCR2 binding sites. An NMR-derived model of the ternary complex revealed that FX interacts with hBD6 along the dimerization interface, primarily contacting the α-helices and β2-β3 loops from each monomer. We further demonstrated that high-pressure NMR spectroscopy could capture an intermediate stage of hBD6-FX interaction, exhibiting features of a cooperative binding mechanism. Collectively, these data suggest a “sandwich-like” model in which two hBD6 molecules bind a single FX chain and provide novel structural insights into how defensin orchestrates leukocyte recruitment through GAG binding and G protein-coupled receptor activation. Despite the similarity to chemokines and hBD2, our data indicate different properties for the hBD6-GAG complex. This work adds significant information to the currently limited data available for the molecular structures and dynamics of defensin carbohydrate binding.     

Age and body mass are more important than horns to determine the social position of dairy cows

Journal of Ethology - The aims of this observational study were to (1) define which animal’s phenotypic characteristics determine social position in the context of a commercial organic farm...     

Detecting natural changes of cone-excitation ratios in simple and complex coloured images.

Ratios of excitations in each cone-photoreceptor class produced by light reflected from pairs of surfaces in a scene are almost invariant under natural illuminant changes. The stability of these spatially defined ratios may explain the remarkable ability of human observers to efficiently discriminate illuminant changes from changes in surface reflectances. Spatial cone-excitation ratios are not, however, exactly invariant. This study is concerned with observers'' sensitivity to these invariance violations. Simulations of Mondrian paintings with either 49 or two natural surfaces under Planckian illuminants were presented as images on a computer-controlled display in a two-interval experimental design: in one interval, the surfaces underwent an illuminant change; in the other interval, the surfaces underwent the same change but the images were then corrected so that, for each cone class, ratios of excitations were preserved exactly. Although the intervals with corrected images corresponded individually to highly improbable natural events, observers systematically misidentified them as containing the illuminant changes, the probability of error increasing as the violation of invariance in the other interval increased. For the range of illuminants and surfaces tested, sensitivity to violations of invariance was found to depend on cone class: it was greatest for long-wavelength-sensitive cones and least for short-wavelength-sensitive cones. Spatial cone-excitation ratios, or some closely related quantities, seem to be the cues preferred by observers for making inferences about surface illuminant changes.     

Immunostimulating effect of D2 dopamine receptor agonist quinpirole

Immunostimulating activity of specific postsynaptic D2 receptor agonist quinpirole (Ly 171555) was studied in CBA mice. The drug was administered intraperitoneally in a dose of 1 mg/kg 30 min before the immunization with SRBC (5 x 10(8)). Considerable stimulation of rosette- and plaque-forming cell number was observed at the early stage (3-d day) and at more late stage of the immune response (5-th day). The increase of rosette- and plaque-forming cell number was provided by IgM-reaction enhancement.     

Syntax at Hand: Common Syntactic Structures for Actions and Language

Evidence that the motor and the linguistic systems share common syntactic representations would open new perspectives on language evolution. Here, crossing disciplinary boundaries, we explore potential parallels between the structure of simple actions and that of sentences. First, examining Typically Developing (TD) children displacing a bottle with or without knowledge of its weight prior to movement onset, we provide kinematic evidence that the sub-phases of this displacing action (reaching + moving the bottle) manifest a structure akin to linguistic embedded dependencies. Then, using the same motor task, we reveal that children suffering from specific language impairment (SLI), whose core deficit affects syntactic embedding and dependencies, manifest specific structural motor anomalies parallel to their linguistic deficits. In contrast to TD children, SLI children performed the displacing-action as if its sub-phases were juxtaposed rather than embedded. The specificity of SLI’s structural motor deficit was confirmed by testing an additional control group: Fragile-X Syndrome patients, whose language capacity, though delayed, comparatively spares embedded dependencies, displayed slower but structurally normal motor performances. By identifying the presence of structural representations and dependency computations in the motor system and by showing their selective deficit in SLI patients, these findings point to a potential motor origin for language syntax.     

Biosynthesis and Uptake of Copper Nanoparticles by Dead Biomass of Hypocrea lixii Isolated from the Metal Mine in the Brazilian Amazon Region

A biological system for the biosynthesis of nanoparticles (NPs) and uptake of copper from wastewater, using dead biomass of Hypocrea lixii was analyzed and described for the first time. The equilibrium and kinetics investigation of the biosorption of copper onto dead, dried and live biomass of fungus were performed as a function of initial metal concentration, pH, temperature, agitation and inoculum volume. The high biosorption capacity was observed for dead biomass, completed within 60 min of contact, at pH 5.0, temperature of 40°C and agitation speed of 150 rpm with a maximum copper biosorption of 19.0 mg g⁻¹. The equilibrium data were better described using the Langmuir isotherm and kinetic analysis indicated that copper biosorption follows a pseudo-second-order model. The average size, morphology and location of NPs biosynthesized by the fungus were determined by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). NPs were mainly spherical, with an average size of 24.5 nm, and were synthesized extracellularly. The X-ray diffraction (XRD) analysis confirms the presence of metallic copper particles. Infrared spectroscopy (FTIR) study revealed that the amide groups interact with the particles, which was accountable for the stability of NPs. This method further confirmed the presence of proteins as stabilizing and capping agents surrounding the copper NPs. These studies demonstrate that dead biomass of Hypocrea lixii provides an economic and technically feasible option for bioremediation of wastewater and is a potential candidate for industrial-scale production of copper NPs.     

Liquid-liquid extraction of lectin from Cratylia mollis seeds using reversed micelles

Extraction of lectin from seeds ofCratylia mollis, camaratu bean, with reversed micelles of 100 mM sodium di(2-ethylhexyl) sulfosuccinate/isooctane was performed firstly with affinity-purified lectin. The best conditions were extraction of the seed extract at pH 5 and back-extraction at pH 10, giving yields of 38% and 100%, respectively.