Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis

Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis.     

Mammalian prion amyloid formation in bacteria

Mammalian prion proteins (PrPs) that cause transmissible spongiform encephalopathies are misfolded conformations of the host cellular PrP. The misfolded form, the scrapie PrP (PrP^Sc), can aggregate into amyloid fibrils that progressively accumulate in the brain, evolving to a pathological phenotype. A particular characteristic of PrP^Sc is to be found as different strains, related to the diversity of conformational states it can adopt. Prion strains are responsible for the multiple phenotypes observed in prion diseases, presenting different incubation times and diverse deposition profiles in the brain. PrP biochemical properties are also strain-dependent, such as different digestion pattern after proteolysis and different stability. Although they have long been studied, strain formation is still a major unsolved issue in prion biology. The recreation of strain-specific conformational features is of fundamental importance to study this unique pathogenic phenomenon. In our recent paper, we described that murine PrP, when expressed in bacteria, forms amyloid inclusion bodies that possess different strain-like characteristics, depending on the PrP construct. Here, we present an extra-view of these data and propose that bacteria might become a successful model to generate preparative amounts of prion strain-specific assemblies for high-resolution structural analysis as well as for addressing the determinants of infectivity and transmissibility.     

Stress distribution of three-unit fixed partial prostheses (conventional and pontic) supported by three or two implants: 3D finite element analysis of ductile materials

In implantology, when financial or biological feasibility limitations appear, it is necessary to use prostheses with geometries that deviate from the conventional, with a pontic in the absence of an intermediate implant. The aim of this study was analyze and understand the general differences in the stresses generated in implants, components and infrastructures according to the configuration of the prosthesis over three or two implants. Thus, this paper analyzes the von Mises equivalent stresses (VMES) of ductile materials on their external surfaces. The experimental groups: Regular Splinted Conventional Group (RCG), which had conventional infrastructures on 3 regular-length Morse taper implants (4x11?mm); Regular Splinted Pontic Group (RPG), which had infrastructures with intermediate pontics on 2 regular-length Morse taper implants (4x11?mm). The simulations of the groups were created with Ansys Workbench 10.0 software. The results revealed that the RPG presented greater areas of possible fragility due to higher stress concentrations, for example, in the cervical area of the union between the implant and component the top platform of the abutment, as well as greater coverage of the stress by the cervical implant threads. The RPG infrastructure was also more affected by stresses in the connection areas between the prostheses and on the occlusal surface. There is an advantage to using prostheses supported by a greater number of implants (RCG) because this decreases the stress in the analyzed structures and consequently improves stress dissipation to the supporting bone, which would preserve the system.     

The structure of shallow water fish assemblages in sandy beaches of a tropical bay in the southwestern Atlantic

Ichthyological Research - The spatial and seasonal dynamics of shallow water fish assemblages and their relationship with physical-chemical variables were investigated on Guanabara Bay, one of the...     

Identification of Biomarkers of Mercury Contamination in Brachyplatystoma filamentosum of the Madeira River,Brazil, Using Metalloproteomic Strategies

Biological Trace Element Research - Predator fish can accumulate high levels of mercury, which qualifies them as potential indicators of this toxic metal. The predatory species Brachyplatystoma...     

Sensible heat transfer and thermal windows in Dasyprocta leporina (Mammalia,Rodentia)

This study aimed to evaluate the diurnal variation of the sensible heat transfer in red-rumped agoutis (Dasyprocta leporina) bred in captivity in a semi-arid environment. In addition, we seek to identify thermal windows by infrared thermography during the daytime period (07:00, 09:00, 11:00, 14:00, and 16:00). The body surface temperature was higher in the pinna (36.84 ± 0.11 °C), followed by the hind limbs (36.55 ± 0.11 °C). These body regions were primarily responsible for heat loss by radiation (which was 10.13 ± 1.17 W m^?2 and 11.19 ± 1.17 W m^?2, respectively), and acted like biological thermal windows. Heat transfer by convection was more intense in the body trunk and hind limbs at all times of the day. Thus, sensible heat transfer is important for maintaining homeothermy in red-rumped agouti in hot environments. In conclusion, these rodents use specialized body regions (pinna and hind limbs) for heat transfer.     

Testosterone suppresses oxidative stress in human neutrophils

The in vitro effect of testosterone on human neutrophil function was investigated. Blood neutrophils from healthy male subjects were isolated and treated with 10 nM, 0.1 and 10 µM testosterone for 24 h. As compared with untreated cells, the testosterone treatment produced a significant decrease of superoxide production as indicated by the measurement of extra‐ and intracellular superoxide content. An increment in the production of nitric oxide was observed at 0.1 and 10 µM testosterone concentrations, whereas no effect was found for 10 nM. Intracellular calcium mobilization was significantly increased at 10 nM, whereas it was reduced at 10 µM testosterone. There was an increase in phagocytic capacity at 10 nM and a decrease of microbicidal activity in neutrophils treated with testosterone at 10 µM. Glutathione reductase activity was increased by testosterone treatment, whereas no effect was observed in other antioxidant enzyme activities. An increase in the content of thiol groups was observed at all testosterone concentrations. Lipid peroxidation in neutrophils evaluated by levels of TBARS was decreased at 10 nM and 0.1 µM testosterone. These results indicate the antioxidant properties of testosterone in neutrophils as suggested by reduction of superoxide anion production, and lipid peroxidation, and by the increase in nitric oxide production, glutathione reductase activity and the content of thiol groups. Therefore, the plasma levels of testosterone are important regulators of neutrophil function and so of the inflammatory response. Copyright © 2010 John Wiley & Sons, Ltd.     

Peptide mapping of β-casein by capillary zone electrophoresis

A method to the study of -casein proteolysis by aspartic proteinases is developed. The 3% trichloroacetic acid-soluble peptides of -casein digested with cardosin A were separated by capillary zone electrophoresis under different experimental conditions in an uncoated fused silica capillary. The best separation was at pH 3.01, 30 kV and 30 °C.     

Capillary electrophoresis of caseino-peptides: influence of applied voltage and column temperature

The peptides formed upon action of purified cardoon rennet on the Ala₁₈₉-Phe₁₉₀-Leu₁₉₁-Leu₁₉₂-Tyr₁93 -casein fragment were separated by capillary electrophoresis in an uncoated fused silica capillary. There was a linear correlation between electrophoretic mobility and Z/M^2/3 (Z, net charge; M, molecular mass) under all experimental conditions tested; under the optimal condicitions, 25 kV and 40 °C, the correlation coefficient was 0.994. The reported method is fast (migration times less than 7 min) and may be used to study the action of aspartic proteinases on the C-terminal domain of -casein and thus to help elucidate their effect on cheese quality.