Morphologic and Pharmacological Investigations in the Epicatechin Gastroprotective Effect

Previous studies of the gastroprotective activity of plants have highlighted the importance of the polyphenolic compound epicatechin (EC) in the treatment of gastric ulcers. This paper aimed to evaluate and characterize the gastroprotective mechanism of action of EC using male rats. The gastroprotective action of EC was analyzed in gastric ulcers induced by ethanol or indomethacin. The involvement of sulfhydryl (SH) groups, K+ATP channels, α2 adrenoceptors, gastric antisecretory activity, and the amount of mucus in the development of gastric ulcers were investigated. The lowest effective dose of EC providing gastroprotective effects was 50 mg/kg in the ethanol-induced gastric ulcers and 25 mg/kg in the indomethacin-induced gastric ulcers. The gastroprotection seen upon treatment with EC was significantly decreased in rats pretreated with a SH compound reagent or an α2-receptor antagonist, but not with a K+ATP channel blocker. Furthermore, oral treatment with EC increased mucus production and decreased H+ secretion. Immunohistochemistry demonstrated the involvement of superoxide dismutase (SOD), nitric oxide (NO), and heat shock protein-70 (HSP-70) in the gastroprotection. These results demonstrate that EC provides gastroprotection through reinforcement of the mucus barrier and neutralization of gastric juice and this protection occurs through the involvement of SH compounds, α2-adrenoceptors, NO, SOD, and HSP-70

A Reduced Order Approach for the Embedded Shifted Boundary FEM and a Heat Exchange System on Parametrized Geometries

A model order reduction technique is combined with an embedded boundary finite element method with a POD-Galerkin strategy. The proposed methodology is applied to parametrized heat transfer problems and we rely on a sufficiently refined shape-regular background mesh to account for parametrized geometries. In particular, the employed embedded boundary element method is the Shifted Boundary Method (SBM), recently proposed in Main and Scovazzi, J Comput Phys [17]. This approach is based on the idea of shifting the location of true boundary conditions to a surrogate boundary, with the goal of avoiding cut cells near the boundary of the computational domain. This combination of methodologies has multiple advantages. In the first place, since the Shifted Boundary Method always relies on the same background mesh, there is no need to update the discretized parametric domain. Secondly, we avoid the treatment of cut cell elements, which usually need particular attention. Thirdly, since the whole background mesh is considered in the reduced basis construction, the SBM allows for a smooth transition of the reduced modes across the immersed domain boundary. The performances of the method are verified in two dimensional heat transfer numerical examples

Reduced-order semi-implicit schemes for fluid-structure interaction problems

POD-Galerkin reduced-order models (ROMs) for fluid-structure interaction problems (incompressible fluid and thin structure) are proposed in this paper. Both the high-fidelity and reduced-order methods are based on a Chorin-Temam operator-splitting approach. Two different reduced-order methods are proposed, which differ on velocity continuity condition, imposed weakly or strongly, respectively. The resulting ROMs are tested and compared on a representative haemodynamics test case characterized by wave propagation, in order to assess the capabilities of the proposed strategies

Reduced basis isogeometric mortar approximations for eigenvalue problems in vibroacoustics

We simulate the vibration of a violin bridge in a multi-query context using reduced basis techniques. The mathematical model is based on an eigenvalue problem for the orthotropic linear elasticity equation. In addition to the nine material parameters, a geometrical thickness parameter is considered. This parameter enters as a 10th material parameter into the system by a mapping onto a parameter independent reference domain. The detailed simulation is carried out by isogeometric mortar methods. Weakly coupled patch-wise tensorial structured isogeometric elements are of special interest for complex geometries with piecewise smooth but curvilinear boundaries. To obtain locality in the detailed system, we use the saddle point approach and do not apply static condensation techniques. However within the reduced basis context, it is natural to eliminate the Lagrange multiplier and formulate a reduced eigenvalue problem for a symmetric positive definite matrix. The selection of the snapshots is controlled by a multi-query greedy strategy taking into account an error indicator allowing for multiple eigenvalues

The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-Inflammatory activities

The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg) or menthol (50 mg/kg) and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70) and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO) was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD) were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-alpha and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms91FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2010/08536-

HelMod in the works: from direct observations to the local interstellar spectrum of cosmic-ray electrons

The local interstellar spectrum (LIS) of cosmic-ray (CR) electrons for the energy range 1 MeV to 1 TeV is derived using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HelMod, are combined to provide a single framework that is run to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. An iterative maximum-likelihood method is developed that uses GALPROP-predicted LIS as input to HelMod, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The optimized HelMod parameters are then used to adjust GALPROP parameters to predict a refined LIS with the procedure repeated subject to a convergence criterion. The parameter optimization uses an extensive data set of proton spectra from 1997-2015. The proposed CR electron LIS accommodates both the low-energy interstellar spectra measured by Voyager 1 as well as the high-energy observations by PAMELA and AMS-02 that are made deep in the heliosphere; it also accounts for Ulysses counting rate features measured out of the ecliptic plane. The interstellar and heliospheric propagation parameters derived in this study agree well with our earlier results for CR protons, helium nuclei, and anti-protons propagation and LIS obtained in the same framework.Comment: 11 pages, 14 figures, 4 tables; ApJ, in pres

Deciphering the local Interstellar spectra of primary cosmic ray species with HelMod

Local interstellar spectra (LIS) of primary cosmic ray (CR) nuclei, such as helium, oxygen, and mostly primary carbon are derived for the rigidity range from 10 MV to ~200 TV using the most recent experimental results combined with the state-of-the-art models for CR propagation in the Galaxy and in the heliosphere. Two propagation packages, GALPROP and HelMod, are combined into a single framework that is used to reproduce direct measurements of CR species at different modulation levels, and at both polarities of the solar magnetic field. The developed iterative maximum-likelihood method uses GALPROP-predicted LIS as input to HelMod, which provides the modulated spectra for specific time periods of the selected experiments for model-data comparison. The interstellar and heliospheric propagation parameters derived in this study are consistent with our prior analyses using the same methodology for propagation of CR protons, helium, antiprotons, and electrons. The resulting LIS accommodate a variety of measurements made in the local interstellar space (Voyager 1) and deep inside the heliosphere at low (ACE/CRIS, HEAO-3) and high energies (PAMELA, AMS-02).Comment: 13 pages, 13 figures, 6 tables, ApJ in press. arXiv admin note: text overlap with arXiv:1704.0633