Recent advances have improved our understanding of the renin‐angiotensin system (RAS). These have included the recognition that angiotensin (Ang)‐(1‐7) is a biologically active product of the RAS ...cascade. The identification of the ACE homologue ACE2, which forms Ang‐(1‐7) from Ang II, and the GPCR Mas as an Ang‐(1‐7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang‐(1‐7). Most available evidence supports a counter‐regulatory role for Ang‐(1‐7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang‐(1‐7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang‐(1‐7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang‐(1‐7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang‐(1‐7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.
In this paper we present a new application for Carrera’s unified Formulation (CUF) to analyse functionally graded plates.
In this paper the authors present explicit governing equations of a ...sinusoidal shear deformation theory for functionally graded plates. It addresses the bending and free vibration analysis and accounts for through-the-thickness deformations.
The equations of motion are interpolated by collocation with radial basis functions. Numerical examples demonstrate the efficiency of the present approach.
In this paper we present a layerwise finite element model for the analysis of sandwich laminated plates with a viscoelastic core and laminated anisotropic face layers. The stiffness and mass matrices ...of the element are obtained by Carrera’s Unified Formulation (CUF). The dynamic problem is solved in the frequency domain with viscoelastic frequency-dependent material properties for the core. The dynamic behaviour of the model is compared with solutions found in the literature, including experimental data.
This paper presents a free-vibration analysis of simply supported, cross-ply beams via several higher-order as well as classical theories. The three-dimensional displacement field is approximated ...along the beam cross-section in a compact form as a generic N-order polynomial expansion. Several higher-order displacements-based theories accounting for non-classical effects can be, therefore, formulated straightforwardly. Classical beam models, such as Euler–Bernoulli’s and Timoshenko’s, are obtained as particular cases. The governing differential equations and the boundary conditions are derived by variationally imposing the equilibrium via the principle of virtual displacements. Thanks to the compact form of the displacement field approximation, governing equations are written in terms of a fundamental nucleo that does not depend upon the approximation order. A Navier-type, closed form solution is adopted in order to derive the governing algebraic equations. Besides the fundamental natural frequency, natural frequencies associated to higher modes (such as torsional, axial, shear and mixed ones) are investigated. A half waves number equal to one is considered. The effect of the length-to-thickness ratio, lamination, aspect ratio and material properties on: (1) the accuracy of the proposed theories and (2) the natural frequencies and modes is presented and discussed. For the latter case, the modes change in order of appearance (modes swapping) and in shape (modes mutation) is investigated. Results are assessed towards three-dimensional FEM solutions. Numerical results show that, upon the choice of the appropriate approximation order, very accurate results can be obtained for all the considered modes.
A study of static deformations and free vibrations of shear flexible isotropic and laminated composite plates with a first-order shear deformation theory is presented. The analysis is based on ...collocation with a Deslaurier Dubuc interpolating basis to produce highly accurate results. Numerical results for isotropic and symmetric laminated composite plates are presented and discussed for various thickness-to-length ratios. The high order collocation method presented in this paper proved to be very accurate for this type of problems and the numerical efficiency is as good as other numerical schemes for first-order shear deformation theories, such as finite element solutions.
Treatable Traits in COPD - A Proposed Approach Cardoso, João; Ferreira, António Jorge; Guimarães, Miguel ...
International journal of chronic obstructive pulmonary disease,
01/2021, Letnik:
16
Journal Article
Recenzirano
Odprti dostop
The well-recognized individual heterogeneity within COPD patients has led to a growing interest in greater personalization in the approach of these patients. Thus, the treatable traits strategy has ...been proposed as a further step towards precision medicine in the management of chronic airway disease, both in stable phase and acute exacerbations. The aim of this paper is to perform a critical review on the treatable traits strategy and propose a guide to approach COPD patients in the light of this new concept. An innovative stepwise approach is proposed - a multidisciplinary model based on two distinct phases, with the potential to be implemented in both primary care and hospital settings. The first phase is the initial and focused assessment of a selected subset of treatable traits, which should be addressed in all COPD patients in both settings (primary care and hospital). As some patients may present with advanced disease at diagnosis or may progress despite this initial treatment requiring a more specialized assessment, they should progress to a second phase, in which a broader approach is recommended. Beyond stable COPD, we explore how the treatable traits strategy may be applied to reduce the risk of future exacerbations and improve the management of COPD exacerbations. Since many treatable traits have already been related to exacerbation risk, the strategy proposed here represents an opportunity to be proactive. Although it still lacks prospective validation, we believe this is the way forward for the future of the COPD approach.
Cardiovascular actions of angiotensin-(1-7) Ferreira, A J; Santos, R A S
Brazilian journal of medical and biological research,
04/2005, Letnik:
38, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Angiotensin-(1-7) (Ang-(1-7)) is now considered to be a biologically active member of the renin-angiotensin system. The functions of Ang-(1-7) are often opposite to those attributed to the main ...effector component of the renin-angiotensin system, Ang II. Chronic administration of angiotensin-converting enzyme inhibitors (ACEI) increases 10- to 25-fold the plasma levels of this peptide, suggesting that part of the beneficial effects of ACEI could be mediated by Ang-(1-7). Ang-(1-7) can be formed from Ang II or directly from Ang I. Other enzymatic pathways for Ang-(1-7) generation have been recently described involving the novel ACE homologue ACE2. This enzyme can form Ang-(1-7) from Ang II or less efficiently by the hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation. The biological relevance of Ang-(1-7) has been recently reinforced by the identification of its receptor, the G-protein-coupled receptor Mas. Heart and blood vessels are important targets for the formation and actions of Ang-(1-7). In this review we will discuss recent findings concerning the biological role of Ang-(1-7) in the heart and blood vessels, taking into account aspects related to its formation and effects on these tissues. In addition, we will discuss the potential of Ang-(1-7) and its receptor as a target for the development of new cardiovascular drugs.
The third-order shear deformation theory of Reddy and collocation with radial basis functions is used to predict the buckling loads of elastic plates. The theory accounts for parabolic distribution ...of the transverse strains through the thickness of the plate. It is shown that the collocation method with radial basis functions produces highly accurate critical buckling loads and modes.
In this study we investigated the effects of the genetic deletion of the angiotensin (Ang)-(1-7) receptor Mas on heart function. Localization of Mas in the mouse heart was evaluated by binding of ...rhodamine-labeled Ang-(1-7). Cardiac function was examined using isolated heart preparations. Echocardiography was used to confirm the results obtained with isolated heart studies. To elucidate the possible mechanisms involved in the cardiac phenotype observed in Mas(-/-) mice, whole-cell calcium currents in cardiomyocytes and the expression of collagen types I, III, and VI and fibronectin were analyzed. Ang-(1-7) binding showed that Mas is localized in cardiomyocytes of the mouse heart. Isolated heart techniques revealed that Mas-deficient mice present a lower systolic tension (average: 1.4+/-0.09 versus 2.1+/-0.03 g in Mas(+/+) mice), +/-dT/dt, and heart rate. A significantly higher coronary vessel resistance was also observed in Mas-deficient mice. Echocardiography revealed that hearts of Mas-deficient mice showed a significantly decreased fractional shortening, posterior wall thickness in systole and left ventricle end-diastolic dimension, and a higher left ventricle end-systolic dimension. A markedly lower global ventricular function, as defined by a higher myocardial performance index, was observed. A higher delayed time to the peak of calcium current was also observed. The changes in cardiac function could be partially explained by a marked change in collagen expression to a profibrotic profile in Mas-deficient mice. These results indicate that Ang-(1-7)-Mas axis plays a key role in the maintenance of the structure and function of the heart.
In this study we evaluate the effects of angiotensin-(1-7) on reperfusion arrhythmias in isolated rat hearts. Rat hearts were perfused according to Langendorff technique and maintained in heated ...(37+/-1 degrees C) and continuously gassed (95% O(2)/5% CO(2)) Krebs-Ringer solution at constant pressure (65 mm Hg). The electrical activity was recorded with an ECG (bipolar). Local ischemia was induced by coronary ligation for 15 minutes. After ischemia, hearts were reperfused for 30 minutes. Cardiac arrhythmias were defined as the presence of ventricular tachycardia and/or ventricular fibrillation after the ligation of the coronary artery was released. Angiotensin II (0.20 nmol/L, n=10) produced a significant enhancement of reperfusion arrhythmias. On the other hand, Ang-(1-7) presented in the perfusion solution (0.22 nmol/L, n=11) reduced incidence and duration of arrhythmias. The antiarrhythmogenic effects of Ang-(1-7) was blocked by the selective Ang-(1-7) antagonist A-779 (2 nmol/L, n=9) and by indomethacin pretreatment (5 mg/kg IP, n=8) but not by the bradykinin B(2) antagonist HOE 140 (100 nmol/L, n=10) or by L-NAME pretreatment (30 mg/kg IP, n=8). These results suggest that the antiarrhythmogenic effect of low concentrations of Ang-(1-7) is mediated by a specific receptor and that release of endogenous prostaglandins.by Ang-(1-7) contributes to the alleviation of reversible and/or irreversible ischemia-reperfusion injury.
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