Comparison of therapeutic triiodothyronine versus metoprolol in the treatment of myocardial infarction in rats

© 2018 Mary Ann Liebert, Inc. Background: Beta blockers are standard therapy for myocardial infarction (MI). Preclinical studies have shown efficacy and safety of thyroid hormone (TH) treatment of cardiovascular disorders. Since THs interact with the sympathoadrenergic system, this study aimed to compare triiodothyronine (T3) and metoprolol (Met) in the treatment of rats with MI on pathophysiology and TH-adrenergic signaling. Methods: Female Sprague-Dawley rats aged 12 weeks underwent left anterior descending coronary artery ligation (MI) or sham surgeries. T3 (5 μg/kg/day) or Met (100 mg/kg/day) was given in drinking water immediately after surgery for eight weeks. At the terminal of the experiments, the rats were subjected to morphological, functional, and molecular examination. Results: T3 and Met significantly enhanced left ventricular contractility (left ventricular fractional shortening 21.37 ± 2.58% and 21.14 ± 3.71%, respectively) compared to untreated MI (17.88 ± 1.23%), and decreased the incidence of inducible atrial tachyarrhythmia by 87.5% and 62.5%, respectively. Although both treatments showed efficacy, T3 but not Met showed statistically significant improvements compared to MI in arrhythmia duration, left atrial diameter (T3 vs. MI 4.33 ± 0.63 vs. 5.65 ± 1.32 mm; p \u3c 0.05), fibrosis (6.1 ± 0.6%, 6.6 ± 0.6% vs. 8.2 ± 0.7%, T3, Met vs. MI, respectively), and aortic vasorelaxation responsiveness to acetylcholine (pD2 6.97 ± 0.22, 6.83 ± 0.21 vs. 6.66 ± 0.22, T3, Met vs. MI, respectively). Quantitative polymerase chain reaction showed that T3 and Met attenuated expression of genes associated with inflammation and oxidative stress and restored expression of ion channels and contractile proteins. Conclusion: These results support comparable efficacy of T3 and Met treatments, suggesting that T3 may provide a therapeutic alternative to standard β-receptor blockade, especially for patients intolerant to treatment with β-blockers after MI

Quantitative assessment of non-conservative radiation forces in an optical trap

The forces acting on an optically trapped particle are usually assumed to be conservative. However, the presence of a non-conservative component has recently been demonstrated. Here we propose a technique that permits one to quantify the contribution of such non-conservative component. This is an extension of a standard optical tweezers calibration technique and, therefore, can easily become a standard test to verify the conservative optical force assumption. Using this technique we have analyzed different-sized optically trapped particles under different trapping conditions. We conclude that the non-conservative effects are effectively negligible and do not affect the standard calibration procedure, unless for extremely low-power trapping, far away from the trapping regimes usually used in experiments.Comment: 8 pages, 4 figures; Europhys. Lett. (EPL) (2009), accepte

Blended wing body with boundary layer ingestion conceptual design in a multidisciplinary design analysis optimization environment

This paper introduces the GENUS multidisciplinary concept level aircraft design and analysis environment developed by Cranfield University in recent years and it has been applied to the conceptual design of blended wing body (BWB) aircraft. Analytical disciplines include a variety of low-to-medium fidelity, physics-based and empirical methods, and aerodynamic analysis of high-order panel method. Boundary layer ingestion (BLI), as a special module, has been incorporated into the aerodynamic and propulsion analysis. The results of the Cranfield BW-11 are presented. In the highly-constrained design space, a type of highly fuel- efficient BWB concept can be studied, and the advantages of the BLI concept can also be explored based on this framework

Docking And Molecular Dynamic Of Microalgae Compounds As Potential Inhibitors Of Beta-Lactamase

Bacterial resistance is responsible for a wide variety of health problems, both in children and adults. The persistence of symptoms and infections are mainly treated with beta-lactam antibiotics. The increasing resistance to those antibiotics by bacterial pathogens generated the emergence of extended-spectrum beta-lactamases (ESBLs), an actual public health problem. This is due to rapid mutations of bacteria when exposed to antibiotics. In this case, beta-lactamases are enzymes used by bacteria to hydrolyze the beta-lactam rings present in the antibiotics. Therefore, it was necessary to explore novel molecules as potential beta-lactamases inhibitors to find antibacterial compounds against infection caused by ESBLs. A computational methodology based on molecular docking and molecular dynamic simulations was used to find new microalgae metabolites inhibitors of beta-lactamase. Six 3D beta-lactamase proteins were selected, and the molecular docking revealed that the metabolites belonging to the same structural families, such as phenylacridine (4-Ph), quercetin (Qn), and cryptophycin (Cryp), exhibit a better binding score and binding energy than commercial clinical medicine beta-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam. These results indicate that 4-Ph, Qn, and Cryp molecules, homologous from microalgae metabolites, could be used, likely as novel beta-lactamase inhibitors or as structural templates for new in-silico pharmaceutical designs, with the possibility of combatting beta-lactam resistanc

Isolation and characterisation of bacteriophages with activity against invasive non-typhoidal Salmonella causing blood-stream infection in Malawi

In recent years, novel lineages of invasive non-typhoidal Salmonella (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection in sub-Saharan Africa. Here, we isolated and characterised 32 phages capable of infecting S. Typhimurium and S. Enteritidis, from water sources in Malawi and the UK. The phages were classified in three major phylogenetic clusters that were geographically distributed. In terms of host range, Cluster 1 phages were able to infect all bacterial hosts tested, whereas Clusters 2 and 3 had a more restricted profile. Cluster 3 contained two sub-clusters, and 3.b contained the most novel isolates. This study represents the first exploration of the potential for phages to target the lineages of Salmonella that are responsible for bloodstream infections in sub-Saharan Africa

ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics

\ua9 2023, The Author(s). Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Typical CADASIL is characterised by subcortical ischemic strokes due to severe arteriopathy and fibrotic thickening of small arteries. Arteriolar vascular smooth muscle cells (VSMCs) are the key target in CADASIL, but the potential mechanisms involved in their degeneration are still unclear. Focusing on cerebral microvessels in the frontal and anterior temporal lobes and the basal ganglia, we used advanced proteomic and immunohistochemical methods to explore the extent of inflammatory and immune responses in CADASIL subjects compared to similar age normal and other disease controls. There was variable loss of VSMC in medial layers of arteries in white matter as well as the cortex, that could not be distinguished whether NOTCH3 mutations were in the epidermal growth factor (EGFr) domains 1–6 or EGFr7-34. Proteomics of isolated cerebral microvessels showed alterations in several proteins, many associated with endoplasmic reticulum (ER) stress including heat shock proteins. Cerebral vessels with sparsely populated VSMCs also attracted robust accrual of perivascular microglia/macrophages in order CD45+ > CD163+ > CD68+cells, with > 60% of vessel walls exhibiting intercellular adhesion molecule-1 (ICAM-1) immunoreactivity. Functional VSMC cultures bearing the NOTCH3 Arg133Cys mutation showed increased gene expression of the pro-inflammatory cytokine interleukin 6 and ICAM-1 by 16- and 50-fold, respectively. We further found evidence for activation of the alternative pathway of complement. Immunolocalisation of complement Factor B, C3d and C5-9 terminal complex but not C1q was apparent in ~ 70% of cerebral vessels. Increased complement expression was corroborated in > 70% of cultured VSMCs bearing the Arg133Cys mutation independent of N3ECD immunoreactivity. Our observations suggest that ER stress and other cellular features associated with arteriolar VSMC damage instigate robust localized inflammatory and immune responses in CADASIL. Our study has important implications for immunomodulation approaches to counter the characteristic arteriopathy of CADASIL

Aperture, A Large Telescope Using Magnetostriction For Post Deployment Corrections: Final Technical Report of NASA Innovative Advanced Concepts (NIAC) Phase I

In summary, astronomical as well as Earth observing applications of the future are counting on larger aperture telescopes than are currently available. Several groups have been working on the topic of enabling large (about 16-m diameter) UV-Vis telescopes for many years. The unique feature of our concept is that magnetic films are used rather than electrostatic films or piezo-electrostatic pads. Our magnetic film concept allows for contiguous correction along the surface, does not require a hard wire connection, and does not require continuous external application of the field. There are many unknowns related to the initial accuracy of the deployed figure prior to the magnetic write head corrections. The length scale over which the corrections need to be applied is also of concern. For, although approximately mm length scale corrections can be made with the MSM plus write head technology, the number of 1 mm patches in a 16 m diameter mirror is too large to contemplate applying individual corrections to each individual patch. However, deployment strategies and the materials available continue to evolve, in particular shape memory composites (SMCs) [34] or alloys (SMAs) [41], such that at this time we see no show-stoppers for this concept. Furthermore, the ability to tune deformations down to much (factors of 10-100) smaller (m) scale opens the futuristic possibility of improving the figure well beyond Strehl values of 90%

Approach to ergodicity in quantum wave functions

According to theorems of Shnirelman and followers, in the semiclassical limit the quantum wavefunctions of classically ergodic systems tend to the microcanonical density on the energy shell. We here develop a semiclassical theory that relates the rate of approach to the decay of certain classical fluctuations. For uniformly hyperbolic systems we find that the variance of the quantum matrix elements is proportional to the variance of the integral of the associated classical operator over trajectory segments of length $T_H$, and inversely proportional to $T_H^2$, where $T_H=h\bar\rho$ is the Heisenberg time, $\bar\rho$ being the mean density of states. Since for these systems the classical variance increases linearly with $T_H$, the variance of the matrix elements decays like $1/T_H$. For non-hyperbolic systems, like Hamiltonians with a mixed phase space and the stadium billiard, our results predict a slower decay due to sticking in marginally unstable regions. Numerical computations supporting these conclusions are presented for the bakers map and the hydrogen atom in a magnetic field.Comment: 11 pages postscript and 4 figures in two files, tar-compressed and uuencoded using uufiles, to appear in Phys Rev E. For related papers, see http://www.icbm.uni-oldenburg.de/icbm/kosy/ag.htm