Abstract P423: Nox2 Mediates Increased Oxidative Stress And Ros Production Leading To Atrial Ion Channel And Structural Remodeling In Obesity-induced Af.

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Arvind Sridhar ◽  
Liang Hong ◽  
Olivia T Ly ◽  
Hanna Chen ◽  
Srikanth Perike ◽  
...  

Background: Inducible atrial fibrillation (AF) in diet-induced obese (DIO) mice is mediated in part by a combined effect of ion channel remodeling and atrial fibrosis. NADPH oxidase 2 (NOX2), a major source of reactive oxygen species (ROS) production in human atria, is increased in DIO mice. Although a mitochondrial antioxidant (MitoTEMPO) reduced AF burden, and reversed ion channel and structural remodeling, the role of NOX2 in increased ROS production and atrial remodeling in obesity-induced AF remains unclear. Objective: To test the hypothesis that increased NOX2 modulates atrial remodeling in obesity-induced AF, we treated DIO mice with apocynin, NOX2 inhibitor, and fed a 60% high fat diet (HFD) to Nox2 -KO mice. Methods: Weight, BP, plasma glucose, trans-esophageal rapid (TE) pacing and F 2 -isoprostanes were measured in DIO mice and compared to controls. Echocardiography, electrophysiology (EP), immunohistochemistry, Western blotting, cellular patch clamping and optical mapping studies were performed. Results: The average weight of DIO mice treated with apocynin (DIO-A) and vehicle control mice was 38.4 ± 3.8 g versus 44.0 ± 7.5 g versus 31.7 ± 1.19 g respectively (P≤0.0001). Both groups of DIO mice displayed progressive increase in weight over 10 weeks of HFD + drug treatment compared to controls (P≤0.0001). After TE pacing, DIO mice treated with apocynin showed significantly reduced pacing-induced AF burden when compared to DIO mice treated with vehicle. DIO mice treated with apocynin displayed 20.2 ± 26.1 sec versus 162.3 ± 133.7 sec and 18.3 ± 18.1 sec in DIO mice treated with vehicle and control mice respectively (P≤0.0001). Western blotting experiments showed that potassium channels, Kv7.1 and Kv1.5 protein expression is restored in Nox2 -KO HFD mice compared to DIO mice thus indicating restoration of ion channel remodeling upon Nox2 inhibition. Conclusions: We showed that genetic and pharmacological inhibition of NOX2 abrogates ion channel remodeling and reverses obesity-induced AF burden. Our findings may have important implications for the management of obesity-mediated AF in patients.

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 168
Author(s):  
Susanna Fiorelli ◽  
Nicola Cosentino ◽  
Benedetta Porro ◽  
Franco Fabbiocchi ◽  
Giampaolo Niccoli ◽  
...  

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.


Cardiology ◽  
2015 ◽  
Vol 131 (1) ◽  
pp. 58-67 ◽  
Author(s):  
Pradeep Poudel ◽  
Yanmin Xu ◽  
Zhanqian Cui ◽  
Deepak Sharma ◽  
Bing Tian ◽  
...  

Atrial fibrillation (AF) is a highly prevalent condition associated with pronounced cardiovascular-related morbidity, mortality and socioeconomic burden. It accounts for more hospitalization days than does any other arrhythmia. This article reviews the basic electrophysiology of AF, electrical and structural remodeling in AF and recent advances in understanding the molecular mechanisms of AF in relation to specific microRNAs. This paper also reviews the potential role of microRNAs as novel therapeutic targets as well as biomarkers in the management of AF. AF shows characteristics typical of altered electrophysiology that promote ectopic activity and facilitate reentry, thereby contributing to the progression from short paroxysmal AF to a persistent, permanent form via atrial remodeling, even in the absence of progressive underlying heart disease. MicroRNAs have been suggested to influence the development of AF by regulating gene expression at the post-transcriptional level. Increasing evidence has identified various microRNA modifications and their impacts on AF initiation and maintenance through electrical and structural remodeling. The discovery of specific microRNAs as novel therapeutic targets and some experimental evidence implicating microRNAs as potential molecular diagnostic markers have had a significant impact on the diagnosis and management of AF and demand further research.


1994 ◽  
Vol 34 (301) ◽  
pp. 387-394
Author(s):  
Cleopas Sila Msuya

As late as the 1970s, conventional wisdom in epidemiology held that communicable diseases were on their way out as the predominant contributor to the world's morbidity profile, and were being replaced by noncommunicable diseases (NCDs) comprising degenerative diseases such as diabetes, circulatory disorders and cancers, and by accidents. Except for the developing countries, most of the rest of the world was already experiencing this so-called “epidemiological transition” from the terrible epoch of famines and pestilence that lasted from the dawn of mankind to the middle of this millenium, followed by the age of epidemics that culminated with the influenza pandemics of the earlier part of this century, to the prevailing situation since the 70s where diseases largely due to changed lifestyles — lack of exercise, high-fat diet, smoking and other substance abuses — predominate.


2020 ◽  
Author(s):  
Mario D'Incau ◽  
Cristian Salogni ◽  
Stefano Giovannini ◽  
Jessica Ruggeri ◽  
Federico Scali ◽  
...  

Abstract Background The serovar Typhimurium (4,[5],12:i:1,2), is the most frequently isolated serovar in case of illness in pigs in Europe and its monophasic variant (4,[5],12:i:-) has been increasingly responsible for Salmonella outbreaks in humans. A total of 29,549 samples were collected, during the years 2002–2017, from 1,359 pig farms located in Northern Italy. Samples were collected from different material sources including fecal samples, gut content and different organs. Results Salmonella was isolated in 16.94% of samples and, among the isolates, 733 were typed as Salmonella Typhimurium (ST) or its monophasic variant (MST). Over time, there was a progressive increase of isolation of MST which outnumbered ST. Most of the strains were isolated in animals during the weaning stage and the growing – fattening period whereas the clinical cases were mainly present in young pigs after weaning. Conclusion This study confirms the role of pig as a source of ST and its monophasic variant MST. In the last few years, ST has been progressively replaced by MST suggesting that MST has a competitive advantage over ST, probably due to its reduced virulence which renders the infection stealthier to recognize and control.


Author(s):  
R. F. Zeigel ◽  
W. Munyon

In continuing studies on the role of viruses in biochemical transformation, Dr. Munyon has succeeded in isolating a highly infectious human herpes virus. Fluids of buccal pustular lesions from Sasha Munyon (10 mo. old) uiere introduced into monolayer sheets of human embryonic lung (HEL) cell cultures propagated in Eagles’ medium containing 5% calf serum. After 18 hours the cells exhibited a dramatic C.P.E. (intranuclear vacuoles, peripheral patching of chromatin, intracytoplasmic inclusions). Control HEL cells failed to reflect similar changes. Infected and control HEL cells were scraped from plastic flasks at 18 hrs. of incubation and centrifuged at 1200 × g for 15 min. Resultant cell packs uiere fixed in Dalton's chrome osmium, and post-fixed in aqueous uranyl acetate. Figure 1 illustrates typical hexagonal herpes-type nucleocapsids within the intranuclear virogenic regions. The nucleocapsids are approximately 100 nm in diameter. Nuclear membrane “translocation” (budding) uias observed.


Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
C Charkhonpunya ◽  
S Sireeratawong ◽  
S Komindr ◽  
N Lerdvuthisopon

TAPPI Journal ◽  
2012 ◽  
Vol 11 (7) ◽  
pp. 37-46 ◽  
Author(s):  
PEDRO E.G. LOUREIRO ◽  
SANDRINE DUARTE ◽  
DMITRY V. EVTUGUIN ◽  
M. GRAÇA V.S. CARVALHO

This study puts particular emphasis on the role of copper ions in the performance of hydrogen peroxide bleaching (P-stage). Owing to their variable levels across the bleaching line due to washing filtrates, bleaching reagents, and equipment corrosion, these ions can play a major role in hydrogen peroxide decomposition and be detrimental to polysaccharide integrity. In this study, a Cu-contaminated D0(EOP)D1 prebleached pulp was subjected to an acidic washing (A-stage) or chelation (Q-stage) before the alkaline P-stage. The objective was to understand the isolated and combined role of copper ions in peroxide bleaching performance. By applying an experimental design, it was possible to identify the main effects of the pretreatment variables on the extent of metals removal and performance of the P-stage. The acid treatment was unsuccessful in terms of complete copper removal, magnesium preservation, and control of hydrogen peroxide consumption in the following P-stage. Increasing reaction temperature and time of the acidic A-stage improved the brightness stability of the D0(EOP)D1AP bleached pulp. The optimum conditions for chelation pretreatment to maximize the brightness gains obtained in the subsequent P-stage with the lowest peroxide consumption were 0.4% diethylenetriaminepentaacetic acid (DTPA), 80ºC, and 4.5 pH.


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