Background Congestive heart failure (CHF) is a leading cause of morbidity and mortality, and oxidative stress has been implicated in the pathogenesis of cachexia (muscle wasting) and the hallmark symptom, exercise intolerance. We have previously shown that a nitric oxide (NO)-dependent antioxidant defense renders oxidative skeletal muscle resistant to catabolic wasting. Here, we aimed to identify and determine the functional role of the NO-inducible antioxidant enzyme(s) in protection against cardiac cachexia and exercise intolerance in CHF. Methods and Results We demonstrated that systemic administration of endogenous nitric oxide donor S-Nitrosoglutathione in mice blocked the reduction of extracellular superoxide dismutase (EcSOD) protein expression, the induction of MAFbx/Atrogin-1 mRNA expression and muscle atrophy induced by glucocorticoid. We further showed that endogenous EcSOD, expressed primarily by type IId/x and IIa myofibers and enriched at endothelial cells, is induced by exercise training. Muscle-specific overexpression of EcSOD by somatic gene transfer or transgenesis [muscle creatine kinase (MCK)-EcSOD] in mice significantly attenuated muscle atrophy. Importantly, when crossbred into a mouse genetic model of CHF [α-myosin heavy chain (MHC)-calsequestrin] MCK-EcSOD transgenic mice had significant attenuation of cachexia with preserved whole body muscle strength and endurance capacity in the absence of reduced heart failure. Enhanced EcSOD expression significantly ameliorated CHF-induced oxidative stress, MAFbx/Atrogin-1 mRNA expression, loss of mitochondria and vascular rarefaction in skeletal muscle. Conclusions EcSOD plays an important antioxidant defense function in skeletal muscle against cardiac cachexia and exercise intolerance in CHF.
Multiple organ dysfunction syndrome (MODS) is a detrimental clinical complication in critically ill patients with high mortality. Emerging evidence suggests that oxidative stress and endothelial activation (induced expression of adhesion molecules) of vital organ vasculatures are key, early steps in the pathogenesis. We aimed to ascertain the role and mechanism(s) of enhanced extracellular superoxide dismutase (EcSOD) expression in skeletal muscle in protection against MODS induced by endotoxemia. We showed that EcSOD overexpressed in skeletal muscle-specific transgenic mice (TG) redistributes to other peripheral organs through the circulation and enriches at the endothelium of the vasculatures. TG mice are resistant to endotoxemia (induced by lipopolysaccharide [LPS] injection) in developing MODS with significantly reduced mortality and organ damages compared with the wild type littermates (WT). Heterogenic parabiosis between TG and WT mice conferred a significant protection to WT mice, whereas mice with R213G knock-in mutation, a human single nucleotide polymorphism leading to reduced binding EcSOD in peripheral organs, exacerbated the organ damages. Mechanistically, EcSOD inhibits vascular cell adhesion molecule 1 expression and inflammatory leukocyte adhesion to the vascular wall of vital organs, blocking an early step of the pathology in organ damage under endotoxemia. Therefore, enhanced expression of EcSOD in skeletal muscle profoundly protects against MODS by inhibiting endothelial activation and inflammatory cell adhesion, which could be a promising therapy for MODS.
Social media use has been increasing among physicians and healthcare professionals over the last decade. With over 330 million active users reported in 2019, Twitter is one of the most popular social media platforms worldwide and is used by academicians and clinicians to share information, debate ideas, network and promote medical education. 1 An increasing number of medical journals and societal organizations now have prominent Twitter presence, harnessing the platform to disseminate scientific content and promote dialogue. For individuals, Twitter provides an open forum to meet like-minded colleagues across the world, engage in conversation and forge a virtual scientific community. This inevitably opens doors for online collaborative research. A successful demonstration of this innovative approach has been the research projects executed by groups such as @MondayNightIBD, EndoTrain survey group and GOAL (Global Online Alliance for Liver group). In this article, we aim to share experiences on transforming ideas generated in the virtual world of Twitter into peer-reviewed publications (Figure 1). THE IDEA The first step in any initiative or manuscript is to have a relevant concept or question. Twitter is ideal for generating and advancing ideas. Most ideas arise from discussions between healthcare professionals, although the inspiration may also come directly from patients and the online-support groups. 2 Regardless of whether an idea has originated offline or on social media, by connecting with people with similar interests who can provide critique and a different viewpoint, simple concepts can quickly mature. In addition to dialogue, the poll feature on Twitter can be used to rapidly survey opinions and practices. 3 Not all discussions will muster sufficient interest or controversy, but if they do, it is important to recognize their potential for scholarly work. Scholarly work should be novel and be able to fulfil a knowledge gap or an area of clinical need. The format of publication can vary depending on the concept or discussion. These may include a letter to the editor, 4 opinion pieces, 5 educational innovation articles, 6,7 narrative reviews, 8 systematic reviews and original research (ranging from surveys to multicentre studies). 3,9 INVITING COLLABORATORS Once you have an idea that gathers enough interest or generates a solid concept, consider reaching out to potential collaborators. Social media provides the unique opportunity to network with different clinicians at all stages of their career, in different types of practice (private, academic, industry or basic science research), from any part of the world. The access to a national and international community, beyond traditional boundaries, creates limitless opportunities to find mentors, sponsors and like-minded collaborators. The collaborators you choose could be the same group of people who helped you develop and enrich the idea or could be someone whose area of expertise and work is likely to complement your vision. Similar to any project, you are mo...
Primary cardiac osteosarcoma is a rare and aggressive neoplasm that can be difficult to diagnose. We report a case of a previously healthy 49-year-old woman who presented with dyspnea, atrial flutter, and heart failure. A mass was visualized in her left atrium by echocardiography and cardiac computed tomography, and the diagnosis of cardiac myxoma was raised. The patient subsequently underwent surgical resection of the mass and atrial reconstruction. Surprisingly, histological and immunohistological analyses revealed the mass to be an osteosarcoma. The patient received chemotherapy and radiotherapy. Eight months later, she has shown evidence of local recurrence. We briefly discuss primary osteosarcomas in the cardiac cavity and their management.
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