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oxidative stress and the diaphragm

Johanna Herajärvi, Tuomas Anttila, Henna Sarja, Caius Mustonen, Henri Haapanen, Tuomas Mäkelä, Fredrik Yannopoulos, Tuomo Starck, Mika Kallio, Hannu Tuominen, Ulla Puistola, Peeter Karihtala, Kai Kiviluoma, Vesa Anttila, Tatu Juvonen
BACKGROUND: Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia. METHODS: The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery...
September 22, 2016: Annals of Thoracic Surgery
Agnieszka Piwkowska
Podocytes and their foot processes form an important cellular layer of the glomerular barrier involved in the regulation of glomerular permeability. Disturbing the function of podocytes plays a central role in the development of proteinuria in diabetic nephropathy. Retraction of the podocyte foot processes that form slit diaphragms is a common feature of proteinuria; although, the correlation between these events in not well understood. Notably, it is unclear whether podocyte foot processes are able to regulate slit diaphragm permeability and glomerular ultrafiltration...
September 23, 2016: Journal of Cellular Physiology
T Scott Bowen, Sophia Eisenkolb, Juliane Drobner, Tina Fischer, Sarah Werner, Axel Linke, Norman Mangner, Gerhard Schuler, Volker Adams
Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham (n = 11), DOCA-salt (n = 11), and DOCA-salt+HIIT (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined...
September 20, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Martin Seiler, T Scott Bowen, Natale Rolim, Maja-Theresa Dieterlen, Sarah Werner, Tomoya Hoshi, Tina Fischer, Norman Mangner, Axel Linke, Gerhard Schuler, Martin Halle, Ulrik Wisloff, Volker Adams
BACKGROUND: A greater understanding of the different underlying mechanisms between patients with heart failure with reduced (HFrEF) and with preserved (HFpEF) ejection fraction is urgently needed to better direct future treatment. However, although skeletal muscle impairments, potentially mediated by inflammatory cytokines, are common in both HFrEF and HFpEF, the underlying cellular and molecular alterations that exist between groups are yet to be systematically evaluated. The present study, therefore, used established animal models to compare whether alterations in skeletal muscle (limb and respiratory) were different between HFrEF and HFpEF, while further characterizing inflammatory cytokines...
September 2016: Circulation. Heart Failure
Hélène Talarmin, Frédéric Derbré, Luz Lefeuvre-Orfila, Karelle Léon, Mickaël Droguet, Jean-Pierre Pennec, Marie-Agnès Giroux-Metgès
OBJECTIVES: The aim of this study was to determine whether non-lethal sepsis induced by cecal ligation and puncture (CLP) modulates oxidative damage and enzymatic antioxidant defenses in diaphragm and hindlimb skeletal muscles (soleus and Extensor Digitorus Longus (EDL)). METHODS: Female Wistar rats were divided into four experimental groups: (1) control animals, (2) animals sacrificed 2 hours or (3) 7 days after CLP, and (4) sham-operated animals. At the end of the experimental procedure, EDL, soleus, and diaphragm muscles were harvested and 4-hydroxynonenal (HNE)-protein adducts and protein carbonyl contents were examined in relation to superoxide dismutase and catalase expression and activities...
September 6, 2016: Redox Report: Communications in Free Radical Research
Christian S Bruells, Thomas Breuer, Karen Maes, Ingmar Bergs, Christian Bleilevens, Gernot Marx, Joachim Weis, Ghislaine Gayan-Ramirez, Rolf Rossaint
BACKGROUND: Mechanical ventilation (MV) is associated with diaphragm weakness, a phenomenon termed ventilator-induced diaphragmatic dysfunction. Weaning should balance diaphragmatic loading as well as prevention of overload after MV. The weaning methods pressure support ventilation (PSV) and spontaneous breathing trials (SBT) lead to gradual or intermittent reloading of a weak diaphragm, respectively. This study investigated which weaning method allows more efficient restoration of diaphragm homeostasis...
2016: BMC Pulmonary Medicine
Irene Dot, Purificación Pérez-Teran, Manuel-Andrés Samper, Joan-Ramon Masclans
Muscle involvement is found in most critical patients admitted to the intensive care unit (ICU). Diaphragmatic muscle alteration, initially included in this category, has been differentiated in recent years, and a specific type of muscular dysfunction has been shown to occur in patients undergoing mechanical ventilation. We found this muscle dysfunction to appear in this subgroup of patients shortly after the start of mechanical ventilation, observing it to be mainly associated with certain control modes, and also with sepsis and/or multi-organ failure...
August 20, 2016: Archivos de Bronconeumología
Anna Salazar-Degracia, David Blanco, Mònica Vilà-Ubach, Gabriel de Biurrun, Carlos Ortiz de Solórzano, Luis M Montuenga, Esther Barreiro
BACKGROUND: Muscle wasting negatively impacts the progress of chronic diseases such as lung cancer (LC) and emphysema, which are in turn interrelated. OBJECTIVES: We hypothesized that muscle atrophy and body weight loss may develop in an experimental mouse model of lung carcinogenesis, that the profile of alterations in muscle fiber phenotype (fiber type composition and morphometry, muscle structural alterations, and nuclear apoptosis), and in muscle metabolism are similar in both respiratory and limb muscles of the tumor-bearing mice, and that the presence of underlying emphysema may influence those events...
2016: Journal of Translational Medicine
Anna Sigurta', Vanessa Zambelli, Giacomo Bellani
Ventilator-induced diaphragmatic dysfunction is a feared complication of mechanical ventilation that adversely affects the outcome of intensive care patients. Human and animal studies demonstrate atrophy and ultrastructural alteration of diaphragmatic muscular fibers attributable to increased oxidative stress, depression of the anabolic pathway regulated by Insulin-like growing factor 1 and increased proteolysis. The renin-angiotensin system, through its main peptide Angiotensin II, plays a major role in skeletal muscle diseases, mainly increasing oxidative stress and inducing insulin resistance, atrophy and fibrosis...
September 2016: Medical Hypotheses
Stefan Matecki, Haikel Dridi, Boris Jung, Nathalie Saint, Steven R Reiken, Valérie Scheuermann, Ségolène Mrozek, Gaetano Santulli, Alisa Umanskaya, Basil J Petrof, Samir Jaber, Andrew R Marks, Alain Lacampagne
Ventilator-induced diaphragmatic dysfunction (VIDD) refers to the diaphragm muscle weakness that occurs following prolonged controlled mechanical ventilation (MV). The presence of VIDD impedes recovery from respiratory failure. However, the pathophysiological mechanisms accounting for VIDD are still not fully understood. Here, we show in human subjects and a mouse model of VIDD that MV is associated with rapid remodeling of the sarcoplasmic reticulum (SR) Ca(2+) release channel/ryanodine receptor (RyR1) in the diaphragm...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yoshiko Nakae, Peter J Stoward
Images of cryostat unstained sections of two skeletal muscles, diaphragm and extensor digitorum longus (EDL), from wild-type normal and dystrophic mdx mice were captured with a fluorescence microscope, binarised and analysed by an automated procedure using ImageJ free software. The numbers, Feret diameters and areas of autofluorescent lipofuscin (LF)-like granules in the sections were determined from the binary images. The mean numbers of counted LF granules per mm(3) muscle tissue correlated highly (r ≥ 0...
November 2016: Histochemistry and Cell Biology
Stephanie Eid, Suzan Boutary, Kawthar Braysh, Ramzi Sabra, Charbel Massaad, Ahmed Hamdy, Awad Rashed, Sarah Moodad, Karen Block, Yves Gorin, Hanna E Abboud, Assaad Antoine Eid
AIM: Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mTORC2 mediates podocyte injury in diabetes. RESULTS: High glucose (HG) induces podocyte injury reflected by alteration in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway...
July 8, 2016: Antioxidants & Redox Signaling
Hila Roshanravan, Eun Young Kim, Stuart E Dryer
N-methyl-d-aspartate (NMDA) receptors are expressed throughout the kidney, and the abundance of these receptors and some of their endogenous agonists are increased in diabetes. Moreover, sustained activation of podocyte NMDA receptors induces Ca(2+) influx, oxidative stress, loss of slit diaphragm proteins, and apoptosis. We observed that NMDA receptor subunits and their transcripts are increased in podocytes and mesangial cells cultured in elevated glucose compared with controls. A similar increase in NMDA subunits, especially NR1, NR2A, and NR2C, was observed in glomeruli and tubules of Akita mice...
October 2016: Diabetes
Norman Mangner, T Scott Bowen, Sarah Werner, Tina Fischer, Yvonne Kullnick, Andreas Oberbach, Axel Linke, Leif Steil, Gerhard Schuler, Volker Adams
PURPOSE: Patient studies have demonstrated the efficacy of exercise training in attenuating respiratory muscle weakness in chronic heart failure (HF), yet direct assessment of muscle fiber contractile function together with data on the underlying intracellular mechanisms remain elusive. The present study, therefore, used a mouse model of HF to assess whether exercise training could prevent diaphragm contractile fiber dysfunction, by potentially mediating the complex interplay between intracellular oxidative stress and proteolysis...
June 20, 2016: Medicine and Science in Sports and Exercise
Li-Fu Li, Yuh-Lih Chang, Ning-Hung Chen, Chien-Ying Wang, Gwo-Jyh Chang, Meng-Chih Lin, Chih-Hao Chang, Chung-Chi Huang, Jen-Hua Chuang, Yi-Pin Yang, Shih-Hwa Chiou, Yung-Yang Liu
Mechanical ventilation (MV) with hyperoxia is required for providing life support to patients with acute lung injury (ALI). However, MV may cause diaphragm weakness through muscle injury and atrophy, an effect termed ventilator-induced diaphragm dysfunction (VIDD). Src protein tyrosine kinase and class O of forkhead box 1 (FoxO1) mediate acute inflammatory responses and muscle protein degradation induced by oxidative stress. Induced pluripotent stem cells (iPSCs) have been reported to improve hyperoxia-augmented ALI; however, the mechanisms regulating the interactions among VIDD, hyperoxia, and iPSCs are unclear...
July 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
David Berger, Stefan Bloechlinger, Stephan von Haehling, Wolfram Doehner, Jukka Takala, Werner J Z'Graggen, Joerg C Schefold
Muscular weakness and muscle wasting may often be observed in critically ill patients on intensive care units (ICUs) and may present as failure to wean from mechanical ventilation. Importantly, mounting data demonstrate that mechanical ventilation itself may induce progressive dysfunction of the main respiratory muscle, i.e. the diaphragm. The respective condition was termed 'ventilator-induced diaphragmatic dysfunction' (VIDD) and should be distinguished from peripheral muscular weakness as observed in 'ICU-acquired weakness (ICU-AW)'...
September 2016: Journal of Cachexia, Sarcopenia and Muscle
Philip Lewis, David Sheehan, Renata Soares, Ana Varela Coelho, Ken D O'Halloran
Mechanisms underpinning chronic sustained hypoxia (CH)-induced structural and functional adaptations in respiratory muscles are unclear despite the clinical relevance to respiratory diseases. The objectives of the present study were to thoroughly assess the putative role of CH-induced redox remodeling in murine diaphragm muscle over time and the subsequent effects on metabolic enzyme activities, catabolic signaling and catabolic processes, and diaphragm muscle contractile function. C57Bl6/J mice were exposed to normoxia or normobaric CH (fraction of inspired oxygen = 0...
July 2016: American Journal of Respiratory Cell and Molecular Biology
Túlio de Almeida Hermes, Aline Barbosa Macedo, Aline Reis Fogaça, Luis Henrique Rapucci Moraes, Felipe Meira de Faria, Larissa Akemi Kido, Valéria Helena Alves Cagnon, Elaine Minatel
This study evaluated the possible protective effects of cilostazol against myonecrosis in dystrophic diaphragm muscle in vivo, focusing on oxidative stress, the inflammatory response and angiogenesis. Young mdx mice, the experimental animal for Duchenne muscular dystrophy, received cilostazol for 14 days. A second group of mdx mice and a control group of C57BL/10 mice received a saline solution. In the mdx mice, cilostazol treatment was associated with reduced loss of muscle strength (-34.4%), decreased myonecrosis, reduced creatine kinase levels (-63...
February 2016: Clinical and Experimental Pharmacology & Physiology
Cristina Martínez-García, Adriana Izquierdo-Lahuerta, Yurena Vivas, Ismael Velasco, Tet-Kin Yeo, Sheldon Chen, Gema Medina-Gomez
In the last few decades a change in lifestyle has led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance (IR), dyslipidemia, type 2 diabetes and renal disease. The excess calories are stored as triglycerides in adipose tissue, but also may accumulate ectopically in other organs, including the kidney, which contributes to the damage through a toxic process named lipotoxicity...
2015: PloS One
Esther Barreiro, Ester Puig-Vilanova, Judith Marin-Corral, Alba Chacón-Cabrera, Anna Salazar-Degracia, Xavier Mateu, Luis Puente-Maestu, Elena García-Arumí, Antoni L Andreu, Luis Molina
Patients with chronic heart failure (CHF) experience exercise intolerance, fatigue and muscle wasting, which negatively influence their survival. We hypothesized that treatment with either the antioxidant N-acetyl cysteine (NAC) or the proteasome inhibitor bortezomib of rats with monocrotaline-induced CHF may restore inspiratory and limb muscle mass, function, and structure through several molecular mechanisms involved in protein breakdown and metabolism in the diaphragm and gastrocnemius. In these muscles of CHF-cachectic rats with and without treatment with NAC or bortezomib (N = 10/group) and non-cachectic controls, proteolysis (tyrosine release, proteasome activities, ubiquitin-proteasome markers), oxidative stress, inflammation, mitochondrial function, myosin, NF-κB transcriptional activity, muscle structural abnormalities, and fiber morphometry were analyzed together with muscle and cardiac functions...
July 2016: Journal of Cellular Physiology
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