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https://www.readbyqxmd.com/read/27911703/understanding-and-preventing-mitochondrial-oxidative-damage
#1
REVIEW
Michael P Murphy
Mitochondrial oxidative damage has long been known to contribute to damage in conditions such as ischaemia-reperfusion (IR) injury in heart attack. Over the past years, we have developed a series of mitochondria-targeted compounds designed to ameliorate or determine how this damage occurs. I will outline some of this work, from MitoQ to the mitochondria-targeted S-nitrosating agent, called MitoSNO, that we showed was effective in preventing reactive oxygen species (ROS) formation in IR injury with therapeutic implications...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910802/near-infrared-spectroscopy-evaluated-cerebral-oxygenation-during-anesthesia
#2
Henrik Sørensen
Likely, maintained organ and notably cerebral perfusion, secures rapid recovery following anesthesia. To secure cerebral blood flow (CBF) at least mean arterial pressure (MAP) and the arterial carbon dioxide tension (PaCO2) need to be considered. CBF is "autoregulated", i.e. stays more or less stable within a MAP of 50-150 mmHg, but the lower limit appears to depend on the central blood volume and/or cardiac output, illustrated by a decrease in CBF at a MAP of 80 mmHg with a compromised central blood volume, while CBF remains constant with a MAP < 40 mmHg, if the central blood volume is maintained...
December 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27910195/mulberrofuran-g-protects-ischemic-injury-induced-cell-death-via-inhibition-of-nox4-mediated-ros-generation-and-er-stress
#3
Sungeun Hong, Jaeyoung Kwon, Dong-Woo Kim, Hak Ju Lee, Dongho Lee, Woongchon Mar
The aim of this study was to investigate the neuroprotective effect of mulberrofuran G (MG) in in vitro and in vivo models of cerebral ischemia. MG was isolated from the root bark of Morus bombycis. MG inhibited nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme activity and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced NOX4 protein expression in SH-SY5Y cells. MG inhibited the expression of activated caspase-3 and caspase-9 and cleaved poly adenine dinucleotide phosphate-ribose polymerase in OGD/R-induced SH-SY5Y cells...
December 2, 2016: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/27909732/early-vegf-inhibition-attenuates-blood-brain-barrier-disruption-in-ischemic-rat-brains-by-regulating-the-expression-of-mmps
#4
Hai-Tao Zhang, Ping Zhang, Yi Gao, Chen-Long Li, Hong-Jun Wang, Ling-Chao Chen, Yan Feng, Rui-Yan Li, Yong-Li Li, Chuan-Lu Jiang
Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion...
November 29, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27903536/persistent-microvascular-obstruction-after-myocardial-infarction-culminates-in-the-confluence-of-ferric-iron-oxide-crystals-proinflammatory-burden-and-adverse-remodeling
#5
Avinash Kali, Ivan Cokic, Richard Tang, Alice Dohnalkova, Libor Kovarik, Hsin-Jung Yang, Andreas Kumar, Frank S Prato, John C Wood, David Underhill, Eduardo Marbán, Rohan Dharmakumar
BACKGROUND: Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI. METHODS AND RESULTS: Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI...
November 2016: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/27901497/curcumin-carrying-nanoparticles-prevent-ischemia-reperfusion-injury-in-human-renal-cells
#6
Yong Xu, Ning Hu, Wei Jiang, Hong-Fang Yuan, Dong-Hui Zheng
Renal ischemia-reperfusion injury (IRI) is a major complication in clinical practice. However, despite its frequency, effective preventive/treatment strategies for this condition are scarce. Curcumin possesses antioxidant properties and is a promising potential protective agent against renal IRI, but its poor water solubility restricts its application. In this study, we constructed curcumin-carrying distearoylphosphatidylethanolamine-polyethylene glycol nanoparticles (Cur-NPs), and their effect on HK-2 cells exposed to IRI was examined in vitro...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896629/remote-limb-ischemic-preconditioning-protects-rats-against-cerebral-ischemia-via-hif-1%C3%AE-ampk-hsp70-pathway
#7
Ming Xia, Qian Ding, Zhidan Zhang, Qinggen Feng
Remote limb ischemic preconditioning (RIPC) is a clinically feasible strategy to protect against ischemia/reperfusion injury, but the knowledge concerning the mechanism underlying RIPC is scarce. This study was performed to examine the effect of RIPC on brain tissue suffering from ischemia challenge and explore its underlying mechanism in a rat model. The animals were divided into four groups: Sham, middle cerebral artery occlusion (MCAO), RIPC, and MCAO+RIPC. We found that previous exposure to RIPC significantly attenuated neurological dysfunction and lessened brain edema in MCAO+RIPC group...
November 28, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27894810/na-ca-2-exchanger-1-inhibition-abolishes-ischemic-tolerance-induced-by-ischemic-preconditioning-in-different-cardiac-models
#8
Pasqualina Castaldo, Maria Loredana Macrì, Vincenzo Lariccia, Alessandra Matteucci, Marta Maiolino, Santo Gratteri, Salvatore Amoroso, Simona Magi
Ca(2+)-handling disturbances play an important role in the genesis of myocardial ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) is a powerful strategy to induce tolerance against subsequent ischemic episodes. IPC signaling pathways may be triggered by Ca(2+) ion. Since Na(+)/Ca(2+) exchanger 1 (NCX1) participates in modulating intracellular Ca(2+) homeostasis, here we further defined its role in I/R and investigated its potential involvement in IPC-induced cardioprotection. In isolated ventricular cardiomyocytes, perfused rat heart and H9c2 cardiomyoblasts, I/R produceda significant cellinjury, assessed by measuring extracellular lactate dehydrogenase (LDH) and, for the whole heart, also by estimating myocardialinfarct size area...
November 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27885275/tdb-protects-vascular-endothelial-cells-against-oxygen-glucose-deprivation-reperfusion-induced-injury-by-targeting-mir-34a-to-increase-bcl-2-expression
#9
Li-Xi Liao, Ming-Bo Zhao, Xin Dong, Yong Jiang, Ke-Wu Zeng, Peng-Fei Tu
Prolonged ischemia can result in apoptotic death of vascular endothelial cells and lead to ischemic vascular diseases including vascular dementia, arteriosclerosis and brain oedema. Finding protective strategies to prevent this is therefore an urgent mission. Recent studies have shown that dysregulation of microRNAs (miRNAs) can lead to imbalance of Bcl-2 family proteins and mitochondrial dysfunction, leading to further damage of vascular cells under ischemic conditions. However, whether miRNAs can be used as a drug target for treating vascular diseases is not fully understood...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884032/-acute-kidney-injury-remote-ischaemic-preconditioning-a-nephroprotective-strategy
#10
Melanie Meersch, Alexander Zarbock
Acute kidney injury is a common and serious complication with a huge impact on morbidity and short- as well as long-term mortality. Sepsis and major surgeries, especially cardiac surgery, are the most common causes of acute kidney injury. Slight increases of serum-creatinine levels are associated with adverse outcomes highlighting the relevance of the need for nephroprotective strategies to reduce the occurrence of acute kidney injury. Remote ischaemic preconditioning is an intervention consisting of brief episodes of ischaemia and reperfusion at a remote site before subsequent ischaemic insults occur...
November 2016: Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie: AINS
https://www.readbyqxmd.com/read/27883078/impaired-endothelial-nitric-oxide-synthase-homodimer-formation-triggers-development-of-transplant-vasculopathy-insights-from-a-murine-aortic-transplantation-model
#11
Rupert Oberhuber, Gregor Riede, Benno Cardini, David Bernhard, Barbara Messner, Katrin Watschinger, Christina Steger, Gerald Brandacher, Johann Pratschke, Georg Golderer, Ernst R Werner, Manuel Maglione
Transplant vasculopathy (TV) represents a major obstacle to long-term graft survival and correlates with severity of ischemia reperfusion injury (IRI). Donor administration of the nitric oxide synthases (NOS) co-factor tetrahydrobiopterin has been shown to prevent IRI. Herein, we analysed whether tetrahydrobiopterin is also involved in TV development. Using a fully allogeneic mismatched (BALB/c to C57BL/6) murine aortic transplantation model grafts subjected to long cold ischemia time developed severe TV with intimal hyperplasia (α-smooth muscle actin positive cells in the neointima) and endothelial activation (increased P-selectin expression)...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27869201/cardioprotection-by-combination-of-three-compounds-from-shengmai-preparations-in-mice-with-myocardial-ischemia-reperfusion-injury-through-ampk-activation-mediated-mitochondrial-fission
#12
Fang Li, Xiaoxue Fan, Yu Zhang, Lizhi Pang, Xiaonan Ma, Meijia Song, Junping Kou, Boyang Yu
GRS is a drug combination of three active components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai preparations, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study explores the cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury compared with ShengMai preparations and investigates the underlying mechanisms. GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy as Shengmai preparations, as evidenced by decreased myocardium infarct size, ameliorated histological features, the decrease of LDH production and improved cardiac function, and also produced a significant decrease of apoptotic index...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27867477/hyperbaric-oxygen-therapy-in-experimental-and-clinical-stroke
#13
REVIEW
Wei-Wei Zhai, Liang Sun, Zheng-Quan Yu, Gang Chen
Stroke, which is defined as a neurologic deficit caused by sudden impaired blood supply, has been considered as a common cause of death and disability for decades. The World Health Organization has declared that almost every 5 seconds a new stroke occurs, placing immense socioeconomic burdens. However, the effective and available treatment strategies are still limited. Additionally, the most effective therapy, such as thrombolysis and stenting for ischemic stroke, generally requires a narrow therapeutic time window after the event...
April 2016: Medical Gas Research
https://www.readbyqxmd.com/read/27867042/poly-adp-ribose-polymerase-1-hyperactivation-in-neurodegenerative-diseases-the-death-knell-tolls-for-neurons
#14
REVIEW
Parimala Narne, Vimal Pandey, Praveen Kumar Simhadri, Prakash Babu Phanithi
Neurodegeneration is a salient feature of chronic refractory brain disorders like Alzheimer's, Parkinson's, Huntington's, amyotropic lateral sclerosis and acute conditions like cerebral ischemia/reperfusion etc. The pathological protein aggregates, mitochondrial mutations or ischemic insults typifying these disease conditions collude with and intensify existing oxidative stress and attendant mitochondrial dysfunction. Interlocking these mechanisms is poly(ADP-ribose) polymerase (PARP-1) hyperactivation that invokes a distinct form of neuronal cell death viz...
November 17, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27861288/innate-immune-regulations-and-liver-ischemia-reperfusion-injury
#15
Ling Lu, Haoming Zhou, Ming Ni, Xuehao Wang, Ronald Busuttil, Jerzy Kupiec-Weglinski, Yuan Zhai
Liver ischemia reperfusion activates innate immune system to drive the full development of inflammatory hepatocellular injury. Damage-associated molecular patterns (DAMPs) stimulate myeloid and dendritic cells via pattern recognition receptors (PRRs) to initiate the immune response. Complex intracellular signaling network transduces inflammatory signaling to regulate both innate immune cell activation and parenchymal cell death. Recent studies have revealed that DAMPs may trigger not only proinflammatory but also immune regulatory responses by activating different PRRs or distinctive intracellular signaling pathways or in special cell populations...
December 2016: Transplantation
https://www.readbyqxmd.com/read/27861263/mechanisms-of-graft-rejection-after-lung-transplantation
#16
Hsi-Min Hsiao, Davide Scozzi, Jason M Gauthier, Daniel Kreisel
PURPOSE OF REVIEW: To date, outcomes after lung transplantation are far worse than after transplantation of other solid organs. New insights into mechanisms that contribute to graft rejection and tolerance after lung transplantation remain of great interest. This review examines the recent literature on the role of innate and adaptive immunity in shaping the fate of lung grafts. RECENT FINDINGS: Innate and adaptive immune cells orchestrate allograft rejection after transplantation...
November 17, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27860548/mitochondrial-dysfunction-and-myocardial-ischemia-reperfusion-implications-for-novel-therapies
#17
Edward J Lesnefsky, Qun Chen, Bernard Tandler, Charles L Hoppel
Mitochondria have emerged as key participants in and regulators of myocardial injury during ischemia and reperfusion. This review examines the sites of damage to cardiac mitochondria during ischemia and focuses on the impact of these defects. The concept that mitochondrial damage during ischemia leads to cardiac injury during reperfusion is addressed. The mechanisms that translate ischemic mitochondrial injury into cellular damage, during both ischemia and early reperfusion, are examined. Next, we discuss strategies that modulate and counteract these mechanisms of mitochondrial-driven injury...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27858909/comparison-of-the-risk-of-left-ventricular-free-wall-rupture-in-taiwanese-patients-with-st-elevation-acute-myocardial-infarction-undergoing-different-reperfusion-strategies-a-medical-record-review-study
#18
Rei-Yeuh Chang, Han-Lin Tsai, Ping-Gune Hsiao, Chao-Wen Tan, Chi-Pin Lee, I-Tseng Chu, Yung-Ping Chen, Cheng-Yun Chen
Ventricular free wall rupture (VFWR) is the second most common cause of death in patients with acute ST-elevation myocardial infarction (STEMI). Nevertheless, few reports have investigated the factors, including different treatment strategies, associated with VFWR in Taiwanese patients. Therefore, the aim of this study was to compare the risk of VFWR in Taiwanese patients with acute STEMI who had received primary percutaneous coronary intervention (PCI), rescue PCI, scheduled PCI, thrombolytic therapy, and pharmacologic treatment...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27856349/reparative-effects-of-interleukin-1-receptor-antagonist-in-young-and-aged-co-morbid-rodents-after-cerebral-ischemia
#19
Jesus M Pradillo, Katie N Murray, Graham A Coutts, Ana Moraga, Fernando Oroz-Gonjar, Herve Boutin, Maria A Moro, Ignacio Lizasoain, Nancy J Rothwell, Stuart M Allan
Neuroprotective strategies for ischemic stroke have failed to translate from bench to bedside, possibly due to the lack of consideration of key clinical co-morbidities. Stroke and co-morbidities are associated with raised levels of the pro-inflammatory cytokine interleukin-1 (IL-1). Inhibition of IL-1 by the administration of interleukin-1 receptor antagonist (IL-1Ra) has shown to be neuroprotective after experimental cerebral ischemia. Stroke can also trigger a robust neuroreparative response following injury, yet many of these new born neurons fail to survive or integrate into pre-existing circuits...
November 14, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27853755/differential-stress-response-mechanisms-in-right-and-left-ventricles
#20
Makhosazane Zungu-Edmondson, Yuichiro J Suzuki
Right ventricular (RV) failure is the major cause of death among patients with pulmonary hypertension. However, differences between the RV and left ventricle (LV) of the adult heart have not been defined, despite myocytes from these two ventricles originate from different progenitor cells. The lack of such knowledge interferes with developing therapeutic strategies to protect the RV. The goal of this study was to identify possible differences between stress responses in the RV and LV free walls of adult rats...
2016: Journal of Rare Diseases Research & Treatment
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