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https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#1
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28632583/incremental-balloon-deflation-following-complete-resuscitative-endovascular-balloon-occlusion-of-the-aorta-results-in-steep-inflection-of-flow-and-rapid-reperfusion-in-a-large-animal-model-of-hemorrhagic-shock
#2
Anders J Davidson, Rachel M Russo, Sarah-Ashley E Ferencz, Jeremy W Cannon, Todd E Rasmussen, Lucas P Neff, M Austin Johnson, Timothy K Williams
INTRODUCTION: To avoid potential cardiovascular collapse after resuscitative endovascular balloon occlusion of the aorta (REBOA), current guidelines recommend methodically deflating the balloon for 5 minutes to gradually reperfuse distal tissue beds. However, anecdotal evidence suggests that this approach may still result in unpredictable aortic flow rates and hemodynamic instability. We sought to characterize aortic flow dynamics following REBOA as the balloon is deflated in accordance with current practice guidelines...
July 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28632582/the-effect-of-resuscitative-endovascular-balloon-occlusion-of-the-aorta-partial-aortic-occlusion-and-aggressive-blood-transfusion-on-traumatic-brain-injury-in-a-swine-multiple-injuries-model
#3
M Austin Johnson, Timothy K Williams, Sarah-Ashley E Ferencz, Anders J Davidson, Rachel M Russo, William T O'Brien, Joseph M Galante, J Kevin Grayson, Lucas P Neff
BACKGROUND: Despite clinical reports of poor outcomes, the degree to which resuscitative endovascular balloon occlusion of the aorta (REBOA) exacerbates traumatic brain injury (TBI) is not known. We hypothesized that combined effects of increased proximal mean arterial pressure (pMAP), carotid blood flow (Qcarotid), and intracranial pressure (ICP) from REBOA would lead to TBI progression compared with partial aortic occlusion (PAO) or no intervention. METHODS: Twenty-one swine underwent a standardized TBI via computer Controlled cortical impact followed by 25% total blood volume rapid hemorrhage...
July 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28628603/field-and-en-route-resuscitative-endovascular-occlusion-of-the-aorta-a-feasible-military-reality
#4
Viktor A Reva, Tal M Hörer, Andrey I Makhnovskiy, Mikhail V Sokhranov, Igor M Samokhvalov, Joseph J DuBose
BACKGROUND: Severe noncompressible torso hemorrhage remains a leading cause of potentially preventable death in modern military conflicts. Resuscitative endovascular occlusion of the aorta (REBOA) has demonstrated potential as an effective adjunct to the treatment of noncompressible torso hemorrhage in the civilian early hospital and even prehospital settings-but the application of this technology for military prehospital use has not been well described. We aimed to assess the feasibility of both field and en route prehospital REBOA in the military exercise setting, simulating a modern armed conflict...
July 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28626072/5-ht-causes-splanchnic-venodilation
#5
Bridget Mahon Seitz, Hakan Orer, Teresa Krieger-Burke, Emma S Darios, Janice M Thompson, Gregory D Fink, Stephanie W Watts
Serotonin (5-HT, 5-hydroxytrypamine) causes relaxation of the isolated superior mesenteric vein (SMV), a splanchnic blood vessel, through activation of the 5-HT7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (>24 hours) infusion of 5-HT lowers blood pressure, we test the hypothesis that 5-HT causes an in vitro and in vivo splanchnic venodilation that is 5-HT7 receptor-dependent. In tissue baths for measurement of isometric contraction, the portal vein (PV) and abdominal inferior vena cava (Ab IVC) relaxed to 5-HT and the 5-HT1/7 receptor agonist 5-carboxamidotryptamine (5-CT); relaxation was abolished by the 5-HT7 receptor antagonist SB269970...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28625587/a-rabbit-model-of-aneurysmal-subarachnoid-hemorrhage-by-ear-central-artery-suprasellar-cistern-shunt
#6
Jing Lu, Fuxiang Chen, Bing Cai, Fan Chen, Dezhi Kang
Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening hemorrhagic cerebrovascular disease. The concept of early brain injury (EBI), induced by sharply increased intracranial pressure (ICP) and low cerebral perfusion pressure (CPP) with cerebral global ischemia following aneurysm rupture, has been increasingly accepted. However, EBI has not been well studied partly due to lack of an ideal animal model. The purpose of this study was to establish a new aSAH model which can mimic the pathophysiological damage of EBI...
June 15, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28625574/rapamycin-decreased-blood-brain-barrier-permeability-in-control-but-not-in-diabetic-rats-in-early-cerebral-ischemia
#7
Oak Z Chi, Geza K Kiss, Scott J Mellender, Xia Liu, Harvey R Weiss
Diabetes causes functional and structural changes in blood-brain barrier (BBB). The mammalian target of rapamycin (mTOR) has been associated with glucose metabolism, diabetes, and altering BBB permeability. Since there is only a narrow therapeutic window (3hours) for stroke victims, it is important to investigate BBB disruption in the early stage of cerebral ischemia. We compared the degree of BBB disruption in diabetic and in control rats at two hours of reperfusion after one hour of middle cerebral artery (MCA) occlusion with or without inhibition of mTOR...
June 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28624225/inhibition-of-mef2a-enhances-neovascularization-via-post-transcriptional-regulation-of-14q32-micrornas-mir-329-and-mir-494
#8
Sabine M J Welten, Margreet R de Vries, Erna A B Peters, Sudhir Agrawal, Paul H A Quax, A Yaël Nossent
Improving the efficacy of neovascularization is a promising strategy to restore perfusion of ischemic tissues in patients with peripheral arterial disease. The 14q32 microRNA cluster is highly involved in neovascularization. The Mef2a transcription factor has been shown to induce transcription of the microRNAs within this cluster. We inhibited expression of Mef2a using gene-silencing oligonucleotides (GSOs) in an in vivo hind limb ischemia model. Treatment with GSO-Mef2a clearly improved blood flow recovery within 3 days (44% recovery versus 25% recovery in control) and persisted until 14 days after ischemia induction (80% recovery versus 60% recovery in control)...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28616838/assessment-of-renal-hemodynamic-toxicity-of-fluid-challenge-with-0-9-nacl-compared-to-balanced-crystalloid-plasmalyte-%C3%A2-in-a-rat-model-with-severe-sepsis
#9
Pierre-Yves Olivier, François Beloncle, Valérie Seegers, Maher Tabka, Mathilde Renou de La Bourdonnaye, Alain Mercat, Paul Cales, Daniel Henrion, Peter Radermacher, Lise Piquilloud, Nicolas Lerolle, Pierre Asfar
BACKGROUND: According to international guidelines, volume expansion with crystalloids is the first-line treatment for hemodynamic management in patients with severe sepsis or septic shock. Compared to balanced crystalloids, 0.9% sodium chloride (0.9% NaCl) induces hyperchloremia and metabolic acidosis and may alter renal hemodynamics and function. We compared the effects of 0.9% NaCl to a less chloride-concentrated fluid, PlasmaLyte(®) (PL) in targeted fluid resuscitation in a randomized, double-blind controlled study in an experimental model of severe sepsis in rats...
December 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28614141/role-of-hemorrhagic-shock-in-experimental-polytrauma
#10
Stephanie Denk, Sebastian Weckbach, Philipp Eisele, Christian K Braun, Rebecca Wiegner, Julia J Ohmann, Lisa Wrba, Felix M Hoenes, Philipp Kellermann, Peter Radermacher, Ulrich Wachter, Sebastian Hafner, Oscar McCook, Anke Schultze, Annette Palmer, Sonja Braumüller, Florian Gebhard, Markus Huber-Lang
Hemorrhagic shock (HS) after tissue trauma increases the complication and mortality rate of polytrauma (PT) patients. Although several murine trauma models have been introduced, there is a lack of knowledge about the exact impact of an additional HS. We hypothesized that HS significantly contributes to organ injury, which can be reliably monitored by detection of specific organ damage markers.Therefore we established a novel clinically relevant PT plus HS model in C57BL/6 mice which were randomly assigned to control, HS, PT or PT+HS procedure (n = 8 per group)...
June 13, 2017: Shock
https://www.readbyqxmd.com/read/28612572/-comparison-of-two-methods-of-lidocaine-administrating-for-neuroprotection-in-rabbit-model-of-subarachnoid-hemorrhage
#11
Xian-Qing Shi, Yong-Jian Fu, Li-Rong Zheng
OBJECTIVES: To compare the neuroprotection effect of two methods of Lidocaine administration in rabbit model of subarachnoid hemorrhage. METHODS: Forty New Zealand white rabbits were randomly divided into sham group, subarachnoid hemorrhage group (SAH), Lidocaine intravenous injection group (L1), and Lidocaine intracisternal administration group (L2). The rabbits were given general anaesthesia, then 1.5 mL autologous nonheparinized arterial blood was injected into cisterna magna to establish SAH model, while 1...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28611661/discovery-and-development-of-calcium-channel-blockers
#12
REVIEW
Théophile Godfraind
In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28611024/platelet-amyloid-precursor-protein-is-a-modulator-of-venous-thromboembolism-in-mice
#13
Ilaria Canobbio, Caterina Visconte, Stefania Momi, Gianni Francesco Guidetti, Marta Zarà, Jessica Canino, Emanuela Falcinelli, Paolo Gresele, Mauro Torti
The amyloid precursor protein (APP), primarily known as the precursor of amyloid peptides that accumulate in the brain of Alzheimer's disease patients, is abundant in platelets but its physiological function remains unknown. In this study, we investigated the role of APP in hemostasis and thrombosis using APP knockout (KO) mice. Ex vivo aggregation, secretion, and integrin αIIbβ3 inside-out activation induced by several agonists were normal in APP-deficient platelets, but the number of circulating platelets was reduced by about 20%, and their size was slightly increased...
June 13, 2017: Blood
https://www.readbyqxmd.com/read/28609584/endothelial-nitric-oxide-synthase-inhibition-triggers-inflammatory-responses-in-the-brain-of-male-rats-exposed-to-ischemia-reperfusion-injury
#14
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Fabio Blandini, Diana Amantea, Cristina Tassorelli
Nitric oxide (NO) derived from endothelial NO synthase (eNOS) plays a role in preserving and maintaining the brain's microcirculation, inhibiting platelet aggregation, leukocyte adhesion, and migration. Inhibition of eNOS activity results in exacerbation of neuronal injury after ischemia by triggering diverse cellular mechanisms, including inflammatory responses. To examine the relative contribution of eNOS in stroke-induced neuroinflammation, we analyzed the effects of systemic treatment with l-N-(1-iminoethyl)ornithine (L-NIO), a relatively selective eNOS inhibitor, on the expression of MiR-155-5p, a key mediator of innate immunity regulation and endothelial dysfunction, in the cortex of male rats subjected to transient middle cerebral artery occlusion (tMCAo) followed by 24 hr of reperfusion...
June 13, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28606867/testosterone-deficiency-prevents-left-ventricular-contractility-dysfunction-after-myocardial-infarction
#15
REVIEW
R F Ribeiro Júnior, K S Ronconi, I C G Jesus, P W M Almeida, L Forechi, D V Vassallo, S Guatimosim, I Stefanon, A A Fernandes
Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups...
June 9, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28604360/chitosan-based-hydrogels-for-developing-a-small-diameter-vascular-graft-in-vitro-and-in-vivo-evaluation
#16
Audrey Aussel, Noélie Thébaud, Xavier Berard, Vincenzo Brizzi, Samantha Delmond, Reine Bareille, Robin Siadous, Chloe James, Jean Ripoche, Marlène Durand, Alexandra Montembault, Béatrice Burdin, Didier Letourneur, Nicolas L'Heureux, Laurent David, Laurence Bordenave
Vascular grafts made of synthetic polymers perform poorly in small-diameter applications (cardiac and peripheral bypass). Chitosan is a biocompatible natural polymer that can provide a novel biological scaffold for tissue engineering development. The goal of this study was to demonstrate the biocompatibility of a novel chitosan preparation in vitro and in vivo, and to assess its potential as a scaffold for vascular applications. Methods and Results. A series of experiments of increasing complexity, ranging from in vitro biocompatibility and hemocompatibility tests to in vivo studies in small and large animals (rat and sheep), was performed to provide a comprehensive analysis of chitosan hydrogels' biological properties...
June 12, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28602809/potential-of-%C3%AE-7-nachr-pet-imaging-in-atherosclerosis
#17
REVIEW
P F Ellen Boswijk, Matthias Bauwens, Felix M Mottaghy, Joachim E Wildberger, Jan Bucerius
Atherosclerotic events are usually acute and often strike otherwise asymptomatic patients. Although multiple clinical risk factors have been associated with atherosclerosis up to date, no further individual prediction can be made as to who will acutely suffer from its consequences based on traditional imaging methods like CT, MRI or angiography, or biomarkers. Previously, non-invasive imaging with (18)F-fluorodeoxyglucose ((18)F-FDG) PET was shown to potentially fill this niche as it offers high sensitive detection of metabolic processes associated with inflammatory changes in atherosclerotic plaques...
June 7, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28602360/the-role-of-platelets-in-autoimmunity-vasculopathy-and-fibrosis-implications-for-systemic-sclerosis
#18
REVIEW
Konstantinos Ntelis, Elena E Solomou, Lazaros Sakkas, Stamatis-Nick Liossis, Dimitrios Daoussis
INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, autoimmunity, and widespread dermal and visceral fibrosis. This article summarizes the current knowledge about the potential contribution of platelets in the disease process and the rationale of targeting platelets as an adjunct treatment for SSc. METHODS: We performed an electronic search (Medline) using the keywords platelets, systemic sclerosis, autoimmunity, fibrosis, Raynaud, and pulmonary arterial hypertension...
May 23, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28600797/the-novel-nitric-oxide-donor-pdno-attenuates-ovine-ischemia-reperfusion-induced-renal-failure
#19
Kristofer F Nilsson, John Sandin, Lars E Gustafsson, Robert Frithiof
BACKGROUND: Renal ischemia-reperfusion injury is a common cause of acute kidney injury in intensive care and surgery. Recently, novel organic mononitrites of 1,2-propanediol (PDNO) were synthesized and shown to rapidly and controllably deploy nitric oxide in the circulation when administered intravenously. We hypothesized that intravenous infusion of PDNO during renal ischemia reperfusion would improve post-ischemic renal function and microcirculation. METHODS: Sixteen sheep were anesthetized, mechanically ventilated, and surgically instrumented...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28597764/microct-analysis-of-vascular-morphometry-a-comparison-of-right-lung-lobes-in-the-sugen-hypoxic-rat-model-of-pulmonary-arterial-hypertension
#20
Erin M Faight, Kostas Verdelis, Lee Zourelias, Rong Chong, Raymond L Benza, Kelly J Shields
Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling within the lung. Clinical computed tomography (CT) scans are routinely used to aid in PAH diagnosis. Animal models, including the Sugen-hypoxic rat model (SU/hyp), of PAH closely mimic human PAH development. We have previously used micro-computed tomography (microCT) to find extensive right lung vascular remodeling in the SU/hyp. We hypothesized that the individual right lung lobes may not contribute equally to overall lung vascular remodeling...
April 2017: Pulmonary Circulation
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