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14 résultats
Pharmacological characterization of the newly synthesized 5-amino-N-butyl-2-(4-ethoxyphenoxy)-benzamide hydrochloride (BED) as a potent NCX3 inhibitor that worsens anoxic injury in cortical neurons, organotypic hippocampal cultures, and ischemic brain.
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The Na(+)/Ca(2+) exchanger (NCX), a 10-transmembrane domain protein mainly involved in the regulation of intracellular Ca(2+) homeostasis, plays a crucial role in cerebral ischemia. In the present paper, we characterized the effect of the newly synthesized compound
(2-Methyl-5-(methylsulfonyl)benzoyl)guanidine Na+/H+ antiporter inhibitors.
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The inhibition of the Na+/H+ exchanger during cardiac ischemia and reperfusion has been shown to be beneficial for the preservation of the cellular integrity and functional performance. The aim of the present investigation was to come up with potent and selective benzoylguanidines as NHE inhibitors
Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis.
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Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none
Blocking Na(+)/H(+) exchange reduces [Na(+)](i) and [Ca(2+)](i) load after ischemia and improves function in intact hearts.
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We determined in intact hearts whether inhibition of Na(+)/H(+) exchange (NHE) decreases intracellular Na(+) and Ca(2+) during ischemia and reperfusion, improves function during reperfusion, and reduces infarct size. Guinea pig isolated hearts were perfused with Krebs-Ringer solution at 37 degrees
Evaluation of cardiac arrhythmic risks using a rabbit model of left ventricular systolic dysfunction.
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Patients with heart disease have a higher risk to develop cardiac arrhythmias, either spontaneously or drug-induced. In this study, we have used a rabbit model of myocardial infarction (MI) with severe left ventricular systolic dysfunction (LVSD) to study potential drug-induced cardiac risks with
Poly(ADP-ribose)polymerase inhibition - where now?
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The poly(ADP-ribose)polymerases (PARPs) catalyse the transfer of ADP-ribose units from the substrate NAD(+) to acceptor proteins, biosynthesising polyanionic poly(ADP-ribose) polymers. A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years. Inhibitors of the
Neuroprotective Action of Human Wharton's Jelly-Derived Mesenchymal Stromal Cell Transplants in a Rodent Model of Stroke.
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Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs) have distinct immunomodulatory and protective effects against kidney, liver, or heart injury. Limited studies have shown that WJ-MSCs attenuates oxygen-glucose deprivation-mediated inflammation in hippocampal slices. The neuroprotective
Epigenetically modified cardiac mesenchymal stromal cells limit myocardial fibrosis and promote functional recovery in a model of chronic ischemic cardiomyopathy.
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Preclinical investigations support the concept that donor cells more oriented towards a cardiovascular phenotype favor repair. In light of this philosophy, we previously identified HDAC1 as a mediator of cardiac mesenchymal cell (CMC) cardiomyogenic lineage commitment and paracrine signaling potency
Structural Insights of Benzenesulfonamide Analogues as NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.
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NLRP3 inflammasome plays critical roles in a variety of human diseases and represents a promising drug target. In this study, we established the in vivo functional activities of JC124, a previously identified NLRP3 inflammasome inhibitor from our group, in mouse models of Alzheimer's disease and
KPR-5714, a Novel Transient Receptor Potential Melastatin 8 (TRPM8) Antagonist, Improves Overactive Bladder via Inhibition of Bladder Afferent Hyperactivity in Rats.
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Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensing ion channel mainly expressed in primary sensory neurons (Aδ-fibers and C-fibers in the dorsal root ganglion). In this report, we characterized KPR-5714
Inhibition of the Na(+)/H(+) exchanger attenuates phase 1b ischemic arrhythmias and reperfusion-induced ventricular fibrillation.
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The sodium-hydrogen exchanger-isotype 1 (NHE-1) plays a critical role in myocardial ischemia-reperfusion injury. While studies employing less selective sodium-hydrogen inhibitors have demonstrated antiarrhythmic activity, only one study has examined the in vivo efficacy of selective NHE-1 inhibition
Antiarrhythmic and proarrhythmic effects of sematilide in canine ventricular arrhythmia models.
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Using canine ventricular arrhythmia models induced by two-stage coronary ligation, digitalis, adrenaline, coronary ligation and reperfusion, and programmed electrical stimulation (PES), we examined the antiarrhythmic or proarrhythmic effects of sematilide,
A novel hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonist prevents ischemic neuronal death.
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Physiological levels of H(2)S exert neuroprotective effects, whereas high concentrations of H(2)S may cause neurotoxicity in part via activation of NMDAR. To characterize the neuroprotective effects of combination of exogenous H(2)S and NMDAR antagonism, we synthesized a novel H(2)S-releasing NMDAR
A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse.
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BACKGROUND
The formation of the NLRP3 inflammasome in the heart during acute myocardial infarction amplifies the inflammatory response and mediates further damage. Glyburide has NLRP3 inhibitory activity in vitro but requires very high doses in vivo, associated with hypoglycemia. The aim of this
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