Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygent, a second-generation perfluorocarbon (Perflubron) emulsion (Alliance Pharmaceutical Corporation, San Diego, CA) with superior oxygen delivery characteristics and greater stability than previous perfluorocarbon emulsions, was evaluated as a cerebroprotective agent in a dog model of partial brain stem ischemia. Six dogs were exposed to 20 minutes of isolated brain stem ischemia after receiving an intravenous bolus of Oxygent at a dose of 1.5 ml/kg. Brain stem auditory evoked potentials (BAEP) and regional cerebral blood flow were measured before and during the ischemia and for 5 hours after reperfusion. Changes in BAEP in this group were compared with those in four control dogs that experienced an identical ischemic period but that did not receive Oxygent. During the ischemic period, both control and Oxygent-treated animals experienced a dramatic decline in BAEP to under 10% of the baseline value. After reperfusion, the BAEP increased in both groups to between 50 and 70% of the baseline. In the Oxygent-treated group, the BAEP continued to recover to a final sustained level of over 80% of baseline. In contrast, the control animals suffered a drop in BAEP to 23% of baseline after the brief postischemic peak. The continued improvement in the BAEP in the Oxygent-treated group compared with the control groups suggests that Oxygent may be of some value as a protective agent to the brain stem during ischemia. This effect may be the result of improved oxygen delivery to the brain stem or may be related to other effects of Oxygent, such as reduction of reperfusion injury. Results suggest that Oxygent may be useful as a cerebroprotectant during cerebrovascular surgeries that require temporarily reducing blood flow to the brain stem.
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PMID:Intravenous perflubron emulsion administration improves the recovery of auditory evoked potentials after temporary brain stem ischemia in dogs. 773 16

Rovelizumab is a humanized monoclonal leukointegrin antibody under development by ICOS as a potential treatment for multiple sclerosis (MS), hemorrhagic shock, myocardial infarction (MI) and stroke. ICOS announced the commencement of phase II studies in MS patients experiencing acute exacerbations in January 1997; a randomized, double-blind, placebo-controlled phase III trial for acute ischemic stroke, to involve 800 patients, was initiated in January 1999 [312467,313014]. The compound is also undergoing preclinical investigation for cerebral vasospasm, head trauma, kidney transplantation and restenosis [346437]. In September 1999, results from a phase II clinical trial in 45 patients suffering from acute exacerbations of MS were presented at the Warburg Dillion Read Global Life Sciences Conference (New York). The study was designed to evaluate the safety and efficacy of four weekly doses of rovelizumab, as compared to placebo. Rovelizumab was shown to be safe, but demonstrated no clinical benefit for the recovery of neurological functioning [341638]. In February 1997, ICOS announced the initiation of a phase II trial in MI. The placebo-controlled trial is being coordinated by the Mayo Physician Alliance for Cardiovascular Trials and will evaluate safety, pharmacokinetics and infarct size in 60 patients [234046,264363]. Patient enrollment for this, and an open label phase II trial in trauma-induced hemorrhagic shock, was completed in September 1997 [264363]. An expanded shock trial in 150 trauma patients, is expected to complete enrollment by the end of 1998 [296831]. An expanded trial for MI was also planned [264363]. The company is to evaluate rovelizumab in patients with ischemic stroke, and a double-blind, dose-escalating, placebo-controlled phase II trial has been initiated at several centers in the US [264363]. A patient population of 48 was tested, with patient dosing occurring within 12 h of stroke onset symptoms. There was no significant difference in SAEs between rovelizumab and placebo treatment, and no immunogenicity was observed [315799]. Neuroprotection was observed in a rabbit model of focal ischemia, with greatest reduction in infarct noted in the cortical areas of the brain. Neutrophil infiltration to ischemic brain parenchyma was reduced by 90% [315799]. Rovelizumab is a monoclonal antibody directed against the CD11/CD18 cell adhesion proteins. By binding to these receptors, rovelizumab prevents the migration and adhesion of neutrophils in the central nervous system, which may cause brain inflammation and neuronal loss [167725]. Rovelizumab binds to all four known leukointegrin receptors, blocking neutrophil adhesion and binding to ICAMs [307344]. ICOS collaborated with the University of Washington on the preclinical development of this compound [175193].
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PMID:Rovelizumab (ICOS Corp). 1610 Jul

Myocardial recovery from ischemia-reperfusion (IR) is shaped by the interaction of many signaling pathways and tissue repair processes, including the innate immune response. We and others previously showed that sustained expression of the transcriptional co-activator yes-associated protein (YAP) improves survival and myocardial outcome after myocardial infarction. Here, we asked whether transient YAP expression would improve myocardial outcome after IR injury. After IR, we transiently activated YAP in the myocardium with modified mRNA encoding a constitutively active form of YAP (aYAP modRNA). Histological studies 2 d after IR showed that aYAP modRNA reduced cardiomyocyte (CM) necrosis and neutrophil infiltration. 4 wk after IR, aYAP modRNA-treated mice had better heart function as well as reduced scar size and hypertrophic remodeling. In cultured neonatal and adult CMs, YAP attenuated H2O2- or LPS-induced CM necrosis. TLR signaling pathway components important for innate immune responses were suppressed by YAP/TEAD1. In summary, our findings demonstrate that aYAP modRNA treatment reduces CM necrosis, cardiac inflammation, and hypertrophic remodeling after IR stress.
Life Sci Alliance 2020 01
PMID:aYAP modRNA reduces cardiac inflammation and hypertrophy in a murine ischemia-reperfusion model. 3184 59

Ischemic heart disease has been associated with an impairment on intercellular communication mediated by both gap junctions and extracellular vesicles. We have previously shown that connexin 43 (Cx43), the main ventricular gap junction protein, assembles into channels at the extracellular vesicle surface, mediating the release of vesicle content into target cells. Here, using a comprehensive strategy that included cell-based approaches, animal models and human patients, we demonstrate that myocardial ischemia impairs the secretion of Cx43 into circulating, intracardiac and cardiomyocyte-derived vesicles. In addition, we show that ubiquitin signals Cx43 release in basal conditions but appears to be dispensable during ischemia, suggesting an interplay between ischemia-induced Cx43 degradation and secretion. Overall, this study constitutes a step forward for the characterization of the signals and molecular players underlying vesicle protein sorting, with strong implications on long-range intercellular communication, paving the way towards the development of innovative diagnostic and therapeutic strategies for cardiovascular disorders.
Life Sci Alliance 2020 12
PMID:Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes. 3309 57