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Mechanisms of protection against ischemic damage in the heart
Title
Mechanisms of protection against ischemic damage in the heart.
Creator
Moench, Ian, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Heart disease including ischemic heart disease is the highest contributor to death and morbidity in the western world. The studies presented were conducted to determine possible pathways of protection of the heart against ischemia/reperfusion. We employed adenovirus mediated over-expression of Methionine sulfoxide reductase A (MsrA) in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation. Cells transfected with MsrA encoding...
Show moreHeart disease including ischemic heart disease is the highest contributor to death and morbidity in the western world. The studies presented were conducted to determine possible pathways of protection of the heart against ischemia/reperfusion. We employed adenovirus mediated over-expression of Methionine sulfoxide reductase A (MsrA) in primary neonatal rat cardiac myocytes to determine the effect of this enzyme in protecting against hypoxia/reoxygenation. Cells transfected with MsrA encoding adenovirus and subjected to hypoxia/reoxygenation exhibited a 45% decrease in apoptosis as compared to controls. Likewise total cell death as determined by levels of Lactate Dehydrogenase (LDH) release was dramatically decreased by MsrA overexpression. The initial hypothesis that led to our testing sulindac was based on the fact that the S epimer of sulindac was a substrate for MsrA and that this compound might function as a catalytic anti-oxidant based on a reaction cycle that involved reductio n to sulindac sulfide followed by oxidation back to sulindac. To test this we examined the protective effect of sulindac in hypoxia re-oxygenation in both cardiac myocytes in culture and using a Langendorff model of myocardial ischemia. Using this model of myocardial ischemia we showed that pre-incubation of hearts with sulindac, or the S and R epimers of sulindac resulted in protection against cell death. We present several lines of evidence that the protective effect of sulindac is not dependent on the Msr enzyme system nor does it involve the well established role of sulindac as a Cyclooxygenase (COX) inhibitor. Numerous signaling pathways have been implicated in myocardial protective mechanisms, many of which require fluctuations in ROS levels as initiators or mediators., Sulindac shows very good potential as a preconditioning agent that could induce tissue protection against oxidative damage.Blocking of preconditioning pathways by administration of the PKC blocker chelerythine abrogated the ischemic protection afforded by sulindac. Secondly, an end-effector of preconditioning, inducible nitric oxide synthase (iNOS),was found to be induced by greater than 5 fold after 48 h prior feeding sulindac.
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Date Issued
2008
PURL
http://purl.flvc.org/FAU/186291
Subject Headings
Biochemical markers, Diagnostic use, Cardiovascular system, Diseases, Diagnosis, Heart, Diseases, Molecular aspects, Medical care, Quality control, Coronary heart disease, Prevention, Apoptosis, Myocardial infarction, Prevention
Format
Document (PDF)
Survival and decontamination of potential bio-warfare agents on hospital surfaces
Title
Survival and decontamination of potential bio-warfare agents on hospital surfaces.
Creator
Moench, Ian, Florida Atlantic University, Esiobu, Nwadiuto
Abstract/Description
Effective decontamination of infectious agents on critical and other hospital surfaces will drastically reduce nosocomial infections and impacts of any biological attack. This research determined the distribution of multiple species of bacteria on 16 different surfaces in two hospitals over a period of time to identify potential reservoirs of infection. The relative efficacy of current hospital disinfectants on endospores were also evaluated to inform policy. Using simulations of endospore...
Show moreEffective decontamination of infectious agents on critical and other hospital surfaces will drastically reduce nosocomial infections and impacts of any biological attack. This research determined the distribution of multiple species of bacteria on 16 different surfaces in two hospitals over a period of time to identify potential reservoirs of infection. The relative efficacy of current hospital disinfectants on endospores were also evaluated to inform policy. Using simulations of endospore-laden surfaces under laboratory conditions, the effects of exposure time, disinfectant concentration and possible synergies with endospore germination stimulant were evaluated. Keyboards, phones, door handles and bed rails were identified as risky hospital surfaces. The location and use of the surfaces were significant determinants of bacterial load. None of the disinfectants tested was sporicidal (<50% reduction). The results of this unique study provide healthcare personnel with a practical guide to control the spread of infection during peace and bio-warfare times.
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Date Issued
2005
PURL
http://purl.flvc.org/fcla/dt/13215
Subject Headings
Bioterrorism--Health aspects, Emergency management--United States, Health facilities--Sanitation--United States, Bioterrorism--United States--Prevention, Disaster medicine, Disinfection and disinfectants
Format
Document (PDF)