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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, the cardioprotective effects of insulin-like growth factor I (IGF-I) were examined in a murine model of myocardial ischemia reperfusion (i.e., 20 min + 24 hr). IGF-I (1-10 micrograms per rat) administered 1 hr prior to ischemia significantly attenuated myocardial injury (i.e., creatine kinase loss) compared to vehicle (P < 0.001). In addition, cardiac myeloperoxidase activity, an index of neutrophil accumulation, in the ischemic area was significantly attenuated by IGF-I (P < 0.001). This protective effect of IGF-I was not observed with des-(1-3)-IGF-I. Immunohistochemical analysis of ischemic-reperfused myocardial tissue demonstrated markedly increased DNA fragmentation due to programmed cell death (i.e., apoptosis) compared to nonischemic myocardium. Furthermore, IGF-I significantly attenuated the incidence of myocyte apoptosis after myocardial ischemia and reperfusion. Therefore, IGF-I appears to be an effective agent for preserving ischemic myocardium from reperfusion injury and protects via two different mechanisms--inhibition of polymorphonuclear leukocyte-induced cardiac necrosis and inhibition of reperfusion-induced apoptosis of cardiac myocytes.
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PMID:Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. 764 33

Rats with carcinoma of the colon implanted into the liver were subjected to hepatic arterial occlusion for 30-120 min. Regrowth of the tumour after reperfusion was evaluated by immunohistological determination of S-phase activity after injection of bromodeoxyuridine. Levels of RNA and nucleotides, and energy charge, were also examined. DNA synthesis was observed in the entire tumour except in necrotic areas of controls and after 30-min ischaemia with 2-h reflow. Almost all tumoral DNA synthesis was abolished by 2 h of ischaemia, except in a few cells in the tumour periphery, which after reperfusion for 22 and 40 h grew into a band-like concentric layer. Levels of energy charge, adenosine, uridine and guanosine 5'-triphosphates, and RNA were unchanged in liver tissue after hepatic arterial occlusion but decreased in the tumour. In conclusion 30 min of ischaemia did not damage the tumour cells substantially. Ischaemia for 2 h seemed able to kill the tumour cells except those in the periphery in areas nourished by the portal vein where tumour regrowth was seen. The liver tissue was not damaged.
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PMID:Tumour S-phase activity, nucleotide profile and RNA levels after hepatic artery occlusion and reperfusion in an experimental model of secondary liver carcinoma. 764 21

Heat shock protein (HSP) synthesis is induced by hyperthermia and other types of stress in mammalian cells in vitro and in vivo. In the present report we describe that in human erythroleukemic cells, aspirin (400 microM), when administered during or immediately after a hyperthermic treatment, causes an increase in the amount of HSP70 synthesized and prolongs HSP70 synthesis for a period of several hours. This effect is not due to increased HSP70 mRNA stability. In the presence of aspirin, the heat shock transcription factor is maintained in the activated DNA-binding state for a period twice as long as control, an effect which results in enhanced and prolonged HSP70 mRNA transcription. A different cyclooxygenase inhibitor, indomethacin (10(-7) M), also provokes similar effects. The modulation of the heat shock response by aspirin and indomethacin is associated with the ability of these drugs to potentiate the effect of hyperthermia and prolong thermotolerance for a period of 48 h. These results indicate that the use of aspirin and indomethacin should be carefully monitored in cancer patients undergoing hyperthermic treatment. On the other hand, the ability of aspirin to enhance HSP70 synthesis suggests that nonsteroidal anti-inflammatory drugs could potentiate the cytoprotective role of HSPs in pathological states, including fever, inflammation, and ischemia.
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PMID:Aspirin enhances thermotolerance in human erythroleukemic cells: an effect associated with the modulation of the heat shock response. 767 Dec 59

The time course of appearance of cells with DNA damage was studied in rats following transient severe forebrain ischemia. This DNA damage could be detected by in situ end-labeling on brain sections. The breaks in DNA appeared selectively by day 1 in the striatum and later in the CA1 region of the hippocampus. It was possible by double labeling to show that there was no DNA damage in astrocytes. The DNA breaks consisted of laddered DNA fragments indicative of an ordered apoptotic type of internucleosomal cleavage, which persisted without smearing for up to 7 days of reperfusion. In contrast, the DNA breaks following ischemia induced by decapitation were random and, after gel electrophoresis, consisted of smeared fragments of multiple sizes. There was some early regional cellular death, restricted to the dentate of the hippocampus, prior to the pannecrotic degeneration. It is concluded that transient forebrain ischemia leads to a type of neuronal destruction that is not random necrosis but that shares some component of the apoptotic cell death pathway.
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PMID:Differences in DNA fragmentation following transient cerebral or decapitation ischemia in rats. 767 68

The expression of the protooncogenes, c-fos, jun B, c-jun, and jun D was investigated in a rat focal cerebral ischemia model by Northern analysis and in situ hybridization. Severe ischemia (reduction of regional blood flow by 88-92%) in this model is confined to cerebral cortex irrigated by the right middle cerebral artery. Ischemia for 30 minutes, which caused only slight cortical damage (infarct size, < 10 mm3), induced both jun B and c-fos mRNAs exclusively in the right cerebral cortex. Ischemia for 90 minutes, which led to large cortical infarction (infarct size, > 140 mm3), also induced the expression of these two genes in the right cerebral cortex as well as the ipsilateral hippocampus. The latter sustained very mild ischemia (reduction of regional blood flow by 10-20%). The coinduction of jun B and c-fos expression occurred immediately after reperfusion and peaked at 60 minutes after reperfusion. The expression of c-jun was enhanced in a similar pattern, but at a much lower magnitude. In contrast, no change in jun D expression was observed. Nuclear run-on assays indicated that the increase in c-fos, jun B, and c-jun mRNA levels was due to the increase of transcription rate in these genes. Mobility shift assays showed a basal DNA binding activity of transcription factor AP-1 in the right cerebral cortex. Ischemia for 30 or 90 minutes followed by reperfusion for 4 hours resulted in a four- to sixfold increase of AP-1 binding activity. The enhanced DNA binding activity persisted for as long as 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of c-fos and c-jun family genes after focal cerebral ischemia. 849 19

Brains from 5 mice subjected to focal ischemia (2 hours)--reperfusion (22 h), revealed a significant increase (P < 0.01) in cells exhibiting DNA fragmentation (100-200 per section)--ipsilateral hemisphere compared to 0-3 per section found in the contralateral hemisphere and normal (n = 5) and sham operated (n = 5) mice. Neurons were the predominant cells (90-95%) exhibiting DNA fragmentation, and were primarily located in the inner boundary zone to the infarct. Apoptosis may contribute to the development of infarct after transient focal cerebral ischemia.
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PMID:In situ detection of DNA fragmentation after focal cerebral ischemia in mice. 770 71

The structural changes that occur in chromatin DNA after ischemic brain injury are poorly understood. The presence of oligonucleosome fragments that are recognized as the characteristic DNA ladder has been demonstrated in global and focal ischemia, associated or not with random DNA fragmentation. Using pulsed-field gel electrophoresis, which improves DNA separation, we have now detected initial stages of DNA fragmentation that occur already 6 h after reversible focal cerebral ischemia in rats. This result confirms that internucleosomal DNA fragmentation precedes random DNA fragmentation in vulnerable striatal and cortical neurons following reversible focal cerebral ischemia.
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PMID:Early endonuclease activation following reversible focal ischemia in the rat brain. 771 95

Neurons grown in culture die when they are exposed to high concentrations (0.1-1 mM) of the neurotransmitter L-glutamate. A similar phenomenon may occur in the mammalian brain during ischemia and other injuries that cause excessive glutamate release. Activation of N-methyl-D-aspartate (NMDA) receptors and the consequent Ca2+ influx are thought to play a critical role in the process of neuronal toxicity. Events subsequent to the Ca2+ influx are not well understood. We have discovered that nonneuronal kidney cells expressing NMDA receptors after DNA transfection undergo cell death unless they are protected by drugs that block the NMDA receptor ion channel. Furthermore, transfected cells expressing a mutated NMDA receptor that conducts less Ca2+ are less vulnerable to cell death. In addition, we find that even though several active forms of NMDA receptors can be synthesized in these cells after transfection with different cloned subunits, not all receptor types are equally toxic. These experiments suggest that Ca2+ influx through NMDA channels may be toxic to nonneuronal cells and that the NMDA receptor expression may be the major neuron-specific component of excitotoxicity.
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PMID:Transfection of N-methyl-D-aspartate receptors in a nonneuronal cell line leads to cell death. 772 86

The effects of glucocorticoid (GC) on ischemic brain remain to be investigated. Since GC modulates immunological system, it also may inhibit macrophage accumulation in the ischemic brain. The GC effect, if any, on macrophages in ischemic brain, may be mediated through modulation of JE/MCP-1 gene, a strong monocyte attractant, which is expressed in the rat brain after ischemia. The purpose of the present study is to elucidate the effect of high dose methylprednisolone (MP) treatment on (1) macrophage infiltration, (2) histopathology of the ischemic lesion, and (3) expression of JE/MCP-1 mRNA, in a focal cerebral ischemia model of the rat. Thirty Wistar rats were used in this study. Focal cerebral ischemia was induced by advancing a nylon monofilament into the internal carotid artery until the origin of the middle cerebral artery (MCA) was occluded. For JE/MCP-1 mRNA study, animals (n = 9) were randomly injected with MP 75 mg/kg (x 3) (n = 3), 100 mg/kg (x 3) (n = 3), or same volume of saline (n = 3) and killed 24 h after onset of MCA occlusion. Three animals were used as a normal control, and a section of the liver from one rat was used as an internal control for JE/MCP-1 mRNA. Northern blot analysis was performed using murine JE c-DNA. For the histopathological study, animals (n = 17) were randomly divided into a MP group (MP 100 mg/kg x 3, n = 9) and a control group (saline treated, n = 8), and killed 72 h after onset of MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High dose methylprednisolone therapy reduces expression of JE/MCP-1 mRNA and macrophage accumulation in the ischemic rat brain. 772 31

The lung is particularly exposed to various inhaled toxic products whose toxicity can be at least partly mediated by the generation of free radicals. Oxidants burden can also result from lung metabolism of xenobiotics or from activation of phagocytes. Free radicals are mainly derived from an univalent sequential reduction of molecular oxygen. Mitochondria is the main location of intracellular production which may also result from auto-oxidation of small molecules or function of some enzymes. To prevent the deleterious effects of free radicals produced by normal metabolism, cells are equipped with an antioxidant system composed of enzymes (superoxide dismutase, catalase, glutathione peroxidase) and non enzymatic substances such as glutathione, iron chelators, vitamin E and C, ceruleoplsamin). Targets of free radicals toxicity are phospholipids by initiation of lipid peroxidation, proteins which may be activated or inactivated via oxidation of sulfhydryl residues. Another target is DNA with possible strand breaks or mutation. Transcription activities can be also altered and it has been recently reported that some transcription factors such as NF-kB can be activated by oxidants. Under these circumstances free radicals may be considered as second messengers. Lung oxygen toxicity has been largely studied. Oxygen-induced lung lesions are non specific. It is possible to induce a resistance to 100% O2 by the pre-exposure of animals to 85% O2. This tolerance phenomenon is associated with an increased lung content in antioxidant substances. The mechanisms of gene regulation of antioxidant enzymes are still poorly understood in eukaryotes. Overproduction of free radicals in the lung is also involved in various clinical settings such as ischemia-reperfusion, exposure to ozone or NO2, acute respiratory distress syndrome, drug induced lung toxicity, pathogenesis of COPD, asthma, cancer and ageing. The precise role of free radicals among other mechanisms of lung injury is still unclear. A better knowledge of free radicals mechanisms of toxicity and of antioxidant regulation is needed to develop antioxidant therapeutic strategies.
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PMID:[Free radicals and respiratory pathology]. 773 56


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