UMLS:C0022116 - FACTA Search

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

Indomethacin-sensitive mechanisms involved in inducible heat shock protein 70 (iHSP 70) synthesis were investigated at 6 h after global cerebral ischemia in parietal cortex and hippocampus. In anesthetized piglets, increased intracranial pressure was used to produce 5 or 10 min of cerebral ischemia. Brain regions were sampled for immunoblot analysis, immunohistochemistry and morphology. Immunoblots revealed differential expression of iHSP 70 in untreated brains. Cerebellum contained substantial amounts of iHSP 70 while lower levels were present in parietal cortex and hippocampus. Detectable increases in iHSP 70 were observed at 2 h after ischemia in parietal cortex and hippocampus. Using immunoblot data, calculation of percent change from control at 6 h after ischemia revealed significant (p<0.05) increases in iHSP 70 of 111±39% (&xmacr;±sem) (n=6) in parietal cortex and 195±69% (n=8) in hippocampus. Increased iHSP 70 immunoreactivity occurred primarily in the granular/subgranular area of the dentate gyrus 6 h after ischemia. Histological staining revealed little cellular injury at 6 h after ischemia in the granular/subgranular region injury whereas the CA3 region, which lacked iHSP 70 staining, displayed modest cellular injury. Cellular injury was also observed in cortical layers II/III and VI. At 6 h after ischemia, indomethacin pretreatment (5 mg/kg, i.v.) attenuated the iHSP 70 increases in parietal cortex and hippocampus (7±30% and 89±30%, respectively n=5; p<0.05 compared to ischemia). Also, the increase in iHSP 70 immunoreactivity and appearance of cellular injury were not detected with indomethacin pretreatment. Thus, prior administration of indomethacin is associated with attenuation of ischemia-induced increases in iHSP 70 and cellular injury.
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PMID:Indomethacin attenuates early increases in inducible heat shock protein 70 after cerebral ischemia/reperfusion in piglets 947 26

Indomethacin-sensitive mechanisms involved in inducible heat shock protein 70 (iHSP 70) synthesis were investigated at 6 h after global cerebral ischemia in parietal cortex and hippocampus. In anesthetized piglets, increased intracranial pressure was used to produce 5 or 10 min of cerebral ischemia. Brain regions were sampled for immunoblot analysis, immunohistochemistry and morphology. Immunoblots revealed differential expression of iHSP 70 in untreated brains. Cerebellum contained substantial amounts of iHSP 70 while lower levels were present in parietal cortex and hippocampus. Detectable increases in iHSP 70 were observed at 2 h after ischemia in parietal cortex and hippocampus. Using immunoblot data, calculation of percent change from control at 6 h after ischemia revealed significant (p < 0.05) increases in iHSP 70 of 111 +/- 39% (x +/- sem) (n = 6) in parietal cortex and 195 +/- 69% (n = 8) in hippocampus. Increased iHSP 70 immunoreactivity occurred primarily in the granular/subgranular area of the dentate gyrus 6 h after ischemia. Histological staining revealed little cellular injury at 6 h after ischemia in the granular/subgranular region injury whereas the CA3 region, which lacked iHSP 70 staining, displayed modest cellular injury. Cellular injury was also observed in cortical layers II/III and VI. At 6 h after ischemia, indomethacin pretreatment (5 mg/kg, i.v.) attenuated the iHSP 70 increases in parietal cortex and hippocampus (7 +/- 30% and 89 +/- 30%, respectively n = 5; p < 0.05 compared to ischemia). Also, the increase in iHSP 70 immunoreactivity and appearance of cellular injury were not detected with indomethacin pretreatment. Thus, prior administration of indomethacin is associated with attenuation of ischemia-induced increases in iHSP 70 and cellular injury.
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PMID:Indomethacin attenuates early increases in inducible heat shock protein 70 after cerebral ischemia/reperfusion in piglets. 949 86

We examined effects of ischemia and asphyxia on levels of prostaglandin H synthase-1 (PGHS-1) and prostaglandin H synthase-2 (PGHS-2) in piglet brain. Ischemia was induced by increasing intracranial pressure and asphyxia was induced by turning off the respirator. Duration of anoxic stress was 10 min. In some animals, indomethacin (5 mg/kg, i.v.) or 7-nitroindazole (7-NI) was administered prior to ischemia to block PGHS or brain nitric oxide synthase (bNOS), respectively. Tissues from cerebral cortex and hippocampus were removed and fixed and/or frozen after 1, 2, 4 and 8 h of recovery from anoxic stress. In addition, tissues were obtained from untreated animals or from time control animals. Levels of mRNA and proteins were determined using RNase protection assay and immunohistochemical approaches, respectively. In the tissues studied, only a few neurons were immunopositive for PGHS-1, and neither ischemia or asphyxia affected PGHS-1 immunostaining at 8 h after recovery. Likewise, PGHS-1 mRNA did not increase following anoxic stress. In contrast, substantial PGHS-2 immunoreactivity was present in neurons and glial cells in the cerebral cortex and hippocampus and there was no difference between time control and non treated animals. PGHS-2 mRNA increased by 2-4 h after ischemia, and heightened immunoreactivity for PGHS-2 was present at 8 h after ischemia in cerebral cortex and hippocampus. However, asphyxia did not increase PGHS-2 mRNA or immunostaining. Indomethacin pretreatment inhibited increases in mRNA and protein for PGHS-2 after ischemia, while 7-NI had little effect on increases in PGHS-2 immunoreactivity. We conclude that: (1) PGHS-2 is the predominant isoform present in piglet cerebral cortex and hippocampus; (2) Ischemia but not asphyxia increases levels of PGHS-2; (3) Ischemia does not increase levels of PGHS-1; and (4) Indomethacin but not 7-NI attenuates ischemia-induced increases in PGHS-2.
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PMID:Effects of anoxic stress on prostaglandin H synthase isoforms in piglet brain. 959 32

Recent studies have shown a close association between reactive oxygen species and DNA fragmentation and that delayed neuronal death after transient forebrain ischemia manifests as DNA fragmentation-like apoptosis. We examined the effect of indomethacin on ischemic-induced delayed hippocampal neuronal death in gerbils using the TUNEL staining method, since indomethacin is neuroprotective in a variety of degenerative processes, such as Alzheimer's disease. Indomethacin (5 mg/kg, i.p.), administered 5 min before the ischemic insult, significantly decreased the number of TUNEL-positive hippocampal CA1 pyramidal neurons and delayed the appearance of TUNEL-positive neurons. Our results indicate that indomethacin is effective in inhibiting DNA fragmentation after transient forebrain ischemia.
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PMID:Indomethacin inhibits delayed DNA fragmentation of hippocampal CA1 pyramidal neurons after transient forebrain ischemia in gerbils. 959 92

Angiotensin-converting enzyme (ACE) inhibitors increase the production of nitric oxide (NO) and prostacyclin and open Ca2+-activated K+ channels. The effects of these actions of ACE inhibitors on infarct size were investigated in open-chest dogs subjected to myocardial ischemia and reperfusion. Infarct size was assessed 6 hours after the onset of reperfusion, subsequent to 90 minutes of occlusion of the left anterior descending coronary artery. The ACE inhibitor cilazaprilat was administered into the coronary artery 10 minutes before coronary occlusion, and infusion was continued until 1 hour after reperfusion. The bradykinin and NO concentrations in coronary venous blood 10 minutes after the onset of reperfusion were significantly higher in dogs treated with cilazaprilat (3 microg x kg(-1) x min(-1)) than in control animals. Although there were no significant differences in collateral flow during ischemia, infarct size in the cilazaprilat group was smaller than that in the control group (15.1+/-3.0% versus 46.7+/-4.2% of the area at risk, P<0.0001). The infarct size-limiting effect of cilazaprilat was partially reduced by either N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) or iberiotoxin (a blocker of Ca2+-activated K+ channels) and was abolished by N(G)-nitro-L-arginine methyl ester plus iberiotoxin. Indomethacin (an inhibitor of cyclooxygenase) had no effect on the beneficial action of cilazaprilat. Inhibition of ACE thus reduced myocardial infarct size, an effect that was mediated by NO and the opening of Ca2+-activated K+ channels in canine hearts.
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PMID:Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition against ischemic myocardial injury. 962 44

We have shown that isolated blood-perfused heat-stressed hearts are protected only when the blood donor animal has not been exposed to hyperthermia. Systematic hyperthermia results in larger infarction of both isolated control and heat-stressed hearts. In this study we investigated whether indomethacin inhibits in vivo the detrimental effect of hyperthermia. Male rabbits were divided into four groups, that is A(30), B(30), C(30), and D(30), representing hearts that ultimately received 30 minutes of ischemia. In a second series, rabbits were divided into groups A(45), B(45), (C45), and D(45) representing hearts that ultimately received 45 minutes of ischemia, and in a third series were divided into groups A(HSP), B(HSP), C(HSP), and D(HSP) representing animals that were heat shocked and their hearts were used to measure heat shock proteins. All the A groups (heat shocked) were subjected to 42 degrees C hyperthermia, all the B groups to the same procedure but with the addition of indomethacin (heat shocked + indomethacin), all the C groups served as controls, and all the D groups were treated with indomethacin only (control + indomethacin). Twenty-four hours later, all (30) and (45) groups were subjected to ischemia, whereas hearts from all (HSP) groups were harvested for heat shock protein measurements. When the animals were exposed to 30-minute ischemia, a significant difference in the infarcted to risk zone ratio (%I/R) was observed: A(30): 33.0 +/- 5.2, B(30): 16.1 +/- 4.4 [conferring a 51.2% reduction in infarct size, P < 0.05], C(30): 48.9 +/- 4.0, and D(30): 47.8 +/- 3.8 [P < 0.001 vs. B (30) and P < 0.05 vs. A(30)]. However, the %I/R did not differ among any of the (45) groups. Heat shock proteins themselves were seen to increase in A(HSP) and B(HSP) groups. Indomethacin enhances the beneficial effect of heat shock after 30-minute ischemia in vivo, reducing the infarct size by 51.2% in comparison with heat shock.
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PMID:Enhanced protection of heat shock in myocardial infarction: inhibition of detrimental effect of systemic hyperthermia. 1043 85

Hyperglycemia worsens ischemic-induced neuronal damage. Many reports argue the delayed neuronal cell death (DND) after forebrain ischemia in gerbils is due to apoptosis. We examined the effects of hyperglycemia and indomethacin on DND after forebrain ischemia in gerbils. Complete occlusion of both common carotid arteries was performed for 3.5 min followed by declamping and reperfusion. Blood glucose levels were maintained at 25-30 mmol/1 for 24 h after reperfusion in the hyperglycemic groups. We examined morphological changes consistent with DND using Nissel-stained sections and DNA fragmentation using TUNEL staining, at 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 h, and 7 days after reperfusion. DND was noted 96-120 h after ischemia in normoglycemic group. Hyperglycemia enhanced the development of DND at an earlier stage (48-84 h after ischemia). TUNEL positive neurons were detected 72-108 h after reperfusion in normoglycemic group, but very few TUNEL positive neurons were detected in hyperglycemic group at 36-48 h. Indomethacin reduced the number of TUNEL-positive cells in normoglycemia and completely inhibited the appearance of TUNEL-positive cells under hyperglycemia. The number of viable neurons at 7 days after ischemia was markedly higher in indomethacin-treated groups than vehicle-treated group. Our results indicate that hyperglycemia worsens DND after forebrain ischemia in gerbils but such process is not associated with DNA fragmentation. Our results also showed that indomethacin provides a neuroprotective effect in normo- and hyperglycemic conditions.
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PMID:Delayed neuronal death in hippocampal CA1 pyramidal neurons after forebrain ischemia in hyperglycemic gerbils: amelioration by indomethacin. 1062 12

Anoxic stress attenuates NMDA-induced pial arteriolar dilation via a mechanism involving actions of cyclooxygenase (COX)-derived reactive oxygen species (ROS). We examined whether the selective COX-2 inhibitor NS398 would protect neuronal function after global hypoxia/ischemia (H/I) in piglets. Pial arteriolar responses to NMDA (10-100 micromol/l) were determined using intravital microscopy in anesthetized piglets before and 1 h after H/I. Study groups received vehicle, 0.3, 1, or 5 mg/kg NS398, or 0.3 mg/kg indomethacin (n = 7, 6, 6, 5 and 8, respectively) i.v. 20 min prior to H/I. H/I reduced NMDA- induced dilation to 44 +/- 6% (100 micromol/l NMDA, mean +/- s.e.m.) of the pre-ischemic response in vehicle animals (p < 0.05). However, NS398 dose-dependently protected arteriolar dilation to NMDA (77 +/- 8, 81 +/- 16, and 102 +/- 10% preservation at 0.3, 1 and 5 mg/kg, respectively). Indomethacin caused similar preservation. However, indomethacin but not NS398 reduced serum thromboxane B(2) levels to undetectable values. In conclusion, COX-2 appears to be a major source of ROS in the piglet cerebral cortex after H/I.
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PMID:Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets. 1174 39

We investigated antioxidative activity and the effect of indomethacin, an agent that inhibits cyclooxygenase, on extracellular glutamate and cerebral blood flow in cerebral ischemia in gerbils. Pre-ischemic administration of indomethacin (5 mg/kg, i.p.) significantly rescued hippocampal CA1 neurons (9+/-6 cells/mm in the ischemia, 87+/-43 cells/mm in the indomethacin group, P<0.001). DNA fragmentation induced by ischemia was also examined using the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) method and indomethacin reduced TUNEL positive cells (140+/-21 in the ischemia, 99+/-31 in the indomethacin group, P<0.01). In addition, indomethacin attenuated the increase in hippocampal blood flow during reperfusion, but not increased extracellular glutamate by ischemia. Eight-hydroxydeoxyguanosine (8-OH-dG), a highly sensitive marker of DNA oxidation, was measured 90 min following ischemia using high-pressure liquid chromatography. Indomethacin significantly decreased the level of ischemia-induced 8-OH-dG in the hippocampus (P<0.05). These results suggest that indomethacin may protect neurons by attenuating oxidative stress and reperfusion injury in ischemic insult.
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PMID:Suppression of hyperemia and DNA oxidation by indomethacin in cerebral ischemia. 1252 44

Oxygen radicals are formed by the endothelium and blood cells and have specific functions in various organs systems. On the level of the microcirculation, oxygen radicals take part in the regulation of the leukocyte-endothelial interaction. The involvement of oxygen radicals has previously been found in conditions such as sepsis, ischemia-reperfusion, and inflammation. Indomethacin is a clinically applied nonsteroidal antiphlogistic, and in previous studies in the rat, it has been found to induce an inflammatory reaction in the small intestine characterized by edema and reddening of the intestinal epithelium, ulceration, and dysregulation in the intestinal-epithelial barrier function. In the present study, we investigated the effect of N-acetylcysteine on erythrocyte velocity and the arteriolar diameter of the main arteriole in single villi, thus providing insight in the perfusion of the mucosa in indomethacin-induced intestinal inflammation. N-Acetylcysteine is known to inactivate superoxide and its precursors. Therefore, we used N-acetylcysteine to investigate whether superoxide and its precursors participate in the regulation of blood supply to single villi in this animal model. We found that indomethacin induced an increase in villous perfusion that was significantly reduced by N-acetylcysteine, indicating that superoxide and its precursors may participate in the regulation of blood supply to the mucosa in this animal model of intestinal inflammation.
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PMID:Effect of N-acetylcysteine on microcirculation of mucosa in rat ileum in a model of intestinal inflammation. 1277 84

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