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)

Patients with acute coronary syndromes who are considered ineligible for thrombolytic therapy are at high risk of recurrent ischemia and death. This trial randomized 201 patients to triage angiography in the first 24 hours of hospital admission versus conventional medical care. Of the 165 patients who underwent angiography that was either protocol-driven or on the basis of physician preference, those who underwent angiography within 6 hours of symptom onset had a reduction in early and late adverse events. The rates of in-hospital recurrent ischemia were 15.4%, 15.4%, 17.5%, 32.4%, and 38.5%, respectively (P = 0.01 for trend), and rates of cumulative recurrent myocardial infarction or death were 0%, 12.8%, 10.0%, 11.8%, and 7.7%, respectively (P = 0.48 for trend) for patients who underwent angiography at 0-6, 6-12, 12-24, 24-48, and over 48 hours, respectively from symptom onset. Future trials of invasive versus conservative therapy should focus on performing angiography within 6 hours of symptom onset.
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PMID:A time-to-treatment analysis in the medicine versus angiography in thrombolytic exclusion (MATE) trial. 1205 95

The definitive closure of the abdominal wall, i.e., a closure of the fascial layer and skin may not be favorable in the treatment of numerous surgical conditions, e.g., peritonitis, trauma, or mesenteric ischemia. In these cases, the abdominal wall is temporarily closed, and a laparostomy is created to facilitate re-exploration or to prevent abdominal compartment syndrome. Regarding the technique and material used for the temporary closure, no prospective randomized data exists, but mesh materials are commonly used. They provide drainage of infectious material, permit visual control of the underlying viscera, facilitate access to the abdominal wall, preserve the fascial margin, enable healing by secondary intention, and allow mobilization of the patient. In the case of decreasing intra-abdominal pressure, meshes can be trimmed to centralize the rectus muscle and to facilitate definitive closure. Non-absorbable meshes have been frequently reported to cause enteric fistulae and persistent infection necessitating mesh explantation. While these infectious complications appear to occur less frequently with the use of absorbable materials, these meshes will finally lead to an incisional hernia, requiring repair with non-absorbable mesh after a period of 6-12 months. Nevertheless, in the complex situation requiring a temporary abdominal wall closure, use of absorbable mesh material is common and represents the state of the art.
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PMID:Temporary closure of the abdominal wall (laparostomy). 1268 24

BACKGROUND: Heparin has been shown to reduce intimal thickening after arterial wall injury by inhibiting vascular smooth muscle cell proliferation and migration. The authors studied the acute and long-term results after local delivery of heparin after balloon angioplasty for in-stent restenosis. METHODS AND RESULTS: Forty-seven in-stent restenosis cases, 32 of them longer than 1 cm, were enrolled. After angioplasty local heparin delivery was performed using the Dispatch coronary infusion catheter (Scimed Life Systems/Boston Scientific Corp, Natick, MA, USA); the infusion rate was 99.9 ml per hour and a target dosage of 4000 iu heparin per site was intended to be delivered. In nine cases (19.15%) heparin delivery had to be stopped because of ischemia. One patient died six days after intervention. After a follow-up interval of 6-12 months target vessel revascularization rate was 28.26%. CONCLUSIONS: For the protocol used ischemia occurred more often than previously reported. Considering the fact that most patients had diffuse in-stent restenosis, the target revascularization rate at follow-up was acceptable.
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PMID:Local heparin delivery for prevention of second in-stent restenosis. Acute and long-term results in 47 consecutive cases. 1247 Mar 69

Rodent models of focal and global ischemia were used to examine caspase activation. Several readouts were employed on identical tissue to provide correlative measurement of caspase induction, activation and enzymatic activity. In a rat focal ischemia model, caspase-3 enzymatic activity, as recorded by DEVD-AMC cleavage, peaked in penumbral cortex at 6-12 h following ischemia, correlating with increases in caspase 3-cleaved substrates of PARP and alpha-spectrin and subsequent disappearance of caspase-3 zymogen. Although induction of caspases 8 and 2 proteins was detectable as early as 6 h following ischemia, examination of the same tissues for caspase 8 or 2 enzymatic activities did not show significant modulation up to 12 h after ischemic insult. Caspase 9 induction was evident only after 24 h postischemia and did not correlate with elevated LDHD-AMC cleavage. Following global ischemia in gerbils, levels of caspase-3 enzyme activity peaked at 12 h in hippocampal tissue extracts. Cleaved caspase-3 signal was prominent in NeuN-positive layers in the CA1 region 6-12 h following ischemia. Interestingly, strong caspase-3 immunoreactivity was also detected in the subgranular zone of the dentate gyrus, a known region of ischemia-induced neurogenesis. Caspase-3 activation may be responsible for the loss of these cells, thereby hindering the endogenous recovery process.
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PMID:Temporal assessment of caspase activation in experimental models of focal and global ischemia. 1291 50

In this study, we examined transient ischemia-induced changes in transcription factor E2F1 and c-myb expressions in the gerbil hippocampus after 5 min of transient forebrain ischemia. E2F1 immunoreactivity significantly increased in the CA1 region 6-12 h after ischemia/reperfusion. c-myb immunoreactivity increased mainly in CA1 pyramidal cells with time by 12 h after ischemia. Thereafter, E2F1 and c-myb immunoreactivities significantly decreased compared to those in the 12 h post-ischemic group. Four days after ischemia/reperfusion, E2F1 and c-myb immunoreactivities were detected in non-pyramidal cells. Ten days after ischemia, c-myb immunoreactivity increased again: at this time, astrocytes as well as non-pyramidal cells showed E2F1 and c-myb immunoreactivities. In the CA2/3 region, E2F1 and c-myb immunoreactivities mainly changed in non-pyramidal cells, and 10 days after ischemia, c-myb immunoreactivity was not expressed in astrocytes. In conclusion, E2F1 and c-myb significantly alter in pyramidal cells and express in astrocytes in the gerbil hippocampal CA1 region after transient ischemia. These results indicate that E2F1 and c-myb in the CA1 region after ischemic damage may be associated with delayed neuronal death.
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PMID:The pattern of E2F1 and c-myb immunoreactivities in the CA1 region is different from those in the CA2/3 region of the gerbil hippocampus induced by transient ischemia. 1678 30

Acidification, which occurs in some pathological conditions, such as ischemia and hypoxia often induces neurotoxicity. The activation of acid-sensing ion channels (ASICs), which are highly permeable to calcium, has been considered the main target responsible for calcium overload in ischemic/hypoxic brain. However, the influence of extracellular proton on GABAergic synaptic transmission is not well understood. In the rat (aged 6-12 postnatal days) hippocampal CA3 neurons dissociated with an enzyme-free, mechanical method, we show that raising the extracellular pH (to 8.5) or lowering it (to 6.0) significantly increased or decreased, respectively, the frequency and the amplitude of spontaneous inhibitory postsynaptic currents mediated by gamma-aminobutyric acid A (GABA(A)) receptors. Interestingly, these modifications were not altered by amiloride (100 microM, an antagonist for ASICs), tetrodotoxin (0.5 microM, a sodium channel blocker), cadmium (100 microM, a nonselective blocker for voltage-gated calcium channels), or a medium containing low calcium (0.5 mM). Significantly, changes in extracellular pH biphasically altered the peak amplitude of the currents elicited by exogenous GABA in CA3 neurons dissociated with enzyme. Raising the extracellular pH (to 8.5) or lowering (to 6.5) shifted the concentration-response curves of GABA to the left or right, respectively, without altering the maximal responses. These data suggest that proton alters the apparent affinity of GABA receptors for agonist. Thus, extracellular proton modifies GABAergic synaptic transmission both presynaptically and postsynaptically, and this could be independent of ASICs and voltage-gated calcium channels. Our finding may constitute a new mechanism underlying acidification-induced neurotoxicity.
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PMID:Extracellular proton modulates GABAergic synaptic transmission in rat hippocampal CA3 neurons. 1732 6

Inflammatory processes are a major cause of hypoxic-ischemic brain damage. The present study focuses on both the cerebral histamine system and mast cells in a model of transient focal ischemia induced by permanent left middle cerebral artery, and homolateral transient common carotid artery occlusion (50 minutes) in the P7 newborn rat. Immunohistochemical analysis revealed that ischemia induces histamine (HA) accumulation in the core of the infarct 6-12 h post-ischemia, and in the penumbra at 24-48 h, although in situ hybridization failed to detect any histidine decarboxylase gene transcripts in these regions. Immunohistochemical co-localization of HA with the MAP2 marker revealed that HA accumulates in neuronal cells before they degenerate, and is accompanied by a very significant increase in the number of mast cells at 12 h and 48 h of reperfusion. In mast cells, histamine immunoreactivity is detected at 2, 6 and 12 h after ischemia, whereas it disappears at 24 h, when a concomitant degranulation of mast cells is observed. Taken together, these data suggest that the recruitment of cerebral mast cells releasing histamine may contribute to ischemia-induced neuronal death in the immature brain.
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PMID:Stroke induces histamine accumulation and mast cell degranulation in the neonatal rat brain. 1792 84

Ischemic brain injury is one of the leading causes of epilepsy in the elderly, and there are currently no adult rodent models of global ischemia, unilateral hemispheric ischemia, or focal ischemia that report the occurrence of spontaneous motor seizures following ischemic brain injury. The rodent hypoxic-ischemic (H-I) model of brain injury in adult rats is a model of unilateral hemispheric ischemic injury. Recent studies have shown that an H-I injury in perinatal rats causes hippocampal mossy fiber sprouting and epilepsy. These experiments aimed to test the hypothesis that a unilateral H-I injury leading to severe neuronal loss in young-adult rats also causes mossy fiber sprouting and spontaneous motor seizures many months after the injury, and that the mossy fiber sprouting induced by the H-I injury forms new functional recurrent excitatory synapses. The right common carotid artery of 30-day old rats was permanently ligated, and the rats were placed into a chamber with 8% oxygen for 30 min. A quantitative stereologic analysis revealed that the ipsilateral hippocampus had significant hilar and CA1 pyramidal neuronal loss compared with the contralateral and sham-control hippocampi. The septal region from the ipsilateral and contralateral hippocampus had small but significantly increased amounts of Timm staining in the inner molecular layer compared with the sham-control hippocampi. Three of 20 lesioned animals (15%) were observed to have at least one spontaneous motor seizure 6-12 months after treatment. Approximately 50% of the ipsilateral and contralateral hippocampal slices displayed abnormal electrophysiological responses in the dentate gyrus, manifest as all-or-none bursts to hilar stimulation. This study suggests that H-I injury is associated with synaptic reorganization in the lesioned region of the hippocampus, and that new recurrent excitatory circuits can predispose the hippocampus to abnormal electrophysiological activity and spontaneous motor seizures.
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PMID:A chronic histopathological and electrophysiological analysis of a rodent hypoxic-ischemic brain injury model and its use as a model of epilepsy. 1793 93

Neonatal hypoxia-ischemia (HI) induces immediate early gene (IEG) c-fos expression as well as neuron death. The precise role of IEGs in neonatal HI is unclear. We investigated the temporal and spatial patterns of c-Fos expression in postnatal day 7 mice after unilateral carotid ligation and exposure to 8% oxygen. mRNA levels of c-fos quantitated by real-time polymerase chain reaction (PCR) increased nearly 40-fold (log 1.2 +/- 0.4) in the ipsilateral hippocampus 3 hr following neonatal HI, then returned to basal levels within 12 hr, although no change was observed in c-jun mRNA. Frozen coronal brain sections were stained with cresyl violet or used for immunohistochemical detection of c-Fos, cleaved caspase-3, glial fibrillary acidic protein (GFAP), and the mature neuron marker NeuN. c-Fos immunoreactivity increased throughout the injured hippocampus 3 hr after HI but became restricted to the CA2-3 subregion and the dentate gyrus (DG) at 6-12 hr and declined by 24 hr. In contrast, cleaved (activated) caspase-3 immunoreactivity was most abundant in the ipsilateral CA1 region at 3-6 hr after neonatal HI, then became more prominent in CA2-3 and DG. Double-labeling experiments showed c-Fos and cleaved caspase-3 immunoreactivity localized in spatially distinct neuron subpopulations. Prominent c-Fos immunoreactivity was observed in surviving CA2-3 and external granular DG neurons, and robust cleaved caspase-3 immunoreactivity was observed in pyknotic CA1, CA2-3, and subgranular DG neurons. The differential expression of c-Fos in HI-resistant hippocampal subpopulations vs. cleaved caspase-3 in dying neurons suggests a neuroprotective role for c-Fos expression in neonatal HI.
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PMID:Differential activation of c-fos and caspase-3 in hippocampal neuron subpopulations following neonatal hypoxia-ischemia. 1803 Jun 77

Recent evidence indicates that inhibition of the Na+/H+ exchanger improves heart and brain injuries induced by I/R. Studies were performed to investigate whether FR183998, a Na/H exchanger inhibitor, has protective effects on hepatic I/R injury in rats. Male Sprague-Dawley rats were subjected to 70% hepatic ischemia by occluding the hepatic artery, portal vein, and bile duct associated with the left and median liver lobes with a microvascular clip for 2 h. FR183998 (1 mg/kg) was administered i.v. 10 min before the hepatic ischemia. Hepatic I/R increased the serum levels of aspartate transaminase, alanine transaminase, and lactate dehydrogenase, which peaked at 9 h after reperfusion. FR183998 reduced these injury markers and recovered liver functions. Histopathologic analysis revealed that FR183998 prevented the incidences of hepatic necrosis, apoptosis, and neutrophil infiltration at 6 and 9 h (P < 0.05). FR183998 reduced the increases in proinflammatory cytokines such as TNF-alpha (1-6 h), IL-6 (1-12 h), interferon-gamma (6-12 h), IL-1beta (1-3 h), and cytokine-induced neutrophil chemoattractant 1 (1-3 h), but enhanced the anti-inflammatory cytokine IL-10 (1 h). FR183998 inhibited the hepatic I/R-induced activation of the transcription factor nuclear factor-kappaB at 1 to 6 h and reduced the induction of iNOS at 6 to 12 h, followed by inhibition of nitric oxide production. Furthermore, FR183998 decreased the expression of the iNOS gene antisense transcript, which is involved in the stability of iNOS messenger RNA, at 9 to 12 h in the liver of hepatic I/R rats. These results demonstrate that FR183998 reduces the induction of proinflammatory cytokines and iNOS at least in part through inhibition of nuclear factor-kappaB activation and iNOS antisense transcript expression, thereby preventing hepatic I/R injury.
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PMID:Protective effect of FR183998, a Na+/H+ exchanger inhibitor, and its inhibition of iNOS induction in hepatic ischemia-reperfusion injury in rats. 1827 53


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