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)

The influence of timing of FK 506 (Tacrolimus) administration on renal function and recovery from renal warm ischemia was studied in Sprague-Dawley rats. Animals were administered FK 506 and subjected to 60 min of renal warm ischemia by temporary occlusion of the renal artery and vein. No significant differences in serum creatinine levels among rats subjected to renal ischemia, FK 506, or FK 506 vehicle (methanol and 5% dextrose in water) were demonstrated. In contrast, FK 506 administration (4 mg/kg intraperitoneally) in combination with renal warm ischemia resulted in significant deterioration of renal function with peaking of serum creatinine on day 2. The timing of FK 506 administration relative to renal ischemia did not significantly affect serum creatinine levels. Rats that received FK 506 either 24 hr pre-ischemia, 4 hr pre-ischemia, 4 hr post-ischemia, or 24 hr post-ischemia all showed similar serum creatinine levels on day 2 (3.85 +/- 0.9, 4.7 +/- 0.5, 3.8 +/- 0.9, and 5.1 +/- 0.6 mg/dl, respectively, p = NS). In all animals, serum creatinine returned to baseline values by day 10. Histopathologic examination of kidneys revealed tubular atrophy and dilatation with tubular calcifications at the corticomedullary junction in FK 506 treated animals with or without ischemia. Our data suggest the timing of FK 506 administration in rats subjected to renal warm ischemia does not influence the extent of renal injury with an equally deleterious effect seen when administered within a 24 hr period of an ischemic event. Changes in kidney morphology, however, were seen in all FK 506 treated rats, with or without a period of warm ischemia.
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PMID:Influence of the timing of FK 506 (Tacrolimus) administration on recovery of renal function from warm ischemic injury in rats. 753 42

Methanol is an ocular toxicant which causes visual dysfunction often leading to blindness after acute exposure. While the manifestation of the toxicity has been widely studied, the mechanism by which the injury is produced is still uncertain. A major unanswered question pertains to the site of action, i.e. direct retinotoxicity versus primary optic nerve toxicity with secondary retinotoxicity. In the present study, the effect of methanol on the oscillatory potentials (OPs) of the electroretinogram (ERG) were evaluated in acutely treated folate sufficient (FS) and folate reduced (FR) Long-Evans rats. The OP amplitudes of the acutely dosed FR rats displayed non-selective decreases in all OP amplitudes and non-selective increases in all OP latencies at methanol doses ranging from 1.5 to 3.0 g/kg. Comparing decreases of op2 and ERG b-wave amplitudes with blood formate concentration demonstrates that the b-wave is more sensitive than op2 in a blood formate concentration range of 6-14 mM, suggesting that retinal ischemia is not involved in methanol-induced visual system toxicity.
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PMID:Evaluation of methanol-induced retinotoxicity using oscillatory potential analysis. 797 8

We evaluated the ability of alpha-phenyl-tert-butyl nitrone (PBN) to trap free radicals and to protect the rat myocardium during ischemia and reperfusion. Isolated bicarbonate buffer-perfused hearts (n = 8) were subjected to 20 min global ischemia (37 degrees C) followed by reperfusion with 0.4 to 4.0 mM PBN. Coronary effluent containing the PBN adduct was extracted in toluene. Electron spin resonance analysis of the toluene extract revealed a PBN-hydroxyl adduct. To verify this assignment, a Fenton system was used to generate an authentic PBN-hydroxyl adduct (n = 8), which yielded the same ESR spectra as the reperfusion-derived adduct. The structure of the adduct formed in the Fenton system was confirmed by gas chromatography-mass spectrometry. The ESR parameters of the PBN-hydroxyl adduct were exquisitely sensitive to solvent polarity during extraction of the adduct. Extraction of an authentic PBN-hydroxyl adduct into chloroform, chloroform:methanol, and toluene closely matched the ESR parameters obtained during reperfusion of ischemic myocardium in other animal models. To determine whether PBN could confer any protective effect during ischemia or reperfusion, hearts (n = 8/group) were subjected to 35 min global ischemia at 37 degrees C with the St. Thomas' II cardioplegic solution followed by 30 min reperfusion. Percent recovery (mean +/- SEM) of developed pressure, rate pressure product, and leakage of lactate dehydrogenase during reperfusion in control hearts were 58 +/- 3%, 48 +/- 4% and 3.2 +/- 0.5 IU/15 min/g wet wt. PBN at a concentration of 0.4 mM or 4.0 mM when present either during ischemia alone or reperfusion alone did not exert any effect upon recovery of developed pressure, rate pressure product or post-ischemic enzyme leakage. We conclude that PBN fails to improve contractile recovery and reduce enzyme leakage during reperfusion of myocardium subjected to global ischemia.
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PMID:Lack of protection of PBN in isolated heart during ischemia and reperfusion: implications for radical scavenging mechanism. 801 39

Oxygen free radicals have been considered as a cause of ischemia-reperfusion injury in several organs, but this injury in a stomach, containing acid, may progress to severe damage. Thus, we examined the effect of ischemia-reperfusion and milk-intake on rabbit gastric mucosa. The gastric mucosal blood flow was increased after milk-intake, and gastric rupture was detected. Superoxide dismutase activity measured by an improved nitroblue tetrazolium reduction method and thiobarbituric acid reactive substances in serum is increased during ischemia-reperfusion and milk-intake. By using alpha-phenyl N-tert-butyl nitrone (PBN) as a spin trap and electron paramagnetic resonance (EPR), we detected lipidic radicals from tissue samples in chloroform-methanol solvent only during reperfusion and milk-intake period; no signal was detected before. The EPR signal of spin adducts obtained in the sample after ischemia-reperfusion and milk-intake would be a mixture of peroxyl and alkoxyl radicals from the analysis of coupling constants.
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PMID:Radical trapping by PBN during reperfusion in rabbit gastric mucosa. 828 23

We employed hyperosmotic concentrations of penetrating cryoprotective agents (CPA) to store the isolated rat hearts unfrozen at subzero temperatures. The effect of acute exposure to CPA was assessed by flushing the hearts with CP-14, a cardioplegic solution, containing methanol (MeOH), ethanol (EtOH), ethylene glycol (EG), or propylene glycol (PG) for 2 min and reperfusing immediately with Krebs-Henseleit buffer in a working-heart model. The maximal doses that did not cause irreversible suppression of heart function were: MeOH, 1.78 M; EtOH, 1.27 M; EG, 0.84 M; and PG, 0.87 M. For nonfreezing storage, the hearts were flushed with CP-14 containing the highest tolerable concentrations of MeOH, EtOH, EG, or PG, stored for 6 h at -3.7, -2.8, and -1.4 degrees C, respectively, and then reperfused. Control cardiac output (CO) was 76.2 +/- 1.8 ml/min. Post-reperfusional recovery of CO was 86% in MeOH hearts, 82% in EtOH hearts, 76% in EG hearts, and 79% in PG hearts. Thus MeOH offered not only the least cardiac-suppressing effect but the lowest nonfreezing storage temperature. When storage time was extended, recovery and myocardial ATP level decreased with time in hearts flushed with CP-14 + 1.78 M MeOH and stored at -3.7 degrees C. The decay of function was faster than the decay of ATP level, suggesting energy was better preserved than function. The low return of function, however, may be related to CPA toxicity, osmotic stress, and ischemia/reperfusion injury. Nonfreezing storage at subzero temperatures using these CPAs may provide a novel approach to long-term cardiac preservation.
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PMID:Subzero nonfreezing storage of the mammalian cardiac explant. I. Methanol, ethanol, ethylene glycol, and propylene glycol as colligative cryoprotectants. 840 87

Myoglobin and myosin light chain 1 (MLC1) are intracellular human cardiac marker proteins which are released as a consequence of ischemia. Human cardiomyocytes were isolated from fresh biopsies and also maintained for several passages in cell culture. The cardiomyocytes were fixed in 100% methanol at -20 degrees C, and labeled. The immunolocalization of intracellular antigen by fluorescence conjugated imaging was compared with scanning electron microscopy (SEM) backscatter electron (BSE) imaging of gold conjugated antibody. Ultra-violet light microscopy showed the intracellular distribution of both proteins to be mainly in the nuclear envelope, the cytoplasm immediately surrounding the nucleus and along portions of the cell membrane. To confirm this observed distribution of myoglobin and MLC1, labeling was repeated with antimyoglobin and anti-MLC1 monoclonal antibodies conjugated to colloidal gold particles. The advantage of colloidal gold labeling is that the intracellular antigen-antibody complexes may be more precisely located because of the significant improvement in resolution provided by BSE imaging in the SEM. BSE imaging confirmed the presence and subsarcolemma localization of myoglobin in cardiomyocytes directly isolated from fresh biopsies. The distribution of colloidal gold-conjugated antibodies did not coincide with the intracellular distribution of the two proteins in the cardiomyocytes grown in cell culture as indicated by immunofluorescence. A relatively random, intracellular gold particle distribution was confirmed by x-ray microanalysis. BSE imaging resulted in consistent auto-backscatter labeling patterns very similar to the labeling patterns obtained with immunofluorescent labeling. X-ray microanalysis confirmed that these auto-backscatter labeling patterns were formed by concentrations of intracellular phosphate. Sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and subsequent Western blotting indicated that myoglobin and MLC1 were no longer present in detectable quantities in these cells after several passages. Polymerase chain reaction (PCR) amplification of mRNA for human myoglobin and cardiac MLC1 confirmed the absence of their transcripts. Electrophoretic analysis of proteins in cardiomyocytes grown in cell culture confirmed an increasing presence of alkaline phosphatase. Staining of this enzyme with 5-bromo-4-chloro-3-indolyl phosphate and nitroblue tetrazolium showed that alkaline phosphatase was distributed in the same intracellular pattern as the fluorescence conjugated anti-body and the phosphatase auto-backscatter. These results indicate that high-resolution backscatter SEM imaging may be used as necessary control to confirm fluorescence light microscope intracellular labeling of antigens.
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PMID:Advantages of backscatter electron imaging scanning electron microscopy for intracellular localization of cardiac analytes by gold conjugated antibody. 865 28

Postnatal rats at 7 and 21 days of age were subjected to unilateral hypoxia-ischemia (H/I) by right carotid artery ligation followed by 1.5 to 2 hours of hypoxia (8% oxygen). Brains were frozen at specific intervals of recovery from 0 to 24 hours. Western blots of samples of right and left forebrain were immunodeveloped with a monoclonal antibody specific for ubiquitin, RHUb1. An elevation of ubiquitin conjugate levels in the right compared with the left forebrain of 7-day-old animals was detectable immediately following H/I and increased by close to 60% of control level within 1 hour of recovery. The conjugate immunoreactivity remained at this level for 6 hours but had declined to control levels by 24 hours of recovery. No such increase was observed in response to hypoxia alone. Similar changes were observed in samples from the 21-day-old rat brain. However, the elevation of ubiquitin conjugate levels was of slower onset and persisted longer than observed for the 7-day-old animals. Immunocytochemical studies of brain fixed by immersion in formaldehyde/acetone/methanol showed that ubiquitin-like immunoreactivity was increased in the right, but not left, cerebral cortex and hippocampus of animals subjected to H/I. The data suggest that elevated ubiquitination may represent a neuroprotective response to H/I.
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PMID:Hypoxia-ischemia induces a rapid elevation of ubiquitin conjugate levels and ubiquitin immunoreactivity in the immature rat brain. 953 2

Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy has been used to study accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia. Lipids were extracted from rat brain homogenates and the extracts were thoroughly washed with aq. potassium ethylenediaminetetraacetic acid (EDTA). The lower organic phases were isolated and evaporated to dryness under a stream of nitrogen and the lipids were redissolved in CDCl3-CH3OH-H2O 100.0:29.9:5.2 (v/v/v) for NMR analysis. Increasing the period of post-decapitative ischemia resulted in an accumulation of two signals in the NMR spectra at 0.18 and 0.22 ppm (relative to the chemical shift of 1,2-diacyl-sn-glycero-3-phosphocholine (PCDIACYL) at -0.84 ppm). These signals were identified as originating from 1,2-diacyl-sn-glycero-3-phospho-(N-acyl)-ethanolamine (NAPEDIACYL) and 1-(1'-alkenyl)-2-acyl-sn -glycero-3-phospho-(N-acyl)-ethanolamine (NAPEPLAS), respectively, by spiking with authentic materials. Additionally, the identification was verified by thin-layer chromatography, which also showed the accumulation of N-acyl-ethanolamine phospholipids. The use of K-EDTA instead of the commonly used Cs-EDTA in the preparation of the NMR samples allowed the separation of the chemical shifts of N-acyl-ethanolamine phospholipids from those of the ethanolamine phospholipids. Moreover, the chemical shift of cardiolipin was moved from 0.15 ppm observed with Cs-EDTA to about 0.31 ppm with K-EDTA. The present study demonstrates that it is possible to detect and quantify post-decapitative accumulation of NAPE subclasses (NAPEDIACYL and NAPEPLAS) in rat brains by the use of 31P NMR spectroscopy.
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PMID:Accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia: a 31p NMR study. 1006 40

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.
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PMID:Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia. 1153 62

In traditional Oriental medicine, Uncaria rhynchophylla has been used to lower blood pressure and to relieve various neurological symptoms. However, scientific evidence related to its effectiveness or precise modes of action has not been available. Thus, in the current study, we evaluated neuroprotective effects of U. rhynchophylla after transient global ischemia using 4-vessel occlusion model in rats. Methanol extract of U. rhynchophylla administered intraperitoneally (100-1000 mg/kg at 0 and 90 min after reperfusion) significantly protected hippocampal CA1 neurons against 10 min transient forebrain ischemia. Measurement of neuronal cell density in CA1 region at 7 days after ischemia by Nissl staining revealed more than 70% protection in U. rhynchophylla-treated rats compared to saline-treated animals. In U. rhynchophylla-treated animals, induction of cyclooxygenase-2 in hippocampus at 24 hr after ischemia was significantly inhibited at both mRNA and protein levels. Furthermore, U. rhynchophylla extract inhibited TNF-alpha and nitric oxide production in BV-2 mouse microglial cells in vitro. These anti-inflammatory actions of U. rhynchophylla extract may contribute to its neuroprotective effects.
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PMID:Neuroprotection by methanol extract of Uncaria rhynchophylla against global cerebral ischemia in rats. 1217 11


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