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

During their life span, leukocytes adhere transiently to one another, to other cell types, such as vascular endothelial cells, and to extracellular matrix proteins. This adhesiveness is mediated by families of specific cell surface adhesion molecules, namely, integrins, immunoglobulin superfamily molecules, and selectins. Adhesion is required for leukocyte-mediated cytotoxicity, phagocytosis, chemotaxis, and induction of lymphocyte proliferation and maturation. It also participates in recirculation and homing of lymphocytes into lymphoid organs and in leukocyte migration from the vascular compartment to extravascular tissues. Adhesion underlies the beneficial or detrimental role of leukocytes in immune and inflammatory responses. In animals, blocking monoclonal antibodies to adhesion molecules dramatically reduce vascular and tissue injury in several organs following ischemia-reperfusion, and delay renal allograft rejection. Moreover, expression of particular adhesion molecules is induced or increased in cells which are targets for allergic or autoimmune reactions and in inflamed tissues. On the other hand, a congenital deficiency of the CD11/CD18 integrins (Leu-CAMs) leads to recurrent, and sometimes fatal, bacterial infections, and lack of particular cell-adhesion molecules on Burkitt's lymphoma cells may enable these cells to escape immunosurveillance.
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PMID:Leukocyte adhesion in host defense and tissue injury. 183 Aug 30

The purpose of this study was to determine the effect of normoxic reperfusion and graded postischemic reoxygenation on cerebral protein synthesis in a cell-free system. Ischemia alone produced a relatively small decrease (15-17%) in activity in all the subcellular systems studied. After a 15-min interval of normoxic reperfusion (75-90 mmHg O2 in arterial blood), a 40% decrease (p less than 0.01) in [14C]leucine incorporation was observed. Reoxygenation with hypoxemic blood containing 37.5 mm Hg O2 at 0-5 min and 56 mm Hg O2 at 6-10 min of recirculation followed by 5 min of normoxic reperfusion resulted in a significant increase (p less than 0.05) of polypeptide chain synthesis in vitro when compared with normoxic reperfusion. The results obtained by this experimental approach tend to show that graded postischemic reoxygenation could be used as a simple and effective neuroprotective tool that substantially diminishes the secondary postischemic damage in nervous tissue, including the newly synthesized proteins.
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PMID:Graded postischemic reoxygenation ameliorates inhibition of cerebral cortical protein synthesis in dogs. 193 77

Excitatory amino acids have been implicated in the production of calcium mediated neuronal death following central nervous system ischemia. We have used microdialysis to investigate changes in the extracellular concentrations of amino acids in the spinal cord after aortic occlusion in the rabbit. Glutamate, aspartate, glutamine, asparagine, glycine, taurine, valine, and leucine were measured in the microdialysis perfusate by high pressure liquid chromatography. The concentrations of glutamate, glycine, and taurine were significantly higher during ischemia and reperfusion than controls. Delayed elevations in the concentrations of asparagine and valine were also detected. The elevation of glutamate is consistent with the hypothesis that excitotoxins may mediate neuronal damage in the ischemic spinal cord. Increased extracellular concentrations of asparagine and valine may reflect preferential use of amino acids for energy metabolism under ischemic conditions. The significance of increased concentrations of inhibitory amino acid neurotransmitters is unclear.
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PMID:Spinal cord ischemia-induced elevation of amino acids: extracellular measurement with microdialysis. 197 91

It is well established that excitatory amino acid neurotransmitters are extensively liberated during ischemia and that they have neurotoxic properties contributing to neuronal injury. To study changes in the liberation of excitatory and other amino acids during cerebral ischemia, we measured their extracellular concentrations and related them to blood flow levels and electrophysiologic activity (electrocorticogram and auditory evoked potentials) before and for up to 2 hours after multiple cerebral vessel occlusion in 14 anesthetized cats. Blood flow levels between 0 and 43 ml/100 g/min were reached. Concentrations of the excitatory amino acid neurotransmitters increased most (aspartate 10-fold, glutamate 30-fold, and gamma-aminobutyric acid 300-fold compared with control values) below a blood flow threshold of 20 ml/100 g/min. The total power of the electrocorticogram and the amplitude of the auditory evoked potentials were affected below the same blood flow threshold. In contrast, concentrations of the nontransmitter amino acids taurine, alanine, asparagine, serine, and glutamine increased 1.5-5-fold as blood flow decreased, while concentrations of the essential amino acids phenylalanine, valine, leucine, and isoleucine did not change during cerebral ischemia. The great increases in concentrations of the excitatory amino acid neurotransmitters below a blood flow threshold close to that for functional disturbance is in accordance with the role of these amino acids in ischemic cell damage. Their release at blood flow levels compatible with cell survival and the increase in their concentrations with severity and duration of cerebral ischemia imply that excitotoxic antagonists may have potential as therapeutic agents.
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PMID:Differences in ischemia-induced accumulation of amino acids in the cat cortex. 197 18

Regional [14C]leucine incorporation into brain proteins was studied in gerbils after global ischemia for 5 min and recirculation times of 45 min to 7 days, using a combination of quantitative autoradiography and biochemical analysis. After recirculation for 45 min, incorporated radioactivity was reduced to approximately 20-40% of control values in all ischemic brain regions. Specific activity of the tracer, in contrast, was increased, a finding indicating that the reduced incorporation of radioactivity was not due to reduced tracer influx from plasma or a dilution of the tracer by increased proteolysis. After recirculation for 6 h, [14C]leucine incorporation returned to control levels in all regions except the CA1 sector of the hippocampus, where it amounted to less than 50%. After 1 day, protein synthesis in the CA1 sector returned to approximately 70% of control values, followed by a secondary decline to less than 50% after 3 days and returned to near control values after 7 days. Histological evaluations revealed selective neuronal death in the CA1 sector of the hippocampus after 3 days of recirculation. The complex time course of protein synthesis in the CA1 sector suggests a biphasic mode of injury, which may be related to similar changes of calcium homeostasis. The final return to near normal after CA1 neurons have disappeared is explained by astroglial proliferation and demonstrates that at this time protein synthesis is not a marker of neuronal viability.
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PMID:[14C]leucine incorporation into brain proteins in gerbils after transient ischemia: relationship to selective vulnerability of hippocampus. 199 94

Perinatal exposure to cocaine has been shown to cause morphological and neurobehavioral abnormalities. In the current study, neonatal rats were given an acute injection of cocaine (30 mg/kg s.c.) at 1, 3, 5, 8, 11 or 15 days of age, and [3H]thymidine incorporation into DNA examined over the ensuing 30 min period. Three brain regions were used that differ in their timetables of cell maturation: cerebellum, cerebral cortex and midbrain + brainstem. Cocaine inhibited DNA synthesis in all brain regions, with diminishing impact as the animals matured; by 15 days of age, the effect of cocaine was no longer significant. Inhibition of macromolecule synthesis was selective for DNA, as [3H]leucine incorporation into protein was much less affected by cocaine. Although inhibition of [3H]thymidine incorporation by a single injection of cocaine was short-lived, repeated administration could have cumulative effects: chronic treatment on days 2, 3 and 4 did not desensitize the adverse effect of a subsequent dose administered on day 5. Additionally, with chronic cocaine, the cerebellum displayed a pronounced rebound elevation of DNA synthesis 24 h after the last dose, a characteristic finding in delayed cell maturation. Inhibition of DNA synthesis by cocaine in developing brain was not secondary to ischemia, nor to local anesthesia, as alpha-adrenergic blockade with phenoxybenzamine afforded no protection, and lidocaine could not substitute for cocaine. In contrast, a small amount (15 micrograms) of cocaine injected directly into the central nervous system readily caused inhibition of DNA synthesis; the same dose given systemically had no effect. These data suggest that cocaine damages the developing brain, in part, through direct interference with DNA synthesis.
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PMID:Cocaine acutely inhibits DNA synthesis in developing rat brain regions: evidence for direct actions. 208 73

Involvement of neuroexcitatory mechanisms in cerebral ischemia and brain injury was explored in experimental models of repetitive forebrain ischemia by temporary occlusion of carotid arteries in gerbils and cryogenic injury to the cerebral cortex in rats and gerbils. Our observations in these models revealed a pattern of injury that involved some anatomic structures outside the areas of direct ischemic or traumatic insult. Such foci of injury revealed conspicuously abnormal uptake of 45Ca associated with slight or moderate neuronal alteration, whereas severely injured areas showed no 45Ca uptake. Electron microscopic observations revealed a characteristic presence of calcium in swollen dendrites, closely resembling pictures obtained in neuroexcitatory conditions such as epileptic seizures. Abnormal uptake of 45Ca was associated with apparent blood-brain barrier changes characterized by intracytoplasmic uptake of extravasated albumin into the neurons. Protein synthesis assayed by in vivo [3H]leucine incorporation was reduced in regions showing calcium accumulation. Our observations suggest that neuroexcitation may play an important role in development of secondary and chronic changes after ischemic or traumatic brain insults.
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PMID:Putative neuroexcitation in cerebral ischemia and brain injury. 223 87

This study was designed to determine the effect of cyclocreatine on the release of neutrophil chemotactic factors (NCF) from isolated rabbit hearts. We tested the hypothesis that if ischemia is important for the formation of NCF from the myocardium, then blocking (or delaying) ischemic changes with cyclocreatine should inhibit the release of NCF. Two models were used, including (1) perfusion of rabbit hearts (Langendorff apparatus) with oxygenated (95% oxygen) Krebs-Henseleit buffer (K-H buffer) containing 5% cyclocreatine for 120 minutes, and (2) incubating hearts with phosphate-buffered saline (PBS) containing 5% cyclocreatine for 120 minutes. For both models, rabbits were injected intravenously with 10 ml of 5% cyclocreatine solution 30 minutes before the animals were killed and the hearts removed. Control rabbits were injected with 5% creatine solution or saline for 30 minutes before perfusing hearts with K-H buffer or incubating with PBS. Chemotactic activity was assayed in the perfusates and supernatants using modified Boyden chambers and rabbit peritoneal neutrophils as indicator cells. The chemoattractant f-Met-Leu-Phe (f-MLP) was the positive control for a 100% response rate. Isolated hearts perfused with cyclocreatine showed significantly lower chemotactic activity (ie, 1.24 +/- 1% f-MLP; P less than 0.0001) compared to hearts perfused with K-H buffer (129 +/- 18%) or creatine (227 +/- 42%) (mean +/- standard error). Similar results were obtained using incubated hearts. Next the effect of cyclocreatine on neutrophils in the Boyden chamber was determined and it was found that it did not alter neutrophil migration, which excludes a direct inhibitory effect on the cells. Furthermore supernatant from cyclocreatine-treated hearts did not inhibit neutrophil chemotaxis to C5a, indicating absence of a chemotaxis inhibitor in this preparation. Results of these studies suggest that the observed low activity recovered in perfusate and supernatant of cyclocreatine-treated hearts is a result of reduction in the synthesis and/or release of the factors from myocardial tissues. Similar to previously established data, cyclocreatine treatment significantly preserved myocardial nucleotide levels (ie, adenosine triphosphate and creatine phosphate), which supports our hypothesis that the formation of NCF is ischemia dependent and that maintaining elevated levels of myocardial energy nucleotides reduced chemotactic factor release.
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PMID:Cyclocreatine inhibits the production of neutrophil chemotactic factors from isolated hearts. 224 Jan 67

The role of oxygen-free radicals for metabolic derangements in the ischemic and reperfused liver is controversial. The effect on hepatic protein synthesis of a 60-minute period of ischemia followed by two hours of reperfusion was studied in four groups of rats with different hepatic contents of the oxygen free radical scavenger glutathione (GSH): group 1, fed rats; group 2, fed rats treated with diethylmaleate (DEM) one hour before use (0.69 mL/kg, i.p.); group 3, 48-hour fasted rats; and group 4, 48-hour fasted rats treated with cobalt-chloride (45 mg/kg, s.c.) ten hours before use. Protein synthesis rates were determined by measuring incorporation of U-14C-leucine into protein in incubated liver slices. Treatment of fed rats with DEM and fasting for 48 hours significantly reduced liver GSH content. The effect of fasting on liver GSH was reversed by treatment with cobalt-chloride. The protein synthesis rate was reduced to approximately 30% of initial value at the end of the ischemic period and recovered to 70% to 100% of initial value after two hours of reperfusion with no differences between the experimental groups. Thus the effect of liver ischemia and reperfusion on protein synthesis was similar in groups of rats with different hepatic GSH contents at the onset of ischemia. The data suggest that oxygen free radicals do not play a major role for the impairment of protein synthesis in the ischemic and reperfused liver.
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PMID:Effects of ischemia and reperfusion on protein synthesis in livers with different glutathione levels. 229 51

Hemodynamic and metabolic consequences of a 90-minute period of liver ischemia followed by 120 minutes of reperfusion were studied in rats that were awake during most of the experiment and in rats anesthetized with either pentobarbital (40 mg/kg body weight) or chloralose (30 mg/kg X hour) during the complete length of the experiment. Ischemia was induced by occluding the blood vessels to the left and median liver lobes with a small vascular clamp, which was removed after 90 minutes. Protein synthesis rate was determined by measuring incorporation rate of 14C-leucine into protein in incubated liver slices. At the end of the ischemic period, adenosine triphosphate levels in liver tissue and protein synthesis rate were reduced by 80% to 90%, with no significant differences among groups. During reperfusion, energy levels and protein synthesis rate remained depressed in the anesthetized animals, but improved, although not to normal values, in the awake rats. Hepatic tissue water increased during ischemia, probably reflecting hepatocellular membrane injury. The increase in hepatic tissue water was more pronounced in the chloralose group than in the other groups of rats. During reperfusion hepatic tissue water remained increased in the anesthetized rats but was normalized in the awake group. Mean arterial blood pressure was stable during ischemia and reperfusion in the pentobarbital anesthetized rats, while a progressive decrease in blood pressure during the experiment was noted in the chloralose group. The results suggest that hemodynamic and metabolic responses to liver ischemia and reperfusion can be influenced by anesthetics. Chloralose may be less suitable than pentobarbital for anesthesia when liver ischemia is inflicted.
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PMID:Influence of pentobarbital and chloralose on metabolic and hemodynamic changes in liver ischemia. 236


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