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)

Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury.
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PMID:Injury-induced inhibition of small intestinal protein and nucleic acid synthesis. 169 45

1. Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. 2. Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. 3. It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells.
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PMID:Opposite alterations in cerebrospinal fluid uridine after severe cerebral ischemia or intrathecal blood injection. 225 61

Protein and RNA synthesis of the brain is affected by focal transient ischemia. Protein synthesis is depressed by the depletion of energy metabolism during ischemia, and its recovery following recirculation is slower than restoration of energy metabolism. On the other hand, RNA synthesis is more tolerable to ischemia than protein synthesis. Present study has designed to evaluate changes of protein and RNA synthesis of the brain after ischemia. We used a hindbrain ischemia model of gerbils, and quantitative autoradiography was applied for estimation of regional protein and RNA synthesis. The model was made by occluding the basilar artery for 15 minutes and recirculating afterwards. 14C-valine was used as a tracer for protein synthesis. In the ischemic group, protein synthesis was inhibited extremely in the medial thalamus, inferior colliculus, gray matter of the pons and midbrain, and cerebellum, RNA synthesis by salvage pathway was evaluated using tracer doses of 14C-uridine. It increased 1.6-2.4 folds of sham controls in the thalamus, and gray matter of the pons and midbrain. De novo synthesis of RNA was evaluated using 14C-carbamoylphosphate and 14C-NaHCO3. 14C-NaHCO3 antoradiogram showed inhibition of tracer incorporation into RNA and protein fraction in the ischemic lesions. 14C-carbamoylphosphate autoradiogram showed no significant change. These results indicate that protein synthesis is inhibited after ischemia but response of RNA synthesis to ischemia is not uniform. De novo synthesis of RNA is inhibited following ischemia, but RNA synthesis by salvage pathway increases in the ischemic lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Changes in protein and RNA synthesis following acute hindbrain ischemia]. 244 43

Intravenous injection of murine recombinant tumor necrosis factor alpha(TNF-alpha) to male NMRI albino mice in doses greater than 4 micrograms/kg (specific activity 4 x 10(7) U/mg) resulted in a fulminant hepatitis when animals had been sensitized 1 hr before by intraperitoneal administration of 700 mg/kg galactosamine. Liver injury was assessed by measurement of serum transaminases as well as sorbitol dehydrogenase activity 8 hr after administration of TNF-alpha. Pretreatment with either galactosamine or 40 micrograms/kg TNF-alpha alone did not cause hepatitis. Pretreatment of galactosamine/TNF-alpha-injured mice with 800 mg/kg uridine or with 6 mg/kg calmidazolium fully protected the animals, while administration of either verapamil or nifedipine (100 mg/kg, respectively) had no significant effect. The following inhibitors of generation or action of leukotriene D4, which were previously shown to block galactosamine/endotoxin-induced hepatitis in mice, failed to protect against galactosamine/TNF-alpha-induced intoxication: 200 micrograms/kg dexamethasone, 174 mg/kg BW 755 C or 13 x 10 mg/kg FPL 55712. In addition, unlike in the galactosamine/endotoxin model no prevention was achieved by pretreatment of galactosamine/TNF-alpha-injured animals with the following substances blocking the development of an ischemia/reperfusion syndrome: 2 x 100 mg/kg allopurinol, 3.3 x 10(4) U/kg superoxide dismutase, 10(6) U/kg catalase or 10 micrograms/kg iloprost. We conclude from our results that tumor necrosis factor alpha is likely to act as a final mediator of endotoxin action in a sequence of events which includes formation of leukotriene D4 and reactive oxygen species.
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PMID:Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. 246 8

To clarify a possible cause of delayed neuronal death, synthesis of protein and ribonucleic acid (RNA) following transient forebrain ischemia was evaluated autoradiographically. Mongolian gerbils were subjected to transient forebrain ischemia for 5 minutes by occluding bilateral common carotid arteries. They were used for autoradiographic study at 1, 2, and 5 days after ischemia. Tracer dose of 14C-valine or 14C-uridine was injected intravenously, and animals were sacrificed 45 minutes thereafter. Brains were frozen and thin sliced for macroautoradiography. After the first autoradiogram was obtained, tissue sections were incubated in cold 5% trichloroacetic acid for 1 hour, dried and again used for autoradiogram. With this preparation we could differentiate the tracer incorporated into protein or RNA fraction from the total tissue radioactivity. In the different set of animals, microautoradiograms of 3H-valine and 3H-uridine was obtained to detect subcellular distribution of synthesized protein or RNA. At 1 day after ischemia, protein synthesis in the CA 1 region of the hippocampus was reduced by 57% of the sham control, but RNA synthesis was not reduced quantitatively. Microautoradiogram of 3H-uridine however, indicated that silver grains in the cytoplasms of the CA 1 pyramidal cells were much reduced as compared to sham controls, though the amount of silver grains in the nucleus was the same as sham controls. Therefore, synthesized RNA in the nucleus was not transported to the cytoplasm. At 2 days after ischemia, protein and RNA synthesis was preserved to the same level as sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Malfunction of gene expression as a possible cause of delayed neuronal death]. 246 13

A high-pressure liquid chromatographic method was developed which achieved a separation and quantitation of 20 biologically important nucleosides and bases. The concentrations of pyrimidine nucleosides and bases, namely deoxycytidine, cytosine, cytidine, uracil, and uridine (22.6, 10.1, 5.2, 2.9, and 2.4 nmol/ml, respectively) were high in plasma, whereas purine nucleosides and bases were present in concentrations less than 2.5 nmol/ml. In erythrocytes, the pools of xanthine, hypoxanthine, and xanthosine were 32-, 27-, and 22-fold larger, respectively, whereas cytidine, uridine, and deoxycytidine were only 21, 12, and 5% of plasma concentrations. The results suggest a compartmental system for transport of some of the purine and pyrimidine nucleosides and bases in the whole blood. Studies on the effect of ischemia on nucleoside and base pools in rat liver indicated marked increases within 30 s in the concentrations of adenine, adenosine, inosine, hypoxanthine, uridine, and xanthine, whereas in hepatoma the effects were less pronounced. By 2 and 5 min ischemia these perturbations were most marked in both liver and hepatoma. These results indicate a need for rapid freeze-clamp preparation of tissue samples to obtain precise and repeatable results in the determination of tissue nucleoside and nucleobase concentrations.
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PMID:Effect of ischemia on nucleosides and bases in rat liver and hepatoma 3924A. 358 Oct 61

The influence of transient myocardial ischemia on recovery uridine incorporation into RNA and histone acetylation was investigated in an isolated perfused rat heart. Hemodynamically, hearts recovered from 15 min of ischemic arrest and were stable for at least 60 min of perfusion. Uridine incorporation was reduced (P less than 0.05) in ischemic hearts by 24 and 26% after 30 and 60 min of recovery perfusion. The incorporation of uridine into RNA from purified myocytes was decreased by 50% in the ischemic muscle cells. The covalent acetylation of total nucleohistones was diminished by 37%. Histone fractionation by urea polyacrylamide gel electrophoresis clearly indicated that histones H3 and H4 preferentially incorporated less acetate during ischemic recovery. However, histone acetylation for proteins H2A + H2B was not effected. These data suggest that a brief period of ischemia disrupts nucleotide incorporation during the recovery phase, with marked decrease associated with the muscle cell. The similar change in histone acetylation indicates a possible link between nucleoproteins and chromatin function during ischemic insult to the heart.
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PMID:Effect of myocardial ischemia on uridine incorporation and histone acetylation. 617 4

Purine and pyrimidine nucleotides are essential energy sources for basic metabolic reactions and play important roles in protein, glycogen, and nucleic acid synthesis, cyclic nucleotide metabolism, and energy transfer reactions. Brief coronary occlusions (12 min) were produced in seven open-chest dogs, and repetitive myocardial samples were taken in order to determine the response of the nucleotide pool to ischemia and reperfusion. During ischemia adenosine 5'-triphosphate (ATP) decreased to 57% of control, and similar decreases occurred in the guanosine 5'-triphosphate (GTP), cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP), and nicotinamide adenine dinucleotide (NAD+) pools. The decrease in nucleotides was accompanied by an increase in nucleosides and bases. After 60 min of reperfusion the content of all nucleotides had increased but was still significantly less than nonischemic values. The content of nucleosides and bases decreased immediately upon reperfusion. In contrast, creatine phosphate (CP) fell to 10% of control during ischemia but rebounded to above control values immediately upon reperfusion. Thus depletion of all nucleotide pools occurs during ischemia, and with reperfusion nucleotide content is restored only slowly. Delayed repletion is not caused by a defect in mitochondrial synthesis of ATP because CP content is restored rapidly. The slow repletion of nucleotides may be secondary to loss of nucleotide precursors during reperfusion and may result in widespread alterations in myocardial metabolism.
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PMID:Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog. 708 54

Extracellular ATP released from nerves onto vascular smooth muscle or released from damaged tissues during traumatic injury, shock, or ischemia profoundly alters cardiovascular physiology. We have used patch-clamp methods to investigate the effects of extracellular ATP on guinea pig ventricular myocytes because guinea pigs are a commonly used model for the study of cardiac electrophysiology. We have found that ATP activates a rapid, desensitizing, inward current. This inward current is activated by a P2 receptor that does not conform to published receptor subclasses. A concentration of 100 microM ATP activates more current than 100 microM alpha, beta-methyleneadenosine 5'-triphosphate, which in turn activates more current than 100 microM ADP. 2-Methylthioadenosine 5'-triphosphate (2-MeS-ATP) and adenosine 5'-O-(3-thiotriphosphate) are also effective agonists. Adenosine, AMP, guanosine 5'-triphosphate, and uridine 5'-triphosphate are ineffective at 100 microM. The inward conductance has a reversal potential near 0 mV and in ion-substitution experiments was found to be carried through nonselective cation channels rather than chloride channels. The conductance has inwardly rectifying current-voltage (I-V) relations. When ATP is used as the agonist, fluctuation analysis yields an apparent unitary conductance of 0.08 pA at a holding potential of -120 mV with sodium as the main charge-carrying ion. The combination of inwardly rectifying I-V relations, the efficacy of 2-MeS-ATP, and the very low conductance distinguish this conductance from other ATP-activated nonselective channels, including those recently cloned from rat vas deferens and PC-12 cells.
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PMID:An ATP-activated nonselective cation channel in guinea pig ventricular myocytes. 757 19

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


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