Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxia is well known to cause an increase in brain anaerobic glycolysis. Ornithine alpha ketoglutarate (OAKG) given to six dogs was shown to attenuate these metabolic disturbances caused by hypoxia. Brain oxygen utilization was higher after ornithine alpha ketoglutarate during hypoxia than during a period of hypoxia alone. It is suggested that the clinical usefulness of OAKG should be explored in those situations where there is cerebral hypoxia or ischemia.
 ...
PMID:Effect of ornithine alpha ketoglutarate (OAKG) on the response of brain metabolism to hypoxia in the dog. 64 19

Pressor amine therapy in circulatory shock has been generally unfavorable, presumably because these drugs produce unselective, intense vasoconstriction and curtail rather than improve true capillary inflow, distribution and outflow in the microcirculation. The present study compares the influence of a new analog of vasopressin, [2-phenylalanine, 8-ornithine]vasopressin (POV), over wide dose ranges and Ringer's solution on: 1) survival after circulatory shock, induced by different means (e.g., hemorrhage, bowel ischemia); 2) blood pressure and hematocrit in shocked animals; and 3) various microcirculatory parameters after induction of hemorrhage and bowel ischemia shock (e.g., lumen diameters of various types of microvessels, reactivity of microvessels, microvascular flow patterns, leukocytic sticking, petechial hemorrhage formations, vasomotion, etc.). Local administration of POV, in contrast to constrictor catecholamines, induces a venular-to-arteriolar profile of constrictor activity in the normal rat mesenteric microcirculation. Systemic administration of POV to rats subjected to either lethal hemorrhage or bowel ischemia shock: 1) increases survival rates 2- to 8-fold over control rats receiving Ringer's solution; 2) produces a plateau-like effect on arterial blood pressure and returns arterial hematocrits toward normal after hemorrhage; and 3) regenerates and sustains vasomotion and venular tone, decreases microvascular hyper-reactivity characteristic of shock syndromes, restores constricted arteriolar lumen sizes toward normal, predisposes to a splanchnic microbed virtually free of stasis and petechiae, and restores capillary perfusion and outflow to near-normal. These findings indicate that it is possible to synthesize vasoactive molecules which exert selective microvascular effects and are highly beneficial in therapy of low-flow states.
 ...
PMID:Microcirculatory approach to the treatment of circulatory shock with a new analog of vasopressin, (2-phenylalanine, 8-ornithine)vasopressin. 93 6

Mongolian gerbils were anesthetized with halothane and forebrain ischemia was induced by occluding both common carotid arteries. After 2, 4, 6, 8, or 10 min of vascular occlusion clips were removed and animals allowed to recover for 8 or 24 h. At the end of the experiments animals were reanesthetized and their brains frozen in situ. Tissue samples were taken from the cerebral cortex, striatum, hippocampus, and thalamus for determination of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activity by measurement of the release of 14CO2 from [14C]ornithine and S-[14C]adenosylmethionine, respectively. A transient increase in ODC activity was found after 8 h of recirculation following cerebral ischemia in all brain structures studied. ODC activity was significantly increased after 8 h of recirculation in the hippocampus of animals subjected to 4 min of ischemia, in the cortex and striatum after 6 min of ischemia, and in the thalamus after 8 min of vascular occlusion. ODC activity had already reached a plateau in the hippocampus after 4 min of vascular occlusion and in the cortex, striatum, and thalamus after 8 min, since there is no further increase in activity even after 10 min of ischemia. After cerebral ischemia and 24 h of recirculation ODC activity returned to control levels throughout the forebrain regardless of the duration of ischemia. SAMDC activity was significantly reduced after 8 h of recirculation following 4 to 10 min of ischemia in the cortex and 8 min of ischemia in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase in transient cerebral ischemia: relationship to the duration of vascular occlusion. 149 93

Ornithine decarboxylase (ODC) is the rate-limiting enzyme that catalyzes the synthesis of polyamines from ornithine and is thought to be involved in the cellular response to growth, differentiation, and stress. Previous studies have demonstrated that transient cerebral ischemia results in an increase in ODC activity and polyamine synthesis. We have used the Mongolian gerbil as a model system to test the hypothesis that the cellular response to ischemia induces a distinct pattern of ODC gene expression. Our results indicate that transient ischemia, induced by bilateral carotid occlusion, elevates ODC mRNA within 1-4 h after reperfusion, which correlates with increased ODC activity and polyamine synthesis. Increased ODC mRNA can be detected in the forebrain, striatum, hippocampus, and midbrain but not the cerebellum, which is not subject to ischemic injury. In contrast, c-fos mRNA increased by 15 min after reperfusion and actin mRNA did not demonstrate alterations in level after ischemia. Pentobarbital prevented the increase in ODC mRNA, whereas the glutamate antagonist MK-801 had no effect on the elevation of ODC gene expression after ischemia. We conclude that the ischemia-induced increase in ODC enzyme activity may be attributed in part to transcriptional activation of the ODC gene.
 ...
PMID:Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain. 193 91

The concentration of 18 alpha-amino acids (AAs) in plasma and renal cortical cell water were measured 3 or 24 hr after 1 hr of unilateral renal artery clamping or 24 or 48 hr after 15 mg/kg body weight HgCl2 injection sc as a test of epithelial integrity. Cellular glycine (Gly), hydroxyproline (Hpr), ornithine (Orn), phenylalanine (Phe), serine (Ser), and tryptophan (Trp) concentrations were depressed 24 hr after HgCl2 (p less than 0.05), but the remaining 12 AAs were not distinguishable from control despite the presence of severe renal failure. ARginine (Arg), glutamic acid (Glu), and valine (Val) also were decreased (P less than 0.05) 24 hr later, but concentrations of half of all measured AAs were still normal. Cellular alanine (Ala), Arg, Glu, Gly, Phe, and Ser concentrations were decreased 3 hr after ischemia, p less than 0.05, but 12 AAs were unchanged and only Arg, Phe, Ser, and threonine (Thr) were reduced 24 hr after ischemia was reversed. Concentrations of even the most affected AAs remained notably higher than in plasma in both forms of acute renal failure (ARF). Total loss of AAs from a small proportion of tubular cells would be hidden by essentially normal concentrations in the rest, and such losses may well have occurred. Unless cellular AAs in ARF are almost completely bound, however, the well-maintained cell:plasma AA concentration ratios indicate that cellular energetics were adequate for AA uptake and that epithelial permeability to AAs in the vast majority of cells was not greatly disturbed. Such findings suggest that most of the epithelium, although seriously damaged, had remained viable.
 ...
PMID:Renal epithelial amino acid concentrations in mercury-induced and postischemic acute renal failure. 221 14

The responses of long and short half-lived proteins to ischemia were measured in rat brain during 6 days of recovery from 30 min of transient forebrain ischemia produced by four-vessel occlusion. At the end of the ischemic interval, the neocortical activities of four vulnerable enzymes [ornithine (ODC) and S-adenosylmethionine (SAMDC) decarboxylases, and RNA polymerases I and II] were unchanged, but within 30 min of reperfusion, their activities dropped by 25-50%. The loss of substance P in the striatum and substantia nigra was slower, reaching about 50% by 12 h. On the other hand, the activities of 5 long half-lived enzymes did not change in the neocortex at 5 and 15 h of reperfusion and regional protein concentrations were essentially unaffected over 6 days survival. The rate and extent of normalization of the amounts or activities of the vulnerable proteins varied. RNA polymerase II and ODC activities were restored within 4 h, and ODC showed a biphasic increase in activity, with peaks at 10 h and 2-3 days. RNA polymerase I and SAMDC activities were restored by 18 h and 5 days, respectively, whereas substance P concentrations did not completely recover, even at 6-15 days. The greater the regional reduction of blood flow during ischemia, the larger the net change (gain or loss) of SAMDC or ODC activity and the longer the time required to normalize the activities of these enzymes. The average rate of proteolysis, assessed by measuring the rate of clearance of 14C from protein prelabeled with [14C]bicarbonate, was abnormal during the first 2 days of reperfusion. Postischemic changes in both protein synthesis and degradation could affect the amounts of some of the proteins responsive to transient ischemia.
 ...
PMID:Temporal profiles of proteins responsive to transient ischemia. 257 82

Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 +/- 0.0013; ischaemia: 1.0355 +/- 0.0021, mean +/- SD; p less than 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development. 290 81

Changes in biochemical and electroencephalographic parameters were followed over time during the development of acute hepatic encephalopathy (HE) in two different experimental models. In the rat, (sub)acute liver failure was obtained either by ligation of the hepatic artery in previously portacaval-shunted animals or by intraperitoneal injection of a high dose of galactosamine (GALN). The EEG changes were characterized in both models by a significant increase in low-frequency activity of the EEG power density spectra: the so-called 'left shift'. This 'left shift' was significant in liver ischemia after 4-5 h and in GALN hepatitis after about 30 h. The changes in plasma biochemical indices also showed a great similarity in both models. The concentration of all measured plasma amino acids (except histidine and arginine in GALN hepatitis and arginine in liver ischemia), NH3 and ALAT were significantly increased during the development of (sub)acute HE. Correlation of the combined data of electroencephalographic and biochemical indices showed a significant (P less than 0.01) correlation between the 'left shift' and NH3, taurine, threonine, proline, alanine, methionine, cystathionine, phenylalanine, tryptophan, ornithine and histidine. It is concluded that EEG spectral analysis is a useful parameter for following the development of (sub)acute hepatic encephalopathy in relation to biochemical parameters.
 ...
PMID:Correlation between electroencephalographic and biochemical indices in acute hepatic encephalopathy in rats. 359 63

This study examines the pathophysiology of stroke secondary to focal cerebral ischemia. The interaction of arachidonic acid metabolites and polyamines, a class of ubiquitous ornithine-derived molecules with important membrane effects on edema, Ca++-dependent endocytosis, platelet function, and prostaglandin (PG) formation, are correlated with regional changes in H2 clearance, cerebral blood flow (rCBF), ischemic edema, and somatosensory evoked responses (SSERs) after middle cerebral artery (MCA) occlusion. Thirty cats were studied up to 3 hours before and 6 hours after right MCA occlusion. Four areas of brain showing different levels of perfusion after MCA occlusion were sampled for tissue levels of PGs: 6-keto-PGF1 alpha, PGE2, and as well as thromboxane B2 (TXB2), ornithine decarboxylase activity (ODC) (a measure of polyamine activity) and gravimetric determination of cerebral edema. After right MCA occlusion, right hemisphere SSER amplitude decreased and interpeak latency increased markedly. rCBF was distributed into zones of dense, partial, and no ischemia ranging from 12.6 to 59.4 ml/100 g/minute. Ischemic edema was distributed inversely to rCBF and was increased in areas of dense ischemia (85.2 +/- 0.5%) and ischemia (82.7 +/- 0.7%), but not in partially ischemic or control areas. 6-Keto-PGF1 alpha (1257.3 pg/mg), PGE2 (1628.5 pg/mg), and TXB2 (1572.8 pg/mg) were all significantly (P less than 0.05) increased in areas of partial ischemia that had not yet developed edema. ODC levels were significantly elevated (3812 pmole/g/hour, P less than 0.05) and increased with time in areas of slightly denser ischemia that showed an intermediate increase in edema, but not the presence of infarction. This is the first demonstration that ODC, the rate-limiting enzyme for polyamine synthesis, is stimulated by cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Polyamine and prostaglandin markers in focal cerebral ischemia. 386 30

We examined the polyamine metabolism in liver transplanted after cold ischemia and effects of putrescine administration on liver injury, liver regeneration, and survival rate after orthotopic liver transplantation in the rat. Male Wistar rats were used as donors and recipients. Grafts were stored in Euro-Collins solution for 6 h at 4 degrees C. Orthotopic liver transplantation was performed by the three cuff technique. The activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase elevated and peaked 4 h after liver transplantation. Hepatic ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities were also elevated and peaked 8 h after the operation. In agreement with the increases in ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities, the putrescine content increased and spermidine content decreased in the transplanted liver. Putrescine administrated intraperitoneally improved the survival rate, decreased serum transaminase level and increased the [3H]thymidine incorporation into the liver DNA. These findings suggest that both biosynthetic and biodegradative pathways are stimulated in liver transplantation, resulting in the increase in the formation of putrescine from ornithine and from spermidine, and that putrescine administration improve the survival rate by protecting the damaged graft after cold ischemia and reperfusion and by stimulating liver regeneration.
 ...
PMID:Polyamine metabolism in the rat liver after orthotopic liver transplantation. 749 79


1 2 3 4 5 Next >>