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 effect of nimodipine on cerebral metabolism during ischemia and reflow was studied in female mongolian gerbils. Animals were divided into three experimental groups. Group 1 received 1 mg/kg nimodipine i.p. 1 h prior to ischemia. Group 2 received an injection of the vehicle, 5% polyethylene glycol 400. Group 3 received an equal volume of normal saline. Cerebral ischemia was induced by bilateral common carotid artery occlusion for 1, 2, or 5 min. Recirculation was established for 0, 1, or 5 min. Sham-operated animals served as nonischemic controls. Gerbils were killed by microwave irradiation. Regional levels of ATP, phosphocreatine, glucose, glycogen, cyclic AMP, and cyclic GMP were measured in brain extracts using standard assay techniques. Levels of metabolites in sham-operated animals did not differ among Groups 1, 2, and 3. At 1 min of ischemia, cortical and striatal ATP levels were highest in Group 1 (p less than 0.05 and p less than 0.01, respectively). After 5 min of recirculation, cortical and striatal glucose levels were highest in Group 1 (p less than 0.005). Regional levels of the metabolites measured at other times did not differ significantly among the three groups. Pretreatment with nimodipine thus retards the fall in ATP and facilitates the recovery of glucose in mongolian gerbils subjected to common carotid artery occlusion. A regional variability of this effect was observed.
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PMID:Effect of nimodipine on cerebral metabolism during ischemia and recirculation in the mongolian gerbil. 299 44

It was found that preliminary (before ischemia) administration of vitamin E in a dose of 200 mg/kg to albino rats causes the changes in energy support of the ischemic myocardium leading to prolonged maintenance of synthesis processes: energy production, cGMP concentration, unsaturation of cell membrane lipids increase. The combination of all these factors probably determines the anti-ischemic effect of vitamin E providing adequate restoration of the myocardial function in the postischemic period.
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PMID:[Effect of vitamin E on the energy allowance of functional and plastic processes in the myocardium during ischemia and reoxygenation]. 341 22

The present experiments were designed to determine the short-term regional changes in the cyclic nucleotides, certain glucose metabolites, high-energy phosphates, gamma-aminobutyric acid (GABA), glutamate, and glutamine in the gerbil brain following bilateral ligation of the common carotid arteries. The brains of the animals were microwaved at 20, 40, 60, 90, 120, and 300 sec of ischemia and the metabolites were measured in the cerebral cortex, hippocampus, and striatum. There were significant decreases in ATP, P-creatine, and glucose within the first 20 sec of ischemia in all three regions examined, whereas the increases in phosphate and lactate, as well as the loss of glycogen, were evident only after 40 sec of ischemia. The high-energy phosphates were essentially depleted (less than 15% of control values) in all three regions by 2 min of ischemia, indicating that the energy imbalance elicited by ischemia was comparable in the three regions. In contrast, the magnitude of the changes in the cyclic nucleotides was greater in the hippocampus than in the cerebral cortex or striatum. In addition, the decrease in cyclic GMP levels at 20 sec of ischemia preceded the increases in cyclic AMP observed at 40 sec in all three regions. The use of microwave irradiation to fix the gerbil brains not only provides a more accurate assessment of the time course of the metabolite changes but also permits studies on the deeper regions of the brain than is possible with freezing techniques.
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PMID:Regional metabolite profiles in early stages of global ischemia in the gerbil. 350 42

A large amount of biochemical, physiological, and pharmacological data has been obtained which supports a mechanistic role of oxygen free radical-induced lipid peroxidation (LP) in post-traumatic spinal cord degeneration. Biochemical evidence of early and progressive lipid peroxidative reactions occurring in the injured spinal cord includes: an increase in polyunsaturated fatty acid peroxidation products (e.g., malonyldialdehyde), a decrease in cholesterol and the appearance of cholesterol oxidation products, an increase in cyclic GMP presumably due to free radical activation of guanylate cyclase, a decrease in tissue anti-oxidant levels (e.g., alpha tocopherol, reduced ascorbate), and inhibition of membrane-bound enzymes such as Na+ + K+-ATPase. In vitro CNS tissue studies have provided support for the possibility that LP may contribute to other early post-traumatic events including intracellular calcium accumulation and arachidonic acid release. Moreover, spinal tissue lactic acidosis, which occurs early after injury, can exacerbate LP reactions. The involvement of LP in the development of progressive post-traumatic spinal white matter ischemia has been strongly inferred from pharmacological studies in cats with known inhibitors of LP. For example, the dose-response curves for the ability of the glucocorticoid methylprednisolone (MP) to inhibit post-traumatic LP and to retard ischemia development are identical. This relationship between LP and post-traumatic ischemia is more directly implied from studies showing that pretreatment of cats with high doses of anti-oxidants (e.g., d-alpha tocopherol plus selenium p.o. or 1-ascorbic acid i.v.) can also significantly antagonize the progressive decrease in spinal cord blood flow that follows severe blunt injury. However, a similar efficacy of certain calcium and prostaglandin antagonists suggests an interrelationship between aberrant calcium fluxes, vasoconstrictor/platelet aggregating prostanoids, and LP in the post-traumatic ischemic phenomenon. In addition to a role of LP in ischemia development, the action of intensive d-alpha tocopherol and selenium pretreatment to retard anterograde cat motor nerve fiber degeneration after nerve section suggests that LP may also be a fundamental mechanism of "Wallerian" axonal degeneration after neural injury. Finally, a critical role of LP in the acute pathophysiology of CNS injury in general has been supported by the finding of an excellent correlation, in terms of efficacy and potency, between the action of glucocorticoid and nonglucocorticoid steroids to inhibit neural tissue LP in vitro and to promote early neurological recovery in severely head-injured mice.
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PMID:Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review. 355 50

Ischemia of the rat brain was induced for 15 min, 2 and 4 hrs, 1 and 3 days. The studies were performed during the ischemia as well as within 15 min and 2 hrs after cerebral blood flow restoration. The same experiments were carried out in animals with removed upper cervical sympathetic ganglia. During ischemia phasic changes of the energy metabolism were revealed (dissociation of oxydation and phosphorylation) as well as of activity of cerebral enzymes and water content in the brain tissue (ischemic and postischemic oedema). Changes of cAMP and cGMP contents corresponded to the above changes which reflected the adren- and cholinergic phases of adaptation. Sympathectomy led to similar though less obvious changes of the metabolism. The ischemia in desympathized animals led to greater changes of metabolism spreading beyond the adaptive shifts to an overtension of adrenergic compensatory mechanisms, increasing the mortality rate from 45 to 70%. The adaptive-trophic effect of the sympathetic innervation seems to tell on the optimal relations between adren- and cholinergic phases of compensation in the brain ischemia. Desympathization makes the effects of brain ischemia more grave.
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PMID:[Role of the sympathetic nervous system in adaptive changes in brain energy metabolism during ischemia and in the postischemic period]. 608 5

Cyclic GMP levels in epidermis of normal subjects and of psoriatic patients were measured with a highly sensitive radioimmunoassay method. Technical improvements for the assay are 2-fold: (1) skin samples were frozen in vivo before biopsy and local injection of any anesthetic was avoided to overcome ischemia effect which could lower cyclic GMP artificially; (2) epidermis was microdissected to avoid contamination of dermis and keratin layers. The results show that on a per mg tissue dry weight basis the cyclic GMP levels are about 200 fmol in the involved lesional epidermis and 70 fmol in the uninvolved or normal epidermis. Similarly increases in the cyclic GMP levels in the lesional epidermis are observed when the data are expressed either on a DNA or protein basis. The cyclic GMP level in normal epidermis from nonpsoriatic subjects is the same as that in the uninvolved epidermis of psoriasis patients.
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PMID:Epidermal cyclic GMP is increased in psoriasis lesions. 625 90

In 12 healthy, adult males, the epidermal content of both cAMP and cGMP was determined radioimmunologically every 6 h over a period of 30 h, avoiding any ischemia, which can alter unphysiologically the in vivo levels of epidermal cyclic nucleotides. For cAMP a diurnal fluctuation with maximal level at midnight could be proved (p less than 0.05), whereas cGMP, in contrast to experiments in mice, revealed no significant variation during the test period. The presented results describe for the first time the diurnal course of human epidermal cGMP.
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PMID:Cyclic nucleotides in human epidermis--diurnal variations. 631

The effect of three modes of anesthesia was evaluated with regard to regional damage to central cyclic nucleotide systems in the gerbil brain as a consequence of bilateral ischemia (clamping the common carotids) followed by various periods of recirculation. The injection of thiopental as much as 90 min before stroke prevented damage to chemical activation [catecholamines, guanosine triphosphate (GTP), or forskolin] of adenylate cyclase. However, the basal enzyme activity was lower in all brain regions whether thiopental was administered to stroke or sham-operated animals. Injection of ketamine drastically shortened the survival times of gerbils undergoing stroke followed by recirculation. About 90% of the animals could tolerate a maximum of only 15 min stroke with 15 min recirculation. At this time frame the patterns of activation of adenylate cyclase in only the olfactory tubercle and hippocampus were altered. When procaine was used as a local anesthetic agent during surgery, damage to catecholamine-, GTP-, or forskolin-activated adenylate cyclase was evident to varying degrees in the frontal cortex, hippocampus or olfactory tubercle, but not in the nucleus accumbens and olfactory bulb of gerbils subjected to 60-min stroke followed by 15 or 150 min of recirculation. The degree of enzyme damage was neither correlated with the fed vs. fasted state of the animal nor with the whole blood concentration of glucose. A depression in the amplitude of visually evoked potentials correlated to neurological signs and to enzyme damage. During anesthesia, ketamine increased steady-state concentrations of cyclic AMP in the frontal cortex and hippocampus from gerbil brains that had been rapidly inactivated by microwave irradiation. Thiopental increased steady-state cyclic AMP in only the olfactory tubercle. Cyclic GMP concentrations were unchanged by any anesthetic agent. In animals completely recovering from anesthesia and occluded for a brief period followed by 10 min of reflow, steady-state concentrations of only cyclic AMP were augmented.
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PMID:Regional cyclic AMP systems during secondary ischemia in gerbils: influence of anesthetic agents. 632 54

A model is proposed for the role of the kidney in the control of erythropoietin production in which the initial trigger is an oxygen deficit created by anemia, hypobaria or ischemia. It is postulated that hypoxia creates a decrease in the oxygen level in a critical renal sensor cell, perhaps in the glomerular tuft, which eventually leads to the production of prostacyclin. It is possible that the endothelial cell in the glomerular tuft responds to this oxygen deficit to produce prostacyclin to trigger erythropoietin production. Recent studies on prostaglandin synthesis by human isolated glomeruli indicate that the most abundant prostanoid synthesized by the glomerular tuft cells was 6-keto PGF1 alpha, a metabolite of prostacyclin (PGI2). PGI2 has also been reported to be produced by isolated vascular endothelial cells. The mechanism by which hypoxia may initiate the synthesis and/or release of prostaglandins and prostacyclin in the renal cell has not been elucidated. Significant to erythropoietin production is the production by hypoxia of prostacyclin which eventually leads to the production of the metabolite 6-keto PGE1. We further propose that 6-keto PGE1 is the prostanoid which activates a specific cell membrane adenylate cyclase, causing the conversion of ATP to cyclic AMP. This is a very critical step in that there must be a sufficient amount of ATP remaining to generate cyclic AMP in order for erythropoietin biosynthesis to occur with the reduced level of ATP which may have caused a perturbation of the cell membrane. The elevated cyclic AMP leads to the activation of protein kinases which are essential in phosphorylating the lysosomal hydrolases released by hypoxia into the cytosol of the cell and may be the precursors of erythropoietin. Neutral proteases and lysosomal hydrolases, documented triggers of erythropoietin production, have been demonstrated to be elevated in the kidney after hypoxia. The mechanism of labilization and release of these enzymes from the renal lysosomes has been postulated to be related to increases in cyclic GMP levels in a renal cell. Hypoxia causes the release of renal lysosomal hydrolases which then undergo phosphorylation through activation by protein kinases following prostanoid stimulation of renal adenylate cyclase to generate cyclic AMP, resulting in increased biosynthesis of erythropoietin.
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PMID:Prostanoid activation of erythropoiesis. 654 29

1-Aminocyclopropanecarboxylic acid is a high affinity ligand with partial agonist properties at strychnine-insensitive glycine sites associated with the N-methyl-D-aspartate subtype of glutamate receptors. Since occupation of these sites appears required for operation of N-methyl-D-aspartate, receptor coupled cation channels, it was hypothesized that a glycine partial agonist could function as an N-methyl-D-aspartate antagonist. This hypothesis was examined by evaluating the in vivo and in vitro neuroprotective actions of 1-aminocyclopropanecarboxylic acid. 1-Aminocyclopropanecarboxlic acid (150-600 mg kg-1) administered to gerbils five minutes following twenty minutes of forebrain ischemia significantly improved seven day survival; the optimal dose (300 mg kg-1) increased 7 days survival > 4-fold, from 20% to 92%. Survival of hippocampal CA1 neurons (quantitated 7 days post-ischemia) was significantly (approximately 3-fold) increased by the 600 mg kg-1 dose. Seven day survival was not significantly increased when the interval between reperfusion and drug administration (300 mg kg-1) was increased from 5 to 30 min. In cerebellar granule cell cultures, NMDA combined with a saturating concentration of glycine (10 microM) resulted in a 500% increase in cGMP levels. cGMP levels were increased by 100% over basal when NMDA was combined with a saturating (10 microM) concentration of ACPC, indicating that in this measure, the efficacy of ACPC relative to glycine was approximately 0.2. Consistent with previous findings, 1-aminocyclopropanecarboxylic acid significantly reduced glutamate-induced neurotoxicity in cerebellar granule cell cultures. ACPC was most effective in blocking neurotoxicity at glutamate concentrations producing low to moderate levels of cell death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroprotective actions of 1-aminocyclopropanecarboxylic acid (ACPC): a partial agonist at strychnine-insensitive glycine sites. 747 40


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