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)

In the present study, the ability of U74006F, the 21-aminosteroid inhibitor of lipid peroxidation, to attenuate posttraumatic spinal cord ischemia has been examined in cats following a moderately severe compression injury. Moreover, in an attempt to assess whether U74006F is affecting in vivo posttraumatic lipid peroxidation, the effect of the compound on injury-induced spinal tissue vitamin E depletion was also studied. Following an initial 10 min postinjury hyperperfusion (+45%), spinal cord blood flow (SCBF) returned to the preinjury level at 30 min before entering a phase of progressive hypoperfusion, which reached -42.0 +/- 4.5% by 4 h postinjury in the vehicle-treated animals. In animals that received 30 min postinjury U74006F i.v. doses of 1.0, 3.0, or 10 mg/kg (plus 0.5, 1.5, and 5.0 mg/kg maintenance doses at 2.5 h.), the SCBF decline was reduced to -23.1%, -22.9%, and -26.1%, respectively (p less than 0.05 vs. vehicle at all three doses). A 0.3 mg/kg dose did not reduce the posttraumatic fall in SCBF. In vehicle-treated cats, the vitamin E content of the injured cord segment was reduced by 78.9% at 4 h postinjury in comparison to cord samples from uninjured vehicle-treated cats. In contrast, the same doses of U74006F (1.0, 3.0, and 10 mg/kg) that attenuated posttraumatic ischemia also significantly reduced the depletion of cord vitamin E. The lowest U74006F dosage (0.3 mg/kg), which failed to affect posttraumatic ischemia development, also had no effect on spinal cord vitamin E content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between attenuation of posttraumatic spinal cord ischemia and preservation of tissue vitamin E by the 21-aminosteroid U74006F: evidence for an in vivo antioxidant mechanism. 281 Mar 81

Incubation of human blood platelets in vitro in Tyrode solution with unsaturated fatty acids, diamide or superoxide (generated in situ) resulted in the oxidation of tocopherol in the platelets. Arachidonate concentrations of (3-5).10(-4) M caused a 50% decrease in platelet alpha-tocopherol. The addition of saturated fatty acids or platelet-active substances such as ADP, dibutyryl cyclic AMP, and some prostaglandins, or peroxidizing agents such as hydrogen peroxide and tert-butylhydroperoxide to the incubation medium did not cause any change in platelet tocopherol content. During incubations of platelets with arachidonate, malonaldehyde as well as alpha-tocopherolquinone were produced. The latter was also produced during incubations with diamide or superoxide. The oxidation of tocopherol induced by unsaturated fatty acids may be one factor responsible for the well-known increase in dietary vitamin E requirements induced by polyunsaturated fatty acids. The oxidative consumption of tocopherol in the membranes could be expected to take place during localized release of oxidants such as superoxide and polyunsaturated fatty acids during normal biological function (e.g., phagocytosis) or pathological processes (e.g., ischemia). Tocopherol utilization is kept low probably by the regeneration of the compound by vitamin C and/or the preferential utilization of the other biological antioxidants.
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PMID:In vitro oxidation of alpha-tocopherol (vitamin E) in human platelets upon incubation with unsaturated fatty acids, diamide and superoxide. 282 39

The role of O2 free radicals in the reduction of sarcolemmal Na+-K+-ATPase, which occurs during reperfusion of ischemic heart, was examined in isolated guinea pig heart using exogenous scavengers of O2 radicals and an inhibitor of xanthine oxidase. Ischemia and reperfusion reduced Na+-K+-ATPase activity and specific [3H]ouabain binding to the enzyme in ventricular muscle homogenates and also markedly lowered sodium pump activity estimated from ouabain-sensitive 86Rb+ uptake by ventricular muscle slices. These effects of ischemia and reperfusion were prevented to various degrees by O2-radical scavengers, such as superoxide dismutase, catalase, dimethyl-sulfoxide, histidine, or vitamin E or by the xanthine oxidase inhibitor, allopurinol. The degree of protection afforded by these agents paralleled that of reduction in enhanced lipid peroxidation of myocardial tissue as estimated from malondialdehyde production. These results strongly suggest that O2 radicals play a crucial role in the injury to sarcolemmal Na+-K+-ATPase during reperfusion of ischemic heart.
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PMID:O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase. 302 76

A pharmacological analysis was carried out to determine the possible role of aberrant calcium fluxes, vasoactive arachidonic acid metabolites, and microvascular lipid peroxidation in the development of posttraumatic spinal cord white matter ischemia. Pentobarbital-anesthetized cats were treated intravenously 30 minutes before a 500-gm-cm contusion injury to the lumbar spinal cord with one of the following test drugs: the Ca++ channel antagonists verapamil, diltiazem, or nifedipine; the cyclo-oxygenase inhibitors ibuprofen or meclofenamate; the thromboxane A2 (TXA2) synthetase inhibitor furegrelate sodium; or the stable epoprostenol (prostacyclin, or PGI2) analogue ciprostene calcium alone or in combination with furegrelate sodium. Another group of animals was pretreated for 5 days before spinal injury with a combination of the antioxidants vitamin E and selenium in high doses. The hydrogen clearance technique was used to make repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus of the injured segment before and for 4 hours after injury. In 11 untreated uninjured cats, the mean preinjury SCBF was 12.7 +/- 1.5 ml/100 gm/min. Following contusion, there was a progressive decline in SCBF to 6.8 +/- 0.4 ml/100 gm/min, or 53.5% of the preinjury level at 4 hours. In comparison, the Ca++ antagonists diltiazem and nifedipine (but not verapamil) prevented a significant posttraumatic decrease in SCBF. Similarly, both cyclo-oxygenase inhibitors (ibuprofen and meclofenamate) maintained SCBF within normal limits (10 ml/100 gm/min or greater). However, neither TXA2 synthetase inhibition nor the stable PGI2 analogue alone had a significant effect in preventing ischemia, whereas a combination of the two agents did serve to support SCBF. The most impressive preservation of posttraumatic SCBF, however, was observed in the antioxidant-treated animals. Based upon these results, a hypothesis is presented concerning the pathogenesis of posttraumatic central nervous system ischemia which integrates an injury-induced rise in intracellular Ca++, the increased synthesis of vasoactive prostanoids (such as prostaglandin F2 alpha and TXA2), and progressive microvascular lipid peroxidation.
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PMID:A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia. 308 21

Phenytoin is well known as the anticonvulsant agent and also said to protect the brain against ischemic damage. The purpose of the present experiment is to study the therapeutic effect of phenytoin on cerebral ischemia and confirm whether the effectiveness of phenytoin could be enhanced by combination of free radical scavengers such as mannitol and vitamin E. In this experiment, twenty-five dogs were subjected to ischemia, using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump at will. Five animals served as untreated control, fifteen received treatment with phenytoin (7 mg/kg in five dogs, 10 mg/kg in five dogs and 30 mg/kg in five dogs) and five treated with 10 mg/kg phenytoin, 2 g/kg of mannitol and 30 mg/kg of vitamin E. These drugs were administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal volume. After one hour, cerebral blood flow was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the group treated with phenytoin, gradual emergence of slow wave ws observed soon after recirculation. The higher the administered dosage is, the better the degree of recovery of EEG was seen. Thus, the dose-related recovery of EEG was observed within the dose ranges tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Protective effect of phenytoin and its enhanced action by combined administration of mannitol and vitamin E in cerebral ischemia]. 308 96

At present we apply the three-drug-combination therapy consisting of mannitol, vitamin E and glucocorticoid (betamethasone) in the treatment of cerebral infarction at acute stage with favorable results. However, much of the action mechanism of these drugs remains unelucidated. For the purpose to elucidate the mechanism by which they exert actions and moreover to evaluate the efficacy of this therapy, we conducted experiments using highly ischemic whole brain models of rats. In this model, chemiluminescence value, energy metabolism, water content and concentrations of Na+, K+ were determined with time. During ischemic period chemiluminescence level increased with time, and more remarkable increase was seen after recirculation of the blood flow. However, in the group with administration of the three drugs combination increase in chemiluminescence was inhibited remarkably. In the analysis of intensity of chemiluminescence by wavelengths, the peaks were observed at 480, 520 - 530, 570, 620 - 640 and 680 - 700 nm. These wavelengths were taken to suggest the release of energy (luminescence) associated with the transition of singlet oxygen to the grounded state during the breakdown of the lipid hydroperoxide. By addition of vitamin E or beta-carotene (quencher of singlet oxygen) on the brain homogenate in vitro, luminescence was remarkably inhibited over whole ranges of wavelength. Determination of adenine nucleotide and carbohydrate revealed that these three drugs combination promoted their recovery at the period of recirculation of the blood flow after ischemia. In particular, increase in lactate was inhibited from the period of ischemia with prevention of progression of lactic acidosis. Moreover, in the group with administration of the three drugs combination and the group with administration of 20% or isotonic mannitol the increase in the cortical water content following recirculation of the blood flow was inhibited. From these result it is considered that each of the three drugs shows not only inhibition of lipid peroxidation as radical scavengers but also protective effect on lowering of activities of ion channel (Na+, K+-ATPase, etc.) by the free radicals.
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PMID:[The protective effect of mannitol, vitamin E, and glucocorticoid in experimental cerebral ischemia--influence on lipid peroxidation, energy metabolism and brain edema]. 311 28

A case of aneurysm of the extracranial internal carotid artery treated by aneurysmal neck resection and end-to-end anastomosis of the internal carotid artery under the administration of Sendai Cocktail, which is composed of 20% mannitol solution, dexamethasone and vitamin E and has brain protective effects from ischemia. The patient, a 55-year-old man, was admitted to Yonezawa City Hospital on October 11, 1984, with chief complaints of transient consciousness disturbance and left hemiparesis. On admission, no neurological deficit was found but pulsatile fixed mass was found in the right submandibular region. CT scan revealed multiple low density areas in the right cerebral hemisphere and right upper cervical mass, which was enhanced in a part. Right carotid angiography revealed aneurysm of the extracranial internal carotid artery. On October 31, 1984, operation was performed. In the operative procedure, it needed temporary occlusion of the right carotid artery for 143 minutes and 14 minutes, because the aneurysm severely adhered to surrounding tissue and extended to the skull base. Collateral circulation through the circle of Willis was poor in this case but ischemic complication was not found. On November 20, 1984, he discharged without neurological deficit. Postoperative angiography, one year after the operation, showed good flow through the site the primary end-to-end anastomosis.
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PMID:[Aneurysm of the extracranial internal carotid artery treated by neck resection and end-to-end anastomosis under the administration of brain protective substances]. 312 11

A study was made of protective effect of several drugs (mannitol, phenytoin, vitamin E and dexamethasone) against the deprivation of both glucose and oxygen from the bathing medium on electrical activities of guinea-pig hippocampal neurons in vitro. Using guinea-pig hippocampal slice, we recorded antidromic field potentials in the granular cell layer of the dentate gyrus with stimulating mossy fibers. "Ischemia" of a slice was achieved by substracting both glucose and oxygen from the perfusing medium. In standard medium, after 10 minutes of ischemia, field potentials had minimum recovery with an amplitude of 5% of control after 60 minutes in the standard medium. Mannitol treatment had no protective effect, but phenytoin, vitamin E and dexamethasone had clear dose-dependent effect. The protective effect was evaluated by recovery of field potential amplitude of the 60 minutes postischemic response and histological examination of the brain slice tissue. The degree of the histological damage was correlated with recovery of field potential. In this experiment we have demonstrated that phenytoin and vitamin E obviously have the protective action against ischemic neuronal damage in the guinea-pig hippocampal slice and the combined application of these drugs were more effective.
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PMID:[Protective effect of various agents against ischemic neuronal damage in guinea pig hippocampal neurons studied in vitro]. 314 4

The effects of vitamin E on compression injury of the spinal cord associated with ischemia were studied in rats. Growing rats were divided into two groups and given diet containing 2 IU/100 g (group C) or 50 IU/100 g (group E) of alpha-tocopherol acetate from 8-10 weeks before experiments. The motor disturbance induced by spinal cord injury was greatly reduced by vitamin E-supplementation. After injury, the value of TBA-reactive substances (TBARS) was immediately increased and the level of alpha-tocopherol was correspondingly decreased in the spinal cord. A higher level of TBARS was observed in the proximal region than in the injured region of the spinal cord. The high level persisted for 24 hrs in group C, but decreased within 1 hr in group E. Pathological examination of the spinal cord revealed less damage, such as bleeding and edema, in group E than in group C.
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PMID:[An experimental study on preventive effect of vitamin E in spinal cord injury]. 323 95

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


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