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)

Platelet-activating factor is released from inflammatory cells. It activates neutrophils, releases secondary messengers, and mediates mucosal ulceration and ischemia in the rat. We assessed its possible role in the pathogenesis of ulcerative colitis. Colonic biopsy specimens from patients with active ulcerative colitis and controls were incubated for 4 h in Tyrode's buffer in the presence or absence of 0.2 microM calcium ionophore (A23187) or 50 microliter of antihuman immunoglobulin E. Platelet-activating factor was determined in the tissue by aggregation assay after extraction with 80% ethanol and was confirmed by thin-layer chromatography and its inactivation by phospholipases. Platelet-activating factor was not detected in normal mucosa. Only A23187 and antihuman immunoglobulin E stimulated its activity: mean +/- SE, 43.2 +/- 8.6 and 33.0 +/- 6.1 pg/10 mg wet wt, respectively. In active ulcerative colitis basal platelet-activating factor activity was 8.9 +/- 3.5 pg/10 mg wet wt. A23187 and antihuman immunoglobulin E induced significantly higher stimulation of platelet-activating factor synthesis when compared with their effects on normal mucosa: 200 +/- 28 and 70 +/- 8.3 pg/10 mg wet wt, respectively. The enhanced stimulation induced by A23187 was dose-dependently inhibited by salazopyrine, 5-amino-salicylic acid, and prednisolone, but not by sulfapyridine. It is thus suggested that platelet-activating factor may be involved in the pathogenesis of the inflammatory response in ulcerative colitis and that its inhibition by steroids, 5-aminosalicylic acid, and salazopyrine may be an additional mechanism to explain their therapeutic effects.
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PMID:Role of platelet-activating factor in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine and prednisolone. 290 95

Evidence is presented which implicates increased oxygen free radicals during ischemia reperfusion of gerbil brain. Salicylate, which reacts with hydroxyl free radicals to yield dihydroxybenzoic acid (DHBA), was used as an in vivo trap. Brain ischemia for at least 5 min followed by reperfusion yielded significantly increased brain DHBA. Without reperfusion or with only 2 min of ischemia and then reperfusion, the production of DHBA was not increased. Increased levels of DHBA in brain correlated with ischemia reperfusion-mediated behavioral modification of gerbils, but salicylate administration did not protect against the behavior changes.
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PMID:Oxygen free radical involvement in ischemia and reperfusion injury to brain. 338 Mar 59

Anterior ischemic optic neuropathy (A.I.O.N.) may cause optic disc edema in type-I diabetes. A.I.O.N. affects diabetic patients of all ages. Such optic neuropathy is more likely to become bilateral in diabetics than in the non-diabetic subjects. A 41-year-old diabetic insulin-dependent woman presented A.I.O.N. in RE; 5 years later, the same affection occurred in LE. The clinical course was relatively benign in both eyes, with good functional restitution. The patient was treated by high doses of Sodium Salicylate and Sulfinpyrazone. The pathogenesis of optic disc edema in type-I diabetes is, according to Hayreh (1981), ischemia of different grade in the district of the posterior ciliary arteries: microangiopathy, rheological anomalies and atherosclerotic added lesions produce a variability of clinical pictures of increasing seriousness. Our case has an intermediate position in such a continuous spectrum. The VEP supported the diagnosia of A.I.O.N.
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PMID:Anterior ischemic optic neuropathy in type I diabetes. 345 16

Experiments were performed on rats subjected to renal ischemia and various treatment procedures to determine the origin and functional consequences of vascular obstruction. To this end, its occurrence and severity was assessed qualitatively and quantitatively in the outer medulla, where it is particularly prominent. The incidence of medullary hyperemia was not influenced by inhibiting thrombocyte aggregation with 5 or 70 mg/kg of acetyl salicylic acid or preventing fibrin deposition with 100 IE/kg of heparin before ischemia, and these substances produced no improvement renal function. The incidence and degree of hyperemia, however, could be substantially reduced or completely eliminated by acutely raising blood pressure after ischemia or by decreasing the number of circulating erythrocytes before ischemia. These procedures were effective in raising filtration rate and tubular reabsorption from 20% to 60% of normal, in restoring renal blood flow and vascular resistance to completely normal, and in diminishing epithelial damage both three and 18 hours after ischemia. The following conclusions are drawn: first, vascular obstruction, which is not lessened by inhibiting thrombus formation but is easily reversed or prevented by raising perfusion pressure or decreasing hematocrit, is probably caused by erythrocyte aggregation during ischemia. Second, vascular obstruction, which appears to raise renal vascular resistance and lower blood flow and filtration rate, cannot be limited to the medulla but must also be present in the cortex. Finally, reversing or preventing vascular obstruction can fully restore renal perfusion, partially restore glomerular and tubular function, greatly reduce tubular necrosis and thus prevent renal failure.
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PMID:The contribution of vascular obstruction to the functional defect that follows renal ischemia. 356 Jun 46

The effects of preconditioning on development of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat heart. Hearts were randomly divided into four groups: group I, aerobically perfused time-matched controls with no preconditioning or ischemia; group II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subjected to one cycle of preconditioning, consisting of 5-min global ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5-min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min reperfusion. The incidences of VF and VT were reduced from their nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively. Maximum malondialdehyde formation, as an indirect marker of free radicals, was observed after 30-min ischemia followed by 10-min reperfusion (0.72 +/- 0.1 nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreconditioned ischemic value of 0.72 +/- 0.1 to 0.35 +/- 0.02 and 0.26 +/- 0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free radical formation was directly detected by salicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of preconditioning on reperfusion arrhythmias, myocardial functions, formation of free radicals, and ion shifts in isolated ischemic/reperfused rat hearts. 751 78

To obtain direct evidence of oxygen radical activity in the course of cerebral ischemia under different intraischemic temperatures, we used a method based on the chemical trapping of hydroxyl radical in the form of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA) following salicylate administration. Wistar rats were subjected to 20 min of global forebrain ischemia by two-vessel occlusion plus systemic hypotension (50 mm Hg). Intraischemic striatal temperature was maintained as normothermic (37 degrees C), hypothermic (30 degrees C), or hyperthermic (39 degrees C) but was held at 37 degrees C before and following ischemia. Salicylate was administered either systemically (200 mg/kg, i.p.) or by continuous infusion (5 mM) through a microdialysis probe implanted in the striatum. Striatal extracellular fluid was sampled at regular intervals before, during, and after ischemia, and levels of 2,3- and 2,5-DHBA were assayed by HPLC with electrochemical detection. Following systemic administration of salicylate, stable baseline levels of 2,3- and 2,5-DHBA were observed before ischemia. During 20 min of normothermic ischemia, a 50% reduction in mean levels of both DHBAs was documented, suggesting a baseline level of hydroxyl radical that was diminished during ischemia, presumably owing to oxygen restriction to tissue at that time. During recirculation, 2,3- and 2,5-DHBA levels increased by 2.5- and 2.8-fold, respectively. Levels of 2,3-DHBA remained elevated during 1 h of reperfusion, whereas the increase in 2,5-DHBA persisted for 2 h. The increases in 2,3- and 2,5-DHBA levels observed following hyperthermic ischemia were significantly higher (3.8- and fivefold, respectively). In contrast, no significant changes in DHBA levels were observed following hypothermic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. 764 4

Salicylate is widely used as a stable trap for the highly reactive hydroxyl radical. The purpose of this study was to determine whether the addition of salicylate to hearts subjected to ischemia and reperfusion was able to prevent some injury. Salicylate was able to inhibit mitochondrial damage, and preserved ascorbate and alpha-tocopherol depletion due to ischemia/reperfusion in rat hearts. It did not prevent the elevation of low molecular weight iron. We conclude that salicylate functions as an antioxidant and afforded protection against ischemia and reperfusion.
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PMID:Salicylate in the perfusate during ischemia/reperfusion prevented mitochondrial injury. 771 5

Transient global ischemia may lead to persistent production of reactive oxygen species in selected brain regions thereby contributing to selective vulnerability to ischemia. Using cerebral microdialysis, we assessed the production of the highly reactive hydroxyl radical (OH.) in rat hippocampus during global ischemia and reperfusion (IR). During IR, perfusate containing salicylic acid was collected and analyzed for non-enzymatic hydroxylation of salicylate to 2,3-DHBA. Since 21-aminosteroids can attenuate excitatory amino acid-mediated OH. production in the brain, we repeated the experiments after administration of the 21-aminosteroid, U-74389G. The data indicate that 2,3-DHBA level increased progressively between 15 and 60 min after reperfusion, reaching values nearly three times the baseline value at 60 min. U-74389G, given 30 min before ischemia, greatly attenuated the increase in 2,3-DHBA during reperfusion. This is the first evidence for prolonged OH. production in the hippocampus after reperfusion in vivo which can be prevented by 21-aminosteroids.
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PMID:Prolonged production of hydroxyl radical in rat hippocampus after brain ischemia-reperfusion is decreased by 21-aminosteroids. 782 63

The difficulty in direct detection of oxygen-derived free radicals (OFR) in the intact kidney has left uncertain the role of OFR in renal hypoperfusion injury. Salicylate hydroxylation was used as a sensitive method of estimating the extent of production of highly reactive hydroxyl radicals in renal ischaemia-reperfusion injury in the intact rat kidney perfused with recirculating cell-free medium. The reaction products were detected and quantified by HPLC with electrochemical detection. Hydroxyl radicals were detected as 2,5-dihydroxybenzoic acid (2,5-DHBA). Ischaemia for 15 min followed by reperfusion for 15 min caused more than a twofold increase in 2,5-DHBA concentration (to 2279 +/- 225 pg/g tissue weight) compared to controls (933 +/- 103, P < 0.001). Addition of 15 mM dimethylthiourea (DMTU) before induction of ischaemia prevented this increase. Induction of hypoxia for 15 min with continued perfusion (as a model of low-flow ischaemia) had no significant effect on hydroxyl radical formation. We conclude that significant quantities of hydroxyl radicals form in the absence of circulating leucocytes during reperfusion following ischaemia, but not during hypoxia in the perfused rat kidney.
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PMID:Hydroxyl radical generation following ischaemia-reperfusion in cell-free perfused rat kidney. 787 60

The formation of hydroxyl radical in the extracellular fluid in striatum of rats subjected to 4-vessel occlusion during ischemia and reperfusion was measured by HPLC with UV detector using salicylic acid as a trapping agent. Hydroxyl radicals react with salicylic acid yielding 2,3- and 2,5-dihydroxybenzoic acids which can be separated by liquid chromatography. The striatum was perfused with artificial cerebrospinal fluid containing 0.5 mmol.L-1 salicylic acid at a flow rate of 2.5 microliters.min-1. The results indicate that the concentration of 2,5-dihydroxybenzoic acid in the perfusates was highest during 25 min reperfusion and no change was found during ischemia. Vit E at 30, 60 and 120 mg.kg-1 i.p. 20 min before ischemia was shown to dose dependently suppress the rise of 2,5-dihydroxybenzoic acid after reperfusion. The results suggest that the HPLC method is useful and reliable for the measurement of hydroxy radical in global ischemia in vivo.
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PMID:[HPLC--detection of hydroxyl radicals in striatum extracellular fluid in rats subjected to reperfusion after cerebral ischemia and the action of vitamin E]. 823 77


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