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)

Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to test the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured free arachidonic acid and slow reacting substance of anaphylaxis (SRS-A) and leukotriene C4 in the brain tissue. Moreover, we studied the influence of inhibitor of SRS-A release on postischemic cerebral edema. Severe forebrain ischemia in rats was induced by the modification of the method described by Pulsinelli and Brierley. Both vertebral arteries were electrocauterized through the alar foramen and then bilateral common carotid arteries were clamped by aneurysmal clips and mean arterial pressure was reduced to 80-90 mmHg. EEG activity was isoelectric throughout the period of carotid clamping. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemic level. Following the desired ischemic or postischemic periods, the brains were frozen in situ with liquid nitrogen. The brains were then chiselled out during irrigation with liquid nitrogen and stored at -80 degrees C until analysis. The brain extracts were analysed by high performance liquid chromatography for free arachidonic acid, by bioassay using the ileum of guinea pig for SRS-A and by radioimmunoassay for leukotriene C4. Brain water content was calculated with dry weight method. Inhibitor of SRS-A release, tranilast, was given intraperitoneally, 100 mg/kg 30 minutes before induction of ischemia and 50 mg/kg immediately before recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Brain tissue leukotrienes in cerebral ischemia and the effect of inhibitor of SRS-A release on postischemic cerebral edema]. 246 14

Arachidonic acid (AA) accumulation in the ischemic myocardial tissue. Its release and subsequent metabolization into several classes of eicosanoids and lipid peroxides occurs in parallel with the development of myocardial ischemic injury and may be initiated by the loss of energy-rich phosphates. The profile of eicosanoid release during ischemia and reperfusion differs both quantitatively and qualitatively from that seen under non-ischemic conditions. This is at least partially due to the presence of stimulated inflammatory cells and platelets with a considerable activity of AA-metabolizing enzymes as well as endothelial injury. Thus, cardiac eicosanoid release in nonischemic conditions is primarily beneficial, resulting in more effective adaption of its function to the needs of the circulation. Eicosanoid release in acute ischemia is primarily deleterious and enhances inflammatory reactions and functional disturbances.
 ...
PMID:Eicosanoids in myocardial ischemia. 251 26

Arachidonic acid metabolites have been implicated as mediators of progressive dermal ischemia. Decubitus ulcer formation results from chronic mechanical pressure on the skin which results in a diminished blood supply to the skin and underlying tissues. To evaluate the role of thromboxanes in pressure wounds, we measured TxB2, a stable metabolite of TxA2, in spontaneously occurring pressure wounds on Greyhound dogs. In pressure wounds in which the skin was showing early signs of pressure necrosis but was still intact, elevated TxB2 concentrations were found in healthy appearing tissues immediately adjacent to the pressure wounds, in the inner edge of the wounds, and in the center of the wounds. Significantly greater TxB2 concentrations (P less than 0.05) were found in the center of the intact wounds versus the TxB2 concentrations in the inner edge of the wounds or in healthy appearing tissues adjacent to the wounds. In pressure wounds in which the center of the wound had ulcerated or had an eschar, elevated TxB2 concentrations were found in tissues in the inner edge of the wounds and in healthy appearing tissues immediately adjacent to the pressure wounds. These results demonstrate the occurrence of elevated thromboxane concentrations in and around spontaneously occurring pressure wounds.
 ...
PMID:Elevation of thromboxane in pressure wounds. 276 67

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.
 ...
PMID:In vitro oxidation of alpha-tocopherol (vitamin E) in human platelets upon incubation with unsaturated fatty acids, diamide and superoxide. 282 39

Arachidonic acid is metabolized to leukotriene (LT) B4, C4, D4, and E4 by lipoxygenase. LTB4 is a chemotactic agent while LTC4 and LTD4 stimulate smooth muscle fibers to contract. Mesenteric vessels have the capacity to release leukotrienes. The possibility that leukotrienes might be responsible for or contribute to mesenteric ischemia during mesenteric low flow, embolism, and thrombosis prompted us to investigate their action on mesenteric vessels. LTB4, C4, and D4 were applied topically on small bowel mesentery of 22 Sprague-Dawley rats in sequentially increasing concentrations. Mesenteric arterioles with diameters of 8-20 microns were observed through a microscope and vessel diameters were measured using a video shear monitor. LTB4 had no effect on diameter, but doses as low as 3 X 10(-8) M induced white blood cell adherence to venular endothelium, reflecting the potent chemotactic properties of this compound. LTC4 and D4 had no effect on systemic blood pressure or white blood cell adherence. Applications of 6.4 X 10(-9), 3.2 X 10(-8), and 6.4 X 10(-8) M LTC4 decreased mesenteric arteriolar diameter to 85.3* +/- 4.7% (mean +/- SD), 75.7* +/- 7.5%, and 66.8* +/- 6.1% of baseline, and 4 X 10(-9), 2 X 10(-8), and 4 X 10(-8) M LTD4 decreased diameter to 84.9* +/- 6.1%, 75.1* +/- 4.2%, and 64.1* +/- 5% of baseline, respectively (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of leukotrienes B4, C4, and D4 on rat mesenteric microcirculation. 303 80

[1-14C-]Arachidonic acid was injected into the lateral ventricle of the gerbils (meriones unguiculatus) two hours before producing brain ischemia by the bilateral ligation of the carotid arteries. Ten minutes before the carotid ligation a group of animals received an additional intraventricular injection of cold cytidine (2.5 mumol/brain). Control animals with and without cytidine, together with the ischemic group, were decapitated directly into liquid nitrogen ten minutes after carotid ligation or sham surgery. Cytidine is able to both stimulate arachidonic acid incorporation into lipids and noticeably correct the release of this acid from polar lipids induced by ischemia. Based on these findings, it is possible to assume that cytidine exerts an effect on the biosynthesis of phosphoglycerides as well as on their catabolic activities.
 ...
PMID:Effect of cytidine on the modification of phospholipid metabolism induced by ischemia. 310 88

Three different levels of global forebrain ischemia were induced in rats and their plasma levels of Thromboxane B2 (TXB2) and 6 Keto PGF1 alpha were determined to investigate the relation between severity of ischemia and eicosanoid production. Ischemia stimulates the activity of cellular lipase whose actions cause deacylation of brain phospholipids and release of free fatty acids. Arachidonic acid (A.A.) is one of the predominant fatty acids which is liberated in brain after ischemia. A.A. is the primary substrate for the synthesis of prostaglandins (PGs), Thromboxane A2 (TXA2) and Prostacyclin (PGI2), which play an important role in regulation of platelet aggregation and vasotonus. Thromboxane is a potent platelet aggregator and vasoconstrictor. On the other hand, PGI2 has the opposite nature. Therefore it can be considered that PGs and moreover, the balance of TXA2 and PGI2 may have an intimate relation to the development of cerebral ischemia. Three different levels of ischemia were produced by bilateral carotid artery ligation (BLCL) using three kinds of rats with different blood pressure ranges, namely, SHRSP (Stroke-prone spontaneously hypertensive rats), SHRSR (Stroke-resistant spontaneously hypertensive rats) and WKY (Wistar kyoto rats). It is known that higher pressure groups suffer severe ischemia by BLCL procedure. Hypertensive rats (SHRSP, SHRSR) were originally produced from WKY. The experimental animals used were about 300 gr and 16 weeks old male rats. The plasma and brain TXB2 and 6 Keto-PGF1 alpha, stable metabolites of TXA2 and PGI2 were measured by radioimmunoassay. The chronological changes of brain and plasma PGs levels after ischemia using SHRSR were also investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effect of bilateral common carotid artery ligation on prostaglandin levels (TXA2, PGI2) in spontaneously hypertensive rats (SHRSP, SHRSR) and normotensive rats (WKY)]. 352 27

Dietary fatty acids and cholesterol have been associated with the development of atherosclerosis. This paper suggest metabolic pathways involved in this process. Specific fatty acids (DGLA, GLA) with high specificity for cholesterol transport enzymes give a high efficiency for transport of cholesterol to the liver. Arachidonic acid (AA) is proposed to block the endogenous conversion of dietary linoleic acid to GLA and DGLA, which results in impared cholesterol transport to the liver and increased serum levels. Increased levels of cholesterol and its oxygenation products promote the release of AA from membrane phospholipids and its conversion to thromboxane, resulting in a positive feedback reaction of thrombus formation and ischemia.
 ...
PMID:Fatty acids, cholesterol, and their roles in ischemia. 361 15

Gerbil forebrains were frozen in situ to inactivate the tissues, and 1,2-diacylglycerols were first measured quantitatively by HPLC. Although 1,2-diacylglycerols were completely recovered from the HPLC column, the control amount of 1,2-diacylglycerol in gerbil forebrain was only 79.6 nmol/g wet weight, which is about one-fourth of that previously reported for gerbil brain inactivated by liquid N2 after decapitation instead of in situ freezing. The fatty acid composition of 1,2-diacylglycerols in gerbil forebrain was first reported and the control 1,2-diacylglycerols were richer in palmitic acid than in stearic acid or arachidonic acid, which is rather different from the data previously reported for mouse or rat brain obtained by decapitation and analyzed by traditional TLC methods. The amount of 1,2-diacylglycerol increased by 82.9% in gerbil forebrain during 5 min of ischemia induced by bilateral carotid ligation. Arachidonic acid and stearic acid were abundant in the 1,2-diacylglycerols produced by 5 min of ischemia. Thus we were able to obtain accurate values of the amount and the fatty acid composition of 1,2-diacylglycerols in gerbil forebrains using HPLC and in situ freezing technique.
 ...
PMID:Accurate evaluation of 1,2-diacylglycerol in gerbil forebrain using HPLC and in situ freezing technique. 373 96

We studied the effect of arachidonic acid on function and CPK release of normal, ischemic and reperfused isolated rat hearts. Under control conditions arachidonate (10 micrograms/ml) produced a transient inotropic effect which gradually reversed during a 90 minute perfusion. Creatinephosphokinase (CPK) release was augmented by arachidonic acid, particularly under high flow (pre-ischemia and reperfusion) conditions. Recovery of contractility following reperfusion of ischemic myocardium was significantly depressed by arachidonic acid. Vitamin E (100 ng/ml) an antioxidant and free radical scavenger, reduced the enzyme leakage and enhanced recovery of contractility of reperfused myocardium. It also prevented the depression in contractility during control perfusion. Similar protective effects were observed by perfusing the heart with reduced calcium but not by nifedipine; a calcium channel blocker, indomethacin; a prostaglandin synthesis inhibitor or nordihydroguarietic acid; a lipoxygenase inhibitor. Arachidonic acid also inhibited membrane Na+/K+-ATPase although it is unlikely that this property mediated its cardiotoxic influence since it was not prevented by vitamin E. In addition, we observed that arachidonic acid increased the coronary resistance of isolated hearts, probably through enhanced calcium influx as this constriction was reduced by low calcium as well as by nifedipine. Thus, arachidonic acid possesses distinct properties. Its cardiotoxic influence is likely mediated by free radical generation.
 ...
PMID:Toxic properties of arachidonic acid on normal, ischemic and reperfused hearts. Indirect evidence for free radical involvement. 392 Jun 82


<< Previous 1 2 3 4 5 6 Next >>