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)

1. We measured redox systems in resting and activated rat peritoneal mast cells under anoxia by using the redox metabolism of free doxyl stearic acid (5DS) and phosphatidylcholine with two 5DS molecules esterified to the glycerol (di5DSPC). 2. In the absence of oxygen, 5DS and di5DSPC were reduced to the corresponding hydroxylamines by resting mast cells, with apparent first-order kinetics of 0.085 and 0.078/min, respectively. 3. The activation of mast cells induced by compound 48/80 and bradykinin did not affect the rates of reduction of the nitroxides, and therefore the activation appeared not to be closely coupled to the redox system of these cells; this finding implies that ischemia is unlikely to affect histamine release from mast cells. 4. The oxidation of the nitroxides by the mast cells was very fast and may be nonenzymatic. 5. We concluded that nitroxides can be useful probes of redox metabolism in the mast cells but, because the characteristics of the cellular reduction-reoxidation systems differed from that of other cells, the use of this approach in other cells will require careful characterization of the redox metabolism of nitroxides in those cells.
 ...
PMID:Characterization of redox activity in resting and activated mast cells by reduction and reoxidation of lipophilic nitroxides. 979 26

We tested the hypothesis that activation of the 12-lipoxygenase (12-LO) pathway of arachidonic acid metabolism contributes to the protective effect of protein kinase C (PKC) activation and ischemic preconditioning (PC), and we report, in perfused rat heart, that both PC and the PKC activator 1,2-dioctanoyl-sn-glycerol (DOG) confer a similar protective effect and stimulate a comparable accumulation of 12-LO metabolites. The 12-LO product, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], was increased in DOG-treated (22.8 +/- 4.4 ng/g wet wt) and PC hearts (26.8 +/- 5.5 ng/g wet wt) compared with control (13.8 +/- 2.1 ng/g wet wt, P < 0. 05), and this increase was blocked by 12-LO or PKC inhibitors. Both DOG pretreatment and PC improved recovery of left ventricular developed pressure (LVDP) nearly twofold after 20 min of ischemia; this improvement was blocked by 12-LO inhibitors and was mimicked by infusion of 12-hydroperoxyeicosatetraenoic acid [12(S)-HpETE; 67 +/- 6% recovery of LVDP vs. 35 +/- 3% for untreated hearts]. Also, the protection afforded by 12(S)-HpETE, as well as by PC, was attenuated by the K+-channel blocker 5-hydroxydecanoate, suggesting that the downstream mechanisms of 12(S)-HpETE-mediated protection are similar to PC. Furthermore, PC stimulates 12-LO metabolism in perfused rabbit heart, and 12-LO inhibition blocks PC-induced cardioprotection. Thus the data suggest that 12-LO metabolism plays an important role in cardioprotection.
 ...
PMID:Lipoxygenase metabolism of arachidonic acid in ischemic preconditioning and PKC-induced protection in heart. 1036 92

The present study focuses on the qualitative and sequential development of myocardial ultrastructural changes during the first 10 min of reperfusion in isolated rat hearts exposed to 60 min of global ischemia. The frequency of and the association between ultrastructural changes were examined by semiquantitative morphometry using the micrograph as unit. In each micrograph the subcellular components of the myocytes (sarcolemma, mitochondria, myofilaments and nucleus) and the endothelial cells were evaluated and graded as slightly, moderately, or severely altered. Ischemia alone induced moderate to severe ultrastructural alterations. The myocytes revealed sarcolemmal disattachment or rupture. The myocytic mitochondria had a clear matrix with abundant broken cristae and amorphous matrix densities. The myofilamental pattern was irregular or even disrupted, and most nuclei had reduced density and showed margination of chromatin. The endothelium showed vacuolization, rupture of the plasma membrane, and extracellular accumulation of cellular debris. During the first 2 min of reperfusion severe ultrastructural alterations were partly reversed. After 10 min of reperfusion both the frequency and grade of myocardial ultrastructural alternations were similar to that observed after ischemia. Cristal adhesions occurred predominately during reperfusion and were associated with moderately and severely altered myocytic mitochondrial alterations. In conclusion, the results showed that ischemic-induced ultrastructural alterations were transiently improved upon reperfusion. With exception of the development of cristal adhesions, the acute phase of reperfusion was not associated with additional ultrastructural changes in isolated buffer-perfused rat hearts exposed to prolonged ischemia.
 ...
PMID:The initial phase of myocardial reperfusion is not associated with aggravation of ischemic-induced ultrastructural alterations in isolated rat hearts exposed to prolonged global ischemia. 1036 3

The role of protein kinase C (PKC) in the protection of ischemic preconditioning (PC) is still controversial, partly because of the multiple isozymes of PKC and the inability to directly measure PKC activity in vivo. In this study we have used novel peptide inhibitors which correspond to part of the amino acid sequence from the isozyme-specific RACK-binding site on the PKC molecule. The peptides prevent binding of a specific activated PKC isozyme to its RACK, thus halting isozyme translocation and function. The inhibitor peptides are cross-linked to the membrane-translocating antennapedia homeodomain peptide that allows their entry into cells. The effect of inhibitors of PKC-beta, -delta, -epsilon and -eta were evaluated. Rabbit adult ventricular myocytes were obtained by enzymatic dissociation. Ischemia was simulated by centrifuging the myocytes into an oxygen-free pellet for 180 min. PC was induced by 10 min of pelleting followed by resuspension in oxygenated medium for 15 min. During simulated ischemia cells undergo a predictable increase in osmotic fragility as judged by determination of the number of stained cells following their incubation in hypotonic (85 mOsm) trypan blue. The percentage of cells experiencing membrane rupture, and thus cell staining, was considered to be an index of ischemic injury. PC significantly delayed the progression of osmotic fragility during simulated ischemia (P<0.01). The protection of PC was abolished by the peptide inhibitor of PKC-epsilon but not by the peptide inhibitors selective for PKC-beta, PKC-delta, or PKC-eta; each was applied at 100 n N. Protection could also be induced by the PKC activator oleoylacetyl glycerol, and that protection was aborted by the inhibitor selective for PKC-epsilon, but not by the inhibitor for PKC-delta. None of the above peptide treatments affected the osmotic fragility in non-PC cells during simulated ischemia. Our studies further support PKC as a critical part of the signal transduction pathway in PC and indicate that PKC-epsilon alone is responsible for the early phase of PC's protection in rabbit cardiomyocytes.
 ...
PMID:Protein kinase C-epsilon is responsible for the protection of preconditioning in rabbit cardiomyocytes. 1052 30

Although protein kinase C (PKC) plays a pivotal role in ischemic preconditioning, it is not clear what the end effector is that protects the myocardium. In isolated, paced (1.25 Hz, 36-37 degrees C) adult rat cardiomyocytes, the effects of PKC preactivation by diacylglycerol on cell motion, intracellular Ca(2+) concentration ([Ca(2+)](i); indo 1), and intracellular pH (pH(i); seminaphthorhodafluor-1) during simulated ischemia-reperfusion (I/R) were investigated. The degree of reperfusion-induced contracture was significantly attenuated in the myocytes pretreated with 10 microM 1, 2-dioctanoyl-sn-glycerol (DOG; n = 19) compared with the untreated myocytes (n = 23, P < 0.02). There were no differences in twitch amplitude, end-diastolic [Ca(2+)](i), or peak-systolic [Ca(2+)](i) during I/R between the DOG-pretreated and untreated myocytes. Although there were no differences in pH(i) during ischemia, the pH(i) overshoot during reperfusion was significantly delayed in the DOG-pretreated myocytes compared with the untreated myocytes (n = 17 for each, P < 0.01). Chelerythrine completely abolished the favorable effects of DOG on the reperfusion-induced contracture and the pH(i) overshoot. These data suggest that diacylglycerol attenuates I/R injury in isolated, paced cardiomyocytes, which may be related to the slower pH(i) overshoot during reperfusion.
 ...
PMID:Diacylglycerol delays pH(i) overshoot after reperfusion and attenuates contracture in isolated, paced myocytes. 1056 23

Ceramides are a class of signaling molecules that can acutely accumulate in tissues as part of a "stress response." They are classically measured by the diacylglycerol kinase assay, which, in general, measures total ceramide rather than individual moieties within the diverse ceramide family. The present study was undertaken to 1) adapt current HPLC-mass spectrometry technology for measuring individual renal ceramides, and 2) use this technique to more fully characterize the nature of the renal ceramide "stress" reaction. Renal cortical tissues were obtained from CD-1 mice under control conditions and 2 or 18 h after renal injury (ischemia-reperfusion and glycerol-mediated myohemoglobinuria). C24, C22, and C16 ceramides were identified in normal renal cortex, constituting 70, 10, and 20% of the total ceramide pool, respectively. Within each of these families, heterogeneity was apparent because of differing degrees of unsaturation (0-3 double bonds) in the constituent fatty acid of ceramide. Renal injury dramatically changed ceramide profiles: 1) total ceramide increased by approximately 300%; 2) although all ceramides participated in this reaction, they did so to differing degrees; 3) this caused pronounced changes in ceramide distribution patterns; 4) injury induced a striking shift toward unsaturated (vs. saturated) fatty acids within the C22 and C24 (but not the C16) ceramide pools; and 5) the extent of these qualitative changes differed according to the etiology of the initiating renal damage. Thus we conclude that ceramide stress response involves major qualitative (and not simply quantitative) changes in ceramide expression that are partially disease dependent. These findings underscore the fact that simply measuring total renal ceramide content (e.g., by diacylglycerol kinase assay) substantially oversimplifies the nature and, hence, the potential implications of the ceramide stress reaction.
 ...
PMID:Renal cortical ceramide patterns during ischemic and toxic injury: assessments by HPLC-mass spectrometry. 1056 35

Intravenous infusion of glycerol has been used in patients with a cerebral infarction, expecting improvement in brain edema and cerebral blood flow (CBF). However, the mechanism of the improvement of CBF has not been clearly demonstrated. The aim of this study in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO) is to examine the effects of glycerol on leukocyte-endothelium interaction, which plays a critical role in the pathogenesis of brain injury by ischemia/reperfusion and concerns induction of secondary brain damage. Rhodamine 6G-labeled leukocytes at the brain surface were visualized with intra-vital fluorescence videomicroscopy through a closed cranial window and an analysis was made of the number of adherent leukocytes and the centerline leukocyte velocity in the venule before MCAO, after reperfusion of MCAO and after infusion of glycerol (Group 1) or saline (Group 2). The number of adherent leukocytes decreased and the centerline leukocyte velocity increased statistically significantly immediately after the infusion of glycerol in Group 1, but there was no significant change in Group 2. The infusion of glycerol washes away the adherent leukocytes and prevents them from interfering with the blood cell and plasma flow. Furthermore, secondary brain damage may be relieved by decreasing the adherence of leukocytes. In conclusion, modulating the adherence of leukocytes is one of the important factors in the neuroprotective effect of glycerol.
 ...
PMID:Glycerol attenuates the adherence of leukocytes in rat pial venules after transient middle cerebral artery occlusion. 1059 90

Short periods of ischemia followed up by reperfusion are known to protect the heart against injury caused by a subsequent sustained ischemia. This phenomenon, known as ischemic preconditioning, has also been recently shown to reduce ischemic liver damage, but the mechanisms involved are still unknown. By using isolated hepatocytes as an in vitro model of liver preconditioning, we have investigated the possible effect of preconditioning on intracellular pH and Na(+) homeostasis. Freshly isolated rat hepatocytes were preconditioned by 10 minutes of incubation under hypoxic conditions followed up by 10 minutes of reoxygenation and subsequently exposed to 90 minutes of hypoxia. Although preconditioning did not ameliorate adenosine triphosphate (ATP) depletion, preconditioned hepatocytes exhibited an increased resistance to cell killing during hypoxic incubation. Intracellular acidosis and Na(+) accumulation developing during hypoxia were appreciably reduced in preconditioned cells. The effects of preconditioning on intracellular pH, Na(+) homeostasis, and cytotoxicity were mimicked by stimulating protein kinase C (PKC) with 4beta-phorbol-12-myristate-13-acetate (PMA) or 1,2 dioctanoyl-glycerol (1,2 DOG). Conversely, inhibiting PKC with chelerythrine or blocking vacuolar proton ATPase (V-ATPase) with bafilomycin A(1) abolished the protection given by preconditioning or by PMA treatment on hypoxic acidosis, Na(+) overload, and hepatocyte killing. Similarly, the addition of Na(+) ionophore monensin also reverted the cytoprotection exerted by preconditioning. This indicated that ischemic preconditioning of isolated hepatocytes decreased cell killing during hypoxia by preventing intracellular Na(+) accumulation. We propose that, after preconditioning, the stimulation of PKC might activate proton extrusion through V-ATPase, thus, limiting intracellular acidosis and Na(+) overload promoted by Na(+)-dependent acid buffering systems.
 ...
PMID:Ischemic preconditioning reduces Na(+) accumulation and cell killing in isolated rat hepatocytes exposed to hypoxia. 1061 42

The aim of this investigation was to follow the metabolism of free TRAM flaps using microdialysis. Microdialysis is a new sampling technique that provide opportunities to follow the biochemistry in specific organs or tissues. A double-lumen microdialysis catheter or probe, with a dialysis membrane at the end, is introduced into the specific tissue. Perfusion fluid is slowly pumped through the catheter and equilibrates across the membrane with surrounding extracellular concentrations of low molecular weight substances. The dialysate is collected in microvials and analyzed by an instrument using very small volumes. Glucose, glycerol, and lactate concentrations were measured in the flaps and compared with those in a reference catheter that was placed subcutaneously in the femur. The investigation continued 72 hr postoperatively. The study group consisted of 14 women who underwent reconstruction with a free TRAM flap, and one woman with a double TRAM flap. During flap ischemia, the concentration of glucose was reduced, while the lactate and glycerol levels increased. The differences between the flaps and controls were statistically highly significant. After reperfusion of the flaps, the concentrations of glucose, lactate, and glycerol approached normal. One flap failed because of an arterial anastomosis thrombosis. This was clearly demonstrated by the samples from the microdialysis: the concentration of glucose fell to an unmeasurable level; the concentration of lactate increased for a period before it stopped due to lack of glucose; and the concentration of glycerol increased to a very high level, probably because ischemia caused damage to the cell membranes of which glycerol is an important part. The authors concluded that microdialysis can detect ischemia in free flaps at an early stage, making early surgical intervention possible.
 ...
PMID:Monitoring of free TRAM flaps with microdialysis. 1070 99

The pathogenesis of acute renal failure may involve, among other causes, ischemia, vascular congestion, arachidonic acid pathways, and reactive oxygen metabolites. The aim of this study is to evaluate the effects of pentoxifylline and vitamin E on the prevention of experimental acute renal failure induced by glycerol. Eighty-five Sprague-Dawley rats weighing 170-230 g were included in the study. The rats were randomly divided into four groups: group 1 was given 1 ml saline; group 2, glycerol; group 3, glycerol plus vitamin E, and group 4, glycerol plus pentoxifylline. Extent of histological renal tubular necrosis and regeneration in each animal were graded. Blood urea nitrogen, serum creatinine, and creatine kinase concentrations were measured. Mean blood urea nitrogen and serum creatinine concentrations and tubular injury scores were significantly lower in group 1 than in groups 2-4 (p < 0.001), but there were no significant differences among groups 2-4. We conclude that postinsult administration of vitamin E and pentoxifylline does not have a beneficial effect on prevention and severity of acute renal failure and that controlled, multicenter studies involving a large number of patients are needed to clarify this subject.
 ...
PMID:Effect of vitamin E and pentoxifylline on glycerol-induced acute renal failure. 1072 Aug 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>