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)

Prostacyclin is an important endothelial mediator involved in the interaction of neutrophils (PMN) with the vessel wall. Many studies have shown the beneficial effects of prostacyclin in ischemia and reperfusion. However, no previous study has investigated the direct effects of the prostacyclin analogs iloprost (ILO) and alprostadil (PGE(1)) on the endothelial part of the adhesion process. Human umbilical vein endothelial cells (HUVECs) were grown to confluence, stimulated with 300 U/ml TNF-alpha and treated with increasing concentrations of ILO and PGE(1). The cells were washed to remove TNF and the inhibitors and adhesion of fluorescence-green labeled PMN was determined microscopically. ICAM-1, VCAM-1 and E-selectin expression were measured by a cell-surface ELISA. The chemoattractant activity of the endothelial cell releasate was tested in a Boyden chamber.ILO and PGE(1) reduced PMN-adhesion in a concentration-dependent manner (ILO: -54 +/- 9 % at 0.5 microM, PGE1: -46 +/- 10 % at 10 microM). However, the surface expression of ICAM-1, VCAM-1 and E-selectin remained unaltered. When the supernatant of iloprost/PGE(1)-treated cells was transferred onto cells that were activated, but not treated with ILO or PGE(1), the reduction of PMN adhesion remains sustained. These data indicate that the inhibitory effect of ILO/ PGE(1) treatment is achieved by a reduced chemoattractant potential. PAF-antagonists were able to block neutrophil adhesion and mimicked the effect of ILO, while exogenous PAF diminished the inhibitory effect of ILO concentration-dependently. This study demonstrates the beneficial effects of ILO and PGE(1) on inflammatorily activated endothelial cells. These prostacyclin analogs inhibit PMN-adhesion despite maximal adhesion molecule expression by regulating the balance of - yet to be determined - endothelial-derived mediators.
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PMID:Prostacyclin inhibits adhesion of polymorphonuclear leukocytes to human vascular endothelial cells due to adhesion molecule independent regulatory mechanisms. 1249 64

In total, 41 consecutive patients with "idiopathic carpal tunnel syndrome" and abnormal electrophysiologic findings who underwent carpal tunnel release were studied prospectively. The focus of this investigation was the evaluation of the levels of specific chemical mediators within the serum and flexor tenosynovium of these patients. Blood was collected from these patients within 1 week prior to carpal tunnel release, and flexor tenosynovium was obtained at time of surgery. Specimens were then analyzed to determine the levels of interleukins 1 and 6, prostaglandin E(2) (PGE(2)), and malondialdehyde bis diethyl acetal. These values were compared to those of controls who had no evidence of carpal tunnel syndrome. A significant increase was noted in the serum malondialdehyde and tenosynovial levels of malondialdehyde, interleukin 6, and prostaglandin PGE(2) compared to controls. The elevated levels of these biologic factors and the absence of interleukin 1 elevation support a noninflammatory ischemia-reperfusion etiology for so-called "idiopathic carpal tunnel syndrome" that causes progressive edema and fibrosis of the tissues within the carpal canal. These findings correlate with previous histopathology reports. We believe that "idiopathic carpal tunnel syndrome" is an "-osis" not an "-itis."
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PMID:Biochemical evaluation of serum and flexor tenosynovium in carpal tunnel syndrome. 1249 76

Both ischemia and reperfusion injury and contractile activity are associated with the generation of reactive oxygen species and free radicals by skeletal muscle. In addition, exercise has been reported to lead to the formation of a circulating free radical species that is detectable in the blood by spin trapping before analysis by electron-spin resonance (ESR) techniques. Previous analysis of the ESR signal indicated that the circulating species is either a carbon- or oxygen-centered lipid-derived free radical. The current data indicate that this species is present in the blood of anesthetized rats after 4-h ischemia and 1 h of reperfusion of a single hindlimb. During 4 h of ischemia, the species was also present in microdialysates from the tibialis anterior muscle but was unchanged in magnitude compared with control tissue. During 1 h of reperfusion, the signal intensity increased by a mean of 420% (P < 0.05, n = 4). Hydroxyl radical activity in the interstitial fluid also significantly increased during ischemia and further increased by a mean of 210% (P < 0.05, n = 4) during reperfusion. No changes in interstitial superoxide levels were seen, but interstitial PGE(2) content also increased during reperfusion. A significant positive correlation was found between the magnitude of the ESR signal and both the hydroxyl radical activity and PGE(2) content of microdialysis fluids. These data support the hypothesis that the circulating free radical species is formed in the interstitial fluid by hydroxyl radical interaction with a lipid that may be released from reperfused tissue with a similar pattern to prostanoids.
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PMID:Ischemia and reperfusion of skeletal muscle lead to the appearance of a stable lipid free radical in the circulation. 1254 39

Prostaglandin E1 (PGE1) may relieve rest pain and heal ulcers in critical limb ischemia, but its mechanism of action is still incompletely understood. To investigate the effects of PGE1 treatment on endothelial function evaluated as brachial artery flow-mediated vasodilation (FMV) and on soluble adhesion molecule plasma levels (vascular adhesion molecule-1 [sVCAM-1] and intercellular adhesion molecule-1 [sICAM-1]), 12 patients with critical limb ischemia were treated with daily PGE IV infusion (alprostadil 60 microg) for 2 weeks. FMV and plasma sICAM-1 and sVCAM-1 concentrations were determined at baseline, after the first infusion, and after 1 and 2 weeks. Compared with 30 healthy control subjects, patients had higher baseline sVCAM-1 (2.402 +/- 296 ng/ml vs 972 +/- 117 ng/ml) and sICAM-1 levels (464 +/- 51 ng/ml vs 206 +/- 37 ng/ml, both p < 0.05) and lower FMV (1.0 +/- 1.1% vs 5.6 +/- 1.6%, p < 0.05). sICAM-1 concentration progressively decreased with treatment (from 464 +/- 51 ng/ml to 326 +/- 56 ng/ml, 288 +/- 42 ng/ml, and 279 +/- 44 ng/ml after the first dose and, respectively, after 1 and 2 weeks; all p < 0.05). sVCAM-1 showed a reduction after 2 weeks (from 2.402 +/- 296 ng/ml to 1.916 +/- 176 ng/ml; p < 0.05). FMV improved after 1 and 2 weeks (from 1.0 +/- 1.1% to 3.1 +/- 0.6% and 5.2 +/- 2.1%, both p < 0.05). In conclusion, treatment with PGE1 determines a significant improvement in endothelial function in patients with critical limb ischemia.
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PMID:Prostaglandin E1 improves endothelial function in critical limb ischemia. 1254 86

OBJECTIVE: To probe into the role of liposomal prostaglandin E(1) (Lipo-PGE(1)) on reperfusion injury in a rabbit ischemia-reperfusion model. METHODS: Twenty-four open-chest rebbits were randomized to receive a 10 min intravenous infusion of either liposome diluent, free PGE(1), or Lipo-PGE(1) after 60 min of left anterior desending (LAD) ligation just before reperfusion. Serum creatine phosphokinase (CPK), malodialdehyde (MDA), superoxide dismutase (SOD) were detected; infarct size and region at risk were measured. RESULTS: Infarct size as a ratio of weight of infarcted tissue to weight at risk (MI/RISK) was significantly reduced with Lipo-PGE(1) (32.20+/-4.70)% compared with PGE(1) (42.09+/-6.93)% or placebo (44.57+/-5.46)% infusion (P<0.01). The values of serum CPK, MDA during reperfusion in treatment of Lipo-PGE(1) group were significantly reduced than in treatment of PGE(1) group or control group (P<0.05), and the values of serum SOD were significantly increased (P<0.05). CONCLUSION: Lipo-PGE(1) can effectively decrease the serum CPK and MDA contents, elevate the SOD activity, and attenuate myocardial reperfusion injury.
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PMID:[Effects of liposomal prostaglandin E(1) on myocardial reperfusion injury in rabbits] 1255 31

Most studies investigating the pathophysiological processes taking place inside an experimental burn wound use in vitro techniques, which only allow for fragmented measurements of the actual and complex processes occurring inside a burn wound in vivo. In the present study, which used a recently developed in vivo technique in the rat, a full-thickness burn was induced and resulted in the formation of a subcutaneous gelatinous edema with distinct borders to the surrounding connective tissue and free communication with the systemic circulation allowing it to be easily separated for further analysis. In the present study, we investigated the effects of topical local anaesthetics (EMLA) on the inflammatory cascade of a burn wound in vivo. Results showed significantly higher myeloperoxidase (MPO) levels in EMLA-treated burned animals (P<0.01) versus placebo-treated burned controls. EMLA treatment induced a significant inhibition of the synthesis of leukotrien B(4) (LTB(4)) (P<0.001), prostaglandin E(1) (PGE(1)) (P<0.001), prostaglandin E(2) (PGE(2)) (P<0.001) and thromboxane B(2) (TXB(2)) (P<0.001) versus control, while free radical formation did not differ significantly between EMLA-treated and control animals. In conclusion, topical local anaesthetics significantly inhibit the release of several mediators known to take important part in the pathophysiological events ensuing a burn injury, such as activation of pain mechanisms (PGE), oedema formation (LTB), and postburn ischemia (TXB). The increased numbers of leukocytes (MPO) in the burn wound induced by topical local anaesthetic treatment could suggest increased influx and/or increased viability of leukocytes postburn.
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PMID:Influence of local anaesthetics on inflammatory activity postburn. 1278 10

Experimental evidence has been presented connecting melatonin with the prevention or treatment of gastrointestinal disorders either by the scavenging properties of active oxygen or by receptor-mediated stimulation of gene expression of neutralizing enzymes. Prostaglandins and nitric oxide are important neuroimmunomodulators in digestive physiology and different studies have indicated that the protective properties of melatonin may be explained by prostaglandin and/or nitric oxide mechanisms. The aim of the present study was to examine the effect of intraperitoneal administration of melatonin on in vivo changes in PGE(2), generated in gastric mucosal lesions by ischemia-reperfusion. Cyclic GMP nucleotide was also studied as an index of the principal enzymatic activity involved in the metabolism of nitric oxide, the nitric oxide synthase. The different immunological tests showed that the intraperitoneal administration of melatonin prevents the postischemic decrease in prostaglandins. The concentration of this eicosanoid in the rat mucosa treated with 20 mg.kg(-1) of melatonin was significantly higher (p < 0.05) than that in the control rats. The amount of cyclic GMP in the stomach decreased because of ischemia-reperfusion. In treated animals however, a marked increase occurred in concentrations of GMP, but the difference was not statistically significant. The results suggest that the mechanism of protection afforded by melatonin against lesions induced by gastric ischemia-reperfusion may be due to stimulation of the synthesis of eicosanoid protectors during the ischemic process.
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PMID:Melatonin modulates the effects of gastric injury in rats: role of prostaglandins and nitric oxide. 1287 1

Increases in COX-2 enzymatic activity and prostaglandin production have been associated with neuronal injury in both acute and age-related degenerative neurological diseases. In this study, we tested the effects of increased COX-2 activity in a model of transient focal ischemia using a transgenic mouse model in which human COX-2 is constitutively expressed selectively in neurons of the striatum, cerebral cortex, and hippocampus. These COX-2 transgenic mice harbor elevated levels of PGE(2) that are 10-fold higher than nontransgenic levels. A significant increase in infarct volume was observed after middle cerebral artery occlusion with 4 days of reperfusion in COX-2 transgenic mice as compared with nontransgenic littermates. Pretreatment of nontransgenic mice with the selective COX-2 inhibitor SC58236 resulted in a significant reduction of infarct volume in nontransgenic mice, consistent with previous pharmacological studies. However, transgenic COX-2 mice treated with SC58236 did not show a significant reduction. This suggests that chronic increases in COX-2 expression and enzymatic activity, which can occur in aging and in pathological states characterized by oxidative stress and chronic inflammatory processes, can lead to downstream cellular changes that have a negative impact on neuronal survival in cerebrovascular disease.
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PMID:Neuronal overexpression of cyclooxygenase-2 increases cerebral infarction. 1289 63

The cytoprotective effect of prostaglandin E(1) (PGE(1)) has been demonstrated experimentally and clinically against hepatic ischemia and reperfusion injury and against the effects of partial hepatectomy in both individual and combined models of noncirrhotic livers. Cirrhotic livers are more vulnerable to ischemia/reperfusion injury during hepatectomy than are noncirrhotic livers, and postoperative malfunctioning complicates life with multiple organ failure. Cirrhotic livers with tumors have mostly been treated conservatively because extended hepatectomy with induced ischemia during surgery is impossible. The purpose of our study was to document postoperative surgical adaptation in inoperable cases with improved survival after extended hepatectomy in a rat model of cirrhosis treated by PGE(1). Cirrhosis was induced by intraperitoneal injections of 1% dimethylnitrosamine. The liver was subjected to 15 minutes of total ischemia by occluding the hepatoduodenal ligament. Hepatectomy was performed during ischemia. Pretreatment with PGE(1) (0.4 microg/kg/min) (or without it in the controls) was given for 15 minutes by intravenous infusion prior to inducing ischemia and during reperfusion. Portal venous flow (PVF) and liver tissue blood flow (LTBF) were measured during reperfusion. At the end of 60 minutes of reperfusion, venous blood was collected for liver function tests. The animals were followed up regarding survival for 48 hours. The PVF and LTBF were significantly improved in the PGE(1) group. The blood chemical analysis indicated that PGE(1) significantly suppressed posthepatectomy liver dysfunction. Most importantly, PGE(1) treatment markedly improved the survival rate, from 42% in the controls to 75% in the test animals at 24 hours after hepatectomy and from 17% in the controls to 58% in the test animals at 48 hours. We concluded that short-term administration of PGE(1) makes extensive hepatectomy possible under ischemic conditions in cirrhotic livers.
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PMID:Effect of short-term administration of prostaglandin E1 on viability after ischemia/reperfusion injury with extended hepatectomy in cirrhotic rat liver. 1292 1

Results from several studies indicate that cyclooxygenase-2 (COX-2) is involved in ischemic brain injury. The purpose of this study was to evaluate the neuroprotective effects of the selective COX-2 inhibitor nimesulide on cerebral infarction and neurological deficits in a standardized model of transient focal cerebral ischemia in rats. Three doses of nimesulide (3, 6 and 12 mg/kg; i.p.) or vehicle were administered immediately after stroke and additional doses were given at 6, 12, 24, 36 and 48 h after ischemia. In other set of experiments, the effect of nimesulide was studied in a situation in which its first administration was delayed for 3-24 h after ischemia. Total, cortical and subcortical infarct volumes and functional outcome (assessed by neurological deficit score and rotarod performance) were determined 3 days after ischemia. The effect of nimesulide on prostaglandin E(2) (PGE(2)) levels in the injured brain was also investigated. Nimesulide dose-dependently reduced infarct volume and improved functional recovery when compared to vehicle. Of interest is the finding that neuroprotection conferred by nimesulide (reduction of infarct size and neurological deficits and improvement of rotarod performance) was also observed when treatment was delayed until 24 h after ischemia. Further, administration of nimesulide in a delayed treatment paradigm completely abolished PGE(2) accumulation in the postischemic brain, suggesting that COX-2 inhibition is a promising therapeutic strategy for cerebral ischemia to target the late-occurring inflammatory events which amplify initial damage.
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PMID:Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat. 1506 40


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