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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main purpose of this study was to investigate the possible protective effect of a single dose of glucocorticoid dexamethasone administered just before reperfusion on the viability of cold-stored inferior epigastric rat skin flaps. We also sought evidence for the antiinflammatory mechanism of action of dexamethasone involved in this model of cold ischemia-reperfusion. The viability of flaps on reperfusion day 7, after 1, 2, 3, 4, or 5 days of cold ischemia, was 80, 74, 60, 47 and 12% respectively. Four days' cold ischemia time was chosen to test the effect of intraperitoneal dexamethasone administration (2.5 mg/kg) 30 min prior to reperfusion. Flap survival after 4 days' cold ischemia/7 days' reperfusion increased significantly from a mean of 37.0% survival in saline-treated controls to 73.3% in dexamethasone-treated rats (p < 0.05). Dexamethasone treatment also resulted in significantly lower skin flap water content (a measure of edema) and myeloperoxidase activity (an indicator of neutrophil infiltration) but had no significant effect on skin levels of hydroperoxides (a measure of free radical activity). In conclusion, dexamethasone attenuates ischemia-reperfusion injury in cold-stored skin flaps by reducing the tissue levels of several proinflammatory mediators.
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PMID:The beneficial antiinflammatory effect of dexamethasone administration prior to reperfusion on the viability of cold-stored skin flaps. 1064 14

Dexamethasone (DEX) pretreatment has been shown to be neuroprotective in a neonatal rat model of hypoxia ischemia (HI). The exact mechanism of this neuroprotection is still unknown. This study used 31P nuclear magnetic resonance spectroscopy to monitor energy metabolism during a 3-h episode of HI in 7-d-old rat pups in one of two groups. The first group was pretreated with 0.1 mL saline (i.p.) and the second group was treated with 0.1 mL of 0.1mg/kg DEX (i.p.) 22 h before HI. Animals pretreated with DEX had elevated nucleoside triphosphate and phosphocreatine levels during HI when compared with controls. Saline-treated animals had significant decreases in nucleoside triphosphate and phosphocreatine and increases in inorganic phosphate over this same period. 31P nuclear magnetic resonance data unequivocally demonstrate preservation of energy metabolism during HI in neonatal rats pretreated with DEX. Animals pretreated with DEX had little or no brain damage following 3 h of HI when compared with matched controls, which experienced severe neuronal loss and cortical infarction. These same pretreated animals had an increase in blood beta-hydroxybutyrate levels before ischemia, suggesting an increase in ketone bodies, which is the neonate's primary energy source. Elevation of ketone bodies appears to be one of the mechanisms by which DEX pretreatment provides neuroprotection during HI in the neonatal rat.
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PMID:Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment. 1092 3

It has been reported that corticosteroids exert their anti-inflammatory action through de novo synthesis of phospholipase-inhibitory proteins called lipocortins (annexins). We postulated that the following may lessen the effectiveness of corticosteroids on acute ischemic brain edema: 1) lipocortins are induced several hours after administration of steroids; 2) de novo synthesis of lipocortins is suppressed in the ischemic brain; and 3) lipocortins induced systemically do not pass through the blood-brain barrier (BBB) to reach the sites of ischemic edema. To test this hypothesis, we examined whether dexamethasone, given long before ischemia or direct administration of recombinant lipocortin-1, combined with or without BBB opening, ameliorate ischemic brain edema. Three hours before occlusion of the middle cerebral artery (MCA) in the cat, 4 mg/kg of dexamethasone was injected intravenously. The animals were subjected to 4 hours of ischemia. Alternatively, 2 ug/ml (total volume 10 ml) of recombinant human lipocortin-1 (annexin-I) was perfused intermittently into the ischemic focus by catheterization into the MCA. Artificial opening of the BBB was performed by intra-arterial mannitol infusion. None of these strategies demonstrated amelioration of ischemic edema. We conclude that: Dexamethasone and recombinant lipocortin-1 seem unlikely to have robust effects on amelioration of acute ischemic edema.
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PMID:Lipocortin-1 fails to ameliorate ischemic brain edema in the cat. 1145 31

Glucocorticoids have been reported to aggravate ischemic neuronal damage. Because energy failure is a crucial factor in the development of ischemic neuronal injury, the effects of dexamethasone on histologic outcome and energy metabolism were investigated in gerbil brain. Dexamethasone (3 microg, i.c.v.) was administered 1 h prior to ischemia, and its effect on delayed neuronal death caused by 2 min of bilateral common carotid artery occlusion was observed in hippocampal CA1 pyramidal neurons. The brain concentration of ATP after various durations of decapitation ischemia was determined, and the effect of dexamethasone (3 microg, i.c.v.) was examined. Na+,K+-activated adenosine triphosphatase (Na+,K+-ATPase) activity was evaluated after the administration of the agent. Forebrain ischemia for 2 min produced neuronal damage in animals pretreated with dexamethasone, although neuronal damage was not observed in vehicle-injected animals. Decapitation ischemia for 0.5 and 1 min reduced the brain ATP concentration to 44% and 15% of the basal level, respectively. Dexamethasone attenuated the ischemia-induced reduction in ATP, and the values were 58% and 25% of the basal level, respectively. Na+,K+-ATPase activity at pH 6.7 was suppressed to 47% by dexamethasone treatment (3 microg, i.c.v.), whereas the activity at pH 7.4 was not influenced by the agent. The results show that a contributing factor to the aggravation of ischemic neuronal damage may be a disturbance in Na+,K+-ATPase despite adequate levels of ATP.
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PMID:Dexamethasone reduces energy utilization in ischemic gerbil brain. 1155 63

The effects of dexamethasone on adenosine 5'-triphosphatase (ATPase) activity and the intracellular Ca(2+) concentration ([Ca(2+)](i)) were investigated in acidotic mouse brain. Dexamethasone (3 mg/kg, i.p.) or vehicle was administered 3 h before decapitation ischemia, and the brain concentration of adenosine 5'-triphosphate (ATP) was determined 0.5-2 min after ischemia. The effects of dexamethasone (0.3-3 mg/kg, i.p.) on Na(+),K(+)-activated ATPase (Na(+),K(+)-ATPase) and Ca(2+)-ATPase activities were evaluated at pH 7.4 and 6.8. Changes in [Ca(2+)](i) in an acidic medium were determined in hippocampal slices by microfluorometry using rhod-2 acetoxymethyl ester as a Ca(2+) marker, and the effects of dexamethasone (240 microg/l) was evaluated. Decapitation ischemia for 0.5 and 1 min reduced the brain ATP contents to 32% and 16% of the basal level, respectively. Dexamethasone slightly suppressed the extent of the decrease in the ATP level. Although dexamethasone did not affect Na(+),K(+)-ATPase activity at pH 7.4, the activity was suppressed by dexamethasone (3 mg/kg) to 68% at pH 6.8. The activity of Ca(2+)-ATPase was not affected by dexamethasone at either pH 7.4 or pH 6.8. When the pH of the medium of the brain slices was changed from 7.4 to 6.8, almost no increase in [Ca(2+)](i) was observed in the control group. The dexamethasone treatment increased [Ca(2+)](i) in the CA1 field and dentate gyrus immediately after induction of the acidic medium, the effect being significant after 150 s. Because anaerobic glucose metabolism in the early stage of ischemia enhances intracellular lactic acidosis, the findings may suggest a mechanism for the aggravation of ischemic neuronal damage by glucocorticoids.
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PMID:Suppression of sodium pump activity and an increase in the intracellular Ca2+ concentration by dexamethasone in acidotic mouse brain. 1244 69

Dexamethasone, a corticosteroid used to treat cerebral edema, is known to produce elevations in the blood glucose concentration, but the effect of a single intraoperative dose of dexamethasone on the blood glucose concentration is unknown. Glucose concentrations in response to either a 10-mg intravenous bolus of dexamethasone or a saline placebo were evaluated in nondiabetic patients undergoing elective craniotomy. Both arterial and venous blood glucose concentrations were obtained immediately before and after treatment and hourly for 4 hours intraoperatively. The arterial blood glucose concentration in those who received 10 mg dexamethasone (n = 10) increased from 97 +/-15 mg/dL (mean +/- SD) to 149 +/- 23 mg/dL over the course of the study, compared with a change from 88 +/- 11 mg/dL to 103+/-12 mg/dL in those who received placebo (n = 10) (P < 0.05 for 4-hour sample vs. baseline for both groups; P < 0.05 between groups at 4 hours). Further, venous blood glucose concentrations were highly predictive of arterial glucose values (R = 0.98; P < 0.001). Since elevations in the blood glucose concentration should be avoided in the setting of central nervous system ischemia, findings from this investigation suggest that contemplated corticosteroid use should be reviewed for appropriateness of treatment. If dexamethasone is used, even as a single dose during craniotomy, intraoperative blood glucose concentrations should be carefully monitored and hyperglycemia treated, particularly in patients at risk for glucose-mediated exacerbation of brain injury.
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PMID:Effect of single-dose dexamethasone on blood glucose concentration in patients undergoing craniotomy. 1502 Dec 80

We investigated the effect of two inhibitors of nitric oxide (NO) synthesis, N(w)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, on lung inflammation caused by intestinal ischemia/reperfusion in rats. Relative to the sham-operated rats, intestinal ischemia/reperfusion (ischemia: 45 min; reperfusion: 30 min, 2 and 4 h) induced neutrophil recruitment (increased myeloperoxidase activity) and increased microvascular permeability (Evans blue dye extravasation) in the lungs and increased tumor necrosis factor (TNF) levels in the serum (L-929 cytotoxicity assay). L-NAME given before the ischemia exacerbated neutrophil accumulation, plasma extravasation, serum TNF and caused death of the animals, which was prevented by concomitant injection of L-arginine. Lung and systemic effects of intestinal ischemia/reperfusion were not modified when L-NAME was given just before reperfusion. Treatment with aminoguanidine inhibited plasma extravasation without affecting the other parameters evaluated. Dexamethasone reduced all the parameters. Our results indicate that during intestinal ischemia/reperfusion both constitutive and inducible NO synthases are called to exert a differential modulatory effect on lung inflammation and that maintenance of adequate levels of NO during ischemia is essential for the animals survival.
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PMID:Lung microvascular permeability and neutrophil recruitment are differently regulated by nitric oxide in a rat model of intestinal ischemia-reperfusion. 1521 81

We investigated the contribution of dexamethasone treatment on the recovery of postischemic cardiac function and the development of reperfusion-induced arrhythmias in ischemic/reperfused isolated rat hearts. Rats were treated with 2 mg/kg of intraperitoneal injection of dexamethasone, and 24 hours later, hearts were isolated according to the 'working' mode, perfused, and subjected to 30 min global ischemia followed by 120 min reperfusion. Cardiac function including heart rate, coronary flow, aortic flow, and left ventricular developed pressure were recorded. After 60 min and 120 min reperfusion, 2 mg/kg of dexamethasone significantly improved the postischemic recovery of aortic flow and left ventricular developed pressure from their control values of 10.7 +/- 0.3 ml/min and 10.5 +/- 0.3 kPa to 22.2 +/- 0.3 ml/min (p < 0.05) and 14.3 +/- 0.5 kPa (p < 0.05), 19.3 +/- 0.3 ml/min (p < 0.05) and 12.3 +/- 0.5 kPa (p < 0.05), respectively. Heart rate and coronary flow did not show a significant change in postischemic recovery after 60 or 120 min reperfusion. In rats treated with 0.5 mg/kg of actinomycin D injected i.v., one hour before the dexamethasone injection, suppressed the dexamethasone-induced cardiac protection. Electrocardiograms were monitored to determine the incidence of reperfusion-induced ventricular fibrillation. Dexamethasone pretreatment significantly reduces the occurrence of ventricular fibrillation. Cytochrome c release was also observed in the cytoplasm. The results suggest that the inhibition of cytochrome c release is involved in the dexamethasone-induced cardiac protection.
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PMID:Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts: the role of cytochrome c release. 1535 Aug 17

We report an autopsy case of acute pancreatitis with a high serum IgG4 concentration complicated by systemic amyloid A amyloidosis and rheumatoid arthritis (RA). The patient was a 42-year-old Japanese female with a 22-year history of rheumatoid arthritis. She was diagnosed with myasthenia gravis when she was 31-year old. At the onset of pancreatitis, the patient was anti-nuclear antibody-positive, and had high serum gamma globulin and IgG4 levels. Dexamethasone and conventional therapy induced clinical remission and significantly decreased the serum IgG4 and gamma globulin. However, despite the decreased disease parameters, the patient developed a bleeding pseudocyst and died of cardiac failure. In the autopsy examination, it was determined that pancreatitis was probably caused by ischemia due to vascular obstruction caused by amyloid deposition in the pancreas. Even though acute pancreatitis is a rare complication in RA patients, we speculate that an autoimmune pancreatitis-related mechanism and ischemia due to vascular obstruction by amyloid deposition might be attributable to a single source that leads to acute pancreatitis in our particular case.
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PMID:An autopsy case of acute pancreatitis with a high serum IgG4 complicated by amyloidosis and rheumatoid arthritis. 1580 Oct 1

Nerve growth factor (NGF) is well-established as a trophic factor that plays a crucial role in neuroregeneration and plasticity after brain insults. Dexamethasone (DEX), a powerful glucocorticoid steroid, has long been used in the clinical management of neurological disorders. We examined the relationship between NGF and DEX after an ischemic insult to the brain. In situ hybridization was used to measure NGF mRNA expression in the rat hippocampus after 20 min of transient forebrain ischemia. Immunostaining for NGF protein was performed using the avidin-biotin peroxidase method. Immunohistochemistry for glial fibrillary acidic protein (GFAP) was also used to study the astrocyte reaction in the hippocampal CA1 area. Ischemic brain from rats not treated with DEX had a 2 and 3 fold increase in NGF mRNA compared to sham-operated rats at 4 and 6 h after ischemia, respectively. The NGF mRNA expression returned to basal levels 12 h to 7 days post-ischemia. Treatment with DEX potentiated the ischemia-induced increase of NGF mRNA to 4 times that of sham-operated rats at 6 h following reperfusion and NGF protein expression was similarly elevated. Additionally, the number of GFAP positive astrocytes in the CA1 region in the ischemic rats was markedly increased. These data suggest that DEX may play a role in modulating NGF mRNA expression in the hippocampal neuronal response to brain ischemia.
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PMID:Dexamethasone enhances upregulation of nerve growth factor mRNA expression in ischemic rat brain. 1611 51


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