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)

Reperfusion injury and the no-reflow phenomenon are manifestations of a complex series of events that culminate in an acute inflammatory reaction within reperfused tissue. Antiinflammatory therapy attenuates ischemia-reperfusion injury. The purpose of this study is to evaluate the effects of dexamethasone on blood flow and viability of ischemic rat island groin flaps. Thirty-three mature male Sprague-Dawley rats were divided into 3 groups. The flaps were subjected to 8 hr of ischemia in the control and treatment groups. Fluorescein studies were performed, and flap viability was assessed. Twenty-four hour fluorescence (after reperfusion) correlated very closely with the percentage of eventual flap viability. The blood flow and viability of the treatment group flaps were significantly better than those in the ischemic control group. Dexamethasone significantly improved ischemic flap survival in the rat 8 hr ischemic island groin flap model in our study.
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PMID:Improved reflow and viability in reperfused ischemic rat island groin flaps using dexamethasone. 778 10

Hepatocyte growth factor (HGF) is the most potent mitogen of mature hepatocytes in primary culture, and is a molecule composed of 69 kD alpha-chain and 34 kD beta-chain. HGF predominantly acts on various epithelial cells as a mitogen, motogen and a morphogen. HGF mRNA and HGF protein increases rapidly in the liver and plasma of rats with liver injury such as hepatitis, ischemia, physical crush and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells, sinusoidal endothelial cells, and Ito cells, but not in hepatocytes. HGF mRNA is also rapidly increased in the intact organs such as lung, kidney and spleen. Thus, HGF may act as a hepatotrophic factor for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, intravenously injected HGF enhances liver regeneration and protects hepatitis in vivo. Consequently, HGF may prove to be useful for the clinical treatment of patients with liver disease. Recently, we found a factor which specially appears in the blood of rats with organ injury and increases the synthesis of HGF, and it was named "injurin". IL-1 alpha and IL-1 beta are also positive regulators for the expression of the HGF gene, while TGF-beta and Dexamethazone down-regulate HGF expression.
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PMID:[Molecular biology of hepatocyte growth factor (HGF)]. 838 41

The antitumor activity of cis-diamminedichloroplatinum(II) (cP) and human recombinant interleukin-1 alpha (IL-1 alpha) was studied in RIF-1 and SC VII solid tumor models and in a cP-resistant subline of RIF-1 designated RIF-R1cP. In RIF-1 tumors, clonogenic cell survival after cP plus IL-1 alpha combinations was highly schedule and IL-1 alpha dose dependent. More than additive clonogenic cell kill was seen when cP was given 6 h before, but not 8 h before or at 2-6 h after IL-1 alpha. Time course studies indicated that maximal clonogenic cell killing was achieved within 4-6 h after the cP plus IL-1 alpha combination, with little or no recovery for up to 24 h. In vivo dose-response studies indicated that cP plus IL-1 alpha combinations induced more clonogenic cell kill than cP alone in all three tumor models, and analysis by the median effect principle indicated highly synergistic antitumor activity. Dexamethasone but not indomethacin inhibited the synergistic interaction. IL-1 alpha had no effect on the cytotoxicity of cP in SCC VII cells in vitro, and neither in vitro hypoxia nor in vivo ischemia, induced by clamping tumor blood supply, significantly affected cP clonogenic cell killing. Increased clonogenic cell killing was seen, however, after removal of the clamp, implicating reperfusion events, such as oxyradical stress, as a potential mechanism for increased cP cytotoxicity in SCC VII solid tumors. The data from our model systems provide a rationale for additional work to define the mechanisms of the synergistic antitumor activity of the cP plus IL-1 alpha combination and indicate that IL-1 alpha might be a useful adjunct to increase the clinical efficacy of cP-containing strategies for both sensitive and cP-resistant cancers.
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PMID:Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tumors. 843 53

Despite the known effectiveness of anti-inflammatory therapy in reducing reperfusion injury, no studies to date involve the use of anti-inflammatory therapy in reducing ischemia-reperfusion injury in fasciocutaneous flaps. Dexamethasone (a phospholipase A2 inhibitor) and specific cyclooxygenase and lipoxygenase inhibitors (indomethacin and BW755C) were administered to rats with ischemic island groin (fasciocutaneous) flaps. Significant improvement in ischemic flap survival was found with dexamethasone and BW755C. The mode of action of dexamethasone was not specifically investigated in our study; however, it may suppress neutrophil function and reduce ischemia-reperfusion injury in its shared ability with BW755C to reduce the formation of leukotrienes. Dexamethasone could be applied in the clinical setting to reduce ischemic flap loss by attenuating the systemic inflammatory response to reperfused ischemic-damaged tissue.
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PMID:Reducing ischemia-reperfusion injury in rat island groin flaps by dexamethasone and BW755C. 852 85

The objective of this study was to investigate the significance of mast cell-induced reactions in the mucosal functional and morphological alterations induced by 30 min segmental ischemia and 120 min reperfusion in anesthetized dogs. The rates of changes in permeability of the mucosa to sodium fluorescein (NaFL) in the plasma-to-lumen and lumen-to-plasma directions were studied, the local hemodynamics, intramucosal pH (pHi) alterations, mast cell number and degranulation, and degree of tissue injury were determined. The effects of pretreatments with cromolyn (a peritoneal-type mast cell stabilizer), quercetin (a mucosal-type mast cell stabilizer), and dexamethasone (an aspecific membrane stabilizer and mast cell depleter) were evaluated. We found that ischemia-reperfusion induced significant tissue injury, elevated the segmental vascular resistance, and decreased pHi. The plasma-to-lumen clearance of NaFL increased significantly during ischemia and reperfusion. Cromolyn and quercetin pretreatments significantly inhibited the permeability changes, but did not influence the pHi and morphological alterations induced by ischemia-reperfusion. Dexamethasone pretreatment did not influence the number of mast cells, but the degree of mast cell degranulation and fluorescein leakage decreased. We conclude that intestinal mast cells and mast cell-induced reactions contribute to the mucosal permeability alterations during reperfusion, but play only a minor role in ischemia-reperfusion-induced structural injury.
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PMID:The role of mast cells in mucosal permeability changes during ischemia-reperfusion injury of the small intestine. 932 30

Lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha independently induce cardioprotection against ischemia in the rat at 24 h after administration, suggesting that endogenously synthesized TNF-alpha may play a role in LPS-induced protection. The purposes of this study were 1) to delineate the time course of LPS-induced cardiac functional protection against ischemia and its relation with myocardial and circulating TNF-alpha profile, 2) to examine whether prior protein synthesis inhibition abrogates the protection, and 3) to assess the effects of TNF-alpha inhibition and neutralization on the protection. Rats were treated with LPS (0.5 mg/kg i.p.). Cardiac functional resistance to normothermic global ischemia-reperfusion was examined at sequential time points after LPS treatment in isolated hearts by the Langendorff technique. Myocardial and circulating TNF-alpha was determined by enzyme-linked immunosorbent assay at 1-24 h after LPS treatment. Protection was apparent at 24 h, 3 days, and 7 days but not at 2 or 12 h. Maximal protection at 3 days was abolished by cycloheximide pretreatment (0.5 mg/kg i.p. 3 h before LPS treatment). Increases in myocardial and circulating TNF-alpha preceded the acquisition of protection. Dexamethasone pretreatment (4.0 or 8.0 mg/kg i.p. 30 min before LPS treatment) abolished peak increase in myocardial TNF-alpha and substantially suppressed circulating TNF-alpha (54.3 and 85.9% inhibition, respectively) without an influence on the maximal protection. Similarly, maximal protection was not affected by TNF binding protein (40 or 80 microg/kg i.v. immediately after LPS treatment). The results suggest that LPS-induced cardiac functional protection against ischemia is a delayed and long-lasting protective response that may involve de novo protein synthesis. Although LPS-induced increase in myocardial and circulating TNF-alpha precedes the delayed protection, it may not be required for the delayed protection.
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PMID:LPS induces late cardiac functional protection against ischemia independent of cardiac and circulating TNF-alpha. 936 58

The objective of this study was to investigate the role of intestinal mast cells in mucosal functional and morphological alterations induced by 30 min segmental ischemia and 120 min reperfusion in anesthetized dogs. The time course of permeability changes of the mucosa to sodium fluorescein (NaFl) in blood-lumen and lumen-blood directions was studied in two separate series of experiments. Local hemodynamics, intramucosal pH (pHi) alterations, mast cell number and degranulation and the degree of tissue injury were determined. The effects of cromolyn (peritoneal-type mast cell stabilizer), quercetin (mucosal-type mast cell stabilizer), and dexamethasone (aspecific membrane stabilizer and mast cell depleter) pretreatments were evaluated. Ischemia-reperfusion induced significant tissue injury, elevated segmental vascular resistance, and decreased pHi. The blood to lumen clearance of NaFl increased significantly during ischemia and reperfusion. Cromolyn and quercetin pretreatment significantly inhibited permeability changes, but did not influence pHi and morphological alterations induced by ischemia-reperfusion. Dexamethasone pretreatment did not influence the number of mast cells, however, the degree of mast cell degranulation and the degree of mucosal damage decreased. These results demonstrate that mast cells or mast cell-induced reactions contribute to the mucosal permeability alterations and barrier lesions during reperfusion, but play a minor role in reperfusion-induced structural injury.
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PMID:Mucosal permeability changes during intestinal reperfusion injury. The role of mast cells. 940 93

Glucocorticoids exacerbate neuronal damage due to hypoxia, ischemia, seizure and hypoglycemia. Because the release of glutamate is closely involved in neuronal damage, the effects of dexamethasone on the ischemia-induced accumulation of extracellular amino acids (aspartate, glutamate, and glycine) were investigated in the gerbil hippocampal CA1 region by a microdialysis-high-performance liquid chromatography procedure in vivo. There were no differences in the extracellular concentrations of amino acids before ischemia between the control group and the dexamethasone (3m microg, i.c.v.)-injected group. The concentration of glutamate reached 246% of that before ischemia within 2.5 min of transient forebrain ischemia. Dexamethasone augmented the increase in glutamate to 508% of that before ischemia. This finding suggests that glucocorticoids aggravate ischemic neuronal damage by causing glutamate to accumulate in the extracellular space.
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PMID:Dexamethasone augments ischemia-induced extracellular accumulation of glutamate in gerbil hippocampus. 965 Aug 49

Dexamethasone (DEX) increases the expression of neurotrophin-3 (NT-3) in normal rat hippocampal neurons, whereas transient forebrain ischemia reduces the NT-3 mRNA level. The effect of DEX on the expression of NT-3 mRNA in injured brain cells after ischemia has not been investigated, however. Using in situ hybridization and ribonuclease protection assay methods, we studied NT-3 mRNA expression in rats with and without DEX administration after transient forebrain ischemia. Without DEX treatment, NT-3 mRNA was down-regulated in the hippocampal neurons at 2, 4, 12 h and returned to basal levels 24 h following ischemia. With DEX treatment, however, NT-3 mRNA showed no change at 2, 4 and 12 h and increased 24 h after ischemia. The results indicate that DEX inhibits ischemia-induced NT-3 mRNA down-regulation during the first 12 h and up-regulates NT-3 mRNA 24 h after ischemia. DEX administration might be effective in influencing some of the pathophysiological effects of ischemia in the hippocampus.
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PMID:Dexamethasone inhibits ischemia-induced transient reduction of neurotrophin-3 mRNA in rat hippocampal neurons. 985 2

Previous investigations have shown that sepsis, while causing cardiac dysfunction, can protect the heart from ischemia-reperfusion injury. Sepsis-induced protection may be due to nitric oxide produced by an inducible form of nitric oxide synthase generated in response to cytokines released during sepsis. The glucocorticoid dexamethasone has been shown to inhibit the synthesis of the inducible form of nitric oxide synthase (iNOS). The goals of this study were to determine if dexamethasone would prevent sepsis-induced cardiac dysfunction and sepsis-induced protection of the heart from ischemia-reperfusion injury. In this experiment, rats were made septic by injecting Escherichia coli into the dorsal subcutaneous space. Control rats were injected with sterile saline. At the time of surgery, some of the control and septic animals were injected intraperitoneally with dexamethasone (3 mg/kg). The next day, 24-26 hr after injection of the first dose of E. coli, animals were anesthetized, and hearts were removed and studied in the isovolumic beating-heart preparation. Left ventricular end diastolic pressure was set to 5 mmHg, and left ventricular pressure was measured continuously throughout the protocol. Left ventricular developed pressure (LVDP) was used as an index of LV function. After stabilization, hearts were made globally ischemic for 35 min and then reperfused for 25 min. As has been shown previously, sepsis depressed LVDP but also protected the heart from further depression of LVDP by ischemia and reperfusion. Dexamethasone prevented both sepsis-induced cardiac dysfunction and sepsis-induced protection of the heart from ischemia-reperfusion injury. In addition plasma nitrite/nitrate levels were not different from control levels in the dexamethasone-treated septic rats whereas levels were elevated in the septic animals. The dexamethasone mediated abrogation of sepsis-induced cardiac dysfunction and protection during ischemia-reperfusion injury may be due to suppression of nitric oxide production.
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PMID:Dexamethasone blocks sepsis-induced protection of the heart from ischemia reperfusion injury. 1063 65


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