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)

Erythropoietin (EPO) is commonly used to treat anemias secondary to renal failure, malignancy, and AIDS. Although therapeutic complications are well described, overdose is rare. A 42-y-o man with AIDS confused his instructions for self-administration of interferon and EPO and began injecting himself daily with 10,000 units of EPO for several weeks. He presented with confusion, pain in his abdomen and feet, and a hemoglobin of 23.2 g/dLwith a hematocrit of 77.1%. The patient was treated with iv fluids, phlebotomy and 2 sessions of erythropheresis which removed 898 mL and 640 mL of red blood cells, respectively; his hemoglobin remained between 12-14 g/dL and symptoms resolved. His only sequelae involved skin loss over his toes, which did not require grafting. This rare case of EPO overdose highlights the complications of essential erythrocytosis, with central nervous system, peripheral, and presumed mesenteric ischemia.
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PMID:Erythropoietin overdose treated with emergent erythropheresis. 1204 68

Monokine-induced by gamma interferon (MIG) and gamma-interferon-inducible protein (IP-10) are members of the CXC chemokine family that have been shown to be induced by interferon-gamma (IFNy) in some cell types. The purpose of this investigation was to determine whether IFNgamma influences CXC chemokine production, particularly MIG and IP-10, in primary rat hepatocytes in culture. Previous experiments in our laboratory have demonstrated that pharmacologic doses of IFNgamma in an in vivo model of hepatic ischemia/reperfusion-induced liver injury resulted in increased hepatic levels of IP-10 and MIG and decreased hepatic levels of macrophage inflammatory protein-2, Kupffer cells, and epithelial neutrophil-activating protein, with a concomitant decrease in neutrophil-mediated hepatic injury. In the current investigation, MIG and IP-10 mRNA and protein were up-regulated in primary rat hepatocytes in vitro in response to IFNgamma. Although MIG and IP-10 mRNA were both somewhat increased at early time points, larger increases in these chemokines were seen at later time points, specifically at 24, 48, and 72 h of incubation as compared to controls. Levels of Kupffer cells and macrophage inflammatory protein-2 mRNA after IFNgamma were negligible and similar to those seen in controls. These findings were confirmed by enzyme-linked immunosorbent assay analysis. These studies demonstrate that IFNgamma in vitro up-regulates the production of MIG and IP-10, at both the mRNA and protein levels.
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PMID:CXC chemokine expression after stimulation with interferon-gamma in primary rat hepatocytes in culture. 1206 90

The gene expression profile in the cortex was analyzed in a rat model of focal cerebral ischemia by use of cDNA array. It was attempted to monitor changes of gene expression and to profile them into functional classification between ipsilateral and contralateral cortex at 6h after middle cerebral artery (MCA) occlusion. Seventy-one genes out of 1174 genes were significantly modulated by ischemia. Metabolism-, cell communication- and signal transduction-related genes were down-regulated, whereas genes involved in stress response were markedly increased. Besides numerous established ischemia-induced gene products such as macrophage inflammatory protein-1 alpha (MIP-1 alpha), orphan nuclear receptor Nurr 77, secretogranin II (SCG-II), and tumor necrosis factor-alpha (TNF-alpha), several genes were identified which have not previously been shown to be modulated following focal ischemia; these genes include interferon-induced protein (IFN-IP), neurodegeneration-associated protein-1 (NDGAP-1), and neuronal pentraxin receptor (NPR). The RT-PCR analyses of these genes at various time points revealed that mRNA level of IFN-IP was up-regulated, while NDGAP-1 and NPR were transcriptionally down-regulated. The results suggest of the involvement of these genes in neuronal cell damage caused by ischemia and the potential use as targets for the development of preventives/therapeutics of brain stroke.
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PMID:DNA array reveals altered gene expression in response to focal cerebral ischemia. 1224 2

Today, the major problem in organ transplantation is not acute graft rejection but chronic graft deterioration. In addition to alloantigen-specific events, alloantigen independent factors like donor age, previous diseases, consequences of brain death, and perioperative events of ischemia/reperfusion injury have a major impact on long-term graft function. The induction of the stress protein heme oxygenase-1 (HO-1) protects cells from injury and apoptosis. Here, we tested the protective effects of HO-1 induction in a clinically relevant kidney transplant model. Induction of HO-1 expression following cobalt-protoporphyrin (CoPP) treatment in organ donors prolonged graft survival and long-term function remarkably following extended periods of ischemia. Positive effects were observed with both optimal and marginal grafts from old donor animals. Structural changes characteristic for chronic rejection, as well as graft infiltration by monocytes/macrophages and CD8+ T cells, were substantially reduced following HO-1 induction. Up-regulation of HO-1 expression before organ transplantation was also associated with reduced levels for tumor necrosis factor (TNF)-alpha mRNA, increased levels for interferon (IFN)-gamma, and bcl-x, and insignificant differences for CD25, interleukin (IL)-2, IL-4, IL-6, and IL-10 mRNA levels. The significant improvement of long-term graft function following induction of HO-1 expression in donor organs suggests that this strategy may be a novel clinical treatment option with particular relevance for transplantation of marginal organs.
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PMID:Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1. 1235 73

Double-stranded (ds) RNA-induced sequence-specific interference with gene expression, RNA interference (RNAi), has been extensively used in invertebrates, allowing for efficient and high-throughput gene silencing and gene function analysis. In vertebrates, however, use of RNAi to study gene function has been limited due to non-specific effects induced by double-stranded RNA (dsRNA)-dependent protein kinase and interferon activation. dsRNA-induced specific inhibition of vertebrate gene expression has only been shown in embryonic and non-differentiated mammalian cells. In this report, we demonstrate dsRNA-induced specific interference of gene expression and gene function in partially as well as fully differentiated mouse neuroblastoma cells. Specific silencing was observed in the expression of an integrated transgene coding for green fluorescent protein and a variety of endogenous genes. Moreover, we show that RNAi-mediated inhibition of poly (ADP-ribose) polymerase (PARP) expression induced cellular resistance to oxygen-glucose deprivation, consistent with the role of PARP in ischemia-induced brain damage. Our results indicate that RNAi can be used as a powerful tool to study gene function in neural cells.
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PMID:Specific interference with gene expression and gene function mediated by long dsRNA in neural cells. 1246 5

Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-gamma-deficient mice, or administration of IFN-gamma at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-gamma response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the beta-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
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PMID:Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. 3162 20

Plasma levels of substance P (SP) and neurokinin A (NKA) tachykinin and of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) cytokines were assayed in plasma obtained from peripheral blood of 19 patients presenting with stable chronic coronary stenosis and 12 patients with acute coronary syndrome (ACS). Plasma samples were obtained before, during, and after percutaneous coronary intervention (PCI) consisting of implantation of a metallic stent. Fourteen healthy subjects without any evident risk factors for coronary artery disease (CAD) were also included for comparison at basal time. We found that plasma levels of both IFN-gamma and TNF-alpha were significantly higher in patients with chronic or acute CAD than those in control subjects at the time of presentation. NKA and IFN-gamma levels were also significantly increased in ACS patients compared with those in patients with stable disease. The analysis performed during and after PCI revealed that IFN-gamma levels increased 15 min after stent implantation in both chronic and ACS patients and that TNF-alpha levels increased in chronic patients only compared to basal values. In addition, a significant decrease of both NKA and SPA levels 48 h after the end of the revascularization procedure was observed in ACS patients. These data suggest that modulation of tachykinin and/or cytokine release with proinflammatory activity in chronic or acute cardiac ischemia and during following coronary stenting might play an important role in heart tissue damage and in long-term inflammatory complications of PCI.
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PMID:Modulation of tachykinin and cytokine release in patients with coronary disease undergoing percutaneous revascularization. 1520 84

Brain ischemia triggers an inflammatory reaction that progresses for days to weeks and seems to have a role in secondary progression of injury. Inflammation induces a complex pattern of signaling molecules with partly contradictory actions, and the responses may be different in the immature and adult brain. The authors characterized the global inflammatory gene expression in the developing brain as a first step toward understanding the protective and deleterious effects of inflammation after hypoxia-ischemia. Oligonucleotide arrays were used to investigate inflammatory genes in cortex, hippocampus, thalamus, and striatum at 2, 8, 24, and 72 hours after hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia. After hypoxia-ischemia, 148 inflammatory genes were differentially expressed. More than 97% of the genes were upregulated and 93% had not previously been reported after hypoxia-ischemia in the immature brain. The results indicate that microglia/macrophages, T- and B-cells, NK-cells, mast cells, dendritic cells, and polymorphonuclear leukocytes may participate in the response to hypoxia-ischemia. In addition, novel cytokines/chemokines, complement-related, interferon-regulated, components of the TIR/nuclear factor-kappaB pathway, and a number of immunomodulatory genes were induced. Several of these genes may of pathophysiologic significance after neonatal hypoxia-ischemia.
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PMID:Inflammatory gene profiling in the developing mouse brain after hypoxia-ischemia. 1562 8

We tested a hypothesis that interactions between fibronectin (FN), a key extracellular matrix component, and its integrin alpha5beta1 receptor are important in the development of ischemia/reperfusion (I/R) injury of steatotic liver transplants. We examined the effect of a cyclic RGD peptide (cRGD), with high affinity for alpha5beta1 integrin, in a well-established steatotic rat liver model of ex vivo cold ischemia followed by isotransplantation. In this model, cRGD peptides were administered through the portal vein of steatotic Zucker rat livers prior to and after cold ischemic storage. Lean Zucker recipients of fatty orthotopic liver transplants (OLTs) received an additional course of cRGD peptides 1 hour posttransplantation. cRGD peptide therapy significantly inhibited the recruitment of monocyte/macrophages, and repressed the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Moreover, it resulted in selective inhibition of inducible nitric oxide synthase (iNOS), and MMP-9 expression. Importantly, cRGD peptide therapy improved the function and histologic preservation of steatotic liver grafts, extending their 14-day survival in lean recipients from 50% in untreated to 100% in cRGD-treated OLTs. Thus, cRGD peptide-mediated blockade of FN-alpha5beta1 interaction protects against severe I/R injury otherwise experienced by steatotic OLTs.
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PMID:Cyclic RGD peptides with high affinity for alpha5beta1 integrin protect genetically fat Zucker rat livers from cold ischemia/reperfusion injury. 1591 28

Complications of interferon (IFN) therapy include cardiac arrhythmias, impaired cardiac function and myocardial ischemia. Decreased heart rate variability (HRV) indices, impaired exercise tolerance and decreased left ventricular (LV) function are related to unfavorable outcome of heart disease. To investigate the effect of IFN therapy on HRV, exercise tolerance and cardiac function, 24-h ambulatory electrocardiographic monitoring (AECG), two-dimensional echocardiography, and exercise treadmill testing (ETT) was performed in 9 patients (age 56 +/- 9 years-old) with chronic hepatitis and without underlying heart disease before and after treatment with IFN (recombinant alpha 2b; 10 x 10(6) U/day for 4 weeks). HRV parameters consisted of standard deviation of RR interval (sdNN, ms), SDANN (ms), S.D. index (ms), rMSSD (ms), pNN50 (%) and frequency analysis of heart rate spectrum resulted in low (ms, 0.04-0.15 Hz), high (ms, 0.15-0.40 Hz) and total (ms, 0.01-1.00 Hz) frequency components. Ischemia was not detected by AECG or ETT, and LV function was normal after INF treatment in all patients. However, INF treatment resulted in a decrease in exercise tolerance time (449 +/- 94 s vs. 329 +/- 67 s, P < 0.05) and a decrease in several HRV parameters (S.D. index, 42 +/- 5 ms vs. 37 +/- 9 ms; rMSSD, 22 +/- 5 ms vs. 19 +/- 4 ms; pNN50, 4 +/- 3% vs. 2 +/- 1%; P < 0.05). Further, patients treated with INF tended to have a lower sdNN and total frequency spectra, although this difference did not reach the level of statistical significance. These data suggest that the arrhythmogenic effect of INF may be mediated by decreases in HRV and impairment of exercise tolerance even in patients without overt heart diseases. Further, INF therapy may be contraindicated in patients with predisposing severe cardiac disorders, including arrhythmias, ischemia and decreased LV function.
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PMID:Recombinant interferon alpha treatment decreases heart rate variability indices and impairs exercise tolerance in patients with chronic hepatitis. 1627 87


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