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)

The importance of melanocortin peptides to host responses was recognized with the observation of the antipyretic effect of centrally administered alpha-melanocyte stimulating hormone (alpha-MSH). It is now clear that this neuropeptide also exerts remarkable antiinflammatory activity via direct actions on peripheral host cells, descending neurogenic antiinflammatory pathways stemming from CNS melanocortin receptors, and local actions on receptors that control inflammation within the brain. Recent studies of the latter influence indicate that alpha-MSH inhibits brain tumor necrosis factor-alpha (TNF-alpha), previously linked to human neurodegenerative diseases, induced by local injection of lipopolysaccharide. Ischemia/reperfusion of the brain, a model of stroke, induces inflammation marked by disturbance of CNS function. alpha-MSH given systemically modulates disturbances of auditory evoked potentials induced by ischemia/reperfusion in the posterior circulation. Such influences of the peptide may occur through inhibition of inflammatory agents produced by glia: alpha-MSH 1-13 and 11-13 modulate TNF-alpha and nitric oxide produced by activated murine microglia, and TNF-alpha produced by human astrocytes. Because glia can secrete alpha-MSH and express melanocortin receptors, they may, like peripheral macrophages, contain autocrine regulatory circuits based on the peptide. alpha-MSH thus modulates both fever and inflammation in the brain by acting on local melanocortin receptors.
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PMID:Peptide modulation of fever and inflammation within the brain. 991 65

Brain angiogenesis is a tightly controlled process that is regulated by neuroectodermal derived growth factors that bind to tyrosine kinase receptors expressed on endothelial cells. In the rat brain, angiogenesis is complete around postnatal day 20, but endothelial cells can proliferate in the adult brain under pathological conditions such as hypoxia/ischemia and brain tumor growth. Current evidence suggests that physiological angiogenesis in the brain is regulated by similar mechanisms as pathological angiogenesis induced by tumors or by hypoxia/ischemia. The hypoxia-inducible endothelial cell mitogen and vascular permeability factor, vascular endothelial growth factor (VEGF) appears to play a pivotal role in most of these processes. VEGF is expressed when angiogenesis is high, as in embryonic neuroectoderm, in glioblastomas and around infarcts, but is expressed at low levels when angiogenesis is absent, as in adult neuroectoderm. Since growth factors such as VEGF and angiopoietins and their receptors appear to be necessary for angiogenesis, targeting of growth factor/receptor pathways for angiogenesis-dependent diseases such as glioblastoma might be useful for therapy. Several compounds, including anti-VEGF antibodies and VEGFR-2 inhibitors are currently in clinical trial. On the other hand, induction of angiogenesis by growth factors (pro-angiogenesis) might prove to be a rational therapy for patients with stroke.
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PMID:Mechanisms of angiogenesis in the brain. 1021 26

The apparent diffusion coefficients (ADCs) of water and brain metabolites were determined by proton MR spectroscopy on a clinical MR scanner for healthy volunteers and for pathological changes in cases of acute cerebral infarction and brain tumor. The ADCs of N-acetyl aspartate (NAA) and creatines in tissue involved in acute infarction were decreased compared to normal control values, while in tumors they showed increased values. Since NAA is a neuronal marker, these findings suggest that neuronal cell viscosity changes according to the pathological status of the tissue. The lactate ADC was significantly larger than the values for other major metabolites in cases of ischemia and tumor, suggesting that lactate is present in a different compartment. These results indicate that metabolite diffusion data can be used to reveal changes in the intracellular environment depending on the pathological status.
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PMID:Diffusion-weighted in vivo localized proton MR spectroscopy of human cerebral ischemia and tumor. 1184 May 55

Clinical and experimental use of positron emission tomography (PET) is expanding and allows quantitative assessment of brain tumor's pathophysiology and biochemistry. PET therefore provides different biochemical and molecular information about primary brain tumors when compared to histological methods or neuroradiological studies. Common clinical indications for PET contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by PET reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by PET could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as PET represents a novel technology for molecular imaging assays of metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. PET probes and drugs are being developed together as molecular probes to image the function of targets without disturbing them and in mass amounts to modify the target's function as a drug. Molecular imaging by PET helps to close the gap between in vitro to in vivo integrative biology of disease.
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PMID:Usefulness of positron emission tomography in diagnosis and treatment follow-up of brain tumors. 1505 51

Murine brain-specific angiogenesis inhibitor 1 and 2 (mBAI1, mBAI2) are involved in angiogenesis after cerebral ischemia. In this study, mBAI3 was cloned and characterized. Northern and Western blot analyses demonstrated a unique developmental expression pattern in the brain. The level of mBAI3 in brain peaked 1 day after birth, unlike mBAI1 and mBAI2, which peaked 10 days after birth. In situ hybridization analyses of the brain showed the same localization of BAI3 as BAI1 and BAI2, which includes most neurons of cerebral cortex and hippocampus. In the in vivo focal cerebral ischemia model, BAI3 expression decreased from 0.5 h after hypoxia until 8 h, but returned to control level after 24 h. The expression of vascular endothelial growth factor following ischemia showed an inverse pattern. The decreased expressions of BAIs in high-grade gliomas were observed, but BAI3 expression was generally lower in malignant gliomas than in normal brain. Our results indicate that the expression and distribution of BAI3 in normal brain, but not its developmental expression, are very similar to those of BAI1 and BAI2, and that BAI3 may participate in the early phases of ischemia-induced brain angiogenesis and in brain tumor progression.
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PMID:Expression of brain-specific angiogenesis inhibitor 3 (BAI3) in normal brain and implications for BAI3 in ischemia-induced brain angiogenesis and malignant glioma. 1522 53

Due to technological advances, it is now feasible to record continuous digital EEG (CEEG), with or without video, in critically ill patients and review recordings remotely. Nonconvulsive seizures (NCSzs) are more common than previously recognized and are associated with worse outcome. The majority of seizures in ICU patients are nonconvulsive and will be missed without CEEG. Factors associated with an increased risk for NCSzs include coma, prior clinical seizures, CNS infection, brain tumor, recent neurosurgery, and periodic epileptiform discharges. In addition to detecting seizures, CEEG is also useful for characterizing paroxysmal spells such as posturing or autonomic changes, detecting ischemia, assessing level of sedation, following long-term EEG trends, and prognosticating. Most NCSzs will be detected in the first 24 hours of CEEG in noncomatose patients, but longer recording periods may be required in comatose patients or in those with periodic epileptiform discharges. EEG patterns in encephalopathic or comatose patients are often equivocal. How aggressively to treat NCSzs and equivocal EEG patterns in these patients is unclear and requires further research. Real-time detection of ischemia at a reversible stage is technologically feasible with CEEG and should be developed into a practical form for prevention of in-hospital infarction in the near future.
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PMID:Continuous EEG monitoring in the intensive care unit: an overview. 1559 7

Nitric oxide (NO) is a chemical messenger implicated in neuronal damage associated with ischemia neurodegenerative disease and excitotoxicity. In the present study, we examined the biological effects of NO and its mechanisms in human malignant glioblastoma cells. Addition of a NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), induced apoptosis in U87MG human glioblastoma cells, accompanied by opening mitochondrial permeability transition pores, release of cytochrome c and AIF, and subsequently by caspase activation. NO-induced apoptosis occurred concurrently with significantly increased levels of the Bak and Bim. Treatment with SNAP resulted in sustained activation of JNK and its downstream pathway, c-Jun/AP-1. The expression of dominant-negative (DN)-JNK1 and DN-c-Jun suppressed the activation of AP-1, the induction of Bak and Bim, and the SNAP-induced apoptosis. In addition, de novo protein synthesis was required for the initiation of apoptosis in that the protein synthesis inhibitor, cycloheximide (CHX), inhibited NO-induced apoptotic cell death as well as up-regulation of Bak and Bim. These results suggest that NO activates an apoptotic cascade, involving sustained JNK activation, AP-1 DNA binding activity, and subsequent Bak and Bim induction, followed by cytochrome c and AIF releases and caspases cascade activation, resulting in human malignant brain tumor cell death.
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PMID:Up-regulation of Bak and Bim via JNK downstream pathway in the response to nitric oxide in human glioblastoma cells. 1615 21

Conversion disorder is caused by previous severe stress, emotional conflict, or an associated psychiatric disorder, and usually presents with one or more neurologic symptoms. Clinically, it is challenging to diagnose diseases such as transient ischemia attack, stroke, brain tumor, spinal cord injury, and neuropathy. In this case report, we present a male stroke patient who had a typical conversion disorder.
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PMID:Conversion disorder in stroke: a case report. 1711 Mar 49

As the research on cellular changes has shed invaluable light on the pathophysiology and biochemistry of brain tumors, clinical and experimental use of molecular imaging methods is expanding and allows quantitative assessment. The term molecular imaging is defined as the in vivo characterization and measurement of biologic processes at the cellular and molecular level. Molecular imaging sets forth to probe the molecular abnormalities that are the basis of disease rather than to visualize the end effects of these molecular alterations and, therefore, provides different additional biochemical or molecular information about primary brain tumors compared to histological methods "classical" neuroradiological diagnostic studies. Common clinical indications for molecular imaging contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by molecular imaging could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as molecular imaging represents a novel technology for visualizing metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. Molecular imaging probes and drugs are being developed to image the function of targets without disturbing them and in mass amounts to modify the target's function as a drug. Molecular imaging helps to close the gap between in vitro and in vivo integrative biology of disease.
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PMID:Molecular imaging of brain tumors: a bridge between clinical and molecular medicine? 1720 38

Reactive oxygen species (ROS) are associated with oxidative stress-mediated alterations under pathophysiological conditions, and particularly brain ischemia, brain tumor, and neurodegenerative diseases. Electron spin resonance (ESR) is recognized as one of the most powerful techniques available for the detection of ROS in tissues and cells. We previously developed an in vitro ESR-based technique for the detection of free radical reactions in biological systems. In addition, significant advances in the field of in vivo ESR techniques over recent years have now made it possible to visualize the distribution and metabolism of oxidative stress, and the degree of tissue oxygenation in vivo. Nitroxyl radicals are very useful as exogenous spin probes for measuring free radical distribution, oxygen concentration, and redox metabolism by in vivo ESR in biological systems, using a combination of these ESR methods collectively focused on animal models of disease such as spontaneously hypertensive rat (SHR) or stroke-prone SHR (SHRSP) for the assessment of antioxidant property of drugs. Our results suggest that ESR could be applied to the assessment of antioxidant property on oxidative stress in target organs, especially brain, using animal disease models, SHR or SHRSP. After screening drugs for antioxidant property using such as in vitro or in vivo ESR assessment, we'll be able to develop and find novel antioxidant drugs for ROS-induced brain disease in the near future.
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PMID:[Biomedical application of electron spin resonance (ESR) spectroscopy--assessment of antioxidant property for development of drugs]. 1845 24


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