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)

Seizures are a common occurrence in the intensive care unit (ICU). The presentation of seizures is usually as focal or generalized motor convulsions, but other seizure types may occur. Etiologies of the seizures are typically secondary either to primary neurologic pathology or a consequence of critical illness and clinical management. Particularly important as precipitants of seizures are hypoxia/ischemia, drug toxicity, and metabolic abnormalities. It is important to properly diagnose the seizure type and its cause to ensure appropriate therapy. Most seizures occur singly, and recurrence is usually prevented with initiation of anticonvulsant therapy. However, status epilepticus may develop, which requires emergent treatment before irreversible brain injury occurs. Treatment with anticonvulsants is not without untoward risks, however, and primary toxicities of these agents is reviewed. After traumatic head injury, brain surgery, or cerebrovascular accidents, many patients are at risk for seizures. Current data on the benefits of prophylactic therapy for such patients is also reviewed.
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PMID:Seizures in the adult intensive care unit. 1129 60

The aim of the study was to examine the role of NMDA receptors in the modulation of brain tolerance after transient cerebral ischemia. Adult mice were exposed for 30 min to bilateral clamping of common carotid arteries (BCCA) under anaesthesia. The non-competitive NMDA antagonist, MK-801 was administered intraperitoneally (ip) in two experimental paradigms: a) acute: twice at 1.0 mg/kg; 1 h before the clamping of the vessels and 6 h after re-circulation; b) chronic at a dose of 0.1 mg/kg, started 24 h after recirculation and continued once daily for 13 days with the last injection 24 h before the induction of convulsions. Seizures were evoked with pilocarpine (400 mg/kg, ip) 14 days after BCCA. It was found that transient incomplete brain ischemia induced protection against pilocarpine toxicity. The acute treatment with MK-801 did not diminish the anticonvulsant action of the procedure. In contrast, the chronic treatment with the drug led to a marked potentiation of the effect. In conclusion, it can be suggested that studied NMDA receptor antagonist used at relatively low dose may enhance the brain tolerance activated after a transient ischemic episode.
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PMID:Effect of MK-801 on pilocarpine-evoked seizures in mice exposed to transient incomplete brain ischemia. 1134 83

The authors report an unusual case of low intracranial pressure (ICP) syndrome that was successfully treated by the placement of an anti-siphon device (ASD). This 36-year-old male had suffered suprasellar germinoma with hydrocephalus and had had a V-P shunt following radiotherapy. Sixteen years later he developed gait disturbance and somnolence and MRI demonstrated a small lateral ventricle as well as a diffuse dural enhancement. A lumbar tap revealed a low ICP of 12 mmH2O. Because of this, an ASD was placed in the patient. Postoperatively, his symptoms of gait and consciousness disturbance improved. Typical clinical findings of low ICP syndrome such as headache were not observed in this case. To our knowledge, no symptom of gait disturbance with low ICP has been reported previously. We present an interesting case of low ICP syndrome with gait disturbance and discuss the mechanism of the symptoms. Symptoms of this patient were due at first to brain ischemia. After convulsion and consciousness disturbance due to low intracranial pressure, the symptoms increased in strength until gait disturbance occurred. The possibility is suggested that gait disturbance in this patient was due both to brain ischemia and low intracranial pressure.
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PMID:[Successful treatment of a patient with low pressure syndrome associated with gait disturbance]. 1159 68

The neuroprotective properties of topiramate were evaluated in a rat model of stroke in which neurodegeneration was induced by temporary global ischemia. In this model, the ischemia resulted from 11 min of cardiac arrest during atraumatic chest compression. Resuscitated rats exhibit a characteristic neurological syndrome characterized by sound-induced convulsions, specific motor and behavioral deficits, and death of hippocampal CA1 pyramidal neurons. Topiramate, when administered i.v. 30 min after resuscitation, reduced the degree of motor impairment (P< 0.05 vs control at doses of 10 and 20 mg/kg) and seizure severity (P< 0.05 vs control at a dose of 10 mg/kg on the fifth recovery day). The highest dose of topiramate (20 mg/kg i.v.) eliminated nearly all histologic signs of hippocampal ischemic neuronal injury (P< 0.001). Phenytoin at 20 mg/kg i.v. exhibited neuroprotectant effects similar to those observed for topiramate at 20 mg/kg i.v.. In normal rats, neither topiramate nor phenytoin at 20 mg/kg i.v. induced any apparent neurological impairment; however, at 40 and 60 mg/kg i.v. both induced a mild impairment typical of most anticonvulsants. The results of this study support the concept that topiramate possesses neuroprotective properties.
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PMID:Topiramate as a neuroprotectant in a rat model of global ischemia-induced neurodegeneration. 1166 69

Ebselen (EBS) is a seleno-organic compound with glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. In this study, we investigated the effect of EBS on quinolinic acid (QA)-induced neurotoxicity. EBS inhibited QA-induced production of thiobarbituric acid reactive species (TBARS) by striatal homogenates in vitro with an IC(50) of 1.85 microM. Intra-striatal injection of QA (360 nmol) increased striatal content of TBARS and induced convulsions and contralateral rotational behavior. Intra-striatal pre-injection of EBS (10 nmol) 15 min before QA abolished QA-induced TBARS production but did not alter QA-induced behavioral effects. The present findings suggest that EBS acts on post-receptor events, neutralizing free radicals produced by overstimulation of N-methyl-D-aspartate receptors.
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PMID:Ebselen blocks the quinolinic acid-induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intra-striatal quinolinic acid administration in the rat. 1180 18

Atherogenesis is a disease of middle-sized and large-caliber blood vessels that can be divided into three major phases. The initial lesions of early atherosclerosis are characterized by the adhesion and subendothelial emigration of blood-borne monocytes, which differentiate into macrophages and provide the morphologic basis for the formation of foam cells and fatty streak lesions. These lesions are found in most children and teenagers in industrialized nations. The next key event in atherogenesis is the proliferation of smooth muscle cells within the intima and media, resulting in the gradual compromise of the vessel lumen. Myofibroblastic cells also contribute to lesion growth through the production of excessive amounts of extracellular matrix. Such lesions are clinically silent unless progression to the next phase continues: the lesions degenerate, forming a mostly necrotic "lipid core" consisting of extracellular lipid, cholesterol crystals, inflammatory cells and necrotic debris. A fibrous cap is formed which prevents the interaction of blood cells, particularly of platelets with the highly proaggregatory material found in the lipid core. However, continuous inflammatory activity and/or heightened mechanical stress (i.e., in hypertension) tends to weaken the fibrous caps. Eventually, plaque rupture ensues, platelets aggregate, and the lesions become clinically manifest in such dramatic events as myocardial infarction, stroke, or mesenteric ischemia. Research into lesion formation and progression is limited by the fact that lesions develop in silence over many decades and that animal models only incompletely model the situation in humans. Most currently debated concepts accept the "response to injury" hypothesis formulated by the late Russell Ross and the multi-factorial nature of atherogenesis. The discussion today circles around the relative contributions of low density lipoproteins (oxidized or enzymatically modified LDL?), the immune response (adaptive or innate?), infectious agents (CMV, Chlamydia pneumoniae?), and/or hereditary factors, to name only a few of the most widely debated concepts. Irrespective of the outcome of this pathomechanistic discussion, the knowledge of established risk factors (hypercholesterolemia, hypertension, diabetes, smoking, etc.) and protective interventions (lifestyle changes, physical exercise, "healthy" diets, effective dietary and pharmacologic control of hyperglycemia, blood pressure or hyperlipidemia) has helped to define atherosclerosis as a "new entity" that has little to do with the archaic concept of a "degenerative" vessel disease. The new concept takes us into the responsibility--puts us in charge of our own and our patients' cardiovascular risk--whether we like it or not. The smoking obese doctor no longer fits into the modern medical landscape.
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PMID:[Atherosclerosis--progression by nonspecific activation of the immune system]. 1197 79

Placental vascular diseases consist of obstetrical pathologies assumed to be linked to placental ischemia. Preeclampsia, defined as the association of hypertension, proteinuria and edema, occur in 3% of deliveries, in a non-selected population. Eclampsia, defined as the occurrence of convulsions in preeclamptic women, occur in 5 per 10,000 deliveries. Risk factors for preeclampsia are: preeclampsia in the previous pregnancy, maternal age <20 years, multiple pregnancies, and nulliparity. Placenta abruption, defined as premature separation of the placenta before delivery, occur in 5 to 15 per 1,000 deliveries. Risk factors are smoking, infertility, and preeclampsia or placental abruption in the previous pregnancy. Stillbirth, defined as fetal death between 24 weeks of gestation and delivery, occur in 1.5 per 1,000 deliveries, with a higher frequency in case of placental abruption, intrauterine growth restriction or preeclampsia.
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PMID:[Epidemiology of vascular placental disease]. 1502 84

A test for detecting acute cellular rejection (ACR) of small intestinal transplants (ITx) would be a major advance. Small preliminary studies suggest that serum citrulline levels correlate with ACR. The results for a group of 26 isolated intestinal and multivisceral transplant recipients are summarized here. Serum citrulline concentrations were determined by ion exchange chromatography and compared to biopsy-based grade of ACR. Other factors considered included patient and donor age and sex, ischemia time, and serum creatinine. Straight-line fits were employed to describe how each patient's citrulline levels changed over time. Estimated times to achieve normal citrulline (>or=30 micromol/L) ranged from 1 to 730 days posttransplant for 21 patients demonstrating increasing citrulline levels over time. Using stepwise linear regression, patients' ranks for time required to achieve normal citrulline levels were the only independent predictors of both maximum ACR (P <.0001) and average ACR (P =.0059) after 14 days posttransplant. The rate and direction of change in citrulline over time may be an indicator of the risk of acute rejection. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.
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PMID:Trends in serum citrulline and acute rejection among recipients of small bowel transplants. 1505 Jan 54

Small preliminary studies suggest that serum citrulline levels may act as a marker for acute cellular rejection in small intestinal transplant recipients. The results comparing serum citrulline concentrations with biopsy-based grades of rejection are summarized here for an expanded group of 26 isolated intestinal and multivisceral transplant recipients. Other factors considered included patient and donor age and sex, ischemia time, serum creatinine, and type of transplant. Straight-line fits reasonably described how each patient's citrulline levels changed over time. Among 21 patients who demonstrated increasing citrulline levels over time, the estimated median time-to-achieve normal citrulline (>or=30 micromol/L) was 79 days post-transplant. Using stepwise linear regression, two characteristics were associated with a significantly higher maximum grade of rejection after 14 d post-transplant: longer time-to-achieve normal citrulline (using ranks, p < 0.00001) and the patient not receiving a multivisceral transplant (p = 0.0005). Only the latter characteristic was significantly associated with maximum grade of rejection during the first 14 d post-transplant (p = 0.01). Clearly, time-to-normalization of citrulline was delayed by the incidence of rejection, and in some cases with moderate-to-severe rejection, normalization of citrulline levels never occurred. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.
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PMID:An analysis of the association between serum citrulline and acute rejection among 26 recipients of intestinal transplant. 1519 71

In the hippocampus, extracellular signal-regulated kinase (ERK) and the non-receptor protein proline-rich tyrosine kinase 2 (PYK2) are activated by depolarization and involved in synaptic plasticity. Both are also activated under pathological conditions following ischemia, convulsions, or electroconvulsive shock. Although in non-neuronal cells PYK2 activates ERK through the recruitment of Src-family kinases (SFKs), the link between these pathways in the hippocampus is not known. We addressed this question using K(+)-depolarized rat hippocampal slices. Depolarization increased the phosphorylation of PYK2, SFKs, and ERK. These effects resulted from Ca(2+) influx through voltage-gated Ca(2+) channels and were diminished by GF109203X, a protein kinase C inhibitor. Inhibition of SFKs with PP2 decreased PYK2 tyrosine phosphorylation dramatically, but not its autophosphorylation on Tyr-402. Moreover, PYK2 autophosphorylation and total tyrosine phosphorylation were profoundly altered in fyn-/- mice, revealing an important functional relationship between Fyn and PYK2 in the hippocampus. In contrast, ERK activation was unaltered by PP2, Fyn knock-out, or LY294002, a phosphatidyl-inositol-3-kinase inhibitor. ERK activation was prevented by MEK inhibitors that had no effect on PYK2. Immunofluorescence of hippocampal slices showed that PYK2 and ERK were activated in distinct cellular compartments in somatodendritic regions and nerve terminals, respectively, with virtually no overlap. Activation of ERK was critical for the rephosphorylation of a synaptic vesicle protein, synapsin I, following depolarization, underlining its functional importance in nerve terminals. Thus, in hippocampal slices, in contrast to cell lines, depolarization-induced activation of non-receptor tyrosine kinases and ERK occurs independently in distinct cellular compartments in which they appear to have different functional roles.
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PMID:Depolarization activates ERK and proline-rich tyrosine kinase 2 (PYK2) independently in different cellular compartments in hippocampal slices. 1553 34


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