Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on accumulating evidence of the role of xanthine oxidase (XO) in generating oxygen free radicals and causing tissue damage during ischemia, we examined the possible role of XO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). After inducing SAH in dogs by two autologous blood injections 2 days apart, chronic vasospasm of the basilar artery was reliably produced. There was a 3.5-fold elevation in uric acid (UA), the product of XO, in the cerebrospinal fluid (CSF) of these animals. Parenteral administration of allopurinol (i.v., 25 mg/kg, every 6 hours), a specific blocker of XO, successfully abolished the elevation in CSF uric acid levels due to SAH. However, angiographic vasospasm measured on Day 7, morphological changes observed by electron microscope, and elevated CSF prostaglandin levels were not altered by the treatment. It can be concluded that the observed activation of the enzyme XO, which is a well-known source of oxygen free radicals in ischemia in various organs, is not playing a major role in the pathogenesis of chronic cerebral vasospasm in this animal.
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PMID:Production of uric acid in cerebrospinal fluid after subarachnoid hemorrhage in dogs: investigation of the possible role of xanthine oxidase in chronic vasospasm. 361 2

Uric acid is the end product of the purine metabolism in the human and is mainly excreted to the urine. The studies on cerebrospinal fluid (CSF) uric acid in patients with various neurological diseases were reported in the literature. In the present study the authors discussed the clinical value of the sequential study of the CSF uric acid content in patients with brain tumors. CSF was investigated for uric acid in 23 controls and 30 cases of brain tumor. The results were as follows: The mean value and standard deviation of the uric acid in CSF in controls was 0.23 +/- 0.13 mg/dl. The uric acid in CSF increased in patients with malignant brain tumor (0.49 +/- 0.22 mg/dl, p less than 0.005), but was in normal range in patients with benign brain tumor (0.32 +/- 0.13 mg/dl, 0.10 less than p less than 0.25). There was no significant correlation between CSF uric acid and CSF protein contents. Uric acid in the lumbar CSF was approximately 4 times higher than in the ventricular CSF in patients with brain tumor. The CSF uric acid had progressively increased during irradiation to the whole brain. The factors contributing to increase of the uric acid in CSF were thought to be increased permeability of blood-CSF barrier, global damage of brain tissue, increased nucleic acid catabolism in the central nervous system (CNS) for example in tumor, inflammation or immunoreaction, increased of xanthine, hypoxanthine or xanthine oxidase activity in the CNS, directly increased of plasma components into the CSF due to such as subarachnoid hemorrhage, intraventricular hemorrhage, bleeding in the tumor or surgical operation, dysfunction of the CSF dynamics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical value of the sequential study of the uric acid in CSF in patients with cerebral diseases: Part I. Brain tumor and the effect of irradiation]. 674 98

N,N'-Propylenedinicotinamide (Nicaraven) is presently being developed for the treatment of cerebral stroke including subarachnoid hemorrhage. This drug is promising because some data suggest it to have an ability to scavenge the hydroxyl radical under physiological conditions in vivo, while it also has a high permeability through the blood brain barrier. Using the kinetic constant of the reaction between the hydroxyl radical and dimethyl sulfoxide, the formula derived by Babbs and Griffin (Free Rad. Biol. Med., 6 1989) was applied to obtain the kinetic constant of Nicaraven with the hydroxyl radical using a dimethyl sulfoxide-xanthine oxidase-hypoxanthine-Fe system, and this yielded the kinetic constant 3.4x10(9) M(-1) s(-1) (1 M=1 mol dm(-3)) for Nicaraven. Structurally related compounds were also investigated. The amide group of Nicaraven was thus found to play an important part in the reaction with the hydroxyl radical. Methanesulfinic acid, which was obtained from the reaction between dimethyl sulfoxide and the hydroxyl radical, was found to be stable under this adopted experimental condition and therefore was used to quantify the kinetic constant of Nicaraven. The structure of Nicaraven has also been investigated in CDCl3 using IR spectra, computer calculations and 1H-NMR analysis, and Nicaraven was thus shown to have an intramolecular hydrogen bond which forms a 7-membered ring that resembles a part of the 1H-1,4-benzodiazepines. This structure may play an important role in the penetration through the blood brain barrier.
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PMID:Quantitative analysis of the kinetic constant of the reaction of N,N'-propylenedinicotinamide with the hydroxyl radical using dimethyl sulfoxide and deduction of its structure in chloroform. 1078 63

Aneurismal subarachnoid haemorrhage (SAH) is a devastating disease that is associated with significant morbidity and mortality. The mortality is approximately 50%, with 30% of survivors having significant morbidity. There is substantial evidence to suggest that oxidative stress is significant in the development of acute brain injury and cerebral vasospasm following SAH. There are several sources for the excessive generation of free radicals following SAH, including disrupted mitochondrial respiration and extracellular hemoglobin. There is also the upregulation of free radical producing enzymes such as inducible nitric oxide synthase (iNOS), xanthine oxidase, NADPH oxidase (NOX), as well as enzymes involved in the metabolism of arachidonic acid. Additionally, intrinsic antioxidant systems such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are inhibited. Experiments have linked free radicals to the apoptosis of neurons and endothelial cells, BBB breakdown and the altered contractile response of cerebral vessels following SAH. Antioxidant therapy has provided neuroprotection and antispasmotic effects in experimental SAH and some therapies have demonstrated improved outcomes in clinical trials. These studies have laid a foundation for the use of antioxidants in the treatment of aneurismal SAH.
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PMID:Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. 1845 95