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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An analytical method has been developed and validated for the quantitative determination of the N-methyl-D-aspartate (NMDA) antagonist cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) in human plasma. It is a member of a new class of compounds with the potential to be neuroprotective and attenuate neuronal damage resulting from brain trauma caused by stroke and head trauma. The method is based on gas chromatography/mass spectrometry and uses stable-isotope labeled CGS 19755 as the internal standard. Samples (1 ml) were first acidified (pH 2), then extracted using a solid-phase aminopropyl ion exchange column. The drug was eluted with NH4OH and evaporated until dry. Extracts were derivatized with a mixture of pentafluoropropionic anhydride and pentafluoropropanol, and analyzed by gas chromatography/mass spectrometry. Separation was accomplished on a DB-225 capillary column (15 m x 0.32 mm) with a 0.25 micron film thickness. Mass spectrometry was carried out under negative ion ammonia chemical ionization conditions with selected ion monitoring at m/z 760 and 764 for derivatized CGS 19755 and the internal standard, respectively. Specificity was shown by the lack of interfering peaks at the retention time of CGS 19755 and internal standard. Recovery and reproducibility assessments show good accuracy, precision and linearity over the validated concentration range of 2-5000 ng ml-1.
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PMID:Quantitative determination of the NMDA antagonist cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) in human plasma using capillary gas chromatography/mass spectrometry. 794 48

Experiments were conducted on male albino rats to study some intracellular metabolites (lactate, pyruvate, malate, glutamate, alpha-ketoglutarate, ammonia) and the redox process in the tissues of the liver, kidneys, myocardium, and skeletal muscles during hyperthermia (40 degrees C for one hour and 45 degrees C for one hour). Changes of the metabolite content and shifts in the redox process in the direction of oxidation in the liver and kidneys at both levels of hyperthermia are evidence of the development of tissue hypoxia of circulatory character in these organs. The mitochondrial NAD/NADH ratio in the myocardium reduced in moderate hyperthermia and increased during a heat stroke. There were no signs of cellular hypoxia in the skeletal muscles. It is concluded on basis of the results that changes of the blood flow in the organs play the leading role in the origin of thermal hypoxia.
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PMID:[Intracellular oxidative-reductive processes in tissues in hyperthermia]. 805 76

This study was conducted to examine the effects of creatine (Cr) supplementation on sprint swimming performance and energy metabolism. Twenty highly trained swimmers (9 female, 11 male) were tested for blood ammonia and for blood lactate after the 25-, 50-, and 100-m performance in their best stroke on two occasions 7 d apart. After the first trial, subjects were evenly and randomly assigned to either a creatine (5 g creatine monohydrate 4 times per day for 5 d) or a placebo group (same dosage of a lactose placebo) in a double-blind research design. No significant differences in performance times were observed between trials. Post-exercise blood ammonia concentration decreased in the 50- and 100-m trials in the creatine group and in the 50-m trial in the placebo group. The supplementation period had no effect on post-exercise blood lactate. Therefore, creatine supplementation cannot be considered as an ergogenic aid for sprint performance in highly trained swimmers although adenine nucleotide degradation may be reduced during sprint exercise after 5 d of creatine ingestion.
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PMID:Creatine supplementation does not improve sprint performance in competitive swimmers. 893 96

A 16-year-old man developed heat stroke during football practice when the temperature was 33.8 degrees C (heat index, 44.4 degrees C). Resuscitation with ice water lavage, external cooling, and intravenous fluids was initially successful, but the patient again became obtunded. Liver chemistry tests and the prothrombin time and serum ammonia increased markedly, and rhabdomyolysis and renal failure became evident, necessitating hemodialysis. He underwent liver transplantation for fulminant hepatic failure approximately 72 hours after admission. Rhabdomyolysis with renal failure and severe electrolyte disturbances continued despite aggressive hemodialysis and the patient had a cardiopulmonary arrest and died 10 days after transplantation. This case shows that liver transplantation cannot always overcome the generalized toxic effects of heat stroke. More aggressive hemodialysis or combined liver/kidney transplantation might result in a positive outcome in selected cases.
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PMID:Fulminant hepatic failure from heat stroke requiring liver transplantation. 1087 74

Excitotoxicity has been implicated in the etiology of ischemic stroke and chronic neurodegenerative disorders. Hence, the development of novel neuroprotectant molecules that ameliorate excitotoxic brain damage is vigorously pursued. We used a neuroprotection-based cellular assay to screen a synthetic combinatorial library of N-alkylglycine trimers. Two compounds (6-1-2 and 6-1-10) that efficiently prevented excitotoxic neurodegeneration in vitro and in vivo were identified. Both molecules protected primary cultures of cerebellar neurons against glutamate-induced neuronal death with an efficiency equivalent to N-methyl-D-aspartate (NMDA) receptor antagonists. These trialkylglycines did not block appreciably the NMDA receptor channel, or attenuated glutamate-induced increase of Ca(2+), or affect the glutamate-nitric oxide-cGMP pathway. Intraperitoneal injection of both peptoids in mice attenuated > or = 80% ammonia-induced, NMDA receptor-mediated animal death. Furthermore, these two molecules reduced by > or = 50% the neurodegeneration in striatum in a rat model of cerebral ischemia. Neuroprotection against ischemia was associated with decreased activation of caspase-3, reflecting prevention of apoptotic neuronal death. Collectively, the results reported indicate that these trialkylglycines are new neuroprotectant leads with important in vivo activity against excitotoxicity, and that they act on a novel, yet-unrecognized cellular target. These lead compounds may become tolerated drugs for the treatment of acute and chronic neurodegenerative diseases with fewer side effects than NMDA receptor antagonists.
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PMID:Prevention of in vivo excitotoxicity by a family of trialkylglycines, a novel class of neuroprotectants. 1190 54

Elucidation of the metabolism and pharmacology of 1,2,3-triazolines (TRs) led to the identification of the triazoline pharmacophore and the evolution of the aminoalkylpyridines (AAPs). The AAPs have no activity in the scMet test but are highly effective in the MES seizure test by the oral route. The AAPs bind to the sigma(1) receptor with low affinity, but high selectivity. They impair Glu release to the same extent as the triazolines and afforded a high degree of protection in the kindled rat. They show no affinity for the NMDA/PCP receptor sites; thus the toxic side effects of NMDA antagonists are absent in the sigma selective AAPs. Variations of the heterocyclic unit, the alkyl chain and the amino group in the AAP leads, indicated that the 4-pyridyl substituent along with a methyl (alkyl) group, and a 4-C1, 3-C1 or 3,4-C1(2) substitution on the N-phenyl group, afforded the most active compounds. Amino group modification by acylation did not improve activity. The hydrazone compounds were the most active. Although the AAPs are very effective in the MES and the kindling models of epilepsy, they showed only low to moderate activity in protecting neuronal cells in stroke-induced cerebral ischemia. In the case of the TR compounds, even the least effective TR afforded 47% protection from neuronal injury. It is not known at this point, whether activity in both the MES and scMet tests, which would imply a role for both Glu and GABA, is a prerequisite for antiischemic activity.
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PMID:Aminoalkylpyridines (AAPs), triazoline metabolite analogues, as anticonvulsants highly effective in the MES test. 1287 Oct 88

An avian influenza (AI) real time reverse transcriptase-polymerase chain reaction (RRT-PCR) test was previously shown to be a rapid and sensitive method to identify AI virus-infected birds in live-bird markets (LBMs). The test can also be used to identify avian influenza virus (AIV) from environmental samples. Consequently, the use of RRT-PCR was being considered as a component of the influenza eradication program in the LBMs to assure that each market was properly cleaned and disinfected before allowing the markets to be restocked. However, the RRT-PCR test cannot differentiate between live and inactivated virus, particularly in environmental samples where the RRT-PCR test potentially could amplify virus that had been inactivated by commonly used disinfectants, resulting in a false positive test result. To determine whether this is a valid concern, a study was conducted in three New Jersey LBMs that were previously shown to be positive for the H7N2 AIV. Environmental samples were collected from all three markets following thorough cleaning and disinfection with a phenolic disinfectant. Influenza virus RNA was detected in at least one environmental sample from two of the three markets when tested by RRT-PCR; however, all samples were negative by virus isolation using the standard egg inoculation procedure. As a result of these findings, laboratory experiments were designed to evaluate several commonly used disinfectants for their ability to inactivate influenza as well as disrupt the RNA so that it could not be detected by the RRT-PCR test. Five disinfectants were tested: phenolic disinfectants (Tek-trol and one-stroke environ), a quaternary ammonia compound (Lysol no-rinse sanitizer), a peroxygen compound (Virkon-S), and sodium hypochlorite (household bleach). All five disinfectants were effective at inactivating AIV at the recommended concentrations, but AIV RNA in samples inactivated with phenolic and quaternary ammonia compounds could still be detected by RRT-PCR. The peroxygen and chlorine compounds were effective at some concentrations for both inactivating virus and preventing amplification by RRT-PCR. Therefore, the RRT-PCR test can potentially be used to assure proper cleaning and disinfection when certain disinfectants are used.
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PMID:The effect of various disinfectants on detection of avian influenza virus by real time RT-PCR. 1457 18

Brain edema with intracranial hypertension is a major complication in patients with acute liver failure. Current therapies for this complication include a variety of pharmacologic and interventional measures, some of which are frequently associated with adverse effects or contraindications. Even though these measures usually allow the control of intracranial hypertension for a certain period of time, recurrence is common. New therapies are therefore needed. Increasing clinical and experimental evidence suggests that induction of mild hypothermia (32 degrees C-35 degrees C) may be a therapeutic alternative. Similar to traumatic brain injury or brain stroke, induction of mild hypothermia seems highly effective to reduce intracranial pressure in patients with acute liver failure. Several mechanisms by which mild hypothermia may prevent brain edema and intracranial hypertension in this condition have been disclosed and may include beneficial effects on ammonia metabolism, as well as on the disturbances of brain osmolarity, cerebrovascular hemodynamics, brain glucose metabolism, inflammation, and others. Improvement of systemic hemodynamics and amelioration of liver injury may be other benefits of the systemic induction of mild hypothermia, but the impact of potential adverse events, such as infection, should also be taken into account. At a time when mild hypothermia is increasingly used in several specialized centers, performance of a randomized controlled trial seems critical to confirm the benefits of mild hypothermia in acute liver failure and to provide adequate guidelines for its use.
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PMID:Mild hypothermia for acute liver failure: a review of mechanisms of action. 1575 51

A previously healthy 5 1/2-year-old male had Reye syndrome. He presented in coma with apnea 1 week after a viral infection and following 2 days of vomiting and progressive obtundation. He was in coma with dystonic posturing and intact brainstem function. Laboratory evaluation revealed initial hypoglycemia, and markedly elevated liver enzymes, prolonged clotting times, and elevated ammonia levels. No underlying metabolic disorder was present, and the patient completely recovered. On a modified diffusion-weighted image magnetic resonance imaging scan, restriction of diffusion in the thalamus and midbrain was observed. While abnormalities of the thalamus and midbrain have previously been reported, this is the first report of diffusion-weighted imaging indicating early impairment of water diffusion, a finding more commonly observed with stroke.
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PMID:The thalamus and midbrain in Reye syndrome. 1664 4

Although the number of fish species that have been studied for both hypoxia/anoxia tolerance and ammonia tolerance are few, there appears to be a correlation between the ability to survive these two insults. After establishing this correlation with examples from the literature, and after examining the role Peter Lutz played in catalyzing this convergent interest in two variables, this article explores potential mechanisms underpinning this correlation. We draw especially on the larger body of information for two human diseases with the same effected organ (brain), namely stroke and hepatic encephalopathy. While several dissimilarities exist between the responses of vertebrates to anoxia and hyperammonemia, one consistent observation in both conditions is an overactivation of NMDA receptors or glutamate neurotoxicity. We propose a glutamate excitotoxicity hypothesis to explain the correlation between ammonia and hypoxia resistance in fish. Furthermore, we suggest several experimental paths to test this hypothesis.
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PMID:Piscine insights into comparisons of anoxia tolerance, ammonia toxicity, stroke and hepatic encephalopathy. 1704 1


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