Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients treated for aneurysmal subarachnoid hemorrhage show, in the long-term follow up, an elevated rate of cognitive disturbances that are mainly related to the impact of the initial bleeding: the neurotoxic effects of blood deposition in subarachnoidal spaces may result in a diffuse encephalopathy, but the intrinsic mechanism and the biochemical correlates are not known. In the present study we have evaluated mitochondrial function after experimental induction of subarachnoid hemorrhage. Mitochondrial function was evaluated in four different rat brain areas (frontal cortex, occipital cortex, hippocampus, and brain stem) after experimental isobaric subarachnoid hemorrhage in rats. Subarachnoid hemorrhage was induced by injecting 0.07 mL of arterial autologous blood into the cisterna magna. Intracranial pressure did not significantly increase. The nonsynaptic mitochondrial fraction was isolated from different rat brain areas, and the maximal rate of enzymatic reactions of some key enzymatic activities related to the Krebs cycle [nicotinamide adenine dinucleotide (oxidized form) (NAD+)-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase] and of the electron transfer chain (cytochrome oxidase) were evaluated. The nonsynaptic mitochondrial fraction was utilized also to check parameters related to the mitochondrial respiration: state 3, state 4, uncoupled state, respiratory control ratio, and adenosine 5'-diphosphate/oxygen ratio. The biochemical parameters were measured at 1 and 72 hours after the subarachnoidal injection of blood. Subarachnoid hemorrhage did not affect the mitochondrial enzymatic activities both at 1 and 72 hours, while the mitochondrial enzymatic activities parameters were significantly affected: in particular, a significant decrease of respiratory control ratio in all tested brain areas was demonstrated. The increased mitochondrial vulnerability in the delayed phases could be one of the biochemical correlates of post-hemorrhagic encephalopathy.
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PMID:Experimental isobaric subarachnoid hemorrhage: regional mitochondrial function during the acute and late phase. 221 48

The D(-) isomer of lactic acid appears to cause a form of metabolic encephalopathy experienced by patients who have had jejunoileal bypass for morbid obesity. However, analysis for D(-)-lactate is not routinely available in clinical or reference laboratories. We describe an enzymic centrifugal-analyzer assay for D(-)-lactate in plasma or serum, with use of D(-)-lactate dehydrogenase. The method involves two-point kinetic calibration and preincubation of specimen and NAD+, thus eliminating the need for specimen-blanking or protein-precipitating pretreatment. This rapid, accurate, and precise assay should be helpful in evaluating patients with "short-bowel syndrome" who display confusion, lethargy, ataxia, or other central nervous-system disturbances that may be ascribable to D(-)-lactic acidosis.
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PMID:Kinetic enzymic assay for D(-)-lactate, with use of a centrifugal analyzer. 661 31

Ethylene glycol ethers (EGEs) are primary alcohols commonly used as solvents in numerous household and industrial products. Exposure to EGEs has been correlated with delayed encephalopathy, metabolic acidosis, sub-fertility and spermatotoxicity in humans. In addition, they also cause teratogenesis, carcinogenesis, hemolysis, etc., in various animal models. Metabolism EGEs parallels ethanol metabolism, i.e., EGEs are first converted to 2-alkoxy acetaldehydes (EGE aldehydes) by alcohol dehydrogenases, and then to alkoxyacetic acids by aldehyde dehydrogenases (ALDHs). The acid metabolite of EGEs is considered responsible for toxicities associated with EGEs. The role of human ALDHs in EGE metabolism is not clear; accordingly, we have investigated the ability of five different human ALDHs (ALDH1A1, ALDH2, ALDH3A1, ALDH5A1 and ALDH9A1) to catalyze the oxidation of various EGE aldehydes. The EGE aldehydes used in this study were synthesized via Swern oxidation. All of the human ALDHs were purified from human cDNA clones over-expressing these enzymes in E. coli. The ALDHs tested, so far, differentially catalyze the oxidation of EGE aldehydes to their corresponding acids (K(m) values range from approximately 10 microM to approximately 20.0mM). As judged by V(max)/K(m) ratios, short-chain alkyl-group containing EGE aldehydes are oxidized to their acids more efficiently by ALDH2, whereas aryl- and long-chain alkyl-group containing EGE aldehydes are oxidized to their acid more efficiently by ALDH3A1. Given the product of ALDH-catalyzed reaction is toxic, this process should be considered as a bio-activation (toxification) process.
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PMID:Human aldehyde dehydrogenase-catalyzed oxidation of ethylene glycol ether aldehydes. 1894 Jan 87

Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, a small number of adults with citrin deficiency develop adult-onset type II citrullinemia (CTLN2), which causes hyperammonemic encephalopathy leading to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. Hepatic glycolysis is coupled with hepatic lipogenesis via the NADH shuttles composed of the malate-aspartate shuttle and malate-citrate shuttle. Citrin deficiency is expected to impair glycolysis and lipogenesis in hepatocytes. We noticed that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. We extended this therapy for CTLN2 and found that an MCT supplementation therapy under a low-carbohydrate formula prevented the relapse of hyperammonemic encephalopathy, normalized the liver dysfunction (including the Fisher ratio), and gradually improved the level of plasma citrulline and fatty liver. An MCT supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to improvement of the cytosolic NAD+/NADH ratio via the malate-citrate shuttle. MCT supplementation could be a promising therapy for citrin deficiency.
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PMID:[Treatment and Pathomechanism of Citrin Deficiency]. 2606 89