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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with chronic renal disease had low plasma total tryptophan but an abnormally high proportion of this was in the free state. The subjects with encephalopathy had raised plasma free tryptophan, CSF tryptophan, and CSF 5-hydroxyindoleacetic acid. CSF tryptophan correlated better with plasma free than with plasma total tryptophan. Plasma and CSF tyrosine concentrations were normal but CSF homovanillic acid was raised especially in subjects with encephalopathy. The possible significance of these changes in advanced renal disease is discussed.
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PMID:Cerebral transmitter precursors and metabolites in advanced renal disease. 2 80

Ventricular fluid concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), the respective metabolites of dopamine and serotonin, were measured in 57 patients undergoing thalamotomy for relief of movement disorders. The diseases included were Parkinson disease, dystonia, cerebral palsy, multiple sclerosis, and posttraumatic or posthypoxic encephalopathy. Untreated parkinsonian patients had the lowest mean HVA level (119 ng per milliliter). Patients with multiple sclerosis or with posttraumatic or posthypoxic encephalopathy with both intellectual impairment and bilateral motor involvement had lower mean HVA levels (197 and 177 ng per milliliter, respectively) than cerebral palsy patients with bilateral motor disease (233 ng per milliliter), dystonia patients (246 ng per milliliter), or multiple sclerosis patients with normal intellect (376 ng per milliliter). The data suggest that diffuse cerebral disease may lead to diminished dopaminergic activity. Ventricular fluid 5-HIAA levels were similar in all groups of patients. Chronic cerebellar stimulation markedly increased ventricular fluid HVA and 5-HIAA levels, indicating that cerebellar stimulation affected cerebral dopaminergic and serotonergic systems.
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PMID:Ventricular fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in patients with movement disorders. 56 83

Effects of octanoic acid on monoamines and their acidic metabolites in the rat brain were analyzed by HPLC. Octanoic acid (1,000 mg/kg i.p.) elevated homovanillic acid levels by 54% in the caudate and 338% in the hypothalamus but increased 5-hydroxyindoleacetic acid (5-HIAA) levels in both the caudate and the hypothalamus by approximately 50% compared with the control. A lower dose of octanoic acid (500 mg/kg) increased 5-HIAA levels by 29% in the caudate and 20% in the hypothalamus. However, it did not produce any changes in the concentration of homovanillic acid in either the caudate or the hypothalamus. Treatment with octanoic acid also failed to change the level of dopamine, serotonin, and 3,4-dihydroxyphenylacetic acid in the caudate and the hypothalamus. The role of carrier-mediated transport in the clearance of 5-HIAA from the rabbit CSF was also evaluated in vivo by ventriculocisternal perfusion. Steady-state clearance of 5-HIAA from CSF exceeded that of inulin and was reduced in the presence of octanoic acid. Because this transport system in the choroid plexus is normally responsible for the excretion of the serotonin metabolite from the brain to the plasma, accumulation of endogenously produced organic acids in the brain, secondary to reduced clearance by the choroid plexus, could be a contributing factor in the development of encephalopathy in children with medium-chain acyl-CoA dehydrogenase deficiency who have elevated levels of octanoic acid systematically.
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PMID:Octanoic acid produces accumulation of monoamine acidic metabolites in the brain: interaction with organic anion transport at the choroid plexus. 137 45

In the Rett syndrome (RS), a progressive encephalopathy affecting girls, deficient neurotransmitter synthesis has been suggested as a pathogenetic mechanism. Nine girls with RS were treated with 0.3 g of tyrosine and 0.1 g of tryptophan per kg body weight for 2 to 17 weeks. This resulted in a median rise in the spinal fluid concentration of the dopamine metabolite homovanillic acid by 31%, and of the serotonin metabolite 5-hydroxyindoleacetic acid by 40%. This finding supports the hypothesis of a compromised neurotransmitter synthesis and indicates that it can be stimulated by supply of amino acid precursors. A double-blind cross-over trial including 11 girls did not show clinical improvement during a treatment period of 8 to 10 weeks.
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PMID:Biochemical and clinical effects of tyrosine and tryptophan in the Rett syndrome. 169 42

Regional amino acids and brain neurotransmitters were studied in 33 normal and 32 rats with sepsis (induced by cecal ligation and puncture) infused with different amino acid formulations. The brain amino acid pattern during sepsis showed increased concentrations of most essential and six of the nonessential amino acids. The most consistent finding was the accumulation of indoleamines in all six brain regions studied during sepsis; increased brain tryptophan levels presumably resulted in enhanced metabolism of serotonin (5HT), increased production of 5-hydroxyindoleacetic acid (5HIAA), and a high 5HT/5HIAA ratio. Infusion of branched-chain amino acid-enriched formulas restored brain amino acid and neurotransmitter profiles, decreasing levels of tryptophan, tyrosine, 5HIAA, and 5HT/5HIAA ratios while increasing norepinephrine levels in some regions. These alterations in brain neurotransmitter metabolism may be at least partially responsible for the development of septic encephalopathy.
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PMID:Regional brain amino acid and neurotransmitter derangements during abdominal sepsis and septic encephalopathy in the rat. The effect of amino acid infusions. 241 5

Previous work suggested that methotrexate (MTX) may cause encephalopathy by inhibiting biosynthetic pathways for dopamine and serotonin in the brain. We examined this issue by measuring the neurotransmitter metabolites homovanillic acid and 5-hydroxyindoleacetic acid in the lumbar CSF of rhesus monkeys receiving continuous intracerebroventricular infusions of MTX or dichloromethotrexate. Infusion of the lowest dose (0.05 mg/day) produced a large (300%) rise in homovanillic acid levels and a modest elevation in 5-hydroxy-indoleacetic acid. During higher dose infusion, which was associated with clinical encephalopathy, the biogenic amine metabolites fell from their previous elevated levels. In one encephalopathic monkey, an injection of 1 mg of leucovorin produced a marked elevation in CSF monoamine metabolites within 1 hour and rapid clinical recovery. In contrast, leucovorin produced no change in monoamine metabolites in control animals. The data suggest that MTX may block egress of monoamine metabolites from CSF at the lower doses and suppress neurotransmitter turnover at toxic doses which cause encephalopathy. Serial measurements of CSF monoamine metabolites deserve further investigation as biochemical markers for toxic effects of MTX on neuronal metabolism in the CNS.
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PMID:Effects of intraventricular methotrexate on cerebrospinal fluid monoamine metabolites in rhesus monkeys. 242 91

Similar neurological disturbances and metabolic alterations have been observed in liver insufficiency and in bacterial sepsis. In both liver failure and sepsis an altered neurotransmitter profile in the central nervous system (CNS) has been implicated in the pathogenesis of encephalopathic symptoms. It has been suggested that equivalent disturbances in brain neurotransmitters, especially serotonin, play a role in the encephalopathy accompanying sepsis and liver failure. The objective of this study was to compare the CNS serotonin metabolism in rats with an end-to-side portacaval shunt (PCS) with that found in rats with 12 or 24 hr of intraabdominal sepsis. The metabolism of CNS serotonin was estimated after inhibition of two enzymes acting in the 5-hydroxyindole synthetic pathway (decarboxylase and monoamine oxidase). The 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in different regions of the CNS, thereby permitting evaluation of the synthetic activity of the serotonin neurotransmitter system. As previously reported, a marked increase in CNS serotonin synthetic rate was noted following PCS. In contrast, and in contradistinction to several recent reports, no major changes in the CNS serotonin synthesis rate were present following 12 or 24 hr of sepsis. CNS levels of the serotonin metabolite 5-HIAA were elevated in both sepsis and PCS rats. These data indicate that sepsis and liver failure have different effects upon serotonin metabolism in the CNS and suggest that differing pathogenetic mechanisms may underlie the encephalopathy clinically associated with these conditions.
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PMID:Serotonin metabolism in the central nervous system following sepsis or portacaval shunt in the rat. 244 49

In rats with a portacaval shunt (PCS), the effect on the serotonin metabolism in the brain after oral administration of blood, a mixed amino acid solution (Vamin 14; KabiVitrum, Sweden) or a 10% glucose solution was studied. One week after PCS, the animals were fed with a gastric tube for 8 h and thereafter tested for behavioral abnormalities before decapitation at 12 h. The concentration of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed chromatographically (HPLC technique with electrochemical detection) in different regions of the brain. Estimation of synthetic rates of 5-hydroxyindoles was facilitated by aromatic aminoacid decarboxylase inhibition (m-hydroxybenzyl-hydrazine; NSD 1015). The brain concentrations of 5-HTP, 5-HT, and 5-HIAA were increased in all shunted rats as compared with sham-operated animals. Whether animals received blood, glucose, or aminoacid solution made no differences in the brain concentrations of 5-HTP and 5-HT. Concentrations of 5-HIAA were lower in those animals receiving blood as compared with the other shunted groups. No reproducible differences in the behavior of the animals were observed. These results suggest that massive blood administration 1 week after PCS in rats has no influence on the rate of brain indole synthesis. While alterations in serotonin metabolism may play a role in some forms of encephalopathy, this study implies that the behavioral and neurologic disorders which follow gastrointestinal tract hemorrhage in patients with liver failure may have other etiologies.
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PMID:The effect of blood ingestion on brain serotonin synthesis in portacaval-shunted rats. 244 52

Alterations in the metabolism of monoamine neurotransmitters have been proposed to be involved in the development of the hepatic encephalopathy (HE) associated with experimental and human liver failure. In order to evaluate this hypothesis, the monoamines and some of their metabolites were measured in homogenates of caudate nucleus (CAU), prefrontal (PFCo) and frontal cortex (FCo) dissected from brains obtained at autopsy from nine cirrhotic patients who had died in hepatic coma and an equal number of control subjects, free from neurological, psychiatric and hepatic disorders, matched for age and time interval from death to freezing of autopsied brain samples. Monoamine measurements were performed by high-performance liquid chromatography with ion-pairing and electrochemical detection after a simple extraction procedure. In all three regions investigated, concentrations of dopamine (DA) were unchanged in cirrhotic patients vs controls while its metabolites, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) were selectively affected i.e. 3-MT was found to be increased in CAU, while HVA levels were increased in FCo and CAU. DOPAC was also found to be unchanged in CAU. Noradrenaline (NA) levels were greatly increased in PFCo and FCo of cirrhotic patients but remained unchanged in CAU. No significant differences in the concentrations of either serotonin (5-HT) or of its precursor 5-hydroxytryptophan (5-HTP) were found in any of the three regions studied. However, 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of 5-HT, was increased in PFCo and CAU of cirrhotic patients. These findings show that selective alterations of catecholamine and 5-HT systems are involved in human HE and therefore, they may play an important role in the pathogenesis of certain neurological symptoms associated with this encephalopathy.
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PMID:Monoamines and metabolites in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. 248 May 34

Patients with sepsis often manifest symptoms of encephalopathy similar to those observed in portasystemic encephalopathy. As a causal relationship has been demonstrated between hepatic encephalopathy and a deranged brain neurotransmitter profile, the catecholaminergic and serotoninergic brain neurotransmitter profile in a septic rat model was investigated. Septic animals exhibited lower levels of norepinephrine (NE), 3,4-dihydroxyphenylacetic acid, and homovanillic acid compared to normal controls. Severely septic animals with encephalopathy exhibited significantly lower levels of NE, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid compared to rats only mildly septic with no encephalopathy. The infusion of branched chain amino acids during sepsis had no effect on this deranged brain neurotransmitter profile. Previous results of derangements in the blood-brain barrier transport mechanism combined with the present findings of a deranged brain amino acid and neurotransmitter profile during sepsis may be responsible, at least in part, for the metabolic encephalopathy observed during sepsis and might suggest a common etiology for septic, hepatic, and other metabolic encephalopathies.
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PMID:Brain neurotransmitter profile is deranged during sepsis and septic encephalopathy in the rat. 285 4


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