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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Elevated brain concentrations of the neurotoxin and NMDA receptor agonist quinolinic acid (QUIN) have been demonstrated in portacaval-shunted (PCS) rats, a chronic hepatic encephalopathy (HE) model. Increased brain QUIN levels have also been shown in acute hyperammonemic rats. In the present study, the plasma and brain (neocortical) QUIN levels in chronic PCS rats were investigated. The study also included a single exogenous ammonium acetate (NH4Ac; 5.2 mmol/kg, i.p.) challenge to precipitate a reversible hepatic coma. Compared with sham-operated controls, chronic PCS rats exhibited decreased rather than increased plasma and brain QUIN levels. The plasma-to-brain QUIN ratio was not found to be altered. The NH4Ac administration induced coma in all of the PCS rats 20–25 min after the challenge, and this coma was resolved within 60–75 min. No relevant temporal relationship between changes in brain QUIN levels and the neurological status in the PCS rats was observed. Therefore, our results do not support the contention that increased brain QUIN levels per se are involved in the pathogenesis of HE.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Regional and whole-brain tryptophan-hydroxylating activity and serotonin turnover were investigated in portacaval shunted (PCS) rats using an in vivo decarboxylase inhibition assay. To saturate tryptophan hydroxylation with amino acid substrate, rats were administered a high dose of tryptophan 1 h prior to analysis of brain tryptophan, 5-hydroxytryptophan, serotonin, and 5-hydroxyindoleacetic acid. The analysis revealed, as expected, higher brain concentrations of tryptophan and 5-hydroxyindoles and increased serotonin synthesis rate in PCS rats as compared with shamoperated controls. Saturating levels of brain tryptophan were achieved in both PCS and sham animals after exogenous tryptophan administration. The tryptophan load resulted in increased brain serotonin turnover in all regions and in whole brain compared with rats that did not receive a tryptophan load. Tryptophan-loaded PCS rats showed increased brain serotonin turnover compared with tryptophan-loaded sham rats. Regionally, this supranormal tryptophan-hydroxylating activity was most pronounced in the mesencephalon-pons followed by the cortex. It is concluded that, at least in the PCS rat, brain tryptophan hydroxylation is an inducible process. Since it is known that brain tissue from PCS rats undergoes a redox shift toward a reduced state and that the essential cofactor tetrahydrobiopterin is active in tryptophan hydroxylation only when present in its reduced form, it is hypothesized that this is the reason for the supranormal tryptophan-hydroxylating activity displayed by the PCS rats. The hypothesis further suggests that alterations in tetrahydrobiopterin availability may serve as a mechanism by which brain tryptophan hydroxylation, and therefore serotonin turnover, can be regulated with high sensitivity in vivo.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le métabolisme des monoamines dans le cerveau des rats au cours de l'insuffisance hépatique aigüe a été étudiée après administration d'aminoacides à chaine branchés (BCAA). Des rats mâles (de la race Sprague-Dawley) ont subi une hépatectomie ou une opération simulée et ont été soumis à une injection intra-veineuse pendant 5 heures d'une solution de glucose à 10% ou d'une solution à 10% + 0.24 mol/l de BCAA (0.08 mol/l chacun de valine, leucine, et isoleucine). Trente minutes après la décapitation des animaux un inhibiteur de la décarboxylase (NSD 1015®) bloquant a conversion du 5-HTP en 5-HT et de la DOPA en dopamine (DA) fut injecté i.p. La concentration de 5-HTP de 5-HT et de 5-HIAA fut analysée par le HPLC, celle de la DOPA, de la DA et de la norépinephrine (NE) par une méthode radioenzymatique, ces analyses portant sur 8 régions différentes du cerveau et de la moelle. La concentration du 5-HTP était augmentée dans les cerveaux des rats hépatectomisés, ce fait témoignant d'une élévation du taux de la synthèse des indolamines. Après l'administration de BCAA aux rats hépatectomisés, le taux de synthèse revenait à la valeur normale ou au dessous de cette valeur dans certaines régions du cerveau. Les concentrations de DOPA et de DA dans le cerveau et dans la moelle étaient inchangées chez les rats hépatectomisés par comparaison à celles des animaux soumis à une opération simulée ces faits indiquant donc une rotation inchangée des catécholamines. Les niveaux de NE du diencéphale et de la moelle etaient abaissés après hépatectomie. Le niveau de la conscience n'était pas modifié par l'injection de BCAA. On peut conclure de ces faits que l'injection de BCAA peut normaliser la synthèse de l'indolamine chez les rats hépatectomisés alors même que la synthèse de la catécholamine et le niveau de la conscience ne sont pas modifiés par l'administration de BCAA.
    Abstract: Resumen El metabolismo de monoaminas en el cerebro de las ratas en falla hepática fulminate fue estudiado después de la administración de aminoácidos de cadena ramificada (AACR). Ratas Sprague-Dawley fueron sometidas a una hepatectomía total o a una operación “fantasma,” e infundidas por vía intravenosa por 5 horas con solución de glucosa al 10% o con glucosa al 10% + 0.24 mol/l AACR (0.08 mol/l de valina, leucina, e isoleucina). Treinta minutos antes de la decapitación se inyectó por vía intraperitoneal un inhibidor de la decarboxilasa (NDS 1015®), para bloquear la conversión de 5-HTP a 5-HT y de DOPA a dopamina (DA). Las concentraciones de 5-HTP, 5-HT, y 5-HIAA fueron analizadas a través de HPLC, DOPA, DA, y norepinefrina (NE) mediante un método enzimático en 8 diferentes regiones del cerebro y de la medula espinal. Las concentraciones de 5-HTP aparecieron aumentadas en los cerebros de las ratas hepatectomizadas, indicando un incremento en la tasa de sintesis de las indolaminas. Después de la administración de AACR a las ratas hepatectomizadas, la tasa de síntesis apareció disminuida a los niveles normales y, en algunas regiones cerebrales, a niveles subnormales. Las concentraciones de DOPA y de DA en el cerebro y en la medula espinal no exhibieron cambio en las ratas hepatectomizadas en comparación con las ratas con operación fantasma, indicando un recambio no alterado de catecolaminas. Los niveles de NE en el diencéfalo y en la medula espinal aparecieron disminuidos después de la hepatectomía. El nivel de conciencia no se modificó con las infusiones de AACR. La conclusión es que la infusión de AACR puede normalizar la síntesis cerebral de indolaminas en las ratas hepatectomizadas, en tanto que la síntesis de catecolaminas y el nivel de conciencia no son afectados por la administración de AACR.
    Notes: Abstract The metabolism of monoamines in the brain of rats in fulminant hepatic failure was studied after administration of branched chain amino acids (BCAA). Male Sprague-Dawley rats were exposed to a total hepatectomy or a sham operation and infused intravenously for 5 hours with a 10% glucose solution alone or 10% glucose + 0.24 mol/l BCAA (0.08 mol/l of each valine, leucine, and isoleucine). Thirty minutes before decapitation, a decarboxylase inhibitor (NSD 1015®), blocking the conversion of 5-hydroxytryphtophan (5-HTP) to 5-hydroxytryptamine (5-HT), and dihydroxyphenylalanine (DOPA) to dopamine (DA), was injected intraperitoneally. The concentrations of 5-HTP, 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed by high-performance liquid chromatography, DOPA, DA, and norepinephrine (NE) by a radio-enzymatic method in 8 different regions of the brain and spinal cord. The concentrations of 5-HTP were increased in the brains of hepatectomized rats, indicating an increased synthesis rate of the indoleamines. After administration of BCAA to hepatectomized rats, the synthesis rate was decreased to normal or, in some brain regions, even to subnormal values. The brain and spinal cord concentrations of DOPA and DA were unchanged in hepatectomized rats compared to sham-operated animals, indicating an unchanged turnover of the catecholamines. The levels of NE in the diencephalon and in the spinal cord were decreased after hepatectomy. The level of consciousness was not influenced by the BCAA infusions. It is concluded that BCAA infusion may normalize brain indoleamine synthesis in hepatectomized rats, whereas the catecholamine synthesis and the level of consciousness are unaffected by the BCAA administration.
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  • 4
    ISSN: 1573-7365
    Keywords: Exploratory behaviour ; GTP-cyclohydrolase I ; L-tryptophan ; portacaval shunt ; portal-systemic encephalopathy ; spontaneous locomotor activity ; tetrahydrobiopterin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with a substantial increase in the brain L-tryptophan (L-TRP) level. Moreover, a supranormal L-TRP hydroxylating activity in the brain suggests an induced enzymatic process in chronic HE. GTP-cyclohydrolase I (GTPCHI) and tetrahydrobiopterin (BH4) are two major factors besides L-TRP that are involved in regulating the brain L-TRP hydroxylating activity. We therefore determined the GTPCHI activity, the total biopterin and the BH4 concentrations in the neocortex and mesencephalon-pons of portacaval shunted (PCS) rats. The encephalopathic component in PCS rats was accounted for by studying open field behaviour. The acute effects of a single parenteral L-TRP challenge were also evaluated. The basal GTPCHI activities in PCS rats were decreased bu 50% (p〈0.05) compared to controls in both investigated brain regions. No significant alterations in brain total biopterin or BH4 levels were present. The PCS rats exhibited a clearly reduced spontaneous locomotor activity. After the exogenous L-TRP load only a lower GTPCHI activity in the neocortex of PCS rats was recorded. We conclude that a perturbation in the brain biopterin metabolism is concomitantly present with behavioural abnormalities in the chronic PCS condition and that the acute effects of a superimposed L-TRP load do not aggravate these disturbances.
    Type of Medium: Electronic Resource
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