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L. Warwick - One of the best experts on this subject based on the ideXlab platform.
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Succinic semialdehyde dehydrogenase deficiency: low excretion of metabolites in a neonate
Journal of Inherited Metabolic Disease, 1997Co-Authors: J. J. Pitt, R. Hawkins, M. Cleary, M. Eggington, D. R. Thorburn, L. WarwickAbstract:A neonate at risk for succinic semialdehyde dehydrogenase deficiency was investigated on day 1. The urine level of 4-Hydroxybutyrate was only slightly elevated (23 µmol/mmol of creatinine; controls 1.6-14, n=18). This value was considerably less than those found for older children with succinic semialdehyde dehydrogenase deficiency and made interpretation of the result uncertain. The diagnosis of succinic semialdehyde dehydrogenase deficiency was confirmed by enzyme assay, and repeat urine testing showed a steady increase in the level of 4-hydroxybutrate to 359 µmol/mmol at 6 months.
J. J. Pitt - One of the best experts on this subject based on the ideXlab platform.
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Succinic semialdehyde dehydrogenase deficiency: low excretion of metabolites in a neonate
Journal of Inherited Metabolic Disease, 1997Co-Authors: J. J. Pitt, R. Hawkins, M. Cleary, M. Eggington, D. R. Thorburn, L. WarwickAbstract:A neonate at risk for succinic semialdehyde dehydrogenase deficiency was investigated on day 1. The urine level of 4-Hydroxybutyrate was only slightly elevated (23 µmol/mmol of creatinine; controls 1.6-14, n=18). This value was considerably less than those found for older children with succinic semialdehyde dehydrogenase deficiency and made interpretation of the result uncertain. The diagnosis of succinic semialdehyde dehydrogenase deficiency was confirmed by enzyme assay, and repeat urine testing showed a steady increase in the level of 4-hydroxybutrate to 359 µmol/mmol at 6 months.
Michel Maitre - One of the best experts on this subject based on the ideXlab platform.
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THE γ-Hydroxybutyrate SIGNALLING SYSTEM IN BRAIN: ORGANIZATION AND FUNCTIONAL IMPLICATIONS
Progress in neurobiology, 1997Co-Authors: Michel MaitreAbstract:gamma-Hydroxybutyrate is a metabolite of GABA which is synthesized and accumulated by neurons in brain. This substance is present in micromolar quantities in all brain regions investigated as well as in several peripheral organs. Neuronal depolarization releases gamma-Hydroxybutyrate into the extracellular space in a Ca(2+)-dependent manner. Gamma-Hydroxybutyrate high-affinity receptors are present only in neurons, with a restricted specific distribution in the hippocampus, cortex and dopaminergic structures of rat brain (the striatum in general, olfactory bulbs and tubercles, frontal cortex, dopaminergic nuclei A9, A10 and A12). Stimulation of these receptors with low amounts of gamma-Hydroxybutyrate induces in general hyperpolarizations in dopaminergic structures with a reduction of dopamine release. However, in the hippocampus and the frontal cortex, it seems that gamma-Hydroxybutyrate induces depolarization with an accumulation of cGMP and an increase in inositol phosphate turnover. Some of the electrophysiological effects of GHB are blocked by NCS-382, a gamma-Hydroxybutyrate receptor antagonist while some others are strongly attenuated by GABAB receptors antagonists. Gamma-Hydroxybutyrate penetrates freely into the brain when administered intravenously or intraperitoneally. This is a unique situation for a molecule with signalling properties in the brain. Thus, the gamma-Hydroxybutyrate concentration in brain easily can be increased more than 100 times. Under these conditions, gamma-Hydroxybutyrate receptors are saturated and probably desensitized and down-regulated. It is unlikely that GABAB receptors could be stimulated directly by GHB. Most probably, GABA is released in part under the control of GHB receptors in specific pathways expressing GABAB receptors. Alternatively, GABAB receptors might be specifically stimulated by the GABA formed via the metabolism of gamma-Hydroxybutyrate in brain. In animals and man, these GHBergic and GABAergic potentiations induce dopaminergic hyperactivity (which follows the first phase of dopaminergic terminal hyperpolarization), a strong sedation with anaesthesia and some EEG changes with epileptic spikes. It is presumed that, under pathological conditions (hepatic failure, alcoholic intoxication, succinic semialdehyde dehydrogenase defects), the rate of GHB synthesis or degradation in the peripheral organ is modified and induces increased GHB levels which could interfere with the normal brain mechanisms. This pathological status could benefit from treatments with gamma-hydroxybutyric and/or GABAB receptors antagonists. Nevertheless, the regulating properties of the endogenous gamma-Hydroxybutyrate system on the dopaminergic pathways are a cause for the recent interest in synthetic ligands acting specifically at gamma-Hydroxybutyrate receptors and devoid of any role as metabolic precursor of GABA in brain.
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Characterization of methionine-enkephalin release in the rat striatum by in vivo dialysis: Effects of gamma-Hydroxybutyrate on cellular and extracellular methionine-enkephalin levels
Neuroscience, 1994Co-Authors: Serge Gobaille, Catherine Schmidt, A. Cupo, F. Herbrecht, Michel MaitreAbstract:Abstract The opioid system is implicated in mediating the effects produced upon administration of gamma-Hydroxybutyrate. Gamma-Hydroxybutyrate occurs endogenously in the mammalian brain, and is most probably involved in the regulation of some basic brain functions, particularly those concerning the dopaminergic nigrostriatal pathway, which is closely linked to the expression of enkephalins in the striatum. In the present study, in vivo microdialysis was used to examine the basic characteristics of methionine-enkephalin (met-enkephalin) release in the striatum of Wistar rats, using a high performance radioimmunoassay. Administration of gamma-Hydroxybutyrate to the rats induced a dose-dependent decrease in the extracellular release of met-enkephalin. In parallel, a dose- and time-dependent gamma-Hydroxybutyrate-induced accumulation of met-enkephalin in striatum was observed. These two phenomena (tissue accumulation and inhibition of release) were blocked by NCS-382, a gamma-Hydroxybutyrate receptor antagonist. The striatal met-enkephalin accumulation does not seem to be exclusively due to the inhibition of its release. Thus, a gamma-Hydroxybutyrate mediating effect on met-enkephalin synthesis is suggested, most probably occurring via functional modulation of striatal dopamine synthesis and release. To understand the role of this dopaminergic mechanism, unilateral lesions of the nigrostriatal dopaminergic pathway were carried out. In gamma-Hydroxybutyrate-treated rats, striata exhibited a similar increase in met-enkephalin content. In untreated rats, only the lesioned striatum showed an identical increase in met-enkephalin levels. Thus, striatal met-enkephalin accumulation could be attributed to the suppression of the dopaminergic impulse flow, due to gamma-Hydroxybutyrate or to the action of 6-hydroxydopamine. In the extracellular spaces (microdialysis experiments), gamma-Hydroxybutyrate administration induced identical modifications of met-enkephalin release in lesioned or non-lesioned striata. These modifications could be reproduced by peripheral or striatal administration of sulpiride, a D 2 /D 3 antagonist. From a functional point of view, the dopaminergic D 2 receptor blockade or the gamma-Hydroxybutyrate-induced inhibition of dopamine release could be considered to induce similar results, with identical consequences on striatal met-enkephalin accumulation and release. These results suggest that gamma-Hydroxybutyrate-induced modifications in metenkephalin release, presumably potentiated by 6-hydroxydopamine treatment, act via a functional modification of the nigrostriatal dopaminergic pathway.
Tom Defoirdt - One of the best experts on this subject based on the ideXlab platform.
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Virulence-inhibitory activity of the degradation product 3-Hydroxybutyrate explains the protective effect of poly-β-Hydroxybutyrate against the major aquaculture pathogen Vibrio campbellii.
Scientific reports, 2018Co-Authors: Tom Defoirdt, Nguyen Thi Mai Anh, Peter De SchryverAbstract:The bacterial storage compound poly-β-Hydroxybutyrate, a polymer of the short-chain fatty acid 3-Hydroxybutyrate, has been reported to protect various aquatic animals from bacterial disease. In order to obtain a better mechanistic insight, we aimed to (1) investigate whether 3-Hydroxybutyrate is released from poly-β-Hydroxybutyrate within sterile brine shrimp larvae, (2) determine the impact of 3-Hydroxybutyrate on the virulence of Vibrio campbellii to brine shrimp larvae and on its cell density in the shrimp, and (3) determine the impact of this compound on virulence factor production in the pathogen. We detected 3-Hydroxybutyrate in poly-β-Hydroxybutyrate-fed brine shrimp, resulting in 24 mM 3-Hydroxybutyrate in the intestinal tract of shrimp reared in the presence of 1000 mg l−1 poly-β-Hydroxybutyrate. We further demonstrate that this concentration of 3-Hydroxybutyrate does not affect the growth of V. campbellii, whereas it decreases the production of different virulence factors, including hemolysin, phospholipase and protease activities, and swimming motility. We hypothesize that by affecting all these virulence factors at once, 3-Hydroxybutyrate (and thus also poly-β-Hydroxybutyrate) can exert a significant impact on the virulence of V. campbellii. This hypothesis was confirmed in a challenge test showing that 3-Hydroxybutyrate protected gnotobiotic brine shrimp from pathogenic V. campbellii, without affecting the number of host-associated vibrios.
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the bacterial storage compound poly β Hydroxybutyrate protects artemia franciscana from pathogenic vibrio campbellii
Environmental Microbiology, 2007Co-Authors: Tom Defoirdt, Dirk Halet, Han Vervaeren, Nico Boon, Patrick Sorgeloos, Peter Bossier, Tom Van De Wiele, Willy VerstraeteAbstract:Infections caused by antibiotic-resistant luminescent Vibrios can cause dramatic losses in aquaculture. In this study, the short-chain fatty acid beta-Hydroxybutyrate and its polymer poly-beta-Hydroxybutyrate were investigated as possible new biocontrol agents. beta-Hydroxybutyrate was shown to completely inhibit the growth of pathogenic Vibrio campbelli at 100 mM. Moreover, the addition of 100 mM of this fatty acid to the culture water of Artemia nauplii infected with the V. campbelli strain significantly increased the survival of the nauplii. As Artemia is a non-selective and particle filter feeder, we also investigated whether poly-beta-Hydroxybutyrate particles could be used to protect Artemia from the pathogenic V. campbellii. The addition of 100 mg l(-1) poly-beta-Hydroxybutyrate or more to the Artemia culture water offered a preventive and curative protection from the pathogen as a significantly enhanced survival was noticed. If added as a preventive treatment, a complete protection of infected nauplii (no significant mortality compared with uninfected nauplii) was observed at 1000 mg l(-1) poly-beta-Hydroxybutyrate. Our data indicate that the use of poly-beta-Hydroxybutyrate might constitute an ecologically and economically sustainable alternative strategy to fight infections in aquaculture.
M. Eggington - One of the best experts on this subject based on the ideXlab platform.
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Succinic semialdehyde dehydrogenase deficiency: low excretion of metabolites in a neonate
Journal of Inherited Metabolic Disease, 1997Co-Authors: J. J. Pitt, R. Hawkins, M. Cleary, M. Eggington, D. R. Thorburn, L. WarwickAbstract:A neonate at risk for succinic semialdehyde dehydrogenase deficiency was investigated on day 1. The urine level of 4-Hydroxybutyrate was only slightly elevated (23 µmol/mmol of creatinine; controls 1.6-14, n=18). This value was considerably less than those found for older children with succinic semialdehyde dehydrogenase deficiency and made interpretation of the result uncertain. The diagnosis of succinic semialdehyde dehydrogenase deficiency was confirmed by enzyme assay, and repeat urine testing showed a steady increase in the level of 4-hydroxybutrate to 359 µmol/mmol at 6 months.
