Search results for "aspartate"
showing 10 items of 195 documents
Pregnenolone sulfate, a naturally occurring excitotoxin involved in delayed retinal cell death.
2002
The present study was designed to investigate the neurosteroid pregnenolone sulfate (PS), known for its ability to modulate NMDA receptors and interfere with acute excitotoxicity, in delayed retinal cell death. Three hours after exposure of the isolated and intact retina to a 30-min PS pulse, DNA fragmentation as assessed by genomic DNA gel electrophoresis and a modified in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method appeared concurrently with an increase in superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) levels. At 7 h, the increased amount of DNA laddering was accompanied by a higher number of TUN…
Acute ammonia intoxication induces an NMDA receptor-mediated increase in poly(ADP-ribose) polymerase level and NAD+ metabolism in nuclei of rat brain…
2004
Acute ammonia toxicity is mediated by excessive activation of NMDA receptors. Activation of NMDA receptors leads to activation of poly(ADP-ribose) polymerase (PARP) which mediates NMDA excitotoxicity. PARP is activated following DNA damage and may lead to cell death via NAD+ and ATP depletion. The aim of the present work was to assess whether acute ammonia intoxication in vivo leads to increased PARP in brain cells nuclei and to altered NAD+ and superoxide metabolism and the contribution of NMDA receptors to these alterations. Acute ammonia intoxication increases PARP content twofold in brain cells nuclei.NAD+ content decreased by 55% in rats injected with ammonia. This was not due to decre…
Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: Implicatio…
2009
Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55(-/-) mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subuni…
Transient oligemia is associated with long-term changes in binding densities of cortical inhibitory GABAA receptors in the rat brain
2009
Recently, we could demonstrate in rats that a short transient oligemic period of only 20-minute duration, induced by systemic hypotension, resulted in a transient decline of spatial memory capacities without any histological damage over a subsequent period of 6 months. In our present study, we checked for more subtle alterations within the highly vulnerable hippocampal CA1 subfield using quantification of neuronal cell density and semi-quantitative analysis of the ischemia-sensitive protein MAP2. Since hippocampal excitatory and inhibitory neurotransmitter receptors are crucially involved in spatial memory processes, quantitative in vitro receptor autoradiography was performed using [(3)H]M…
Pravastatin treatment causes a shift in the balance of hippocampal neurotransmitter binding densities towards inhibition
2009
Since pravastatin, a HMG-CoA reductase inhibitor, has recently been shown to reduce infarct volumes and glutamate release in a rat model of ischemic stroke, the aim of the present study was to investigate whether this neuroprotective effect may be due to a modulation of excitatory and inhibitory neurotransmitter receptors. Therefore, Wistar rats were treated six times in 4 days with pravastatin or saline and allowed to survive for 6 hours or 5 days (n=10 per time point and group), respectively. Using quantitative receptor autoradiography, ligand binding densities of [(3)H]MK-801, [(3)H]AMPA, and [(3)H]muscimol for labeling of NMDA, AMPA, and GABA(A) receptors were analyzed in sensorimotor c…
Aspartate aminotransferase and carbohydrate metabolism of rat brain
1969
E stato determinato il rapporto tra forma «piridossalica» e forma «piridossaminica» dell'aspartato aminotransferasi nell'encefalo totale di ratti albini durante l'ipoglicemia da insulina e l'iperglicemia da allossana. Il rapporto tra le due forme catalitiche dell'enzima e stato considerato un indice dell'efficienza del ciclo degli acidi tricarbossilici, ed e stata prospettata la possibilita che l'aspartato aminotransferasi abbia una funzione regolativa nei riguardi del ciclo.
Lack of Correlation between Liver Tests Abnormalities and Trabectedin Efficacy in the Treatment of Soft Tissue Sarcoma: A Retrospective Study
2015
AbstractElevation in liver transaminases is common in patients treated with the marine antitumor agent trabectedin. However, the impact of trabectedin-related transaminase elevations on treatment outcomes is unclear. This retrospective study investigated the correlation between liver tests abnormalities and treatment outcomes in patients with unresectable advanced or metastatic soft tissue sarcomas (STS) treated with trabectedin 1.5 mg/m2 once every 3 weeks at three reference centers in Italy. The effect of grade 3/4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the first two cycles and at any time during trabectedin treatment on progression-free su…
Evidence for an involvement of NMDA and non-NMDA receptors in synaptic excitation of phrenic motoneurons in the rabbit
1991
Abstract The action of endogenous excitatory amino acids on phrenic motoneurons was studied in anesthetized, vagotomized, paralyzed and artificially ventilated rabbits. The NMDA receptor antagonists APV and ketamine, as well as the non-NMDA receptor antagonists GAMS and DNQX were administered by microinjection into the ventral horn of the spinal segments C3-C5. Injection of each antagonist resulted in a reversible reduction of the phrenic nerve activity. Results suggest an important function of endogenous excitatory amino acids in the excitation of phrenic motneurons. NMDA as well as non-NMDA receptors are involved. The functional role of both receptor types in bulbospinal neurotransmission…
A surgical model for isolating the pig liver in vivo for gene therapy.
2013
Several studies report results that suggest the need of vascularization blocking for efficient gene transfer to the liver, especially in nonviral gene therapy. In this study, we describe a surgical strategy for in vivo isolation of the pig liver, resulting in a vascular watertight organ that allows the evaluation of several gene injection conditions. The hepatic artery and portal, suprahepatic and infrahepatic cava veins were dissected. Then, liver vascularization was excluded for 5-7 min. In that time, we first injected 200 ml saline solution containing the p3c-eGFP plasmid (20 µg/ml) simultaneously through two different catheters placed in the portal and cava veins, respectively. Vital co…
Variations of acidic functions at position 2 and substituents at positions 4, 5 and 6 of the indole moiety and their effect on NMDA-glycine site affi…
2003
The synthetic procedures to obtain indole derivatives with different acidic functions at position 2 of the indole are reported. The synthesised and tested derivatives comprise 5-tetrazolyl, 1,3,4-oxadiazol-5-yl-2-one, and indole-2-carboxylic acid amides with 5-aminotetrazole, methanesulphonamide and trifluoromethanesulphonamide moieties. The binding affinity was evaluated using [3H]MDL 105,519 and pig cortical brain membranes. In general, compounds with acidic functions different from a carboxylic acid moiety are less potent than indole-2-carboxylic acid derivatives. Also, the 4,6-dichloro substitution pattern was compared to 5-tert-butyl derivatives and compounds not substituted in the ben…