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Biomedical subjects

N de Vera

Publications and source records attributed to N de Vera.

12 recordsLinked to original sources
PubMed2001

Polyamine metabolism and glutamate receptor agonists-mediated excitotoxicity in the rat brain.

Putrescine (PUT) increases have been seen in a range of models of neuropathological disturbances. The present study was designed to compare the ability of various types of glutamate receptor agonist to promote excitotoxic brain damage and to examine whether a PUT increase is a general marker of excitotoxic brain damage. To that end, we evaluated features of brain damage associated with the excitotoxicity induced by both ionotropic glutamate receptor (iGluR) and metabotropic glutamate receptor (mGluR) agonists in the conscious rat and the changes produced in the regulation of polyamine metabolism. Intracerebroventricular infusion of N-methyl-D-aspartate (NMDA; 80 nmol), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 15 nmol), kainic acid (KA; 2.3 nmol), (R,S)-3,5-dihydroxyphenylglycine (3,5-DHPG; 1.5 micromol), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 2 micromol) produced similar seizure incidences (76-84%) in the rat. The convulsant episodes appeared sooner after iGluR (13-22 min) than after mGluR agonists (50-179 min). Histological analysis of the hippocampus 24 hr after seizures indicated several degrees of excitotoxic injury after equiconvulsive doses of the iGluR and mGluR agonists assayed. The agonists can be placed in the following order, according to the degree of damage they produce: AMPA > 3,5-DHPG approximately KA > NMDA > 1S,3R-ACPD. In the frontal cortex, moderate to low levels of damage were observed after all GluR agonists. Both iGluR- and mGluR-induced seizures produced an overshoot in the hippocampal and cortical PUT concentration, whereas spermidine and spermine levels were similar to control. Moreover, a concurrence of increased PUT levels and brain damage was observed, indicating that PUT is a general marker of excitotoxic brain damage.

Animals↗
PubMed2001

Polyamines in the basal ganglia of human brain. Influence of aging and degenerative movement disorders.

The distribution of polyamines in the human basal ganglia was examined, using dansyl-derivatives and high pressure liquid chromatography with fluorimetric detection. A heterogeneous distribution of putrescine, spermidine (SD) and spermine (SM) was observed in control brains. A consistent negative correlation between SD and SM content and age was found in different brain areas. These results suggest an involvement of polyamines in age-related changes occurring in white-matter. When the influence of degenerative movement disorders -Parkinson's disease, Huntington's disease (HD) and progressive supranuclear palsy- was analyzed, significant changes were observed only in HD, where a decrease in the concentration of SM was found in the putamen. These results suggest that in advanced stages of neurodegenerative processes, polyamines maintain their regulation. Only in the presence of severe atrophy, SM concentration is reduced.

Aged↗
PubMed1998

Long-term effects of status epilepticus induced by kainic acid on hippocampal polyamines.

Putrescine has been suggested to have an inhibitory effect on the excitability of the central nervous system. In the present study we found that 2 and 3 weeks after status epilepticus induced by kainic acid, rats had increased concentrations of putrescine (3- and 1.7-fold, respectively) and spermidine (1.6- and 1.4-fold, respectively) in the hippocampus. These animals exhibited a higher susceptibility to pentylentetrazol than the saline group. In addition, several hours after the pentylentetrazol injection, the concentration of putrescine and spermidine increased again in the brain and also in the plasma. In conclusion, increased hippocampal putrescine and spermidine concentrations seem to be linked with a lower threshold of excitability.

Animals↗
PubMed1998

Seizures and neuronal damage induced in the rat by activation of group I metabotropic glutamate receptors with their selective agonist 3,5-dihydroxyphenylglycine.

While it is well documented that the overactivation of ionotropic glutamate receptors leads to seizures and excitotoxic injury, little is known about the role of metabotropic glutamate receptors (mGluRs) in epileptogenesis and neuronal injury. Intracerebroventricular (i.c.v.) infusion of the group I mGluR specific agonist (R,S)-3,5-dihydroxyphenylglycine (3,5-DHPG) (1.5 micromol) to conscious rats produced severe and delayed seizures (onset at 4 hr) in 70% of the animals. The i.c.v. infusion of the group I mGluR non-selective agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (2 micromol) produced a similar rate of severe seizures, but with an early onset (0.6 hr). The analysis of motor activity showed that 3,5-DHPG elicited higher central stimulatory action than did 1S,3R-ACPD. Histopathological analysis of the hippocampus showed that 3,5-DHPG produced severe neuronal damage mainly in the CA1 pyramidal neurons and, to a lesser extent, in the CA3. Although 1S,3R-ACPD infusion also induced a slight injury of the CA1 and CA3 pyramidal neurons, damage was greater in the CA4 and dentate gyrus cells. In conclusion, the in vivo activation of group I mGluRs with the selective agonist 3,5-DHPG produces hyperexcitatory effects that lead to seizures and neuronal damage, these effects being more severe than those observed after infusion of the non-selective agonist 1S,3R-ACPD.

Analysis of Variance↗
PubMed1997

Changes in brain putrescine concentration associated with nonconvulsant behavioral patterns induced by systemic N-methyl-D-aspartate injection.

The relationship between the behavioral effects and motor activity induced by N-methyl-D-aspartate (NMDA) (150 mg/kg, ip) and brain polyamine concentration was studied in male Wistar rats. Motor activity was evaluated by an automated subtraction analysis system to measure the duration and vigor of any kind of movement. The behavioral modifications exhibited by the nonconvulsant NMDA-treated rats were evaluated according to the composition and sequence of behavioral components as: hypoactivity (pattern A), partially stereotyped activity (pattern B), and generalized stereotyped activity (pattern C). The concentration of polyamines in the frontal cortex and hippocampus was measured 8 and 24 h after drug injection. A relationship was found between the concentration of putrescine in both regions and the motor activity. In addition, the concentrations of putrescine also correlated with the vigor of the movements performed. Moreover, the putrescine concentration in the frontal cortex and hippocampus paralleled the behavioral patterns. The histological examination of the frontocortical and hippocampal areas did not reveal any evidence of damage. In conclusion, partially or generalized stereotyped activity elicited by systemic NMDA administration induces an increase in putrescine in the brain not linked to histological damage.

Animals↗
PubMed1996

Concentration of putrescine in plasma, frontal cortex and hippocampus of rats after systemic administration of the convulsants N-methyl-D-aspartate, pentylentetrazol, picrotoxinine, lindane and 4-aminopyridine.

The motor responses (such as stereotypic behavior or convulsions induced in rats by N-methyl-D-aspartate (NMDA) administered systemically were followed by a rapid, moderate increase in the putrescine concentration in plasma which preceded an increase in this amine in the brain. This effect was not observed following the convulsions evoked by pentylentetrazol, picrotoxinine, lindane or 4-aminopyridine. However, all the convulsants assayed induced a mild increase in the concentration of putrescine in the frontal cortex and hippocampus. A differential activation of the ornithine decarboxylase (ODC)/polyamine system in both cerebral and peripheral tissues could account for these results.

Aminopyrine↗
PubMed1995

Blood polyamines in the rat.

The physiological concentrations of polyamines in plasma, serum and red blood cells were determined in male Wistar rats, using HPLC with fluorometric detection. The analysis of the metabolic ratio between polyamines and the frontal cortex/plasma relationship for putrescine, spermidine and spermine, suggest the existence of common mechanisms in the regulation of spermidine in blood and brain.

Animals↗
PubMed1994

On the neurotoxicity of systemically administered putrescine: influence of kinetic factors.

Putrescine (PUT) given ip to male rats produced a dose-dependent behavioural response. The observed signs were mainly shaking behaviour and motor disorders. The severity of the motor signs closely correlated with cortical PUT levels. After [14C]-PUT, the levels of related radioactivity ([14C]-PUTrr) in frontal cortex paralleled the levels of tracer in blood. Furthermore, the levels of tracer in blood and in frontal cortex were higher in the animals with toxicity signs than in non-affected ones. The frontal cortex levels of polyamines determined by HPLC revealed that only PUT paralleled the severity of the clinical status of the rats. No modifications of spermidine (SD) or spermine (SM) content were detected. Two hours after [14C]-PUT administration, only about 30% of the cortical [14C]-PUTrr was analyzed as PUT itself and no radioactivity was detected as SD and SM. Our results suggest that the radioactivity not associated to PUT could be related to more polar metabolites than SD or SM as acetylated derivatives.

Animals↗
PubMed1991

Differential response of rat brain polyamines to convulsant agents.

The polyamines putrescine (PUT), spermidine (SD) and spermine (SM) have been studied in rat brain after treatment with several convulsant agents. Kainic acid (10 mg/kg), picrotoxinin (1.5 mg/kg), pentylenetetrazol (60 mg/kg) and lindane (gamma-hexachlorocyclohexane) (60 mg/kg) were given to male Wistar rats. Twenty-four hours later, the animals were sacrificed and their brains removed. Cortical polyamines were analyzed by HPLC with fluorimetric detection of their respective dansyl derivatives, using 1,6-diaminohexane as internal standard for the measurements. Polyamine levels are not affected by short periods of time (30 min) of brain exposure to room temperature before freezing the samples, as compared to a quick procedure (less than 40 s from animal death). Kainic acid induced a 14-fold increase of cortical PUT with respect to control values, leaving unchanged the other polyamines. Lindane also increased cortical PUT (4-fold) without affecting SM or SD. Neither picrotoxinin, nor pentylenetetrazol groups were different from controls for any of the polyamines assayed. The results are discussed in relation to the possible mechanism of action of these convulsant agents and the role of the polyamines in cell injury.

Animals↗
PubMed1991

Changes in polyamine levels in rat brain after systemic kainic acid administration: relationship to convulsant activity and brain damage.

We have examined the effects of systemic kainic acid (KA) administration (9 mg/kg, i.p.) on rat behavior, brain damage, and polyamine levels and the action of the specific ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) on these effects. KA elicited convulsant activity in 63% of the animals. In the acute convulsant phase (1-3 h after KA), a rapid decline (-39% at 3 h) of spermidine content in frontal cortex was found. After the acute convulsant phase, levels of hippocampal spermidine and spermine were reduced (-70 and -66%, respectively, at 8 h). A dramatic increase of putrescine content (68.1, 1,382, and 336% at 8 h, 24 h, and 9 days, respectively, after KA) was found, associated with histological signs of cortical brain damage (ischemia and necrosis). There was a close relationship between the concentration of putrescine and signs of delayed toxicity (body weight losses) 24 h and 9 days after KA. DFMO partially antagonized the convulsant activity and reduced the increased putrescine levels to approximately 50% of values in KA-treated animals at 24 h but did not change the pattern of histological damage. The role of polyamines in the early and late phases of KA-induced neurotoxicity is discussed.

Animals↗
PubMed1988

Protein binding and stability of norepinephrine in human blood plasma. Involvement of prealbumin, alpha 1-acid glycoprotein and albumin.

The binding of norepinephrine (NE) to plasma proteins of fresh human blood obtained from healthy volunteers was studied by ultrafiltration at different NE concentrations and incubation times at 37 degrees C. At 1.7 nM L-[3H]-NE binding was approximately 25%. The binding was rapid and was not influenced by the incubation time. [3H]-NE could be dissociated from its binding sites by acid precipitation and, after HPLC, showed to be unchanged NE. No difference in NE binding was found between plasma collected in EGTA-GSH or heparin solution. There was no degradation of NE when incubated in plasma at 37 degrees C for 10 h, even without the addition of antioxidants. Therefore, in the present study, binding represented interaction of unchanged NE with plasma proteins. The whole plasma binding was saturable over the range of 0.66 nM to 0.59 mM of NE. Scatchard plot of specific binding revealed high-affinity sites with a Kd of 5.4 nM and a Bmax of 3.9 fmoles.mg-1 protein, and low-affinity sites with a Kd of 2.7 microM and a Bmax of 3.3 pmoles.mg-1 protein. Electrophoretic characterization of NE-binding proteins showed that about 60% of bound NE was associated to albumin, and 20% to prealbumin. NE binding to pure human plasma proteins was also studied using ultrafiltration. Scatchard analyses revealed a single class of very high-affinity binding sites for prealbumin (Kd 4.9 nM), a single class of binding sites for alpha 1-acid glycoprotein (Kd 54 microM) and two classes of binding sites for albumin with high (Kd 1.7 microM) and low (Kd 0.8 mM) affinities respectively. The main results obtained in this study - a) reversibility of NE binding, b) stability of free and bound NE in plasma, c) involvement of the prealbumin as a specific binding protein - point out to a specific transport for NE in human blood plasma.

Adult↗