PubMed Health⌕ Search

Biomedical subjects

F Angelatou

Publications and source records attributed to F Angelatou.

11 recordsLinked to original sources
PubMed1993

Upregulation of A1 adenosine receptors in human temporal lobe epilepsy: a quantitative autoradiographic study.

A significant increase of A1 adenosine receptor binding (48% increase of mean) was detected in human neocortex obtained from patients suffering from temporal lobe epilepsy as compared to control neocortex from non-epileptic patients. Such increase was equally distributed in the six cortical layers and reached similar levels in each of the five specimens tested independently of age, sex and pharmacological treatment of the patient. Since adenosine exerts a depressant effect on neocortical neurons in slices obtained from epileptic patients, this upregulation of A1 receptor binding may constitute a protective mechanism against subsequent seizures, which is exerted by elevating the depressant response of the brain to endogenous adenosine.

Adenosine↗
PubMed1993

Effect of pentylentetrazol-induced seizures on A1 adenosine receptor regional density in the mouse brain: a quantitative autoradiographic study.

Adenosine has been shown to be a major regulator of neuronal activity in convulsive disorders, exerting its anticonvulsant effect through central A1 adenosine receptors. The aim of the present study was to investigate the effect of generalized tonic-clonic seizures induced by pentylentetrazol on regional changes in A1 adenosine receptor density and distribution in the mouse brain by in vitro quantitative autoradiography. As radioligand the specific agonist of A1 receptors [3H]cyclohexyladenosine was used. After two consecutive (once daily) pentylentetrazol-induced convulsions a widespread upregulation of A1 receptor density was detected with a marked enhancement in structures that mediate seizure activity like hippocampus, mamillary bodies, septum, substantia nigra, thalamic nuclei and cerebral cortices. On the contrary, in basal ganglia a significant downregulation of A1 receptors was observed. These results indicate that: (i) the observed increases or decreases in A1 receptor density are organized in selective anatomical structures related to seizure development rather than uniform in the brain; and (ii) since the upregulation of A1 receptors is sufficient to enhance the physiological depressive response of adenosine, the overall evoked increases seen here may lead to a stronger inhibitory tone and accordingly to a more efficient anticonvulsant effect of endogenous adenosine.

Adenosine↗
PubMed1992

Reduction of A1 adenosine receptors in cortex, hippocampus and cerebellum in ageing mouse brain.

Age related changes in A1 adenosine receptor binding were investigated in mouse brain using the selective agonist, [3H]-cyclohexyladenosine ([3H]CHA). In the cortex, hippocampus and cerebellum of aged mice (28 months old), a significant decrease of about 44%, 50% and 12%, respectively, in [3H]CHA binding compared to young animals (3 months old) was observed. According to the Scatchard analysis of the binding data in the cortex, this decrease was due to a receptor density reduction and not to a Kd change. Since the weight and protein content of each tissue tested did not differ significantly between the old and the young animals, our findings may be partly explained by specific reductions of A1 receptors rather than a general cell degeneration in old age.

Aging↗
PubMed1991

Changes in seizure latency correlate with alterations in A1 adenosine receptor binding during daily repeated pentylentetrazol-induced convulsions in different mouse brain areas.

The seizure latency changed during daily pentylentetrazol (PTZ) induced convulsions showing an increase between days 2 and 4, a rapid decrease between days 5 and 10 and a slight increase again between days 11 and 14. At the respective timepoints, [3H]CHA binding, in cortex and cerebellum of PTZ treated animals followed exactly the same pattern, suggesting that the alterations in A1 receptors in these areas may partly determine the PTZ seizure latency curve. On the contrary, the changes of [3H]CHA binding in hippocampus (sustained increase) and striatum (sustained decrease) didn't follow the latency curve pattern. These results suggest that changes in A1 receptor density in specific brain areas may be involved in the modulation of seizure susceptibility.

Adenosine↗
PubMed1990

Alterations of A1 adenosine receptors in different mouse brain areas after pentylentetrazol-induced seizures, but not in the epileptic mutant mouse 'tottering'.

Single and repeated Pentylentetrazol (PTZ)-induced convulsions are associated with significant changes of A1 adenosine receptors (detected using the radioligand [3H]cyclohexyladenosine, [3H]CHA) in 4 different brain areas of the mouse, namely cortex, hippocampus, cerebellum and striatum. In hippocampus and cerebellum, a rapid increase in [3H]CHA binding, by 26% and 30% respectively, was observed 1 h after a single PTZ convulsion. In striatum, on the contrary, a significant decrease by 30% in [3H]CHA binding was seen, whereas in cortex no significant change could be detected. After daily repeated PTZ convulsions, a significant increase of A1 receptors by 26% appeared also in cortex, while the changes of A1 receptors observed in the other brain areas after a single PTZ convulsion were maintained in almost the same range. All the alterations observed were due to changes of the total number of A1 receptors (Bmax) without changes in receptor affinity (Kd). A significant increase in the latency of PTZ seizure (time between the PTZ-injection and the beginning of the seizure) was also observed after repeated PTZ-induced convulsions at the time when the changes in A1 adenosine receptors were noted. Considered together, these results provide further evidence for an A1 receptor-mediated modulation of seizure susceptibility and indicate that specific brain areas may play different roles in this modulation. The binding of [3H]CHA to membranes from different cortical and subcortical areas of the epileptic mutant mouse 'tottering' was not different from that in control animals.

Adenosine↗
PubMed1987

Absence of modification in GABA and benzodiazepine binding and in choline acetyltransferase activity in brain areas of the epileptic mutant mouse tottering.

1. In the tottering mutant mouse, which suffers from epilepsy and cerebellar ataxia, we examined whether possible changes in GABA, benzodiazepine receptors and choline acetyltransferase (ChAT) activity are implicated in the pathophysiology of these animals. 2. No alteration in GABAA and GABAB binding could be detected in cerebellar membranes of epileptic mice as compared to normal mice. 3. Benzodiazepine receptor density and affinity showed no statistical difference in cerebellar membranes of epileptic and normal mice. 4. The activity of ChAT determined in the cortices of epileptic and normal mice did not differ significantly between the two groups.

Acetylcholine↗
PubMed1987

L-aspartate and L-glutamate binding sites in developing normal and 'nervous' mutant mouse cerebellum.

This study concerns the ontogeny and the cellular localization of L-aspartate and L-glutamate binding sites in normal and 'nervous' mutant mouse cerebellar membranes. The binding kinetics revealed for L-aspartate a single binding system (Kd = 750 nM) and for L-glutamate also a single binding component of higher affinity (Kd = 344 nM). The pharmacological study, using various amino acid analogues, revealed a differential specificity for the binding sites of the two amino acids. The developmental study showed that the binding sites of both amino acids appear mainly during the second and third week of life, a period when parallel and climbing fiber synaptogenesis occurs, but they follow a slightly different developmental pattern. The study using 'nervous', mutant mouse cerebellum showed an age-dependent decrease of L-aspartate and L-glutamate binding, which coincides in time with the Purkinje cell degeneration in this mutant, indicating a cellular localization of these binding sites on the Purkinje cell membranes. These results suggest that L-aspartate and L-glutamate binding sites may be respectively associated with the postsynaptic target of climbing and parallel fibers on the Purkinje cell dendrites. However, the decrease of specific binding in 'nervous' mutant mouse cerebellum was about 50% for L-aspartate and 60% for L-glutamate, implying that a significant number of L-aspartate and L-glutamate binding sites are located on cerebellar elements other than the Purkinje cell membranes.

Aging↗
PubMed1982

Purification and properties of two gentamicin-modifying enzymes, coded by a single plasmid pPK237 originating from Pseudomonas aeruginosa.

A broad host range multiresistance plasmid pPK237, originating from Pseudomonas aeruginosa mediates high-level resistance to gentamicin and tobramycin. It was found to code for two gentamicin modifying enzymes, which from their substrate profile by radioenzymatic assay were characterized as aminoglycoside acetyltransferase AAC(3)-I and aminoglycoside adenylyltransferase AAD(2"). The two enzymes were studied after purification from an Escherichia coli K12 host. The two gentamicin-modifying enzymes coded by PPK237 were completely separated by DEAE chromatography. The purification (126 fold) of the acetyltransferase was achieved by (NH4)2SO4 precipitation, DEAE chromatography and affinity chromatography. The purification of the adenylyltransferase was performed by affinity chromatography directly after (NH4)2SO4 precipitation. Both purified enzyme preparations showed a single protein band on disc electrophoresis. The Km for gentamicin C1 of the acetyltransferase was 0.066 mM. The amino acid analysis of the acetyltransferase coded by pPK237 showed a different aminoacid composition than that of the gentamicin acetyltransferase AAC(3)-I purified by Williams and Northrop17). The acetyltransferase after DEAE chromatography is stable for many months at -20 degrees C, while the adenylyltransferase after purification is highly unstable; it shows enzymatic activity only in the presence of Mg++.

Acetyltransferases↗
PubMed1976

Multiresistant plasmids from Pseudomonas aeruginosa highly resistant to either or both gentamicin and carbenicillin.

High-level resistance to gentamicin and carbenicillin was found in 30 and 10.7%, respectively, of Pseudomonas aeruginosa strains, especially in isolates from urine. In 23 out of 25 strains tested, these resistances were R mediated and linked to multiresistant plasmids, carrying genes for resistances to five other aminoglycosides, tobramycin, kanamycin, neomycin, streptomycin, and spectinomycin, and for resistances to chloramphenicol, tetracycline, sulfonamides, and mercury chloride. Carbenicillin resistance was unstable in Pseudomonas, and in its presence the multiresistant plasmids had a host range extended to the Enterobacteriaceae (group I plasmids). Otherwise they were transferable intragenerically only (group II plasmids). The extended host range plasmids were, as a rule, in fi(-) incompatibility class A-C. Segregants incompatible with both class A-C and P plasmids were detected. The beta-lactamase specified by the carbenicillin marker was of the TEM-like type. Multiple linkages of resistance determinants to the aminoglycosides were concomitantly present in most of the plasmids. Results from the bioassay indicated the presence of at least two aminoglycoside-inactivating enzymes.

Anti-Bacterial Agents↗
PubMedDate not supplied

Pentylenetetrazol-induced seizures decrease gamma-aminobutyric acid-mediated recurrent inhibition and enhance adenosine-mediated depression.

To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonic-clonic convulsions after administration of pentylenetetrazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before decapitation. Control mice were injected with saline. Input/output curves of the extracellular synaptic responses in the CA1 area of hippocampal slices showed that PTZ-induced seizures do not establish the persistent change in hippocampal excitability itself that can be detected in vitro. However, use of the paired-pulse stimulation paradigm showed that gamma-aminobutyric acid A (GABAA)-mediated recurrent inhibition was significantly weaker (by 19-25%) in the CA1 area of slices from PTZ-treated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABAA receptors (high-affinity component) was also lower in hippocampus (by 19%) and cortex (by 14%) of PTZ-treated mice. A GABA-related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing the brain to subsequent seizures. On the other hand, the depressant effect of a single dose of adenosine 10 microM on the CA1 synaptic response was stronger (by 35% on population spikes) and longer lasting in PTZ slices as compared with controls. This could be attributed to significantly higher adenosine A1 receptor density in hippocampus (Bmax of [3H]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A1-mediated adaptive mechanism that offers protection from subsequent seizures.

Action Potentials↗