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P Mares

Publications and source records attributed to P Mares.

At least 19 recordsLinked to original sources
PubMed2002

NMDA receptor antagonists impair motor performance in immature rats.

RATIONALE: Antagonists of NMDA receptors are excellent anticonvulsants in adult animals but serious side effects prevent their clinical use. The effects of two antagonists on motor performance were studied to find out if they develop in parallel with previously described anticonvulsant action. METHODS: Motor performance of 12-, 18- and 25-day-old rats was studied using a battery of tests (surface righting, negative geotaxis, bar holding and wire mesh ascending and three age-specific tests). A competitive NMDA antagonist CGP 40116 (0.1, 0.5 and/or 1 mg/kg IP) and a noncompetitive one dizocilpine (0.1, 0.5 and/or 1 mg/kg IP) were tested. RESULTS: Ten minutes after CGP 40116, the performance was compromised in all tests but there was negative geotaxis in all age groups. A decrease in efficacy with age was clearly demonstrated. Righting ability remained untouched in 25-day-old animals. Dizocilpine also influenced the performance in all tests but righting (compromised only in the youngest group) when studied 10 min after the injection. The relation to age was not so marked as with CGP 40116. When the tests were applied 4 h after dizocilpine administration the results were similar to those at 10-min interval. Twenty-four hours after dizocilpine only cliff avoidance exhibited prolonged latencies in 12-day-old rats but significant effects were observed in 18-day-old (negative geotaxis, bar holding and wire mesh ascending) as well as 25-day-old animals (bar holding, jumping down with choice). CONCLUSIONS: The acute effects of both NMDA antagonists studied decreased with age; this age-related change was more marked with CGP 40116 than with dizocilpine. In contrast, duration of dizocilpine effects did not exhibit a clear developmental tendency.

2-Amino-5-phosphonovalerate↗
PubMed2002

Changes of cortical epileptic afterdischarges under the influence of convulsant drugs.

Convulsant drugs picrotoxin (0.5 and/or 1 mg/kg, intraperitoneal (i.p.)) and pentylenetetrazol (10 and/or 20 mg/kg, i.p.) were used to compromise GABAergic inhibition, caffeine (75 and/or 150 mg/kg, i.p.) to antagonize adenosinergic system to study the role of inhibition in cortical epileptic afterdischarges. Rats with implanted cortical stimulation and registration electrodes were stimulated four times at 10-min intervals, drugs were injected between the first and second stimulation. Four different phenomena were evaluated: movements directly bound to stimulation were intensified by all three drugs, i.e., excitability of the cerebral cortex was increased. Incidence of two types of afterdischarges (spike-and-wave rhythm and "limbic" type) was not changed by any drug, i.e., the transition of epileptic activity into limbic structures was not increased. Afterdischarges were most efficiently prolonged by caffeine, i.e., caffeine probably interferes with mechanism(s) arresting cortical afterdischarges. The intensity of clonic seizures accompanying spike-and-wave afterdischarges, i.e., spread of epileptic activity into the motor system was only transiently increased by picrotoxin, the effects of caffeine did not reach the level of statistical significance. Our results indicate various mechanisms and diverse role of the two inhibitory systems in generation of evaluated phenomena.

Animals↗
PubMed2002

Interaction of excitatory amino acid agonists with cortical afterdischarges in developing rats.

PURPOSE: To determine the role of excitatory amino acids (EAAs) in genesis of two types of epileptic afterdischarges. METHODS: Cortical stimulation and recording electrodes were implanted in 12-, 18-, and 25-day-old rats. Epileptic afterdischarges were induced by rhythmic stimulation of sensorimotor cortex. The stimulation was repeated 6 times with 20-min intervals. Ten minutes after the first afterdischarge, N-methyl-d-aspartate, homocysteine, or kainic acid was injected. The doses were chosen individually for different age groups to be subconvulsive. Type and duration of afterdischarges as well as type and severity of motor correlates were evaluated. RESULTS: N-methyl-d-aspartate prolonged afterdischarges only in 12-day-old rats, whereas two other drugs did it in all age groups. Motor correlates of afterdischarges were changed to flexion seizures in 12-day-old rats after N-methyl-d-aspartate and homocysteine; in 25-day-old rats homocysteine led to generalized tonic-clonic seizures (i.e., both patterns seen after substantially higher doses of these drugs in nonstimulated rats). Seizures lasted tens of minutes. Kainic acid did not change the motor pattern in any age group, but nonconvulsive EEG seizures were recorded in the interstimulation periods mainly in 18- and 25-day-old rats. Increased transition into the limbic type of afterdischarges appeared only after homocysteine in 18- and 25-day-old rats. CONCLUSIONS: A mutual potentiation of epileptic phenomena was induced by two agents. The actions of N-methyl-d-aspartate and kainic acid differ in all age groups; the effects of homocysteine were identical with those of N-methyl-d-aspartate in 12-day-old rats but not later. Only homocysteine augmented transition into the limbic type of afterdischarges.

Aging↗
PubMed2002

Effects of classical antiepileptics on thresholds for phenomena induced by cortical stimulation in rats.

Our aim was to study the effects of phenobarbital, phenytoin and ethosuximide on epileptic afterdischarges induced by cortical stimulation in rats. Fifteen-second series of low-frequency (8 Hz) rhythmic stimulation of the sensorimotor cortex were applied in rats with chronically implanted electrodes. Intervals between the stimulation series were at least 10 min and intensity was increased in a step-wise manner. Threshold current intensities were estimated for movements directly induced by stimulation, epileptic afterdischarges of the spike-and-wave type, clonic seizures accompanying this type of afterdischarge and transition into the limbic type of afterdischarge. Phenobarbital, phenytoin and ethosuximide were administered intraperitoneally before the first stimulation series. Phenobarbital (20, 40 and 80 mg kg(-1)) significantly increased the thresholds for the first three phenomena in a dose-dependent manner. Transition into the limbic afterdischarge was influenced only by the highest dose. Phenytoin (60 mg kg(-1)) only increased the thresholds insignificantly and ethosuximide (125 mg kg(-1)) was ineffective. We concluded that our model is useful for testing anticonvulsant effects. Results with three antiepileptic drugs correspond with their efficacy against myoclonic seizures in man.

Animals↗
PubMed2002

Are acute changes after status epilepticus in immature rats persistent?

Early consequences of lithium-pilocarpine convulsive status epilepticus (SE) were studied six days after this status had been induced in rat pups at the age of either 12 or 25 days. Studies of spontaneous EEG activity demonstrated the presence of epileptic phenomena (isolated spikes) in both hippocampus and cortex (cortical spikes were more expressed in the older group). There were no marked behavioral correlates of spikes and transition into the ictal phase was exceptional. The motor performance on a rotorod and a horizontal bar was the same in experimental and control rats of both ages. Behavior in the open field was changed in a reverse manner in the two age groups: the locomotor activity of rats with induced seizures at the age of 12 days was significantly lower than that of their control siblings, whereas animals undergoing status at the age of 25 days were hyperactive. In addition, they also exhibited increased exploratory activity (rearing) and their habituation to the open field was deranged. Nissl-stained brain sections demonstrated extensive brain damage in the older group in contrast to the negative findings in younger animals. EEG, behavioral and morphological changes induced by status epilepticus in developing rats persisted for 6 days after the status. They markedly differed according to the age of animals.

Acute Disease↗
PubMed2002

Does vigabatrin possess an anticonvulsant action against pentylenetetrazol-induced seizures in developing rats?

Anticonvulsant action of vigabatrin (300, 600, 900 and/or 1200 mg/kg i.p.), an inhibitor of GABA-transaminase, was studied in a model of motor sezures elicited by pentylenetetrazol. Five age groups of rats (7, 12, 18, 25 and 90 days old) received a s.c. injection of pentylenetetrazol 4, 6 and/or 24 hours after vigabatrin administration. The incidence of minimal, predominantly clonic seizures was not changed in any age group, but their latencies were prolonged in 18- and 25-day-old rats. Generalized tonic-clonic seizures were influenced in a more complex manner. Incidence of these seizures was decreased in 7-day-old rat pups 24 hours after vigabatrin administration. Higher doses of vigabatrin exhibited a similar effect in adult rats at all intervals studied. Specific suppression or at least restriction of the tonic phase was observed in all groups of immature rats, the effect was more marked 24 hours after vigabatrin than at shorter intervals. The anticonvulsant action of vigabatrin, which could be demonstrated mainly against generalized tonic-clonic seizures, varies markedly during development.

Animals↗
PubMed2002

Disturbance of motivated behavior in rats by epileptic afterdischarges.

Nearly all epileptic seizures in patients are characterized by deranged consciousness. We started to study changes in motivated behavior (drinking in thirsty rats) as a possible analogue of compromised consciousness during and after epileptic seizures. Epileptic afterdischarges (ADs) were elicited by stimulation of the dorsal hippocampus and/or thalamus. Rats with implanted electrodes (deprived of water for 24 hours) were trained to lick water from a narrow tube. After pretraining ADs were elicited eight times in each animal and access to water was allowed during different phases of the AD. Stimulation did not affect licking if no AD was induced. If stimulation was successful, licking was stopped in nearly 70 % of stimulations and modified (biting the tube) in 30 %. Hippocampal ADs (characterized by serrated waves in the EEG and by an arrest of behavior with subsequent automatisms) completely blocked licking, signs of recovery appeared during the interval between the AD and recurrent AD and it progressed during recurrent ADs. Thalamic ADs abolished licking in 82% of cases and immediately after ADs normal licking reappeared in 49 % of these observations. Our results suggest that changes in motivated behavior might serve as an analogue of compromised human consciousness.

Animals↗
PubMed2002

[Intensive therapy with paclitaxel (Taxol) and cyclophosphamide followed by administration of G-CSF as a mobilization regimen in patients with breast carcinoma and indications for autologous hematopoietic cell transplantation].

Cyclophosphamide (4 g/m2) and paclitaxel (Taxol) (175, 200 or 250 mg/m2) therapy with subsequent administration of G-CSF (10 micrograms/kg) has been used as intensification and as mobilization therapy for patients with breast cancer. This regimen was used in 19 patients, as part of adjuvant therapy in 14 and as part of therapy of metastatic disease in five. Median number of collected CD34+ cells was 17.5 x 10(6)/kg (2.9-48.1). All patients except one (94.7%) reached minimal required number of CD34+ cells (> or = 3 x 10(6)/kg). Median number of leukapheresis was two. The required number of cells (> or = 3 x 10(6)/kg) was collected in one leukapheresis in 17 out of 19 patients (89.5%) and more than five and 10 x 10(6)/kg CD34+ cells respectively were collected in 14 (73.7%) and 11 (57.9%) patients respectively. No factor significantly influencing the amount of collected cells (except the trend in favour of later year of therapy and large-volume leukapheresis) was identified. Leukopenia gr. 4 was observed in 88.9% of treated patients and febrile neutropenia developed in 46.2% patients. Although the antitumour activity of this chemotherapy was not possible to assess it seems that this intensification could be successfully used as a therapy and as very potent mobilization regimen.

Adult↗
PubMed2001

Single systemic dose of vigabatrin induces early proconvulsant and later anticonvulsant effect in rats.

Vigabatrin (VGB), an inhibitor of gamma-aminobutyric acid-aminotransferase, exhibits an antiepileptic effect but several studies indicate that its effect may be biphasic. A time course of an effect of a single injection of VGB on hippocampal epileptic afterdischarges (AD) elicited by an electric stimulation of the angular bundle was examined in adult rats with chronically implanted electrodes. VGB (600 or 1200 mg/kg intraperitoneally) proved to be an efficient anticonvulsant in the intervals of 24 and 48 h--duration of ADs was shortened and behavioral phenomena were less intense. In contrast, ADs were lengthened 4 h after administration. The biphasic effect of VGB was demonstrated, the initial proconvulsant effect might be due to a different onset of VGB action in individual brain structures, but an additional mechanism of action cannot be excluded.

Action Potentials↗
PubMed2001

Attenuation of seizures induced by homocysteic acid in immature rats by metabotropic glutamate group II and group III receptor agonists.

Previous studies demonstrated that selected agonists for metabotropic glutamate group II and group III receptors can provide protection against seizures in adult animals. The present study has examined the potential effect of some of these compounds on seizures induced in immature rats by intracerebroventricular infusion of DL-homocysteic acid (DL-HCA, 600 nmol/side). Rat pups were sacrificed during generalised clonic-tonic seizures, 50--60 min after infusion. Comparable time intervals were used for sacrificing the pups which had received the protective drugs. The anticonvulsant effect was evaluated according to the suppression of behavioural manifestations of seizures and the protection of energy metabolite changes which normally accompany these seizures (large decreases of glucose and glycogen, and approximately 7- to 10-fold accumulation of lactate). Partial protection was exhibited by group II mGluR agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV, 0.6 nmol) and this effect was abolished after pretreatment with an antagonist for group II mGluRs (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG, 100 nmol). In high doses (5--100 nmol), however, DCG IV evoked seizures which were prevented by AP7, suggesting that the convulsant effect was mediated by interaction with NMDA receptors. A pronounced anticonvulsant effect against DL-HCA-induced seizures was achieved with low doses of a highly selective group II mGluR agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC, 0.6 nmol), group II agonist and group I mGluR antagonist (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4-C3HPG, 0.6 nmol) and group III mGluR agonist (RS)-1-amino-3-(phosphonomethylene) cyclobutane-carboxylic acid (32 nmol). Generalised clonic--tonic seizures were completely suppressed and the metabolic changes were markedly ameliorated, there being only a 1.5-, 2- and 2.5-fold rise of lactate, respectively. Higher doses of (S)-4-C3HPG (1--100 nmol) were, however, less anticonvulsant than low doses. The present results have confirmed that mGluRs may be considered a potential target for treatment of epilepsy.

Animals↗
PubMed2001

[Vaginal dryness].

Vaginal dryness is one of the "little problems" that are too often, ignored. The disorder essentially manifests at the time of menopause, but can occur at other times, such as with oral contraception, following vaginal infection, after treatment for infection, etc. Screening for the disorder should become routine. Management should have precise objectives: cure of the infection and restablishment of the vaginal flora in order to reconstitute a natural balance. Treatment can be adapted for each patient to obtain effective and lasting results.

Contraceptives, Oral↗
PubMed2001

Influence of convulsants on rat brain activities of alanine aminotransferase and aspartate aminotransferase.

There exist differences between 12-day-old and adult rats in the onset of seizures induced by some inhibitors of glutamate decarboxylase (GAD). The aim of study was to investigate if there are differences between both groups in activities of rat brain alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the enzymes involved in glutamate metabolism, after the administration of 3-mercaptopropionic acid as specific GAD inhibitor or isoniazid as less specific general inhibitor of pyridoxal enzymes. Activities of both aminotransferases in a supernatant 20,000 g of the whole brain (containing predominantly cytosolic isoforms of enzymes) were increased at the beginning of 3-mercaptopropionic acid-induced generalized tonic-clonic seizures. At isoniazid-induced generalized tonic-clonic seizures, a significant increase in both enzyme activities was observed in adult rat brain. In the 12-day-old rat brain, ALT and AST activities reached about 40% and about 50-60% of adult control levels, respectively. In in vitro experiments, no influence of 3-mercaptopropionic acid on transaminase activities was found and an inhibitory effect of isoniazid on the enzymes was confirmed. Increased aminotransferase activities might participate in the enhanced synthesis of excitatory amino acid neurotransmitters in the nervous system, which may take a part in the initiation of epileptic seizures. Alternatively, the increased AST activity may be connected with an increased transport of NADH from the cytosol to mitochondria, while the increased ALT activity would represent the transformation of pyruvate to alanine as a consequence of increased glycolysis.

3-Mercaptopropionic Acid↗
PubMed2001

Prevalence of HFE mutations in people from North Africa living in southern France.

The two main mutations of the HFE (haemochromatosis) gene, C282Y and H63D, were found previously to be rare or absent among Africans. Dried blood samples of 1276 newborns from southern France were analysed for both HFE mutations, and the origins of the four grandparents of each newborn were recorded. The allele frequency of C282Y and H63D was 3.0% +/- 0.7% and 16.9% +/- 1.5% respectively. In a subgroup of 171 newborns with four North African ancestries (mainly from Morocco and Algeria) the allele frequency was 0.9%+2.5%-0.2% for the C282Y and 13.2% +/- 3.6% for H63D. HFE mutations are not absent in individuals with North African origins living in southern Europe. This finding has implications for the diagnosis and screening of hereditary haemochromatosis in these populations.

Africa, Northern↗
PubMed2001

Maturation of rat brain is accompanied by differential expression of the long and short splice variants of G(s)alpha protein: identification of cytosolic forms of G(s)alpha.

Distribution of the alpha subunit of the stimulatory G protein (G(s)alpha) was analyzed in membrane and cytosolic (supernatant 200 000 g) fractions from rat cortex, thalamus and hippocampus during the course of post-natal development. In parallel, changes in beta-adrenoceptor density and adenylyl cyclase activity were determined. Long (G(s)alphaL) and short (G(s)alphaS) variants of G(s)alpha were assessed by immunoblotting using specific polyclonal antisera reacting with both G(s)alpha isoforms. Post-natal development was associated with an increase in the total amount of brain G(s)alpha. G(s)alphaL was the dominant isoform of G(s)alpha in the membrane fractions of all studied brain regions and its amount increased markedly between post-natal day (PD) 1 and 90. The level of membrane-bound G(s)alphaS also elevated during post-natal development, but more pronounced changes were found in cytosolic G(s)alphaS. Although only a small amount of G(s)alphaS (much smaller than G(s)alphaL) was detected among soluble proteins shortly after birth, G(s)alphaS prevailed over G(s)alphaL at PD90. The G(s)alphaL/G(s)alphaS ratio decreased, respectively, from 3.2 to 1.2 and from 5.0 to 1.5 in the membrane fractions of cortex and hippocampus, but remained almost constant in thalamus between PD1 and 90. More dramatic changes were found in the cytosolic fractions of all studied brain regions: the G(s)alphaL/G(s)alphaS ratio decreased sharply in cortex (from 14.1 to 0.9), hippocampus (from 3.7 to 0.8), and also in thalamus (from 9.5 to 0.5). These results demonstrate that the membrane-cytosol balance of G(s)alpha proteins alters dramatically during the course of brain development. Both G(s)alphaL and G(s)alphaS were expressed in a region- and age-specific manner, which suggests different roles in the maturation of the brain tissue. A cyc(-) reconstitutive assay of cytosolic G(s)alpha indicated that only approximately 20% of this protein was functional, compared with membrane-bound G(s)alpha, and its ability to reconstitute adenylyl cyclase activity increased during the course of maturation. The number of beta-adrenoceptors increased sharply during early post-natal development but only slightly in adulthood, and both GTP- and isoproterenol-stimulated adenylate cyclase activity reached peak values around PD12.

Adenylyl Cyclases↗
PubMed2001

An animal model of nonconvulsive status epilepticus: a contribution to clinical controversies.

PURPOSE: To characterize electroencephalographic and behavioral effects as well as electrophysiologic and morphologic consequences of a subconvulsive dose of pilocarpine in lithium chloride-pretreated rats. METHODS: Pilocarpine (15 mg/kg) was administered intraperitoneally to adult rats pretreated with lithium chloride (3 mEq/kg, i.p.). Behavior was observed for 2 h and videotaped in three consecutive sessions. At the same time, EEG was recorded from the sensorimotor cortex and the dorsal hippocampus. Threshold intensities of currents necessary to elicit hippocampal afterdischarges were determined 24 h and 1 week after the pilocarpine administration. The brains were histologically examined 1 week after pilocarpine administration using Nissl stain. RESULTS: Pilocarpine induced time-limited nonconvulsive status epilepticus (NCSE). Epileptic EEG activity concurrent with prominent behavioral features was observed both in the neocortex and, predominantly, in the hippocampus. No changes in afterdischarge thresholds were observed in the dorsal hippocampus 24 h and 1 week after NCSE. One week after NCSE, seizure-related brain damage was found mainly in the motor neocortical fields. CONCLUSIONS: Pilocarpine-induced NCSE in rats strongly resembles a short-term human complex partial status epilepticus. Our animal model is suitable for studying the possible adverse effects of prolonged nonconvulsive seizures.

Animals↗
PubMed2001

APC resistance and third-generation oral contraceptives: Acquired resistance to activated protein C, oral contraceptives and the risk of thromboembolic disease.

Using a newly-developed technique, a severe acquired plasma resistance to activated protein C has been described in women using third-generation (rather than second-generation) oral contraceptives. The following items are discussed: (i) the technical parameters used to appreciate the effect of activated protein C induce a bias of interpretation, the mean intrinsic effect of activated protein C, in plasmas from women on second or third-generation oral contraceptives being strictly identical; (ii) there are no data available to show that this assay can indicate a thromboembolic risk in asymptomatic women on oral contraceptives; and (iii) this assay is a global and non-specific test, basically sensitive to the plasma concentrations of many coagulation factors which are increased or decreased by oestrogens and progestogens. For instance protein S, in which oral contraceptive-induced modifications account for the differential effect of oral contraceptives on Rosing's assay, but which modifications are not related to the thromboembolic risk of oral contraceptives. The androgenic potential of the progestogen may counteract the effect of oestrogens in the test. More generally, in such a complex situation in which there is a 'modification of the modification', there is no haemostasis-related test which provides a risk indicator for thrombosis. Based on testing of the plasma response to activated protein C, it is impossible to state that third-generation oral contraceptives induce a more important thromboembolic risk than oral contraceptives containing a more androgenic progestogen.

Activated Protein C Resistance↗