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Biomedical subjects

P Mares

Publications and source records attributed to P Mares.

At least 163 records · Page 9Linked to original sources

Effects of alprazolam on a model of human absences--rhythmic metrazol activity in rats.

Two doses of alprazolam (0.1 and 0.5 mg.kg-1) were tested against a model of human absences--rhythmic EEG activity elicited by low doses of pentylenetetrazol (35 mg.kg-1)--in 10 unrestrained rats with implanted cortical electrodes. Alprazolam delayed the onset of epileptic EEG activity, decreased the number of rhythmic episodes and shortened the total duration of rhythmic activity in a dose-dependent manner. The average duration of episodes of rhythmic activity remained unchanged; other benzodiazepines studied previously were able to influence this measure.

Alprazolam↗

Plasma fibrinolytic activators and their inhibitors in women suffering from early recurrent abortion of unknown etiology.

The fibrinolytic response to a venous occlusion test was evaluated in 116 consecutive patients who had each had early recurrent miscarriages of unknown origin. A normal response to venous occlusion was defined from the statistical analysis of data obtained in a matched group of 90 women with no past abortion. Seventy-four patients had at least one abnormal fibrinolysis-related test, whereas no member of the control group had any (p < 10(-6)). Fifty-six of the patients had a stasis-induced shortening of the euglobulin clot lysis time that was less than normal (median decrement 3.5% [normal > or = 28%] [p < 10(-6)]). In this subgroup, 17 women also had a poor tissue-type plasminogen activator (tPA) response (median increment 18% [normal > or = 34%] [p < 0.001]). Twenty-one of the 56 had high plasma levels of type 1 plasminogen activator inactivator (PAI-1) as well as a high PAI activity level (p < 0.001 for comparison with normal controls). Sixteen patients had both abnormalities (tPA response blunted and high PAI values). When retested in the same patients, the patterns persisted over time. Nine other habitual aborters had abnormally high type 2 plasminogen activator inhibitor plasma levels (> 4.2 ng/ml). Six other patients had a poor urokinase-type plasminogen activator reactivity to venous occlusion (post-stasis levels lower than 0.18 ng/ml). Thus activators and inhibitors of the fibrinolytic system are frequently abnormal in primary habitual aborters. The current pathogeneses of high PAI-1 concentrations and of impaired tPA reactivity to venous occlusion were not found in these patients. The role of the fibrinolytic components in trophoblast invasiveness has been suspected in animals, and an impaired plasmin-dependent proteolysis in women might favor recurrent abortion by promoting fibrin deposition in early placental circulation or by limiting trophoblast development, or both.

Abortion, Habitual↗

Developmental changes of thresholds for cortical epileptic afterdischarges.

Threshold intensities for elicitation of movements and of epileptic afterdischarges by rhythmic stimulation of the sensorimotor cortex were estimated in 90 rats with implanted electrodes. Four age groups were studied--animals 12, 18, 25 and 90 days old. Both thresholds exhibited significantly higher values for adult animals in comparison with all groups of young pups. Whereas no differences were found among the rat pups in thresholds for movements accompanying stimulation, epileptic afterdischarges demonstrated a lower threshold in 18-day-old in comparison with 25-day-old animals. The development of cortical excitability is rather complicated and deserves further studies.

Animals↗

N-methyl-D-aspartate (NMDA)-induced seizures in developing rats.

Intraperitoneal administration of N-methyl-D-aspartate (NMDA) elicited epileptic motor seizures in developing rats aged from 7 to 25 days as well as in young adults. The very first sign of NMDA action is locomotor hyperactivity which is followed by clonic and tonic seizures. In rat pups during the first 3 postnatal weeks flexion seizures (emprosthotonus) appeared as the first pattern of motor seizures; later they were replaced by generalized tonic clonic seizures. Only regular tonic-clonic seizures were observed in 25-day-old and adult rats. The youngest animals are the most sensitive to NMDA. CD50 for tonic-colonic seizures is 6.7 mg/kg in 7-day-old rat pups and it increases up to 86.6 mg/kg in 25-day-old animals. Similar changes could also be demonstrated for LD50, a lethal outcome being very frequent. EEG recordings demonstrated mainly suppressed activity, thus exhibiting a lack of correlation with motor phenomena.

Aging↗

Favourable outcome in 33 triplet pregnancies managed between 1985-1990.

In this paper, we describe the outcome of 33 triplet pregnancies referred to us between 1985 and 1990. They were managed as follows: management at home as soon as the diagnosis was made, then hospitalization at 28 weeks' gestation. Progesterone and beta-mimetics were administered daily, a cesarean section was always performed. One late abortion occurred at 21 weeks. The rate of prematurity was 90.6%, mean gestational age at delivery was 34.1 +/- 3 weeks, and 62.5% of deliveries occurred between 34 and 37 weeks. Ninety-four fetuses were delivered alive. Mean birth weight was 1880 +/- 410 g. Fetal growth retardation rate was 61.8%, including 28 infants under the third centile and 31 under the 10th centile. Perinatal death rate was 4.16% including 2 in utero deaths and 2 neonate deaths. All infants are healthy except for one child with severe mental retardation. These results show that triplet pregnancies can be safely managed, and that selective first-trimester reduction in triplet pregnancies does not appear to be necessary.

Adult↗

Pentylenetetrazol-induced seizures in rats: an ontogenetic study.

A quantitative description of motor seizures induced by pentylenetetrazol (PTZ, metrazol) was performed. Seizures were induced by PTZ in doses from 40 to 120 mg/kg s.c. in 477 male albino rats of the Wistar strain 7 to 90 days old. Two patterns of seizures were elicited: minimal, i.e. predominantly clonic seizures of facial and forelimb muscles with preserved righting ability, and major, i.e. generalized tonic-clonic seizures with a loss of righting reflex. Minimal seizures could be reliably elicited since the age of 18 days; the CD50 for these seizures did not significantly differ with age. Major seizures were elicited regularly at all developmental stages studied. Their CD50 did not significantly differ among 7-, 12- and 25-day-old rat pups but the value for 18-day-old rats was smaller and for adult animals larger than these three age groups.

Aging↗

Trans-uterine venography. Normal anatomy and pathologic appearances.

From a series of 110 trans-uterine venographies, the authors present the normal radiological anatomy of the uterine venous vascularization and of its efferent venous drainage. They also present the most frequent variations from normal and examples of the pathologies encountered.

Adult↗

The effect of ontogenetic development on the anticonvulsant activity of midazolam.

The anticonvulsant effects and duration of protective action of midazolam against Metrazol induced seizures were studied in 528 rats aged 7,12,18,25 and 90 days. The doses of 0.025, 0.05, 0.25, 0.5 and 1.0 mg/kg were administered immediately before Metrazol (100 mg/kg in all but 18-day-old animals where 90 mg/kg were given) for detection of antimetrazol activity at all age groups. The doses of 0.05, 0.25, and/or 0.5 mg/kg were used to study the time course of the protective action of midazolam. Each experimental group consisted of eight animals. Dose-dependent antimetrazol effects of midazolam till now described only in adult animals were demonstrated at all developmental stages studied. There were no qualitative differences in these effects among age groups studied. Midazolam action was better expressed against major Metrazol seizures than against minimal Metrazol seizures. Duration of the protective action depended on the dose tested at all developmental stages, as a rule, lasted longer in young animals than in adult rats. Only quantitative changes of action were found.

Animals↗

Ketamine blocks cortical epileptic afterdischarges but not paired-pulse and frequency potentiation.

Cortical epileptiform afterdischarges (spike-and-wave rhythm) induced by low-frequency stimulation of the sensorimotor cortex were dose-dependently shortened by ketamine (10, 20 and 40 mg/kg, i.p.). Myoclonic jerking during stimulation was unaffected by ketamine whereas the same motor pattern accompanying afterdischarges was markedly suppressed by this drug. Paired-pulse as well as frequency potentiation of the cortical interhemispheric (transcallosal) responses were not significantly altered by the 40 mg/kg dose of ketamine. The two simple potentiation phenomena studied probably did not play a role in initiation of cortical epileptic afterdischarges.

Animals↗

Anticonvulsant action of lamotrigine during ontogenesis in rats.

The anticonvulsant actions of lamotrigine and phenytoin against pentylenetetrazol-induced seizures were compared in laboratory rats during ontogenesis. Both drugs (lamotrigine in doses of 2.5, 5, 10, and 20 mg/kg and phenytoin in doses of 5, 10, 30 and 60 mg/kg) were injected intraperitoneally 30 min before pentylenetetrazol. Phenytoin and lamotrigine did not affect the incidence or latency of minimal (i.e., predominantly clonic, nongeneralized) seizures, although pretreatment with phenytoin changed the pattern of this phenomenon from short (10-30-s) seizures to long-lasting 'status of minimal seizures'. Both drugs abolished selectively the tonic phase of major, i.e., generalized tonic-clonic seizures, usually without any influence on the clonic phase of these seizures. Only the highest dose of phenytoin in adult animals suppressed the generalized tonic-clonic seizures as a whole. The study did not reveal any change of action of lamotrigine or phenytoin against pentylenetetrazol-induced motor seizures throughout development.

Aging↗

Differential effects of naloxone on postictal depression.

The influence of naloxone on the duration of the postictal depression was determined in 2 seizure models in the adult rats: hippocampal afterdischarges and maximal electroshock. For testing the intensity of postictal depression 2 subsequent stimulations were used. The interstimulation intervals were 3, 5, 10 and 60 min. Using interstimulation intervals 3, 5 and 10 min there was marked depression of the afterdischarge duration. Wet dog shakes accompanying hippocampal afterdischarges were suppressed only in 3- and 5-min intervals. Naioxone (1 mg/kg i.p.) abolished the suppression of afterdischarges when 10-min interstimulation interval was used. In maximal electroshock seizures where the duration of tonic flexion and extension was determined, no postictal depression was registered nor were any effects of naloxone present. The results suggest a limited role of the mu opioid receptor system in the late phases of postictal depression following hippocampal stimulation and different effects of the mu opioid system in tonic flexion/extension and behavioral depression induced by maximal electroshock.

Animals↗

Fallopian tube recanalization by selective salpingography: an alternative to more invasive techniques?

Selective salpingography was used in a total of 64 patients, engaged in evaluation for infertility and in whom standard hysterograms showed no tubal passage of contrast medium. Fallopian tube catheterization was successful in 92% of the cases; a peritoneal spill of contrast medium was obtained in 74% of the cases by manual injection. Recanalization of an obstructed oviduct was successful in 61% of the cases. Thus, after the procedure, 82% of the patients had at least one patent tube. We conclude that selective tubal catheterization, and recanalization when needed, should be included in the therapeutic procedures for tubal infertility, prior to in-vitro fertilization or tubal microsurgery.

Adult↗

Influence of phenobarbital on ECoG phenomena induced by metrazol in rats during ontogenesis.

Effect of phenobarbital (PhB, 20 and/or 40 mg/kg) on epileptic ECoG phenomena induced by metrazol was studied in acute experiments in rats aged 7, 12, 18, 25 and 90 days. Fractionated administration of metrazol (20 mg/kg i.p. each 300 s) was used to quantify the effects of PhB. First signs of metrazol action (sharp elements and/or rhythmic metrazol activity) were not reliably influenced by PhB. On the contrary, the latency of the first EEG seizures as well as of the first generalized EEG seizures was prolonged and thus a dose necessary for their elicitation was increased in all age groups. These differences reached statistical significance in 12-, 18- and 25-day-old rats. A lack of effect of PhB against the rhythmic metrazol activity supports the adequacy of this activity as a model of human absences. Differences between the development of antiepileptic and hypnotic effects of PhB (described earlier) suggest two different mechanisms of action.

Aging↗

Effects of clonazepam on picrotoxin-induced convulsions.

The convulsant effects of four doses of picrotoxin (PX)-2, 3, 4, and 6 mg/kg s.c.-were evaluated in the first part of the study. The 4-mg/kg dose, which elicited minimal seizures in all animals, generalized tonic-clonic (major) seizures in 75% of rats and fatal outcome in 69% of rats, was chosen for the second part, i.e. for testing the anticonvulsant action of clonazepam (Rivotril Roche, 0.1 or 1 mg/kg i.p.). Clonazepam exhibited a dose-dependent action against PX-induced seizures, being more efficient against major than against minimal seizures.

Animals↗

Morphological changes of the presynaptic and postsynaptic element in excitatory synapses during kindling.

In a previous study of a kindling model using stimulation of the entorhinal cortex we found a redistribution of synaptic vesicles into the close vicinity of the active zone of synapses of Type I (Gray 1959) in the hippocampal gyrus dentatus. In this paper, ultrastructural studies of the same model are being continued using planimetry of the synaptic apparatus. A significant increase of the postsynaptic apparatus, area enlargement by 53%, increase of the perimeter by 28% and shape irregularity are being reported. No changes in shape or in size have been demonstrated in presynaptic structures or in the morphology of presynaptic mitochondria. These findings are discussed in relation to increased functional readiness of the synapses as signs of active reconstruction of the synaptic apparatus.

Animals↗

Antimetrazol action of two potential anticonvulsants, CM 40907 and SR 41378, in immature rats.

The action of two potential anticonvulsants, CM 40907 (10-50 mg/kg i.p.) and SR 41378 (1.25-20 mg/kg i.p.) against metrazol-induced seizures was studied in rats 7, 12, 18 and 25 days old. Two types of motor seizures--minimal, clonic and major, generalized tonic-clonic--were elicited by a 100-mg/kg dose of metrazol (s.c.) and their incidence and latency were evaluated. The severity of seizures was expressed as a score on a 5-point scale. Dimethylsulfoxide, an organic solvent, exhibited anticonvulsant action only in doses far exceeding those used for dissolving the two anticonvulsants. Both drugs suppressed minimal as well as major seizures in all age groups studied in a dose-dependent manner, SR 41378 being approximately four times more potent than CM 40907. The latencies could be measured only in animals given low doses of anticonvulsants. CM 40907 did not change the latencies whereas SR 41378 prolonged them. The severity of seizures was decreased again in a dose-dependent manner. There were only minor changes in the efficacy of CM 40907 among the four age groups. On the contrary, SR 41378 exhibited an extreme efficacy in 7-day-old rat pups, where even the 1.25 mg/kg dose significantly decreased the incidence and severity of seizures. The efficacy in the remaining three age groups was approximately at the same level as in adult rats.

Animals↗

Influence of phenytoin and valproate on thalamocortical evoked potentials and their paired-pulse potentiation.

The action of phenytoin and valproate on thalamocortical responses was studied in adult rats. Single responses were not influenced by either drug. Paired-pulse potentiation of the initial components (first positive and first negative) observed with intervals from 50 to 200 ms under control conditions was abolished by phenytoin (60 mg/kg i.p.) but only moderately influenced by valproate (400 mg/kg i.p.). Paired-pulse potentiation of thalamocortical phenomena cannot be put into connection with the generation of the spike-and-wave rhythm.

Action Potentials↗

Ovarian consequences of the transient interruption of combined oral contraceptives.

The combined oral contraceptive pill is an efficient means of contraception. It acts at different levels of the genital tract. Despite its efficiency, it is universally suggested that patients take the pill at regular daily intervals. Little attention has been given to the question of what happens if you miss the pill one day or more. A study was undertaken to evaluate the consequences of pill misses at different times of the cycle. Forty-seven young, healthy, normally menstruating patients voluntarily enrolled. All were given Cilest (ethinyl estradiol 35 micrograms and norgestimate 250 mg, Cilag France) for 21 days without any misses. Then, after a 7-day interval, they were prescribed one (group 1), two (group 2), three (group 3) or four days of pill misses, to occur respectively on day 1 (group a), 6 (group b), 12 (group c) or 18 (group d) of a new 21 day cycle; supplementary contraceptive means were recommended. Four patients had no miss prescribed and served as controls. Ovarian function was evaluated with daily estrogen measurements (E1 + E2 enzymatic dosage, BioMérieux, France) and ultrasound examinations. When required, because of significant increase in estrogen or because of follicular growth detected on ultrasound, LH and progesterone were measured. None of the patients experienced a normal ovulation. Four patients (1 control, 1 from group 2a, and 2 from group 3a) had a significant increase in estrogen levels and had a follicular image on ultrasounds. One of them (group 3a) had a follicular rupture, but none had a LH surge or increase in progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗