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Biomedical subjects

P Mares

Publications and source records attributed to P Mares.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2001

[The allergic pregnant woman].

Drugs administrated to pregnant women must be carefully monitored. Prevention of dietary sensitization in foetus via the mother is still discussed. However, it must not induce any dietary deficiency to both the mother and the foetus. Environmental prevention is also controversial. Asthmatic pregnant women must be treated because under- or non treatment is more dangerous for both the woman and the foetus compared to eventual drug side effect. Asthma must be treated with inhaled glucocorticosteroid in order to be stabilized because giving birth is the only moment which can not be interrupted. Antihistamine-H1 which can be used during pregnancy are dexchlorpheniramine for the first and second third and cetirizine during the last third of the pregnancy.

Abnormalities, Drug-Induced↗
PubMed2000

Nonconvulsive status epilepticus in rats: impaired responsiveness to exteroceptive stimuli.

An animal model of human complex partial status epilepticus induced by lithium chloride and pilocarpine administration was developed in our laboratory. The objective of the study was to provide a detailed analysis of both ictal and postictal behavior and to quantify seizure-related morphological damage. In order to determine the animal's responsiveness to either visual or olfactory stimuli, adult male rats were submitted to the following behavioral paradigms: the object response test, the social interaction test, and the elevated plus-maze test. The rotorod test was used to evaluate motor performance. Two weeks after status epilepticus, brains were morphologically examined and quantification of the brain damage was performed. Profound impairment of behavior as well as responsiveness to exteroceptive stimuli correlated with the occurrence of epileptic EEG activity. When the epileptic EEG activity ceased, responsiveness of the pilocarpine-treated animals was renewed. However, remarkable morphological damage persisted in the cortical regions two weeks later. This experimental study provides support for the clinical evidence that even nonconvulsive epileptic activity may cause brain damage. We suggest that the model can be used for the study of both functional and morphological consequences of prolonged nonconvulsive seizures.

Animals↗
PubMed2000

Barriers in cancer pain management.

Inadequate pain management of cancer patients remains a striking problem despite impressive scientific progress in the knowledge of the pathophysiology, pathogenesis and therapy of pain. Our paper focuses on three topics: 1. physician-related barriers, 2. patient-related barriers, and 3. society- and tradition-related barriers as well as government regulations. It is imperative to overcome these barriers, especially since legal regulations for pain management were embodied into statutory regulations in Austria two years ago.

Analgesics, Opioid↗
PubMed2000

Behavioral and metabolic changes in immature rats during seizures induced by homocysteic acid: the protective effect of NMDA and non-NMDA receptor antagonists.

Bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA) (600 nmol on each side) to immature 12-day-old rats induced generalized clonic-tonic seizures, recurring frequently for at least 90 min, with a high rate of survival. Electrographic recordings from sensorimotor cortex, hippocampus, and striatum demonstrated isolated spikes in the hippocampus and/or striatum as the first sign of dl-HCA action. Generalization of epileptic activity occurred during generalized clonic-tonic seizures, but electroclinical correlation was very low; dissociation between EEG pattern and motor phenomena was common. Seizures were accompanied by large decreases of cortical glucose and glycogen and by approximately 7- to 10-fold accumulation of lactate. ATP and phosphocreatine (PCr) levels remained unchanged even during longlasting (3 h) convulsions. Metabolite levels became normalized during the recovery period (24 h). The examination of the effect of selected antagonists of NMDA [AP7 (18.5 and 37 mg/kg, respectively), MK-801 (0.5 mg/kg)] and non-NMDA [NBQX (10, 15 and 30 mg/kg, respectively)] receptors revealed that seizures could be attenuated or prevented (depending on the dose employed) by antagonists of both NMDA and non-NMDA receptors, as evaluated not only according to the suppression of behavioral manifestations of seizures, but also in terms of the protection of metabolite changes accompanying seizures. All antagonists employed, when given alone in the same doses as those used for seizure protection, did not influence metabolite levels, with the exception of increased glucose concentrations. Furthermore, the pronounced anticonvulsant effect could be achieved by the combined treatment with low subthreshold doses of NMDA (AP7) and non-NMDA (NBQX) receptor antagonists, which may be of potential significance for a new approach to the treatment of epilepsy.

2-Amino-5-phosphonovalerate↗
PubMed2000

Interstrain differences in cognitive functions in rats in relation to status epilepticus.

Cognitive functions of Long Evans (N=30) and Wistar rats (N=32) were compared using a Morris water maze. Under control conditions the Long Evans rats were more efficient in this test, their average escape latency after 5 days of training (6.4+/-0.1 s, mean+/-S.E.M.) was significantly shorter than that of the Wistar rats (11.0+/-0.1 s). When the training was completed seizures were induced by an intraperitoneal injection of pilocarpine (330 mg/kg in the Long Evans strain and 350 mg/kg in the Wistar rats) 30 min after pretreatment with N-methylscopolamine (1 mg/kg i.p.). Clonazepam (1 mg/kg i.p.) was used to interrupt clonic seizures after 2 hours of continuous activity. Approximately one quarter of rats in both strains did not develop seizures. Severe convulsive status epilepticus was common in Long Evans rats (23 out of 30). In contrast, only 12 Wistar rats generated convulsive status epilepticus and the same number of animals exhibited only bursts of motor seizures separated by periods without convulsions (temporary seizures). Mortality after pilocarpine-induced status epilepticus was considerably higher in the Long Evans rats than in the Wistar rats. After a latency of 2-3 weeks spontaneous recurrent seizures appeared in all animals surviving status. Cognitive memory was tested during the 'silent period' between status and recurrent seizures. The Long Evans rats were unable to find the platform at the 3rd and 6th day after status but then their performance rapidly improved. The performance of the Wistar rats undergoing status epilepticus was seriously deteriorated and it never normalized, whereas the animals with temporary seizures exhibited only a transitory marginal prolongation of latencies. The hippocampal formation was damaged by status epilepticus in rats of both strains - the Long Evans rats exhibited more extensive damage of subfields CA1 and CA3, whereas in the Wistar rats a complete destruction of hilar neurons was observed in addition to partial CA1 and CA3 damage.

Animals↗
PubMed2000

Convulsant action of systemically administered glutamate and bicuculline methiodide in immature rats.

Developmental changes of transport of drugs into the brain play an important role in ontogenetic neuropharmacology. Two convulsant drugs with different mechanisms of action (glutamate and bicuculline methiodide) were chosen to demonstrate these changes in developing rats. High dose of glutamate (4 g/kg i.p.) induced both minimal (predominantly clonic) and generalized tonic-clonic seizures in rat pups 7, 12, and 18 days old. In contrast, seizures were only exceptionally observed in 25 and 90 days old animals. Bicuculline methiodide was administered in a dose of 2 or 20 mg/kg i.p. The first sign of bicuculline methiodide action in all age groups was represented by automatisms, a symptomatology never seen after bicuculline hydrochloride administration. Minimal seizures were induced in 12-day-old and in a few 18-day-old and adult rats. Generalized seizures were common after the higher dose of bicuculline methiodide in 7- and 12-day-old rat pups, seldom in 18-day-old ones and never seen in 25-day-old and adult animals. Both glutamate and bicuculline methiodide enter the brain in immature rats but the mechanisms are probably different - glutamate is transported actively through the blood-brain barrier whereas no similar system is known for bicuculline methiodide.

Age Factors↗
PubMed2000

Proconvulsant effect of aminophylline on cortical epileptic afterdischarges varies during ontogeny.

Effect of aminophylline on epileptic afterdischarges (ADs) induced repeatedly by rhythmic electrical stimulation of sensorimotor cortical area was studied in rat pups 12, 18 and 25 days old. The proconvulsant effect of aminophylline (50 and/or 100 mg/kg i.p.) was more expressed in 12- and 18-day-old rats than in the oldest group. In 12-day-old rat pups there was an enormous increase of transition of the spike-and-wave type of ADs into the second, limbic type, a situation observed only exceptionally under control conditions. A prolongation of ADs was related to this transition (limbic ADs are always longer than spike-and-wave ones). Eighteen-day-old rats exhibit this transition less frequently but a marked prolongation of spike-and-wave ADs was recorded in a part of these animals forming a pattern of status lasting some tens of minutes. Aminophylline led only to a transient prolongation of spike-and-wave ADs in the oldest group. The transition into the limbic type of ADs was seen in this age group only exceptionally what is in contrast to age-matched controls in which this transition is common. The effect of aminophylline on cortical ADs which is most marked in the youngest group changes qualitatively during postnatal development.

Aminophylline↗
PubMed2000

Pulsatility does not change cerebral oxygenation during cardiopulmonary bypass.

BACKGROUND: To determine the effect of pulsatility during cardiopulmonary bypass (CPB) on cerebral oxygenation, we measured oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and oxidised cytochrome aa3 (CtO2) with near-infrared spectroscopy (NIRS) in 14 patients electively scheduled for cardiac surgery. METHODS: Cerebral oxygenation was measured during steady state CPB at a core temperature of 32 degrees C. Non-pulsatile flow and pulsatile flow were performed for 10 min each. RESULTS: After 14 min of CPB, HbO2, Hb and CtO2 were significantly below prebypass values. HbO2 and CtO2 did not alter with changing flow patterns. Hb significantly increased both during the period of nonpulsatile (median: -0.7 vs. 0.25 micromol/l; P<0.05) and pulsatile flow (median: 0.25 vs. 0.5 micromol/l; P<0.001). This increase was independent of flow pattern. CONCLUSIONS: Neither oxygenated haemoglobin, nor intracellular oxygenation, represented by CtO2, indicated a beneficial effect of pulsatile perfusion during hypothermic CPB. These results, however, are only valid for short time effects within 10 min before rewarming from CPB and patients without flow-limiting stenoses of the carotid artery.

Brain↗
PubMed2000

Dissociated overexpression of cathepsin D and estrogen receptor alpha in preinvasive mammary tumors.

The role of estrogen as a promoter agent of sporadic breast cancer has been considered by assaying, in benign breast disease (BBD) and in situ carcinomas (CIS), 2 markers, the estrogen receptor alpha (ERalpha) and cathepsin D (cath-D) involved in estrogen action on mammary tissue. ERalpha and cath-D were assayed by quantitative immunohistochemistry using an image analyzer in 170 lesions of varying histological risk (94 BBD and 76 CIS), and in "normal" glands close to these lesions. The ERalpha level increased significantly in proliferative BBD with atypia (P < .001), in non-high-grade CIS (P < .001), and in adjacent "normal" glands. ERalpha level was decreased in high-grade ductal CIS (DCIS) and also in adjacent "normal" glands. Cath-D level increased in ductal proliferative BBD (P < or = .01) and in high-grade DCIS (P < or = .003), but not in the other lesions. After menopause, ERalpha level was increased (P = .012) but not cath-D level. According to Mac Neman test, the high-grade DCIS were predominantly ERalpha negative and cath-D positive (P = .0017), and the other CIS were predominantly ERalpha positive and cath-D negative (P = .0002). The 2 markers are overexpressed early in premalignant lesions, but independently. This dissociation suggests a branched model of mammary carcinogenesis involving 1 estrogen-independent pathway with high cath-D and low ERalpha levels (including high-grade DCIS) and 1 estrogen-dependent pathway, with high ERalpha level (including proliferative BBD with atypia and low-grade DCIS). We propose that ERalpha-negative breast cancers may develop directly from high-grade DCIS and that ERalpha assay in preinvasive lesions should be considered in prevention trials with antiestrogens.

Adult↗
PubMed2000

Pulmonary artery thromboendarterectomy: a comparison of two different postoperative treatment strategies.

UNLABELLED: Pulmonary artery thromboendarterectomy (PTE) is a potentially curative surgical procedure for chronic thromboembolic pulmonary hypertension. It is, nevertheless, associated with considerable mortality caused by postoperative complications, such as reperfusion pulmonary edema (RPE) (i.e., pulmonary infiltrates in regions distal to vessels subjected to endarterectomy) and right heart failure (RHF). However, there are no reports about the influence of different postoperative treatment strategies on complications and mortality. Therefore, we compared two different treatment strategies. In Group I (n = 33), positive inotropic catecholamines and vasodilators were avoided during termination of cardiopulmonary bypass (CPB) and thereafter, and mechanical ventilation was performed with low tidal volumes < 8 mL/kg, duration of inspiration:duration of expiration = 3:1, and peak inspiratory pressures < 18 cm H(2)O. In Group II (n = 14), positive inotropic catecholamines and vasodilators were regularly used for termination of CPB and thereafter, and ventilation was performed with high tidal volumes (10-15 mL/kg) and peak inspiratory pressures up to 50 cm H(2)O. Hemodynamics, the incidence of RPE and RHF, duration of ventilation, morbidity, and mortality were recorded. Cardiac index was comparable before surgery (2.11 +/- 0.09 vs 2.08 +/- 0.09 L. min(-1). m(-2)) and 20 min after CPB (2.26 +/- 0.09 vs 2.60 +/- 0.20 L. min(-1). m(-2)). RPE occurred in 6.1% (Group I) versus 14.3% (Group II), and RHF was observed in 9.1% (Group I) versus 21.4% (Group II). Mortality was 9.1% (Group I) versus 21.4% (Group II). Thus, the avoidance of positive inotropic catecholamines and vasodilators in combination with nonaggressive mechanical ventilation after PTE was associated with a low incidence of RPE, RHF, duration of ventilation, and mortality after PTE. IMPLICATIONS: The avoidance of positive inotropic catecholamines and vasodilators in combination with nonaggressive mechanical ventilation was associated with a low incidence of reperfusion pulmonary edema and/or right heart failure after pulmonary artery thromboendarterectomy.

Adult↗
PubMed2000

Inhaled nitric oxide reduces pulmonary vascular resistance more than prostaglandin E(1) during heart transplantation.

UNLABELLED: Heart transplantation in patients with increased pulmonary vascular resistance is often associated with postbypass right heart failure. We therefore compared the abilities of prostaglandin E(1) (PGE(1)) and inhaled nitric oxide to reduce pulmonary vascular resistance during heart transplantation. Patients undergoing orthotopic heart transplantation for congestive heart failure were randomly assigned to either a PGE(1) infusion at a rate of 8 ng. kg. (-1)min(-1) starting 10 min before weaning from cardiopulmonary bypass (CPB) (n = 34) or inhalation of 4 ppm nitric oxide starting just before weaning from CPB (n = 34). Both treatments were increased stepwise, if necessary, and were stopped 6 h postoperatively. Hemodynamic values were recorded after the induction of anesthesia, 10 and 30 min after weaning from CPB, and 1 h and 6 h postoperatively. Immediately after weaning from CPB, pulmonary vascular resistance was nearly halved in the nitric oxide group but reduced by only 10% in the PGE(1) group. Pulmonary artery pressure was decreased approximately 30% during nitric oxide inhalation, but only approximately 16% during the PGE(1) infusion. Six hours after surgery, pulmonary vascular resistance and pulmonary artery pressure were similar in the two groups. The ratio between pulmonary vascular resistance and systemic vascular resistance was significantly less in the nitric oxide patients at all postbypass times. In contrast, the pulmonary-to-systemic vascular resistance ratio increased approximately 30% in the patients given PGE(1). Cardiac output, heart rate, mean arterial pressure, right atrial pressure, and pulmonary wedge pressure did not differ between the groups. Weaning from CPB was successful in all patients assigned to nitric oxide inhalation; in contrast, weaning failed in six patients assigned to PGE(1) (P = 0.03). IMPLICATIONS: Nitric oxide inhalation selectively reduces pulmonary vascular resistance and pulmonary artery pressure immediately after heart transplantation which facilitates weaning from cardiopulmonary bypass.

Administration, Inhalation↗
PubMed2000

Safe and efficient emergency transvenous ventricular pacing via the right supraclavicular route.

UNLABELLED: Infraclavicular and internal jugular central venous access are techniques commonly used for temporary transvenous pacing. However, the procedure still has a considerable complication rate, with a high risk/benefit ratio because of insertion difficulties and pacemaker malfunction. To enlarge the spectrum of alternative access sites, we prospectively evaluated the right supraclavicular route to the subclavian/innominate vein for emergency ventricular pacing with a transvenous flow-directed pacemaker as a bedside procedure. For 19 mo, 17 consecutive patients with symptomatic bradycardia, cardiac arrest, or torsade de pointes requiring immediate bedside transvenous pacing were enrolled in the study. The success rate, insertional complications, pacemaker performance, and patients' outcomes were recorded. Supraclavicular venipuncture was successful in all patients, in 16 of 17 at the first attempt. Adequate ventricular pacing was achieved within 1 to 5 min (median, 2 min) after venipuncture and within 10 s to 4 min (median, 30 s) after lead insertion (</=30 s in 15 of 17 patients). The median pacing threshold was 1 mA (range, 0.7 to 2.5 mA). No procedure-related complications were recorded. Throughout the pacing period of 1538 h (median: 62 h, range, 1-280 h) two reversible malfunctions caused by inadvertent lead dislodgement after 122 and 171 h were recorded; in one patient the pacemaker had to be removed because of local infection after 14 days of pacing. We conclude that the right supraclavicular route is an easy, safe, and effective first approach for transvenous ventricular pacing and might provide a useful alternative to traditional puncture sites, even in a preclinical setting. IMPLICATIONS: Temporary transvenous cardiac pacing can yield high complication rates especially under emergency conditions. We investigated emergency pacing via the right supraclavicular access in 17 consecutive hemodynamically compromised patients and found good safety, efficacy, and a low complication rate.

Aged↗
PubMed2000

Two different anticonvulsant actions of tiagabine in developing rats.

PURPOSE: Our goal was to study the anticonvulsant action of tiagabine (TGB) at different levels of brain maturation in rats. METHODS: Wistar rats in five age groups (7, 12, 18, 25, and 90 days old) were injected intraperitoneally with TGB at doses of 0.5-32 mg/kg. Thirty minutes later, motor seizures were induced by the subcutaneous adminstration of pentylenetetrazol (PTZ) in a dose of 100 mg/kg for all of the groups except the 18-day-old rat pups, which received a 90-mg/kg dose. The incidence and latency of two types of motor seizures, minimal clonic and generalized tonic-clonic seizures (GTCSs), were evaluated, and the seizure severity was scored. The time profile of TGB action at the 8-mg/kg dose was studied in the 12-and 25-day-old rats. RESULTS: Minimal clonic seizures were reliably induced in rats 18 days old or older, and the seizures were suppressed by TGB in all of these age groups. Although TGB was very effective against this type of seizure in the 18-day-old rats, the efficacy of the drug decreased with the age of the animal. GTCSs were suppressed by TGB in the adult and 25-day-old rats, and a U-shaped dose-response curve was outlined in these two groups. The 18-and 12-day-old rat pups exhibited a selective suppression of the tonic phase of GTCSs. A mixture of these two effects was observed in the youngest group. TGB demonstrated a markedly longer action in the 12-day-old rats than in the 25-day-old rats. CONCLUSIONS: TGB exhibits anticonvulsant action against both minimal seizures and GTCSs. Ontogenetic development of these two actions is markedly different.

Age Factors↗