Search PubMed⌕ Search

Biomedical subjects

P Mares

Publications and source records attributed to P Mares.

At least 127 records · Page 7Linked to original sources
PubMed1996

Moderate anticonvulsant action of baclofen does not change during development.

The possible anticonvulsant action of baclofen, a GABAB (gamma-aminobutyric acid) receptor agonist, was studied using two types of motor seizures (minimal, clonic and generalized tonicoclonic) elicited by pentylenetetrazol in adult rats and rat pups, 7, 12, 18, and 25 days old. If baclofen was administered intraperitoneally (only in 12- and 25-day-old rats), no effect could be observed in 25-day-old animals. In 12-day-old rats, only the 12-mg/kg dose led to a prolongation of the generalized tonicoclonic seizure latency. Subcutaneous administration of baclofen (3, 6, or 12 mg/kg 30 min before subcutaneous pentylenetetrazol injection) led to a moderate action against the tonic phase of generalized tonicoclonic seizures: the tonic phase of hind limbs was significantly suppressed in all age groups, whereas total suppression of the tonic phase was only outlined. Minimal, i.e., clonic, seizures with preserved righting ability were not influenced by baclofen. The conclusion could be made that the anticonvulsant action of baclofen is dependent on the model of seizures used and that there is no change of baclofen action against pentylenetetrazol-induced seizures during postnatal development in rats.

Animals↗
PubMed1996

The action of pramiracetam on consequences of hypobaric hypoxia is only moderate.

The possible protective action of pramiracetam, a pyrrolidinone nootropic drug, against hypobaric hypoxia was studied in two age groups of immature rats with implanted electrodes. Epileptic afterdischarges induced by hippocampal stimulation were used as a measure of hypoxic damage. Pramiracetam did not substantially change these afterdischarges in 12- and 18-day-old rat pups which were not exposed to hypoxia. Hypobaric hypoxia (simulated altitude of 7000 m for one hour) led to prolongation of the first afterdischarge in both age groups. Pramiracetam did not influence this prolongation in 12-day-old rats. The first afterdischarge was shortened significantly in 18-day-old animals but not to the level of rats not exposed to hypoxia. The afterdischarges elicited by repeated stimulations (four times at 10 min intervals) did not differ in pramiracetam-treated and control rats.

Animals↗
PubMed1995

Kainate/AMPA receptor antagonists are anticonvulsant against the tonic hindlimb component of pentylenetetrazol-induced seizures in developing rats.

Non-NMDA receptor antagonists CNQX, DNQX, and NBQX (10-40 mg/kg IP) were tested against pentylenetetrazol-induced (100 mg/kg SC) seizures in 7 to 90-day-old rats. All three drugs significantly decreased the incidence of tonic hindlimb component of tonic-clonic pentylenetetrazol seizures, often in favor of increased incidence of forelimb tonus throughout development. In addition, in 7 to 25-day-old rats, DNQX and NBQX decreased the severity of seizures due to a decrease in total incidence of the tonic component of tonic-clonic seizures compared to age-matched controls. However, neither drug was able to consistently suppress the incidence or increase latency to onset of clonic and tonic-clonic pentylenetetrazol seizures. The data suggest that, during development, non-NMDA receptor transmission may play a role in the generation of the tonic component, but not in the generation of other components of pentylenetetrazol-induced seizures.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Suppression of cortical epileptic afterdischarges by ketamine is not stable during ontogenesis in rats.

Anticonvulsant action of ketamine, a noncompetitive NMDA antagonist, was studied in three groups of immature rats (12-, 18-, and 25-day-old) using cortically elicited epileptic afterdischarges (ADs) as a model. Rats with implanted electrodes were used, so that EEG and motor phenomena could be recorded. Stimulation (bipolar pulses of 1-ms duration and 8-Hz frequency) lasting 15 s was repeated four times with intervals of 10 min. Ketamine was administered IP 5 min after the first AD in doses of 5, 10, 20, or 40 mg/kg. Control groups did not receive any drug. Ketamine shortened ADs and suppressed motor correlates of stimulation as well as of ADs in a dose-dependent manner in 12- and 25-day-old rats. No significant changes were observed in 18-day-old animals, demonstrating thus a rather complicated development of anticonvulsant action of ketamine. Not only NMDA antagonism, but also other possible effects of ketamine must be taken into account.

Animals↗
PubMed1995

Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis: III. The action of kynurenic acid and glutamic acid diethylester.

N-methyl-D-aspartate (NMDA) receptor antagonists are anticonvulsant drugs with specific activity against tonic-clonic pentylenetetrazol-induced seizures. However, they do not affect clonic seizures with preserved righting reflexes. In these experiments, we tested the anticonvulsant activity of strychnine-insensitive glycine receptor (at the NMDA site) antagonist kynurenic acid and nonspecific excitatory amino acid receptor antagonist glutamic acid diethylester (GDEE) in the pentylenetetrazol-induced seizure model in developing rats 7, 12, 18, 25, and 90 days old. Control rats were injected with pentylenetetrazol (100 mg/kg subcutaneously). Other rats were pretreated either with kynurenic acid (40, 80, or 240 mg/kg IP) or with GDEE (0.48-480 mg/kg IP), followed by pentylenetetrazol (100 mg/kg). In very young rats (7 and 12 days), both kynurenic acid and GDEE increased the incidence of clonic seizures, whereas the occurrence of tonic-clonic seizures was suppressed or delayed compared to controls. This effect is very similar to the anticonvulsant action of the competitive and noncompetitive NMDA receptor antagonists. In adult rats, the pretreatment with rather higher doses of kynurenic acid or GDEE suppressed or delayed clonic seizures as well as tonic-clonic seizures. Both drugs also induced behavioral side effects: repetitive orientation, wet dog shakes, and frequent jumping. Our data show that there are only weak and nonconsistent age-specific anticonvulsant effects resulting from the blockade of strychnine-insensitive glycine receptor often associated with serious side effects, thus decreasing chances to develop effective antiepileptic treatment in this drug class.

Age Factors↗
PubMed1995

Differences between immature and adult rats in brain glutamate decarboxylase inhibition by 3-mercaptopropionic acid.

Glutamate decarboxylase (EC 4.1.1.15, GAD) activity was studied in the brain of 12-day-old and adult rats treated with 3-mercaptopropionic acid (3-MPA), an inhibitor of GAD competitive with glutamate. Control GAD activity in the brains of immature animals (91.8 +/- 18.2 nmol/h/mg of protein) was lower than that of the adult rats (228 +/- 37.5 nmol/h/mg of protein). Brain GAD inhibition in adult rats was 58% at the onset of seizures (9 min on the average after administration of 70 mg 3-MPA/kg). At the same time, 3-MPA-treated young rats exhibited 76% inhibition of GAD despite the fact that at 9 min these animals were not yet having seizures. At the onset of seizures (19 min after 3-MPA on the average) their GAD activity remained at the same level. The difference between the groups was not related to the presence of the coenzyme pyridoxal-5'-phosphate in the enzyme assay. The inhibition of GAD by 3-MPA in vitro in the immature and adult brains was similar (Ki at 5.1 microM and 4.8 microM concentrations of 3-MPA, respectively). Identical values were found for Km of GAD (at 4.5 mM concentration of L-glutamate). Calculations based on the results suggest that 3-MPA enters the immature brain more easily than the brain of the adult animals. While GAD inhibition by 3-MPA is the primary cause of seizures, their onset is influenced by other factors, in which the immature brain differs from the adult one and which may include less sensitivity to GABA decrease due to relative overactivity of the GABA system.

3-Mercaptopropionic Acid↗
PubMed1995

Effects of dobutamine versus insulin on cardiac performance, myocardial oxygen demand, and total body metabolism after coronary artery bypass grafting.

OBJECTIVE: The purpose was to study whether the hemodynamic benefit of a catabolic catecholamine (dobutamine) induces a certain oxygen cost for the myocardial energy demand and whether this effect would be less pronounced if an anabolic intervention, such as the administration of insulin, was used. DESIGN: A prospective and randomized study. SETTING: A university hospital. PARTICIPANTS: Investigation of two comparable groups of cardiac patients. INTERVENTIONS: The interventions were postoperative infusions of dobutamine, 7 micrograms/kg/min, and of insulin, 1.5 U/kg/h, respectively, over a period of 30 minutes. MEASUREMENTS AND MAIN RESULTS: The effects of the interventions were measured using parameters relating to cardiac work and myocardial oxygen demand. Moreover, parameters relating to total body metabolism were also recorded. In the dobutamine group, cardiac index (CI) and left ventricular stroke work index (LVSWI) increased significantly (p < 0.05) during therapy by 30% and 40%, respectively. Cardiac effort index (CEI) and tension time index (TTI) also increased (p < 0.05) during therapy by 41% and 30%, respectively. However, in the insulin group, CI and LVSWI also increased (p < 0.01 and p < 0.05) during therapy, although to a lesser extent (16% and 14%), but CEI and TTI did not change at all during therapy. Total body CO2 production (VCO2) and O2 consumption (VO2) in the dobutamine group increased (p < 0.05) during therapy by 9% and 11%, respectively, whereas in the insulin group only CO2 production increased (p < 0.05) by 13%. O2 consumption remained unchanged in this group. CONCLUSIONS: It is concluded that dobutamine as well as insulin administration increase cardiac performance. However, in contrast to dobutamine, insulin does not appear to increase myocardial oxygen demand. Therefore, the anabolic insulin administration may represent a more economic pattern of energy-consuming hemodynamic intervention than does the catabolic catecholamine administration.

Adult↗
PubMed1995

Seizures induced by homocysteine in rats during ontogenesis.

We studied the convulsant action of homocysteine in 211 immature and adult Wistar albino rats. Homocysteine elicited minimal, predominantly clonic, and major generalized tonic-clonic seizures at six different developmental stages, from 7 days to adulthood. Nevertheless, some age-dependent differences in the seizure pattern were apparent. Minimal seizures in immature rats lasted < or = 20 min, thus representing an epileptic status, whereas in adult animals these seizures were much shorter, lasting only < or = 40 s. In addition, flexion seizures were observed in 7- and 12-day-old rats, only rarely in 15- and 18-day-old animals, and never in the 25-day-old and adult rats. ECoG recordings demonstrated a nearly isoelectric pattern during homocysteine-induced seizures in 7- and 12-day-old rat pups. In older rats, spikes or sharp waves were recorded, but precise electroclinical correlations were poor. The greater sensitivity of younger animals to kainic acid (KA) and N-methyl-D-aspartate (NMDA), as reported previously, was not evident in the case of homocysteine-induced seizures. This observation, together with a different behavioral pattern, suggests that homocysteine cannot be considered a simple agonist of the kainate or NMDA type of excitatory amino acid receptors. The exact mechanism of the convulsant action of homocysteine, both during development and in adulthood, remains to be clarified.

Animals↗
PubMed1995

Different postnatal development of convulsions and lethality induced by strychnine in rats.

The convulsant action of strychnine was studied in 310 male albino rats, aged 3 to 25 days. Doses of 0.25-4 mg/kg were administered intraperitoneally and the animals were observed for 30 min. Generalized tonic-clonic seizures involving also tonic hindlimb extension occurred in all age groups. The convulsant effects of strychnine increased from day 3 to day 18, and decreased again from day 25, as indicated by the incidence and latencies of seizures. Lethal effects did not occur before day 12. Hyperactivity was seen as the first sign of strychnine action in rats during the first week of life, automatisms predominating in 18-day-old animals. Electroencephalographic study in 30 rat pups with implanted electrodes demonstrated an extremely poor electro-clinical correlation.

Aging↗
PubMed1995

[Chronic thromboembolic pulmonary hypertension and its treatment with pulmonary thrombendarterectomy].

Chronic recurrent pulmonary embolism can lead to extensive pulmonary hypertension by obstruction of the pulmonary vessels. Pulmonary thrombendarteriectomy is a new approach to normalizing the elevated pulmonary vascular resistance by removal of the adsorbed thrombi. Between 1992 and 1994 we have operated on 8 patients aged between 34 and 62 years. The first patient died due to extensive reperfusion edema, all others showed significant improvement in hemodynamic parameters (mean pulmonary artery pressure preop. 63 +/- 5 mmHg; postop. 30 +/- 9 mmHg; Cardiac Index preop. 2.0 +/- 0.2 l/min; postop. 3.5 +/- 0.5 l/min; pulmonary vascular resistance preop. 1169 +/- 75 dyn; postop. 228 +/- 55 dyn) and exercise performance (NYHA classification preop. III-IV, postop. I-II). Pulmonary thrombendarteriectomy represents an efficient method to normalize elevated pulmonary pressure and exercise performance of patients with far-advanced chronic thromboembolic pulmonary hypertension.

Adult↗
PubMed1994

[Differential diagnosis of round opacities after lung transplantation].

Incidence, aetiology, diagnosis and treatment of round lesions in the lungs were analysed in 64 patients after lung transplantation (33 men, 31 women; mean age 45 [21-68] years; postoperative survival > 2 weeks). These lesions were found in 8 patients 1-10 months (median of 5.8 months) after the transplantation, singly in two, multiple in six. In six patients it was an incidental finding, further elucidated by computed tomography or fine-needle biopsy. The aetiology varied from B-cell "lymphoma" (posttransplant lymphoproliferative disorder-PTLD) in three patients, aspergilloma in two, and bacterial abscess in one. Two patients died of septicaemia (Aspergillus; Pseudomonas aeruginosa/Staphylococcus aureus), while four had a full remission. The solitary lesions disappeared without specific treatment in 2-3 weeks. If round lesions are noted after lung transplantation, rapid histological and microbiological diagnosis and aggressive treatment are necessary to combat an otherwise high death-rate. PTLD and infection (bacterial or mycotic) are the most frequent causes.

Adult↗
PubMed1994

Developmental changes of ketamine action against epileptic afterdischarges induced by hippocampal stimulation in rats.

Action of ketamine (5-40 mg/kg) was tested against electrically induced hippocampal afterdischarges (four stimulations in one session; 8 Hz, 15 s) in rats 7, 12, 18, 25 and 90 days old. In control sessions, there was either stable afterdischarge (AD) duration and wet dog shakes (WDS) number or there was an increase in ADs' duration with repeated stimulations. Ketamine had dose-dependent and age-dependent effects. In 7-18-day-old rats, ketamine suppressed better WDS number than AD duration, with nearly absent action on AD duration in 18-day-old animals. Ketamine was equipotent for both phenomena in 25-day-old rats and, in contrast, it decreased more AD duration than WDS number in 90-day-old rats. The data suggest a differentiation induced by ketamine in the expression of motor and electrographic phenomena of the experimental seizures.

Age Factors↗
PubMed1994

Convulsant action of a benzodiazepine receptor agonist/inverse agonist Ro 19-4603 in developing rats.

An inverse benzodiazepine receptor agonist Ro 19-4603, administered intraperitoneally, was found to induce two types of motor seizures, i.e. minimal, predominantly clonic and major, generalized tonic-clonic, in rats at all developmental stages studied (7, 12, 18 and 25 days old). The developmental profile of the two types of seizure was different. Minimal seizures could be induced easily in the two youngest groups, whereas there were no marked differences in the induction of major seizures between the age groups. A lethal outcome was more common in 18- and 25-day-old rats than in younger animals. The convulsant action of the benzodiazepine agonist/inverse agonist Ro 19-4603 shows only quantitative changes during post-natal development in the rat.

Aging↗
PubMed1994

Decrease of extracellular catecholamine content in the vicinity of cortical penicillin-induced epileptogenic focus: voltammetric study in the rat.

Differential pulse voltammetry with carbon-fibre microelectrodes was used in chloralhydrate-anaesthetized rats to test the influence of the penicillin-G-Na (PNC)-induced (topical application, approximately 2000 IU) epileptic activity on the catecholamine content (catechol-oxidative current, CA.OC) in the parietal cortex. In the experimental group (n = 4) after PNC a nonlinear CA.OC lowering was observed; this decrease during the first 10 min was faster than in the control group (n = 4). Significantly different values were observed from the 4th min after application. The best fit for this experimental curve gave the logarithmic function (f(t) = a+b.ln(t), a = 105.8, b = -10.6) with regression coefficient r = 0.98. From the 12th min after PNC application until the end of the experiments (54th min) CA.OC values ranged from 78% to 84% of the control group.

Anesthesia↗