Search PubMed⌕ Search

Biomedical subjects

P Mares

Publications and source records attributed to P Mares.

At least 217 records · Page 12Linked to original sources

Anticonvulsant effects of clonazepam on chemically induced convulsions.

The anticonvulsant effects of two doses of clonazepam (CZP, Rivotril Roche, 0.1 and 1 mg/kg i.p.) were studied on model motor seizures induced by strychnine, bicuculline, 3-mercaptopropionic acid and metrazol in male laboratory rats (Wistar strain). In the first part the effects of different doses of the convulsants were investigated and for interaction with CZP doses were chosen after which more than 70% of the animals displayed generalized tonic-clonic convulsions (a grand mal seizure). Strychnine induced this type of seizure only: two doses (2 and 3 mg/kg s.c.) were used. CZP reduced the incidence of convulsions only after the larger dose, but plain solvent (propylene glycol, ethanol, water) was equally effective. The other substances first induced a seizure of minimal (mainly clonic) convulsions and only later a grand mal seizure. CZP was highly effective against bicuculline (3 mg/kg s.c.) and metrazol (100 mg/kg s.c.), but was less so against 3-mercaptopropionic acid. The effect on grand mal seizures was more pronounced in every case than on minimal seizures. The decisive role in the anticonvulsant effect of CZP is played by the mechanisms by which the convulsants induce epileptic manifestations. CZP is most effective against substances acting on the supramolecular complex GABA receptor (benzodiazepine receptor) chloride ionophore (bicuculline and probably metrazol).

3-Mercaptopropionic Acid↗

[Hormone therapy in the 40-year-old woman].

Hormone replacement therapy is frequently prescribed in 40-year old women because of the hormonal changes which start to occur at this age. A progestogen-only treatment is often prescribed to restore the oestrogen/progestogen balance. This treatment alone can be sufficient on the therapeutic level as well as on the contraceptive level. However, in order to minimize the risks of such a treatment, a non-androgenic derivative must be chosen. There are no contra-indications for oral contraceptives in women who are over 40 years old on condition that the risk factors are not cumulated. Here also, it is advisable to use the lowest possible dose of steroids which has an adequate contraceptive action and enables a good cycle control. As for oestrogens, the minimum ethinyloestradiol dose must be sought. For the progesterone dose, a non-androgenic derivative should be chosen. The GnRH agonists may have some indications, but their exact place is yet to be defined.

Adult↗

[The effect of ethosuximide on epileptic after-discharges induced by thalamic stimulation in young laboratory rats].

An influence of ethosuximide on thalamically induced epileptic afterdischarges was studied in 47 rats aged 12 and 18 days. An afterdischarge formed by spike-and-wave rhythm was induced only in 18-day-old rats. It exhibited a tendency to progressive prolongation with repeated stimulations (with 15 min intervals). Ethosuximide in a dose of 125 mg/kg i.p. immediately after the first afterdischarge did not change the duration of subsequent afterdischarges. The second type of epileptic afterdischarge formed by spikes and/or serrated waves could be induced in both age groups studied. Ethosuximide even worsened the tendency to progression of epileptic afterdischarges in 12- as well as 18-day-old animals. Ethosuximide did not exhibit an anticonvulsant action against the spike-and-wave afterdischarge in 18-day-old rats. On the contrary, it aggravated the course of progressive changes with repeated stimulations in both age groups.

Aging↗

Are there morphological changes in presynaptic terminals of kindled rats?

Excitatory synapses were studied in the hippocampal dentate gyrus ipsilateral to the stimulated entorhinal cortex in fully kindled rats 2 weeks after the last (3rd) stage 5 seizure. No change was observed in the absolute number of synaptic vesicles. On the other hand, marked redistribution of the vesicles in the synaptic apparatus was found, with a shift to a strategic position in the vicinity of the synaptic cleft. This redistribution evidently makes it possible to increase the supply of neurotransmitter needed for hyperfunction of the synaptic apparatus in kindling.

Animals↗

[Pulsatile administration of LH-RH: diagnostic and therapeutic applications].

Hypothalamic hypogonadotropic hypogonadism (HHH), a disorder occurring in both sexes, is characterized by a partial or complete inability to synthesize and/or release LH-RH from the hypothalamus which result in absence or defects of amplitude and frequency of gonadotropin secretion. Long term substitution by pulsatile exogenous LH-RH usually result in complete normalization of both pituitary and gonadic hormones. Such a treatment allows differentiation between hypothalamic and pituitary causes of hypogonadotrophic hypogonadism. Ovulation and fertility can be achieved in most of women with hypothalamic amenorrhea treated with pulsatile LH-RH using i.v. bolus doses of 25-100 ng/kg at 1-2 h intervals. In opposite LH-RH therapy yields inferior results to human menopausal gonadotropin (hMG) in chronic anovulatory patients with persistent LH secretion or polycystic ovary syndrome (PCOS) as shown by one randomized and several non-controlled studies. Successful pulsatile LH-RH treatment following a 2 months LH-RH analog suppression in PCOS previously refractory to LH-RH alone represents a new promising approach. The majority of men with complete HHH begin to produce sperm only after 1 year of therapy. Both the testicular volume and the mean sperm concentrations were below the normal values after 2 years of treatment in spite of normalization of testosterone, LH and FSH levels. Pulsatile LH-RH does not seem significantly improve the treatment of infertile HHH men compared to hMH/hCG.

Amenorrhea↗

Effects of ketamine on metrazol-induced seizures during ontogenesis in rats.

An anticonvulsant action of ketamine, a noncompetitive NMDA receptor antagonist (1-40 mg/kg IP), on the metrazol-induced seizures was assessed in male Wistar rats aged 7, 12, 18, 25 and 90 days. Ketamine alone caused ataxia even in the lowest dose used. As concerens its interaction with metrazol it exerted a clearcut anticonvulsant effect against generalized tonic-clonic seizures at all developmental stages. On the contrary, the effects on clonic (i.e., minimal) seizures were only moderate or absent. Higher efficacy of ketamine was observed in young animals. Our results suggest a role of excitatory amino acids in the generation of generalized tonic-clonic metrazol seizures, but their share on the induction of clonic (minimal) seizures seems to be very small.

Aging↗

Results of IVF attempts in patients with unexplained infertility.

From January 1986 to July 1987, 143 patients with unexplained infertility (UI) following 217 IVF attempts were studied and randomly assigned for statistical analysis to be compared with 434 tubal infertility (TI) patients undergoing 748 IVF attempts. The age of patients, previous pregnancy history and stimulation protocols were identical in both groups. In comparison with tubal patients, IVF attempts on the UI group were characterized by the same rates of cycle failure, mean number of oocytes retrieved per cycle, a lower fertilization rate (45.7% UI/59.8% TI) (P less than 0.01) and no difference in cleavage and nidation rates. However, a decrease in the pregnancy rate/attempt (13.8% UI/19.5% TI) tended towards a significant value (P = 0.06). Although the semen parameters were found to be in the normal range during the previous fertility screening in both groups, the incidence of at least one abnormality (count less than 20 X 10(6)/ml, and/or total motility less than 30% and/or abnormal forms greater than 75%) on the day of insemination was found to be significantly higher in UI (20%) than in TI (11%) patients. Moreover, 25% of UI patients did not fertilize any oocytes inseminated, whatever the number of oocytes retrieved. This rate of failed fertilization was significantly lower (9%) in tubal patients. The oestrogen response profiles were similar in both groups, analyzed according to the stimulation protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Buserelin↗

Ethosuximide affects both pentylenetetrazole- and kainate-induced clonic seizures but differentiates between tonic-clonic seizures.

Young (25-day-old) and adult (90-day-old) rats pretreated with ethosuximide (62.5 or 125 mg/kg i.p.) were injected with either s.c. pentylenetetrazole (100 mg/kg) or i.p. kainate (10 or 14 mg/kg). The incidences and latencies of minor (clonic) and major (tonic-clonic) seizures were registered. Ethosuximide (125 mg/kg) completely blocked clonic seizures induced by the lower dose of kainate, and slightly suppressed or delayed those induced by the higher dose of kainate or pentylenetetrazole in both age groups. The effect of ethosuximide on major kainate-induced seizures (elicited in young rats only) was insignificant (ethosuximide only partially decreased the incidence of major seizures), whereas ethosuximide abolished major pentylenetetrazole-induced seizures in both age groups. Ethosuximide also failed to affect the latencies of kainate-induced automatisms (e.g., scratching, wet dog shakes). Similarities between kainate- and pentylenetetrazole-induced clonic seizures, as well as a similar action of ethosuximide on both, suggest a common generator for the pattern of clonic seizures.

Animals↗

Rhythmic metrazol activity in rats as a model of human absences.

Rhythmic activity of the spike-and-wave type was induced by administration of metrazol (25 or 50 mg/kg s.c.) in male rats with implanted cortical electrodes. The animals were deprived of water and then allowed to lick water from a tube. Under control conditions they licked for 3-4 min without an interruption. Rhythmic metrazol activity deranged the licking; when this pathologic activity represented about one third of the time, the licking was fully blocked. We conclude that the impairment of highly motivated behaviour confirms the adequacy of the rhythmic metrazol activity as a model of human primary generalized seizures of the absence type.

Animals↗

Excitability cycles of epileptic after-discharges in rats.

An epileptic seizure is regularly followed by a postictal depression and then by a phase of increased excitability. The time course of these two phases was described for two types of epileptic after-discharges induced by stimulation of the hippocampus and/or the thalamus in acute experiments in rats. Using hippocampal stimulation, an interval of 10 min was necessary for induction of the second self-sustained after-discharge (SSAD) of the same duration as the first one. Significant prolongation of the second SSAD appeared with a 30-min interstimulation interval. The spike-and-wave rhythm induced by stimulation of thalamic nuclei exhibited a shorter refractory phase - up to 5 min - and also the facilitation took place sooner: with 15-min intervals a significant increase in duration of SSAD was recovered. The results are discussed in connection with the kindling model of epilepsy.

Animals↗

Antimetrazol action and plasma levels of valproate in developing rats.

The duration of protective action of valproate (VPA, 400 mg/kg i.p.) against metrazol-induced seizures was studied in rats aged 7, 12, 18 and 90 days. Fifteen, protected. The results differed between the various age groups after longer intervals: The protection was longest in 18-day-old rats--seizures did not appear even six hours after VPA administration. On the contrary, all 7-day-old rat pups exhibited seizures two hours after VPA. Plasma levels of VPA were measured by means of gas chromatography in the same age groups after an identical dose of VPA. After a single injection of VPA a clear-cut two-peak curve of plasma level was found in all young groups, which may be due to an enterohepatic recirculation of VPA. The maximum plasma levels were lowest in 7-day-old rats, the three older groups exhibited similar values. Plasma half-life was longest in the youngest animals (9.24) and decreased with age; values for 18- and 901 day-old rats did not differ (2.57 and 3.05 h respectively). No clear-cut correlation was found between the antimetrazol action and its plasma levels.

Aging↗

Hippocampal afterdischarges and localization of the stimulating electrodes.

Electrically evoked hippocampal afterdischarges are used as a model of partial epileptic seizures with a complex symptomatology and for testing anticonvulsants and toxic substances. Stimulating electrodes were implanted in the dorsal hippocampus of 16 laboratory rats and when the animals had recovered they were stimulated (15-s series, 8 Hz, pulse length 1 ms) with a voltage double the threshold value for a tissue response. The following features of the evoked afterdischarge were evaluated: the duration of the first phase of the afterdischarge, the duration of the non-active interphase, the duration of the second phase and the number of "wet dog shakes" (a constant accompaniment of hippocampal afterdischarges). Localization of the electrodes in the CA1 (n = 7) and CA3 (n = 7) region of the hippocampus made no difference to these parameters and in both cases the measured and evaluated data were the same. The afterdischarges were always accompanied by a marked orientation reaction. The study showed that when using macroelectrodes to stimulate the dorsal hippocampus, their localization in the CA1/CA3 is not of critical importance.

Animals↗

Cortical Na+,K+-ATPase of immature rats following bicuculline-induced seizures.

The Na+,K+-ATPase activity was investigated in cerebral cortex homogenates of 7-, 12- and 18-day-old rats in which seizures were induced by systemic (i.p.) administration of bicuculline. Na+,K+-ATPase activities in control animals increased during postnatal development, but they were not significantly influenced by seizure activity when determined under optimal conditions in vitro. Although the ratio of neuronal vs. non-neuronal cells in cortical samples of 7-, 12- and 18-day-old rats was different, there was a remarkable similarity in the activation curves for K+, obtained for Na+,K+-ATPase of all age groups under normal conditions; 50% of enzyme activities were attained at 1 mmol.l-1 K+ and the maximal activities were found around 10 mmol.l-1 K+. The activation curves for K+ in rats with bicuculline-induced seizures were not significantly different from those of the controls.

Aging↗