effect of different lipophyllic beta-blockers on the minimal electro-shock seizure threshold [MEST] in mice

The effect of different beta-blockers on the minimal electro-shock seizure threshold [MEST] in mice, an index of generalized seizure susceptibility, was studied. Equipolent doses of the lipophilic beta-adrenergic blockers propranolol, pindolol,.oxprenolol and metoprolol significantly reduced the MEST after acute or chronic use [P < 0.05], however, this reduction was not significantly dose-dependant or significantly different between them. These drugs also antagonised the effect of beta agonists sulbutamol and isoprenaline, as well as that of the antiepileptic drugs phenytoin, valproate and clonazepam in elevating the seizure threshold. No significant change in blood glucose level or brain GABA content accompanied these acute or chronic effects on MEST, except for propranolol. It is concluded that lipophylic beta-adrenergic blockers enhanced seizure susceptibility mainly by blocking beta-adrenoceptors in brain. The magnitude of. this effect does not seem to be significantly altered by the selectivity of the beta block or by the possession of partial agonist activity by some of these drugs

comparative study of clondine and bromocrytine on growth in some growth-retarded children

Children with short stature, but otherwise healthy, and showing a subnormal GH [growth hormone] release to insulin hypoglycemia were evaluated for growth after 3 months of treatment with each of placebo [multivitamin tablet b.i.d.], Clonidine [b.i.d.] or bromocryptine 2.5 mg/d nocte], consecutively. Clonidine significantly increased OH release in these dwarfs, and this was associated with significant increase in height 3 months after treatment Bromocryptine had a mild enhancing effect on linear growth and plasma Gil level, while placebo had no significant effect. It is suggested that clonidine, probably acting centrally to augment hypothothalamic GHRH secretion and consequently GM release, might be more useful agent than bromocryptine in such growth retarded children. The results also suggest that alpha 2-adrenergic dysfunction in hpothalmus is more involved than a dopaminergic disorder 4 disturbing GM release from anterior pituitry with subsequent retardation of growth

Effect of GABA modifying agents on seizure susceptibility in insulin hypoglycaemic mice

Insulin hypoglycaemia produced significant catalepsy, reduction in brain GABA content, and enhanced seizure susceptibility as evident by the reduction in the minimal electroshock seizure threshold [MEST]. These effects of insulin were dose-dependent, and were prevented by i. p. treatment with glucose [2 g/kg]. Enhancement of brain GABA content and/or neurotransmission by valproate [300mg/kg] or clonazpam [5 mg/kg] i.p., respectively, prevented the effect of insulin [2U/kg] hypoglycamia on the MEST but potentiated the catalepsy, while depletion of brain GABA content by subconvulsive dose of isoniazid [50 mg/ kg] further enhanced brain excitability in these animals inducing spontaneous convulsion Clonazepam partially corrected the hypoglycaemia, while valproate further reduced the blood glucose level, but isoniazid did not affect it significantly, lt is concluded that the increased seizure susceptibility during hypoglycaemia involves both lack of energy supply to neurones as well as reduction in GABA minergic neuronal inhibition. Clonazepam, and possibly other anticonvulsant benzodiazepines seem to be suitable alternatives to glucose in correcting both these factors, and more preferable to other antiepileptic agents in treating hypoglycaemic convulsions

Effect of GABA modifying agents on electroshock seizure threshold in alloxan diabetic mice

The effect of different Gabaminergic manipulations on the minimal electroshock seizure threshold [MEST] [an index of brain excitability] were studied in alloxan-diabetic mice. Treatment of diabetic mice by clonazepam which potentiates central endogenous GABA neurotransmission, or by valproate which inhibits GABA catabolism, produced a greater rise in MEST than in normal mice. The i.v. injection of gluose in these animals produced marked hyperglycemia associated with increased brain GABA content and MEST. Seizures induced by isoniazid, which inhibits GABA formation, were delayed and attenuated in alloxan-diabetic mice. It is Concluded that diabetic hyperglycemia, partly by enhancing brain GABA formation and turnover, decreases the tendency to seizures and can potentiate anticonvulsants that act largely by Gabaminergic mechanisms

Effect of feeding of artemisia Hebra alba on glucokinase and ATPase activity in normal and diabetic rabbits

Since acute or chronic feeding on extract of the plant herb Artemisia herbal alba [AHA] was shown to reduce fasting blood sugar level in alloxan-diabetic [ALX-D] rabbits without altering plasma insulin or intestinal glucose absorption, the following work was done to show its effect on hepatic glucokinase [GK] and dinitrophenal [DNP]-stimulated mitochondrial ATPase [DSM-A TPase] activities. Diabetes mellitus resulted in a significant decrease in the activity of hepatic glucokinase [GK] [P < 0.05 after 4 weeks] and DSM-ATPase [60% after 12. weeks]. Daily oral treatment with AHA [0.5 p/kg/day] for 16 weeks reduced fasting blood glucose in normal [from 113.8 +/- 11.0 to 80.8 +/- 8.4 mg/Dl] and ALX-D animals [from 385.3 +/- 35.6 to 231.8 +/- 12.5 mg/Dl], and impeded the reduction in activities of [GK] [P < 0.05 after 4 weeks] and ATPase [P < 0.05 after 4 weeks] in ALX-D rabbits when compared with untreated animals. These effects were less than that of insulin, but persisted for I week after AHA withdrawal. Fasting for 72h reduced GK activity in normal animals [from 0.73 +/- 008 to 0.37 +/- 0.04 micro mol/g tissue/min] and diabetic animals [from 0.46 +/- 0.03 to 0.30 +/- 0.03 micro mol/g tissue/min], and this was partially impeded by AHA pretreatment. It is concluded that AHA constituents might have an insulin-like orpotentiating. action which protects KG and ATPase activities in liver and possibly other tissues and help to control the hyperglycaemia of diabetes, but can potentiate the hypoglycaemia of starvation

study on the effect of propranolol on seizure threshold in mice: its possible mechanisms and interaction

The effect of propranolol on the minimal electroshock seizure threshold [MEST] in mice, an index of generalised seizure susceptibility, was studied This lipophylic, non-selective beta-adrenergic blocker reduced the MEST after acute or chronic use [P < 0.01]; it also antagonised the effect of the beta-adrenergic agonists isoprenaline and salbutamol as well as that of the anti-epileptic agents phenytoin, valproate, and clonazepam in elevating the MEST. These acute or chronic effects were not accompanied by any significant hypoglycaemia, but the chronic effect was associated with a significant reduction in brain GABA content [P <0.01]. Hepatic microsomal enzyme induction with rifamycin effectively blocked the chronic effect of the drug in reducing the MEST. It is concluded that the effect of propranolol in enhancing seizure susceptibility is due the parent compound and is mainly mediated by blocking central beta-adreno ceptors; reduction in brain GABA might be implicated in the chronic effect of this drug. It is possible that this drug could aggravate or disturb the control of generalized epilepsy in man

Relation of brain GABA to variations in electroseizure threshold during hyperglycemia

Moderate hyperglycemia in alloxan-diabetic mice or following i.v. glucose injection in normal mice causes a non-significant elevation in brain GABA and minimal electro-shock seizure threshold [MST]. However severe hyperglycemia seen at 5 min following i.v. glucose in normal mice or at 1 hr after i.v. glucose in alloxan-diabetic mice produced a significant elevation of brain GABA, activity which was reflected in elevation of the MST and therefore a reduction in seizure susceptibility. It is concluded that hyperglycemia tends to elevate brain GABA activity but this becomes statistically significant in severe hyperglycemia. This may explain the reduced susceptibility and severity of seizures in some patients with diabetes mellitus

Effect of mebendazole and metronidazole in the survival of hydatid protoscolices of echinococcus granulosus in vitro and in viro

The effect of metronidazole and mebendazole on the survival of protoscolicies of Echinococcus granulosus was studied. In vitro, a concentration of 10 ug/ml of either drug in hydatid fluid significantly reduced the survival of protoscolicies. This effect was marked 4-5 days after incubation. In vivo, in mice, the i.p. administration for 10 days of either metronidazole [100 mg/kg/day] or mebendazole [10 mg/kg/day] or both drugs together inhibited the development of hydatid cysts in mice challenged with protoscolicies suspension [about 4000 scolex/ml] at the beginning of the experiment. Both the number and size of cysts that resulted were reduced, but cyst development was not abolished. The combination of both drugs showed some synergism in reducing cyst size but not number, when compared to animals receiving either drug alone. The daily administration of mebendazole in a dose of 50 mg/kg i.p. for 10 days completely prevented the development of abdominal hydatid cysts after challenge with protoscolicies suspension at the beginning of treatment. It is concluded that metronidazole could inhibit the survival of E. granulosus protoscolicies both in vitro and in vivo in mice in a manner comparable to mebendazole and may even be synergistic with it