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Biomedical subjects

B Meldrum

Publications and source records attributed to B Meldrum.

At least 55 records · Page 3Linked to original sources
PubMed1980

Effects of the bicyclic GABA agonist, THIP, on myoclonic and seizure responses in mice and baboons with reflex epilepsy.

THIP, 4,5,6,7-tetra hydroisoxazolo[5,4-C]pyridine-3-ol, has been evaluated as an anticonvulsant in DBA/2 mice showing audiogenic seizures, and in baboons, Papio papio, with photosensitive epilepsy. No protection against seizures was seen after THIP, 1-4 mg/kg, intraperitoneally in mice. THIP, 8 mg/kg, reduced clonic and subsequent seizure responses at 1 h. It also reduced rectal temperature and impaired posture and spontaneous activity. In baboons THIP, 0.25-8 mg/kg, iv, failed to protect against photically induced myoclonic responses. Toxic signs after THIP, 8 mg/kg, included focal or generalised myoclonus. THIP is thus not effective against reflex epilepsy.

Animals↗
PubMed1980

Noradrenergic influences on sound-induced seizures.

The preferential alpha-2 noradrenergic agonists, clonidine (0.2--0.4 mg/kg), oxymetazoline (2.5--10.0 mg/kg) and UK 14,304 (0.6 mg/kg), when given i.p., reduce the severity of audiogenic seizures in 19- to 26-day-old DBA/2 mice. This protective effect can be diminished or reversed by alpha-2 noradrenergic antagonists such as yohimbine (2.5 mg/kg) or piperoxan (20--50 mg/kg) given i.p. or phentoalamine (100 micrograms) given intracerebroventricularly. It is not reversed by the preferential alpha-1 noradrenergic antagonist phenoxybenzamine (5 mg/kg) given i.p. Yohimbine, (1--2.5 mg/kg), piperoxan (20--50 mg/kg) or phenoxybenzamine (5 mg/kg) given i.p. alone did not change the severity of audiogenic seizure responses. Phentolamine (10--100 micrograms) or prazosin (10--50 micrograms) given intracerebroventricularly induced spontaneous limb myoclonus in some mice. Audiogenic seizure responses were unchanged after phentolamine (10--100 micrograms) but were reduced after prazosin (25--50 micrograms). Activation of a receptor pharmacologically similar to the peripheral alpha-2 noradrenergic receptor protects against seizures in this epilepsy model.

Acoustic Stimulation↗
PubMed1978

Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid).

The anticonvulsant potency and neurological toxicity of two new catalytic inhibitors of GABA-transaminase have been assessed in acute experiments in baboons with a natural syndrome of photic epilepsy. gamma-Acetylenic GABA, 160--200 mg/kg, or gamma-vinyl GABA, 450--950 mg/kg, intravenously, gave complete protection against generalised myoclonus or seizure responses induced by photic stimulation (in baboons without or with priming with subconvulsant doses of allylglycine). The protection became maximal 1--3 h after injection, and continued for 7--24 h. Signs characteristic of the acute toxicity of anticonvulsant drugs (nystagmus and ataxia) were not seen. The potential use of these compounds in human epilepsy deserves investigation.

4-Aminobutyrate Transaminase↗
PubMed1978

Blockade of photically induced epilepsy by 'dopamine agonist' ergot alkaloids.

The effect of the intravenous administration of ergot alkaloids on epileptic responses to intermittent photic stimulation )IPS) has been studied in adolescent baboons, Papio papio, from Senegal. Ergocornine, 1--2 mg/kg, produced marked autonomic and behavioural effects, slowed the EEG, and abolished myoclonic responses to IPS for 30--90 min. Ergometrine, 1 mg/kg, activated the EEG and blocked the induction of myoclonic responses for 1--3 h. Bromocriptine, 0.5--4 mg/kg, did not consistently prevent myoclonic responses to IPS. After pretreatment with a subconvulsant dose of allylglycine (180--200 mg/kg), lysergic acid diethylamide, 0.1 mg/kg, retained the capacity to block myoclonic responses to IPS, and ergocornine 1 mg/kg reduced such responses. The convulsant effect of allylglycine was enhanced, however, so that prolonged seizure sequences began 19--96 min after ergocornine administration. The protective action of ergot alkaloids against epileptic responses induced by sensory stimulation is interpreted in terms of effects at several sites, including dopaminergic and serotoninergic synapses.

Allyl Compounds↗
PubMed1978

Physiological changes during prolonged seizures and epileptic brain damage.

The role of physiological changes occurring during prolonged seizures in the causation of epileptic brain damage has been investigated experimentally in baboons and rats. Prolonged drug-induced myoclonic seizure activity is associated with initial arterial hypertension and subsequent hypotension, increased venous pressure, early hyperglycaemia and subsequent hypoglycaemia, variable arterial hypoxia and lactacidosis, and hyperpyrexia. Cerebral metabolic rate for oxygen and glucose is increased 2--3 fold throughout prolonged seizures provided the physiological status of the animal is well maintained. Ischaemic neuronal change is found after seizures lasting 1.5--7 hours, involving the small neurones of the third cortical lamina, Purkinje and basket cells in the cerebellum, and pyramidal neurons in the endfolium and Sommer sector of the hippocampus. Muscular paralysis and artificial ventilation minimise late physiological changes such as arterial hypotension and hyperpyrexia, and protect against cerebellar damage, but only slightly against neocortical and hippocampal damage. When arterial hypotension, hypoxia or hypoglycaemia lead to a reduction in the intensity of seizure discharge in paralysed, ventilated rats, there is also a reduction in hippocampal and neocortical damage. Factors intimately related to the intensity and duration of the neuronal discharge are responsible for neocortical and hippocampal lesions.

Animals↗
PubMed1977

Seizure activity in photosensitive baboons following antidepressant drugs and the role of serotoninergic mechanisms.

Laboratroy and clinical evidence indicates that tricyclic antidepressants lower seizure threshold and in high doses may induce generalised seizures. In baboons with photosensitive epilepsy (Papio papio) the effects of 2 tricyclic antidepressants (imipramine and chlorimipramine) and of maprotiline and Nomi fensine have been studied (i.v. dose range 1-20 mg/kg. Imipramine, chlorimipramine and maprotiline (10 mg/kg i.v.) lowered seizure threshold to a comparable extent, whereas Nomifensine (10 mg/kg i.v-) did not enhance myoclinic responses to photic stimulation. Generalised seizures were seen 15-30 min after imipramine or chlorimipramine (20 mg/kg), and these two drugs showed no difference in their epileptogenicity. Administration of 5-hydroxytryptophan (25 mg/kg i.v.) 90 min before chlorimipramine or imipramine (10 mg/kg) completely blocked the usual augmentation of photically-induced epileptic responses. It is concluded that enhancement of serotoninergic activity following blockade of 5-HT re-uptake within the brain is unlikely to be responsible for enhanced myoclonic responses and epileptogenic seizures seen after tricyclic antidepressants. Nomifensine is significantly less epileptogenic than imipramine or chlorimipramine.

5-Hydroxytryptophan↗
PubMed1976

Ergot alkaloids as dopamine agonists: comparison in two rodent models.

A series of ergot alkaloids, together with the DA agonists apomorphine and piribedil, were tested for protective effects against audiogenic seizures in an inbred strain of mice (DBA/2) and for induction of circling behaviour in mice with unilateral destruction of one nigrostriatal DA pathway. The order of potency against audiogenic seizures was apomorphine greater than ergocornine greater than bromocryptine greater than ergometrine greater than LSD greater than methysergide greater than piribedil while that observed in the rotating mouse model was apomorphine greater than ergometrine greater than ergocornine greater than bromocryptine greater than piribedil. LSD caused only weak circling behaviour even when administered in high doses (greater than 1 mg/kg). Methysergide was ineffective. Prior administration of the neuroleptic agent haloperidol blocked the effect of DA agonists and of ergot alkaloids in both animal models. The possible action of ergot alkaloids as DA agonists is discussed.

Acoustic Stimulation↗
PubMed1976

Inhibition of reflex epilepsy by (+/-)-N-n-propylnorapomorphine.

In baboons, Papio papio, spontaneously showing photosensitive epilepsy, myoclonic responses to intermittent photic stimulation were reduced or abolished for up to four hours by (+/-)-N-n-propylnorapomorphine (NPA) 0.05-0.2 mg/kg body weight, given i.v. In animals pretreated with allyglycine, 200 mg/kg, a transient abolition of myoclonic responses followed NPA, 0.2 mg/kg. In DBA/2 mice, seizures following auditory stimulation were attenuated or abolished by NPA 0.025-0.1 mg/kg given intraperitoneally (ED50 for abolition of clonic phase = 0.032 mg/kg). The ED50 for pentylenetetrazol seizures in MF 1 mice was not altered by NPA 0.25 mg/kg.

Animals↗
PubMed1975

Comparison of the antiviral effects of 5-methoxymethyl-deoxyuridine with 5-iododeoxyuridine, cytosine arabinoside, and adenine arabinoside.

The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), cytosine arabinoside (Ara-C), and adenine arabinoside (Ara-A). At concentrations of 2 to 4 mug/ml, MMUdR was inhibitory to herpes simplex virus type 1, but concentrations as high as 128 mug/ml were not inhibitory to three other herpesviruses tested (equine rhinopneumonitis virus, murine cytomegalovirus, and feline rhinopneumonitis virus) or to vaccinia virus. The other nucleosides, in contrast, were inhibitory at similar concentrations (1 to 8 mug/ml) against all viruses tested. The inhibition of HSV-1 by MMUdR appeared to be the result of interference with virus replication rather than the result of drug toxicity to host cells. The drug was not toxic to host cells at 100 times the antiviral concentrations, and pretreatment of host cells with high concentrations of MMUdR had no effect on subsequent virus replication. Combination of MMUdR with either IUdR, Ara-A, or Ara-C gave an enhanced antiviral effect, suggesting that the mechanism of action of MMUdR is different from that of the other three drugs. Antiviral indexes were calculated for each compound and were found to be >250, 80, 40, and 8 for MMUdR, IUdR, Ara-A, and Ara-C, respectively. These were defined as the minimum dose at which toxicity was observed microscopically divided by the dose which reduced plaque numbers by 50%.

Animals↗
PubMed1975

Survey of antibiotic residues in Canadian slaughter animals.

Kidneys and urine of cattle, swine, sheep and chickens were tested for bacterial growth inhibitors using Bacillus subtilis and Sarcina lutea as test organisms. Results were as follows: 211 beef kidneys four positive, 611 swine kidneys five positive, 27 sheep and 120 chicken kidneys all negative, 2108 beef urine 76 positive, 2409 swine urine 186 positive, 176 sheep urine 17 positive. Strongest reactions were obtained with B. subtilis on phosphate buffered pH 6.0 plates. Larger zones were produced by urine from injected animals than by tissue samples.

Abattoirs↗
PubMedDate not supplied

Drugs modifying dopaminergic activity and behaviour, the EEG and epilepsy in Papio papio.

Acute changes in spontaneous motor activity, the EEG and photically induced epileptic responses have been observed in baboons (Papio papio) following the i.v. injection of drugs acting on dopaminergic transmission. Apomorphine hydrochloride, 0.5-1.0 mg/kg, produced a phase of acute excitement with accentuated vigilance and abnormal buccal motor activity lasting 30-40 min; during this phase myoclonic responses to intermittent photic stimulation were absent. After piribedil (ET 495, 1,2'' -pyrimidyl-4-piperonylpiperazine), 2-10 mg/kg, acute excitement was not seen. Intermittent delta activity was prominent in the EEG for 1-3 hr, and was associated with a slight reduction in photically induced epileptic responses. Haloperidol 0.6-1.2 mg/kg, produced a long-lasting reduction in spontaneous motor activity with an increased incidence of spontaneous EEG spikes and waves and a great enhancement of paroxysmal EEG activity during photic stimulation. Pimozide, 0.5-2.5 mg/kg, normally produced mild sedation and some EEG slowing. 2 animals responded idiosyncratically to both haloperidol and pimozide, displaying intermittent dystonic episodes with bucco-facial dyskinesia. These findings suggest that activation of dopaminergic receptors can lead to a reduction in myoclonic responses to photic stimulation.

Allyl Compounds↗