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Biomedical subjects

B S Meldrum

Publications and source records attributed to B S Meldrum.

At least 235 records · Page 13Linked to original sources
PubMed1979

Electroencephalographic and behavioral effects of a GABA agonist (muscimol) on photosensitive epilepsy in the baboon, papio papio.

Muscimol, 0.25-1.0 mg/kg, i.v., was administered acutely to 4 adolescent baboons, Papio papio, that show photically induced epilepsy. On the EEG, slowing of background rhythms was associated with the appearance of spikes, polyspikes, and recurring symmetrical spike-wave complexes. These changes were maximal 0.5-2 hr after muscimol injection. Regular testing with intermittent light stimulation showed either no change from control responses or a more severe epileptiform EEG 0.1-3 hr after muscimol. Photically induced myoclonus was not modified by muscimol. Despite its GABA-abonist properties, muscimol is not an effective anticonvulsant.

Animals↗
PubMed1979

Endocrine factors and glucose metabolism during prolonged seizures in baboons.

Changes in plasma glucose, nonesterified fatty acids, insulin, glucagon, cortisol, growth hormone, and prolactin have been studied in baboons during the course of generalized epileptic seizures induced by intravenous bicuculline. Plasma glucose rose to a peak at 25 min but fell to hypoglycemic levels after 60 min of seizure activity. This hypoglycemia was accompanied by a marked elevation in plasma insulin. Plasma glucagon rose to a peak at 14 min, then returned to normal. Plasma growth hormone levels were elevated after 60 min of seizure activity. Plasma prolactin and cortisol levels also rose during the seizure. These changes result from sequential interaction of (1) autonomic activation at seizure onset, (2) spread of neuronal activity to the hypothalamus leading to the liberation of releasing factors, and (3) indirect physiologic consequences of seizure activity.

Animals↗
PubMed1978

Epileptic brain damage: the role of systemic factors that modify cerebral energy metabolism.

The possible role of systemic physiological changes (occurring secondarily during status epilepticus) in the causation of epileptic brain damage has been evaluated in rats. Animals were anaesthetized, paralysed and mechanically ventilated; sustained electrocortical seizure discharges were induced by the intravenous injection of bicuculline, 1.2 mg/kg. After two hours of seizure activity brains were fixed by perfusion for histology. Physiological variables were maintained within certain limits from the end of the initial seizure phase (approximate duration twenty minutes) until two hours after onset of seizure to provide six groups: (1) Standard: mean arterial pressure above 120 mmHg, no hypoxia or hypoglycaemia, rectal temperature close to 37 degrees C. (2) Moderate Hypotension: mean arterial pressure at 70-75 mmHg. (3) Severe Hypotension: mean arterial pressure at 50 mmHg. (4) Hypoxia: arterial oxygen tension at 50 mmHg. (5) Hypoglycaemia: non-fed animals, with blood glucose close to 3.0 mumol/g. (6) Hyperthermia: rectal temperature at 40 degrees C. Microvacuolation and ischaemic cell change were identified by light microscopy in scattered neurons in the cortex (principally in the outer layers) in animals in three groups (Standard, Severe Hypotension and Hyperthermia). Similar neuronal changes were seen in the hippocampus (predominantly in the h1 or Sommer sector) in the Standard and Hyperthermia Groups. It is tentatively proposed that neuronal damage in animals with unrestricted cerebral oxygen and glucose availability is due to oxidative mechanisms in cells with excessively enhanced neuronal activity and that lesions caused by failing energy production do not appear until severe degrees of hypoxia are reached.

Animals↗
PubMed1978

Anticonvulsant action of a 1,5-benzodiazepine, clobazam, in reflex epilepsy.

Clobazam, an anxiolytic 1,5-benzodiazepine, has been evaluated as an anticonvulsant in 2 animal models. In mice showing sound induced seizures, clobazam, 1--4 mg/kg, i.p., blocked seizure responses for 1--2 hr. In Senegalese baboons Papio papio showing photically induced myoclonus or seizures, clobazam, 2--12 mg/kg, i.v., totally prevented such responses for up to 6 hr. In baboons pretreated with allylglycine, 170--185 mg/kg, a similar but briefer protection was induced by clobazam. Neurological toxicity was not prominent (transient, slight nystagmus after clobazam, 2--6 mg/kg; muscular hypotonia after clobazam, 12 mg/kg). The possibility that 1,5-benzodiazepines are superior to 1,4-benzodiazepines in the therapy of epilepsy requires clinical investigation.

Acoustic Stimulation↗
PubMed1978

Photosensitive epilepsy in Papio papio as a model for drug studies.

Photically-induced epilepsy in Papio papio provides a convenient model for assessing the efficacy and the acute neurological toxicity of new anticonvulsant drugs prior to clinical trial. Its drug sensitivity is broadly comparable to that of generalized seizures in man. It also shares some specific properties with syndromes of reflex epilepsy in man.

Animals↗
PubMed1977

Monoamine and GABA metabolism and the anticonvulsant action of di-n-propylacetate and ethanolamine-O-sulphate.

The time course of changes in behaviour, seizure response and cerebral monoamine and gamma-aminobutyric acid (GABA) metabolism has been studied in relation to the anticonvulsant actions of di-n-propylacetic acid (DPA) and ethanolamine-O-sulphate (EOS) on sound-induced seizures in DBA/2 mice. Changes in cerebral monoamine metabolism after EOS (75 or 150 mug, intracerebroventricularly) were not related to its anticonvulsant action. The primary effect was GABA-transaminase inhibition (by 50-70%) leading to a 2-4 fold increase in cerebral GABA concentration. Increases in brain GABA concentration (maximally 36%), 5-hydroxyindoleacetic acid (5HIAA, maximally 134%) and homovanillic acid (HVA, maximally 183%) were seen after DPA (400-600 mg/kg, i.p.). The time course of the increases in HVA and 5HIAA did not correlate with the anticonvulsant effect. Elimination of these increases by the use of inhibitors of monoamine synthesis (alpha-methyl-p-tyrosine and p-chlorophenyl-alanine) did not alter the anticonvulsant effect of DPA. Experiments using probenecid suggested that the increases in 5HIAA and HVA after DPA result from inhibition of their active transport out of the brain.

Acoustic Stimulation↗
PubMed1977

Acute dystonia as an idiosyncratic response to neuroleptics in baboons.

Among 25 baboons, Papio papio, 2 consistently showed acute dystonic reactions, with mouthing, compulsive gnawing and limb and trunk dystonia, following the intravenous administration of neuroleptics and related drugs (haloperidol, 0-6-1-2 mg/kg; pimozide 0-5-2-5 mg/kg; chlorpromazine 5-25 mg/kg; metoclopramide 1-5-1-7 mg/kg; oxyperomide 0-25-1-0 mg/kg). The syndrome was not seen after thioridazine (3-7 mg/kg). The dystonic responses occurred within 1-2 h of drug injection and lasted for 2-24 h. They were abolished for 1-3 h within 1-2 min of the intravenous injection of acetylcholine antagonists (benztropine 0-2 mg/kg; hyoscine 0-02 mg/kg). Pre-treatment with a combination of reserpine (2 mg/kg) and alpha-methylparatyrosine (2 X 200 mg/kg) substantially reduced the dystonic response to haloperidol. A second larger dose of haloperidol (5 mg/kg), given 60-90 min after 0-5 mg/kg) initially reduced the intensity of the dystonic response, but after 29 min induced vomiting and generalized seizures in the idiosyncratic baboons. The hypothesis is advanced that the dystonic responses result from release of dopamine on to a sub-population of receptors in the striatum that are relatively insensitive to blockade by neuroleptics.

5-Hydroxytryptophan↗