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Biomedical subjects

M E Brodie

Publications and source records attributed to M E Brodie.

9 recordsLinked to original sources
PubMed1990

Neurochemical changes in hippocampal and caudate dialysates associated with early trimethyltin neurotoxicity in rats.

Following a control period of dialysis of the hippocampus (Hc) or caudate (Cd) of conscious freely-moving rats, a single dose of trimethyltin chloride (TMT, 10 mg/kg) was administered by gavage and dialysis continued for up to 51 hr after dosing. During this time dialysate levels of amino acids, catechols and indoles were continually monitored, GABA A and B and glutamate (Glu) binding was measured at 48 hr, and histological damage was assessed at 24, 48 and 72 hr after dosing. The earliest change to occur was a significant 2-fold increase at 24 hr in Hc and Cd dialysate levels of glutamine (Gln), followed at 48 hr by an almost 4-fold increase in Gln and increases also in Glu, GABA and threonine levels. 5-Hydroxyindoleacetic acid (5-HIAA) levels were also increased in Cd dialysates 24 and 48 hr after dosing. The initial increase in Gln occurred at a time (24 hr) when there was no necrosis, only mild cytoplasmic changes in the CA3b region of the Hc and none in the Cd. By 72 hr cytoplasmic and necrotic changes were well established in both Hc and Cd. GABA A binding was significantly decreased in both Hc and Cd 48 hr after dosing, while Glu binding was unchanged. The results suggest that one component of TMT-induced neurotoxicity may be a consequence of increased extracellular levels of the excitotoxic amino acid, glutamate.

Amino Acids↗
PubMed1986

Cancer Program Administrators' survey results.

In summary, cancer programs across the country have been developing since 1975. A more formal organizational structure has been adopted to program activities since 1980. The full-time Cancer Program Administrator position exists in about one-third of the programs reporting. Persons occupying the position are at least bachelors degreed with many also having a masters degree. Strengths, weaknesses, and obstacles to program development are basically the same items across the country. It appears that programs that have one problem resolved are still working towards the solution of another problem and vice versa among programs. All programs are struggling for identity within the hospital and are in developmental stages with a lot of activity focused on clarifying the position of an organized cancer program within the hospital organization.

Cancer Care Facilities↗
PubMed1985

Dissociation between circling behaviour and striatal dopamine activity following unilateral deltamethrin administration to rats.

The neurotoxic pyrethroid, deltamethrin, induces a severe motor syndrome characterised by tremor and choreoathetosis when injected systemically to rats. The interaction between deltamethrin and the two major dopaminergic pathways - the nigrostriatal and mesolimbic pathways - was investigated in rats. Striatal catecholamines, indoleamines and metabolites were measured by HPLC with electrochemical detection. Unilateral injection of deltamethrin (1.0 microgram) into the ventral tegmental nucleus or substantia nigra induced rapid ipsilateral or contralateral circling respectively but was ineffective at other basal ganglia sites. Both the sham and vehicle injections at either site, resulted in a marked increase above normal in DA turnover in the ipsilateral striatum without inducing circling behaviour. DA turnover was increased to the same extent in the ipsilateral stratum of deltamethrin-treated rats where rapid circling was present. Therefore the neurochemical findings were not consistent with the rotation theories based on striatal DA asymmetry but rather followed alternative mechanisms previously proposed, where circling behaviour can occur by mechanisms not causally related to striatal DA. These findings also indicate that a degree of selectivity exists in the action of deltamethrin, a sodium channel toxin that might be expected to act on all neuronal systems within the SN or VTN or equally at other sites within the basal ganglia associated with circling behaviour.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Correlations between cerebellar cyclic GMP and motor effects induced by deltamethrin: independence of olivo-cerebellar tract.

The latencies and incidence of deltamethrin-induced motor symptoms were compared in rats pretreated with saline or 3-acetylpyridine (3-AP) (75 mg/kg i.p. 4 days before). 3-AP produced considerable degeneration of the inferior olive and hence the climbing fiber afferents to the cerebellar cortex. The times of onset of whole body tremor and spontaneous choreiform episodes were accelerated significantly in lesioned rats. Therefore the olivocerebellar tract is not important in mediating deltamethrin symptoms, but is necessary to compensate for the disruption of motor activity and coordination induced by deltamethrin at another site. Cerebellar cyclic guanosine monophosphate (cyclic GMP) levels were elevated significantly during the deltamethrin syndrome. The increase in cyclic GMP levels correlated directly with the duration of motor symptoms. This suggests that deltamethrin has an indirect effect on cerebellar cyclic GMP levels. Lesion of the olive-cerebellar tract did not abolish this rise in cerebellar cyclic GMP levels. The sequential development of the motor symptoms, whole body tremor followed by choreiform episodes was found to have an additive effect in raising cerebellar cyclic GMP levels. This suggests that both the nature and the general level of motor activity can influence cerebellar cyclic GMP levels.

Animals↗
PubMed1980

Noradrenaline release from slices of the thalamus of normal and morphine-dependent rats.

The effect of morphine on potassium-induced stimulation of (3H)-noradrenaline release from slices of the rat thalamus was investigated. The in vitro addition of morphine (10(-6)M) significantly depressed potassium-induced tritium overflow by 42% and this was prevented by the prior addition of naloxone (3 x 10(-6)M) to the medium. The stimulation-evoked overflow of tritium from slices of the thalamus of morphine-dependent rats was not significantly different from normal controls. Addition of naloxone (10(-5)M) 10 min before exposure of the tissues to 20 mM K+ significantly enhanced noradrenaline release from 'dependent' slices. The results suggest that the basic release mechanism may have adapted to the continuous presynaptic inhibition of release by morphine.

Animals↗
PubMedDate not supplied

Deltamethrin infusion into different sites in the neuraxis of freely-moving rats.

A comparison of signs induced by deltamethrin infusion at 3 sites within the neuraxis was made in freely-moving rats. Cannulae were placed prior to experiment into either lateral ventricle, cisterna magna or spinal subarachnoid space and animals allowed to recover. Deltamethrin was active at all levels of the neuraxis in a dose dependent manner. All signs induced by intraperitoneal deltamethrin administration, except profuse salivation and choreoathetosis, were generated by direct infusion of the compound into the CNS. In addition other signs developed which cannot be observed following systemic administration. They seemed to reflect a local disturbance in function around each injection site. With regard to the major symptom of choreoathetosis associated with systemic deltamethrin administration, the results suggest that for such a complex response to develop, a more global activation at many levels of the neuraxis (and possibly in the periphery) is required.

Animals↗
PubMedDate not supplied

Elevated cerebellar cyclic GMP levels during the deltamethrin-induced motor syndrome.

Adult male Porton albino rats received deltamethrin (0.5--40.0 mg/kg IP) or glycerol formal solvent IP. Their behaviour was observed during the subsequent 110 minutes and the incidence and latency of salivation, tremor and incoordination and spontaneous choreiform episodes were noted. Cyclic GMP levels in the cerebellum were determined by radioimmunoassay at various times after deltamethrin administration. The development of the motor syndrome was dose-dependent and followed a specific time course. The threshold dose for profuse salivation and tremor and incoordination was 2.5 mg/kg IP, and for spontaneous choreiform episodes, 5.0 mg/kg IP. The latency of tremor and incoordination decreased significantly as the deltamethrin dose was increased. The first significant increase in cyclic GMP levels in the cerebellum was at 70 minutes, which was 10 minutes after the mean latency of tremor and incoordination. The levels increased further at 100 minutes which was approximately 20 minutes after the mean latency of spontaneous choreiform episodes. Deltamethrin did not have a dose-dependent effect on cyclic GMP levels. The results suggest that deltamethrin changes cerebellar cyclic GMP levels indirectly.

Animals↗