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Biomedical subjects

D Dewar

Publications and source records attributed to D Dewar.

66 records · Page 4Linked to original sources
PubMed1990

5 HT2 receptors in dementia of Alzheimer type: a quantitative autoradiographic study of frontal cortex and hippocampus.

Using both quantitative autoradiography in sections and a homogenate preparation assay, the distribution and density of 3H-ketanserin binding to 5 HT2 receptors was examined in frontal cortex and the hippocampal region from six control subjects and seven subjects who had dementia of the Alzheimer type (DAT). There was no difference between control and DAT subjects in the levels of ketanserin binding in any region of the frontal cortex or hippocampus determined by quantitative autoradiography or in parallel experiments using homogenate preparations (e.g. left frontal cortex, layer III; controls, 34.4 +/- 1.6 pmol/g, DAT, 37.1 +/- 4.6 pmol/g). In all of the DAT brains there were abundant neuritic plaques (e.g. superficial layers of left frontal cortex; 35 +/- 7 plaques/mm2), and a marked reduction of choline acetyltransferase activity, (by 30-60% relative to controls), in both frontal cortex and the hippocampus. Thus, despite the presence of morphological abnormalities and a loss of cholinergic function, two classic features of DAT, 5 HT2 receptor binding was unaltered in this group of DAT brains compared to controls.

Alzheimer Disease↗
PubMed1990

Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type.

Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-[3H]aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. [3H]Kainate receptor binding was significantly increased by approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive [3H]glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. [3H]Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others.

Aged↗
PubMed1989

Alterations in the N-methyl-D-aspartate receptor complex following focal cerebral ischemia.

The functional integrity of the N-methyl-D-aspartate receptor complex following focal cerebral ischemia in the rat has been examined at a time when brain tissue is irreversibly damaged. Twelve hours after unilateral permanent middle cerebral artery occlusion, [3H]-MK-801 binding was not significantly altered in the ischemic cerebral cortex compared to sham-operated animals. Moreover, the enhancement of [3H]MK-801 binding by exogenous glutamate was preserved in an area of the brain that was permanently damaged by the ischemic insult.

Animals↗
PubMed1986

Purification and characterization of tribulin, and endogenous inhibitor of monoamine oxidase and of benzodiazepine receptor binding.

A low molecular weight fraction of human urine (less than 500 daltons) which both inhibits monoamine oxidase and benzodiazepine binding to central and peripheral receptors has been purified by ethyl acetate extractions, HPLC and thin layer chromatography. This material extracted equally well at acid and basic pH and was insoluble in heptane. It competitively inhibited binding of 3H-clonazepam, a central benzodiazepine receptor agonist and, in addition, displaced 3H-Ro 5-4864, a specific peripheral benzodiazepine receptor ligand, from its binding sites. It showed no GABA shift with the benzodiazepine receptor antagonist, Ro-15 1788. MAO A and B were inhibited approximately equipotently and the material competitively inhibited tyramine oxidation by rat liver. It was stable on boiling and is unlikely to be a peptide.

Animals↗
PubMed1986

Equol and other compounds from bovine urine as monoamine oxidase inhibitors.

Equol, its methylated derivative, and a carbazole, all isolated from bovine urine, are relatively potent inhibitors of monoamine oxidase with IC50 values of 158, 28, and 16 microM respectively (using 83 microM tyramine as substrate). The probable dietary origin of these compounds suggests that "natural" monoamine oxidase inhibitors may be more widespread than had previously been suspected.

Animals↗
PubMed1985

Behavioural effects in rats of unilateral and bilateral injections of opiate receptor agonists into the globus pallidus.

Unilateral injections of a putative kappa-opiate receptor agonist, ethylketocyclazocine, into the globus pallidus of rats caused dose-dependent ipsiversive circling which was inhibited by prior systemic administration of the opiate receptor antagonist naloxone. Neither a putative delta-opiate receptor agonist ( [D-Ala2, D-Leu5]enkephalin) nor a putative mu-opiate receptor agonist (Tyr-D-Ala-Gly-MePhe-Met(0)-ol) induced circling behaviour after unilateral intrapallidal injection. Bilateral intrapallidal injection of the delta-opiate receptor agonist or the mu-opiate receptor agonist caused an increase in locomotor activity which in both cases was reduced by systemic administration of naloxone. A specific delta-receptor antagonist, (N,N-bisalyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH) had no effect on the increase in locomotor activity caused by the delta-opiate receptor agonist. Bilateral intrapallidal injection of the kappa-opiate receptor agonist had no effect on locomotor activity. It is suggested that different opiate receptor subtypes within the globus pallidus differentially mediate circling and locomotor behaviour.

Animals↗
PubMed1983

Lesions of the globus pallidus, entopeduncular nucleus and substantia nigra alter dopamine mediated circling behaviour.

Unilateral kainic acid lesions of the globus pallidus in the rat caused weak spontaneous circling at 3 and 10 days after surgery. Unilateral kainic acid lesions of the entopeduncular nucleus caused no spontaneous circling at any time after surgery. Systemic administration of apomorphine to such lesioned animals caused ipsiversive circling in both groups. Pallidal lesions in animals with a prior ipsilateral 6-OHDA lesion of the medial forebrain bundle attenuated apomorphine-induced, but not amphetamine-induced, circling. Entopeduncular nucleus lesions in the 6-OHDA lesioned animal attenuated both apomorphine- and (+)-amphetamine-induced circling. Kainic acid lesions of the globus pallidus or entopeduncular nucleus did not alter nigral glutamic acid decarboxylase (GAD) activity. Unilateral electrolytic lesions of the globus pallidus or entopeduncular nucleus caused ipsiversive circling in response to apomorphine. An electrolytic lesion of the globus pallidus in animals with a prior 6-OHDA lesion did not alter (+)-amphetamine-induced circling but reversed the direction of apomorphine-induced circling. Electrolytic lesions of the entopeduncular nucleus enhanced (+)-amphetamine-induced circling and attenuated apomorphine-induced circling. Nigral GAD activity was reduced by electrolytic lesions of the globus pallidus but not by those of the entopeduncular nucleus. Large kainic acid lesions in the area of the substantia nigra caused weak spontaneous contraversive circling 3 days after surgery, and ipsiversive circling in response to the systemic administration of apomorphine. Similar lesions in animals with a prior ipsilateral 6-OHDA lesion of the medial forebrain bundle initially attenuated the response to (+)-amphetamine, but the response returned with time. The direction of apomorphine-induced circling was reversed in these animals. The strio-nigral pathway and nigral efferents are confirmed to be involved in circling induced by dopamine agonists in rats with a unilateral lesion of the medial forebrain bundle. Both the globus pallidus and the entopeduncular nucleus also appear to be involved in this dopamine-mediated circling behaviour.

Animals↗
PubMed1976

In vivo synchronization of murine sarcoma 37 ascites tumor cells by use of hydroxyurea.

Synchrony of DNA synthesis in mouse sarcoma 37 ascites cells was achieved in vivo by injection of 0.75 mg hydroxyurea per gram weight of mouse. DNA synthesis was gauged by comparing 3H-labeled thymidine incorporation, under defined conditions, to total DNA measured colorimetrically. DNA synthesis in the sarcoma 37 cells fell to negligible levels 4 hours after injection and remained at or below levels observed in randomly dividing cells up to 18 hours after injection. A sharp increase in DNA synthesis occurred at 20 hours, followed by a decline again at 22 hours after hydroxyurea injection. DNA synthesis in the intestine remained below control values at 20 hours.

Animals↗
PubMedDate not supplied

Cerebral ischemia induces alterations in tau and ubiquitin proteins.

Excessive stimulation of glutamate receptors and elevation of intracellular calcium levels initiate the neurodegenerative process resulting from cerebral ischemia. However, the subsequent cascade of molecular changes which are of pathogenic significance is less well understood. Breakdown of the cytoskeleton may be involved in the progression from compromise of neuronal viability to irreversible damage. Alteration of the microtubule-associated protein tau, as reflected by increased Alz-50 immunoreactivity, was induced by permanent focal cerebral ischemia in vivo but only in a proportion of neurones. Alz-50 immunoreactive neurones did not exhibit the characteristics of irreversible ischemic cell damage. Increased immunoreactivity to the stress response protein ubiquitin was also induced by ischemia in a proportion of neurones. Both proteins are components of neurofibrillary tangles in Alzheimer's disease. Alterations of the microtubule-associated protein tau may be a feature of the early stages of the ischemia-induced degeneration and the ubiquitin response may be an attempt by compromised neurones to deal with the presence of abnormal proteins.

Animals↗
PubMedDate not supplied

Syringe pumps and start-up time: ensuring safe practice.

The start-up time is the delay between starting an infusion pump and the delivery of fluid at the set flow rate. Mechanical slack in syringe pumps can lead to start-up delays of an hour or more at low-flow rates. During this period no medication is delivered to the patient. The causes of the start-up time delay, its implications and methods of minimising the delay are explained.

Documentation↗