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Biomedical subjects

J T Coyle

Publications and source records attributed to J T Coyle.

At least 289 records · Page 16Linked to original sources
PubMed1981

Association of postoperative delirium with raised serum levels of anticholinergic drugs.

Drugs with anticholinegic effects are often used in surgical procedures and may impair higher cognitive functions and produce delirious states. This prospective study examined the relation between serum levels of anticholinergic drugs, measured by a radioreceptor assay, and the development of delirium in patients undergoing cardiac surgery. Most patients who had postoperative delirium had high serum levels of anticholinergic drugs, whereas those who remained cognitively intact had low levels; and impairment in cortical function correlated with serum levels of anticholinergic drugs (p less than 0.001). Raised serum levels of drugs with anticholinergic effects may contribute to the development of delirium, and to the increase in risk of morbidity following cardiac surgery.

Adult↗
PubMed1981

N-Methyl-D-aspartate acid: a convulsant with weak neurotoxic properties.

N-Methyl-D-aspartic acid (NMDA) is 100-fold less potent as a neurotoxin than kainic acid when injected into the rat striatum. However, NMDA, when injected into the hippocampus, causes a more severe seizure disorder than kainic acid and doses of NMDA than produce much smaller lesions than those caused by kainate. These results indicate a poor correlation between convulsant and neurotoxic properties of acidic excitatory amino acids.

Animals↗
PubMed1981

Development of central neurotransmitter systems.

Inter-neuronal communication is mediated primarily by chemical neurotransmitters, which are released from the nerve terminal, diffuse across the synaptic cleft and interact with specific receptors on adjacent neurons. The development of the biochemical machinery for neurotransmission is closely linked to the functional maturation of the brain's neuronal circuitry. Components essential for neurotransmission (e.g., synthetic enzymes, endogenous neurotransmitters, re-uptake processes and receptors) serve as specific biochemical markers for neuronal systems. The appearance of and developmental increases in these markers during fetal and postnatal life occur with the cessation of neuronal replication and initiation of neuropil elaboration. Discrete groups of neurotransmitter-specific neurons develop according to different timetables, resulting in a shifting pattern of their relative influence in the maturing brain. Human and animal studies demonstrate an early innervation of the neocortex by catecholaminergic axons while neurons using gamma-aminobutyric acid (GABA) mature somewhat later; and the ontogeny of the acetylcholine neurons lags behind both of these. Within each neuronal group the individual biochemical components for neurotransmission also follow differing time courses of maturation. Animal studies, in which cortical neurons were ablated by administering a toxin to the fetus, illustrate the interplay between intrinsic programmes and environmental influences in the assembly of neuronal circuits. The brain's preparation for independent life is characterized by a continual reorganization of neurotransmitter pathways.

Animals↗
PubMed1981

Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis.

The nucleus basalis of Meynert provides diffuse cholinergic input to the neocortex. When compared with an age- and sex-matched control, the nucleus basalis from a patient with Alzheimer disease demonstrated substantial reduction of neurons. Loss of this neuronal population may represent an anatomical correlate of the well-documented cholinergic derangement in Alzheimer disease.

Aged↗
PubMed1981

Laminar distribution of cholinergic markers in neocortex: effects of lesions.

The distribution of presynaptic markers for cholinergic and GABAergic neurons in the various layers of the lateral neocortex was determined with a technique in which sections of increasing depth horizontal to the pial surface were obtained on a frozen-stage microtome and analyzed for the markers. The specific activities of choline acetyltransferase and acetylcholinesterase had an uneven distribution in the cortex with lowest levels of activity associated with lamina II and III, whereas glutamate decarboxylase activity was highest in lamina II, III, and IV. Fetally-induced hypoplasia of the cortex resulted in an enrichment in both choline acetyltransferase and acetylcholinesterase activity in all layers with no significant change in the activity of glutamate decarboxylase. Lesion of the nucleus basalis-cortical cholinergic pathway resulted in marked reductions in the activities of acetylcholinesterase and choline acetyltransferase in all cortical layers and an elimination of the uneven distribution of these markers within the cortex. These results provide further evidence that acetylcholinesterase activity is specifically associated with cortical cholinergic afferents and support the existence of cortical intrinsic cholinergic neurons.

Acetylcholinesterase↗
PubMed1981

Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rat.

Electrothermic lesion of the peri-pallidal region of the rat caused a marked reduction in the activity of choline acetyltransferase in the ipsilateral fronto-parietal cortex without affecting the activity of glutamate decarboxylase. Only lesions that involved the ventral globus pallidus significantly reduced cortical choline acetyltransferase activity; and lesions limited to the thalamus, internal capsule, pyriform cortex or zone incerta were ineffective. Excito-toxin lesions of the ventral globus pallidus caused 45-5% reductions in all presynaptic markers for cholinergic neurons but did not significantly decrease presynaptic markers for noradrenergic, serotonergic or histaminergic neurons in the cortex. The maximal reductions in cortical choline acetyltransferase activity achieved with the pallidal lesion was 70%; and enzyme activity reached its nadir by four days after placement of the lesion. The pallidal lesion, which ablated the large isodendritic acetylcholinesterase positive neuronal perikarya, resulted in a profound loss in histochemically stained acetylcholinesterase-reactive fibers in the fronto-parietal cortex but not in the cingulate, pyriform and occipital cortex or hippocampal formation; analysis of the subregions in choline acetyltransferase activity. The kainate lesion of the parietal cortex to ablate intrinsic neurons did not reduce the activity of tyrosine hydroxylase, a marker for noradrenergic terminals, but depressed glutamate decarboxylase by 68%; in contrast choline acetyltransferase activity fell only 29%. The results indicate that approximately 70% of the cholinergic innervation in the fronto-parietal cortex is derived from acetylcholinesterase positive neurons in the peripallidal nucleus basalis, whereas the remainder appears to be localized in cortical intrinsic neurons.

Acetylcholinesterase↗
PubMed1981

Acute extrapyramidal side effects: serum levels of neuroleptics and anticholinergics.

An assay technique for measuring anticholinergic drugs in human serum based upon their inhibition of the specific binding of [3H]-quinuclidinyl benzilate to rat brain muscarinic receptors is described. The assay was validated by demonstrating a close correlation (r = 0.99) between serum levels of nortriptyline measured by the radioenzymatic assay and a GLC technique. The assay measures free anticholinergics, and under standard assay conditions, approximately 95% of benztropine is bound to serum protein. Marked variation in serum anticholinergic levels in patients receiving the same oral dose was observed, and in individual patients there was a non-linear relationship between increasing oral dose and serum anticholinergic levels. In a cross-sectional study of 109 patients receiving concurrently neuroleptics and anticholinergics, there was no correlation (r = 0.029) between serum neuroleptic levels measured by radioreceptor assay and extrapyramidal side effects (EPS). In the patients whose serum anticholinergic levels were also determined, there was a significant inverse correlation (r = 0.44) between anticholinergic levels of EPS. In this cohort of patients, there was no significant correlation between serum anticholinergic and serum neuroleptic levels (r = 0.16) and the ratio of serum anticholinergic to serum neuroleptic was a poor predictor of EPS (r = 0.26). The results suggest a marked variation in sensitivity of patients to the EPS-inducing of neuroleptics; nevertheless, the incidence of EPS decreases with increasing serum levels of anticholinergics. An optimal serum anticholinergic level of 10 pmole atropine equivalent per ml was associated with a low incidence of EPS and is relevant to drug action at the striatal muscarinic receptor.

Acute Disease↗
PubMed1981

Effects of spinal transection on presynaptic markers for glutamatergic neurons in the rat.

To evaluate the hypothesis that glutamic acid may be the neurotransmitter of descending, excitatory supraspinal pathways, the uptake and release of L-[3H] glutamate and the levels of endogenous glutamate were measured in preparations from rat lumbar spinal cord following complete mid-thoracic transection. Following transection, the activity of the synaptosomal high-affinity glutamate uptake process was increased in both dorsal and ventral halves of lumbar cord between 1 and 14 days after transection and returned to control levels by 21 days posttransection. At 7 days, the increased activity of the uptake process for L-[3H]glutamate resulted in elevation of Vmax with no significant alteration in KT as compared to age-matched controls. Depolarization-induced release of L-[3H]glutamate from prelabeled slices did not differ significantly from control in the lesioned rat except at 21 days after lesion when the amount of tritium release was significantly greater in the transected preparations than in control. Amino acid analysis of the lumbar cord from control and transected rats indicated only a 10% decrease in the level of endogenous glutamate and no alterations in the concentration of GABA and glycine 7 days after lesion. These findings do not support the hypothesis that glutamate serves as a major excitatory neurotransmitter in supraspinal pathways innervating the lumbar cord of the rat.

Animals↗
PubMed1981

Ontogeny of receptor binding sites for [3H]glutamic acid and [3H]kainic acid in the rat cerebellum.

The development of the specific binding sites for L-[3H]glutamic acid (KD = 370 nM) and for [3H]kainic acid (KD = 39 nM) was studied in the rat cerebellum. Specific binding at both sites remains low during the first week after birth but increases markedly during the second and third weeks after birth, when glutamatergic parallel fiber synaptogenesis occurs. The development of the kainate site lags behind that of the glutamate site, indicating their autonomy.

Aging↗
PubMed1981

Effects of fetal treatment with methylazoxymethanol acetate at various gestational dates on the neurochemistry of the adult neocortex of the rat.

The effects of gestational date (13, 14, 15, and 17 days) or administration of methylazoxymethanol acetate (20 mg/kg) on the cortical synaptic chemistry and morphology of the rat has been examined in adult offspring. Treatment at 13 days of gestation (DG) resulted in cortical hypoplasia that affected primarily the deep layers whereas treatment at 14 and 15 days gestation caused a severe hypoplasia of cortical neurons above layer V and a 66 to 77% reduction in cortical mass. The 17-DG treatment caused only a 20% reduction in cortical weight with effects apparent only in the superficial layers. At no treatment date did the specific activity of glutamate decarboxylase differ significantly from control. In contrast, presynaptic markers for noradrenergic (tyrosine hydroxylase and norepinephrine) and for serotonergic (serotonin) terminals were increased in concentration in direct proportion to the degree of cortical hypoplasia. The specific activity of choline acetyltransferase was significantly increased at all treatment dates but total activity per cortical slab was significantly reduced on treatment days 13-15.

Age Factors↗
PubMed1981

Ultrastructural demonstration of noradrenergic synapses in the rat central nervous system by dopamine-beta-hydroxylase immunocytochemistry.

Noradrenergic (NA) cell bodies and axonal processes were identified in the electron microscope by the immunocytochemical localization of the norepinephrine-synthesizing enzyme, dopamine-beta-hydroxylase (DBH). DBH immunoreactivity, visualized by the peroxidase-antiperoxidase method, was observed in the somata and proximal processes of locus coeruleus neurons and in the distal axons of several NA terminal fields. DBH immunoreactivity is distributed throughout the cytoplasm of the NA neuron, but demonstrates a selective association with endoplasmic reticulum, Golgi apparatus, mitochondrial outer membranes, large granular vesicles, and small, round synaptic vesicles. DBH-positive axonal profiles, typically interspersed between unlabeled dendrites, form two distinct populations: a) thin, unmyelinated intervaricose segments (ca. 0.28 micron) and b) spherical varicosities (ca. 1.00 micron). No DBH-positive varicosities were observed in contact with intracerebral capillaries. In order to determine whether or not NA axons typically form synaptic contacts, a quantitative analysis of selected areas of the diencephalon, cerebellum, and limbic cortex was carried out. More than half (58%) of all DBH-positive varicosities form axodendritic synapses characterized by specialized junctional appositions. The results suggest that NA neurons typically exert their influence on other neurons through highly restricted synaptic contacts.

Animals↗